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The National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management., Introduction: The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older., Methods: Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence., Results: Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement., Conclusion: The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases., (© 2022. The Author(s).)

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.

Bisphosphonates are widely used in the treatment of osteoporosis in postmenopausal women and older men. In clinical trials they have been shown to reduce fractures in women with osteoporosis and there is increasing evidence that they are also effective in women with osteopenia, in whom the majority of fractures occur. In addition to their role as initial therapy in individuals at increased risk of fracture, bisphosphonates are used as sequential therapy after treatment with anabolic drugs. There are no head-to head studies to compare the anti-fracture efficacy of different bisphosphonates, but there is limited evidence that zoledronate treatment results in greater increases in BMD than risedronate or alendronate. This, together with the need for less frequent administration of zoledronate, supports its wider use in clinical practice, particularly if longer dosing intervals than those currently recommended are shown to be effective., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bone mineral density (BMD) can be measured at multiple skeletal sites using various technologies to aid clinical decision-making in bone and mineral disorders. BMD by dual-energy X-ray absorptiometry (DXA) has a critical role in predicting risk of fracture, diagnosis of osteoporosis, and monitoring patients. In clinical practice, DXA remains the most available and best validated tool for monitoring patients. A quality baseline DXA scan is essential for comparison with all subsequent scans. Monitoring patients with serial measurements requires technical expertise and knowledge of the least significant change in order to determine when follow-up scans should be repeated. Prior ISCD Official Positions have clarified how and when repeat DXA is useful as well as the interpretation of results. The 2019 ISCD Official Positions considered new evidence and clarifies if and when BMD should be repeated. There is good evidence showing that repeat BMD measurement can identify people who experience bone loss, which is an independent predictor of fracture risk. There is good evidence showing that the reduction in spine and hip fractures with osteoporosis medication is proportional to the change in BMD with treatment. There is evidence that measuring BMD is useful following discontinuation of osteoporosis treatment. There is less documentation addressing the effectiveness of monitoring BMD to improve medication adherence, whether monitoring of BMD reduces the risk of fracture, or effectively discriminates patients who should and should not recommence treatment following an interruption of medication. Further research is needed in all of these areas., (Copyright © 2019 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Glucocorticoid-induced osteoporosis is the most common secondary cause of osteoporosis and the resulting fractures cause significant morbidity. Following initiation of oral glucocorticoids, rapid bone loss occurs, and fracture risk increases within a few months in a dose-dependent manner. These adverse effects are due to inhibition of bone formation accompanied by an early but transient increase in bone resorption. Multiple mechanisms underlie these changes in bone remodeling; direct effects include upregulation of PPARγR2, increased expression of sclerostin and increased RANKL/OPG ratio, whilst hypogonadism, altered renal and intestinal calcium handling, and reduced production of insulin-like growth factor 1 also contribute. Fracture risk assessment should be performed as soon as possible after glucocorticoids are initiated and bone protective therapy started promptly in individuals at high-risk, with calcium and vitamin D supplements where appropriate. Oral bisphosphonates are currently regarded as first line options on the grounds of their low cost. However, teriparatide has been shown to be superior in its effects on BMD and vertebral fracture risk in glucocorticoid-treated individuals with osteoporosis and should be considered as an alternative first line option in high-risk patients.

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.

Introduction: In 2008, the UK National Osteoporosis Guideline Group (NOGG) produced a guideline on the prevention and treatment of osteoporosis, with an update in 2013. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women and men age 50 years or over., Methods: Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence., Results: Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment, lifestyle measures and pharmacological interventions, duration and monitoring of bisphosphonate therapy, glucocorticoid-induced osteoporosis, osteoporosis in men, postfracture care and intervention thresholds., Conclusion: The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals who are involved in its management.

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 1 st July 2013 and 30 th 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.

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence., (Copyright © 2017. Published by Elsevier Inc.)

