Efficacy of weekly teriparatide does not vary by baseline fracture probability calculated using FRAX

Summary The aim of this study was to determine the efficacy of once-weekly teriparatide as a function of baseline fracture risk. Treatment with once-weekly teriparatide was associated with a statistically significant 79 % decrease in vertebral fractures, and in the cohort as a whole, efficacy was not related to baseline fracture risk. Introduction Previous studies have suggested that the efficacy of some interventions may be greater in the segment of the population at highest fracture risk as assessed by the FRAX® algorithms. The aim of the present study was to determine whether the antifracture efficacy of weekly teriparatide was dependent on the magnitude of fracture risk. Methods Baseline fracture probabilities (using FRAX) were computed from the primary data of a phase 3 study (TOWER) of the effects of weekly teriparatide in 542 men and postmenopausal women with osteoporosis. The outcome variable comprised morphometric vertebral fractures. Interactions between fracture probability and efficacy were explored by Poisson regression. Results The 10-year probability of major osteoporotic fractures (without BMD) ranged from 7.2 to 42.2 %. FRAX-based hip fracture probabilities ranged from 0.9 to 29.3 %. Treatment with teriparatide was associated with a 79 % (95 % CI 52–91 %) decrease in vertebral fractures assessed by semiquantitative morphometry. Relative risk reductions for the effect of teriparatide on the fracture outcome did not change significantly across the range of fracture probabilities (p = 0.28). In a subgroup analysis of 346 (64 %) participants who had FRAX probabilities calculated with the inclusion of BMD, there was a small but significant interaction (p = 0.028) between efficacy and baseline fracture probability such that high fracture probabilities were associated with lower efficacy. Conclusion Weekly teriparatide significantly decreased the risk of morphometric vertebral fractures in men and postmenopausal women with osteoporosis. Overall, the efficacy of teriparatide was not dependent on the level of fracture risk assessed by FRAX in the cohort as a whole

A high incidence of vertebral fracture in women with breast cancer

Because treatment for breast cancer may adversely affect skeletal metabolism, we investigated vertebral fracture risk in women with non-metastatic breast cancer. The prevalence of vertebral fracture was similar in women at the time of first diagnosis to that in an age-matched sample of the general population. The incidence of vertebral fracture, however, was nearly five times greater than normal in women from the time of first diagnosis [odds ratio (OR), 4.7; 95% confidence interval (95% CI), 2.3–9.9], and 20-fold higher in women with soft-tissue metastases without evidence of skeletal metastases (OR, 22.7; 95% CI, 9.1–57.1). We conclude that vertebral fracture risk is markedly increased in women with breast cancer. © 1999 Cancer Research Campaig

FRAX™ and the assessment of fracture probability in men and women from the UK

SUMMARY: A fracture risk assessment tool (FRAX) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK. INTRODUCTION: The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily. METHODS: Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions. RESULTS: Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m(2)) ranged from 0.2% at the age of 50 years for women without CRF's to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter. CONCLUSION: The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD

Calibration of FRAX ® 3.1 to the Dutch population with data on the epidemiology of hip fractures

SummaryThe FRAX tool has been calibrated to the entire Dutch population, using nationwide (hip) fracture incidence rates and mortality statistics from the Netherlands. Data used for the Dutch model are described in this paper.IntroductionRisk communication and decision making about whether or not to treat with anti-osteoporotic drugs with the use of T-scores are often unclear for patients. The recently developed FRAX models use easily obtainable clinical risk factors to estimate an individual's 10-year probability of a major osteoporotic fracture and hip fracture that is useful for risk communication and subsequent decision making in clinical practice. As of July 1, 2010, the tool has been calibrated to the total Dutch population. This paper describes the data used to develop the current Dutch FRAX model and illustrates its features compared to other countries.MethodsAge- and sex-stratified hip fracture incidence rates (LMR database) and mortality rates (Dutch national mortality statistics) for 2004 and 2005 were extracted from Dutch nationwide databases (patients aged 50+ years). For other major fractures, Dutch incidence rates were imputed, using Swedish ratios for hip to osteoporotic fracture (upper arm, wrist, hip, and clinically symptomatic vertebral) probabilities (age- and gender-stratified). The FRAX tool takes into account age, sex, body mass index (BMI), presence of clinical risk factors, and bone mineral density (BMD).ResultsFracture incidence rates increased with increasing age: for hip fracture, incidence rates were lowest among Dutch patients aged 50–54 years (per 10,000 inhabitants: 2.3 for men, 2.1 for women) and highest among the oldest subjects (95–99 years; 169 of 10,000 for men, 267 of 10,000 for women). Ten-year probability of hip or major osteoporotic fracture was increased in patients with a clinical risk factor, lower BMI, female gender, a higher age, and a decreased BMD T-score. Parental hip fracture accounted for the greatest increase in 10-year fracture probability.ConclusionThe Dutch FRAX tool is the first fracture prediction model that has been calibrated to the total Dutch population, using nationwide incidence rates for hip fracture and mortality rates. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Dutch FRAX tool a good candidate for implementation into clinical practice

Use of anthropometric indicators in screening for undiagnosed vertebral fractures: A cross-sectional analysis of the Fukui Osteoporosis Cohort (FOC) study

