A surrogate FRAX® model for Mongolia has been constructed using age- and sex-specific hip fracture rates for mainland China and age- and sex-specific mortality rates from Mongolia.

FRAX models are frequently requested for countries with little or no data on the incidence of hip fracture. In such circumstances, the development of a surrogate FRAX model is recommended based on country-specific mortality data but using fracture data from a country, usually within the region, where fracture rates are considered to be representative of the index country.

This report describes the development and characteristics of a surrogate FRAX model for Mongolia.

The FRAX model used the ethnic-specific incidence of hip fracture in mainland China, combined with the death risk for Mongolia in 2015-2019. Intervention thresholds were developed based on fracture probabilities equivalent to women with a prior fragility fracture, and their impact was assessed in a referral cohort comprising men at age 50 and above and postmenopausal women. The number of hip fractures in 2015 and 2050 was estimated based on United Nations' predicted changes in population demography.

The surrogate model gave similar hip fracture probabilities to estimates from China. Age-dependent intervention thresholds for a major osteoporotic fracture ranged from a 10-year probability of 2.4% at the age of 40 years to 13.7% at the age of 90 years. In the cohort of those eligible for assessment, 46% of men and 36% of women were eligible for treatment because of a prior fracture. Based on intervention thresholds, a further 0.5% of men and 7.0% of women would be eligible for treatment. It was estimated that 440 hip fractures arose in 2015 in individuals aged 50 years and older in Mongolia, with a predicted 4.3-fold increase expected by 2050, when 1896 hip fractures are expected nationally.

The surrogate FRAX model for Mongolia provides an opportunity to determine fracture probability within the Mongolian population and help guide decisions about treatment.

A surrogate FRAX® model for Nepal has been constructed using age- and sex-specific hip fracture rates for Indians living in Singapore and age- and sex-specific mortality rates from Nepal.

FRAX models are frequently requested for countries with little or no data on the incidence of hip fractures. In such circumstances, the development of a surrogate FRAX model is recommended based on country-specific mortality data but using fracture data from a country, usually within the region, where fracture rates are considered to be representative of the index country.

This report describes the development and characteristics of a surrogate FRAX model for Nepal.

The FRAX model used the ethnic-specific incidence of hip fracture in the Indian community of Singapore, combined with the death risk for Nepal in 2015-2019. The number of hip fractures in 2015 and 2050 was estimated based on the United Nations' predicted changes in population demography.

The surrogate model gave similar hip fracture probabilities to estimates from Sri Lanka, India and Pakistan but lower 10-year fracture probabilities for men and women at older ages compared to the model for Singapore, reflecting a higher mortality risk in Nepal compared with Singapore. There were very close correlations in fracture probabilities between the Nepalese and the Singapore models (r > 0.995) so that the use of the Nepalese model had little impact on the rank order of risk, i.e. a person at the xth percentile of risk with one model will be at the xth percentile of risk with the other. It was estimated that 6897 hip fractures arose in 2015 in individuals aged 50 years and older in Nepal, with a predicted 3-fold increase expected by 2050, when 23,409 hip fractures are expected nationally.

The surrogate FRAX model for Nepal provides an opportunity to determine fracture probability within the Nepalese population and help guide decisions about treatment.

Using race and ethnicity in clinical algorithms potentially contributes to health inequities. The American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee convened the ASBMR Task Force on Clinical Algorithms for Fracture Risk to determine the impact of race and ethnicity adjustment in the US Fracture Risk Assessment Tool (US-FRAX). The Task Force engaged the University of Minnesota Evidence-based Practice Core to conduct a systematic review investigating the performance of US-FRAX for predicting incident fractures over 10 years in Asian, Black, Hispanic, and White individuals. Six studies from the Women's Health Initiative (WHI) and Study of Osteoporotic Fractures (SOF) were eligible; cohorts only included women and were predominantly White (WHI > 80% and SOF > 99%), data were not consistently stratified by race and ethnicity, and when stratified there were far fewer fractures in Black and Hispanic women vs White women rendering area under the curve (AUC) estimates less stable. In the younger WHI cohort (n = 64 739), US-FRAX without bone mineral density (BMD) had limited discrimination for major osteoporotic fracture (MOF) (AUC 0.53 (Black), 0.57 (Hispanic), and 0.57 (White)); somewhat better discrimination for hip fracture in White women only (AUC 0.54 (Black), 0.53 (Hispanic), and 0.66 (White)). In a subset of the older WHI cohort (n = 23 918), US-FRAX without BMD overestimated MOF. The Task Force concluded that there is little justification for estimating fracture risk while incorporating race and ethnicity adjustments and recommends that fracture prediction models not include race or ethnicity adjustment but instead be population-based and reflective of US demographics, and inclusive of key clinical, behavioral, and social determinants (where applicable). Research cohorts should be representative vis-à-vis race, ethnicity, gender, and age. There should be standardized collection of race and ethnicity; collection of social determinants of health to investigate impact on fracture risk; and measurement of fracture rates and BMD in cohorts inclusive of those historically underrepresented in osteoporosis research.

The Fracture Risk Assessment Tool (FRAX®) is a widely utilized country-specific calculator for identifying individuals with high fracture risk; its score is calculated from 12 variables, but its formulation is not publicly disclosed. We aimed to decompose and simplify the FRAX® by utilizing a nationwide community survey database as a reference module for creating a local assessment tool for osteoporotic fracture community screening in any country. Participants (n = 16384; predominantly women (75%); mean age = 64.8 years) were enrolled from the Taiwan OsteoPorosis Survey, a nationwide cross-sectional community survey collected from 2008 to 2011. We identified 11 clinical risk factors from the health questionnaires. BMD was assessed via dual-energy X-ray absorptiometry in a mobile DXA vehicle, and 10-year fracture risk scores, including major osteoporotic fracture (MOF) and hip fracture (HF) risk scores, were calculated using the FRAX®. The mean femoral neck BMD was 0.7 ± 0.1 g/cm2, the T-score was -1.9 ± 1.2, the MOF was 8.9 ± 7.1%, and the HF was 3.2 ± 4.7%. Following FRAX® decomposition with multiple linear regression, the adjusted R2 values were 0.9206 for MOF and 0.9376 for HF when BMD was included and 0.9538 for MOF and 0.9554 for HF when BMD was excluded. The FRAX® demonstrated better prediction for women and younger individuals than for men and elderly individuals after sex and age stratification analysis. Excluding femoral neck BMD, age, sex, and previous fractures emerged as 3 primary clinical risk factors for simplified FRAX® according to the decision tree analysis in this study population. The adjusted R2 values for the simplified country-specific FRAX® incorporating 3 premier clinical risk factors were 0.8210 for MOF and 0.8528 for HF. After decomposition, the newly simplified module provides a straightforward formulation for estimating 10-year fracture risk, even without femoral neck BMD, making it suitable for community or clinical osteoporotic fracture risk screening.

