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- Kanis, J A, et al.
(author)
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A family history of fracture and fracture risk: a meta-analysis.
- 2004
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In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 35:5, s. 1029-37
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Journal article (peer-reviewed)abstract
- The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.
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| 2. |
- Kanis, J A, et al.
(author)
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A meta-analysis of previous fracture and subsequent fracture risk.
- 2004
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In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 35:2, s. 375-82
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Journal article (peer-reviewed)abstract
- Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.
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| 3. |
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| 4. |
- Kanis, John A, et al.
(author)
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A reference standard for the description of osteoporosis.
- 2008
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In: Bone. - : Elsevier BV. - 8756-3282. ; 42:3, s. 467-75
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Journal article (peer-reviewed)abstract
- In 1994, the World Health Organization published diagnostic criteria for osteoporosis. Since then, many new technologies have been developed for the measurement of bone mineral at multiple skeletal sites. The information provided by each assessment will describe the clinical characteristics, fracture risk and epidemiology of osteoporosis differently. Against this background, there is a need for a reference standard for describing osteoporosis. In the absence of a true gold standard, this paper proposes that the reference standard should be based on bone mineral density (BMD) measurement made at the femoral neck with dual-energy X-ray absorptiometry (DXA). This site has been the most extensively validated, and provides a gradient of fracture risk as high as or higher than that of many other techniques. The recommended reference range is the NHANES III reference database for femoral neck measurements in women aged 20-29 years. A similar cut-off value for femoral neck BMD that is used to define osteoporosis in women can be used for the diagnosis of osteoporosis in men - namely, a value for BMD 2.5 SD or more below the average for young adult women. The adoption of DXA as a reference standard provides a platform on which the performance characteristics of less well established and new methodologies can be compared.
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| 5. |
- Kanis, John A, et al.
(author)
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Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX
- 2009
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In: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 44:6, s. 1049-54
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Bazedoxifene has been shown to significantly decrease the risk of vertebral fractures in postmenopausal women. No significant effect was noted on the risk of clinical fractures, but fracture risk reduction was reported in a post hoc subgroup analysis in a high risk group categorised on the basis of BMD and prior fracture. AIMS: The aim of this study was to re-evaluate the efficacy of bazedoxifene on fracture outcomes avoiding subgroup analysis by examining the efficacy of intervention as a function of fracture risk. METHODS: The phase III study was a double-blind, randomised, placebo- and raloxifene-controlled randomised 3-year multinational study that enrolled 7492 osteoporotic women aged 55 years or more (mean age=66 years). For the present analysis, women taking raloxifene were excluded (n=1849), and we compared the effects of two doses of bazedoxifene (20 and 40 mg daily combined) with placebo on the risk of all clinical fractures as well as the risk of morphometric vertebral fracture. The risk of a major osteoporotic fracture was assessed using region specific FRAX algorithms, and the relationship between pre hoc 10-year fracture probabilities and efficacy examined by Poisson regression. RESULTS: Overall, bazedoxifene was associated with a significant 39% decrease in incident morphometric vertebral fractures (hazard ratio HR=0.61; 95% CI=0.43-0.86; p=0.005) and a non-statistically significant 16% decrease in all clinical fractures (hazard ratio HR=0.84; 95% CI=0.67-1.06; p=0.14) compared to placebo. Hazard ratios for the effect of bazedoxifene on all clinical fractures decreased with increasing fracture probability. In patients with 10-year fracture probabilities at or above 16%, bazedoxifene was associated with a significant decrease in the risk of all clinical fractures. The 16% probability threshold corresponded to the 80th percentile of the study population. Hazard ratios for the effect of bazedoxifene on morphometric vertebral fractures also decreased with increasing fracture probability. In patients with 10-year fracture probabilities above 6.9% (corresponding to the 41st percentile), bazedoxifene was associated with a significant decrease in the risk of morphometric vertebral fractures. At equivalent fracture probability percentiles, the treatment effect of bazedoxifene was greater on vertebral fracture risk than on the risk of all clinical fractures. For example, at the 90th percentile of FRAX probability, bazedoxifene was associated with a relative risk reduction of 33% (95% CI=7-51%) for all clinical fractures and 51% reduction (95% CI=21-69%) for morphometric vertebral fractures. The findings were robust to several sensitivity analyses. CONCLUSION: Bazedoxifene (20 and 40 mg doses combined) significantly decreased the risk of all clinical fractures and morphometric vertebral fractures in women at or above a FRAX based fracture probability threshold. These results, consistent with the previous subgroup analysis, suggest that bazedoxifene should be targeted preferentially to women at high fracture risk.