<p>Abstract</p> <p>Background</p> <p>Vertebral fractures are the most common type of osteoporotic fracture. Although often asymptomatic, each vertebral fracture increases the risk of additional fractures. Development of a safe and simple screening method is necessary to identify individuals with asymptomatic vertebral fractures.</p> <p>Methods</p> <p>Lateral imaging of the spine by single energy X-ray absorptiometry and vertebral morphometry were conducted in 116 Japanese women (mean age: 69.9 ± 9.3 yr). Vertebral deformities were diagnosed by the McCloskey-Kanis criteria and were used as a proxy for vertebral fractures. We evaluated whether anthropometric parameters including arm span-height difference (AHD), wall-occiput distance (WOD), and rib-pelvis distance (RPD) were related to vertebral deformities. Positive findings were defined for AHD as ≥ 4.0 cm, for WOD as ≥ 5 mm, and for RPD as ≤ two fingerbreadths. Receiver operating characteristics curves analysis was performed, and cut-off values were determined to give maximum difference between sensitivity and false-positive rate. Expected probabilities for vertebral deformities were calculated using logistic regression analysis.</p> <p>Results</p> <p>The mean AHD for those participants with and without vertebral deformities were 7.0 ± 4.1 cm and 4.2 ± 4.2 cm (p < 0.01), respectively. Sensitivity and specificity for use of AHD-positive, WOD-positive and RPD-positive values in predicting vertebral deformities were 0.85 (95% CI: 0.69, 1.01) and 0.52 (95% CI: 0.42, 0.62); 0.70 (95% CI: 0.50, 0.90) and 0.67 (95% CI: 0.57, 0.76); and 0.67 (95% CI: 0.47, 0.87) and 0.59 (95% CI: 0.50, 0.69), respectively. The sensitivity, specificity, and likelihood ratio for a positive result (LR) for use of combined AHD-positive and WOD-positive values were 0.65 (95% CI: 0.44, 0.86), 0.81 (95% CI: 0.73, 0.89), and 3.47 (95% CI: 3.01, 3.99), respectively. The expected probability of vertebral deformities (P) was obtained by the equation; P = 1-(exp [-1.327-0.040 × body weight +1.332 × WOD-positive + 1.623 × AHD-positive])^-1. The sensitivity, specificity and LR for use of a 0.306 cut-off value for probability of vertebral fractures were 0.65 (95% CI: 0.44, 0.86), 0.87 (95% CI: 0.80, 0.93), and 4.82 (95% CI: 4.00, 5.77), respectively.</p> <p>Conclusion</p> <p>Both WOD and AHD effectively predicted vertebral deformities. This screening method could be used in a strategy to prevent additional vertebral fractures, even when X-ray technology is not available.</p

Ethnic difference of clinical vertebral fracture risk

Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. Introduction: Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups. Methods: Four thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations. Results: The mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical vertebral fracture and hip fracture rates were 299/100,000 and 332/100,000 person-years, respectively, in men, and 594/100,000 and 379/100,000 person-years, respectively, in women. Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians. At the age of 65 or above, the hip fracture rates for Asian (Hong Kong Chinese and Japanese) men and women were less than half of that in Caucasians, but the vertebral fracture rate was higher in Asians, resulting in a high vertebral-to-hip fracture ratio. Conclusions: The incidences of vertebral and hip fractures, as well as the vertebral-to-hip fracture ratios vary in Asians and Caucasians. Estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Increased fracture rate in women with breast cancer: a review of the hidden risk

Women with breast cancer, particularly individuals diagnosed at a relatively early age, have an increased incidence of fractures. Fractures can have serious clinical consequences including the need for major surgery, increased morbidity and mortality, increased cost of disease management, and reduced quality of life for patients. The primary cause of the increased fracture risk appears to be an accelerated decrease in bone mineral density (BMD) resulting from the loss of estrogenic signaling that occurs with most treatments for breast cancer, including aromatase inhibitors. However, factors other than BMD levels alone may influence treatment decisions to reduce fracture risk in this setting. Our purpose is to review current evidence for BMD loss and fracture risk during treatment for breast cancer and discuss pharmacologic means to reduce this risk.Journal ArticleResearch Support, Non-U.S. Gov'tReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations

Vertebral Fracture Analysis enables the detection of vertebral fractures in the same session as bone mineral density testing. Using this method in 2,424 patients, we found unknown vertebral fractures in approximately one out of each six patients with significant impact on management. The presence of osteoporotic vertebral fractures (VF) is an important risk factor for all future fractures independent of BMD. Yet, determination of the VF status has not become standard practice. Vertebral Fracture Assessment (VFA) is a new feature available on modern densitometers. In this study we aimed to determine the prevalence of VF using VFA in all patients referred for BMD testing in a university medical center and to evaluate its added clinical value. Prospective diagnostic evaluation study in 2,500 consecutive patients referred for BMD. Patients underwent VFA in supine position after BMD testing. Questionnaires were used to assess perceived added value of VFA. In 2,424 patients (1,573 women), results were evaluable. In 541 patients (22%), VFA detected a prevalent VF that was unknown in 69%. In women, the prevalence was 20% versus 27% found in men (p <0.0001). The prevalence of VF was 14% in patients with normal BMD (97/678), increased to 21% (229/1,100) in osteopenia and to 26% in those with osteoporosis (215/646) by WHO criteria. After excluding mild fractures VF prevalence was 13% (322/2,424). In 468 of 942 questionnaires (50% response rate), 27% of the referring physicians reported VFA results to impact on patient management. VFA is a patient friendly new tool with a high diagnostic yield, as it detected unknown VF in one out of each six patients, with significant impact on management. We believe these findings justify considering VFA in all new patients referred for osteoporosis assessment in similar populations