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- Kanis, J A, et al.
(författare)
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Smoking and fracture risk: a meta-analysis.
- 2005
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:2, s. 155-62
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is widely considered a 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 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, 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 using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than 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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- Uitterlinden, André G, et al.
(författare)
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The association between common vitamin D receptor gene variations and osteoporosis : a participant-level meta-analysis
- 2006
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Ingår i: Annals of Internal Medicine. - 0003-4819. ; 145:4, s. 255-264
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear.OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures.DESIGN: Prospective multicenter large-scale association study.SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams.PARTICIPANTS: 26,242 participants (18,405 women).MEASUREMENTS: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures.RESULTS: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model).LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis.CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.
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- Kanis, J A, et al.
(författare)
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The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women.
- 2007
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 18:8, s. 1033-46
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY: BMD and clinical risk factors predict hip and other osteoporotic fractures. The combination of clinical risk factors and BMD provide higher specificity and sensitivity than either alone. INTRODUCTION AND HYPOTHESES: To develop a risk assessment tool based on clinical risk factors (CRFs) with and without BMD. METHODS: Nine population-based studies were studied in which BMD and CRFs were documented at baseline. Poisson regression models were developed for hip fracture and other osteoporotic fractures, with and without hip BMD. Fracture risk was expressed as gradient of risk (GR, risk ratio/SD change in risk score). RESULTS: CRFs alone predicted hip fracture with a GR of 2.1/SD at the age of 50 years and decreased with age. The use of BMD alone provided a higher GR (3.7/SD), and was improved further with the combined use of CRFs and BMD (4.2/SD). For other osteoporotic fractures, the GRs were lower than for hip fracture. The GR with CRFs alone was 1.4/SD at the age of 50 years, similar to that provided by BMD (GR = 1.4/SD) and was not markedly increased by the combination (GR = 1.4/SD). The performance characteristics of clinical risk factors with and without BMD were validated in eleven independent population-based cohorts. CONCLUSIONS: The models developed provide the basis for the integrated use of validated clinical risk factors in men and women to aid in fracture risk prediction.
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- van Meurs, Joyce B, et al.
(författare)
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Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.
- 2008
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Ingår i: JAMA : the journal of the American Medical Association. - Chicago : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 299:11, s. 1277-90
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. OBJECTIVE: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. DESIGN AND SETTING: Prospective, multicenter, collaborative study of individual-level data on 37,534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. MAIN OUTCOME MEASURES: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. RESULTS: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25,052 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 x 10(-8)), as was the Val1330 allele (n = 24,812; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 x 10(-9)). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2 (P = 3.8 x 10(-5)) and 8 mg/cm2 (P = 5.0 x 10(-6)) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20,096 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31,435 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6 Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments. CONCLUSIONS: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10(-7)] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis.
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