Assessment of fracture risk: who should be treated for osteoporosis?

The clinical significance of osteoporosis arises from the fractures that occur. Of these, the hip fracture in particular is associated with high morbidity, mortality and socio-economic costs. The primary goal of osteoporosis treatment is fracture prevention. In this chapter we try to answer the question of how to assess fracture risk and how to identify those above a given risk threshold so that treatment can be given to those in whom fractures can be prevented (cost-) effectively. At first, the two main strategies for fracture prevention--population screening and case finding--are discussed. Then a fracture risk assessment score, based on easily identifiable clinical risk factors, is proposed. This clinical risk factor analysis can guide the decisions whether additional bone assessment is relevant and whether treatment should be started. Finally, we advocate that absolute fracture risk is important for communication with the patient about the decision whether or not to initiate treatment.     

Validation of the clinical consensus recommendations on the management of fracture risk in postmenopausal women with type 2 diabetes

Background and aimsBone fragility is recognized as a complication of type 2 diabetes (T2D). However, the fracture risk in T2D is underestimated using the classical assessment tools. An expert panel suggested the diagnostic approaches for the detection of T2D patients worthy of bone-active treatment. The aim of the study was to apply these algorithms to a cohort of T2D women to validate them in clinical practice.Methods and resultsThe presence of T2D-specific fracture risk factors (T2D ≥ 10 years, ≥1 T2D complications, insulin or thiazolidinedione use, poor glycaemic control) was assessed at baseline in 107 postmenopausal T2D women. In all patients at baseline and in 34 patients after a median follow-up of 60.2 months we retrospectively evaluated bone mineral density and clinical and morphometric vertebral fractures. No patient was treated with bone-active drug. Following the protocols, 34 (31.8%) and 73 (68.2%) patients would have been pharmacologically and conservatively treated, respectively. Among 49 patients without both clinical fractures and major T2D-related risk factors, who would have been, therefore, conservatively followed-up without vertebral fracture assessment, only one showed a prevalent vertebral fracture (sensitivity 90%, negative predictive value 98%). The two patients who experienced an incident fracture would have been pharmacologically treated at baseline.ConclusionsThe clinical consensus recommendations showed a very good sensitivity in identifying T2D postmenopausal women at high fracture risk. Among those with treatment indication as many as 13% of patients experienced an incident fracture, and, conversely, among those without treatment indication no incident fractures were observed.     

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.     

Management of bone fragility in type 2 diabetes: Perspective from an interdisciplinary expert panel

AimBone fragility is increasingly recognized as a relevant complication of type 2 diabetes (T2D) and diabetic patients with fragility fractures have higher mortality rates than non diabetic individuals or diabetic patients without fractures. However, current diagnostic approaches for fracture risk stratification, such as bone mineral density measurement or the use of risk assessment algorithms, largely underestimate fracture risk in T2D patients. A multidisciplinary expert panel was established in order to in order to formulate clinical consensus recommendations on bone health assessment and management of fracture risk in patients with T2D.Data synthesisThe following key questions were addressed: a) which are the risk factors for bone fragility in T2D?, b) which diagnostic procedures can be currently used to stratify fracture risk in T2D patients?, c) which are the effects of antidiabetic treatments on bone?, and d) how to prevent and treat bone fragility in T2D patients? Based on the available data members of this panel suggest that the stratification of fracture risk in patients with diabetes should firstly rely on the presence of a previous fragility fracture and on the individual risk profile, with the inclusion of T2D-specific risk factors (namely T2D duration above 10 yrs, presence of chronic T2D complications, use of insulin or thiazolidinediones and persistent HbA1c levels above 8% for at least 1 year). Two independent diagnostic approaches were then suggested in the presence or the absence of a prevalent fragility fracture, respectively.ConclusionsClinical trials in T2D patients at risk for fragility fractures are needed to determine the efficacy and safety of available antiresorptive and anabolic agents in this specific setting.     

Managing osteoporosis in ulcerative colitis: Something new?