We compared the performance of FRAX according to frailty status in 3554 individuals from the Framingham Study. During 10-year follow-up, 6.9% and 3.0% of participants with and without frailty experienced MOF. Discrimination profiles were lower in participants with frailty compared to those without, but they improved when FRAX included BMD.

Frailty increases fracture risk. FRAX was developed to predict fractures but never validated in individuals with frailty. We aimed to compare the predictive performance of FRAX (v4.3) in individuals with and without frailty.

We conducted a cohort study using the Framingham Heart Study. Frailty was defined by the Fried phenotype. Major osteoporotic fractures (MOF) were ascertained from medical records during 10-year follow-up. To evaluate discrimination and calibration of FRAX, we calculated the area-under-the-receiver-operating characteristics curves (AUC) using logistic regression models and observed-to-predicted fracture probabilities. Analyses were stratified by frailty status.

Frailty was present in 550/3554 (15.5%) of participants. Participants with frailty were older (81.1 vs. 67.6 years), female (68.6% vs. 55.1%), and had greater mean FRAX scores (MOF: 15.9% vs. 10.1%) than participants without frailty. During follow-up, 38 participants with frailty (6.9%) and 91 without (3.0%) had MOFs. The AUC for FRAX (without BMD) was lower in participants with frailty (0.584; 95% CI 0.504-0.663) compared to those without (0.695; 95% CI 0.649-0.741); p value = 0.02. Among participants with frailty, the AUC improved when FRAX included BMD (AUC 0.658, p value < 0.01). FRAX overestimated MOF risk, with larger overestimations in individuals without frailty. Performance of FRAX for hip fracture was similar.

FRAX may have been less able to identify frail individuals at risk for fracture, as compared with individuals without frailty, unless information on BMD is available. This suggests that BMD captures features important for fracture prediction in frail persons. Future fracture prediction models should be developed among persons with frailty.

Fracture probabilities derived from the original FRAX model for Brazil were compared to those from an updated model based on more recent regional estimates of the incidence of hip fracture. Fracture probabilities were consistently lower in the updated FRAX model. Despite large differences between models, differences in the rank order of fracture probabilities were minimal.

Recent epidemiological data indicate that the risk of hip fracture in Brazil is lower than that used to create the original FRAX model. This paper describes the epidemiology of hip fracture in Brazil and the synthesis of an updated FRAX model with the aim of comparing this new model with the original model.

Hip fracture rates from three cities in three regions were combined, weighted by the population of each region. For other major fractures, incidence rates for Brazil were estimated using Swedish ratios for hip to other major osteoporotic fracture (humerus, forearm or clinical vertebral fractures). Mortality estimates were taken from the UN.

Compared to the original FRAX model, the updated model gave lower 10-year fracture probabilities in men and women at all ages. Notwithstanding, there was a very close correlation in fracture probabilities between the original and updated models (r > 0.99) so that the revisions had little impact on the rank order of risk.

The disparities between the original and updated FRAX models indicate the importance of updating country-specific FRAX models with the advent of significant changes in fracture epidemiology.

Hip fractures are common in the aging population, with complications such as avascular necrosis. We describe a case of an 85-y-old woman with early avascular necrosis as a complication from femoral neck fracture discovered on routine bone densitometry screening.

Osteoporosis is the most common metabolic bone disease in the USA and the world. It is a subclinical condition until complicated by fracture(s). These fractures place an enormous medical and personal burden on individuals who suffer from them and take a significant economic toll. Any new fracture in an adult aged 50 years or older signifies imminent elevated risk for subsequent fractures, particularly in the year following the initial fracture. What a patient perceives as an unfortunate accident may be seen as a sentinel event indicative of bone fragility and increased future fracture risk even when the result of considerable trauma. Clinical or subclinical vertebral fractures, the most common type of osteoporotic fractures, are associated with a 5-fold increased risk for additional vertebral fractures and a 2- to 3-fold increased risk for fractures at other sites. Untreated osteoporosis can lead to a vicious cycle of recurrent fracture(s), often resulting in disability and premature death. In appropriate patients, treatment with effective antifracture medication prevents fractures and improves outcomes. Primary care providers and medical specialists are critical gatekeepers who can identify fractures and initiate proven osteoporosis interventions. Osteoporosis detection, diagnosis, and treatment should be routine practice in all adult healthcare settings. The Bone Health and Osteoporosis Foundation (BHOF) - formerly the National Osteoporosis Foundation - first published the Clinician's Guide in 1999 to provide accurate information on osteoporosis prevention and treatment. Since that time, significant improvements have been made in diagnostic technologies and treatments for osteoporosis. Despite these advances, a disturbing gap persists in patient care. At-risk patients are often not screened to establish fracture probability and not educated about fracture prevention. Most concerning, the majority of highest risk women and men who have a fracture(s) are not diagnosed and do not receive effective, FDA-approved therapies. Even those prescribed appropriate therapy are unlikely to take the medication as prescribed. The Clinician's Guide offers concise recommendations regarding prevention, risk assessment, diagnosis, and treatment of osteoporosis in postmenopausal women and men aged 50 years and older. It includes indications for bone densitometry as well as fracture risk thresholds for pharmacologic intervention. Current medications build bone and/or decrease bone breakdown and dramatically reduce incident fractures. All antifracture therapeutics treat but do not cure the disease. Skeletal deterioration resumes sooner or later when a medication is discontinued-sooner for nonbisphosphonates and later for bisphosphonates. Even if normal BMD is achieved, osteoporosis and elevated risk for fracture are still present. The diagnosis of osteoporosis persists even if subsequent DXA T-scores are above - 2.5. Ongoing monitoring and strategic interventions will be necessary if fractures are to be avoided. In addition to pharmacotherapy, adequate intake of calcium and vitamin D, avoidance of smoking and excessive alcohol intake, weight-bearing and resistance-training exercise, and fall prevention are included in the fracture prevention armamentarium. Where possible, recommendations in this guide are based on evidence from RCTs; however, relevant published data and guidance from expert clinical experience provides the basis for recommendations in those areas where RCT evidence is currently deficient or not applicable to the many osteoporosis patients not considered for RCT participation due to age and morbidity.

