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Ljunggren, Östen
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Publications (10 of 138) Show all publications
Jonsson, E., Hansson-Hedblom, A., Ljunggren, Ö., Akesson, K., Spangeus, A., Kanis, J. A. & Borgstrom, F. (2018). A health economic simulation model for the clinical management of osteoporosis. Osteoporosis International, 29(3), 545-555
Open this publication in new window or tab >>A health economic simulation model for the clinical management of osteoporosis
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2018 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 3, p. 545-555Article in journal (Refereed) Published
Abstract [en]

The objective was to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. Results showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings.

Introduction

The purpose of this study is to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice.

Methods

The analysis was carried out using a model that simulates the individual patients considered for pharmacological treatment during 1 year and their projected osteoporosis treatment pathway, quality-adjusted life years (QALYs) and costs over their remaining lifetime. All patients regardless of treatment or no treatment were simulated. Information on current management of osteoporosis in terms of patient characteristics and treatment patterns were derived from a Swedish osteoporosis research database based on national registers and patient records. Current (standard) clinical management was compared with alternative scenarios mirroring Swedish treatment guidelines.

Results

The national burden in terms of lost QALYs was estimated at 14,993 QALYs and the total economic cost at €776M. Scenario analyses showed that 382–3864 QALYs could be gained at a cost/QALY ranging from cost-saving to €31368, depending on the scenario. The margin of investment, i.e. the maximum amount that could be invested in the healthcare system to achieve these improvements up to the limit of the willingness to pay/QALY, was estimated at €199M on a population level (€3,634/patient).

Conclusions

The analysis showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. From a cost-effectiveness perspective, there is also considerable room for investment to achieve these improvements in the management of osteoporosis.

Keywords
Cost, Fracture, Osteoporosis, Quality-of-life, Register, Sweden
National Category
Health Care Service and Management, Health Policy and Services and Health Economy Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-351263 (URN)10.1007/s00198-017-4325-4 (DOI)000426646900003 ()29196775 (PubMedID)
Available from: 2018-06-11 Created: 2018-06-11 Last updated: 2018-06-11Bibliographically approved
Napoli, N., Langdahl, B. L. L., Ljunggren, Ö., Lespessailles, E., Kapetanos, G., Kocjan, T., . . . Marin, F. (2018). Effects of Teriparatide in Patients with Osteoporosis in Clinical Practice: 42-Month Results During and After Discontinuation of Treatment from the European Extended Forsteo (R) Observational Study (ExFOS). Calcified Tissue International, 103(4), 359-371
Open this publication in new window or tab >>Effects of Teriparatide in Patients with Osteoporosis in Clinical Practice: 42-Month Results During and After Discontinuation of Treatment from the European Extended Forsteo (R) Observational Study (ExFOS)
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2018 (English)In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 103, no 4, p. 359-371Article in journal (Refereed) Published
Abstract [en]

This study aimed to describe clinical outcomes in patients prescribed teriparatide and followed up for 18months after stopping the drug in real-life conditions. The Extended Forsteo (R) Observational Study analysed incident clinical fractures in 6-month intervals using logistic regression with repeated measures. Changes in back pain (visual analogue scale) and health-related quality of life (HRQoL; EQ-5D questionnaire) were analysed using mixed models for repeated measures. Patients were analysed if they had a post-baseline visit, regardless of whether and for how long they took teriparatide. Of 1531 patients analysed (90.7% female, mean age: 70.3years), 76 (5.0%) never took teriparatide. Median treatment duration was 23.6months. The adjusted odds of clinical fracture decreased by 47% in the >12- to 18-month treatment period (p=0.013) compared with the first 6-month period, with no statistically significant reduction in the >18- to 24-month interval. The clinical fracture rate remained stable during the 18 months' post-teriparatide, when approximately 98% of patients took osteoporosis medication (51% bisphosphonates). Clinical vertebral fractures were reduced at every time period compared with the first 6months. Adjusted mean back pain scores decreased and EQ-5D scores increased significantly at each post-baseline observation. In a real-life clinical setting, the risk of clinical fractures declined during 24months of teriparatide treatment. This reduction was maintained 18months after stopping teriparatide. In parallel, patients reported significant improvements in back pain and HRQoL. The results should be interpreted in the context of the non-controlled design of this observational study.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
Back pain, Fracture, Observational study, Osteoporosis, Quality of life, Teriparatide
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-365280 (URN)10.1007/s00223-018-0437-x (DOI)000444448000001 ()29909449 (PubMedID)
Funder
Eli Lilly and Company
Available from: 2018-11-13 Created: 2018-11-13 Last updated: 2018-11-13Bibliographically approved
Harvey, N. C., Oden, A., Orwoll, E., Lapidus, J., Kwok, T., Karlsson, M. K., . . . Johansson, H. (2018). Falls Predict Fractures Independently of FRAX Probability: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study. Journal of Bone and Mineral Research, 33(3), 510-516
Open this publication in new window or tab >>Falls Predict Fractures Independently of FRAX Probability: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study
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2018 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, no 3, p. 510-516Article in journal (Refereed) Published
Abstract [en]

