Can fall risk be incorporated into fracture risk assessment algorithms: a pilot study of responsiveness to clodronate.

SUMMARY: Fall risk does not significantly impact on the efficacy of the bisphosphonate clodronate in reducing the incidence of fracture. INTRODUCTION: The debate about the efficacy of skeletal therapies on fracture risk in women at increased risk of falling continues. We determined whether fall risk impeded the efficacy of clodronate to reduce osteoporotic fracture incidence. METHODS: This is a post hoc analysis of a 3-year placebo-controlled study of bisphosphonate clodronate involving 5,212 women aged 75 years or more. At entry, self-reported multiple falls in the previous month and ability to rise from a chair were documented. Their interaction with treatment efficacy was examined using Poisson regression. RESULTS: Oral doses of clodronate at 800 mg daily reduced osteoporotic fracture incidence by 24% (hazard ration (HR) 0.76, 95% confidence interval 0.63-0.93). The efficacy was similar in women with recent multiple falls compared to those without (HR 0.61 vs. 0.77, p value for interaction >0.30) or impaired ability in rising compared to those with no impairment (HR 0.79 vs. 0.74, respectively; p value > 0.30). CONCLUSION: Fall risk does not significantly impact on the anti-fracture efficacy of clodronate. If confirmed with other agents, fall risk may be incorporated into risk assessment tools designed to target skeletal therapies.

Ten-year fracture probability identifies women who will benefit from clodronate therapy--additional results from a double-blind, placebo-controlled randomised study.

UNLABELLED: Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors. This study demonstrates that the estimation of an individual's 10-year probability of fracture by the FRAX algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy. INTRODUCTION: Treatments for osteoporosis are targeted largely to patients with low bone density (BMD) or a prior fragility fracture. Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors, but it is important to determine whether the risk so identified can be reduced by intervention. We determined the effect of a bisphosphonate on fracture rates when risk was calculated using a new risk algorithm (FRAX). METHODS: Women aged 75 years or more were recruited to a randomised, double-blind controlled trial of 800 mg oral clodronate (Bonefos) daily over 3 years. Baseline clinical risk factors were entered in the FRAX model to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. The interaction between fracture probability and treatment efficacy was examined by Poisson regression. RESULTS: In 3,974 women, the interaction between fracture probability and treatment efficacy was significant when probability was assessed without BMD (p = 0.043), but not when BMD was included (p = 0.10). Efficacy was more evident in those deemed at highest risk. For example women lying at the 75th percentile of fracture probability in the absence of BMD (10-year probability 24%) treatment reduced fracture risk by 27% (HR 0.73, 95%CI 0.58-0.92). In those with a fracture probability of 30% (90th percentile), the fracture risk reduction was 38% (HR 0.62, 0.46-0.84). CONCLUSIONS: The estimation of an individual's 10-year probability of fracture by the FRAX algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.

Performance of clinical referral criteria for bone densitometry in patients under 65 years of age assessed by spine bone mineral density.

BACKGROUND: A case finding strategy based on a number of established risk factors has been suggested by Royal College of Physicians' (RCP) guidelines to optimise bone densitometry referrals for assessment of osteoporosis. OBJECTIVE: The performance of clinical referral criteria was examined in women and men aged <65 years referred for bone mineral density (BMD) assessment. STUDY DESIGN: Cross sectional observational study over six months. RESULTS: Though BMD tended to be lower in patients with multiple criteria for referral, differences from those referred with a single criterion were not statistically significant. The overall prevalence of osteoporosis was higher than expected in both sexes, 11.6% in women and 27.5% in men (expected prevalences were 8% and <1% respectively). BMD was significantly lower in patients referred with a single criterion compatible with the RCP guidelines than in age matched controls or in those patients referred with non-RCP criteria (mean (SD) Z score -0.47(1.38) v 0.35(1.41), p<0.001). Low body mass index was also significantly associated with a lower than expected BMD. In contrast, spine BMD was higher than expected in those with self reported back pain, loss of height, or spinal curvature (p = NS). CONCLUSION: Most of the criteria recommended by the RCP performed well in identifying relatively younger patients with low BMD and osteoporosis. However, prior fractures and corticosteroid use did not reach statistical significance probably due to inclusion of all energy fractures, and current or past steroid use of unspecified dose or duration. Criteria like loss of height and/or spine curvature perform relatively poorly, reflecting the need for further investigation to better identify those needing BMD assessment.

Studies of bone density, quantitative ultrasound, and vertebral fractures in relation to collagen type I alpha 1 alleles in elderly women.

Previous studies have demonstrated that an Sp1 binding site polymorphism in the collagen type I gene (COLIA1) is related to reduced bone mineral density (BMD) and osteoporotic fractures in certain populations, particularly in the elderly. We have examined the relationship among these COLIA1 Sp1 alleles, BMD, quantitative ultrasound properties of bone, and fractures in a population-based cohort of elderly women from the UK. The study group comprised 314 women aged 75 years and over who agreed to participate in a clinical study of bisphosphonate therapy in preventing bone loss at the hip. Women were enrolled regardless of the presence or absence of osteoporosis, but those with other diseases that might affect skeletal metabolism were excluded. The genotype distribution for the Sp1 polymorphism was in Hardy-Weinberg equilibrium (SS - 78%; Ss - 20%; ss - 2%) but the proportion of individuals who carried the "s" allele (22%) was significantly lower than previously observed in another study of the UK population (37.1%) (P < 0.001). There were no significant associations between COLIA1 genotypes and metacarpal cortical index, BMD of the forearm, tibial SOS, calcaneal SOS, or calcaneal BUA. While there was a trend towards lower BMD values at the hip in patients with Ss and ss genotypes, this was not statistically significant (SS = 0.721 +/- 0.14; Ss = 0.704 +/- 0.13; ss = 0.683 +/- 0.20 P = 0.6). Prevalent vertebral fractures occurred in 22% of subjects and prior fractures of the wrist, ankle, and hip were reported by 20%, but there was no significant difference in COLIA1 genotype distribution between fracture patients and controls. We conclude that COLIA1 Sp1 alleles are not significantly associated with BMD, ultrasound properties of bone, or fractures in this population-based sample of elderly women.

Atypical familial Paget's disease of bone.

We report unusual clinical and radiological features of Paget's disease of bone in three family members. All three patients had satisfactory biochemical and symptomatic response to treatment with an intravenous bisphosphonate (clodronate).