| 1. |
- Aspenberg, Per, 1949-, et al.
(författare)
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Artrosskolan : evidensen måste stärkas
- 2018
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 115
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 2. |
- Eliasson, Pernilla T., et al.
(författare)
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Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release - a cohort study design combined with an experimental study
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin induced tendinopathy. We studied association between statin use and different tendon injuries in two population-based Swedish cohorts by time-dependent Cox regression analysis. Additionally, we tested simvastatin in a 3D cell culture model with human tenocytes. Compared with never-users, current users of statins had a higher incidence of trigger finger with adjusted hazard ratios (aHRs) of 1.50 for men (95% confidence interval [CI] 1.21-1.85) and 1.21 (1.02-1.43) for women. We also found a higher incidence of shoulder tendinopathy in both men (aHR 1.43; 1.24-1.65) and women (aHR 1.41; 0.97-2.05). Former users did not confer a higher risk of tendinopathies. In vitro experiments revealed an increased release of matrix metalloproteinase (MMP)-1 and MMP-13 and a weaker, disrupted matrix after simvastatin exposure. Current statin use seems to increase the risk of trigger finger and shoulder tendinopathy, possibly through increased MMP release, and subsequently, a weakened tendon matrix which will be more prone to injuries.
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| 3. |
- Jarvinen, T. L. N., et al.
(författare)
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Osteoporosis: the emperor has no clothes
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley: 12 months. - 0954-6820 .- 1365-2796. ; 277:6, s. 662-673
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Tidskriftsartikel (refereegranskat)abstract
- Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed. PathophysiologyMost fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty. ScreeningCurrently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture. TreatmentThe evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65-80years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20-25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment.
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| 4. |
- Kharazmi, Mohammad, et al.
(författare)
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Mortality After Atypical Femoral Fractures: A Cohort Study
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 31:3, s. 491-497
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Tidskriftsartikel (refereegranskat)abstract
- Although osteoporotic fracture rates can be reduced by bisphosphonates, prolonged therapy is associated with higher risk of atypical femoral fractures. Ordinary fragility fractures are linked to high mortality rates. We aimed to determine whether atypical femoral fractures also confer excess mortality. Radiographs were reviewed for all patients aged 55 years who had experienced a subtrochanteric or femoral shaft fracture in Sweden in 2008 to 2010. The fractures were classified as either atypical or ordinary. Data on medication use, coexisting conditions, and date of death were obtained from national registers. We estimated multivariable-adjusted relative risks of death after atypical femoral fractures compared with ordinary subtrochanteric or femoral shaft fractures and calculated age- and sex-standardized mortality ratios (SMRs) for atypical and ordinary fractures compared with the population average. During a mean of 4 years of follow-up, 39 of 172 (23%) patients with an atypical fracture had died compared with 588 of 952 (62%) with an ordinary fracture, corresponding to a relative risk of 0.51 (95% confidence interval [CI] 0.38-0.68). The lower risk was evident in both users and nonusers of bisphosphonates. No patient with atypical fracture died in the first year after fracture. Individuals with an ordinary fracture had a higher mortality risk than the general population (SMR=1.82; 95% CI 1.69-1.99), but no excess risk was found in patients with atypical fracture (SMR=0.92; 95% CI 0.65-1.26). We conclude that in contrast to ordinary subtrochanteric and femoral shaft fractures, atypical femoral fractures are not associated with excess mortality. (c) 2015 American Society for Bone and Mineral Research.
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| 5. |
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| 6. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
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Postmenopausal Osteoporosis
- 2016
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 374:21, s. 2095-2097
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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| 7. |
- Schilcher, Jörg, et al.