A prospective hospital-based survey in representative regions of Saudi Arabia determined the incidence of fractures at the hip. The hip fracture rates were used to create a FRAX® model to facilitate fracture risk assessment in Saudi Arabia.

This paper describes the incidence of hip fracture in the Kingdom of Saudi Arabia that was used to characterize the current and future burden of hip fracture, to develop a country-specific FRAX® tool for fracture prediction and to compare fracture probabilities with neighbouring countries.

During a 2-year (2017/2018) prospective survey in 15 hospitals with a defined catchment population, hip fractures in Saudi citizens were prospectively identified from hospital registers. The number of hip fractures and future burden was determined from national demography. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Saudi Arabia. Fracture probabilities were compared with those from Kuwait and Abu Dhabi.

The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 2,949 and is predicted to increase nearly sevenfold to 20,328 in 2050. Hip fracture rates were comparable with estimates from Abu Dhabi and Kuwait. By contrast, probabilities of a major osteoporotic fracture or hip fracture from the age of 70 years were much lower than those seen in Abu Dhabi and Kuwait due to higher mortality estimates for Saudi Arabia.

A country-specific FRAX tool for fracture prediction has been developed for Saudi Arabia which is expected to help guide decisions about treatment.

Hip fracture data were retrieved from electronical medical records for the years 2017-2019 in the State of Qatar and used to create a FRAX® model to facilitate fracture risk assessment. Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi, and Kuwait but fracture probabilities varied due to differences in mortality.

This paper describes the epidemiology of osteoporotic fractures in the State of Qatar that was used to develop the country-specific fracture prediction FRAX® tool.

Hip fracture data were retrieved from electronic medical records for the years 2017-2019 in the State of Qatar. The age and sex specific incidence of hip fracture in Qatari residents and national mortality rates were used to create a FRAX® model. Fracture probabilities were compared with those from neighboring countries having FRAX models.

Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi and Kuwait. In contrast, probabilities of a major osteoporotic fracture or hip fracture were lower in Qatar than in Kuwait but higher than those in Abu Dhabi and Saudi Arabia due to differences in mortality.

The FRAX model should enhance accuracy of determining fracture probability among the Qatari population and help guide decisions about treatment.

Osteoporosis and fragility fractures result in significant morbidity and mortality and contribute to substantial healthcare costs. Despite being a treatable disease, osteoporosis remains both underdiagnosed and undertreated in the US general population, with significant disparities in care between non-White and White women. These disparities are evident from screening to post-fracture treatment. Non-White women are less likely to be screened for osteoporosis, to be prescribed pharmacotherapy, or to receive treatment post-fracture; furthermore, the mortality rate after fracture is higher in non-White women. Given existing diagnostic and treatment disparities, additional studies and interventions are needed to optimize the bone health of Asian, Black, Hispanic, and Native American women, and to reduce morbidity and mortality from osteoporosis and fragility fractures.

The Fracture Risk Assessment Tool (FRAX) is the most widely used tool for fracture prediction. It provides 10-year probabilities for hip and major osteoporotic fracture (MOF). It uses country-specific hip fracture incidence and life expectancy data, and for most countries, MOF/hip fracture incidence rate ratios (IRRs) from Malmo Sweden. However, the risk of MOF varies by age, sex, and geography. The objective is to compare the MOF/hip IRRs across countries, by sex and age. This systematic review targeted observational studies of MOF and hip fractures in individuals >50 years (PROSPERO 2019 CRD42019129259). One reviewer screened potential articles. Two reviewers completed duplicate and independent data abstraction, and assessed study quality based on population representativeness, study design and duration, definition of ethnicity, and fracture characteristics. We calculated the MOF/hip IRRs (95% confidence interval) and Z-values to compare IRRs in various countries to those for Sweden. We included 27 studies, of fair to good quality in the majority, from Europe (15), US and Canada (7), Asia (3), and Australia (2). The IRRs were twofold to 10-fold higher in younger compared to older age categories, and in women compared to men, with few exceptions. Within Europe, and using Sweden as a reference, MOF/Hip IRRs in women 50-54 years from Finland, Italy, Netherlands, Denmark, and UK were significantly lower by 38% to 60%. Findings were similar in men. At older ages, MOF/Hip IRRs were consistently lower in women from European countries compared to Sweden, by 10%-40% and 11%-51%, at 75-79 years and 85-89 years, respectively. Findings were heterogenous in men and in non-European countries. In conclusion, the MOF/hip fracture IRR may vary between countries. The variability at older ages may affect FRAX prediction when country-specific fracture IRRs are not used. Further research is needed to elucidate the implication of our findings to FRAX-derived MOF estimates in various countries. © 2021 American Society for Bone and Mineral Research (ASBMR).

An informatics-driven population bone health clinic was implemented to identify, screen, and treat rural US Veterans at risk for osteoporosis. We report the results of our implementation process evaluation which demonstrated BHT to be a feasible telehealth model for delivering preventative osteoporosis services in this setting.

An established and growing quality gap in osteoporosis evaluation and treatment of at-risk patients has yet to be met with corresponding clinical care models addressing osteoporosis primary prevention. The rural bone health tea m (BHT) was implemented to identify, screen, and treat rural Veterans lacking evidence of bone health care and we conducted a process evaluation to understand BHT implementation feasibility.

For this evaluation, we defined the primary outcome as the number of Veterans evaluated with DXA and a secondary outcome as the number of Veterans who initiated prescription therapy to reduce fracture risk. Outcomes were measured over a 15-month period and analyzed descriptively. Qualitative data to understand successful implementation were collected concurrently by conducting interviews with clinical personnel interacting with BHT and BHT staff and observations of BHT implementation processes at three site visits using the Promoting Action on Research Implementation in Health Services (PARIHS) framework.

Of 4500 at-risk, rural Veterans offered osteoporosis screening, 1081 (24%) completed screening, and of these, 37% had normal bone density, 48% osteopenia, and 15% osteoporosis. Among Veterans with pharmacotherapy indications, 90% initiated therapy. Qualitative analyses identified barriers of rural geography, rural population characteristics, and the infrastructural resource requirement. Data infrastructure, evidence base for care delivery, stakeholder buy-in, formal and informal facilitator engagement, and focus on teamwork were identified as facilitators of implementation success.

