Osteoporosis Fracture Risk Assessment Research Articles

Update on fracture risk assessment in osteoporosis.

The assessment of fracture risk is playing an ever-increasing role in osteoporosis clinical management and informing international guidelines for osteoporosis. FRAX, a fracture risk calculator that provides individualized 10-year probabilities of hip and major osteoporotic fracture, has been widely used since 2008. In this review, we recap the development and limitations of intervention thresholds and the role of absolute fracture risk. There is an increasing awareness of disparities and inequities in the setting of intervention thresholds in osteoporosis. The limitations of the simple use of prior fracture or the DXA-derived BMD T -score threshold are increasingly being discussed; one solution is to use fracture risk or probabilities in the setting of such thresholds. This approach also permits more objective assessment of high and very high fracture risk to enable physicians to make choices not just about the need to treat but what agents to use in individual patients. Like all clinical tools, FRAX has limitations that need to be considered, but the use of fracture risk in deciding who to treat, when to treat and what agent to use is a mechanism to target treatment equitably to those at an increased risk of fracture.

Implementation of personalized medicine for fracture risk assessment in osteoporosis.

The present review summarizes our efforts to identify genetic polymorphisms associated with osteoporotic fractures and to establish a genetic risk score (GRS) to predict fracture risk in consecutive Japanese autopsy cases carried out at Tokyo Metropolitan Geriatric Hospital between 1995 and 2011. Three single nucleotide polymorphisms in transforming growth factor β-1, rs1800470; thrombospondin, type 1, domain-containing 7A, rs12673692; and formiminotransferase N-terminal subdomain-containing gene, rs7605378, showed a significant association with vertebral fracture prevalence, whereas five (α-l-iduronidase, rs3755955; C7orf58, rs190543052; homeobox C4, rs75256744; G patch domain-containing gene 1, rs2287679; and Werner syndrome, rs2230009) were significantly associated with femoral fracture. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or of weighted scores estimated from logistic regression coefficients (weighted GRS). Both GRS values using the five single nucleotide polymorphisms adequately predicted femoral fracture prevalence for 924 male subjects; the areas under receiver-operating characteristic curves were 0.750 (95% confidence interval [CI] 0.660-0.840) and 0.770 (95% CI 0.681-0.859), respectively. Logistic regression analysis showed that the odds ratio for the association between fracture prevalence and unweighted GRS ≥3 (n = 124) was 8.39 (95% CI 4.22-16.69, P < 0.001) relative to GRS < 3 (n = 797). Likewise, the odds ratio for a weighted GRS of 6-15 (n = 135) was 7.73 (95% CI 3.89-15.36, P < 0.001) relative to GRS 0-5 (n = 786). Therefore, the GRS based on the risk allele profiles of these five single nucleotide polymorphisms could help identify at-risk individuals and enable implementation of preventive measures for femoral fracture.

Clinical prediction rules in practice: review of clinical guidelines and survey of GPs.

The publication of clinical prediction rules (CPRs) studies has risen significantly. It is unclear if this reflects increasing usage of these tools in clinical practice or how this may vary across clinical areas. To review clinical guidelines in selected areas and survey GPs in order to explore CPR usefulness in the opinion of experts and use at the point of care. A review of clinical guidelines and survey of UK GPs. Clinical guidelines in eight clinical domains with published CPRs were reviewed for recommendations to use CPRs including primary prevention of cardiovascular disease, transient ischaemic attack (TIA) and stroke, diabetes mellitus, fracture risk assessment in osteoporosis, lower limb fractures, breast cancer, depression, and acute infections in childhood. An online survey of 401 UK GPs was also conducted. Guideline review: Of 7637 records screened by title and/or abstract, 243 clinical guidelines met inclusion criteria. CPRs were most commonly recommended in guidelines regarding primary prevention of cardiovascular disease (67%) and depression (67%). There was little consensus across various clinical guidelines as to which CPR to use preferentially. Of 401 responders to the GP survey, most were aware of and applied named CPRs in the clinical areas of cardiovascular disease and depression. The commonest reasons for using CPRs were to guide management and conform to local policy requirements. GPs use CPRs to guide management but also to comply with local policy requirements. Future research could focus on which clinical areas clinicians would most benefit from CPRs and promoting the use of robust, externally validated CPRs.

3D reconstruction of the proximal femur with low-dose digital stereoradiography

Objective: Accurate three-dimensional (3D) geometry of the proximal femur may be helpful for fracture risk evaluation, as well as for planning and assisting surgical procedures. The purpose of this study was to apply and validate a stereoradiographic 3D reconstruction method on the proximal femur from radiographic contours identified on bi-planar radiographs.Materials and Methods: Twenty-five excised non-pathologic proximal femurs were investigated using a low-dose digital radiographic device. Three-dimensional personalized models were reconstructed using the Non-Stereo Corresponding Contours (NSCC) algorithm. Three-dimensional CT-scan reconstructions were defined as geometric references for the comparison protocol, in order to assess the accuracy and reproducibility of the personalized 3D stereoradiographic reconstructions. In addition, the reliability of a set of 3D parameters obtained from stereoradiographic models was evaluated.Results: This study demonstrated the validity of the NSCC method when applied to the proximal femur, with good results for accuracy (mean error = 0.7 mm) and reproducibility (Wilcoxon test: p > 0.28). Moreover, a precision study for the set of 3D parameters yielded a coefficient of variation lower than 5%.Conclusions: Once this approach has been validated in vivo, it should find multiple applications in therapeutic fields (e.g., for surgical planning, computer assisted surgery, etc.), as well as in diagnostic contexts (e.g., equilibrium studies or osteoporosis fracture risk assessment).

Comments on the hypotheses underlying fracture risk assessment in osteoporosis as proposed by the World Health Organization.

It was shown in a recent multivariate analysis of lumbar vertebral (L1-L3) CT scans of 171 women without fractures and 57 fractures somewhere in their skeletons, that regional assessment of the spinal mineral distribution can result in the discrimination of the above patient groups with an accuracy of about 90%. This level of discrimination was possible even in those cases with bone densities below the fracture threshold, where the overlap of patients with and without fractures is the greatest and clinically the most significant. In this region this new analytical technique could also identify a subgroup of patients who not yet had a fracture, but for whom all three lumbar vertebrae were classified as osteoporotic. From these results it follows that the osteoporosis model proposed by the World Health Organization (WHO), which assumes that fragility depends only on a single mean value of bone mineral density (BMD) for a patient, is overly simplistic and requires upgrading to include indices representing the distribution of bone mineral.