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  • 201.
    Hailer, Yasmin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Montgomery, Scott M.
    Ekbom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nilsson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bahmanyar, Shahram
    Legg-Calve-Perthes Disease and Risks for Cardiovascular Diseases and Blood Diseases2010Ingår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 125, nr 6, s. E1308-E1315Artikel i tidskrift (Refereegranskat)
  • 202.
    Hailer, Yasmin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Penno, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Agreement of radiographic measurements and patient-reported outcome in 61 patients with Legg-Calvé-Perthes disease at mean follow-up of 28 years.2019Ingår i: Journal of pediatric orthopedics. Part B, ISSN 1060-152X, E-ISSN 1473-5865, Vol. 28, nr 2, s. 100-106Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is unclear how patient-reported outcome in patients with Legg-Calvé-Perthes disease (LCPD) is correlated with radiographic outcome. It was therefore the aim of our long-term follow-up to evaluate the agreement of patient-reported outcome measures (PROM) with radiographic outcome in patients with a history of unilateral LCPD and a femoral head involvement of more than 50%. We further investigated to what extent the functional outcome (range of motion and Trendelenburg sign) correlates with PROM and radiographic outcome. At a mean follow-up of 28 years (15-42), 61 patients were investigated clinically and by plain radiography to evaluate the sphericity deviation score, femoral head enlargement and femoral neck growth inhibition. The patients also completed questionnaires for generic measures of health-related quality-of-life (ED-5D, EQ-visual analogue scale), the joint-specific Harris hip score and the nonarthritic hip score questionnaire. The radiographic measures sphericity deviation score, femoral head enlargement and femoral neck growth inhibition were strongly correlated with the joint-specific PROMs (Harris hip score and nonarthritic hip score) but not with EQ-5D and EQ-visual analogue scale. Inferior range of flexion and abduction and a positive Trendelenburg sign were associated with an inferior patient-reported outcome. Our findings highlight the importance of supporting femoral head re-modelling and containment and balancing trochanteric and femoral neck growth in patients with LCPD. To capture the whole picture of the outcome after LCPD, future studies should include a combination of radiographic measurements and joint-specific and generic outcome scores. Level of Evidence: Level III.

  • 203.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kurland, L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, K.
    Öhman, K. P.
    Nyström, F.
    Liljedahl, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)2004Ingår i: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 27, nr 5, s. 287-290Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Studies suggest that endothelin-1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin-1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment.

    HYPOTHESIS:

    This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol.

    METHODS:

    We determined the preproendothelin-1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double-blind fashion to treatment with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol.

    RESULTS:

    The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin-1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype (-21.9 mmHg [13.9] vs. -8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T-allele were seen among women.

    CONCLUSIONS:

    Our finding suggests a gender-specific relationship between the G5665T preproendothelin-1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.

  • 204.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, Karl Peter
    Nyström, Fredrik
    Liljedahl, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy2003Ingår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 18, nr 3, s. 11-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Adipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension.

    Methods

    We evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing.

    Results

    After adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03).

    Conclusions

    The ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.

  • 205.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Digoxin for the treatment of heart failure2003Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 348, nr 7, s. 661-662Artikel i tidskrift (Refereegranskat)
  • 206.
    Hallström, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Coffee Consumption in Relation to Osteoporosis and Fractures: Observational Studies in Men and Women2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    During the past decades, the incidence of osteoporotic fractures has increased dramatically in the Western world. Consumption of coffee and intake of caffeine have in some studies been found to be associated with increased risk of osteoporotic fractures, but overall results from previous research are inconsistent. Despite weak evidence, some osteoporosis organisations recommend limiting daily coffee or caffeine intake.

    The primary aim of this thesis was to study the association between long-term consumption of coffee and bone mineral density (BMD), incidence of osteoporosis and fractures. A secondary aim was to study the relation between tea consumption and fracture risk.

    An increased risk of osteoporotic fractures in individuals who consumed ≥ 4 cups of coffee vs < 1 cup coffee per day was demonstrated in a study of 31,257 Swedish middle-aged and elderly women (a part of the Swedish Mammography Cohort - SMC) when calcium intake was low (< 700 mg/day). However, no higher risks of osteoporosis or fractures were observed in the full SMC with increasing coffee consumption. In the full SMC (n = 61,433) the follow-up was longer and the number of fractures was higher. Similarly, no statistically significant associations between consumption of coffee (≥ 4 cups of coffee vs < 1 cup) and incidence of osteoporotic fractures were observed in the Cohort of Swedish Men (COSM), including 45,339 men. Calcium intake did not modify the results from the investigations performed in the full SMC or COSM.

    Nonetheless, a 2 - 4% lower BMD at measured sites was observed in men participating in the PIVUS cohort and in women from a sub-cohort of the SMC who consumed ≥ 4 cups of coffee vs < 1 cup daily. Individuals with high coffee intake and rapid metabolism of caffeine had lower BMD at the femoral neck.

    No association between tea consumption and risk of fractures was found in the studies.

    In conclusion, the findings presented in this thesis demonstrate that high consumption of coffee may be associated with a modest decrease in BMD. However, there was no evidence of a substantially increased incidence of osteoporosis or fractures typically associated with osteoporosis.

    Delarbeten
    1. Coffee, tea and caffeine consumption in relation to osteoporotic fracture risk in a cohort of Swedish women
    Öppna denna publikation i ny flik eller fönster >>Coffee, tea and caffeine consumption in relation to osteoporotic fracture risk in a cohort of Swedish women
    2006 (Engelska)Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 17, nr 7, s. 1055-64Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    INTRODUCTION: Consumption of coffee and tea, and total intake of caffeine has been claimed to be associated with osteoporotic fracture risk. However, results of earlier studies lack consistency. METHODS: We examined this relation in a cohort of 31,527 Swedish women aged 40-76 years at baseline in 1988. The consumption of coffee, caffeinated tea and the intake of caffeine were estimated from a self-administered food frequency questionnaire (FFQ). Multivariate-adjusted hazards ratios (HRs) of fractures with 95% confidence intervals (95% CIs) were estimated by Cox proportional hazards models. RESULTS: During a mean follow-up of 10.3 years, we observed 3,279 cases with osteoporotic fractures. The highest (>330 mg/day) compared with the lowest (<200 mg/day) quintile of caffeine intake was associated with a modestly increased risk of fracture: HR 1.20 (95% CI: 1.07-1.35). A high coffee consumption significantly increased the risk of fracture (p for trend 0.002), whereas tea drinking was not associated with risk. The increased risk of fracture with both a high caffeine intake and coffee consumption was confined to women with a low calcium intake (<700 mg/day): HR 1.33 (95% CI: 1.07-1.65) with > or =4 cups (600 ml)/day of coffee compared to <1 cup (150 ml)/day. The same comparison but risk estimated for women with a high propensity for fractures (> or =2 fracture types) revealed a HR of 1.88 (95% CI: 1.17-3.00). CONCLUSIONS: In conclusion, our results indicate that a daily intake of 330 mg of caffeine, equivalent to 4 cups (600 ml) of coffee, or more may be associated with a modestly increased risk of osteoporotic fractures, especially in women with a low intake of calcium.

    Nyckelord
    Caffeine, Coffee, Cohort study, Fracture, Tea
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-18937 (URN)10.1007/s00198-006-0109-y (DOI)16758142 (PubMedID)
    Tillgänglig från: 2006-11-24 Skapad: 2006-11-24 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
    2. Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study
    Öppna denna publikation i ny flik eller fönster >>Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study
    Visa övriga...
    2010 (Engelska)Ingår i: Nutrition & metabolism, ISSN 1743-7075, Vol. 7, s. 12-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    ABSTRACT: BACKGROUND: Drinking coffee has been linked to reduced calcium conservation, but it is less clear whether it leads to sustained bone mineral loss and if individual predisposition for caffeine metabolism might be important in this context. Therefore, the relation between consumption of coffee and bone mineral density (BMD) at the proximal femur in men and women was studied, taking into account, for the first time, genotypes for cytochrome P450 1A2 (CYP1A2) associated with metabolism of caffeine. METHODS: Dietary intakes of 359 men and 358 women (aged 72 years), participants of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), were assessed by a 7-day food diary. Two years later, BMD for total proximal femur, femoral neck and trochanteric regions of the proximal femur were measured by Dual-energy X-ray absorptiometry (DXA). Genotypes of CYP1A2 were determined. Adjusted means of BMD for each category of coffee consumption were calculated. RESULTS: Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (p = 0.04) compared with low or non-consumers of coffee. This difference was not observed in women. In high consumers of coffee, those with rapid metabolism of caffeine (C/C genotype) had lower BMD at the femoral neck (p = 0.01) and at the trochanter (p = 0.03) than slow metabolizers (T/T and C/T genotypes). Calcium intake did not modify the relation between coffee and BMD. CONCLUSION: High consumption of coffee seems to contribute to a reduction in BMD of the proximal femur in elderly men, but not in women. BMD was lower in high consumers of coffee with rapid metabolism of caffeine, suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee.

    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Ortopedi
    Identifikatorer
    urn:nbn:se:uu:diva-123254 (URN)10.1186/1743-7075-7-12 (DOI)000275964400001 ()20175915 (PubMedID)
    Tillgänglig från: 2010-04-27 Skapad: 2010-04-27 Senast uppdaterad: 2013-08-30Bibliografiskt granskad
    3. Long-term coffee consumption in relation to fracture risk and bone mineral density in women
    Öppna denna publikation i ny flik eller fönster >>Long-term coffee consumption in relation to fracture risk and bone mineral density in women
    Visa övriga...
    2013 (Engelska)Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 178, nr 6, s. 898-909Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    High consumption of coffee has been suggested to reduce the risk of some late-onset diseases and death but also to contribute to the development of osteoporotic fractures. Results of previous fracture studies have been inconsistent, and a comprehensive study is needed. The longitudinal population-based Swedish Mammography Cohort, including 61,433 women born in 1914-1948, was followed up from 1987 through 2008. Coffeeconsumption was assessed with repeated food frequency questionnaires. During follow-up, 14,738 women experienced fracture of any type, and 3,871 had a hip fracture. In a subcohort (n = 5,022), bone density was measured and osteoporosis determined (n = 1,012). After multivariable adjustment, there was no evidence of a higher rate of any fracture (hazard ratio per 200 mL coffee = 0.99; 95% confidence interval: 0.98, 1.00) or hip fracture (hazard ratio per 200 mL coffee = 0.97, 95% confidence interval: 0.95, 1.00) with increasing coffeeconsumption. A high coffee intake (>= 4 cups daily) versus a low intake (<1 cup daily) was associated with a 2%-4% lower bone density, depending on site (P < 0.001), but the odds ratio for osteoporosis was only 1.28 (95% confidence interval: 0.88, 1.87). Thus, high coffeeconsumption was associated with a small reduction in bone density that did not translate into an increased risk of fracture.

