Management of osteoporosis with FRAX: assessment and intervention thresholds for the UK

The fracture risk assessment tool (FRAX®) tool has recently become available to compute the 10-year probability of fractures in men and women from clinical risk factors (CRFs) with or without the measurement of femoral neck bone mineral density (BMD). The aim of this study [1] was to develop a case-finding strategy for men and women from the UK at high risk of osteoporotic fracture by delineating the fracture probabilities at which BMD testing or intervention should be recommended. Fracture probabilities were computed using the FRAX® tool calibrated to the epidemiology of fracture and death in the UK. An intervention threshold was set by age in men and women, based on the fracture probability equivalent to that of women with a history of a prior osteoporosis-related fracture. In addition, assessment thresholds for the use of BMD testing were explored. Assessment thresholds for the measurement of BMD followed current practice guidelines where individuals were considered to be eligible for assessment in the presence of one or more CRF. An upper assessment threshold (ie, a fracture probability above which patients could be treated without recourse to BMD), was based on optimization of the positive predictive value of the assessment tool. The consequences of assessment and intervention thresholds on the requirement for BMD test and interventions were assessed using the distribution of clinical risk factors and femoral neck BMD for women in the source cohorts used for the development of the FRAX® models.

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Bone loss, weight loss, and weight fluctuation predict mortality risk in elderly men and women

Bone mineral density (BMD) is a dynamic variable and is known to decline with advancing age. Although it has been shown that either low BMD or the greater the difference between two measurements in BMD is associated with all-cause mortality in women, it is not known whether the rate of BMD loss contributes to mortality risk independent of baseline BMD. Furthermore, the associations between BMD and bone loss and mortality in men have not been studied. Body weight is strongly related to BMD, such that higher weight is associated with higher BMD and reduced fracture risk. Although it was suggested that weight loss and weight fluctuation are associated with an increased risk of mortality, it is unknown whether the effect of weight loss or weight fluctuation on mortality is independent of baseline BMD and rate of bone loss. To answer these questions, a recent study [1] collected data from 1059 women and 644 men, older than 60 (as of 1989), of white background. All-cause mortality was recorded annually between 1989 and 2004. BMD at the femoral neck was measured by DXA at baseline and at approximately every 2 yr afterward. Data on incident osteoporotic fractures and concomitant diseases, including cardiovascular diseases, all types of cancer, and type I/II diabetes mellitus, was also recorded.
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Determination of forearm fracture risk in postmenopausal women

A real bone mineral density (aBMD) at the distal radius can predict subsequent wrist fractures, but the actual basis for this association is uncertain. In particular, it is not clear whether fracture risk is determined by BMD per se or by some related parameter. Previously available technologies allowed some assessment of bone size (a confounder of aBMD) and geometry. However, it is now possible to explore this issue in more detail using high-resolution peripheral quantitative computerized tomography (pQCT), which can measure numerous micro- and macrostructural variables in the distal radius, along with volumetric BMD (vBMD) of cortical and trabecular bone separately. The purpose of this report [1] was to evaluate these diverse measures (BMD, bone geometry, bone microstructure, bone strength, and fall load to bone strength ratios) in a population sample of postmenopausal women with and without a prior distal forearm (Colles’) fracture (n=18 in each group).

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Femoral neck BMD is a strong predictor of hip fracture susceptibility in elderly men and women

Despite the sexual dimorphism of bone, hip fracture risk is very similar in men and women at the same absolute bone mineral density (BMD). A recent study was conducted with the objective of elucidating the main structural properties of bone that underlie the measured BMD and that ultimately determine the risk of hip fracture in elderly men and women [1]. This study is part of the Rotterdam Study (a large prospective population-based cohort) and included 147 incident hip fracture cases in 4806 participants with DXA-derived hip structural analysis (mean follow-up, 8.6 y).
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Serum biomarker profile associated with high bone turnover and BMD in postmenopausal women

Early diagnosis of onset osteoporosis is essential for the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD) by dual energy X-ray absorptiometry. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. In this study [1], the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface-enhanced laser-desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine-learning tools. The diagnostic fingerprint was validated in a separate test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 y.

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