People living with HIV and fracture risk.

PLHIV have an increased risk of osteoporosis and fractures when compared with people of the same age and sex. In this review, we address the epidemiology and the pathophysiology of bone disease and fractures in PLHIV. The assessment of fracture risk and fracture prevention in these subjects is also discussed. The spectrum of HIV-associated disease has changed dramatically since the introduction of potent antiretroviral drugs. Today, the survival of people living with HIV (PLHIV) is close to that of the general population. However, the longer life-span in PLHIV is accompanied by an increased prevalence of chronic diseases. Detrimental effects on bone health are well recognised, with an increased risk of osteoporosis and fractures, including vertebral fractures, compared to the general population. The causes of bone disease in PLHIV are not fully understood, but include HIV-specific risk factors such as use of antiretrovirals and the presence of chronic inflammation, as well as traditional risk factors for fracture. Current guidelines recommend the use of FRAX to assess fracture probability in PLHIV age ≥ 40 years and measurement of bone mineral density in those at increased fracture risk. Vitamin D deficiency, if present, should be treated. Bisphosphonates have been shown to increase bone density in PLHIV although fracture outcomes are not available.

Type 2 diabetes mellitus and bone.

Type 2 diabetes (T2DM) is a rapidly growing public health problem. It is associated with an increased risk of fracture, particularly of the hip, despite normal or high bone mineral density. Longer duration of disease and poor glycaemic control are both associated with higher fracture risk. The factors underlying increased fracture risk have not been clearly established, but increased falls risk, obesity, sarcopenia and co-morbidities are likely to contribute. The basis for reduced bone strength despite higher bone mineral density remains to be fully elucidated. Bone turnover is reduced in individuals with T2DM, with evidence of impaired bone formation. Most studies indicate normal or superior trabecular bone structure although reduced lumbar spine trabecular bone score (TBS) has been reported. Deficits in cortical bone structure have been demonstrated in some, but not all, studies whilst reduced bone material strength index (BMSi), as assessed by microindentation, has been a consistent finding. Accumulation of advanced glycation end products in bone may also contribute to reduced bone strength. The use of FRAX in individuals with T2DM underestimates fracture probability. Clinical management should focus on falls prevention strategies, avoidance of known risk factors, maintenance of good glycaemic control and bone protective intervention in individuals at high risk of fracture. Dietary and surgical strategies to reduce weight have beneficial effects on diabetes but may have adverse effects on skeletal health. Future research priorities include better definition of the mechanisms underlying increased fracture risk in T2DM and optimal strategies for identifying and treating those at high risk.

Cost-effective but clinically inappropriate: new NICE intervention thresholds in osteoporosis (Technology Appraisal 464).

PURPOSE: To comment on the latest technology appraisal of the National Institute for Clinical Excellence (NICE) in osteoporosis. METHODS: Review of NICE Technology Appraisal (TA464) on bisphosphonate use in osteoporosis. RESULTS: The NICE appraisal on bisphosphonate use in osteoporosis indicates that treatment with oral bisphosphonates may be instituted at a FRAX 10-year probability of major osteoporotic fracture above 1%. Implementation would mean that all women aged 50 years or older are deemed eligible for treatment, a position that would increase the burden of rare long-term side effects across the population. CONCLUSION: Cost-effectiveness thresholds for low-cost interventions should not be used to set intervention thresholds but rather to validate the implementation of clinically driven intervention thresholds.

Access to fracture risk assessment by FRAX and linked National Osteoporosis Guideline Group (NOGG) guidance in the UK-an analysis of anonymous website activity.