    Nyckelord
    Bone mineral density, coffee, cohort study, fracture, osteoporosis
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Epidemiologi
    Identifikatorer
    urn:nbn:se:uu:diva-196322 (URN)10.1093/aje/kwt062 (DOI)000325150600012 ()
    Forskningsfinansiär
    Vetenskapsrådet
    Tillgänglig från: 2013-03-07 Skapad: 2013-03-07 Senast uppdaterad: 2018-08-24Bibliografiskt granskad
    4. Coffee Consumption and Risk of Fracture in the Cohort of Swedish Men (COSM)
    Öppna denna publikation i ny flik eller fönster >>Coffee Consumption and Risk of Fracture in the Cohort of Swedish Men (COSM)
    Visa övriga...
    2014 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e97770-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Recent research in a large cohort of women showed that coffee consumption is not associated with increased risk of fracture. Whether this is the case also among men is less clear. Methods: In the Cohort of Swedish Men (COSM) study, 42,978 men aged 45-79 years old at baseline in 1997 answered a self-administered food frequency questionnaire covering coffee consumption and a medical and lifestyle questionnaire covering potential confounders. Our main outcomes first fracture at any site and first hip fracture were collected from the National Patient Registry in Sweden. The association between coffee consumption and fracture risk was investigated using Cox's proportional hazards regression. Results: During a mean follow-up of 11.2 years, 5,066 men had a first fracture at any site and of these, 1,186 (23%) were hip fractures. There was no association between increasing coffee consumption (per 200 ml) and rate of any fracture (hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.99-1.02) or hip fracture (HR 1.02; 95% CI 0.99-1.06) after adjustment for potential confounders. For men consuming >= 4 cups of coffee/day compared to those consuming <1 cup of coffee/day, HR for any type of fracture was 0.91 (95% CI 0.80-1.02) and for hip fracture: 0.89 (95% CI 0.70-1.14). Conclusions: High coffee consumption was not associated with an increased risk of fractures in this large cohort of Swedish men.

    Nyckelord
    Coffee, cohort, fracture, men, osteoporosis
    Nationell ämneskategori
    Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
    Forskningsämne
    Epidemiologi
    Identifikatorer
    urn:nbn:se:uu:diva-196326 (URN)10.1371/journal.pone.0097770 (DOI)000336789500113 ()
    Forskningsfinansiär
    Vetenskapsrådet
    Tillgänglig från: 2013-03-07 Skapad: 2013-03-07 Senast uppdaterad: 2018-08-24Bibliografiskt granskad
  • 207.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Glynn, Anders
    Livsmedelsverket.
    Warensjö Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Institutet för miljömedicin, Karolinska institutet.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Long-term coffee consumption in relation to fracture risk and bone mineral density in women2013Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 178, nr 6, s. 898-909Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High consumption of coffee has been suggested to reduce the risk of some late-onset diseases and death but also to contribute to the development of osteoporotic fractures. Results of previous fracture studies have been inconsistent, and a comprehensive study is needed. The longitudinal population-based Swedish Mammography Cohort, including 61,433 women born in 1914-1948, was followed up from 1987 through 2008. Coffeeconsumption was assessed with repeated food frequency questionnaires. During follow-up, 14,738 women experienced fracture of any type, and 3,871 had a hip fracture. In a subcohort (n = 5,022), bone density was measured and osteoporosis determined (n = 1,012). After multivariable adjustment, there was no evidence of a higher rate of any fracture (hazard ratio per 200 mL coffee = 0.99; 95% confidence interval: 0.98, 1.00) or hip fracture (hazard ratio per 200 mL coffee = 0.97, 95% confidence interval: 0.95, 1.00) with increasing coffeeconsumption. A high coffee intake (>= 4 cups daily) versus a low intake (<1 cup daily) was associated with a 2%-4% lower bone density, depending on site (P < 0.001), but the odds ratio for osteoporosis was only 1.28 (95% confidence interval: 0.88, 1.87). Thus, high coffeeconsumption was associated with a small reduction in bone density that did not translate into an increased risk of fracture.

  • 208.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Glynn, Anders
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study2010Ingår i: Nutrition & metabolism, ISSN 1743-7075, Vol. 7, s. 12-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ABSTRACT: BACKGROUND: Drinking coffee has been linked to reduced calcium conservation, but it is less clear whether it leads to sustained bone mineral loss and if individual predisposition for caffeine metabolism might be important in this context. Therefore, the relation between consumption of coffee and bone mineral density (BMD) at the proximal femur in men and women was studied, taking into account, for the first time, genotypes for cytochrome P450 1A2 (CYP1A2) associated with metabolism of caffeine. METHODS: Dietary intakes of 359 men and 358 women (aged 72 years), participants of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), were assessed by a 7-day food diary. Two years later, BMD for total proximal femur, femoral neck and trochanteric regions of the proximal femur were measured by Dual-energy X-ray absorptiometry (DXA). Genotypes of CYP1A2 were determined. Adjusted means of BMD for each category of coffee consumption were calculated. RESULTS: Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (p = 0.04) compared with low or non-consumers of coffee. This difference was not observed in women. In high consumers of coffee, those with rapid metabolism of caffeine (C/C genotype) had lower BMD at the femoral neck (p = 0.01) and at the trochanter (p = 0.03) than slow metabolizers (T/T and C/T genotypes). Calcium intake did not modify the relation between coffee and BMD. CONCLUSION: High consumption of coffee seems to contribute to a reduction in BMD of the proximal femur in elderly men, but not in women. BMD was lower in high consumers of coffee with rapid metabolism of caffeine, suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee.

  • 209.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, A.
    Glynn, Anders
    Warensjö, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Coffee consumption in relation to osteoporotic fracture risk and bone mineral density: A prospective longitudinal cohort study2012Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, s. S36-S36Artikel i tidskrift (Övrigt vetenskapligt)
  • 210.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Institutet för Miljömedicin, Karolinska Institutet.
    Glynn, Anders
    Livsmedlesverket.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Coffee Consumption and Risk of Fracture in the Cohort of Swedish Men (COSM)2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e97770-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recent research in a large cohort of women showed that coffee consumption is not associated with increased risk of fracture. Whether this is the case also among men is less clear. Methods: In the Cohort of Swedish Men (COSM) study, 42,978 men aged 45-79 years old at baseline in 1997 answered a self-administered food frequency questionnaire covering coffee consumption and a medical and lifestyle questionnaire covering potential confounders. Our main outcomes first fracture at any site and first hip fracture were collected from the National Patient Registry in Sweden. The association between coffee consumption and fracture risk was investigated using Cox's proportional hazards regression. Results: During a mean follow-up of 11.2 years, 5,066 men had a first fracture at any site and of these, 1,186 (23%) were hip fractures. There was no association between increasing coffee consumption (per 200 ml) and rate of any fracture (hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.99-1.02) or hip fracture (HR 1.02; 95% CI 0.99-1.06) after adjustment for potential confounders. For men consuming >= 4 cups of coffee/day compared to those consuming <1 cup of coffee/day, HR for any type of fracture was 0.91 (95% CI 0.80-1.02) and for hip fracture: 0.89 (95% CI 0.70-1.14). Conclusions: High coffee consumption was not associated with an increased risk of fractures in this large cohort of Swedish men.

  • 211.
    Hantikainen, Essi
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden..
    Grotta, Alessandra
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden..
    Ye, Weimin
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden..
    Adami, Hans-Olov
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.;Harvard Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA..
    Surkan, Pamela J.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, 615 North Wolfe St,Room E8527, Baltimore, MD 21205 USA..
    Serafini, Mauro
    Council Agr Res & Econ, Ctr Nutr, Funct Food & Metab Stress Prevent Lab, Via Ardeatina 546, I-00100 Rome, Italy..
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bellocco, Rino
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.;Univ Milano Bicocca, Dept Stat & Quantitat Methods, Edificio U7,Via Bicocca Arcimboldi 8, I-20126 Milan, Italy..
    Lagerros, Ylva Trolle
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, T2, SE-17176 Stockholm, Sweden.;Kamlinska Univ Hosp, Dept Med, C2 84, SE-14186 Stockholm, Sweden..
    Prospective study of dietary Non Enzymatic Antioxidant Capacity on the risk of hip fracture in the elderly2016Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 90, s. 31-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dietary antioxidants may play an important role in the prevention of bone loss and associated fractures by reducing levels of oxidative stress. We prospectively investigated the association between dietary Non Enzymatic Antioxidant Capacity (NEAC) and the risk of hip fracture and whether this effect was modified by smoking. Method: In the Swedish National March Cohort 13,409 men and women over the age of 55 who had not experienced cancer, cardiovascular disease or hip fracture, were followed through record-linkages from 1997 through 2010. NEAC was assessed by a validated food frequency questionnaire collected at baseline. We categorized the distribution of NEAC into sex-specific quartiles and used multivariable adjusted Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (95% CI). Results: During a mean follow-up time of 12.4 years, we identified 491 incident cases of first hip fracture. Subjects in the highest quartile of dietary NEAC had a 39% lower risk of incident hip fracture compared to those in the lowest quartile (HR: 0.61; 95% CI: 0.44-0.85). The association was non-linear (p for non-linearity: 0.004) with a potential threshold between the first and the second quartile and no further risk reduction at higher levels of dietary NEAC. Due to a low smoking prevalence in our study population, we had limited power to detect effect modification between dietary NEAC and smoking on a multiplicative or additive scale. Conclusion: Higher dietary NEAC intake is associated with lower risk of hip fracture in the elderly.