In the past three decades, there have been major advances in our understanding of bone biology and these have been -accompanied by a significant improvement in the management of osteoporosis. Fracture risk prediction algorithms using -clinical risk factors, with or without measurement of bone mineral density, have enabled more accurate targeting of treatment and a range of cost-effective pharmacological interventions is available to reduce fracture risk. Despite these advances, a number of challenges remain. In particular, treatment rates in high-risk individuals are low and adherence to treatment is poor. Addressing this treatment gap through measures such as fracture liaison services, which provide a coordinated and cost-effective strategy for secondary fracture prevention, is an important future priority., (© Royal College of Physicians 2016. All rights reserved.)

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., (© 2016 The Association for the Publication of the Journal of Internal Medicine.)

Bone mineral density (BMD) measurements have been widely used in clinical practice for the diagnosis of osteoporosis, monitoring of treatment, and prediction of fracture risk. However, although BMD values show high specificity for prediction of fractures, their sensitivity is quite low. Fracture risk algorithms such as FRAX improve prediction by including clinical risk factors that act independently of BMD. This mini-review discusses the strengths and limitations of FRAX relevant to its use in clinical practice., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Loss of muscle or bone mass occurs with ageing, immobility and in association with a variety of systemic diseases. The interaction of these two processes is most evident in the major contribution of falls to the risk of fractures in the elderly population. Exercise and nutrition are key common physiological variables that allow for preservation or formation of greater muscle or bone mass. However, although several pharmacological approaches have the potential to benefit both muscle and bone health, for example vitamin D, selective androgen receptor modulators and ghrelin mimetics, clinical trials with appropriate primary outcomes are lacking. Conventional approaches to address muscle loss are being extended to include stem cell biology and conserved molecular mechanisms of atrophy/hypertrophy. Pharmacological interventions to reduce fracture risk are exploring new mechanisms of action, in particular the uncoupling of bone resorption and formation. Emerging key issues for clinical trial design include adequate phenotyping of patients (personalised medicine), optimisation of the physiological background (multimodal approach) and the use of meaningful and robust outcomes relevant to daily clinical practice. At present, effective treatments that combine beneficial effects on both muscle and bone are lacking, although this is an important target for the future. This review therefore considers current and developing strategies to improve muscle function and bone strength in separate sections., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Low bone mineral density (BMD) is common in HIV-positive patients, although the role played by HIV infection versus sociodemographic and metabolic factors remains unclear., Methods: Understanding the Pathology of Bone Disease in HIV-infected individuals (HIV UPBEAT) is a prospective cohort study, enrolled HIV-positive and HIV-negative participants from similar demographic backgrounds. Dual X-ray absorptiometry at femoral neck, total hip and lumbar spine and blood tests were performed. Associations between BMD and factors of interest were assessed using multivariable linear regression., Results: A total of 474 participants were recruited. Two hundred and ten were HIV-positive, of whom, 59% were male, 40% African and median (interquartile range) age was 39 (33, 46) years. HIV acquisition risks were heterosexual sex (46.9%), homosexual sex (25.4%) and intravenous drug use (18.7%). Of the HIV-negative participants, 44% were male, 25% were African and median (interquartile range) age was 42 (34-49) years. HIV infection was independently associated with a 0.062 (P < 0.0001), 0.078 (P < 0.0001) and 0.060 g/cm (P =  0.0002) lower BMD at femoral neck, total hip and lumbar spine, respectively, after adjustment for demographic/ lifestyle factors and BMI. After further adjustment for bone biomarkers, HIV remained independently associated with reduced BMD at each site, although effect sizes were reduced. The HIV-positive group had significantly higher bone turnover (all between-group P < 0.0001). Treatment variables and cumulative exposure to antiretroviral therapy were not associated with lower BMD at femoral neck or total hip, but acquisition of HIV infection via intravenous drug use and longer time since HIV diagnosis were independently associated with lower lumbar spine BMD., Discussion: HIV is independently associated with lower BMD, and its effect is likely mediated, in part, by alterations in bone metabolism.

