Fracture Risk Assessment in Clinical Practice: T-scores,FRAX, and Beyond

Assessment of fracture risk is a key component in the evaluation of skeletal health and a critical step in determining whether to initiate pharmacological therapy to reduce fracture risk. The identification of high risk patients allows clinicians to direct limited healthcare resources to those who are most likely to benefit. Bone mineral density (BMD) and clinical risk factors (CRFs) for fracture predict fracture risk better than BMD or CRFs alone. Dual-energy X-ray absorptiometry (DXA) is a technology for the measurement of BMD to diagnose osteoporosis, assess fracture risk, and monitor the BMD response to therapy. Validated CRFs and femoral neck BMD by DXA, when available, provide the input for the World Health Organization fracture risk assessment tool (FRAX) to estimate the 10-year probability of fracture in untreated patients. Economic models have included FRAX in calculations to estimate when pharmacological intervention is likely to be cost-effective in reducing fracture risk. Cost-effectiveness is one of many factors to consider in making treatment decisions. This is a review of the benefits and limitations of BMD testing, CRFs, and FRAX in the management of patients in clinical practice.     

Diagnosis of osteoporosis and assessment of fracture risk

The diagnosis of osteoporosis centres on the assessment of bone mineral density (BMD). Osteoporosis is defined as a BMD 2.5 SD or more below the average value for premenopausal women (T score < -2.5 SD). Severe osteoporosis denotes osteoporosis in the presence of one or more fragility fractures. The same absolute value for BMD used in women can be used in men. The recommended site for diagnosis is the proximal femur with dual energy X-ray absorptiometry (DXA). Other sites and validated techniques, however, can be used for fracture prediction. Although hip fracture prediction with BMD alone is at least as good as blood pressure readings to predict stroke, the predictive value of BMD can be enhanced by use of other factors, such as biochemical indices of bone resorption and clinical risk factors. Clinical risk factors that contribute to fracture risk independently of BMD include age, previous fragility fracture, premature menopause, a family history of hip fracture, and the use of oral corticosteroids. In the absence of validated population screening strategies, a case finding strategy is recommended based on the finding of risk factors. Treatment should be considered in individuals subsequently shown to have a high fracture risk. Because of the many techniques available for fracture risk assessment, the 10-year probability of fracture is the desirable measurement to determine intervention thresholds. Many treatments can be provided cost-effectively to men and women if hip fracture probability over 10 years ranges from 2% to 10% dependent on age.     

Clinical Application of Spine Trabecular Bone Score (TBS)

Trabecular bone score (TBS) is a software program recently approved by the US Food and Drug Administration for post-acquisition processing of lumbar spine dual-energy X-ray absorptiometry images that allows assessment of bone texture as a surrogate for bone microarchitecture. Low TBS values are associated with increased risk of major osteoporotic fracture risk in postmenopausal women and men aged 40 years and older independent of BMD. TBS data can be used to adjust FRAX probability of fracture. As such, TBS data can be useful in osteoporosis treatment initiation decisions. Following treatment initiation, TBS increases are smaller than seen with BMD; at present, there is insufficient evidence that TBS can be used to monitor treatment. TBS may be particularly helpful in fracture risk prediction for those with diabetes mellitus or receiving glucocorticoid therapy, but additional validation of existing observations is needed. In summary, TBS should not be used alone to guide treatment initiation, but can be used with FRAX to estimate fracture probability in postmenopausal women and older men, thereby facilitating treatment initiation decisions.     

How to implement guidelines and models of care

In subjects older than 50 years, the presence of clinical risk factors (CRFs) for fractures or a recent fracture is the cornerstone for case finding. In patients who are clinically at high short- and long-term risk of fractures (those with a recent clinical fracture or with multiple CRFs), further assessment with bone mineral density (BMD) measurement using dual-energy absorptiometry (DXA), imaging of the spine, fall risk evaluation and laboratory examination contributes to treatment decisions according to the height and modifiability of fracture risk. Treatment is available with anti-resorptive and anabolic drugs, and from the start of treatment a lifelong strategy is needed to decide about continuous, intermittent, and sequential therapy. Implementation of guidelines requires further initiatives for improving case finding, public awareness about osteoporosis and national policies on reimbursement of assessment and therapy.     