  • 212.
    Harvey, Nicholas C.
    et al.
    Univ Southampton, Lifecourse Epidemiol Unit, MRC, Southampton, Hants, England;Univ Southampton, Southampton Biomed Res Ctr, NIHR, Southampton, Hants, England;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England.
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
    Karlsson, Magnus K.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Rosengren, Bjorn E.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Ribom, Eva L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cooper, Cyrus
    Univ Southampton, Lifecourse Epidemiol Unit, MRC, Southampton, Hants, England;Univ Southampton, Southampton Biomed Res Ctr, NIHR, Southampton, Hants, England;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England;Univ Oxford, Biomed Res Ctr, NIHR, Oxford, England.
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
    Kanis, John A.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Johansson, Helena
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia.
    McCloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England;Univ Sheffield, Ctr Integrated Res Musculoskeletal Ageing CIMA, Mellanby Ctr Bone Res, Sheffield, S Yorkshire, England.
    Measures of Physical Performance and Muscle Strength as Predictors of Fracture Risk Independent of FRAX, Falls, and aBMD: A Meta-Analysis Of The Osteoporotic Fractures In Men (MrOS) Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 12, s. 2150-2157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measures of muscle mass, strength, and function predict risk of incident fractures, but it is not known whether this risk information is additive to that from FRAX (fracture risk assessment tool) probability. In the Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, Hong Kong, United States), we investigated whether measures of physical performance/appendicular lean mass (ALM) by DXA predicted incident fractures in older men, independently of FRAX probability. Baseline information included falls history, clinical risk factors for falls and fractures, femoral neck aBMD, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the relationship between time for five chair stands, walking speed over a 6 m distance, grip strength, ALM adjusted for body size (ALM/height(2)), FRAX probability (major osteoporotic fracture [MOF]) with or without femoral neck aBMD, available in a subset of n = 7531), and incident MOF (hip, clinical vertebral, wrist, or proximal humerus). Associations were adjusted for age and time since baseline, and are reported as hazard ratios (HRs) for first incident fracture per SD increment in predictor using meta-analysis. 5660 men in the United States (mean age 73.5 years), 2764 men in Sweden (75.4 years), and 1987 men in Hong Kong (72.4 years) were studied. Mean follow-up time was 8.7 to 10.9 years. Greater time for five chair stands was associated with greater risk of MOF (HR 1.26; 95% CI, 1.19 to 1.34), whereas greater walking speed (HR 0.85; 95% CI, 0.79 to 0.90), grip strength (HR 0.77; 95% CI, 0.72 to 0.82), and ALM/height(2) (HR 0.85; 95% CI, 0.80 to 0.90) were associated with lower risk of incident MOF. Associations remained largely similar after adjustment for FRAX, but associations between ALM/height(2) and MOF were weakened (HR 0.92; 95% CI, 0.85 to 0.99). Inclusion of femoral neck aBMD markedly attenuated the association between ALM/height(2) and MOF (HR 1.02; 95% CI, 0.96 to 1.10). Measures of physical performance predicted incident fractures independently of FRAX probability. Whilst the predictive value of ALM/height(2) was substantially reduced by inclusion of aBMD requires further study, these findings support the consideration of physical performance in fracture risk assessment.

  • 213.
    Harvey, Nicholas
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Rosengren, Bjorn
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Ribom, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cawthon, Peggy
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Ensrud, Kristine
    Univ Minnesota, Med & Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.
    Kanis, John
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Johansson, Helena
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.
    Mccloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.
    Definitions of sarcopenia as predictors of fracture risk independent of FRAX, falls and BMD: A meta-analysis of the Osteoporotic Fractures in Men (MrOS) Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, s. 13-14Artikel i tidskrift (Övrigt vetenskapligt)
  • 214.
    Heary, Robert F.
    et al.
    Rutgers New Jersey Med Sch, Dept Neurol Surg, Newark, NJ USA.
    MacDowall, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Agarwal, Nitin
    Univ Pittsburgh, Dept Neurol Surg, Med Ctr, Pittsburgh, PA 15260 USA.
    Cervical spondylotic myelopathy: A two decade experience2019Ingår i: Journal of Spinal Cord Medicine (JSCM), ISSN 1079-0268, E-ISSN 2045-7723, Vol. 42, nr 4, s. 407-415Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Context: Cervical myelopathy occurs as a result of compression of the cervical spinal cord. Symptomatology includes, but is not limited to, pain, weakness, paresthesias, or gait/balance difficulties. Objective: To present a two-decade experience with the management of cervical myelopathy. Methods: Literature was reviewed to provide current guidelines for management as well as accompanying clinical presentations. Results: Surgical decompression, if necessary, may be achieved from either an anterior, a posterior, or a combined anterior-posterior (AP) approach. The indications for each approach, as well as the surgical techniques, are described. Conclusion: Several etiologies may lead to cord compression and cervical myelopathy. The best vector of approach with regard to anterior versus posterior surgical intervention is still under investigation. Regardless, management via surgical decompression has been demonstrated repeatedly to improve the CSM patients' quality of life.

  • 215.
    Hedin, Hanne
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    External Fixation of Femoral Fractures in Children: Clinical, radiological and functional outcome and cost analysis2003Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The overall aim of this thesis was to evaluate the outcome when treating children for displaced femoral fractures with external fixation.

    In a consecutive and prospective study during the period 1993-2000, 96 children aged 3-15 years with 98 displaced femoral fractures were treated with external fixation and early mobilisation. The mean age was 8.1 years, the mean hospital stay was 8.7 days and the mean treatment time was 61 days. All fractures healed. Minor complications included pin tract infections (18%), clinical insignificant malunions, heterotopic ossification and two re-reductions. Major complications (6%) included two re-fractures after significant trauma and three plastic deformations after premature fixator removal leading to an osteotomy.

    Radiological evaluation was performed up to one year for the whole group and for a subgroup up to two years. The evaluation showed that malunions were few and prone to remodelling almost completely. Although the fractures were fixated without shortening, as recommended earlier, the overgrowth was far less than expected.

    Isokinetic muscle strength was measured in both hamstrings and quadriceps in 31 of the patients and compared with 31 matched children without previous injury to the legs. Early mobilisation seems to prevent residual muscle weakness previously shown after treatment with traction or cast for femoral fractures in children.

    A cost analysis was performed, comparing three different treatment modalities of femoral shaft fractures: traction in hospital, traction in hospital/at home and external fixation. The analysis included both total medical costs and costs for the care provider. The most important factors were days spent at the hospital and the sick leave for the care provider. Treatment that can minimise these factors will contribute strongly to a lowering of health care costs.

    Conclusion: External fixation of displaced femoral fractures in children can be used as standard treatment in children aged 3-15 years. The treatment provides satisfactory results with a low rate of major complications. Early mobilisation seems to prevent residual muscle weakness. The treatment reduce the number of days in hospital and the number of days of sick leave for the care provider and contributes strongly to lowering health care costs.

  • 216.
    Hellström, Hans-Olov
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mjöberg, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The aluminium content of bone, and mortality risk2008Ingår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 37, nr 2, s. 217-20Artikel i tidskrift (Refereegranskat)
  • 217.
    Hellström, Hans-Olov
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mjöberg, Bengt
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    No association between the aluminium content of trabecular bone and bone density, mass or size of the proximal femur in elderly men and women2006Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 7, s. 69-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Aluminium is considered a bone toxic metal since poisoning can lead to aluminium-induced bone disease in patients with chronic renal failure. Healthy subjects with normal renal function retain 4% of the aluminium consumed. They might thus also accumulate aluminium and eventually be at risk of long-term low-grade aluminium intoxication that can affect bone health. METHODS: We therefore examined 62 patients with femoral neck fractures or osteoarthritis of the hip (age range 38-93), with the aim of examining whether aluminium in bone is associated with bone-mineral density (BMD), content (BMC) or width of the femoral neck measured by dual-energy X-ray absorptiometry (DXA). During operations bone biopsies were taken from the trabecular bone of the proximal femur. The samples were measured for their content of aluminium using a mass spectrometer. RESULTS: No significant association between the aluminium content in bone and femoral neck BMD, BMC or width could be found after multivariate adjustment. CONCLUSION: Our results indicate that the accumulated aluminium content in bone during life does not substantially influence the extent of osteoporosis.

  • 218.
    Henriques, Thomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cunningham, Bryan
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Shimamoto, Norimichi
    Lee, Guy
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    McAfee, Paul
    Biomechanical comparison of five different atlantoaxial posterior fixation techhniques2000Ingår i: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 25, nr 22, s. 2877-2883Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY DESIGN:

    Five different reconstructions of the atlantoaxial complex were biomechanically compared in vitro in a nondestructive test.

    OBJECTIVES:

    To determine whether non-bone graft-dependent one-point fixation affords stability levels equivalent to three-point reconstructions.

    SUMMARY OF BACKGROUND DATA:

    Previous investigations have demonstrated that three-point fixation, using bilateral transarticular screws in combination with posterior wiring, provide the most effective resistance to minimize motion around C1-C2. However, placement of transarticular screws is technically demanding. Posterior wiring techniques affording one-point fixation have failure rates of approximately 15%, with failure considered to be secondary to structural bone graft failures. One-point, non-bone graft-dependent fixations have not been tested.

    METHODS:

    Eight human cervical specimens, C0-C3 were loaded nondestructively. Unconstrained three-dimensional segmental motion was measured. The reconstructions tested were two one-point fixations, one two-point fixation, and two three-point fixations.

    RESULTS:

    Under axial rotation two and three-point reconstructions provided better stiffness than the one-point reconstructions (P < 0.05). During flexion-extension, higher stiffness levels were observed in one- and three-point fixations when compared with the intact spine (P < 0.05). In lateral bending no significant differences were observed among the six groups, although the trend was that reconstructions including transarticular screws provided greater stability than one-point fixations.

    CONCLUSION:

    The current findings substantiate the use of three-point fixation as the treatment of choice for C1-C2 instability. [l: atlantoaxial fixation, biomechanics, cervical spine, instability, spinal instrumentation, transarticular screws]

  • 219. Henriques, Thomas
    et al.
    Cunningham, Bryan W.
    Mcafee, Paul C.
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    In vitro biomechanical evaluation of four fixation techniques for distractive-flexion injury stage 3 of the cervical spine2015Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, nr 3, s. 198-206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose. Anterior plate fixation has been reported to provide satisfactory results in cervical spine distractive flexion (DF) injuries stages 1 and 2, but will result in a substantial failure rate in more unstable stage 3 and above. The aim of this investigation was to determine the biomechanical properties of different fixation techniques in a DF-3 injury model where all structures responsible for the posterior tension band mechanism are torn. Methods. The multidirectional three-dimensional stiffness of the subaxial cervical spine was measured in eight cadaveric specimens with a simulated DF-3 injury at C5-C6, stabilized with four different fixation techniques: anterior plate alone, anterior plate combined with posterior wire, transarticular facet screws, and a pedicle screw-rod construct, respectively. Results. The anterior plate alone did not improve stability compared to the intact spine condition, thus allowing considerable range of motion around all three cardinal axes (p > 0.05). The anterior plate combined with posterior wire technique improved flexion-extension stiffness (p = 0.023), but not in axial rotation and lateral bending. When the anterior plate was combined with transarticular facet screws or with a pedicle screws-rod instrumentation, the stability improved in flexion-extension, lateral bending, and in axial rotation (p < 0.05). Conclusions. These findings imply that the use of anterior fixation alone is insufficient for fixation of the highly unstable DF-3 injury. In these situations, the use of anterior fixation combined with a competent posterior tension band reconstruction (e.g. transarticular screws or a posterior pedicle screws-rod device) improves segmental stability.