(författare)
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Atypical femoral fractures are a separate entity, characterized by highly specific radiographic features. A comparison of 59 cases and 218 controls
- 2013
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Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 52:1, s. 389-392
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Tidskriftsartikel (refereegranskat)abstract
- Background: Estimations of the risk of bisphosphonate associated atypical femoral fractures vary between different population-based studies, from considerable to neglectable. A possible explanation for these discrepancies could be different definitions of atypical fractures. We aimed to identify specific radiographic fracture characteristics associated with bisphosphonate use. less thanbrgreater than less thanbrgreater thanMethods: In a previous nationwide study, 59 atypical and 218 ordinary fractures were diagnosed. The atypical fractures were defined by their stress-type fracture pattern. All fractures were now re-assessed by a physician in training, without information about bisphosphonate use. The fracture angle (0-180 degrees) was measured. Presence of local lateral cortical thickening (a callus reaction), more than 2 fragments, or a medial spike was noted. The reader then made a judgment whether the fracture appeared as an atypical fracture based on the ASBMR criteria. less thanbrgreater than less thanbrgreater thanResults: Frequency distribution analysis of the fracture angle showed a distinct subgroup, comprising 25% of all 277 fractures, with a mean of 89 and SD of 10 degrees. Forty-two of 57 patients in this subgroup used bisphosphonates, whereas only 27 of 213 others did (specificity 0.93; 95% CI 0.88-0.96). Presence of a callus reaction had also a high specificity for bisphosphonate use (0.96; 95% CI 0.92-0.98). The ASBMR criteria had a lower specificity, increasing the number of atypical fractures without bisphosphonate use from 13 to 31. This led to a decrease in age-adjusted relative risk associated with bisphosphonate use from 47 (95% CI 26-87) to 19 (95% CI 12-29). less thanbrgreater than less thanbrgreater thanInterpretation: Stress fractures of the femoral shaft are a specific entity, which is easily diagnosed on radiographs and strongly related to bisphosphonate use. Differences in diagnostic criteria may partially explain the large differences in relative risk between different population-based studies.
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| 8. |
- Schilcher, Jörg, et al.
(författare)
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Bisphosphonate Use and Atypical Fractures of the Femoral Shaft
- 2011
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 364:18, s. 1728-1737
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Studies show conflicting results regarding the possible excess risk of atypical fractures of the femoral shaft associated with bisphosphonate use. METHODS In Sweden, 12,777 women 55 years of age or older sustained a fracture of the femur in 2008. We reviewed radiographs of 1234 of the 1271 women who had a subtrochanteric or shaft fracture and identified 59 patients with atypical fractures. Data on medications and coexisting conditions were obtained from national registries. The relative and absolute risk of atypical fractures associated with bisphosphonate use was estimated by means of a nationwide cohort analysis. The 59 case patients were also compared with 263 control patients who had ordinary subtrochanteric or shaft fractures. RESULTS The age-adjusted relative risk of atypical fracture was 47.3 (95% confidence interval [CI], 25.6 to 87.3) in the cohort analysis. The increase in absolute risk was 5 cases per 10,000 patient-years (95% CI, 4 to 7). A total of 78% of the case patients and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33.3 (95% CI, 14.3 to 77.8). The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. The duration of use influenced the risk (odds ratio per 100 daily doses, 1.3; 95% CI, 1.1 to 1.6). After drug withdrawal, the risk diminished by 70% per year since the last use (odds ratio, 0.28; 95% CI, 0.21 to 0.38). CONCLUSIONS These population-based nationwide analyses may be reassuring for patients who receive bisphosphonates. Although there was a high prevalence of current bisphosphonate use among patients with atypical fractures, the absolute risk was small.
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| 9. |
- Schilcher, Jorg, et al.