In the UK, fracture risk guidance is provided by the National Osteoporosis Guideline Group (NOGG). NOGG usage showed widespread access through direct web-based linkage to FRAX. The facilitated interaction between fracture risk assessment and clinical guidelines could usefully be adopted in other countries. INTRODUCTION: In the UK, guidance on assessment of osteoporosis and fracture risk is provided by the National Osteoporosis Guideline Group ( www.shef.ac.uk/NOGG ). We wished to determine access to this guidance by exploring website activity. METHODS: We undertook an analysis of FRAX and NOGG website usage for the year between 1st July 2013 and 30th June 2014 using Google Analytics software. RESULTS: During this period, there was a total of 1,774,812 sessions (a user interaction with the website) on the FRAX website with 348,964 of these from UK-based users; 253,530 sessions were recorded on the NOGG website. Of the latter, two-thirds were returning visitors, with the vast majority (208,766; 82 %) arising from sites within the UK. The remainder of sessions were from other countries demonstrating that some users of FRAX in other countries make use of the NOGG guidance. Of the UK-sourced sessions, the majority was from England, but the session rate (adjusted for population) was the highest for Scotland. Almost all (95.7 %) of the UK sessions arose from calculations being passed through from the FRAX tool ( www.shef.ac.uk/FRAX ) to the NOGG website, comprising FRAX calculations in patients without a bone mineral density (BMD) measurement (74.5 %) or FRAX calculations with a BMD result (21.2 %). National Health Service (NHS) sites were identified as the major source of visits to the NOGG website, comprising 79.9 % of the identifiable visiting locations, but this is an underestimate as many sites from within the NHS are not classified as such. CONCLUSION: The study shows that the facilitated interaction between web-based fracture risk assessment and clinical guidelines is widely used in the UK. The approach could usefully be adopted in other countries for which a FRAX model is available.

Self-perception of fracture risk: what can it tell us?

In this study, we report that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake. It suggests that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment. INTRODUCTION: This study aimed to assess how well self-perception of fracture risk, and fracture risk as estimated by the fracture prediction tool FRAX, related to fracture incidence and uptake and persistence of anti-osteoporosis medication among women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study involving 723 physician practices across 10 countries in Europe, North America and Australia. Aged ≥ 55 years, 60,393 women completed baseline questionnaires detailing medical history, including co-morbidities, fractures and self-perceived fracture risk (SPR). Annual follow-up included self-reported incident fractures and anti-osteoporosis medication (AOM) use. We calculated FRAX risk without bone mineral density measurement. RESULTS: Of the 39,241 women with at least 1 year of follow-up data, 2132 (5.4%) sustained an incident major osteoporotic fracture over 5 years of follow-up. Within each SPR category, risk of fracture increased as the FRAX categorisation of risk increased. In GLOW, only 11% of women with a lower baseline SPR were taking AOM at baseline, compared with 46% of women with a higher SPR. AOM use tended to increase in the years after a reported fracture. However, women with a lower SPR who were fractured still reported lower AOM rates than women with or without a fracture but had a higher SPR. CONCLUSIONS: These results suggest that SPR captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is also associated with improved medication uptake.

HIV infection and bone disease.

The success of antiretroviral therapy in treating HIV infection has greatly prolonged life expectancy in affected individuals, transforming the disease into a chronic condition. A number of HIV-associated non-AIDS comorbidities have emerged in the ageing HIV-infected population, including osteoporosis and increased risk of fracture. The pathogenesis of fracture is multifactorial with contributions from both traditional and HIV-specific risk factors. Significant bone loss occurs on initiation of antiretroviral therapy but stabilizes on long-term therapy. Fracture risk assessment should be performed in HIV-infected individuals and bone mineral density measured when indicated. Lifestyle measures to optimize bone health should be advised and, in individuals at high risk of fracture, treatment with bisphosphonates considered.

The role of tenofovir alafenamide in future HIV management.

HIV infection has become a chronic condition rather than an acute life-threatening disease in developed countries, thanks to consistent innovation and evolution of effective interventions. This has altered HIV management and created new challenges. People living with HIV (PLWHIV) are living longer and so encounter comorbidities linked not only with their disease, but also with ageing, lifestyle and chronic exposure to antiretroviral therapy (ART). Although longevity, viral suppression and the prevention of viral transmission remain key goals, more needs to be achieved to encompass the vision of attaining an optimum level of overall health. Treatment choices and management practices should ensure patients' long-term health with minimal comorbidity. Treatments that balance optimal efficacy with the potential for improved long-term safety are needed for all patients. In this review, we consider the evolution and development of tenofovir alafenamide (TAF), a novel prodrug of tenofovir which offers high antiviral efficacy at doses over ten times lower than that of tenofovir disoproxil fumarate (TDF). Emerging clinical data suggest that elvitegravir, cobicistat, emtricitabine and TAF (E/C/F/TAF) as a single-tablet regimen offers highly effective viral suppression in treatment-naïve and treatment-experienced patients with an improved renal and bone safety profile compared with TDF, this having been demonstrated in diverse groups including patients with existing renal impairment and adolescents. The profile of TAF identifies it as an agent with a promising role within future ART regimens that aim to deliver the vision of undetectable viral load, while requiring less monitoring and having a safety profile designed to minimize comorbid risks while supporting good long-term health.

Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015.

Osteonecrosis of the jaw (ONJ) has been associated with the use of aminobisphosphonates and denosumab. The vast majority (>90%) of cases occur in the oncology patient population receiving high doses of intravenous bisphosphonates or subcutaneous denosumab. The incidence of ONJ in the osteoporosis patient population is very low and is estimated at 1-90 per 100,000 patient-years of exposure. In the oncology patient population the incidence appears to be related to dose and duration of exposure, and prevalence has been estimated to be as high as 18.6%. A number of risk factors in addition to antiresorptive therapy have been identified. These include the presence of periodontal disease, oral surgical procedures with extractions or implants, radiation therapy, chemotherapy, diabetes, glucocorticoid use, and smoking. Antiangiogenic agents appear to contribute to the risk of ONJ, however, data at this time are limited and further evidence is required prior to confirming a causal relationship. ONJ may be prevented with optimization of oral hygiene, the use of oral antimicrobial mouth rinses, as well as systemic antibiotic therapy. Individuals not responding to conservative management or in the advanced stages of ONJ may be considered for surgery, as data over the past several years have demonstrated surgical success in this patient population. Case reports have indicated that teriparatide may enhance healing. A number of experimental therapies are being evaluated and include the use of bone marrow stem cell intralesional transplantation, local application of platelet-derived growth factor, hyperbaric oxygen, tissue grafting, and low-level laser therapy. This paper summarizes the current research as well as the international consensus on the diagnosis and management of ONJ.

FRAX-based assessment and intervention thresholds--an exploration of thresholds in women aged 50 years and older in the UK.

UNLABELLED: Under current guidelines, based on prior fracture probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold (a fixed threshold from the age of 70 years) reduces this disparity, increases treatment access and decreases the need for bone densitometry. INTRODUCTION: Several international guidelines set age-specific intervention thresholds at the 10-year probability of fracture equivalent to a woman of average BMI with a prior fracture. At older ages (≥70 years), women with prior fracture selected for treatment are at lower average absolute risk than those selected for treatment in the absence of prior fracture, prompting consideration of alternative thresholds in this age group. METHODS: Using a simulated population of 50,633 women aged 50-90 years in the UK, with a distribution of risk factors similar to that in the European FRAX derivation cohorts and a UK-matched age distribution, the current NOGG intervention and assessment thresholds were compared to one where the thresholds remained constant from 70 years upwards. RESULTS: Under current thresholds, 45.1% of women aged ≥70 years would be eligible for therapy, comprising 37.5% with prior fracture, 2.2% with high risk but no prior fracture and 5.4% selected for treatment after bone mineral density (BMD) measurement. Mean hip fracture probability was 11.3, 23.3 and 17.6%, respectively, in these groups. Under the alternative thresholds, the overall proportion of women treated increased from 45.1 to 52.9%, with 8.4% at high risk but no prior fracture and 7.0% selected for treatment after BMD measurement. In the latter group, the mean probability of hip fracture was identical to that observed in women with prior fracture (11.3%). The alternative threshold also reduced the need for BMD measurement, particularly at older ages (>80 years). CONCLUSIONS: The alternative thresholds equilibrate fracture risk, particularly hip fracture risk, in those with or without prior fracture selected for treatment and reduce BMD usage at older ages.

Disease-specific perception of fracture risk and incident fracture rates: GLOW cohort study.