  • 220.
    Henriques, Thomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bergman, Antonina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Jonsson, Halldor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Distractive flexion injuries of the subaxial cervical spine treated with anterior plate alone2004Ingår i: Journal of Spinal Disorders & Techniques, ISSN 1536-0652, E-ISSN 1539-2465, Vol. 17, nr 1, s. 1-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The clinical and radiographic effect of anterior plate fixation alone was evaluated in 36 consecutive patients with distractive flexion (DF) injuries in the lower cervical spine. Mean follow-up time was 15 months. The aim of the present study was to determine whether anterior plate fixation alone provides sufficient stability when treating DF injuries in the cervical spine. Solid union was seen in 6 of 6 patients with stage 1 injury and in 15 of 17 patients with stage 2 injury. In the patients with stage 3 injury, 7 of 13 of the anterior fixations failed. These failures occurred mainly among the patients with severe neurologic injuries. We believe these findings substantiate the use of anterior plate alone for DF injuries at stage 1 and 2 but disqualify anterior plate fixation alone for DF injuries at stage 3, with neurologic injury present.

  • 221. Herlin, Maria
    et al.
    Kalantari, Fereshteh
    Stern, Natalia
    Sand, Salomon
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Viluksela, Matti
    Tuomisto, Jouni T.
    Tuomisto, Jouko
    Tuukkanen, Juha
    Jämsä, Timo
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Håkansson, Helen
    Quantitative characterization of changes in bone geometry, mineral density and biomechanical properties in two rat strains with different Ah-receptor structures after long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin2010Ingår i: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 273, nr 1-3, s. 1-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Both industrial chemicals and environmental pollutants can interfere with bone modeling and remodeling. Recently, detailed toxicological bone studies have been performed following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which exerts most of its toxic effects through the aryl hydrocarbon receptor (AhR). OBJECTIVES: The aims of the present study were to quantitatively evaluate changes in bone geometry, mineral density and biomechanical properties following long-term exposure to TCDD, and to further investigate the role of AhR in TCDD-induced bone alterations. To this end, tissue material used in the study was derived from TCDD-exposed Long-Evans (L-E) and Han/Wistar (H/W) rats, which differ markedly in sensitivity to TCDD-induced toxicity due to a strain difference in AhR structure. METHODS: Ten weeks old female L-E and H/W rats were administered TCDD s.c. once per week for 20 weeks, at doses corresponding to calculated daily doses of 0, 1, 10, 100 and 1000ngTCDD/kgbw (H/W only). Femur, tibia and vertebra from the L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose-response modeling was performed to establish benchmark doses for the analyzed bone parameters, and to quantify strain sensitivity differences for those parameters, which were affected by TCDD exposure in both rat strains. RESULTS: Bone geometry and bone biomechanical parameters were affected by TCDD exposure, while bone mineral density parameters were less affected. The trabecular area at proximal tibia and the endocortical circumference at tibial diaphysis were the parameters that showed the highest maximal responses. Significant strain differences in response to TCDD treatment were observed, with the L-E rat being the most sensitive strain. For the parameters that were affected in both strains, the differences in sensitivity were quantified, showing the most pronounced (about 49-fold) strain difference for cross-sectional area of proximal tibia. CONCLUSION: The study provides novel information about TCDD-induced bone alterations at doses, which are of relevance from a health risk assessment point of view. In addition, the obtained results provide further support for a distinct role of the AhR in TCDD-induced bone alterations, and suggest that the benchmark dose modeling approach is appropriate for quantitative evaluation of bone toxicity parameters.

  • 222. Hermsen, Sanne A. B.
    et al.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Arima, Akihiro
    Muneoka, Atsunobu
    Ihara, Toshio
    Sumida, Hiroshi
    Fukusato, Toshio
    Kubota, Shunichiro
    Yasuda, Mineo
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone tissue in rhesus monkeys2008Ingår i: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 253, nr 1-3, s. 147-152Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bone tissue is one of the target tissues for dioxins and dioxin-like compounds. Therefore, the aim of this study was to investigate effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), oil bone tissue in rhesus monkey, the most human-like experimental model available, Pregnant rhesus monkeys (Macaca mulatta; age 4-10 years) were exposed to TCDD with a total dose of 40.5-42.0 or 405-420 ng/kg bodyweight by repeated subcutaneous injections starting at gestational day 20 and followed by injections every 30 days until 90 clays after delivery. At a mean age of 7 years the offspring were sacrificed and the femur bone dissected. Results from peripheral Quantitative Computed Tomography (pQCT) analyses of the metaphyseal part of the femur bones in female offspring showed significant increases in trabecular bone mineral content (BMC; +84.6%, p < 0.05, F-value (F)=5.9) in the low-dose treatment group compared with the controls. In the same animals, analysis of the mid-diaphyseal part revealed increases in total BMC (+21.3%. p < 0.05, F = 5.2) and cortical cross-sectional area (CSA; +16.4%. p < 0.01, F=7.4) compared with the controls. In males, changes in biomechanical properties indicating more fragile bone were observed. Displacement at failure were significantly increased in the male low-dose group compared to the controls (+38.0%, p, < 0.05, F=11). The high dose of TCDD did not induce any significant changes in bone morphology.

  • 223.
    Hernefalk, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Borg, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Estimating pre-traumatic quality of life in patients with surgically treated acetabular fractures and pelvic ring injuries: Does timing matter?2016Ingår i: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, nr 2, s. 389-394Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: Evaluation of patient-assessed functional outcome in traumatic conditions has specific challenges. To obtain pre-traumatic data to allow for comparison during follow-up, retrospective assessments are needed. How such data is affected by posttraumatic time-point chosen for evaluation is unknown. The primary purpose of this study was to investigate how the time-point chosen for retrospective assessment of pre-traumatic quality of life (QoL) in patients with surgically treated acetabular fractures and pelvic ring injuries influenced the results. A secondary purpose was to examine the pre-traumatic QoL-profile in patients with these injuries.

    PATIENTS AND METHODS: 73 patients were included, where 50 had an acetabular fracture and 23 a pelvic ring injury. Pre-traumatic QoL was evaluated using the generic instruments SF-36 and EQ5D in conjunction with the condition-specific Pelvic Trauma Questionnaire (PTQ). Questionnaires were completed at three time points: 0, 1 and 2 months post-surgery.

    RESULTS: Number of responders were 73 patients at 0 months, 61 patients at 1 month and 53 patients at 2 months. 50 patients answered the questionnaires at all three time-points. A trend was observed with all instruments where patients estimated a better pre-traumatic status with narrower distributions when assessment was delayed. At 2 months, scores for 4 out of 8 SF-36 domains where significantly higher compared to 0 months. For EQ5D, EQ VAS improved at 1 and 2 months compared to month 0 results but no other significant differences between time-points were found. Results from the PTQ demonstrated no significant differences over time. Pre-traumatic quality of life was high and for SF-36 comparable to a population norm. A very low level of pre-existing discomfort from the pelvic region was reported through the PTQ.

    CONCLUSION: Patients with surgically treated acetabular fractures and pelvic ring injuries estimate a higher pre-traumatic functional status when assessment is carried out at 1 or 2 months post-surgery compared to perioperative measurements. The SF-36 seems to be more sensitive than the EQ5D in this respect. Pre-traumatic QoL in patients with surgically treated acetabular fractures and pelvic ring injuries is generally high and pre-existing discomfort from the pelvic region is uncommon.

  • 224. Heyde, Christoph-E.
    et al.
    Fakler, Johannes K.
    Hasenboehler, Erik
    Stahel, Philip F.
    John, Thilo
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Tschoeke, Sven K.
    Kayser, Ralph
    Pitfalls and complications in the treatment of cervical spine fractures in patients with ankylosing spondylitis2008Ingår i: Patient safety in surgery, ISSN 1754-9493, Vol. 2, s. 15-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ABSTRACT: Patients with ankylosing spondylitis are at significant risk for sustaining cervical spine injuries following trauma predisposed by kyphosis, stiffness and osteoporotic bone quality of the spine. The risk of sustaining neurological deficits in this patient population is higher than average. The present review article provides an outline on the specific injury patterns in the cervical spine, diagnostic algorithms and specific treatment modalities dictated by the underlying disease in patients with ankylosing spondylitis. An emphasis is placed on the risks and complication patterns in the treatment of these rare, but challenging injuries.

  • 225.
    Heyde, Christoph-E.
    et al.
    Universitätsklinikum Leipzig AöR, Klinik u. Poliklinik für Orthopädie, Unfallchirurgie u. Plastische Chirurgie, Bereich Wirbelsäulenchirurgie.
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Deszöe, Jeszenszky
    Wirbelsäulenchirurgie, Schulthess Klinik Zürich, Lengghalde 2, CH-8808 Zürich, Schweiz.
    Ätiologie und Pathogenese der Spondylodiszitis2017Ingår i: Die Wirbelsäule, ISSN 2509-8241, Vol. 01, nr 04, s. 237-244Artikel i tidskrift (Refereegranskat)
    Abstract [de]

    Die Häufigkeit der unspezifischen „pyogenen“ und der verschiedenen Formen der spezifischen Spondylodiszitiden nimmt zu. Die Gründe dafür sind vielfältig. Diese Erkrankungen sind auch heute noch mit einer relevanten Morbidität und Mortalität vergesellschaftet. Die Diagnose erfolgt aufgrund der unspezifischen klinischen Manifestation häufig verzögert. Die Kenntnis der Epidemiologie, der Ätiologie und der Pathogenese der verschiedenen Formen der Spondylodiszitis kann die frühzeitige Diagnose und damit den Beginn der Therapie als auch die Therapie an sich erleichtern. In diesem Artikel werden deshalb epidemiologische Daten und wesentliche Aspekte der Ätiologie und Pathogenese der unspezifischen pyogenen Spondylodiszitis sowie der verschiedenen Formen der spezifischen Spondylodiszitis bei Tuberkulose, bei Brucellose und bei Pilzinfektionen diskutiert.

  • 226.
    Heyde, Christoph-E.
    et al.
    Klinik und Poliklinik für Orthopädische Chirurgie der Universität Leipzig.
    Tschöke, Sven-Kevin
    Klinik und Poliklinik für Orthopädische Chirurgie der Universität Leipzig.
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kayser, Ralph
    Klinik und Poliklinik für Orthopaedie und Orthopädische Chirurgie des Klinikums Greifswald.
    Kyphoplastie: Indikation und praktische Durchführung2012Ingår i: Internistische Praxis, ISSN 0020-9570, Vol. 52, nr 3, s. 561-572Artikel i tidskrift (Refereegranskat)
  • 227. Heyde, Christoph-Eckhard
    et al.
    Tschöke, Sven-Kevin
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kayser, Ralph
    Kyphoplastie: Indikation und Durchführung2013Ingår i: Chirurgische Praxis, ISSN 0009-4846, Vol. 76, nr 1, s. 63-74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The minimally invasive procedure of kyphoplasty has become an established method of treatment in both osteoporotic compression fractures and malignant osteolytic lesions of the spine. In cautious consideration of the correct indication and technical implementation, kyphoplasty is a safe procedure with low risk of complications. In comparison to conservative treatment regimens, postoperative clinical outcome parameters have shown promising results in pain reduction and the improvement of function and quality of life in both short-term and mid-term evaluations. However, kyphoplasty as a surgical procedure shall always be considered a component within the overall therapeutic concept. Thus, a comprehensive medical attendance and the consistent treatment of the underlying disease are essential to a successful therapeutic outcome.