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| 6. |
- Kanis, John A, et al.
(author)
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FRAX and its applications to clinical practice
- 2009
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In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 44:5, s. 734-43
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Journal article (peer-reviewed)abstract
- The introduction of the WHO FRAX algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. FRAX integrates the influence of several well validated risk factors for fracture with or without the use of BMD. Its use in fracture risk prediction poses challenges for patient assessment, the development of practice guidelines, the evaluation of drug efficacy and reimbursement, as well as for health economics which are the topics outlined in this review.
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| 7. |
- Lindahl, Hans, 1950, et al.
(author)
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The excess mortality due to periprosthetic femur fracture. A study from the Swedish national hip arthroplasty register
- 2007
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In: Bone. - : Elsevier BV. - 8756-3282. ; 40:5, s. 1294-8
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Journal article (peer-reviewed)abstract
- A rare but serious adverse event of total hip replacement (THR) is periprosthetic femoral fracture. The aim of the present study was to assess whether there was an excess mortality due to such a fracture and to estimate the probability of death caused by the fracture. We studied primary total hip replacement in 27,652 men and 35,930 women with osteoarthritis from The Swedish National Hip Arthroplasty Register operated from 1979 to 2000. From the same register we also studied 392 men and 344 women with periprosthetic fracture from 1979 to 2000, all with osteoarthritis as the primary diagnosis. By the special method applied, it was possible to perform the estimation of death due to the fracture event though we could not determine in the individual case whether the fracture caused the death. Compared to the total population of patients operated with a primary THR there was a higher mortality rate immediately after the surgery for patients with periprosthetic fracture and in the longer run for patients below the age of 70 years. At the age of 70 years the estimated probability of death due to the fracture was 2.1% for men and 1.2% for women. At the age of 80 years at fracture the corresponding probabilities were 3.9% and 2.2% for men and women, respectively.
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| 8. |
- Lindberg, Marie, 1975, et al.
(author)
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Liver-derived IGF-I is permissive for ovariectomy-induced trabecular bone loss
- 2006
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In: Bone. - : Elsevier BV. - 8756-3282. ; 38:1, s. 85-92
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Estrogen deficiency results in trabecular bone loss, associated with T-cell proliferation in the bone marrow. Insulin-like growth factor I (IGF-I) is involved in the regulation of both bone metabolism and lymphopoiesis. A major part of serum IGF-I is derived from the liver. The aim of the present study was to investigate the role of liver-derived IGF-I for ovariectomy (ovx)-induced trabecular bone loss. MATERIALS AND METHODS: Mice with adult liver-specific IGF-I inactivation (LI-IGF-I-/-) and wild type mice (WT) were either ovx or sham operated. After 5 weeks, the skeletal phenotype was analyzed by pQCT and microCT. The bone marrow cellularity was analyzed using FACS technique, and mRNA levels were quantified using real-time PCR. RESULTS: Ovx resulted in a pronounced reduction in trabecular bone mineral density (-52%, P < 0.001), number (-45%, P < 0.01) and thickness (-13%, P < 0.01) in WT mice while these bone parameters were unaffected by ovx in LI-IGF-I-/- mice. Furthermore, ovx increased the number of T-cells in the bone marrow of the femur in WT but not in LI-IGF-I-/- mice. Interleukin 7 (IL-7) has been reported to stimulate the formation and function of osteoclasts by inducing the expression of receptor activator of NF-kappaB ligand (RANKL) on T-cells. IL-7 mRNA levels and the RANKL/osteoprotegerin ratio in bone were increased by ovx in WT but not in LI-IGF-I-/- mice. CONCLUSIONS: Liver-derived IGF-I is permissive for ovx-induced trabecular bone loss. Our studies indicate that IGF-I might exert this permissive action by modulation of the number of T-cells and the expression of IL-7, which in turn is of importance for the RANKL/OPG ratio and consequently osteoclastogenesis in the bone marrow.
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