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Summary: We examined variations in proportions of hip fractures and major fractures among postmenopausal women using the Global Longitudinal Study of Osteoporosis in Women (GLOW). The proportion of major fractures that were hip fractures varied with age and region, whereas variations in the proportion of fractures that were major fractures appeared modest. Introduction: In many countries, the World Health Organization fracture risk assessment tool calculates the probability of major fractures by assuming a uniform age-associated proportion of major fractures that are hip fractures in different countries. We further explored this assumption, using data from the GLOW. Methods: GLOW is an observational population-based study of 60,393 non-institutionalized women aged ≥55 years who had visited practices within the previous 2 years. Main outcome measures were self-reported prevalent fractures after the age of 45 years and incident fractures during the 2 years of follow-up. Results: The adjusted proportion of prevalent and incident major fractures after the age of 45 years that were hip fractures was higher in North America (16%, 17%) than in northern (13%, 12%) and southern Europe (10%, 10%), respectively. The proportion of incident major fractures that were hip fractures increased more than five-fold with age, from 6.6% among 55-59-year-olds to 34% among those aged ≥85 years. Regional and age-associated variations in the proportion of all incident fractures that were major fractures were less marked, not exceeding 16% and 28%, respectively. Conclusions: The data suggest that there may be regional differences in the proportion of major fractures that are hip fractures in postmenopausal women. In contrast, the regional and age-related variations in the proportion of fractures that are major fractures appear to be modest. However, because of the limited number of fractures in our sample, further studies are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Summary: Treatment criteria published by the National Osteoporosis Guideline Group (NOGG) in the UK make more efficient use of bone mineral density (BMD) resources than the previous Royal College of Physicians (RCP) guideline. Introduction: We compared the effectiveness of the RCP case-finding strategy previously used in the UK and the updated guideline published by NOGG, which incorporates the FRAX® fracture probability tool. Methods: Comparisons were made by simulating population samples of 1000 women at ages between 50 and 85 years, using age-specific prevalence of risk factors and UK-derived fracture and mortality rates. Comparators comprised the number identified at high risk, the incidence of hip fracture and the femoral neck BMD in those identified, the number needed to scan to identify a hip fracture, the acquisition cost and the cost per hip fracture averted Results: Compared with the RCP strategy, NOGG identified slightly reduced numbers of women at high risk (average 34.6% vs. 35.7% across all ages), but with lower numbers of scans required at each age. For example, NOGG required only 3.5 scans at the age of 50 years to identify one case of hip fracture, whereas RCP required 13.9. At 75 years, the corresponding numbers were 0.9 and 1.5. Thus, the acquisition costs for identifying a hip fracture case and the total costs (acquisition and treatment) per hip fracture averted were lower. Conclusion: Compared to the RCP strategy, the FRAX-based NOGG strategy uses BMD resources more efficiently with lower acquisition costs and lower costs per hip fracture averted. [ABSTRACT FROM AUTHOR]

Summary Meta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures. Introduction Clinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach. Methods We conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions. Results Twenty-one studies including 55,164 women and 13,742 men were included in the meta-analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43–2.00), SOS was 1.96 (95% CI 1.64– 2.34), SI was 2.26 (95%CI 1.71–2.99) and QUI was 1.99 (95% CI 1.49–2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p values> 0.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUA=1.34 [95%CI 1.22–1.49]). Conclusions This study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world. [ABSTRACT FROM AUTHOR]

In recent years, atypical femoral fractures and osteonecrosis of the jaw have emerged as potential complications of long-term bisphosphonate therapy; osteonecrosis of the jaw has also been reported in patients receiving high doses of denosumab. The pathophysiology of both conditions is poorly defined, and the underlying mechanisms are likely to differ. The initiation of atypical fractures in the lateral femoral shaft suggests that reduced tensile strength, possibly secondary to alterations in the material properties of bone resulting from low bone turnover, may be an important pathogenetic factor. Osteonecrosis of the jaw is characterised by infection, inflammation, bone resorption and bone necrosis, but the sequence in which these occur has not been established. However, the observation that bone resorption occurs in close proximity to microbial structures suggests that infection may be the most important trigger, often as a result of dental disease. Other possible pathogenetic factors include suppression of bone turnover, altered immune status and adverse effects of bisphosphonates on the oral mucosa. [ABSTRACT FROM AUTHOR]