  • 228. Heyde, Christoph-Eckhard
    et al.
    Tschöke, Sven-Kevin
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kayser, Ralph
    Kyphoplastie: Indikation und praktische Durchführung. [Kyphoplasty. Indication and practical guidelines]2012Ingår i: Tägliche Praxis, ISSN 0494-464X, Vol. 53, nr 4, s. 799-810Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The minimally invasive procedure of kyphoplasty has become an established method of treatment in both osteoporotic compression fractures and malignant osteolytic lesions of the spine. In cautious consideration of the correct indication and technical implementation, kyphoplasty is a safe procedure with low risk of complications. In comparison to conservative treatment regimens, postoperative clinical outcome parameters have shown promising results in pain reduction and the improvement of function and quality of life in both short-term and mid-term evaluations. However, kyphoplasty as a surgical procedure shall always be considered a component within the overall therapeutic concept. Thus, a comprehensive medical attendance and the consistent treatment of the underlying disease are essential to a successful therapeutic outcome.

  • 229.
    Hirasawa, Atsuhiko
    et al.
    Aichi Med Univ, Dept Spine Ctr, Nagakute, Aichi, Japan; Aichi Med Univ, Dept Orthopaed Surg, Nagakute, Aichi, Japan.
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wakao, Norimitsu
    Aichi Med Univ, Dept Spine Ctr, Nagakute, Aichi, Japan.
    Kamiya, Mitsuhiro
    Aichi Med Univ, Dept Spine Ctr, Nagakute, Aichi, Japan; Aichi Med Univ, Dept Orthopaed Surg, Nagakute, Aichi, Japan.
    Murotani, Kenta
    Aichi Med Univ, Div Biostat, Clin Res Ctr, Nagakute, Aichi, Japan.
    Deie, Masataka
    Aichi Med Univ, Dept Orthopaed Surg, Nagakute, Aichi, Japan.
    Regional Differences in Diffuse Idiopathic Skeletal Hyperostosis: A Retrospective Cohort Study from Sweden and Japan2018Ingår i: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 43, nr 24, s. E1474-E1478Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study Design: We retrospectively reviewed computed tomography (CT) records of patients in Japan and Sweden, which are both aging populations. Objective. To research the influence of ethnicity and region on diffuse idiopathic skeletal hyperostosis (DISH) prevalence.

    Summary of Background Data_ DISH can complicate nonsurgical treatment of spinal fractures and often requires surgical intervention. We previously reported a prevalence of DISH in Japan that was higher than that reported in other studies.

    Methods: We retrospectively reviewed CT records of patients in Japan and Sweden, which have both aging populations. Patients undergoing whole body CT during trauma examinations at an acute outpatient clinic in Uppsala University Hospital in a 1-year period were eligible for inclusion. Excluded were those less than 40 and more than or equal to 90 years old, and those with previous spinal surgery. The prevalence of DISH by sex and age was determined according to radiographic criteria by Resnick. Results from Sweden were compared with the Japan data, which we previously reported.

    Results: Age of the eligible subjects (265 men and 153 women) ranged from 40 to 89 years, with a mean age of 63.4 years. Among men, 86 (32.5%) were diagnosed with DISH, and the results by age (40s, 50s, 60s, 70s, and 80s) were: 6 (10.7%), 13 (22%), 35 (46.1%), 17 (34%), and 15 (62.5%) patients, respectively. Among women, 16 (10.5%) had DISH, and the results by age were as follows: 1 (2.6%), 1 (3.3%), 2 (6.7%), 6 (22.2%), and 6 (22.2%) patients, respectively. These results did not differ from those previously published for Japan (Fisher exact test, men: P = 1, 0.27, 0.12, 0.06, and 1, respectively; women: P = 0.49, 0.62, 0.5, 0.8, and 0.3, respectively).

    Conclusion: The presented cohort study revealed that ethnicity and region may not be notable factors of DISH prevalence, since patients from both Japan and Sweden had similar DISH prevalence.

    Level of Evidence: 3

  • 230. Hollberg, Karin
    et al.
    Marsell, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Norgård, Maria
    Larsson, Tobias E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jonsson, Kenneth B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Andersson, Göran
    Osteoclast polarization is not required for degradation of bone matrix in rachitic FGF23 transgenic mice2008Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 42, nr 6, s. 1111-1121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hypophosphatemic transgenic (tg) mice overexpressing FGF23 in osteoblasts display disorganized growth plates and reduced bone mineral density characteristic of rickets/osteomalacia. These FGF23 tg mice were used as an in vivo model to examine the relation between osteoclast polarization, secretion of proteolytic enzymes and resorptive activity. Tg mice had increased mRNA expression levels of the ostcoblast differentiation marker Runx2 and mineralization-promoting proteins alkaline phosphatase and bone sialoprotein in the long bones compared to wild type (wt) mice. In contrast, expression of alpha 1 (1) collagen, osteocalcin, dentin matrix protein 1 and osteopontin was unchanged, indicating selective activation of osteoblasts promoting mineralization. The number of osteoclasts was unchanged in tg compared to wt mice, as determined by histomorphometry, serum levels of TRAP 5b activity as well as mRNA expression levels of TRAP and cathepsin K. However, tg mice displayed elevated serum concentrations of C-terminal telopeptide of collagen I (CTX) indicative of increased bone matrix degradation. The majority of osteoclasts in FGF23 tg mice lacked ultrastructural morphological signs of proper polarization. However, they secreted both cathepsin K and MMP-9 at levels comparable to osteoclasts with ruffled borders. Mineralization of bone matrix thus appears essential for inducing osteoclast polarization but not for secretion of osteoclast proteases. Finally, release of CTX by freshly isolated osteoclasts was increased on demineralized compared to mineralized bovine bone slices, indicating that the mineral component limits collagen degradation. We conclude that ruffled borders are implicated in acidification and subsequent demineralization of the bone matrix, however not required for matrix degradation. The data collectively provide evidence that osteoclasts, despite absence of ruffled borders, effectively participate in the degradation of hypomineralized bone matrix in rachitic FGF23 tg mice.

  • 231. Holvik, K
    et al.
    Gjesdal, C G
    Tell, G S
    Grimnes, G
    Schei, B
    Apalset, E M
    Samuelsen, S O
    Blomhoff, R
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Meyer, H E
    Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture: A NOREPOS study2014Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 25, nr 11, s. 2545-2554Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51 % higher risk in the lowest compared to the highest quartile.

    INTRODUCTION:

    Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (α-tocopherol) has potent antioxidant properties in humans. The relationship between circulating α-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum α-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up.

    METHODS:

    We performed a case-cohort analysis among 21,774 men and women aged 65-79 years who participated in four community-based health studies in Norway 1994-2001. Serum α-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample (n = 1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed.

    RESULTS:

    Median (25, 75 percentile) serum α-tocopherol was 30.0 (22.6, 38.3) μmol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95 % confidence interval (CI) 1.04-1.20) per 10-μmol/L decrease in serum α-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95 % CI 1.17-1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95 % CI 1.05-1.77) in first versus fourth quartile of serum α-tocopherol/total cholesterol ratio.

    CONCLUSIONS:

    Low serum concentrations of α-tocopherol were associated with increased risk of hip fracture in older Norwegians.

  • 232. Hostmann, Arwed
    et al.
    Jasse, Kerstin
    Schulze-Tanzil, Gundula
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Oberholzer, Andreas
    Ertel, Wolfgang
    Tschoeke, Sven K
    Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins2008Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, nr 1, s. R8-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: The innate immune response to trauma hemorrhage involves inflammatory mediators, thus promoting cellular dysfunction as well as cell death in diverse tissues. These effects ultimately bear the risk of post-traumatic complications such as organ dysfunction, multiple organ failure, or adult respiratory distress syndrome. In this study, a murine model of resuscitated hemorrhagic shock (HS) was used to determine the apoptosis in spleen as a marker of cellular injury and reduced immune functions. METHODS: Male C57BL-6 mice were subjected to sham operation or resuscitated HS. At t = 0 hours, t = 24 hours, and t = 72 hours, mice were euthanized and the spleens were removed and evaluated for apoptotic changes via DNA fragmentation, caspase activities, and activation of both extrinsic and intrinsic apoptotic pathways. Spleens from untreated mice were used as control samples. RESULTS: HS was associated with distinct lymphocytopenia as early as t = 0 hours after hemorrhage without regaining baseline levels within the consecutive 72 hours when compared with sham and control groups. A rapid activation of splenic apoptosis in HS mice was observed at t = 0 hours and t = 72 hours after hemorrhage and predominantly confirmed by increased DNA fragmentation, elevated caspase-3/7, caspase-8, and caspase-9 activities, and enhanced expression of intrinsic mitochondrial proteins. Accordingly, mitochondrial pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were inversely expressed within the 72-hour observation period, thereby supporting significant pro-apoptotic changes. Solely at t = 24 hours, expression of the anti-apoptotic Mcl-1 protein shows a significant increase when compared with sham-operated and control animals. Furthermore, expression of extrinsic death receptors were only slightly increased. CONCLUSION: Our data suggest that HS induces apoptotic changes in spleen through a biphasic caspase-dependent mechanism and imply a detrimental imbalance of pro- and anti-apoptotic mitochondrial proteins Bax, Bcl-2, and Mcl-1, thereby promoting post-traumatic immunosuppression.

  • 233. Hovelius, Lennart
    et al.
    Rahme, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Primary anterior dislocation of the shoulder: long-term prognosis at the age of 40 years or younger.2016Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 24, nr 2, s. 330-42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: We describe the long-term prognosis in 257 first-time anterior shoulder dislocations (255 patients, aged 12-40 years) registered at 27 Swedish emergency units between 1978 and 1979.

    METHODS: Half the shoulders were immobilised for 3-4 weeks after repositioning. Follow-ups were performed after two (questionnaire), five (questionnaire), 10 (questionnaire and radiology) and 25 (questionnaire and radiology) years in 227 patients (229 shoulders). Twenty-eight patients died during the 25 years of observation.