Osteoporosis has emerged as an important co-morbidity of HIV infection and a modest increase in fracture risk has been documented. Bone loss from the spine and hip occurs after initiation of antiretroviral therapy but most data indicate that bone mineral density is stable in HIV-infected individuals established on long-term antiretroviral therapy. Assessment of fracture probability should be performed in individuals who have clinical risk factors for fracture. Adequate dietary calcium intake and vitamin D status should be ensured and in individuals with a high fracture probability, bisphosphonate therapy may be appropriate., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Since the launch in 2008 by the National Osteoporosis Guideline Group (NOGG), of guidance for the diagnosis and management of osteoporosis in postmenopausal women and older men in the UK there have been significant advances in risk assessment and treatment. These have been incorporated into an updated version of the guideline, with an additional focus on the management of glucocorticoid-induced osteoporosis, the role of calcium and vitamin D therapy and the benefits and risks of long-term bisphosphonate therapy. The updated guideline is summarised below. The recommendations in the guideline are intended to aid management decisions but do not replace the need for clinical judgement in the care of individuals in clinical practice., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

We review the various aspects of health technology assessment in osteoporosis, including epidemiology and burden of disease, and assessment of the cost-effectiveness of recent advances in the treatment of osteoporosis and the prevention of fracture, in the context of the allocation of health-care resources by decision makers in osteoporosis. This article was prepared on the basis of a symposium held by the Belgian Bone Club and the discussions surrounding that meeting and is based on a review and critical appraisal of the literature. Epidemiological studies confirm the immense burden of osteoporotic fractures for patients and society, with lifetime risks of any fracture of the hip, spine, and forearm of around 40 % for women and 13 % for men. The economic impact is also large; for example, Europe's six largest countries spent €31 billion on osteoporotic fractures in 2010. Moreover, the burden is expected to increase in the future with demographic changes and increasing life expectancy. Recent advances in the management of osteoporosis include novel treatments, better fracture-risk assessment notably via fracture risk algorithms, and improved adherence to medication. Economic evaluation can inform decision makers in health care on the cost-effectiveness of the various interventions. Cost-effectiveness analyses suggest that the recent advances in the prevention and treatment of osteoporosis may constitute an efficient basis for the allocation of scarce health-care resources. In summary, health technology assessment is increasingly used in the field of osteoporosis and could be very useful to help decision makers efficiently allocate health-care resources.

Summary: The scorecard summarises key indicators of the burden of osteoporosis and its management in each of the member states of the European Union. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe., Introduction: The scorecard for osteoporosis in Europe (SCOPE) is an independent project that seeks to raise awareness of osteoporosis care in Europe. The aim of this project was to develop a scorecard and background documents to draw attention to gaps and inequalities in the provision of primary and secondary prevention of fractures due to osteoporosis., Methods: The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union (EU27). The information researched covered four domains: background information (e.g. the burden of osteoporosis and fractures), policy framework, service provision and service uptake e.g. the proportion of men and women at high risk that do not receive treatment (the treatment gap)., Results: There was a marked difference in fracture risk among the EU27. Of concern was the marked heterogeneity in the policy framework, service provision and service uptake for osteoporotic fracture that bore little relation to the fracture burden. For example, despite the wide availability of treatments to prevent fractures, in the majority of the EU27, only a minority of patients at high risk receive treatment for osteoporosis even after their first fracture. The elements of each domain in each country were scored and coded using a traffic light system (red, orange, green) and used to synthesise a scorecard. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe., Conclusions: The scorecard will enable healthcare professionals and policy makers to assess their country's general approach to the disease and provide indicators to inform future provision of healthcare.