We describe the case of a 53-year-old woman who presented with a metatarsal fracture and was found to have a bone mineral density (BMD) T-score of +11 in the lumbar spine and +7.6 in the hip. Subsequent investigation revealed very high serum, urine and tissue fluoride levels, associated with excessive tea and toothpaste consumption. The case emphasises the need to exclude fluorosis in individuals with unexpectedly high BMD levels. [ABSTRACT FROM AUTHOR]

Summary: The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review Introduction: The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. Methods: This study reviews the resource documents and joint position statements of ISCD and IOF. Results: Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. Conclusions: The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice. [ABSTRACT FROM AUTHOR]

Although age-related changes in cancellous bone structure in human are relatively well characterized, few studies have addressed changes in cortical bone. We have investigated age-related changes in iliac crest bone biopsy specimens from 54 normal subjects, 23 men and 31 women, aged 18-90 years. A significant decrease in cortical width and area was seen ( P = 0.002 and < 0.001 respectively), with no difference between sexes. Haversian canal density increased significantly with age by approximately 9% per decade ( P = 0.032) but Haversian canal area tended to be lower, resulting in no overall age-related difference in cortical porosity. Haversian canal area was significantly higher in the endosteal section than in the periosteal section of the cortex ( P = 0.019) but the Haversian canal density was lower, resulting in similar overall porosity in the two sections. In conclusion, our results demonstrate an age-related decrease in iliac crest cortical width in men and women and an increase in Haversian canal density, but no overall change in cortical porosity. [ABSTRACT FROM AUTHOR]

Summary: This article describes the development of a model for postmenopausal osteoporosis (PMO) based on Swedish data that is easily adaptable to other countries. Introduction: The aims of the study were to develop and validate a model to describe the current/future burden of PMO in different national settings. Methods: For validation purposes, the model was developed using Swedish data and provides estimates from 1990. For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and death. Fracture by site (hip, vertebral, and non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected site-specific risk of death and subsequent fractures. Bone mineral density (BMD) was included as a model output; model inputs included population size and life tables from 1970 to 2020, incidence of fracture, relative risk of subsequent fractures based on prior fracture, relative risk of death following a fracture by site, and BMD by age (mean and standard deviation). Results: Model predictions averaged across age groups estimated the incidence of hip, vertebral, and other osteoporotic fractures within a 5% margin of error versus published data. In Sweden, the number of osteoporotic fractures is expected to rise by 11.5% between 2009 and 2020, with a shift towards more vertebral fractures and multiple fractures. Conclusion: The current PMO disease model is easily adaptable to other countries, providing a consistent measure of present and future burden of PMO in different settings. [ABSTRACT FROM AUTHOR]

Background: A past history of low trauma fracture is a strong risk factor for future fractures in postmenopausal women and national guidance recommends treatment in the majority of such women [ABSTRACT FROM PUBLISHER]

Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% ( p < 0.001). QoL, assessed by the QUALIOST®, was significantly better ( p = 0.025), and patients without back pain were greater ( p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

The Global Longitudinal study of Osteoporosis in Women (GLOW) is a prospective cohort study involving 723 physicians and 60,393 women subjects ≥55 years. The data will provide insights into the management of fracture risk in older women over 5 years, patient experience with prevention and treatment, and distribution of risk among older women on an international basis. Data from cohort studies describing the distribution of osteoporosis-related fractures and risk factors are not directly comparable and do not compare regional differences in patterns of patient management and fracture outcomes. The GLOW is a prospective, multinational, observational cohort study. Practices typical of each region were identified through primary care networks organized for administrative, research, or educational purposes. Noninstitutionalized patients visiting each practice within the previous 2 years were eligible. Self-administered questionnaires were mailed, with 2:1 oversampling of women ≥65 years. Follow-up questionnaires will be sent at 12-month intervals for 5 years. A total of 723 physicians at 17 sites in ten countries agreed to participate. Baseline surveys were mailed (October 2006 to February 2008) to 140,416 subjects. After the exclusion of 3,265 women who were ineligible or had died, 60,393 agreed to participate. GLOW will provide contemporary information on patterns of management of fracture risk in older women over a 5-year period. The collection of data in a similar manner in ten countries will permit comparisons of patient experience with prevention and treatment and provide insights into the distribution of risk among older women on an international basis. [ABSTRACT FROM AUTHOR]