    RESULTS: Early movement or immobilisation after the primary dislocation resulted in the same long-term prognosis. Recurrences increased up to 10 years of follow-up, but, after 25 years, 29 % of the shoulders with ≥2 recurrences appeared to have stabilised over time. Arthropathy increased from 9 % moderate to severe and 11 % mild at 10 years, to 34 % moderate to severe and 27 % mild after 25 years. Alcoholics had a poorer prognosis with respect to dislocation arthropathy (P < 0.001). Age <25 years and/or bilateral instability represent a poorer prognosis, where stabilising surgery is necessary in every second shoulder. Fracture of the greater tuberosity means a good prognosis, and we have found no evidence that athletic activity, gender, a Hill-Sachs lesion and minor rim fractures had any prognostic impact. During the 25 years in which these patients were followed, 28/255 died (11 %), representing a mortality rate (SMR) that was more than double that of the general Swedish population (P < 0.001).

    CONCLUSION: Almost half of all first-time dislocations at the age of <25 years will have stabilising surgery and two-thirds will develop different stages of arthropathy within 25 years.

  • 234. Hovelius, Lennart
    et al.
    Sandström, Björn
    Olofsson, Anders
    Svensson, Olle
    Rahme, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The effect of capsular repair, bone block healing, and position on the results of the Bristow-Latarjet procedure (study III): long-term follow-up in 319 shoulders2012Ingår i: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 21, nr 5, s. 647-660Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    We evaluated the results of the May modification of the Bristow-Latarjet procedure ("coracoid in standing position") in 319 shoulders with respect to (1) coracoid healing and position and (2) surgical treatment of the joint capsule.

    METHODS:

    From 1980 until 2004, all shoulders with a Bristow-Latarjet repair were registered at our hospital. This study consists of 3 different cohorts with respect to follow-up. Series 1, 118 shoulders operated on during 1980 through 1985, had 15 years' radiographic and clinical follow-up. Series 2, 167 shoulders that had surgery during 1986 through 1999, underwent retrospective follow-up by a questionnaire and scores-Western Ontario Shoulder Instability Index; Disabilities of the Arm, Shoulder and Hand; and Subjective Shoulder Value-after 10 to 23 years. Series 3, 34 shoulders treated during 2000 through 2004, with an added modified Bankart repair ("capsulopexy") in 33 shoulders, were prospectively followed up for 5 to 8 years with the same questionnaire and scores as series 2.

    RESULTS:

    Of 319 shoulders, 16 (5%) had 1 or more redislocations and 3 of these (1%) had revision surgery because of remaining instability. One or more subluxations were reported in 41 shoulders (13%). The worst scores were found in 16 shoulders with 2 or more subluxations (P < .001). Radiographs showed bony healing in 246 of 297 shoulders (83%), fibrous union in 34 (13%), migration by 0.5 cm or more in 14 (5%), and no visualization in 3 (1%). Five of six shoulders that had the transplant positioned 1 cm or more medial to the glenoid rim had redislocations (83%, P = .001). Shoulders with migrated transplants did not differ from those with bony or fibrous healing with respect to redislocations and subluxations. When just a horizontal capsular shift was added to the transfer, the recurrence rate (redislocations or subluxations) decreased, with 2 of 53 (4%)compared with 37 of 208 (18%) with just anatomic closure of the capsule (P = .005), and the Western Ontario Shoulder Instability Index score improved (92 vs 85.6, P = .048). In total, for 307 of 319 shoulders (96%), patients were satisfied or very satisfied at final follow-up.

    CONCLUSION:

    The open Bristow-Latarjet procedure yields good and consistent results, with bony fusion of the coracoid in 83%. A position of the coracoid 1 cm or more medial to the rim meant significantly more recurrences. The rate of recurrences decreased and subjective results improved when a horizontal capsular shift was added to the coracoid transfer.

  • 235. Hovelius, Lennart
    et al.
    Vikerfors, Ola
    Olofsson, Anders
    Svensson, Olle
    Rahme, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bristow-Latarjet and Bankart: a comparative study of shoulder stabilization in 185 shoulders during a seventeen-year follow-up2011Ingår i: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 20, nr 7, s. 1095-1101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In 2 Swedish hospitals, 88 consecutive shoulders underwent Bankart repair (B), and 97 consecutive shoulders underwent Bristow-Latarjet repair (B-L) for traumatic anterior recurrent instability.

    Materials and methods: Mean age at surgery was 28 years (B-L group) and 27 years (B group). All shoulders had a follow-up by letter or telephone after a mean of 17 years (range, 13-22 years). The patients answered a questionnaire and completed the Western Ontario Shoulder Index (WOSI), Disability of Arm Shoulder and Hand (DASH), and SSV (Simple Shoulder Value) assessments.

    Results: Recurrance resulted revision surgery in 1 shoulder in the B-L group and in 5 shoulders in the B group (P=.08). Redislocation or subluxation after the index operation occurred in 13 of 97 B-L shoulders and in 25 of 87 of B shoulders (after excluding 1 patient with arthroplasty because of arthropathy, P=.017). Of the 96 Bristow shoulders, 94 patients were very satisfied/satisfied compared with 71 of 80 in the B series (P=.01). Mean WOSI score was 88 for B-L shoulders and 79 for B shoulders (P=.002). B-L shoulders also scored better on the DASH (P=.002) and SSV (P=.007). Patients had 11 degrees loss of subjectively measured outward rotation with the arm at the side after B-L repair compared with 19 degrees after Bankart (P=.012). The original Bankart, with tunnels through the glenoid rim, had less redislocation(s) or subluxation(s) than shoulders done with anchors (P=.048).

    Conclusions: Results were better after the Bristow-Latarjet repair than after Bankart repairs done with anchors with respect to postoperative stability and subjective evaluation. Shoulders with original Bankart repair also seemed to be more stable than shoulders repaired with anchors.

    Level of evidence: Level III, Retrospective Case Control Study, Treatment Study.

  • 236. Hsu, Yi-Hsiang
    et al.
    Zillikens, M. Carola
    Wilson, Scott G.
    Farber, Charles R.
    Demissie, Serkalem
    Soranzo, Nicole
    Bianchi, Estelle N.
    Grundberg, Elin
    Liang, Liming
    Richards, J. Brent
    Estrada, Karol
    Zhou, Yanhua
    van Nas, Atila
    Moffatt, Miriam F.
    Zhai, Guangju
    Hofman, Albert
    van Meurs, Joyce B.
    Pols, Huibert A. P.
    Price, Roger I.
    Nilsson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Pastinen, Tomi
    Cupples, L. Adrienne
    Lusis, Aldons J.
    Schadt, Eric E.
    Ferrari, Serge
    Uitterlinden, Andre G.
    Rivadeneira, Fernando
    Spector, Timothy D.
    Karasik, David
    Kiel, Douglas P.
    An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits2010Ingår i: PLoS genetics, ISSN 1553-7390, Vol. 6, nr 6, s. e1000977-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6 x 10(-8)), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6 x 10(-13); SOX6, p = 6.4 x 10(-10)) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation.

  • 237.
    Hu, Lijuan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin, Klinisk virologi.
    Andersson, G.
    Jonsson, Kenneth B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Lind, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Adamts1 is highly induced in rachitic bones of FGF23 transgenic mice and participates in degradation of non-mineralized bone matrix collagen2013Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 430, nr 3, s. 901-906Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transgenic mice overexpressing fibroblast growth factor 23 (FGF23) in osteoblasts have a rachitic bone phenotype. These mice display hypomineralized bones, increased expression of osteoblast markers, but osteoclast numbers are unaltered or slightly reduced. Paradoxically, they show increased serum levels of the bone resorption marker CTX, a type I collagen degradation fragment. Here we analyzed a matrix metalloproteinase- (MMP-) like secreted protease, Adamts1, that has previously been associated with osteoblastic type I collagen breakdown in vitro. Bones from FGF23 transgenic (tg) mice displayed increased Adamts1 protein upon both immunohistological staining and Western blotting. We further found Adamts1 protein together with excessively degraded type I collagen in the non-mineralized bone fraction of FGF23 tg mice. A similar degradation pattern of type I collagen was noticed upon forced expression of Adamts1 in osteoblastic cells in vitro. Importantly, these Adamts1-expressing osteoblastic cells exhibited increased release of CTX fragments when cultured on demineralized bone discs. Together, these results demonstrate for the first time that Adamts1 can be highly induced in bone tissue and that this MMP-like protease can increase osteoblastic release of CTX fragments from non-mineralized bone. Thus, Adamts1 potentially contributes to the increased serum levels of CTX in rickets/osteomalacia.

  • 238.
    Hu, Lijuan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Jonsson, Kenneth B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Andersén, Harriet
    Edenro, Anne
    Bohlooly-Y, Mohammad
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Lind, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Over-expression of Adamts1 in mice alters bone mineral density2012Ingår i: Journal of Bone and Mineral Metabolism, ISSN 0914-8779, E-ISSN 1435-5604, Vol. 30, nr 3, s. 304-311Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ADAMTS1, a secreted multifunctional metalloproteinase with disintegrin and thrombospondin motifs, is an early response gene of parathyroid hormone (PTH) in osteoblasts. Mice engineered to lack Adamts1 are smaller compared to wild-type (WT) mice and ADAMTS1 metalloproteinase activity has been shown to increase osteoblastic growth in collagen gels. However, there are no reports investigating the consequence of Adamts1 over-expression on bone tissue in vivo. Here, we analyze bones of female and male transgenic (TG) mice over-expressing mouse Adamts1 using peripheral quantitative computed tomography to evaluate its effect on bone shape and mineral density. Western blotting of protein extracts and immunohistochemistry of bone sections reveal increased presence of Adamts1 protein in TG bones compared to WT bones. Phenotypic analyses of femur show that female TG mice have reduced metaphyseal total density, trabecular bone mineral density and trabecular mineral content. In contrast, male TG mice which were without changes in the metaphysis showed increased total density and cortical density at the mid-diaphysis cortical site. Female TG mice showed no significant changes at the cortical site compared to WT mice. Furthermore, diaphyseal endosteal compartment was only affected in male TG mice. Along these lines, Adamts1 increased blood levels of PTH only in females whereas it reduced osteocalcin levels only in males. These results reveal that Adamts1 has an impact on bone mineral density and thus further confirm Adamts1 as a potent regulator of bone remodeling.

  • 239. Huisstede, Bionka M A
    et al.
    Hoogvliet, Peter
    Coert, J Henk
    Fridén, Jan
    Wilbrand, Stephen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Dupuytren disease: european hand surgeons, hand therapists, and physical medicine and rehabilitation physicians agree on a multidisciplinary treatment guideline: results from the HANDGUIDE Study2013Ingår i: Plastic and reconstructive surgery (1963), ISSN 0032-1052, E-ISSN 1529-4242, Vol. 132, nr 6, s. 964e-976eArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Multidisciplinary treatment guidelines for Dupuytren disease can aid in optimizing the quality of care for patients with this disorder. Therefore, this study aimed to achieve consensus on a multidisciplinary treatment guideline for Dupuytren disease.