The BHT is a feasible population telehealth model for delivering preventative osteoporosis care to rural Veterans.

A surrogate FRAX® model for Pakistan has been constructed using age-specific hip fracture rates for Indians living in Singapore and age-specific mortality rates from Pakistan.

FRAX models are frequently requested for countries with little or no data on the incidence of hip fracture. In such circumstances, the International Society for Clinical Densitometry and International Osteoporosis Foundation have recommended the development of a surrogate FRAX model, based on country-specific mortality data but using fracture data from a country, usually within the region, where fracture rates are considered to be representative of the index country.

This paper describes the development and characteristics of a surrogate FRAX model for Pakistan.

The FRAX model used the ethnic-specific incidence of hip fracture in Indian men and women living in Singapore, combined with the death risk for Pakistan.

The surrogate model gave somewhat lower 10-year fracture probabilities for men and women at all ages compared to the model for Indians from Singapore, reflecting a higher mortality risk in Pakistan. There were very close correlations in fracture probabilities between the surrogate and authentic models (r ≥ 0.998) so that the use of the Pakistan model had little impact on the rank order of risk. It was estimated that 36,524 hip fractures arose in 2015 in individuals over the age of 50 years in Pakistan, with a predicted increase by 214% to 114,820 in 2050.

The surrogate FRAX model for Pakistan provides an opportunity to determine fracture probability within the Pakistan population and help guide decisions about treatment.

The hip fracture rates in South Africa were used to create ethnic-specific FRAX® models to facilitate fracture risk assessment.

The aim of this study was to develop FRAX models to compute the 10-year probability of hip fracture and major osteoporotic fracture and assess their potential clinical application.

Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for the White, Black African, Coloured and Indian population of South Africa. Age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women to determine fracture probabilities at a femoral neck T score of -2.5 SD, or those equivalent to a woman with a prior fragility fracture. Fracture probabilities were compared with those from selected countries.

Probabilities were consistently higher in Indian than in Coloured men and women, in turn, higher than in Black South Africans. For White South Africans, probabilities were lower than in Indians at young ages up to the age of about 80 years. When a BMD T score of -2.5 SD was used as an intervention threshold, FRAX probabilities in women age 50 years were approximately 2-fold higher than in women of the same age but with an average BMD and no risk factors. The increment in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T score of -2.5 SD was no longer a risk factor. Probabilities equivalent to women with a previous fracture rose with age and identified women at increased risk at all ages.

These FRAX models should enhance accuracy of determining fracture probability amongst the South African population and help guide decisions about treatment.

Prolonged use of anti-cancer treatments in breast and prostate tumors alters physiological bone turnover leading to adverse skeletal related events, such as osteoporosis, loss of bone mass, and increased risk of fractures. These complications known as cancer treatment-induced bone loss (CTIBL) should be managed with bone targeting agents such as the bisphosphonates and denosumab. The latter is a monoclonal antibody against the receptor activator of nuclear factor-kB ligand (RANKL) that suppresses osteoclasts function and survival increasing bone mass.

This review will focus on the mechanisms associated with bone loss induced by cancer treatments and the most recent evidence about the use of denosumab as preventive and therapeutic strategy to protect bone health. Moreover, we will discuss several key aspects regarding the clinical practical use of denosumab to optimize the management of CTLIB in breast and prostate cancer.

Denosumab treatment strongly prevents cancer therapies-related skeletal issues in breast and prostate cancer with a good safety profile. Adjuvant six-monthly denosumab delays the time to first fracture onset in early stage breast cancer patients with normal or altered bone mineral density (BMD). Similarly, denosumab treatment is able to prevent fractures and BMD loss in nonmetastatic prostate cancer patients.

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Methods: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options. Conclusion: This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis. Abbreviations: 25(OH)D = 25-hydroxyvitamin D; AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; AFF = atypical femoral fracture; ASBMR = American Society for Bone and Mineral Research; BEL = best evidence level; BMD = bone mineral density; BTM = bone turnover marker; CI = confidence interval; CPG = clinical practice guideline; CTX = C-terminal telopeptide type-I collagen; DXA = dual-energy X-ray absorptiometry; EL = evidence level; FDA = U.S. Food and Drug Administration; FRAX® = Fracture Risk Assessment Tool; GI = gastrointestinal; HORIZON = Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly Pivotal Fracture Trial (zoledronic acid and zoledronate are equivalent terms); ISCD = International Society for Clinical Densitometry; IU = international units; IV = intravenous; LSC = least significant change; NOF = National Osteoporosis Foundation; ONJ = osteonecrosis of the jaw; PINP = serum amino-terminal propeptide of type-I collagen; PTH = parathyroid hormone; R = recommendation; ROI = region of interest; RR = relative risk; SD = standard deviation; TBS = trabecular bone score; VFA = vertebral fracture assessment; WHO = World Health Organization.

Patients with inflammatory arthropathies have a high rate of fragility fractures. Diagnostic assessment and monitoring of bone density and quality are therefore critically important. Here, we review standard and advanced techniques to measure bone density and quality, specifically focusing on patients with inflammatory arthropathies.

Current standard procedures are dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). DXA-based newer methods include trabecular bone score (TBS) and vertebral fracture assessment (VFA). More advanced imaging methods to measure bone quality include high-resolution peripheral quantitative computed tomography (HR-pQCT) as well as multi-detector CT (MD-CT) and magnetic resonance imaging (MRI). Quantitative ultrasound has shown promise but is not standard to assess bone fragility. While there are limitations, DXA remains the standard technique to measure density in patients with rheumatological disorders. Newer modalities to measure bone quality may allow better characterization of bone fragility but currently are not standard of care procedures.

The Canadian Association of Radiologists and Osteoporosis Canada currently endorse a fracture risk prediction tool called CAROC. It has been used in Canada since 2005 with an update in 2010. It is an integral part of bone mineral densitometry reporting across the country. New osteoporosis guidelines from Osteoporosis Canada (OC) are expected in the near future. There has been pressure on radiologists to report fracture risk using an alternative fracture risk prediction platform called FRAX. In addition, OC collaborated in the development of the Canadian FRAX model and has been copromoting both FRAX and CAROC, raising the prospect that new guidelines may seek to replace CAROC with FRAX for fracture risk determination. A number of concerns have been raised about FRAX, including: (1) FRAX has not released its algorithms to the public domain with the consequence that it is impossible to verify results for an individual patient; (2) FRAX has incorrectly claimed that it was developed by the World Health Organization (WHO) and has used this affiliation to promote itself until recently ordered by the WHO to desist; (3) FRAX requires collection of additional clinical information beyond that needed for CAROC, and this patient-reported medical data is prone to substantial error; and (4) despite claims to the contrary, there are no valid studies comparing FRAX to CAROC. We believe it is important that radiologists be aware of these issues in order to provide input into future Technical Standards for Bone Mineral Densitometry Reporting of the Canadian Association of Radiologists.