UNLABELLED: Accurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles. INTRODUCTION: We compared self-perceived fracture risk and 3-year incident fracture rates in postmenopausal women with a range of morbidities in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study involving 723 physician practices across ten countries (Europe, North America, Australasia); 60,393 women aged ≥55 years completed baseline questionnaires detailing medical history and self-perceived fracture risk. Annual follow-up determined self-reported incident fractures. RESULTS: In total 2,945/43,832 (6.8%) sustained an incident fracture over 3 years. All morbidities were associated with increased fracture rates, particularly Parkinson's disease (hazard ratio [HR]; 95% confidence interval [CI], 3.89; 2.78-5.44), multiple sclerosis (2.70; 1.90-3.83), cerebrovascular events (2.02; 1.67-2.46), and rheumatoid arthritis (2.15; 1.53-3.04) (all p < 0.001). Most individuals perceived their fracture risk as similar to (46%) or lower than (36%) women of the same age. While increased self-perceived fracture risk was strongly associated with incident fracture rates, only 29% experiencing a fracture perceived their risk as increased. Under-appreciation of fracture risk occurred for all morbidities, including neurological disease, where women with low self-perceived fracture risk had a fracture HR 2.39 (CI 1.74-3.29) compared with women without morbidities. CONCLUSIONS: Postmenopausal women with morbidities tend to under-appreciate their risk, including in the context of neurological diseases, where fracture rates were highest in this cohort. This has important implications for health education, particularly among women with Parkinson's disease, multiple sclerosis, or cerebrovascular disease.

Epidemiological burden of postmenopausal osteoporosis in Italy from 2010 to 2020: estimations from a disease model.

The article describes the adaptation of a model to estimate the burden of postmenopausal osteoporosis in women aged 50 years and over in Italy between 2010 and 2020. For this purpose, a validated postmenopausal osteoporosis disease model developed for Sweden was adapted to Italy. 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 deaths. Fracture by site (hip, clinical vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected fracture site-specific risk of death and subsequent fractures. Model inputs specific to Italy included population size and life tables from 1970 to 2020, incidence of hip fracture and BMD by age in the general population (mean and standard deviation). The model estimated that the number of postmenopausal osteoporotic women would increase from 3.3 million to 3.7 million between 2010 and 2020 (+14.3%). Assuming unchanged incidence rates by age group over time, the model predicted the overall number of osteoporotic fractures to increase from 285.0 to 335.8 thousand fractures between 2010 and 2020 (+17.8%). The estimated expected increases in hip, vertebral and non-hip non-vertebral fractures were 22.3, 17.2 and 16.3%, respectively. Due to demographic changes, the burden of fractures is expected to increase markedly by 2020.

Screening for chronic comorbid diseases in people with HIV: the need for a strategic approach.

Among people living with HIV, the proportion of deaths attributed to chronic noninfectious comorbid diseases has increased over the past 15 years. This is partly a result of increased longevity in the era of highly active antiretroviral therapy (HAART), and also because HIV infection is related, causally or otherwise, to several chronic conditions. These comorbidities include conditions that are strongly associated with modifiable risk factors, such as cardiovascular disease (CVD), diabetes, and renal and bone diseases, and increasingly management guidelines for HIV recommend risk evaluation for these conditions. The uptake of these screening approaches is often limited by the resources required for their application, and hence the management of risk reduction in most HIV-infected populations falls below a reasonable standard. The situation is compounded by the fact that few risk calculators have been adjusted for specific use in HIV infection. There is substantial overlap of risk factors for the four common comorbid diseases listed above that are especially relevant in HIV infection, and this offers an opportunity to develop a simple screening approach that encompasses the key risk factors for lifestyle-related chronic disease in people with HIV infection. This would identify those patients who require more in-depth investigation, and facilitate a stepwise approach to targeted management. Such a tool could improve communication between patient and clinician. A significant proportion of people with HIV are sufficiently engaged with their care to participate in health promotion and take the lead in using patient-centric screening measures. Health-based social networking offers a mechanism for dissemination of such a tool and is able to embed educational messages and support within the process.

Non-hip, non-spine fractures drive healthcare utilization following a fracture: the Global Longitudinal Study of Osteoporosis in Women (GLOW).