The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis(UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool(FRAX tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a followup only. An intermediate risk supports the decision to prescribe bone mineral density(BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that are also applied to the patients with osteoporosis. Therefore, a reasonable advice is to consider pharmacological treatment for osteoporosis in those UC patients who already present fragility fractures, which bring a high risk of subsequent fractures. Therapy has also to be considered in patients with a high risk of fracture even if it did not yet happen, and particularly when they had long periods of corticosteroid therapy or cumulative high dosages. In patients without fragility fractures or steroid treatment, a medical decision about treatment could be guided by the FRAX tool to determine the intervention threshold. Among drugs for osteoporosis treatment, the bisphosphonates are the most studied ones, with the best and longest evidence of efficacy and safety. Despite this, several questions are still open, such as the duration of treatment, the necessity to discontinue it, the indication of therapy in young patients, particularly in those without previous fractures. Further, it has to be mentioned that a longterm bisphosphonates use in primary osteoporosis has been associated with an increased incidence of dramatic side-effects, even if uncommon, like osteonecrosis of the jaw and atypical sub-trochanteric anddiaphyseal femoral fractures.UC is a long-lasting disease and the majority of patients is relatively young.In this scenario primary prevention of fragility fracture is the best cost-effective strategy.Vitamin D supplementation,adequate calcium intake,suitable physical activity(when possible),removing of risk factors for osteoporosis like smoking,and avoiding falling are the best medical acts.     

Strategies for prevention and treatment of osteoporosis at the primary, secondary, and tertiary level in Leuven, Belgium

The first strategy to prevent osteoporosis is to detect patients at risk for osteoporosis in time before fracture occurs. The known risk factors for osteoporosis can be divided according to modifiable or not modifiable, and according to vertebral or proximal femur fracture site. The importance of accumulation of several risk factor for the incidence of fragility fractures in the population is stressed. Preventive and curative therapy for osteoporosis is possible in all phases of life. Even a recent fracture should be treated, it is never too late to prevent further fractures. Strategies are proposed for the building up period of the skeleton in the adolescence (primary prevention) , for the period when accelerated bone loss starts, as in the perimenopause, during immobilisation and corticosteroid use (secondary prevention) ;and finally at the time of bone loss or fracture (tertiary prevention) . For each of these periods, general and specific therapies are listed. An algorithm for "case finding" and consequent management in clinical practice are discussed as a problem-solving and clinical reasoning exercise. A plea is made for an individualised intervention because preventive and curative treatment for osteoporosis is a long-term treatment and thus an important decision. This decision should be based on cost/benefit, pathophysiology of the case and bone active drugs. If available, it is advisable to share responsibility with an expert in the field, this will improve compliance and outcome.     

Fracture liaison programs

In view of the high imminent risk of having subsequent fractures after a fracture, early evaluation and treatment decisions to prevent subsequent fractures are advocated. After a hip fracture, the fracture liaison service (FLS) and orthogeriatric care are considered the most appropriate organisational approaches for secondary fracture prevention following a recent fracture.Their introduction and implementation have been shown to increase evaluation and treatment of patients at high risk for subsequent fracture. Of real-world cohort studies, most, but not all studies, indicate a lower incidence of fracture and longer survival after treatment with nitrogen-containing bisphosphonates.     

Secondary prevention and estimation of fracture risk

The key questions addressed in this chapter are:? How can individual risk of fracture be best estimated?? What is the best system to prevent a further fracture?? How to implement systems for preventing further fractures?Absolute fracture risk calculators (FRCs) provide a means to estimate an individual's future fracture risk. FRCs are widely available and provide clinicians and patients a platform to discuss the need for intervention to prevent fragility fractures.Despite availability of effective osteoporosis medicines for almost two decades, most patients presenting with new fragility fractures do not receive secondary preventive care. The Fracture Liaison Service (FLS) model has been shown in a number of countries to eliminate the care gap in a clinically and cost-effective manner.Leading international and national organisations have developed comprehensive resources and/or national strategy documents to provide guidance on implementation of FLS in local, regional and national health-care systems.     

