Prediction and discrimination of osteoporotic hip fracture in postmenopausal women.

Osteoporotic hip fractures increase dramatically with age and are responsible for considerable morbidity and mortality. Several treatments to prevent the occurrence of hip fracture have been validated in large randomized trials and the current challenge is to improve the identification of individuals at high risk of fracture who would benefit from therapeutic or preventive intervention. We have performed an exhaustive literature review on hip fracture predictors, focusing primarily on clinical risk factors, dual X-ray absorptiometry (DXA), quantitative ultrasound, and bone markers. This review is based on original articles and meta-analyses. We have selected studies that aim both to predict the risk of hip fracture and to discriminate individuals with or without fracture. We have included only postmenopausal women in our review. For studies involving both men and women, only results concerning women have been considered. Regarding clinical factors, only prospective studies have been taken into account. Predictive factors have been used as stand-alone tools to predict hip fracture or sequentially through successive selection processes or by combination into risk scores. There is still much debate as to whether or not the combination of these various parameters, as risk scores or as sequential or concurrent combinations, could help to better predict hip fracture. There are conflicting results on whether or not such combinations provide improvement over each method alone. Sequential combination of bone mineral density and ultrasound parameters might be cost-effective compared with DXA alone, because of fewer bone mineral density measurements. However, use of multiple techniques may increase costs. One problem that precludes comparison of most published studies is that they use either relative risk, or absolute risk, or sensitivity and specificity. The absolute risk of individuals given their risk factors and bone assessment results would be a more appropriate model for decision-making than relative risk. Currently, a group appointed by the World Health Organization and lead by Professor John Kanis is working on such a model. It will therefore be possible to further assess the best choice of threshold to optimize the number of women needed to screen for each country and each treatment.

Microstructural alterations of trabecular and cortical bone in long-term HIV-infected elderly men on successful antiretroviral therapy.

OBJECTIVE: Progress in antiretroviral therapy (ART) has resulted in an almost normal life expectancy for HIV-infected individuals, but an increased risk of fragility fractures has been identified. We investigated the influence of long-term HIV infection on successful ART on bone microstructure in elderly men. DESIGN: A cross-sectional, case­control study. METHODS: Dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) were performed in 28 HIV-positive men between 60 and 70 years old on successful ART. Controls were 112 HIV-negative men matched for age 4 years and BMI (4 kg/ m²). RESULTS: HIV-positive men (median CD4þ cell count, 589 cells/ml; BMI, 24.8 kg/m²) had a median duration of HIV infection of 18.2 years. Compared with HIV-negative men, they had a lower DXA-measured areal bone mineral density at total hip (3.2%, P»0.050) and ultra-distal radius (8.4%, P»0.001). At distal radius and tibia, we observed microstructural alterations with a lower total density (16%, P» 0.005 and 14.3%, P» 0.039), trabecular density (11.6%, P» 0.012 and 12.2%, P» 0.007) and cortical area (17.5%, P» 0.002 and 12.2%, P» 0.01). In addition, they had a lower trabecular number (P» 0.036), higher trabecular spacing (P» 0.027) and lower cortical thickness (19.9%; P» 0.008) at distal radius. beta-crosslaps (CTX) and vitamin D levels were higher than in controls. By multivariate analyses, HIV status, higher CTX levels, lower physical activity and estradiol levels were determinants of bone density and microstructure alterations. CONCLUSION: HIV-infected elderly men on successful ART have trabecular and cortical bone microstructure alterations associated with higher bone resorption, despite adequate vitamin D supplementation.

Association of circulating sclerostin with bone mineral mass, microstructure, and turnover biochemical markers in healthy elderly men and women.

CONTEXT: Sclerostin inhibits bone formation and is involved in the bone response to mechanical loading, but the role and significance of circulating sclerostin are poorly understood. OBJECTIVE: We assessed the association between serum sclerostin and calcitropic hormones, bone turnover marker levels, bone mineral content/density, and microstructure using 3 different immunoassays. DESIGN, SETTING, AND PARTICIPANTS: In a cross-sectional study, serum sclerostin was measured in a cohort of 187 healthy subjects (98 women; 89 men) aged 65 ± 1 (±SD) years. RESULTS: Overall, mean sclerostin (95% confidence interval) was 37.3 (18.0-69.2) ng/L, 1165.8 (464.0-2296.4) ng/L, and 513.5 (250.7-950.9) ng/L with assays I, II, and III, respectively. Serum sclerostin was higher in men with assays II and III. In all 3 assays, sclerostin and PTH were inversely correlated, only after adjustment for whole-body bone mineral content (WB-BMC). After adjustment for sex and WB-BMC, the bone turnover markers amino-terminal propeptide of type I procollagen and carboxyterminal cross-linked telopeptide of type I collagen negatively correlated only with assay II. In all 3 assays, sclerostin positively correlated to WB-BMC, the distal radius and the distal tibia cortical area, cancellous bone volume and trabecular number, and lumbar spine and proximal femur areal bone mineral density after adjustment for sex. CONCLUSION: Sclerostin levels are markedly different according to the immunoassay used. Detection of an association with calcitropic hormones or turnover markers relies on the epitope recognized by the immunoassay and adjustment for bone mass.

Assessment of the 10-year probability of osteoporotic hip fracture combining clinical risk factors and heel bone ultrasound: the EPISEM prospective cohort of 12,958 elderly women.

This study aimed to develop a hip screening tool that combines relevant clinical risk factors (CRFs) and quantitative ultrasound (QUS) at the heel to determine the 10-yr probability of hip fractures in elderly women. The EPISEM database, comprised of approximately 13,000 women 70 yr of age, was derived from two population-based white European cohorts in France and Switzerland. All women had baseline data on CRFs and a baseline measurement of the stiffness index (SI) derived from QUS at the heel. Women were followed prospectively to identify incident fractures. Multivariate analysis was performed to determine the CRFs that contributed significantly to hip fracture risk, and these were used to generate a CRF score. Gradients of risk (GR; RR/SD change) and areas under receiver operating characteristic curves (AUC) were calculated for the CRF score, SI, and a score combining both. The 10-yr probability of hip fracture was computed for the combined model. Three hundred seven hip fractures were observed over a mean follow-up of 3.2 yr. In addition to SI, significant CRFs for hip fracture were body mass index (BMI), history of fracture, an impaired chair test, history of a recent fall, current cigarette smoking, and diabetes mellitus. The average GR for hip fracture was 2.10 per SD with the combined SI + CRF score compared with a GR of 1.77 with SI alone and of 1.52 with the CRF score alone. Thus, the use of CRFs enhanced the predictive value of SI alone. For example, in a woman 80 yr of age, the presence of two to four CRFs increased the probability of hip fracture from 16.9% to 26.6% and from 52.6% to 70.5% for SI Z-scores of +2 and -3, respectively. The combined use of CRFs and QUS SI is a promising tool to assess hip fracture probability in elderly women, especially when access to DXA is limited.