Aging bone and osteoporosis: strategies for preventing fractures in the elderly

As the older population increases, the incidence of osteoporotic fractures is expected to dramatically rise during the next few decades. Older patients are much more susceptible to fracture at any given bone mineral density (BMD) than are younger patients because of various factors, including the quality of aging bone, which involves more than BMD. Suppression of increased bone turnover by antiresorptive therapies, even with only small changes in BMD, can reduce fracture risk, especially in the lumbar spine. Bisphosphonate treatment can significantly reduce vertebral and nonvertebral fractures, including hip fractures, even in the very elderly. Prospective analyses show that risedronate therapy consistently and significantly reduces the risk of new morphometric vertebral fractures after 1 year in postmenopausal women. Post hoc analyses report significant reductions in the risk of 1 new clinical vertebral fracture after 6 months of risedronate therapy and after 1 year of alendronate therapy. Oral raloxifene therapy and salmon calcitonin nasal spray therapy have been shown to reduce the risk of vertebral fracture after 3 and 5 years, respectively, and post hoc data show a significant reduction in clinical vertebral fracture risk at 1 year with raloxifene use. However, neither raloxifene therapy nor calcitonin therapy reduce the risk of nonvertebral and hip fractures at currently approved doses. Bisphosphonates have been shown to be safe and efficacious with 7 years' risedronate sodium and 10 years' alendronate sodium data published, and bisphosphonates reduce bone turnover and increase BMD to a greater degree than raloxifene and calcitonin, which may partly account for their nonvertebral and hip fracture reduction effect. Therefore, bisphosphonate therapy with risedronate or alendronate should be considered in patients with low BMD at the hip and in older patients with osteoporosis and osteopenia, particularly those with an existing fracture.     

Bone disease in patients with haemophilia A and B – where are we now?

It is evident that haemophilia A and B are associated with decreased bone mass in both adults and children. Decreased physical activity and vitamin D deficiency are some of the major factors leading to bone loss. Hepatitis C virus (HCV) infection may also contribute to low bone mineral density (BMD). However, definite conclusions regarding the exact prevalence and pathogenesis of osteoporosis cannot be conducted yet, due to the small sample size and significant heterogeneity among studies. Discordant findings with regard to the skeletal site of low BMD have also been reported. Furthermore, data on fracture risk are sparse. The use of the Fracture Risk Assessment Tool (FRAX) for assessing fracture risk, regular BMD assessment at the age of 25 and thereafter, careful evaluation of risk factors associated with bone loss and optimal calcium and vitamin D intake are recommended. Long‐term prophylactic factor replacement therapy, resistance exercise and bisphosphonates, in severe cases of increased fracture risk, can prevent bone loss.     

Increased Fracture Risk Assessed by Fracture Risk Assessment Tool in Greek Patients with Crohn’s Disease

Background

The World Health Organization has recently developed the Fracture Risk Assessment Tool (FRAX) based on clinical risk factors and bone mineral density (BMD) for evaluation of the 10-year probability of a hip or a major osteoporotic fracture. The aim of this study was to evaluate the use of the FRAX tool in Greek patients with inflammatory bowel disease (IBD).

Methods

FRAX scores were applied to 134 IBD patients [68 Crohn’s disease (CD); 66 ulcerative colitis (UC)] who underwent dual-energy X-ray absorptiometry scans at the femoral neck and lumbar spine during the period 2007–2012. Calculation of the FRAX scores, with or without BMD, was made through a web-based probability model used to compute individual fracture probabilities according to specific clinical risk factors.

Results

The median 10-year probability of a major osteoporotic fracture for IBD patients based on clinical data was 7.1 %, and including the BMD was 6.2 %. A significant overestimation with the first method was found (P = 0.01). Both scores with and without BMD were significantly higher in CD patients compared with UC patients (P = 0.02 and P = 0.005, respectively). The median 10-year probability of hip fracture based on clinical data was 0.8 %, and including the BMD was 0.9 %. The score with use of BMD was significantly higher in CD compared with UC patients (P = 0.04).

Conclusions

CD patients have significantly higher FRAX scores and possibly fracture risk compared with UC patients. The clinical FRAX score alone seems to overestimate the risk of osteoporotic fracture in Greek IBD patients.     

