Probability Of Major Osteoporotic Fracture Research Articles

Cost-effectiveness of bazedoxifene incorporating the FRAX® algorithm in a European perspective

The cost-effectiveness of bazedoxifene was compared to placebo in France, Germany, Italy, Spain, Sweden and the UK from a healthcare perspective using FRAX® for both fracture risks and for treatment efficacy. Cost/QALY differences were explained to a large extent by differences in fracture risk. In cost-effectiveness modelling of osteoporosis treatments, the fracture risk has traditionally been calculated with risk adjustments based on age, bone mineral density and prior fracture. However, knowledge of additional clinical risk factors contributes to fracture risk assessment as demonstrated by the FRAX® tool. Bazedoxifene, a new selective estrogen receptor modulator for the treatment and prevention of osteoporosis, has been shown in a phase III clinical trial to reduce the risk of osteoporotic fractures in women. In an analysis using FRAX®, the efficacy of bazedoxifene was greater in patients with higher fracture risk. The aim of this study was to evaluate the cost-effectiveness of bazedoxifene compared to placebo in France, Germany, Italy, Spain, Sweden and the UK from a healthcare perspective using FRAX®. A Markov cohort model was adapted to incorporate the FRAX® risk factors. FRAX® produces relative risks for hip fractures and major osteoporotic fractures. Patients were given a 5-year intervention, reducing the risk of fractures in a risk-dependent manner. The effect of treatment on fractures was assumed to decline linearly over 5 years after the intervention. There are large cost/quality-adjusted life year variations between countries in the European setting studied. The base case values ranged from cost saving (Sweden) to EUR 105,450 (Spain) in 70-year-old women with a T-score of -2.5 SD and a prior fracture. Bazedoxifene can be a cost-effective treatment for postmenopausal osteoporosis. The variability between countries was explained to a large extent by differences in fracture risk, and the estimated cost-effectiveness was highly dependent on the population's FRAX®-estimated probability of major osteoporotic fracture.

Correlation between lumbar BMD percentage change and ten-year probability of major osteoporotic fracture by FRAX and total number of previous fracture in postmenopausal osteoporotic women treated with PTH 1-84

Forest fragmentation is a major conservation issue, which includes interdependent components of forest loss and changes in their spatial patterns. Over the years, the Himalayan forests have experienced major changes, but data and documentation on patterns and causes of forest fragmentation are limited. In this study, we analyzed temporal changes (1990–2014) of forest loss and fragmentation using Landsat imageries in the Kumaon division of Uttarakhand state, India. To assess mechanisms causing forest fragmentation, we investigated changes in following quantitative parameters describing forest fragmentation: (i) forest area density (Pf), (ii) overall forest connectivity (Pff), (iii) anthropogenic fragmentation (Pfa), and (iv) natural fragmentation (Pfn). We found that this region is undergoing intensive forest fragmentation, shifting from forest-dominated landscapes to fragmented forests intermixed with agricultural lands and urban settlements. Overall, intact forest patches decreased between 1990 and 2009 (1442 km2), followed by a small gain from 2009 to 2014 (260 km2). In lower altitudes, anthropogenic activities caused fragmentation; while in higher altitudes, fragmentation can be attributed to natural causes. All districts within the region show a decreasing trend of forest cover area, with the highest rate of forest cover loss for the low-lying district of Udham Singh Nagar and the lowest rate for the high-lying district of Bageshwar. This trend can be associated with increasing population density in low-lying districts than high-lying districts. Our results emphasize on delineating spatial trends of forest loss and fragmentation to support the identification of conservation sites. The findings can further help in developing forest policies for maintaining local livelihood options in the Himalayan region.

