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  • 1.
    Melhus, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Snellman, Greta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Blomhoff, Rune
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden2010In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 6, p. 2637-2645Article in journal (Refereed)
    Abstract [en]

    Context: Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. Objective: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. Design and Participants: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. Setting: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. Main Outcome Measure: Time to fracture was measured. Results: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09-2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. Conclusions: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60 degrees , only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

  • 2.
    Michaëlsson, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Baron, John A
    Snellman, Greta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Blomhoff, Rune
    Wolk, Alicja
    Garmo, Hans
    Regional Oncologic Center, Uppsala University, Uppsala.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Plasma vitamin D and mortality in older men: a community-based prospective cohort study2010In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, no 4, p. 841-848Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. Objective: We aimed to examine how vitamin D status relates to overall and cause-specific mortality. Design: The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). Results: During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk. Conclusions: Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.

  • 3.
    Robinson, Yohan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Snellman, Greta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Triebel, Jan
    Department of Rheumatology, Stadtspital Triemli, Zürich, Switzerland..
    Strömqvist, Fredrik
    Lunds Universitet.
    Spine registries generate patient benefit in the century of big data2017In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 17, no 5, p. 755-756, article id S1529-9430(16)31245-1Article in journal (Other academic)
  • 4.
    Snellman, Greta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Boning up on Vitamin D: Observational Studies on Bone and Health2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The primary function of vitamin D in humans is to maintain sufficient circulating calcium concentrations. Low vitamin D levels could result in excessive calcium resorption from bone. Vitamin deficiency may therefore decrease bone mineral density (BMD), resulting in an increased risk of fracture. This thesis sought to determine the association between vitamin D intake and bone health and to estimate circulating levels of vitamin D optimal for bone health without increasing the risk for non-bone disease. Furthermore, the thesis assessed the difference in performance between common serum vitamin D assays and the genetic influence of vitamin D status.

    In prospective population-based cohorts, blood concentrations <40 nmol/L (lowest 5%) increased the risk of fracture in elderly men. Low levels were further associated with a slight decrease in lumbar spine BMD. Both high (>98 nmol/L) and low (<46 nmol/L) vitamin D levels were associated with higher cancer and overall mortality. In another cohort, also of older men and women, no association was found between vitamin D levels and fracture. Low vitamin D levels were weakly associated with decreased total body BMD in men but not in women.

    Dietary intake of vitamin D over a 20-year period in more than 60,000 Swedish women was not associated with osteoporosis or fracture, regardless of calcium intake. During summer, dietary vitamin D intake and other life style habits are of minor importance for the variation in vitamin D levels relative to sun exposure and genes. In summer time, genes explain about half  of the variation in vitamin D levels, but none of the variance in winter time. The variability between vitamin D assays was substantial. Three assays classified 8, 22 and 43% of the same study population as vitamin D insufficient if <50 nmol/L was set as the insufficiency level.

    Based on the results in this thesis, low 25(OH)D levels and low dietary vitamin D intake are not a major cause of fractures in community-dwelling elderly Swedish women and men. Differences in assay performance and potential negative health outcomes of high 25(OH)D levels need to be considered.

    List of papers
    1. Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study
    Open this publication in new window or tab >>Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study
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    2009 (English)In: PloS one, ISSN 1932-6203, Vol. 4, no 11, p. e7747-Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 204 same-sex twins, aged 39-85 years and living at northern latitude 60 degrees, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0-88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3-32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48-86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season. CONCLUSIONS/SIGNIFICANCE: There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.

    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-110673 (URN)10.1371/journal.pone.0007747 (DOI)000271721900006 ()19915719 (PubMedID)
    Available from: 2009-11-23 Created: 2009-11-23 Last updated: 2018-11-30
    2. Determining Vitamin D Status: A Comparison between Commercially Available Assays
    Open this publication in new window or tab >>Determining Vitamin D Status: A Comparison between Commercially Available Assays
    Show others...
    2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 7, p. e11555-Article in journal (Refereed) Published
    Abstract [en]

    Background: Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays. Methodology/Principal Findings: Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLCAPCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81-89), intermediate for RIA (70 nmol/L, 95% CI 66-74) and lowest with CLIA (60 nmol/L, 95% CI 56-64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D. Conclusions/Significance: There are substantial inter-assay differences in performance. The most valid method was HPLCAPCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.