    METHODS:

    A European Delphi consensus strategy was initiated. A systematic review reporting on the effectiveness of interventions was conducted and used as an evidence-based starting point for this study. In total, 39 experts (hand surgeons, hand therapists, and physical medicine and rehabilitation physicians) participated in the Delphi consensus strategy. Each Delphi round consisted of a questionnaire, an analysis, and a feedback report.

    RESULTS:

    After four Delphi rounds, consensus was achieved on the description, symptoms, and diagnosis of Dupuytren disease. No nonsurgical interventions were included in the guideline. Needle and open fasciotomy, and a limited fasciectomy and dermofasciectomy, were seen as suitable surgical techniques for Dupuytren disease. Factors relevant for choosing one of these surgical techniques were identified and divided into patient-related (age, comorbidity), disease-related (palpable cord, previous surgery in the same area, skin involvement, time of recovery, recurrences), and surgeon-related (years of experience) factors. Associations of these factors with the choice of a specific surgical technique were reported in the guideline. Postsurgical rehabilitation should always include instructions and exercise therapy; postsurgical splinting should be performed on indication. Relevant details for the use of surgical and postsurgical interventions were described.

    CONCLUSION:

    This treatment guideline is likely to promote further discussion on related clinical and scientific issues and may therefore contribute to better treatment of patients with Dupuytren disease.

  • 240.
    Hulsart Billström, Gry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bone Regeneration with Cell-free Injectable Scaffolds2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Autologous bone grafting is commonly used throughout the world. Autograft both fills the void and is bone inductive, housing the particular cells that are needed for bone regeneration. However, a regenerative complement to autograft is of great interest as the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of a limited volume of material. Two such regenerative products that utilise bone morphogenetic protein (BMP)-7 and -2 have been used for more than a decade clinically. Unfortunately, several side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery and use of supra physiological doses of the BMPs due to poor localisation and retention of the growth factor. The purpose of this thesis was to harness the strong inductive capacity of the BMP-2 by optimising the carrier of this bioactive protein, thereby minimising the side effects that are associated with the clinical products and facilitating safe and localised bone regeneration. We focused on an injectable hyaluronan-based carrier developed through polymer chemistry at the University of Uppsala. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident enzymes. Earlier studies have shown improved properties when adding hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that bone formation was enhanced when using nano-sized hydroxyapatite. In Paper II, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. We wished to further develop the carrier system, but were lacking an animal model with relatively high throughput, facilitated access, paired data, and we were also committed to the 3Rs of refinement, reduction, and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper III. In Paper IV, we sought to further optimise the biomaterial properties of the hydrogel through covalent bonding of bisphosphonates to the hyaluronan hydrogel. This resulted in exceptional retention of the growth factor BMP-2. In Paper V, SPECT/PET/µCT was combined as a tri-modal imaging method to allow visualisation of the biomaterial’s in situ action, in terms of drug retention, osteoblast activity and mineralisation. Finally, in Paper VI the correlation between existing in vitro results with in vivo outcomes was observed for an array of biomaterials. The study identified a surprisingly poor correlation between in vitro and in vivo assessment of biomaterials for osteogenesis.

    Delarbeten
    1. Calcium phosphates compounds in conjunction with hydrogel as carrier for BMP-2: A study on ectopic bone formation in rats
    Öppna denna publikation i ny flik eller fönster >>Calcium phosphates compounds in conjunction with hydrogel as carrier for BMP-2: A study on ectopic bone formation in rats
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    2011 (Engelska)Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 7, nr 8, s. 3042-3049Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Current treatment of fractures often involves the use of bone graft or bone morphogenetic proteins (BMP) to induce fracture healing, especially in patients with a compromised healing capacity. BMP has to be delivered in conjunction with a carrier. Unfortunately, there are drawbacks and limitations with current carriers, including their bovine origin which carries the risk of an immunological response. The physical properties also limit the use to open surgical procedures, as it cannot be injected. New carriers with improved properties are therefore needed. The aim of this study was to assess the ectopic bone forming capability of various calcium phosphate compounds when used in conjunction with a hydrogel as the carrier for BMP-2. Five different ceramic additives were tested, including beta-tricalcium phosphate and four types of hydroxyapatite (HAP) (nanoHAP, HAP, clods of HAP >100 mu m, and the biomimetic HAP Ostim35 (R)). The compounds were injected into the thigh muscle of rats, where it formed a gel in situ. After 4 weeks bone formation was evaluated by peripheral quantitative computed tomography and histology. The major finding was that the 20 nm nanoHAP yielded a higher bone density than the other additives (P = 0.0008, ANOVA with Tukey's multiple comparison test). We hypothesize that the higher bone density induced by nanoHAP might be due to nanocrystals of calcium phosphate acting as direct building blocks for biomineralization.

    Nyckelord
    Calcium phosphates, Hydrogel, Injectable, Nanosized, In vivo
    Nationell ämneskategori
    Medicin och hälsovetenskap Polymerkemi Teknik och teknologier
    Forskningsämne
    Kemi med inriktning mot polymerkemi; Teknisk fysik med inriktning mot materialvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-157018 (URN)10.1016/j.actbio.2011.04.021 (DOI)000293259500004 ()
    Tillgänglig från: 2011-08-16 Skapad: 2011-08-15 Senast uppdaterad: 2018-06-26Bibliografiskt granskad
    2. Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates
    Öppna denna publikation i ny flik eller fönster >>Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates
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    2013 (Engelska)Ingår i: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 24, nr 5, s. 1201-1209Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The possibility to affect bone formation by using crushed versus solid hydrogels as carriers for bone morphogenetic protein 2 (BMP-2) was studied. Hydrogels, based on chemical crosslinking between hyaluronic acid and poly(vinyl alcohol) derivatives, were loaded with BMP-2 and hydroxyapatite. Crushed and solid forms of the gels were analyzed both in vitro via a release study using I-125 radioactive labeling of BMP-2, and in vivo in a subcutaneous ectopic bone model in rats. Dramatically different morphologies were observed for the ectopic bone formed in vivo in the two types of gels, even though virtually identical release profiles were observed in vitro. Solid hydrogels induced formation of a dense bone shell around non-degraded hydrogel, while crushed hydrogels demonstrated a uniform bone formation throughout the entire sample. These results suggest that by crushing the hydrogel, the construct's three-dimensional network becomes disrupted. This could expose unreacted functional groups, making the fragment's surfaces reactive and enable limited chemical fusion between the crushed hydrogel fragments, leading to similar in vitro release profiles. However, in vivo these interactions could be broken by enzymatic activity, creating a macroporous structure that allows easier cell infiltration, thus, facilitating bone formation.

    Nationell ämneskategori
    Teknik och teknologier Naturvetenskap Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-201244 (URN)10.1007/s10856-013-4877-6 (DOI)000318510200008 ()
    Tillgänglig från: 2013-06-10 Skapad: 2013-06-10 Senast uppdaterad: 2018-12-04
    3. A uni-cortical femoral defect model in the rat: evaluation using injectable hyaluronan hydrogel as a carrier for bone morphogenetic protein-2
    Öppna denna publikation i ny flik eller fönster >>A uni-cortical femoral defect model in the rat: evaluation using injectable hyaluronan hydrogel as a carrier for bone morphogenetic protein-2
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    2015 (Engelska)Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 9, nr 7, s. 799-807Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The development of biomaterial for bone regeneration requires animal models that are reliable and designed to mimic clinically relevant situations. We have previously investigated hydrogels comprised of modified hyaluronic acid and polyvinyl alcohol in models of ectopic bone formation. This hydrogel induces bone regeneration when loaded with bone morphogenetic proteins (BMPs). To allow further optimization of hydrogels, we developed a new, femoral, non-critical-sized cortical defect model. In the rat femur, we drilled standardized, elongated unilateral cortical defects that did not require stabilization and that could be created bilaterally to allow paired comparisons of biomaterials. After optimizing the defect size, subsequent stress fractures occurred in only 8% and the defect healed partially over the 40 day study period. In a time-course experiment, we treated bone defects with the previously studied hyaluronan hydrogel loaded with 10 µg hydroxyapatite and 6 µg BMP-2. The shape of the defect allowed controlled containment of the material within the defect. The defect in the right leg was left untreated, while the left defect was filled with 40 µl of the BMP hydrogel. As determined by pQCT analysis, the treated defects had a higher bone mineral content, bone area and bone density than control defects. The relative difference was greatest between the groups at 10 and 20 days and diminished as the defect healed in the untreated legs. We conclude that this animal model allows facile and rapid screening of biomaterials for bone regeneration in cortical femoral defects without requiring external fixation.

    Nationell ämneskategori
    Annan naturvetenskap Övrig annan medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-189868 (URN)10.1002/term.1655 (DOI)000357881900006 ()23225778 (PubMedID)
    Tillgänglig från: 2013-01-04 Skapad: 2013-01-04 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    4. Bisphosphonate-Linked Hyaluronic Acid Hydrogel Sequesters and Enzymatically Releases Active Bone Morphogenetic Protein-2 for Induction of Osteogenic Differentiation
    Öppna denna publikation i ny flik eller fönster >>Bisphosphonate-Linked Hyaluronic Acid Hydrogel Sequesters and Enzymatically Releases Active Bone Morphogenetic Protein-2 for Induction of Osteogenic Differentiation
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    2013 (Engelska)Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 14, nr 9, s. 3055-3063Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Regeneration of bone by delivery of bone morphogenetic proteins (BMPs) from implantable scaffolds is a promising alternative to the existing autologous bone grafting procedures. Hydrogels are used extensively in biomaterials as delivery systems for different growth factors. However, a controlled release of the growth factors is necessary to induce bone formation, which can be accomplished by various chemical functionalities. Herein we demonstrate that functionalization of a hyaluronan (HA) hydrogel with covalently linked bisphosphonate (BP) ligands provides efficient sequestering of BMP-2 in the resulting HA-BP hydrogel. The HA-BP hydrogel was investigated in comparison with its analogue lacking BP groups (HA hydrogel). While HA hydrogel released 100% of BMP-2 over two weeks, less than 10% of BMP-2 was released from the HA-BP hydrogel for the same time. We demonstrate that the sequestered growth factor can still be released by enzymatic degradation of the HA-BP hydrogel. Most importantly, entrapment of BMP-2 in HA-BP hydrogel preserves the growth factor bioactivity, which was confirmed by induction of osteogenic differentiation of mesenchymal stem cells (MSCs) after the cells incubation with the enzymatic digest of the hydrogel. At the same time, the hydrogels degradation products were not toxic to MSCs and osteoblasts. Furthermore, BP-functionalization of HA hydrogels promotes adhesion of the cells to the surface of HA hydrogel. Altogether, the present findings indicate that covalent grafting of HA hydrogel with BP groups can alter the clinical effects of BMPs in bone tissue regeneration.