Osteoporosis screening and fracture risk assessment in patients with inflammatory bowel disease

Introduction: Patients with inflammatory bowel disease (IBD) have an increased risk of osteoporosis. The Fracture Risk Assessment Tool (FRAX) evaluates the fracture risk of individuals in the general population. IBD-specific risk factors of osteoporosis remained unclear. In 2008, the Dutch IBD-guideline (IBDG) formulated a high-risk profile of osteoporosis based on IBD-specific risk factors. This study assessed the accuracy of the IBDG-based osteoporosis screening using the FRAX-tool as reference. Methods: Adult IBD patients attending the gastroenterology outpatient unit were screened for osteoporosis using the IBDG and FRAX-method. Patients were not previously diagnosed with osteoporosis. Patient characteristics and medication usage were collected by a questionnaire and the medical record. Fracture risk was calculated without bone mineral density using the online FRAX-tool. Quartiles were stratified based on the 10-year probability of a major osteoporotic (MO) fracture and hip fracture, with the highest quartiles of risk used as reference (SPSS 17.0). According to the IBDG, patients with ≥1 of the following characteristics are at risk of osteoporosis: low energy fracture, multiple fractures in the past, systemic glucocorticoids (>1 year, >7.5 mg daily for six months), IBD since child age, inflammation of small intestines, short bowel syndrome, colestyramine usage, lactose/ calcium deficient diet, postmenopausal women, and age >55 years in men. Results: 287 Patients were included with a mean age of 48.5 years (SD 14.7). Mean 10-years probability was 4.2% (1.5-20.0%) for MO fracture and 0.9% (0.1-10.0%) for hip fracture. The number of patients classified in the highest risk quartiles for MO and hip fractures, were respectively 70 (24%) and 66 (23%). 195 Patients were classified as high risk by the IBDG. Sixty-six percent of these patients had MO and hip fracture risks in the three lowest quartiles (respectively <4.8% and <0.8%) leading to positive predictive values of respectively 34% and 33%, and negative predictive values of 97% and 100%. Conclusion: Based on the IBDG, two-third of the patients is at risk of osteoporosis. Although most patients in the highest fracture risk quartiles are recognized by the IBDG, this guideline lacks accuracy caused by low positive predictive values. Furthermore, this study shows that high-risk IBDG patients have relatively low fracture risks according to the FRAX-method.

The FRAX tool in French women: How well does it describe the real incidence of fracture in the OFELY cohort

The FRAX tool estimates an individual's fracture probability over 10 years from clinical risk factors with or without bone mineral density (BMD) measurement. The aim of our study was to compare the predicted fracture probabilities and the observed incidence of fracture in French women during a 10-year follow-up. The probabilities of fracture at four major sites (hip, clinical spine, shoulder, or wrist) and at the hip were calculated with the FRAX tool in 867 women aged 40 years and over from the Os des Femmes de Lyon (OFELY) cohort.The incidence of fracture was observed over 10 years. Thus 82 women sustained 95 incident major osteoporotic (OP) fractures including 17 fractures at the hip. In women aged at least 65 years (n = 229), the 10-year predicted probabilities of fracture with BMD were 13% for major OP fractures and 5% for hip fractures, contrasting with 3.6% and 0.5% in women younger than 65 years (p < .0001). The predicted probabilities of both major OP and hip fractures were significantly higher in women with osteoporosis (n = 77, 18% and 10%) and osteopenia (n = 390, 6% and 2%) compared with women with normal BMD (n = 208, 3% and <1%; p < .0001. The predicted probabilities of fracture were two and five times higher in women who sustained an incident major OP fracture and a hip fracture compared with women who did not (p < .0001). Nevertheless, among women aged at least 65 years with low BMD values (T-score < or = -1; n = 199), the 10-year predicted probability of major OP fracture with BMD was 48% lower than the observed incidence of fractures (p < .01). A 10-year probability of major OP fracture higher than 12% identified more women with incident fractures than did BMD in the osteoporotic range (p < .05). In French women from the OFELY cohort, the observed incidence of fragility fractures over 10 years increased with age following a pattern similar to the predicted probabilities given by the FRAX tool. However, in women aged at least 65 years with low BMD, the observed incidence of fractures was substantially higher than the predicted probability.