Abstract: In 1999 and 2000 the Royal College of Physicians published guidelines for the prevention and treatment of osteoporosis [; Royal College of Physicians and Bone and Tooth Society of Great Britain. Update on pharmacological interventions and an algorithm for management. London, UK: Royal College of Physicians; 2000.; ]. Since then, there have been significant advances in the field of osteoporosis including the development of new techniques for measuring bone mineral density, improved methods of assessing fracture risk and new treatments that have been shown to significantly reduce the risk of fractures. Against this background, the National Osteoporosis Guideline Group (NOGG), in collaboration with many Societies in the UK, have updated the original guidelines [, Osteoporosis Dorset, Primary Care Rheumatology Society, Society for Endocrinology. Osteoporosis. Clinical guideline for prevention and treatment, Executive Summary. University of Sheffield Press; 2008], a practical summary of which is detailed below. The management algorithms are underpinned by a health economic analysis applied to the epidemiology of fracture in the UK. [Copyright &y& Elsevier]

The article focuses on the recommendations for the registration of agents for the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) updated by the Group for the Respect of Ethics and Excellence in Science (GREEC). The update directed the design of clinical studies on the treatment of GIOP in postmenopausal women. Moreover, it aims to consider suitable recommendations for the registration of agents for use in GIOP in postmenopausal women, men, and premenopausal women.

About 50% of patients fail to comply or persist with anti-osteoporosis treatment regimens within 1 year. Poor compliance is associated with higher fracture rates. Causes of poor compliance are unknown. As it is not possible to predict poor compliance, close monitoring of compliance is needed. Despite evidence supporting the anti-fracture efficacy of several pharmacological agents, approximately 50% of patients do not follow their prescribed treatment regimen and/or discontinue treatment within 1 year. Poor compliance is associated with higher fracture rates and increased morbidity, mortality and cost. However, as poor compliance, even to placebo, is associated with adverse outcomes, the higher morbidity appears to be only partly the result of lack of treatment: as yet, undefined characteristics place poor compliers at higher risk of morbidity and mortality. Only a small proportion (e.g., 6%) of the variability in compliance is explained by putative causal factors such as older age, co-morbidity or greater number of medications. Regimens with longer dosing intervals, such as weekly dosing, improve compliance, persistence and outcomes, but only modestly. As it is not possible to predict poor compliance, close monitoring of compliance should be an obligatory duty in clinical care. How this is best achieved has yet to be established, but poor persistence occurs as early as 3 months of starting treatment, indicating the need for early monitoring. [ABSTRACT FROM AUTHOR]

Osteoporosis is a serious complication of anorexia nervosa and in affected adolescents may result in a permanent deficit in bone mass. The pathophysiology of this bone disease has not been clearly defined. In this prospective study of 26 young women with anorexia nervosa aged 13–20 years (mean 16.5) we have measured changes in bone mineral density, total body composition and biochemical indices of bone turnover over 1 year. Over this period there was a mean weight gain of 10 kg and significant height gain with baseline and final values for body mass index of 14.2±1.7 and 17.6±2.3 kg/m2 ( P<0.001). However, no significant changes were seen in bone mineral density in the spine or proximal femur during the study; total body bone mineral content was significantly higher than baseline at 3 months and 12 months ( P=0.001 and P<0.0001), but total body bone mineral density at 3 months was significantly lower than baseline ( P=0.003). Serum osteocalcin and bone-specific alkaline phosphatase values increased significantly and remained higher than baseline at all time points whereas urinary NTX/creatinine excretion showed a non-significant increase over the first 6 months of the study, but at 12 months, the mean value was significantly lower than baseline. Mean serum 25-hydroxyvitamin D levels showed a significant decrease at 6 months ( P<0.05), but returned towards baseline thereafter. There was a significant increase in serum parathyroid hormone levels at all time points compared to baseline, these occurring within the normal range. These results indicate that although weight gain in young anorexics is associated with linear growth, bone mineral density does not increase. Whether this deficit can be corrected subsequently requires longer-term prospective studies. [ABSTRACT FROM AUTHOR]

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required. [ABSTRACT FROM AUTHOR]