Retrospective population-based survey in 2 regions of the Republic of Moldova determined the incidence of fractures at the hip, proximal humerus and distal forearm. The estimated number of such fractures nationwide for 2015 was 11,271 and is predicted to increase to 15,863 in 2050. The hip fracture rates were used to create a FRAX model to help guide decisions about treatment.

This paper describes the epidemiology of osteoporotic fractures in Republic of Moldova that was used to develop the country-specific fracture prediction FRAX® tool.

We carried out a retrospective population-based survey in 2 regions of the Republic of Moldova (Anenii Noi district and Orhei district) representing approximately 6% of the country's population. We identified hip, forearm and humerus fractures in 2011 and 2012 from hospital registers and primary care sources. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Moldova. Fracture probabilities were compared with those from neighbouring countries having FRAX models.

The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 3911 and is predicted to increase by 60% to 6492 in 2050. Hip fracture incidence was a good predictor of forearm and humeral fractures. FRAX-based probabilities were higher in Moldova than neighbouring countries (Ukraine and Romania).

The FRAX model should enhance accuracy of determining fracture probability among the Moldavan population and help guide decisions about treatment.

The hip fracture rates from Kazakhstan were used to create a surrogate FRAX® model for the Kyrgyz Republic.

The International Society for Clinical Densitometry and International Osteoporosis Foundation recommend utilizing a surrogate FRAX model, based on the country-specific risk of death, and fracture data based on a country where fracture rates are considered to be representative of the index country.

This paper describes a surrogate FRAX model for the Kyrgyz Republic.

The FRAX model used the incidence of hip fracture from the neighbouring country of Kazakhstan and the death risk for the Kyrgyz Republic.

Compared with the model for Kazakhstan, the surrogate model gave somewhat higher 10-year fracture probabilities for men between 60 and 80 years of age and lower probabilities for men above the age of 80. For women the probabilities were similar up to the age of 75-80 years and then lower. There were very close correlations in fracture probabilities between the surrogate and authentic models (1.00) so that the use of the Kyrgyz model had little impact on the rank order of risk. It was estimated that 2752 hip fractures arose in 2015 in individuals over the age of 50 years in the Kyrgyz Republic, with a predicted increase by 207% to 8435 in 2050.

The surrogate FRAX model for the Kyrgyz Republic provides the opportunity to determine fracture probability among the Kyrgyz population and help guide decisions about treatment.

Retrospective and prospective population-based survey in a region of the Republic of Kazakhstan determined the incidence of fractures at the hip, proximal humerus and distal forearm. The hip fracture rates were used to create a FRAX® model to enhance fracture risk assessment in Kazakhstan.

This paper describes the epidemiology of osteoporotic fractures in the Republic of Kazakhstan that was used to develop a country specific FRAX® tool for fracture prediction.

We carried out a retrospective population-based survey in Taldykorgan in the Republic of Kazakhstan representing approximately 1% of the country's population. Hip, forearm and humerus fractures were identified retrospectively in 2015 and 2016 from hospital registers and the trauma centre. Hip fractures were prospectively identified in 2017 from the same sources and additionally from primary care data. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Kazakhstan. Fracture probabilities were compared with those from neighbouring countries having FRAX models.

The difference in hip fracture incidence between the retrospective and prospective survey indicated that approximately 25% of hip fracture cases did not come to hospital attention. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 11,690 and is predicted to increase by 140% to 28,000 in 2050. Hip fracture incidence was a good predictor of forearm and humeral fractures in men but not in women.

The FRAX model should enhance accuracy of determining fracture probability among the Kazakh population and help guide decisions about treatment.

A prospective population-based survey in a region of the Republic of Uzbekistan determined the incidence of fractures at the hip. The hip fracture rates were used to create a FRAX® model to facilitate fracture risk assessment in Uzbekistan.

This paper describes the epidemiology of hip fracture in the Republic of Uzbekistan that was used to develop a country-specific FRAX® tool for fracture prediction.

During a 1-year (2016/17) prospective population-based survey in the Pap district of the Republic of Uzbekistan, hip fractures were prospectively identified from hospital registers, trauma centres and primary care and community sources. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Uzbekistan. Fracture probabilities were compared with those from neighbouring Kazakhstan and Kyrgystan.

Approximately 41% of hip fracture cases did not come to medical attention, and two thirds of patients overall were not admitted to hospital. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 16,764 and is predicted to increase more than three-fold to 60,272 in 2050. FRAX-based probabilities were higher in Uzbekistan than Kazakhstan or Kyrgystan.

The FRAX model should enhance accuracy of determining fracture probability among the Uzbek population and help guide decisions about treatment.

Invited narrative review.

The aim of this review was to summarize current literature regarding risk factors that surgeons can optimize in the preoperative setting in the spinal surgery patient, in order to reduce complications and improve patient-reported outcomes.

Review of the relevant literature by the authors.

Modifiable risk factors identified relative to the patient include obesity, malnutrition/nutrient deficiency, diabetes/hyperglycemia, preoperative anemia, vitamin D/DEXA (dual-energy radiograph absorptiometry), nicotine use/smoking, and opioid use/psychosocial factors.

By maximizing a patient's physiological and psychological status prior to elective spine surgery, we may move closer to achieving the goals of value-based care: improving patient-reported outcomes while decreasing the cost of care.

A retrospective population-based survey was undertaken in a region of Bulgaria to determine the incidence of hip fracture. The estimated number of hip fractures nationwide for 2015 was 9322 and is predicted to increase to 11,398 in 2050. The hip fracture rates were used to create a FRAX model.

To describe the epidemiology of hip fractures in Bulgaria, which was then used to develop the country-specific fracture prediction FRAX® tool.