New and Emerging Therapies for Osteoporosis

New and Emerging Therapies for Osteoporosis

Usefulness of FRAX and future issues in women's health

With the recent development of diverse therapeutic modalities for osteoporosis, there is an increasingly recognized need to develop cost-effective strategies to determine which patients will benefit most from pharmacologic treatment. The World Health Organization (WHO) has developed a 10-year osteoporotic fracture risk assessment tool (FRAX) based on clinical risk factors combined with bone mineral density measured at the femoral neck. In postmenopausal women, age and prior history of fragility fracture were found to be major contributing factors to osteoporotic fracture risk as assessed by FRAX. In the US, the National Osteoporosis Foundation (NOF) guidelines recommend treatment in patients with osteopenia when the 10-year probability of major osteoporotic fracture is = 20% or the hip fracture is = 3%. On the other hand, in the UK, the National Osteoporosis Guideline Group (NOGG) has developed a case finding approach for individuals whose 10-year probability of major osteoporotic fracture exceeds age-specific thresholds. The FRAX algorithms may be worth incorporating in a cost-effectiveness model for socioeconomic analyses to determine the pharmacological intervention threshold for osteoporosis treatment. FRAX represents a significant advance for practitioners in women's health as an easy-to-use calculator of osteoporotic fracture probability. However, it should be noted that FRAX is intended as a guideline for clinical decision making only and does not force the decision to treat on physicians.

Application of the National Osteoporosis Foundation Guidelines to postmenopausal women and men: the Framingham Osteoporosis Study.

We applied the 2008 National Osteoporosis Foundation (NOF) Guidelines to Framingham Osteoporosis Study participants and found nearly one half of Caucasian postmenopausal women and one sixth of men aged 50 years and older would be recommended for osteoporosis treatment. Given the high proportion of persons recommended for treatment, NOF Guidelines may need to be re-evaluated with respect to budget impact. Little is known about the public health impact of the NOF Guidelines. Therefore, we determined the proportion of US Caucasians recommended for treatment of osteoporosis according to NOF Guidelines (2003 and 2008). One thousand nine hundred and forty-six postmenopausal women and 1,681 men aged > or =50 years from the Framingham Study with information on bone mineral density (1987-2001) were included. Information on clinical predictors was used to estimate the 10-year probability of hip and major osteoporotic fracture by FRAX (version 3.0). Overall proportion of women meeting treatment criterion was less when the 2008 NOF Guidelines were applied (41.1%) compared with 2003 Guidelines (47.8%). The proportion of women aged <65 years meeting treatment criterion was much less when applying 2008 Guidelines (23.1% in 2003, 8.3% in 2008), whereas the proportion of women aged >75 years increased slightly (78.3% in 2003, 86.0% in 2008). Seventeen percent of men aged > or =50 years met treatment criterion (2.5% aged 50-64 years, 49.8% aged >75 years). Nearly one half of Caucasian postmenopausal women and one sixth of men aged 50 years and older would be recommended for osteoporosis treatment according to 2008 NOF Guidelines. Given the high proportion of persons recommended for treatment, NOF Guidelines may need to be re-evaluated with respect to budget impact.

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

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. 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). 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. 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). 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.

(ii) Fracture risk assessment

Summary Osteoporotic fractures cause excess mortality, substantial morbidity and health and social service expenditure in older people. The risk of these fractures is determined by skeletal factors, including bone mineral density (BMD), bone turnover, architecture, bone size, and skeletal geometry, together with non-skeletal factors associated with falling. With the advent of treatments which decrease the incidence of fractures and the development of strategies for preventing falls, there is growing interest in identifying people at high risk of fragility fractures, in whom to target therapeutic intervention. The World Health Organization (WHO) has recently developed a Fracture Risk Assessment Tool (FRAX™). This uses clinical risk factors, including prior fracture after age of 50 years, parental hip fracture, current smoking, oral steroid therapy, alcohol intake >2units/day and chronic conditions such as rheumatoid arthritis, with or without femoral neck BMDt, to estimate the ten year probability of hip and other major osteoporotic fractures.