    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-135969 (URN)10.1371/journal.pone.0011555 (DOI)000279822300010 ()20644628 (PubMedID)
    Available from: 2010-12-09 Created: 2010-12-09 Last updated: 2018-08-24
    3. Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden
    Open this publication in new window or tab >>Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden
    Show others...
    2010 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 6, p. 2637-2645Article in journal (Refereed) Published
    Abstract [en]

    Context: Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. Objective: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. Design and Participants: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. Setting: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. Main Outcome Measure: Time to fracture was measured. Results: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09-2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. Conclusions: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60 degrees , only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

    National Category
    Medical and Health Sciences Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-123253 (URN)10.1210/jc.2009-2699 (DOI)000278444000017 ()20332246 (PubMedID)
    Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2018-08-24Bibliographically approved
    4. Serum 25-hydroxyvitamin D in relation to BMD and fractures in a Swedish cohort of women and men
    Open this publication in new window or tab >>Serum 25-hydroxyvitamin D in relation to BMD and fractures in a Swedish cohort of women and men
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background/aim

    Vitamin D insufficiency has been suggested to be common and to cause osteoporotic fractures. Results from previous studies are inconsistent. The aim of our study was to assess if circulating vitamin D is associated with incident fractures and bone mineral density (BMD) among elderly Swedish men and women.

    Method

    A population-based cohort consisting of 1002 Swedish men and women, aged 70-years at baseline with a setting at latitude 60o north, was followed for 7 years. Serum vitamin D (25(OH)D) at baseline was analysed by an immunoassay. Fractures during follow-up were identified from registry data and BMD was measured with DXA. Association between 25(OH)D levels and time to fracture was our primary endpoint and BMD our secondary outcome.

    Result

    Mean S-25(OH)Dlevel was 58 (SD 20) nmol/L and 38% of the participants had levels <50 nmol/L. After multivariable adjustment, S-25(OH)D was only associated with total body BMD among men (P=0.03) but the relation was weak. Each SD increase in S-25(OH)D (approximately 20 nmol/L) conferred a 1% increase in total body BMD. Low vitamin D levels were not associated with lower BMD at the total hip or the lumbar spine in men or women. During follow-up, 155 (15%) of the participants sustained a fracture. No association between 25(OH)D and the rate of fracture was evident. The lowest quintile compared to highest quintile of 25(OH)D conferred a HR of 1.13 (95% CI 0.65-1.94).

    Conclusion

    In a general population of elderly Swedish men and women, serum vitamin D is not a strong determinant of fractures or of low bone mineral density.

    Keywords
    Vitamin D, fracture, BMD, observational study
    National Category
    Orthopaedics
    Research subject
    Epidemiology; Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-159837 (URN)
    Available from: 2011-10-10 Created: 2011-10-10 Last updated: 2018-08-24
    5. Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women
    Open this publication in new window or tab >>Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women
    Show others...
    2012 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no Suppl 1, p. S65-S65Article in journal, Meeting abstract (Other academic) Published
    Abstract [en]

    Context: Vitamin D deficiency may lead to osteoporosis and fracture but the importance of dietary vitamin D intake for skeletal health in adults is uncertain.

    Objective: To investigate associations between long-term dietary intake of vitamin D with risk of fractures and osteoporosis.

    Design: A prospective longitudinal cohort study.

    Setting: The population-based Swedish Mammography Cohort and the subcohort SMC Clinical.

    Participants: 61,433 women (age range 38 to 76 years) were followed for 19 years. Of these, 5,022 participated in the subcohort. Diet was assessed by repeated food frequency questionnaires.   

    Main outcome measures: Incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort.

    Results: 14,738 women experienced any type of first fracture during follow-up, with 3,871 of these being hip fractures. Twenty percent of the women in the subcohort were classified as osteoporotic. A multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for any first fracture was 0.96 (95% CI 0.92-1.01) for the lowest and 1.02 (95% CI 0.96-1.07) for the highest quintile when compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (95% CI, 0.96-1.08) for the lowest and 1.14 (95% CI, 1.03-1.26) for the highest quintile. The odds ratio of osteoporosis by quintiles of vitamin D intake was 1.20 (95% CI, 0.85-1.71) for the lowest and 0.99 (95% CI, 0.78-1.25) for the highest quintile. Bone mineral density, however, were 2% higher at the lumbar spine and 0.3% higher at the total hip in women with highest vs. women with lowest intake of vitamin D (p<0.0001).

    Conclusions: Dietary intake of vitamin D seems to be of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish middle-aged and elderly women.

    Keywords
    Vitamin D, fraktur, BMD, observationsstudie
    National Category
    Orthopaedics
    Research subject
    Epidemiology; Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-159833 (URN)10.1016/j.bone.2012.02.182 (DOI)000304503500157 ()
    Conference
    39th Annual Congress of the European-Calcified-Tissue-Society (ECTS), MAY 19-23, 2012, Stockholm, SWEDEN
    Note
    Also published in the same volume of Bone on pages S136-S137 with DOI 10.1016/j.bone.2012.02.421Available from: 2011-10-10 Created: 2011-10-10 Last updated: 2018-08-24Bibliographically approved
    6. Plasma vitamin D and mortality in older men: a community-based prospective cohort study
    Open this publication in new window or tab >>Plasma vitamin D and mortality in older men: a community-based prospective cohort study
    Show others...
    2010 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, no 4, p. 841-848Article in journal (Refereed) Published
    Abstract [en]

    Background: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. Objective: We aimed to examine how vitamin D status relates to overall and cause-specific mortality. Design: The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). Results: During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk. Conclusions: Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.