Unlabelled: This report describes epidemiology, burden, and treatment of osteoporosis in each of the 27 countries of the European Union (EU27)., Introduction: In 2010, 22 million women and 5.5 million men were estimated to have osteoporosis in the EU; and 3.5 million new fragility fractures were sustained, comprising 620,000 hip fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000 other fractures. The economic burden of incident and prior fragility fractures was estimated at € 37 billion. Previous and incident fractures also accounted for 1,180,000 quality-adjusted life years lost during 2010. The costs are expected to increase by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining. The aim of this report was to characterize the burden of osteoporosis in each of the EU27 countries in 2010 and beyond., Methods: The data on fracture incidence and costs of fractures in the EU27 were taken from a concurrent publication in this journal (Osteoporosis in the European Union: Medical Management, Epidemiology and Economic Burden) and country specific information extracted., Results: The clinical and economic burden of osteoporotic fractures in 2010 is given for each of the 27 countries of the EU. The costs are expected to increase on average by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining., Conclusions: In spite of the high cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by aging populations, the use of pharmacological prevention of osteoporosis has decreased in recent years, suggesting that a change in healthcare policy concerning the disease is warranted.

Unlabelled: This report describes the epidemiology, burden, and treatment of osteoporosis in the 27 countries of the European Union (EU27)., Introduction: Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risk of fragility fractures which represent the main clinical consequence of the disease. Fragility fractures are associated with substantial pain and suffering, disability and even death for affected patients and substantial costs to society. The aim of this report was to characterize the burden of osteoporosis in the EU27 in 2010 and beyond., Methods: The literature on fracture incidence and costs of fractures in the EU27 was reviewed and incorporated into a model estimating the clinical and economic burden of osteoporotic fractures in 2010., Results: Twenty-two million women and 5.5 million men were estimated to have osteoporosis; and 3.5 million new fragility fractures were sustained, comprising 610,000 hip fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000 other fractures (i.e. fractures of the pelvis, rib, humerus, tibia, fibula, clavicle, scapula, sternum and other femoral fractures). The economic burden of incident and prior fragility fractures was estimated at 37 billion. Incident fractures represented 66 % of this cost, long-term fracture care 29 % and pharmacological prevention 5 %. Previous and incident fractures also accounted for 1,180,000 quality-adjusted life years lost during 2010. The costs are expected to increase by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining., Conclusions: In spite of the high social and economic cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by the aging populations, the use of pharmacological interventions to prevent fractures has decreased in recent years, suggesting that a change in healthcare policy is warranted.

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.

Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

Context: A high prevalence of obesity has recently been reported in postmenopausal women with low trauma fracture, suggesting that higher bone mineral density (BMD) in obese individuals may not be protective against fracture., Objective: The aim of this study was to compare BMD and other risk factors for nonvertebral fracture in 1377 obese postmenopausal women., Design: Characteristics of obese women with and without incident nonvertebral fracture were investigated among the prospective cohort in the Study of Osteoporotic Fractures., Setting: The Study of Osteoporotic Fractures is a multicenter study of 9704 women (>99% Caucasian) aged 65 yr and over who were recruited between September 1986 and October 1988 from population-based listings at four U.S. clinical centers., Main Outcome Measure: The main outcome measure was nonvertebral fracture., Results: BMD T-scores in the spine, femoral neck, and total hip were significantly lower in obese women who experienced fractures than in obese women without fracture: mean differences, -0.56 [95% confidence interval (CI) = -0.73 to -0.39], -0.46 (95% CI = -0.57 to -0.36), and -0.51 (95% CI = -0.62 to -0.39), respectively (P < 0.0001 for all). A previous history of fracture [odds ratio = 1.69 (95% CI = 1.33-2.14); P < 0.0001] and femoral neck BMD [1.62 (95% CI = 1.42-1.85) per sd decrease in BMD; P < 0.0001] were independently associated with incident nonvertebral fracture., Conclusions: Obese postmenopausal women who sustain nonvertebral fractures have significantly lower BMD on average than obese women without fracture and are more likely to have a past history of fracture. Fractures in obese postmenopausal women thus exhibit some characteristics of fragility fractures.