Glucocorticoids and osteoporosis

Treatment with glucocorticoids (GC) has no alternative in many medical disciplines for their anti-inflammatory and immunosuppressive effect. However, osteoporosis and the related fractures are a serious complication brought about by long-term GC therapy. The risk of fractures, especially of the vertebras and the ribs, becomes higher as early as in the first months of oral GC therapy. It grows in proportion to the daily dose of GC, and is present even if low doses are administered (2.5-7.5 mg of prednisone per day). Decreasing bone density (BMD) is not accountable for the higher risk of fractures in GC therapy and fractures occur with higher values of BMD than in primary osteoporosis. There is still no tool that we could use to quantify the changes in the bone quality and the increased risk of fracture in clinical practice. The principal mechanism by which GC induces osteoporosis is inhibition of bone formation caused by the suppression of osteoblastogenesis as well as the activity of functional osteoblasts, with accelerated osteocyte and osteoblast apoptosis. There are significant differences between individuals in terms of GC sensitivity, the reasons of which have not yet been explained. Prior to planned long-term GC therapy (> 3 months) with daily doses higher than 2.5 mg of prednisone p.o. (or higher doses of inhaled GC), it is recommended to perform a densitometry exam using dual-energy X-ray absorptiometry (DXA) in the lumbar region of the spine and femoral collum to evaluate additional risk factors of osteoporosis and fractures for a more precise estimate of the risk of fracture in the specific patient. Sufficient intake of calcium (1,000-1,500 mg of elementary calcium per day) and of the vitamin D (800 IU per day) should be assured in all patients treated by GC. Endogenous production of sexagens should be evaluated and possible substitution therapy should be considered in premenopausal women and younger men. Today, bisphosphonates can be given to patients with a high risk of fracture, the effects of which in preventing the decrease of BMD and vertebral fractures have been documented in randomised clinical studies, even though the evaluation of the risk of fractures was not the primary endpoint of those studies. However, in view of the antiremodelling effect of bisphosphonates, it is clear that this therapy does not eliminate the cause of GC induced osteoporosis and drugs with stimulating effect on osteoblasts will certainly be preferred in the future. Very promising are the first clinical studies of injection parathormone (PTH 1-34) which stimulated bone formation in a continuing GC treatment.     

Bone damage in type 2 diabetes mellitus

This review focuses on the mechanisms determining bone fragility in patients with type 2 diabetes mellitus (T2DM). Despite bone mineral density (BMD) is usually normal or more often increased in these patients, fracture incidence is high, probably because of altered bone ”quality”. The latter seems to depend on several, only partly elucidated, mechanisms, such as the increased skeletal content of advanced glycation end-products causing collagen deterioration, the altered differentiation of bone osteogenic cells, the altered bone turnover and micro-architecture. Disease duration, its severity and metabolic control, the type of therapy, the presence or absence of complications, as like as the other known predictors for falls, are all relevant contributing factors affecting fracture risk in T2DM. In these patients the estimate of fracture risk in the everyday clinical practice may be challenging, due to the lower predictive capacity of both BMD and risk factors-based algorithms (e.g. FRAX).     

Significantly higher estimated 10-year probability of fracture in lupus patients with bone mineral density comparable to that of healthy individuals

This study aimed at comparing the FRAX^® 10-year fracture risk between SLE patients and demographically- and anthropometrically matched healthy individuals. Consecutive SLE patients aged ≥40 were analyzed for the FRAX^® 10-year probability of major osteoporotic and hip fractures and their risk was compared with healthy controls matched for age, gender and body mass index. Potential determinants associated with higher 10-year fracture probability in the SLE patients were studied by regression models. Ninety subjects (45 SLE patients and 45 healthy controls) were studied. While the bone mineral density (BMD) of the lumbar spine and dominant hip was comparable between the two groups, the FRAX^® 10-year probability of major and hip fractures was significantly higher in SLE patients. Significantly more SLE patients had high 10-year fracture risk as defined by the National Osteoporosis Foundation compared with healthy controls (16 vs. 2 %, p = 0.026). After controlling for glucocorticoid use and premature menopause which were significant univariate risk factors, the difference in the 10-year fracture risk became insignificant. Amongst SLE patients, increasing age, lower hip BMD and cumulative glucocorticoid dose independently predicted higher 10-year major fracture risk while higher anti-dsDNA level independently predicted higher hip fracture risk in addition to age and lower hip BMD. Chronic glucocorticoid use and premature menopause led to higher 10-year probability of major osteoporotic and hip fractures in SLE patients compared with their healthy counterparts although their BMD was comparable. Advanced age, lower hip BMD, cumulative glucocorticoid and higher anti-dsDNA level independently predicted higher 10-year fracture risk amongst SLE patients.     