    Nationell ämneskategori
    Medicinsk bioteknologi
    Identifikatorer
    urn:nbn:se:uu:diva-219176 (URN)10.1021/bm400639e (DOI)000330095500012 ()
    Tillgänglig från: 2014-02-24 Skapad: 2014-02-24 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    5. Non-invasive tri-modal visualisation of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept.
    Öppna denna publikation i ny flik eller fönster >>Non-invasive tri-modal visualisation of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept.
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    bone tissue engineering; hydrogel; computed tomography; positron emission tomography; single-photon emission computed tomography; bone morphogenetic protein 2
    Nationell ämneskategori
    Biologiska vetenskaper Annan medicin och hälsovetenskap
    Forskningsämne
    Biologi
    Identifikatorer
    urn:nbn:se:uu:diva-234698 (URN)
    Forskningsfinansiär
    EU, FP7, Sjunde ramprogrammet
    Tillgänglig från: 2014-10-24 Skapad: 2014-10-23 Senast uppdaterad: 2017-01-10
    6. A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: Results of a multicentre analysis
    Öppna denna publikation i ny flik eller fönster >>A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: Results of a multicentre analysis
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    2016 (Engelska)Ingår i: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 31, s. 312-322Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines.

    Nyckelord
    in vivo, in vitro, correlation, biomaterials, multicentre study
    Nationell ämneskategori
    Biomaterialvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-306778 (URN)10.22203/eCM.v031a20 (DOI)000384895100020 ()27215739 (PubMedID)
    Forskningsfinansiär
    EU, FP7, Sjunde ramprogrammet, 262948
    Tillgänglig från: 2016-11-16 Skapad: 2016-11-03 Senast uppdaterad: 2017-11-29Bibliografiskt granskad
  • 241.
    Hulsart Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Blom, Ashley W.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Beswick, Andrew D.
    Application of scaffolds for bone regeneration strategies: Current trends and future directions2013Ingår i: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 44, s. S28-S33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Scaffolds are extensively used in surgery to replace missing bone and to achieve bony union and fusion. An ideal scaffold should not only maintain, induce, and restore biological functions where cells, extracellular matrix, and growth factors are needed, but also have the right properties with respect to degradation, cell binding, cellular uptake, non-immunogenicity, mechanical strength, and flexibility. Here we examine both the basic science behind the development of scaffolds and comprehensively and systematically review the clinical applications. 

  • 242.
    Hulsart Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Janson, Oscar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Welch, Ken
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Hong, Jaan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Thromboinflammation as bioactivity assessment of H2O2-alkali modified titanium surfaces2019Ingår i: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 30, nr 6, artikel-id 66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The release of growth factors from platelets, mediated by the coagulation and the complement system, plays an important role in the bone formation around implants. This study aimed at exploring the thromboinflammatory response of H2O2-alkali soaked commercially pure titanium grade 2 discs exposed to whole human blood, as a way to assess the bioactivity of the discs. Commercially pure titanium grade 2 discs were modified by soaking in H2O2, NaOH and Ca(OH)2. The platelet aggregation, coagulation activation and complement activation was assessed by exposing the discs to fresh whole blood from human donors. The platelet aggregation was examined by a cell counter and the coagulation and complement activation were assessed by ELISA-measurements of the concentration of thrombin-antithrombin complex, C3a and terminal complement complex. The modified surface showed a statistically significant increased platelet aggregation, coagulation activation and complement activation compared to unexposed blood. The surface also showed a statistically significant increase of coagulation activation compared to PVC. The results of this study showed that the H2O2-alkali soaked surfaces induced a thromboinflammatory response that indicates that the surfaces are bioactive.

  • 243.
    Hulsart Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Selvaraju, Ram Kumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Asplund, Veronika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Bergman, Kristoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen.
    Marsell, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Antoni, Gunnar
    Enheten för nuklearmedicin och PET, Section of Nuclear Medicine and PET.
    Non-invasive tri-modal visualisation of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept.Manuskript (preprint) (Övrigt vetenskapligt)
  • 244.
    Hulsart Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Selvaraju, Ramkumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Asplund, Veronika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Bergman, Kristoffer
    TERMIRA, Stockholm, Sweden.
    Marsell, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept2018Ingår i: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 285, s. 178-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bone morphogenetic proteins (BMP's) are vital for bone and cartilage formation, where bone morphogenetic protein-2 (BMP-2) is acknowledged as a growth factor in osteoblast differentiation. However, uncontrolled delivery may result in adverse clinical effects. In this study we investigated the possibility for longitudinal and non-invasive monitoring of implanted [125I]BMP-2 retention and its relation to ossification at the site of implantation. A unilateral critically sized femoral defect was produced in the left limb of rats while the right femur was retained intact as a paired reference control. The defect was filled with a hyaluronan hydrogel with 25% hydroxyapatite alone (carrier control; n = 2) or combined with a mixture of [125I]BMP-2 (150 μg/ml; n = 4). Bone formation was monitored using micro computed tomography (μCT) scans at 1, 3, 5, 7, 9 and 12 weeks. The retention of [125I]BMP-2 was assessed with single photon emission computed tomography (SPECT), and the bone healing process was followed with sodium fluoride (Na18F) using positron emission tomography (PET) at day 3 and at week 2, 4, and 6. A rapid burst release of [125I]BMP-2 was detected via SPECT. This was followed by a progressive increase in uptake levels of [18F]fluoride depicted by PET imaging that was confirmed as bone formation via μCT. We propose that this functional, non-invasive imaging method allows tri-modal visualisation of the release of BMP-2 and the following in vivo response. We suggest that the potential of this novel technique could be considered for preclinical evaluation of novel smart materials on bone regeneration.

  • 245.
    Hulsart-Billstrom, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    BMP-2 Induced bone regeneration visualized by PET and SPECT2014Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 513-513Artikel i tidskrift (Övrigt vetenskapligt)
  • 246.
    Hulsart-Billstrom, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nouhi, Shirin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Öhman, Caroline
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Iodine-enhanced contrast applicable for microcomputed tomography2014Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 245-246Artikel i tidskrift (Refereegranskat)
  • 247.
    Hulsart-Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bergman, Kristoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Andersson, Brittmarie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Jonsson, Kenneth B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    A uni-cortical femoral defect model in the rat: evaluation using injectable hyaluronan hydrogel as a carrier for bone morphogenetic protein-22015Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 9, nr 7, s. 799-807Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The development of biomaterial for bone regeneration requires animal models that are reliable and designed to mimic clinically relevant situations. We have previously investigated hydrogels comprised of modified hyaluronic acid and polyvinyl alcohol in models of ectopic bone formation. This hydrogel induces bone regeneration when loaded with bone morphogenetic proteins (BMPs). To allow further optimization of hydrogels, we developed a new, femoral, non-critical-sized cortical defect model. In the rat femur, we drilled standardized, elongated unilateral cortical defects that did not require stabilization and that could be created bilaterally to allow paired comparisons of biomaterials. After optimizing the defect size, subsequent stress fractures occurred in only 8% and the defect healed partially over the 40 day study period. In a time-course experiment, we treated bone defects with the previously studied hyaluronan hydrogel loaded with 10 µg hydroxyapatite and 6 µg BMP-2. The shape of the defect allowed controlled containment of the material within the defect. The defect in the right leg was left untreated, while the left defect was filled with 40 µl of the BMP hydrogel. As determined by pQCT analysis, the treated defects had a higher bone mineral content, bone area and bone density than control defects. The relative difference was greatest between the groups at 10 and 20 days and diminished as the defect healed in the untreated legs. We conclude that this animal model allows facile and rapid screening of biomaterials for bone regeneration in cortical femoral defects without requiring external fixation.

  • 248.
    Hulsart-Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bergman, Kristoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Engstrand, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The Effect of Incubation Time of Preformed Injectable Hydrogels on Bone Formation when used as Carrier for rhBMP-22011Ingår i: TERMIS-EU 2011 Abstracts, 2011Konferensbidrag (Refereegranskat)
  • 249.
    Hulsart-Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Carlsson, Elin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Xia, Wei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    In vivo and in vitro performance of Sr-doped hydroxyapatite composite in the form of hollow nano-spheres2012Konferensbidrag (Refereegranskat)
  • 250.
    Hulsart-Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Univ Southampton, Inst Dev Sci, Ctr Human Dev Stem Cells & Regenerat, Bone & Joint Res Grp, Southampton SO9 5NH, Hants, England.
    Dawson, J. I.
    Univ Southampton, Inst Dev Sci, Ctr Human Dev Stem Cells & Regenerat, Bone & Joint Res Grp, Southampton SO9 5NH, Hants, England..
    Hofmann, S.
    Swiss Fed Inst Technol Zurich ETHZ, Inst Biomech, Vladimir Prelog Weg 3, CH-8093 Zurich, Switzerland.;Eindhoven Univ Technol, Dept Biomed Engn, POB 513, NL-5600 MB Eindhoven, Netherlands.;Eindhoven Univ Technol, Inst Complex Mol Syst, POB 513, NL-5600 MB Eindhoven, Netherlands..
    Müller, R.
    Swiss Fed Inst Technol Zurich ETHZ, Inst Biomech, Vladimir Prelog Weg 3, CH-8093 Zurich, Switzerland..
    Stoddart, M. J.
    AO Res Inst Davos, Davos, Switzerland..
    Alini, M.
    AO Res Inst Davos, Davos, Switzerland..
    Redl, H.
    Ludwig Boltzmann Inst Expt & Clin Traumatol, European Inst Excellence Tissue Engn & Regenerat, AUVA Res Ctr, Austrian Cluster Tissue Regenerat,Vienna Branch, Vienna, Austria..
    El Haj, A.
    Keele Univ, Inst Sci & Technol Med, Stoke On Trent, Staffs, England..
    Brown, R.
    UCL, Tissue Repair & Engn Ctr, Inst Orthopaed, Stanmore Campus, London, England..
    Salih, V.
    Univ Plymouth, Peninsula Sch Med & Dent, Plymouth, Devon, England.;UCL, Eastman Dent Inst, London, England..
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Oreffo, R. O. C.
    Univ Southampton, Inst Dev Sci, Ctr Human Dev Stem Cells & Regenerat, Bone & Joint Res Grp, Southampton SO9 5NH, Hants, England..
    A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: Results of a multicentre analysis2016Ingår i: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 31, s. 312-322Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines.

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