Glucocorticoid-induced osteoporosis is common, and the resulting fractures cause significant morbidity and mortality. Rapid bone loss and increased fracture risk occur soon after the initiation of glucocorticoid therapy and are dose dependent. The increase in fracture risk is partly independent of bone mineral density, probably as a result of changes in bone material properties and increased risk of falling. Fracture risk can be assessed using the FRAX algorithm, although risk may be underestimated in patients taking higher doses of glucocorticoids. Because of the rapidity of bone loss and increase in fracture risk after the start of glucocorticoid therapy, primary prevention should be advised in high-risk individuals, for example older women and men, individuals with a previous fracture history and those with low bone mineral density. Bisphosphonates are the front-line choice for the prevention of fracture in the majority of glucocorticoid-treated patients, with teriparatide as a second-line option. Calcium and vitamin D supplements should be co-prescribed unless there is evidence of an adequate dietary calcium intake and vitamin D status., (© 2011 Blackwell Publishing Ltd.)

The epidemiology of osteoporosis is reviewed, with a discussion of secular changes in incidence, geographical variation, and economic costs. The morbidity and mortality associated with hip, vertebral, and forearm fractures are outlined. The main pathogenetic factors contributing to age-related bone loss and osteoporosis are reviewed. Finally, there is a discussion of the recent advances in fracture risk prediction and the use of independent clinical risk factors to improve bone mineral density-based prediction., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Glucocorticoid-induced osteoporosis is a common condition that results in significant morbidity and mortality. The skeletal effects of glucocorticoids include both direct and indirect actions on bone that result in an early, transient increase in bone resorption accompanied by a decrease in bone formation, which is maintained for the duration of glucocorticoid therapy. Rapid bone loss and increased fracture risk occur soon after the initiation of glucocorticoid therapy and are dose dependent. The increase in fracture risk is partly independent of bone mineral density, probably as a result of changes in bone material properties and an increased risk of falling. Bisphosphonates are the front-line choice for prevention of fracture in glucocorticoid-treated patients, with teriparatide as the second-line option; calcium and vitamin D supplements should be co-prescribed in the majority of individuals. Future guidelines for the management of glucocorticoid-induced osteoporosis should recognize the limitations of FRAX in assessing fracture risk in glucocorticoid-treated patients, and should include recently approved interventions, such as zoledronate and teriparatide.

Bone mineral density (BMD) measurements are recommended in some guidelines for monitoring osteoporosis treatment. However, evidence to support this approach is lacking, since treatment-induced changes in bone density may take up to 3 years to detect and do not predict fracture reduction. Biochemical markers of bone turnover have potential for monitoring since they change rapidly in response to treatment and are more predictive of fracture reduction, but variability of their measurement reduces their value in clinical practice. Neither approach has been shown to improve adherence to therapy. By contrast, there is evidence that discussion with a health-care professional improves treatment adherence, regardless of feedback about monitoring tests. At present, there is no justification for the use of bone-density measurement or bone-turnover markers in routine monitoring, but patients should be fully informed about their treatment and provided with the opportunity to discuss treatment-related issues with a health-care professional.

Osteoporosis is characterized by reduced bone mass and alteration in bone architecture, resulting in increased fracture risk. These fractures are a major cause of morbidity and mortality in the elderly and impose a huge economic burden on health services. Oestrogen deficiency plays a major role in the pathogenesis of bone loss and fracture in both women and men. Other pathogenetic factors include reduced physical activity and vitamin D insufficiency. A range of options is available for the prevention of fractures in high risk postmenopausal women. These include the bisphosphonates, strontium ranelate, raloxifene and parathyroid hormone peptides. Because of their broad spectrum of demonstrated anti-fracture efficacy, alendronate, risedronate, zoledronate and strontium ranelate are generally considered as front-line options for most women. The optimum duration of treatment has not been established but re-evaluation of risk and the need for continued therapy after 5 years of treatment may be appropriate. Compliance and persistence with long-term treatment is poor but may be improved by less frequent dosing regimens.