Clinical evaluation of osteoporosis and fracture risk in postmenopausal women

For the advanced practice nurse, the goal of identifying postmenopausal women at risk for or diagnosed with osteoporosis is to prevent fractures. The first step to achieving this goal is to assess the patient's risk factors for fracture. The patient assessment, includes obtaining a medical history, performing a physical examination, and ordering a bone mineral density (BMD) test. A combined clinical picture is essential with regard to appropriate pharmacological and nonpharmacological therapy decisions for individual patients. BMD diagnostic categories should not be relied on in the absence of important clinical risk factors when determining an osteoporosis treatment threshold for fracture protection. Advanced practice nurses with expertise in health promotion, disease prevention, and patient education are in a unique position to evaluate the risk of osteoporotic fractures in patients who present for care in primary care settings.     

Alcohol intake and its relationship with bone mineral density, falls, and fracture risk in older men

OBJECTIVES: To examine the association between alcohol intake and problem drinking history and bone mineral density (BMD), falls and fracture risk. DESIGN: Cross-sectional and prospective cohort study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Five thousand nine hundred seventy-four men aged 65 and older. MEASUREMENTS: Alcohol intake and problem drinking histories were ascertained at baseline. Follow-up time was 1 year for falls and a mean of 3.65 years for fractures. RESULTS: Two thousand one hundred twenty-one participants (35.5%) reported limited alcohol intake (<12 drinks/y); 3,156 (52.8%) reported light intake (<14 drinks/wk), and 697 (11.7%) reported moderate to heavy intake (> or =14 drinks/wk) in the year before baseline. One thousand one men (16.8%) had ever had problem drinking. In multivariate models, as alcohol intake increased, so did hip and spine BMD (P for trend < .001). Greater alcohol intake was not associated with greater risk for nonspine or hip fractures. Men with light intake, but not moderate to heavy intake, had a lower risk of two or more incident falls (light intake: relative risk (RR) = 0.77, 95% confidence interval (CI) = 0.65-0.92; moderate to heavy intake: RR = 0.83, 95% CI = 0.63-1.10) than abstainers. Men with problem drinking had higher femoral neck (+1.3%) and spine BMD (+1.4%), and a higher risk of two or more falls (RR = 1.59; 95% CI = 1.30-1.94) than those without a history of problem drinking and similar total hip BMD and risk of fracture. CONCLUSION: In older men, recent alcohol intake is associated with higher BMD. Alcohol intake and fracture risk is unclear. Light alcohol intake may decrease the risk of falling, but a history of problem drinking increased fall risk.     

Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma

OBJECTIVE: Untreated hyperthyroidism and treatment with high doses of thyroid hormone are associated with osteoporosis. However, their effect on bone turnover, their contribution to bone mineral density (BMD) in the context of other clinical risk factors for osteoporosis and the prevalence of vertebral fractures is not well documented. DESIGN: Cross-sectional study. METHODS: We studied 59 patients receiving L-thyroxine suppressive therapy for differentiated thyroid carcinoma (DTC). BMD of the hip was measured by dual X-ray absorptiometry (DXA) and lateral DXA pictures of the lumbar and thoracic vertebrae were performed. Bone resorption was measured by C-telopeptides of type I collagen (ICTP) and bone formation by procollagen type I N-propeptide (PINP). Clinical risk factors for osteoporosis were evaluated using a questionnaire. RESULTS: Z-scores of BMD were similar as the NHANES (National Health and Nutrition Examination Survey) III reference group in women and men, also after long-term (> 10 years) suppression therapy. Patients in the lowest and highest quartile of BMD showed significant differences in the presence of clinical risk factors. ICTP levels were significantly higher than in age-matched controls, PINP levels were not different. We found four patients with a prevalent vertebral fracture. CONCLUSIONS: We conclude that patients with well-differentiated thyroid carcinoma are not at increased risk of developing low bone mass nor have a higher prevalence of vertebral fracture at least when treated with relatively low doses of L-thyroxine.     