We carried out a retrospective population-based survey in Stara Zagora, Bulgaria, representing approximately 4.6% of the country's population. We identified hip fractures occurring in 2015, 2016 and 2017 from hospital registers and primary care sources held by the regional health insurance agency. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Bulgaria. Fracture probabilities were compared with those from neighbouring countries having FRAX models.

The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 9322 and is predicted to increase to 11,398 in 2050. FRAX-based probabilities were higher in Bulgaria than those in Serbia or Romania, lower than those in Turkey and similar to those in Greece.

The FRAX model should enhance accuracy of determining fracture probability among the Bulgarian population and help guide decisions about treatment.

The FRAX tool incorporates data on the incidence of fractures and mortality in each country. The epidemiology of fractures changes over time, this makes it necessary to update the specific FRAX model of each population. It is shown that there are differences between old and new FRAX models in older individuals.

A new FRAX® model for Ecuador was released online in April 2019. This paper describes the data used to build the revised model, its characteristics, and how intervention and assessment thresholds were constructed.

The national rates of hip fracture incidence standardized by age and sex from the age of 40 years for 2016 were used to synthesize a FRAX model for Ecuador. For other major fractures, Ecuadorian incidence rates were calculated using ratios obtained in Malmö, Sweden, for other major osteoporotic fractures. The new FRAX model was compared with the previous model released in 2012. Assessment and intervention thresholds were based on age-specific probabilities of a major osteoporotic fracture equivalent to women with a previous fracture.

Fracture incidence rates increase with age. The probability of hip or major fractures at 10 years increased in patients with a clinical risk factor, lower BMI, female sex, a higher age, and a lower BMD T-score. Compared to the previous model, the new FRAX model gave similar 10-year fracture probabilities in men and women age less than70 years but substantially higher above this age. Notwithstanding, there were very close correlations in fracture probabilities between the two models (> 0.99) so that the revision had little impact on the rank order of risk.

The FRAX tool provides a country-specific fracture prediction model for Ecuador. This update of the model is based on the original FRAX methodology, which has been validated externally in several independent cohorts. The FRAX model is an evolving tool that is being continuously refined, as the databases of each country are updated with more epidemiological information.

AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial (FIT) Long-term Extension FRAX_® = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B ligand RCT = randomized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization.

Despite growing rates of fragility fractures, there has been a lack of research investigating the risk and characteristics of recurrent fragility fractures.

The Medicare Standard Analytic Files database was used to identify patients from 2005 to 2009 who were older than 65 years, had a diagnosis of osteoporosis or osteopenia, and sustained a fragility fracture of the proximal humerus, distal radius, hip, ankle, or vertebral column. The incidence and type of recurrent fragility fracture were tracked over a 36-month period.

A total of 1,059,212 patients had an initial fragility fracture from 2005 to 2009. Of these patients, 5.8% had a subsequent fragility fracture within 1 year for their initial fracture, 8.8% within 2 years, and 11.3% within 3 years. At 3-year follow-up, hip fractures were the most common type of subsequent fracture, regardless of the initial fracture type (6.5%, P < 0.001). Vertebral compression and proximal humerus fractures (13.8% and 13.2%, respectively) were most likely to be associated with a recurrent fragility fracture.

Patients who have any type of fragility fracture have a notable risk of subsequent fractures within 3 years, especially hip fractures. These patients should be evaluated and treated for underlying risks factors, including osteoporosis and/or osteopenia.

Retrospective, level III.

To determine the association between dual-energy x-ray absorptiometry (DXA) testing for osteoporosis and subsequent fractures in US male veterans without a previous fracture.

This is a propensity score-matched observational study using Centers for Medicare and Medicaid Services and Veterans Affairs (VA) data from January 1, 2000, through December 31, 2010, with a mean follow-up time of 4.7 years (range, 0-10 years). Men receiving VA primary care aged 65 to 99 years without a previous fracture (N=2,539,812) were included. Men undergoing DXA testing were propensity score matched with untested controls in a 1:3 ratio, indicating the probability of DXA testing within the next year. Time to first clinical fracture was the primary outcome. Comorbidities, demographic characteristics, medications, DXA results, and osteoporosis treatment were defined using administrative data and natural language processing. A landmark analysis contingent on surviving to 12 months after screening was completed, accounting for competing risk of mortality.

During follow-up of 153,311 men tested by DXA and 390,158 controls, 56,083 (10.3%) had sustained a fracture and 111,774 (20.6%) died. Overall, DXA testing was not associated with a decrease in fractures; conclusions are limited by unmeasured confounders and low medication initiation and adherence in those meeting treatment thresholds (12% of follow-up time). In contrast, DXA testing in prespecified subgroups was associated with a lower risk of fracture in comparison to the overall population who underwent DXA testing: androgen deprivation therapy (hazard ratio [HR], 0.77; 95% CI, 0.66-0.89), glucocorticoids (HR, 0.77; 95% CI, 0.72-0.84), age 80 years and older (HR, 0.85; 0.81-0.90), 1 or more VA guideline risk factors (HR, 0.91; 95% CI, 0.87-0.95), and high Fracture Risk Assessment Tool using body mass index score (HR, 0.90; 95% CI, 0.86-0.95).

Current VA DXA testing practices are ineffective overall; interventions to improve treatment adherence are needed. Targeted DXA testing in higher-risk men was associated with a lower fracture risk.

Fracture probabilities resulting from the newly generated FRAX model for Belarus based on regional estimates of the hip fracture incidence were compared with FRAX models of neighboring countries. Differences between the country-specific FRAX patterns and the rank orders of fracture probabilities were modest.

This paper describes the epidemiology of hip fractures in Belarus that was used to develop the country-specific fracture prediction FRAX® tool and illustrates its features compared to models for the neighboring countries of Poland, Russia, and Lithuania.

We carried out a population-based study in a region of Belarus (the city of Mozyr) representing approximately 1.2% of the country's population. We aimed to identify all hip fractures in 2011-2012 from hospital registers and primary care sources. Age- and sex-specific incidence and national mortality rates were incorporated into a FRAX model for Belarus. Fracture probabilities were compared with those derived from FRAX models in neighboring countries.

The estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 8250 in 2015 and is predicted to increase to 12,918 in 2050. The annual incidence of fragility hip fractures in individuals aged 50 years or more was 24.6/10,000 for women and 14.6/10,000 for men, standardized to the world population. The comparison with FRAX models in neighboring countries showed that hip fracture probabilities in men and women in Belarus were similar to those in Poland, Russia, and Lithuania. The difference in incidence rates between the surveys including or excluding data from primary care suggested that 29.1% of patients sustaining a hip fracture were not hospitalized and, therefore, did not receive specialized medical care.