(författare)
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Bisphosphonates and Atypical Femoral Shaft Fractures REPLY
- 2011
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:4, s. 377-377
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Tidskriftsartikel (refereegranskat)abstract
- Any judgment about the magnitude of a risk must be seen in relation to other risks and benefits. Women with osteoporosis run a high risk of fracture, which is substantially reduced by bisphosphonate therapy.1 The numbers needed to treat with bisphosphonates for 3 years are 91 for hip fractures and 14 for radiologic vertebral fractures.1 Without consideration of duration of use, we found that the number needed to harm given 3 years of treatment was 667 — that is, the benefits with the therapy outweigh the risks. The absolute risk of stress (atypical) fracture in our study tended to be higher with a longer duration of bisphosphonate use. With more than 2 years of treatment, the difference in absolute risk as compared with no treatment was 8 per 10,000 women per year of treatment. This estimate corresponds to a number needed to harm of 417 for a 3-year treatment period. Thus, theoretically, for each stress fracture caused, at least 30 vertebral and about 5 hip fractures will be prevented. This is reassuring. However, without a proper indication, the benefit–risk ratio with bisphosphonate use may not be advantageous.
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| 10. |
- Schilcher, Jörg, 1978-
(författare)
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Epidemiology, Radiology and Histology of Atypical Femoral Fractures : Development of understanding
- 2013
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Ingår i: Acta Orthopaedica. - Linköping : Linköping University Electronic Press. - 1745-3674 .- 1745-3682. ; 84:S352, s. 1-26
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bisphosphonates have been used successfully in the prevention of osteoporosis-related fractures for over two decades. Only recently an association between bisphosphonate use and femoral insufficiency fractures – atypical femoral fractures – has been found.Bone remodeling is necessary to maintain a healthy skeleton. With age this process can get out of balance and bone resorption can outweigh formation of new bone. This can lead to osteoporosis and fractures that occur after minor trauma. Almost half of all women 50 years of age or older will suffer an osteoporosis related fracture during their remaining life. Bisphosphonates inhibit bone resorption, and after some years of treatment an increase in bone mass can be noted. This increase in bone mass can reduce fracture risk by as much as half. However, bisphosphonate use seems associated with the development of femoral insufficiency fractures, so called atypical femoral fractures. This thesis aimed to estimate the risk of atypical femoral fractures in the population and its association with bisphosphonate use. It also describes the radiographic and histologic features of these fractures in order to improve our understanding of the pathophysiological background.Study 1) All women 55 years of age and older, who had sustained a femoral shaft fracture during 2008, were identified through the Swedish National Patient Register. Radiographs of 1234 women were reviewed, and 59 patients with atypical fractures and 263 control patients with common femoral shaft fractures were identified. Atypical femoral fractures were defined by their stress fracture-like appearance. In a cohort analysis, we estimated an age-adjusted relative risk of 47 for bisphosphonate users to suffer an atypical femoral fracture compared to non-users. A total of 78% of the patients with an atypical fracture and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33. The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. These results indicate that bisphosphonate use is strongly associated with atypical femoral fractures. The absolute risk is low and benefits of treatment will outweigh the risks.Study 2) A transverse fracture line and a small but visible callus reaction are well established radiographic features of stress fractures. Radiographs from 59 atypical fracture patients and 218 control patients from Study 1 were re-reviewed to measure fracture angles and to detect callus reactions. The majority of the patients with a transverse fracture angle used bisphosphonates. Fracture angle and callus reaction had a high specificity to detect bisphosphonate treatment. When an oblique fracture line was chosen to define atypical femoral fractures in the cohort from Study 1, the association of atypical femoral fractures to bisphosphonate use became attenuated. Therefore, a correct case definition of atypical femoral fractures is necessary for adequate risk calculations.Study 3) Bone biopsies from 8 patients with atypical femoral fractures were obtained during surgical fixation. The histological analysis of the fracture site itself showed a thin fracture line running perpendicular to the long axis of the femur. Despite ongoing remodeling in the bone adjacent to the fracture gap, no healing occurred within the gap itself. Necrotic material in the gap suggests that strains within the gap might prohibit ingrowth of cells necessary for healing. This mechanism of inhibited healing might share similarities with that of stress fractures in athletes. Although it is highly likely that bisphosphonates play a causative role, the pathogenesis of these fractures is still unclear. It may involve a reduced capacity for targeted remodeling.
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