Osteoporosis: strategies for prevention and management

Osteoporosis is a serious public health issue, affecting up to 1 in 2 women and 1 in 5 men over the age of 50 years. The common osteoporotic fractures occur at the spine, wrist and hip. For the patient affected by osteoporosis, these fractures are associated with significant morbidity and, in the case of hip and spine fractures, an excess mortality. The treatment of osteoporotic fractures is also associated with a significant healthcare cost for society. Currently, measurement of bone mineral density using dual energy X-ray absorptiometry is the gold standard for the diagnosis of osteoporosis. In the future, however, assessment of fracture risk will be based on algorithms incorporating clinical risk factors and bone density measurements, where appropriate. The goal of treatment is to reduce the risk of future fracture. Patients at high risk for fracture should be assessed and screened to exclude secondary causes for osteoporosis. Bisphosphonates (alendronate, etidronate, ibandronate, risedronate) are the first-line therapy for the majority of patients and these treatments can be given either orally or intravenously. Alternative treatment options include strontium ranelate and raloxifene. Anabolic therapy with parathyroid hormone can be considered for patients with severe disease. These patients will often require referral for specialist assessment and monitoring. All patients at risk of developing osteoporosis should be given lifestyle advice regarding dietary intake of calcium and vitamin D and regular weight-bearing exercise.     

Risk assessment tools for osteoporosis and fractures in 2022

Osteoporosis is one of the frequently encountered non-communicable diseases in the world today. Several hundred million people have osteoporosis, with many more at risk. The clinical feature is a fragility fracture (FF), which results in major reductions in the quality and quantity of life, coupled with a huge financial burden. In recognition of the growing importance, the World Health Organisation established a working group 30 years ago tasked with providing a comprehensive report to understand and assess the risk of osteoporosis in postmenopausal women. Dual-energy X-ray absorptiometry (DXA) is the most widely endorsed technology for assessing the risk of fracture or diagnosing osteoporosis before a fracture occurs, but others are available. In clinical practice, important distinctions are essential to optimise the use of risk assessments. Traditional tools lack specificity and were designed for populations to identify groups at higher risk using a ‘one-size-fits-all’ approach. Much has changed, though the purpose of risk assessment tools remains the same. In 2022, many tools are available to aid the identification of those most at risk, either likely to have osteoporosis or suffer the clinical consequence. Modern technology, enhanced imaging, proteomics, machine learning, artificial intelligence, and big data science will greatly advance a more personalised risk assessment into the future. Clinicians today need to understand not only which tool is most effective and efficient for use in their practice, but also which tool to use for which patient and for what purpose. A greater understanding of the process of risk assessment, deciding who should be screened, and how to assess fracture risk and prognosis in older men and women more comprehensively will greatly reduce the burden of osteoporosis for patients, society, and healthcare systems worldwide. In this paper, we review the current status of risk assessment, screening and best practice for osteoporosis, summarise areas of uncertainty, and make some suggestions for future developments, including a more personalised approach for individuals.     

Diagnosis and management of vertebral fractures in elderly adults

We reviewed the epidemiology, diagnosis, and treatment of vertebral fractures due to osteoporosis in the elderly. Vertebral fractures are underdiagnosed despite their high prevalence in both men and women. Clinical consequences of vertebral fractures include increased risk of future vertebral and hip fracture, acute and chronic back pain, decreased quality of life, and increased mortality. Patients with vertebral fractures have functional impairment and increased mortality similar to those with hip fractures. Asymptomatic fractures identified on radiograph also affect quality of life and mortality. A vertebral fracture is a clinical marker for a subsequent fracture and should trigger assessment and diagnosis of osteoporosis. The care of patients with vertebral fractures includes pain management, rehabilitation, and prevention of further fractures. There is evidence from randomized controlled trials that pharmacologic therapy can reduce the risk of future fractures by 40% to 50%. Vertebroplasty may be effective in the control of pain and in obtaining stability of the spine.     

Treating osteoporosis to prevent fractures: current concepts and future developments

Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40–70%), nonvertebral (by 25–40%) and hip fractures (by 40–53%) in postmenopausal women with osteoporosis. Due to the risk of rare side‐effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well‐proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk‐based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long‐term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone‐building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long‐term fracture prevention and should be the golden standard of future osteoporosis treatment.     