Although prior falls are a well-established predictor of future fracture, there is currently limited evidence regarding the specific value of falls history in fracture risk assessment relative to that of other clinical risk factors and bone mineral density (BMD) measurement. We therefore investigated, across the three Osteoporotic Fractures in Men (MrOS) Study cohorts, whether past falls predicted future fracture independently of FRAX and whether these associations varied with age and follow-up time. Elderly men were recruited from MrOS Sweden, Hong Kong, and USA. Baseline data included falls history (over the preceding 12 months), clinical risk factors, BMD at femoral neck, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the associations between falls, FRAX probability, and incident fracture, adjusting for age, time since baseline, and cohort in base models; further models were used to investigate interactions with age and follow-up time. Random-effects meta-analysis was used to synthesize the individual country associations. Information on falls and FRAX probability was available for 4365 men in USA (mean age 73.5 years; mean follow-up 10.8 years), 1823 men in Sweden (mean age 75.4 years; mean follow-up 8.7 years), and 1669 men in Hong Kong (mean age 72.4 years; mean follow-up 9.8 years). Rates of past falls were similar at 20%, 16%, and 15%, respectively. Across all cohorts, past falls predicted incident fracture at any site (hazard ratio [HR]=1.69; 95% confidence interval [CI] 1.49, 1.90), major osteoporotic fracture (MOF) (HR=1.56; 95% CI 1.33, 1.83), and hip fracture (HR=1.61; 95% CI 1.27, 2.05). Relationships between past falls and incident fracture remained robust after adjustment for FRAX probability: adjusted HR (95% CI) any fracture: 1.63 (1.45, 1.83); MOF: 1.51 (1.32, 1.73); and hip: 1.54 (1.21, 1.95). In conclusion, past falls predicted incident fracture independently of FRAX probability, confirming the potential value of falls history in fracture risk assessment.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
OSTEOPOROSIS, EPIDEMIOLOGY, FRAX, FALLS, FRACTURE, INTERACTION
National Category
Orthopaedics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-350898 (URN)10.1002/jbmr.3331 (DOI)000426731100017 ()29220072 (PubMedID)
Funder
Swedish Research Council
Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-05-17Bibliographically approved
Robinson-Cohen, C., Bartz, T. M., Lai, D., Ikizler, T. A., Peacock, M., Imel, E. A., . . . Kestenbaum, B. R. (2018). Genetic Variants Associated with Circulating Fibroblast Growth Factor 23. Journal of the American Society of Nephrology, 29(10), 2583-2592
Open this publication in new window or tab >>Genetic Variants Associated with Circulating Fibroblast Growth Factor 23
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2018 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 29, no 10, p. 2583-2592Article in journal (Refereed) Published
Abstract [en]

Background: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.

Methods: We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m(2) to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.

Results: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0x10(-24)), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.

Conclusions: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.

Place, publisher, year, edition, pages
AMER SOC NEPHROLOGY, 2018
Keywords
human genetics, fibroblast growth factor 23, mineral metabolism
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-369511 (URN)10.1681/ASN.2018020192 (DOI)000448256700016 ()30217807 (PubMedID)
Funder
Swedish Research CouncilSwedish Research Council, K2009-53X-14691-07-3
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Björk, A., Mellström, D., Ohlsson, C., Karlsson, M., Mallmin, H., Johansson, G., . . . Kindmark, A. (2018). Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden). PLoS ONE, 13(12), Article ID e0209268.
Open this publication in new window or tab >>Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden)
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0209268Article in journal (Refereed) Published
Abstract [en]

Objective: Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD).

Methods: Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69-81), were analyzed. Genotyping was performed for eight SNPs covering the CYP2R1 gene in 2868 men with available samples of DNA. Subjects were followed up concerning incidence of fracture during five years.

Results: There was a significant genetic association with circulating levels of 25(OH)D (4.6-18.5% difference in mean values between SNP alleles), but there were no correlations with levels of calcium, phosphate, PTH or FGF23 for any genetic variant. No differences were found in fracture incidence between the variants. There was an inverse relationship between lower BMD and concomitant higher 25(OH)D for three of the haplotypes (p < 0.005).

Conclusions: Common variants in the CYP2R1 gene encoding Vitamin D 25-hydroxylase correlate with levels of circulating 25(OH)D but do not otherwise associate with measures of calcium and phosphate homeostasis. Presence of the specific haplotypes may be an indicator of risk for low 25(OH)D levels, and may in addition be correlated to bone mineral density.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-373326 (URN)10.1371/journal.pone.0209268 (DOI)000454149400035 ()30576350 (PubMedID)
Funder
Swedish Research Council, 2011-2535
Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-15Bibliographically approved
Westerberg, P.-A., Sterner, G., Ljunggren, Ö., Isaksson, E., Elvarson, F., Dezfoolian, H. & Linde, T. (2018). High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD Stages 3-4: results of a 12-week double-blind, randomized, controlled study. Nephrology, Dialysis and Transplantation, 33(3), 466-471
Open this publication in new window or tab >>High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD Stages 3-4: results of a 12-week double-blind, randomized, controlled study
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2018 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no 3, p. 466-471Article in journal (Refereed) Published
Abstract [en]

Background: Calcidiol insufficiency may accelerate the development of secondary hyperparathyroidism (SHPT). We tested the effect of a substantial increase in calcidiol on mineral metabolism in patients with chronic kidney disease (CKD).