Risk factors for osteoporosis in Japan

Risk factors for osteoporosis based on literally analysis were reviewed. For the prevention for the incidence of osteoporosis, the risk factors were low BMI, smoking and low impact exercise. Calcium and Vitamin D intake was the important preventive factor for the disease. Risk factors to assess the prevalent osteoporosis early were also reviewed. Finally, risk assessment for osteoporosis integrated by members of WHO collaborating centre for metabolic bone diseases were stated. They have undertaken a series of meta-analyses to identify clinical risk factors for fracture to determine their dependence upon age and sex. These were based on the individual data from prospective population-based studies. They concluded the risk factors for osteoporosis were age female-sex, low BMI, family history of fracture, current smoking, ever use of systemic corticosteroids, alcohol intake more than two units per day, rheumatoid arthritis and low BMD at the femoral neck or total hip.     

Bone density testing in clinical practice

The diagnosis of osteoporosis and monitoring of treatment is a challenge for physicians due to the large number of available tests and complexities of interpretation. Bone mineral density (BMD) testing is a non-invasive measurement to assess skeletal health. The "gold-standard" technology for diagnosis and monitoring is dual-energy X-ray absorptiometry (DXA) of the spine, hip, or forearm. Fracture risk can be predicted using DXA and other technologies at many skeletal sites. Despite guidelines for selecting patients for BMD testing and identifying those most likely to benefit from treatment, many patients are not being tested or receiving therapy. Even patients with very high risk of fracture, such as those on long-term glucocorticoid therapy or with prevalent fragility fractures, are often not managed appropriately. The optimal testing strategy varies according to local availability and affordability of BMD testing. The role of BMD testing to monitor therapy is still being defined, and interpretation of serial studies requires special attention to instrument calibration, acquisition technique, analysis, and precision assessment. BMD is usually reported as a T-score, the standard deviation variance of the patient's BMD compared to a normal young-adult reference population. BMD in postmenopausal women is classified as normal, osteopenia, or osteoporosis according to criteria established by the World Health Organization. Standardized methodologies are being developed to establish cost-effective intervention thresholds for pharmacological therapy based on T-score combined with clinical risk factors for fracture.     

Genetic control of susceptibility to osteoporosis

Osteoporosis is a common disease with a strong genetic component. Twin studies have shown that genetic factors play an important role in regulating bone mineral density (BMD), ultrasound properties of bone, skeletal geometry, and bone turnover as well as contributing to the pathogenesis of osteoporotic fracture itself. These phenotypes are determined by the combined effects of several genes and environmental influences, but occasionally, osteoporosis or unusually high bone mass can occur as the result of mutations in a single gene. Examples are the osteoporosis-pseudoglioma syndrome, caused by inactivating mutations in the lipoprotein receptor-related protein 5 gene and the high bone mass syndrome, caused by activating mutations of the same gene. Genome-wide linkage studies in man have identified loci on chromosomes 1p36, 1q21, 2p21, 5q33-35, 6p11-12, and 11q12-13 that show definite or probable linkage to BMD, but so far, the causative genes remain to be identified. Linkage studies in mice have similarly identified several loci that regulate BMD, and a future challenge will be to investigate the syntenic loci in humans. A great deal of research has been done on candidate genes; among the best studied are the vitamin D receptor and the collagen type I alpha 1 gene. Polymorphisms of vitamin D receptor have been associated with bone mass in several studies, and there is evidence to suggest that this association may be modified by dietary calcium and vitamin D intake. A functional polymorphism affecting an Sp1 binding site has been identified in the collagen type I alpha 1 gene that predicts osteoporotic fractures independently of bone mass by influencing collagen gene regulation and bone quality. An important problem with most candidate gene studies is small sample size, and this has led to conflicting results in different populations. Some researchers are exploring the use of meta-analysis to try and address this issue and gain an accurate estimate of effect size for different polymorphisms in relation to relevant clinical endpoints, such as BMD and fracture. From a clinical standpoint, advances in knowledge about the genetic basis of osteoporosis are important, because they offer the prospect of developing genetic markers for the assessment of fracture risk and the opportunity to identify molecules that will be used as targets for the design of new drugs for the prevention and treatment of bone disease.     