Introduction: We have reported that after an acute stroke, intravenous zoledronate prevented bone loss in the hemiplegic hip. Participants from the trial also volunteered for trans-iliac bone biopsy, to assess the early effects of stroke and zoledronate on iliac bone remodelling., Methods: Patients with acute stroke were randomly assigned to a single intravenous dose of zoledronate 4 mg or placebo within 5 weeks of stroke. Biopsies from 14 patients (3 female, 11 male, mean age 71+/-11) were suitable for analysis. These were taken at mean 10 weeks (+/-2) post-stroke, and included 5 patients who had received zoledronate. Histomorphometry was performed on undecalcified sections using light and fluorescence microscopy. Static and dynamic indices of remodelling were compared to a local reference range from healthy controls. Osteoclasts and their precursors were identified on frozen sections using tartrate resistant acid phosphatase (TRAP) staining. Dual-energy x-ray absorptiometry (DXA) of the proximal femora was performed at baseline and 6 months later., Results: The eroded surface in cancellous bone (ES/BS) was significantly higher in stroke patients than controls (5.7% vs. ref 1.6%, p<0.0001). Although ES/BS did not differ between zoledronate and placebo-treated groups, there were significantly fewer osteoclasts and their precursors in zoledronate-treated individuals (p=0.023). Bone formation indices (osteoid surface, OS/BS and mineralising surface, MS/BS) were significantly lower in stroke patients than controls and although OS/BS was higher in the zoledronate group than the placebo group (p=0.033), MS/BS was not different (p=0.924). There were no differences between hemiplegic and unaffected sides for any histomorphometric parameter despite asymmetric reductions in hip bone mineral density (p=0.013)., Conclusion: Stroke patients had higher resorption indices and lower bone forming surfaces than controls, consistent with uncoupling of bone remodelling. These findings are preliminary and a larger study is required to evaluate the contributions of gender, age and hemiplegic status to the remodelling imbalance. Zoledronate therapy was associated with a reduction in osteoclastic cell numbers consistent with its known mode of action in bone.

In 1999 and 2000 the Royal College of Physicians published guidelines for the prevention and treatment of osteoporosis [Royal College of Physicians. Osteoporosis: clinical guidelines for the prevention and treatment. London: Royal College of Physicians; 1999; 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.; Royal College of Physicians. Glucocorticoid-induced osteoporosis. Guidelines on prevention and treatment; Bone and Tooth Society of Great Britain, National Osteoporosis Society and Royal College of Physicians. London, UK: Royal College of Physicians; 2002]. 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 [Royal College of Physicians, National Osteoporosis Guideline Group on behalf of the Bone Research Society, British Geriatrics Society, British Orthopaedic Association, British Society of Rheumatology, National Osteoporosis Society, Osteoporosis 2000, 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.

Bone-turnover suppression is central to the therapeutic benefit of many interventions used to prevent osteoporotic fractures. There are theoretical concerns that long-term suppression may have adverse effects on bone strength, although at present no direct evidence exists that this happens. Nevertheless, further research is required to establish the optimal duration of treatment with antiresorptive agents.

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.

Rationale: At the request of a Dutch governmental organization, a multidisciplinary group of osteoporosis experts in the Netherlands published in 2002 a guideline on case finding, diagnosis, prevention and treatment of osteoporosis. These guidelines were evaluated for their validity and applicability., Methods: Analysis by 5 external osteoporosis experts using the 'Appraisal of Guidelines for Research & Evaluation' ('AGREE') instrument., Results: The score for the 6 domains of AGREE was 88% for the scope and purpose domain, 76% for stakeholder involvement, 81% for rigour of development, 84% for clarity and presentation, 77% for applicability and 73% for editorial independence. For single components of the domains of AGREE, highest scores were found for systematic methods used to search for evidence (100%), inclusion of individuals from all the relevant professional groups (95%) and ease of identifying key recommendations (95%). Lowest scores to single components of the several domains were given for piloting among target users (44%). All experts recommended the guidelines for use in practice., Conclusions: The AGREE instrument scored high for development, clarity and presentation but low for piloting among target users and implementation. Based on the guideline, algorithms from case finding to treatment were constructed that could be tested for piloting among target users and for implementation of the guideline.