    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-134811 (URN)10.3945/ajcn.2010.29749 (DOI)000282234100022 ()20720256 (PubMedID)
    Available from: 2010-12-01 Created: 2010-12-01 Last updated: 2018-08-24
  • 5.
    Snellman, Greta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lemming, Eva Warensjo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, Alicja
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Long-Term Dietary Vitamin D Intake and Risk of Fracture and Osteoporosis: A Longitudinal Cohort Study of Swedish Middle-aged and Elderly Women2014In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 3, p. 781-790Article in journal (Refereed)
    Abstract [en]

    Context: The importance of dietary vitamin D for osteoporotic fracture prevention is uncertain. Objective: Our objective was to investigate associations between dietary vitamin D intake with risk of fracture and osteoporosis. Design and Participants: In the population-based Swedish Mammography Cohort (including 61 433 women followed for 19 years), diet was assessed by repeated food frequency questionnaires. Setting: The study was conducted in 2 municipalities in central Sweden. Main Outcome Measure: Incident fractures were identified from registry data. In a subcohort (n = 5022), bone mineral density was determined by dual-energy x-ray absorptiometry and serum 25-hydroxyvitamin D was measured using HPLC-tandem mass spectrometry. Results: A total of 14 738 women experienced any type of first fracture during follow-up, and 3871 had a hip fracture. Multivariable-adjusted hazard ratio (HR) for any first fracture was 0.96 (95% confidence interval, 0.92-1.01) for the lowest (mean, 3.1 mu g/d) and 1.02 (0.96-1.07) for the highest (mean, 6.9 mu g/d) quintile compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (0.96-1.08) for the lowest and 1.14 (1.03-1.26) for the highest quintile. Intakes >10 mu g/d, compared with <5 mu g/d, conferred an HR of 1.02 (0.92-1.13) for any fracture and an HR of 1.27 (1.03-1.57) for hip fracture. The intake of vitamin D did not affect the odds for osteoporosis, although higher levels were associated with higher bone mineral density (0.3%-2%, P < .0001). A positive association was observed between vitamin D intake and serum 25-hydroxyvitamin D. Conclusions: Dietary intakes of vitamin D seem of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish women.

  • 6.
    Snellman, Greta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Serum 25-hydroxyvitamin D in relation to BMD and fractures in a Swedish cohort of women and menManuscript (preprint) (Other academic)
    Abstract [en]

    Background/aim

    Vitamin D insufficiency has been suggested to be common and to cause osteoporotic fractures. Results from previous studies are inconsistent. The aim of our study was to assess if circulating vitamin D is associated with incident fractures and bone mineral density (BMD) among elderly Swedish men and women.

    Method

    A population-based cohort consisting of 1002 Swedish men and women, aged 70-years at baseline with a setting at latitude 60o north, was followed for 7 years. Serum vitamin D (25(OH)D) at baseline was analysed by an immunoassay. Fractures during follow-up were identified from registry data and BMD was measured with DXA. Association between 25(OH)D levels and time to fracture was our primary endpoint and BMD our secondary outcome.

    Result

    Mean S-25(OH)Dlevel was 58 (SD 20) nmol/L and 38% of the participants had levels <50 nmol/L. After multivariable adjustment, S-25(OH)D was only associated with total body BMD among men (P=0.03) but the relation was weak. Each SD increase in S-25(OH)D (approximately 20 nmol/L) conferred a 1% increase in total body BMD. Low vitamin D levels were not associated with lower BMD at the total hip or the lumbar spine in men or women. During follow-up, 155 (15%) of the participants sustained a fracture. No association between 25(OH)D and the rate of fracture was evident. The lowest quintile compared to highest quintile of 25(OH)D conferred a HR of 1.13 (95% CI 0.65-1.94).

    Conclusion

    In a general population of elderly Swedish men and women, serum vitamin D is not a strong determinant of fractures or of low bone mineral density.

  • 7.
    Snellman, Greta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Warensjö-Lemming, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, Alicja
    Institutet för miljömedicin, Karolinska Institutet.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no Suppl 1, p. S65-S65Article in journal (Other academic)
    Abstract [en]

    Context: Vitamin D deficiency may lead to osteoporosis and fracture but the importance of dietary vitamin D intake for skeletal health in adults is uncertain.