Methods: Ninety-five patients with CKD Stages 3-4, parathyroid hormone (PTH) above 6.8 pmol/L and calcidiol below 75 nmol/L were randomized to receive either cholecalciferol 8000 IU/day or placebo for 12 weeks. The primary endpoint was difference in the mean change in iPTH after 12 weeks. The proportion of participants having a 30% reduction in PTH and the effect on hand grip strength, fatigue and different biochemical variables were also investigated.

Results: Baseline calcidiol was 57.5 ± 22 and 56.8 ± 22 nmol/L in the cholecalciferol and placebo groups, respectively. The corresponding concentrations of PTH were 10.9 ± 5 and 13.1 ± 9 pmol/L. Calcidiol increased to 162 ± 49 nmol/L in patients receiving cholecalciferol, and PTH levels remained constant at 10.5 ± 5 pmol/L. In the placebo group, calcidiol remained stable and PTH increased to 15.2 ± 11 pmol/L. The mean change in PTH differed significantly between the two groups (P < 0.01). The proportion of subjects reaching a 30% decrease in PTH did not differ. No effect on grip strength, fatigue, phosphate or fibroblast growth factor 23 was observed. Cholecalciferol treatment resulted in stable calcium concentrations and a substantial increase in calcitriol.

Conclusion: Treatment with high daily doses of cholecalciferol in patients with CKD Stages 3-4 halts the progression of SHPT and does not cause hypercalcaemia or other side effects.

Keywords
FGF23, cholecalciferol, chronic renal failure, secondary hyperparathyroidism, vitamin D
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-342579 (URN)10.1093/ndt/gfx059 (DOI)000426868500017 ()29156056 (PubMedID)
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-05-23Bibliographically approved
Harvey, N. C., Oden, A., Orwoll, E., Lapidus, J., Kwok, T., Karlsson, M., . . . McCloskey, E. V. (2018). Physical Performance Or Function, But Not Appendicular Lean Mass, Predict Incident Fractures Independently Of FRAX Probability And BMD: Results From The Osteoporotic Fractures In Men (MROS) Cohort. Paper presented at WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, APR 19-22, 2018, Krakow, POLAND. Osteoporosis International, 29, S69-S70
Open this publication in new window or tab >>Physical Performance Or Function, But Not Appendicular Lean Mass, Predict Incident Fractures Independently Of FRAX Probability And BMD: Results From The Osteoporotic Fractures In Men (MROS) Cohort
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2018 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, p. S69-S70Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer London, 2018
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-365681 (URN)10.1007/s00198-018-4470-4 (DOI)000440102400040 ()
Conference
WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, APR 19-22, 2018, Krakow, POLAND
Available from: 2018-11-19 Created: 2018-11-19 Last updated: 2018-11-19Bibliographically approved
Kristjansdottir, H., Lewerin, C., Lerner, U., Waern, E., Ljunggren, Ö., Johansson, H., . . . Mellstrom, D. (2017). Both High And Low Serum Serotonin Levels Predict Incident Non-Vertebral Fractures. Paper presented at WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY. Osteoporosis International, 28, S181-S182
Open this publication in new window or tab >>Both High And Low Serum Serotonin Levels Predict Incident Non-Vertebral Fractures
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2017 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S181-S182Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-347302 (URN)000406278600265 ()
Conference
WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Jonsson, E., Hansson-Hedblom, A., Ljunggren, Ö., Akesson, K., Spangeus, A., Borgstrom, F. & Kanis, J. A. (2017). Cost-Effectiveness Of Complying With Treatment Guidelines In Sweden. Paper presented at WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY. Osteoporosis International, 28, S440-S440
Open this publication in new window or tab >>Cost-Effectiveness Of Complying With Treatment Guidelines In Sweden
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2017 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S440-S440Article in journal, Meeting abstract (Other academic) Published
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:uu:diva-347301 (URN)000406278601034 ()
Conference
WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Mellstrom, D., Ohlsson, C., Ljunggren, Ö., Lorentzon, M., Nilsson, A. G., Lewerin, C., . . . Karlsson, M. (2017). Increased Risk For Incident Hip Fracture In Men With Type 2 Diabetes. Paper presented at WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY. Osteoporosis International, 28, S529-S530
Open this publication in new window or tab >>Increased Risk For Incident Hip Fracture In Men With Type 2 Diabetes
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2017 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S529-S530Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-347303 (URN)000406278601222 ()
Conference
WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
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