A substantial proportion of hip fractures in Belarus does not come to hospital attention. The FRAX model should enhance accuracy of determining fracture probability among the Belarus population and help guide decisions about treatment.

The substantial increase in the burden of non-communicable diseases in general and osteoporosis in particular, necessitates the establishment of efficient and targeted diagnosis and treatment strategies. This chapter reviews and compares different tools for osteoporosis screening and diagnosis; it also provides an overview of different treatment guidelines adopted by countries worldwide. While access to dual-energy X-ray absorptiometry to measure bone mineral density (BMD) is limited in most areas in the world, the introduction of risk calculators that combine risk factors, with or without BMD, have resulted in a paradigm shift in osteoporosis screening and management. To-date, forty eight risk assessment tools that allow risk stratification of patients are available, however only few are externally validated and tested in a population-based setting. These include Osteoporosis Self-Assessment Tool; Osteoporosis Risk Assessment Instrument; Simple Calculated Osteoporosis Risk Estimation; Canadian Association of Radiologists and Osteoporosis Canada calculator; Fracture Risk Assessment Calculator (FRAX); Garvan; and QFracture. These tools vary in the number of risk factors incorporated. We present a detailed analysis of the development, characteristics, validation, performance, advantages and limitations of these tools. The World Health Organization proposes a dual-energy X-ray absorptiometry-BMD T-score ≤ -2.5 as an operational diagnostic threshold for osteoporosis, and many countries have also adopted this cut-off as an intervention threshold in their treatment guidelines. With the introduction of the new fracture assessment calculators, many countries chose to include fracture risk as one of the major criteria to initiate osteoporosis treatment. Of the 52 national guidelines identified in 36 countries, 30 included FRAX derived risk in their intervention threshold and 22 were non-FRAX based.  No universal tool or guideline approach will address the needs of all countries worldwide.  Osteoporosis screening and management guidelines are best tailored according to the needs and resources of individual counties. While few countries have succeeded in generating valuable epidemiological data on osteoporotic fractures, to validate their risk calculators and base their guidelines, many have yet to find the resources to assess variations and secular trends in fractures, the performance of various calculators, and ultimately adopt the most convenient care pathway algorithms.

Fracture probabilities derived from the surrogate FRAX model for Armenia were compared to those from the model based on regional estimates of the incidence of hip fracture. Disparities between the surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal.

Armenia has relied on a surrogate FRAX model based on the fracture epidemiology of Romania. This paper describes the epidemiology of fragility fractures in Armenia used to create an Armenia-specific FRAX model with an aim of comparing this new model with the surrogate model.

We carried out a population-based study in two regions of Armenia (Ararat and Vayots Dzor representing approximately 11% of the country's population). We aimed to identify all low-energy fractures: retrospectively from hospital registers in 2011-2012 and prospectively in 2013 with the inclusion of primary care sources.

The differences in incidence between the surveys with and without data from primary care suggested that 44% of patients sustaining a hip fracture did not receive specialized medical care. A similar proportion of forearm and humeral fractures did not come to hospital attention (48 and 49%, respectively). Only 57.7% of patients sustaining a hip fracture were hospitalized. In 2013, hip fracture incidence at the age of 50 years or more was 201/100,000 for women and 136/100,000 for men, and age- and sex-specific rates were incorporated into the new "authentic" FRAX model for Armenia. Compared to the surrogate model, the authentic model gave lower 10-year fracture probabilities in men and women aged less than 70 years but substantially higher above this age. Notwithstanding, there were very close correlations in fracture probabilities between the surrogate and authentic models (> 0.99) so that the revisions had little impact on the rank order of risk.

A substantial proportion of major osteoporotic fractures in Armenia do not come to hospital attention. The disparities between surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal.

A country-specific FRAX model has been developed for the Ukraine to replace the Austrian model hitherto used. Comparison of the Austrian and Ukrainian models indicated that the former markedly overestimated fracture probability whilst correctly stratifying risk.

FRAX has been used to estimate osteoporotic fracture risk since 2009. Rather than using a surrogate model, the Austrian version of FRAX was adopted for clinical practice. Since then, data have become available on hip fracture incidence in the Ukraine.

The incidence of hip fracture was computed from three regional estimates and used to construct a country-specific FRAX model for the Ukraine. The model characteristics were compared with those of the Austrian FRAX model, previously used in Ukraine by using all combinations of six risk factors and eight values of BMD (total number of combinations =512).

The relationship between the probabilities of a major fracture derived from the two versions of FRAX indicated a close correlation between the two estimates (r > 0.95). The Ukrainian version, however, gave markedly lower probabilities than the Austrian model at all ages. For a major osteoporotic fracture, the median probability was lower by 25% at age 50 years and the difference increased with age. At the age of 60, 70 and 80 years, the median value was lower by 30, 53 and 65%, respectively. Similar findings were observed for men and for hip fracture.

The Ukrainian FRAX model should enhance accuracy of determining fracture probability among the Ukrainian population and help to guide decisions about treatment. The study also indicates that the use of surrogate FRAX models or models from other countries, whilst correctly stratifying risk, may markedly over or underestimate the absolute fracture probability.

Falls is a risk factor for fracture. The FRAX^® predicts fractures. Whether the FRAX^® is associated with fall in both gender is inconclusive. The aim of our study is to evaluate the association between FRAX scores and falls.

The cross-sectional study set from 2009 to 2010 included 1200 community-dwelling people who were systematically sampled in central Taiwan. The 1200 participants (men: 524; women: 676; ≥40 years old) completed questionnaires about socioeconomic status; lifestyle; medical and fall history were completed. FRAX scores with and without bone mineral density (BMD) were calculated by using the Taiwan calculator.

A total of 19.8% participants fell down. Binary regression models showed that diabetes mellitus history (OR: 1.61; 95% CI: 1.03-2.52), the FRAX without BMD in a continuous major score (OR: 1.06; 95% CI: 1.03-1.09), continuous hip score (OR: 1.11; 95% CI: 1.05-1.16), categorical major score ≥ 10% (OR: 1.81; 95% CI: 1.25-2.61), and categorical hip score ≥ 3% (OR: 1.80; 95% CI: 1.30-2.50) were independent risk factors for falls. FRAX with BMD in a continuous major score (OR: 1.04; 95% CI: 1.02-1.06), continuous hip score (OR: 1.06; 95% CI: 1.02-1.09), categorical major score ≥ 10% (OR: 1.52; 95% CI: 1.09-2.12), and categorical hip score ≥ 3% (OR: 1.53; 95% CI: 1.13-2.09) were also independent risk factors.