Long-term prediction of incident hip fracture risk in elderly white women: study of osteoporotic fractures

OBJECTIVES: To identify independent risk factors for first hip fracture over 10 years of follow-up. DESIGN: Prospective cohort study. SETTING: Four U.S. clinical centers. PARTICIPANTS: A total of 6,787 women aged 66 and older in the Study of Osteoporotic Fractures. MEASUREMENTS: Total hip bone mineral density (BMD) using dual-energy x-ray absorptiometry and a comprehensive set of potential risk factors were collected. Incident hip fractures were identified prospectively and confirmed using radiographic report. RESULTS: Six hundred two women (8.9%) had a hip fracture during a mean +/- standard deviation (SD) follow-up of 10.1 +/- 3.2 years. Older age, previous self-reported fracture after age 50, maternal history of hip fracture after age 50, greater height at age 25, impaired cognition, slower walking speed, nulliparity, type II diabetes mellitus, Parkinson's disease, and depth perception each independently predicted a 1.17- to 1.83-fold increase in hip fracture risk, whereas each SD (0.13 g/cm2) decrease in hip BMD was independently associated with a 1.84-fold increase in risk. Lower body mass index also was associated with an increased risk of hip fracture, although lower hip BMD largely explained this association. CONCLUSION: Although hip BMD is strongly related to hip fracture risk in elderly white women, other clinical risk factors also are independent predictors of long-term risk and provide additional insight into the prevention of fracture in high-risk women. Clinicians should be alert to factors other than BMD that place older women at a high risk of hip fracture.     

Antiresorptive Therapy for the Prevention of Postmenopausal Osteoporosis

Osteoporosis is a condition associated with decreased bone strength and an increased fracture risk. It may be defined based on bone mineral density (BMD) with a T-score at the hip or spine of less than -2.5 standard deviations in young healthy individuals or from an osteoporotic fracture (i.e. a fracture occurring after low-energy trauma or no apparent trauma). Risk factors predisposing to fractures include: increasing age; female gender; low BMD; a prior fragility fracture; a family history of fragility fractures; low bodyweight; lack of estrogen in women (i.e. post menopause); corticosteroid use; smoking; a number of diseases; deficiency in calcium and vitamin D; an increased risk of falls (i.e. impaired vision); immobilization; and Caucasian race. The more risk factors that are present the higher the risk of fractures over the following 10 years. The need to initiate preventive therapy with anti-osteoporotic treatment increases steeply with the absolute fracture risk. Indications for referral for dual energy x-ray absorptiometry measurement of BMD include: age >65 years; age <65 years in postmenopausal women with any of the risk factors already mentioned; premature menopause (<45 years); prolonged amenorrhea (>1 year) in younger women; fragility fractures; and diseases or conditions known to lead to osteoporosis.Anti-resorptive therapies include calcium plus vitamin D, bisphosphonates (alendronate, etidronate, risedronate, ibandronate), selective estrogen receptor modulators (raloxifene), hormone replacement therapy, and calcitonin. Guidelines from several countries on when to initiate anti-resorptive therapy state that therapy may be started in patients with a prior fragility fracture (some guidelines state that in this situation no BMD measurements are necessary) or in patients with a T-score of less than -2.5 (some guidelines state that additional risk factors need to be present in this situation). Some guidelines state that anti-resorptive therapy may be initiated in patients with a T-score in the osteopenic range (from -1 to -2.5, i.e. not frank osteoporosis) in the presence of other risk factors. The cost effectiveness of anti-resorptive therapy increases with the absolute fracture risk. In some scenarios, treatment with bisphosphonates may be cost effective in a 50-year-old woman with an absolute hip fracture risk of >or=1.1% over the next 10 years.     

Assessment and management of bone health in women with oestrogen receptor‐positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia,the Australian and New Zealand Bone & Mineral Society,the Australasian Menopause Society and the Clinical Oncology Society of Australia

To formulate clinical consensus recommendations on bone health assessment and management of women with oestrogen receptor‐positive early breast cancer receiving endocrine therapy, representatives appointed by relevant Australian Medical Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence‐informed position statement addressing 5 key questions. Women receiving adjuvant aromatase inhibitors and the subset of premenopausal woman treated with tamoxifen have accelerated bone loss and increased fracture risk. Both bisphosphonates and denosumab prevent bone loss; additionally, denosumab has proven antifracture benefit. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density (BMD) measurement, with monitoring based on risk factors. Weight‐bearing exercise, vitamin D and calcium sufficiency are recommended routinely. Antiresorptive treatment should be considered in women with prevalent or incident clinical or morphometric fractures, a T‐score (or Z‐scores in women <50 years) of 相似文献