    Objective: To investigate associations between long-term dietary intake of vitamin D with risk of fractures and osteoporosis.

    Design: A prospective longitudinal cohort study.

    Setting: The population-based Swedish Mammography Cohort and the subcohort SMC Clinical.

    Participants: 61,433 women (age range 38 to 76 years) were followed for 19 years. Of these, 5,022 participated in the subcohort. Diet was assessed by repeated food frequency questionnaires.   

    Main outcome measures: Incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort.

    Results: 14,738 women experienced any type of first fracture during follow-up, with 3,871 of these being hip fractures. Twenty percent of the women in the subcohort were classified as osteoporotic. A multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for any first fracture was 0.96 (95% CI 0.92-1.01) for the lowest and 1.02 (95% CI 0.96-1.07) for the highest quintile when compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (95% CI, 0.96-1.08) for the lowest and 1.14 (95% CI, 1.03-1.26) for the highest quintile. The odds ratio of osteoporosis by quintiles of vitamin D intake was 1.20 (95% CI, 0.85-1.71) for the lowest and 0.99 (95% CI, 0.78-1.25) for the highest quintile. Bone mineral density, however, were 2% higher at the lumbar spine and 0.3% higher at the total hip in women with highest vs. women with lowest intake of vitamin D (p<0.0001).

    Conclusions: Dietary intake of vitamin D seems to be of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish middle-aged and elderly women.

  • 8.
    Snellman, Greta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Berglund, Lars
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Determining Vitamin D Status: A Comparison between Commercially Available Assays2010In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 7, p. e11555-Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays. Methodology/Principal Findings: Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLCAPCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81-89), intermediate for RIA (70 nmol/L, 95% CI 66-74) and lowest with CLIA (60 nmol/L, 95% CI 56-64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D. Conclusions/Significance: There are substantial inter-assay differences in performance. The most valid method was HPLCAPCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.

  • 9.
    Snellman, Greta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Olofsson, Sylvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Pedersen, Nancy L.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study2009In: PloS one, ISSN 1932-6203, Vol. 4, no 11, p. e7747-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 204 same-sex twins, aged 39-85 years and living at northern latitude 60 degrees, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0-88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3-32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48-86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season. CONCLUSIONS/SIGNIFICANCE: There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.

  • 10.
    Triebel, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Snellman, Greta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Strömqvist, Fredrik
    Skåne Univ Hosp, Dept Clin Sci & Orthopaed, S-20502 Malmö, Sweden.
    Robinson, Yohan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Women do not fare worse than men after lumbar fusion surgery: Two-year follow-up results from 4,780 prospectively collected patients in the Swedish National Spine Register with lumbar degenerative disc disease and chronic low back pain.2017In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 17, no 5, p. 656-662Article in journal (Refereed)
    Abstract [en]

    BACKGROUND CONTEXT: Proper patient selection is of outmost importance in surgical treatment of degenerative disc disease (DDD) with chronic low back pain (CLBP). Among other factors gender was previously found to influence lumbar fusion surgery outcome.

    PURPOSE: This study investigates whether gender affects clinical outcome after lumbar fusion.

    STUDY DESIGN: National registry cohort study PATIENT SAMPLE: Between 2001 and 2011, 2251 men and 2521 women were followed prospectively within the Swedish National Spine Registry (SWESPINE) after lumbar fusion surgery for DDD and CLBP.

    OUTCOME MEASURES: Patient-reported outcome measures (PROM) visual analogue scale (VAS) for leg and back pain, Oswestry Disability Index (ODI), quality-of-life (QoL) parameter EQ5D and labour status and pain medication were collected preoperatively, 1 and 2 years after surgery.

    METHODS: Gender-differences of baseline data and PROM improvement from baseline were analysed. The effect of gender on clinically important improvement of PROM was determined in a multivariate logistic regression model. Furthermore, gender-related differences in return-to-work were investigated.

    RESULTS: Preoperatively women had worse leg pain (p<0.001), back pain (p=0.002), lower QoL (p<0.001) and greater disability than men (p=0.001). Postoperatively women presented greater improvement 2 years from baseline for pain, function and QoL (all p<0.01). Women had better chances of a clinically important improvement than men for leg pain (OR=1.39, 95% C.I.: 1.19-1.61, p<0.01) and back pain (OR=1.20,95% C.I.:1.03-1.40, p=0.02) as well as ODI (OR=1.24, 95% C.I.:1.05-1.47, p=0.01), but improved at a slower pace in leg pain (p<0.001), back pain (p=0.009), and disability (p=0.008). No gender differences were found in QoL and return-to-work at 2 years postoperatively.

    CONCLUSIONS: Swedish women do not have worse results than men after spinal fusion surgery. Female patients present with worse pain and function preoperatively, but improve more than men do after surgery.

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