We concluded that FRAX^® scores with and without BMD were unanimously correlated with falls in community-dwelling middle-aged and elderly males and females.

This systematic review identified assessment guidelines for osteoporosis that incorporate FRAX. The rationale for intervention thresholds is given in a minority of papers. Intervention thresholds (fixed or age-dependent) need to be country-specific.

In most assessment guidelines, treatment for osteoporosis is recommended in individuals with prior fragility fractures, especially fractures at spine and hip. However, for those without prior fractures, the intervention thresholds can be derived using different methods. The aim of this report was to undertake a systematic review of the available information on the use of FRAX® in assessment guidelines, in particular the setting of thresholds and their validation.

We identified 120 guidelines or academic papers that incorporated FRAX of which 38 provided no clear statement on how the fracture probabilities derived are to be used in decision-making in clinical practice. The remainder recommended a fixed intervention threshold (n = 58), most commonly as a component of more complex guidance (e.g. bone mineral density (BMD) thresholds) or an age-dependent threshold (n = 22). Two guidelines have adopted both age-dependent and fixed thresholds.

Fixed probability thresholds have ranged from 4 to 20 % for a major fracture and 1.3-5 % for hip fracture. More than one half (39) of the 58 publications identified utilised a threshold probability of 20 % for a major osteoporotic fracture, many of which also mention a hip fracture probability of 3 % as an alternative intervention threshold. In nearly all instances, no rationale is provided other than that this was the threshold used by the National Osteoporosis Foundation of the USA. Where undertaken, fixed probability thresholds have been determined from tests of discrimination (Hong Kong), health economic assessment (USA, Switzerland), to match the prevalence of osteoporosis (China) or to align with pre-existing guidelines or reimbursement criteria (Japan, Poland). Age-dependent intervention thresholds, first developed by the National Osteoporosis Guideline Group (NOGG), are based on the rationale that if a woman with a prior fragility fracture is eligible for treatment, then, at any given age, a man or woman with the same fracture probability but in the absence of a previous fracture (i.e. at the 'fracture threshold') should also be eligible. Under current NOGG guidelines, based on age-dependent 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 using a hybrid model reduces this disparity.

The use of FRAX (fixed or age-dependent thresholds) as the gateway to assessment identifies individuals at high risk more effectively than the use of BMD. However, the setting of intervention thresholds needs to be country-specific.

Adults who require long-term anticoagulation with low-molecular-weight heparin (LMWH) such as cancer patients or the elderly may be at increased risk of fractures.

To determine the effects of LMWH therapy of at least 3 months' duration on fractures and bone mineral density (BMD) in non-pregnant adult populations.

We systematically reviewed electronic databases (e.g., MEDLINE, EMBASE), conferences and bibliographies until June 2015 and included comparative studies in non-pregnant adult populations that examined the effects of LMWH (≥3 months) on fractures and BMD. We synthesized evidence qualitatively and used random-effects meta-analysis to quantify the effect of LMWH on fractures.

Sixteen articles reporting 14 studies were included: 10 clinical trials (n = 4865 participants) and four observational cohort studies (3 prospective, n = 221; 1 retrospective, n = 30). BMD and fractures were secondary outcomes in the majority of trials, while they were primary outcomes in the majority of observational studies. In participants with venous thromboembolism and underlying cardiovascular disease or cancer (5 RCTs, n = 2280), LMWH for 3-6 months did not increase the relative risk of all fractures at 6-12 months compared to unfractionated heparin, oral vitamin K antagonists or placebo [pooled risk ratio (RR) = 0.58, 95 % CI: 0.23-1.43; I(2) = 12.5 %]. No statistically significant increase in the risk of fractures at 6-12 months was found for cancer patients (RR = 1.08, 95 % CI: 0.31-3.75; I(2) = 4.4 %). Based on the data from two prospective cohort studies (n = 166), LMWH for 3-24 months decreased mean BMD by 2.8-4.8 % (depending on the BMD site) compared to mean BMD decreases of 1.2-2.5 % with oral vitamin K antagonists.

LMWH for 3-6 months may not increase the risk of fractures, but longer exposure for up to 24 months may adversely affect BMD. Clinicians should consider monitoring BMD in adults on long-term LMWH who are at increased risk of bone loss or fracture.

The FRAX® tool estimates the risk of a fragility fracture among the population and many countries have been evaluating its performance among their populations since its creation in 2007. The purpose of this study is to update the first FRIDEX cohort analysis comparing FRAX with the bone mineral density (BMD) model, and its predictive abilities.

The discriminatory ability of the FRAX was assessed using the 'area under curve' of the receiver operating characteristic (AUC-ROC). Predictive ability was assessed by comparing estimated risk fractures with incidence fractures after a 10-year follow up period.

One thousand three hundred eight women ≥ 40 and ≤ 90 years followed up during a 10-year period. The AUC for major osteoporotic fractures using FRAX without DXA was 0.686 (95 % CI 0.630-0.742) and using FN T-score of DXA 0.714 (95 % CI 0.661-0.767). Using only the traditional parameters of DXA (FN T-score), the AUC was 0.706 (95 % CI 0.652-0.760). The AUC for hip osteoporotic fracture was 0.883 (95 % CI 0.827-0.938), 0.857 (95 % CI 0.773-0.941), and 0.814 (95 % CI 0.712-0.916) respectively. For major osteoporotic fractures, the overall predictive value using the ratio Observed fractures/Expected fractures calculated with FRAX without T-score of DXA was 2.29 and for hip fractures 2.28 and with the inclusion of the T-score 2.01 and 1.83 respectively. However, for hip fracture in women < 65 years was 1.53 and 1.24 respectively.

The FRAX tool has been found to show a good discriminatory capacity for detecting women at high risk of fragility fracture, and is better for hip fracture than major fracture. The test of sensibility shows that it is, at least, not inferior than when using BMD model alone. The predictive capacity of FRAX tool needs some adjustment. This capacity is better for hip fracture prediction and better for women < 65 years. Further studies in Catalonia and other regions of Spain are needed to fine tune the FRAX tool's predictive capability.