UNLABELLED: We evaluated healthcare utilization associated with treating fracture types in >51,000 women aged ≥55 years. Over the course of 1 year, there were five times more non-hip, non-spine fractures than hip or spine fractures, resulting in twice as many days of hospitalization and rehabilitation/nursing home care for non-hip, non-spine fractures. INTRODUCTION: The purpose of this study is to evaluate medical healthcare utilization associated with treating several types of fractures in women ≥55 years from various geographic regions. METHODS: Information from the Global Longitudinal Study of Osteoporosis in Women (GLOW) was collected via self-administered patient questionnaires at baseline and year 1 (n = 51,491). Self-reported clinically recognized low-trauma fractures at year 1 were classified as incident spine, hip, wrist/hand, arm/shoulder, pelvis, rib, leg, and other fractures. Healthcare utilization data were self-reported and included whether the fracture was treated at a doctor's office/clinic or at a hospital. Patients were asked if they had undergone surgery or been treated at a rehabilitation center or nursing home. RESULTS: During 1-year follow-up, there were 195 spine, 134 hip, and 1,654 non-hip, non-spine fractures. Clinical vertebral fractures resulted in 617 days of hospitalization and 512 days of rehabilitation/nursing home care; hip fractures accounted for 1,306 days of hospitalization and 1,650 days of rehabilitation/nursing home care. Non-hip, non-spine fractures resulted in 3,805 days in hospital and 5,186 days of rehabilitation/nursing home care. CONCLUSIONS: While hip and vertebral fractures are well recognized for their associated increase in health resource utilization, non-hip, non-spine fractures, by virtue of their 5-fold greater number, require significantly more healthcare resources.

A comparison of case-finding strategies in the UK for the management of hip fractures.

UNLABELLED: 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.

Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis.

UNLABELLED: 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.

Regional and age-related variations in the proportions of hip fractures and major fractures among postmenopausal women: the Global Longitudinal Study of Osteoporosis in Women.

UNLABELLED: 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.

Treatment failure in osteoporosis.

UNLABELLED: Guidelines concerning the definition of failure of therapies used to reduce the risk of fracture are provided. INTRODUCTION: This study aims to provide guidelines concerning the definition of failure of therapies used to reduce the risk of fracture. METHODS: A working group of the Committee of Scientific Advisors of the International Osteoporosis Foundation was convened to define outcome variables that may assist clinicians in decision making. RESULTS: In the face of limited evidence, failure of treatment may be inferred when two or more incident fractures have occurred during treatment, when serial measurements of bone remodelling markers are not suppressed by anti-resorptive therapy and where bone mineral density continues to decrease. CONCLUSION: The provision of pragmatic criteria to define failure to respond to treatment provides an unmet clinical need and may stimulate research into an important issue.

A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis.

UNLABELLED: This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral glucocorticoid therapy is considered for 3 months or longer. INTRODUCTION: The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010. METHODS AND RESULTS: The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review. CONCLUSIONS: Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country.

Burden of non-hip, non-vertebral fractures on quality of life in postmenopausal women: the Global Longitudinal study of Osteoporosis in Women (GLOW).

UNLABELLED: Among 50,461 postmenopausal women, 1,822 fractures occurred (57% minor non-hip, non-vertebral [NHNV], 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D, followed by major NHNV and hip fractures. Decreases in physical function and health status were greatest for spine or hip fractures. INTRODUCTION: There is growing evidence that NHNV fractures result in substantial morbidity and healthcare costs. The aim of this prospective study was to assess the effect of these NHNV fractures on quality of life. METHODS: We analyzed the 1-year incidences of hip, spine, major NHNV (pelvis/leg, shoulder/arm) and minor NHNV (wrist/hand, ankle/foot, rib/clavicle) fractures among women from the Global Longitudinal study of Osteoporosis in Women (GLOW). Health-related quality of life (HRQL) was analyzed using the EuroQol EQ-5D tool and the SF-36 health survey. RESULTS: Among 50,461 women analyzed, there were 1,822 fractures (57% minor NHNV, 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D summary scores, followed by major NHNV and hip fractures. The number of women with mobility problems increased most for those with major NHNV and spine fractures (both +8%); spine fractures were associated with the largest increases in problems with self care (+11%), activities (+14%), and pain/discomfort (+12%). Decreases in physical function and health status were greatest for those with spine or hip fractures. Multivariable modeling found that EQ-5D reduction was greatest for spine fractures, followed by hip and major/minor NHNV. Statistically significant reductions in SF-36 physical function were found for spine fractures, and were borderline significant for major NHNV fractures. CONCLUSION: This prospective study shows that NHNV fractures have a detrimental effect on HRQL. Efforts to optimize the care of osteoporosis patients should include the prevention of NHNV fractures.

Age-related changes in iliac crest cortical width and porosity: a histomorphometric study.

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.