胫骨定量超声测量对老年妇女骨折危险性的评价及其临床意义

目的　探讨胫骨定量超声(QUS)骨量分析系统预测老年妇女骨折危险性的临床实用性以及骨折的阈值。　方法　采用QUS技术检测63例骨折患者(骨折组)和85名社区健康老年妇女志愿者(对照组)的胫骨超声传导速度（SOS）值,并对其变化规律进行分析。　结果　骨折组的SOS值(3712.7m/s)明显低于对照组（3831.4m/s,P＜0.01）,且SOS值与骨折危险性呈负相关,SOS值每下降100m/s,骨折危险性增加约1倍。若以骨折危险性高于20%为骨折高危人群,则骨折的SOS阈值为3850m/s。　结论　胫骨QUS测量对诊断老年妇女骨质疏松症和预测骨折危险性有很大的临床应用潜力。     

Monitoring osteoporosis therapy:Can FRAX help assessing success or failure in achieving treatment goals?

AIM: To assess:(1) Whether the World Health Organization fracture risk assessment tool(FRAX) can be used for monitoring osteoporosis patients receiving treatment as well as its clinical implications; and(2) The relation between fracture incidence and post-treatment FRAX.METHODS: Five hundred and seventy-nine osteoporotic women known to be adherent to the prescribed osteoporosis medication, had dual-energy X-ray absorptiometry scan and fracture probability calculated at baseline, 2 and 5-year of osteoporosis treatment. Those patients who responded to treatment and did not sustain a new low trauma fracture during the first 2 years, continued their treatment and were re-assessed 3-year later. The patient subgroup who did not achieve an improvement in their bone mineral density(BMD)or sustain any fracture within the first 2-year, had their osteoporosis treatment changed. Outcome measures included BMD and FRAX assessment calculated 3-year after commencing new osteoporosis treatment. RESULTS: There was a significant negative correlation between 10-year probability of major osteoporotic and hip fractures and BMD at the total proximal femur at 2-year of treatment(R =-0.449 and-0.479 respectively), and at 5-year(R =-0.489 and-0.594 respectively). At both 2 years and 5 years of treatment, the 10-year fracture probability showed significant correlation with the incidence of fracture(P 0.01). On comparing fracture probability, there was a significant difference(P 0.05) between the responders and non-responders to osteoporosis treatment.CONCLUSION: In women currently or previously treated for osteoporosis, the FRAX tool can be used to predict fracture probability. Osteoporosis treatment does not annul prediction of fractures. FRAX tool may be of value in guiding clinicians towards the need for continuation or withdrawal of treatment.     

Low handgrip strength is a predictor of osteoporotic fractures: cross-sectional and prospective evidence from the Hong Kong Osteoporosis Study

Handgrip strength (HGS) is a potentially useful objective parameter to predict fracture since it is an indicator of general muscle strength and is associated with fragility and propensity to fall. Our objective was to examine the association of HGS with fracture, to evaluate the accuracy of HGS in predicting incident fracture, and to identify subjects at risk of fracture. We analyzed a cross-sectional cohort with 2,793 subjects (1,217 men and 1,576 women aged 50-101 years) and a subset of 1,702 subjects which were followed for a total of 4,855 person-years. The primary outcome measures were prevalent fractures and incident major fragility fractures. Each standard deviation (SD) reduction in HGS was associated with a 1.24-fold increased odds for major clinical fractures even after adjustment for other clinical factors. A similar result was obtained in the prospective cohort with each SD reduction in HGS being associated with a 1.57-fold increased hazard ratio of fracture even after adjustment for clinical factors. A combination of HGS and femoral neck bone mineral density (FN BMD) T-score values (combined T-score), together with other clinical factors, had a better predictive power of incident fractures than FN BMD or HGS T-score alone with clinical factors. In addition, combined T-score has better sensitivity and specificity in predicting incidence fractures than FN BMD alone. This study is the first study to compare the predictive ability of HGS and BMD. We showed that HGS is an independent risk factor for major clinical fractures. Compared with using FN BMD T-score of -2.5 alone, HGS alone has a comparable predictive power to BMD, and the combined T-score may be useful to identify extra subjects at risk of clinical fractures with improved specificity.     

Assessment of fracture risk in a cohort of Egyptian female Systemic Lupus erythematosus patients

Aim of the work

To assess the fracture risk in a cohort of Egyptian systemic lupus erythematosus (SLE) females in correlation to some disease variables.

Assessment of fracture risk

Osteoporosis-related fractures are associated with significant morbidity, mortality, and health care expenditure worldwide. The low sensitivity of bone density testing alone to predict fractures has led to the development of a variety of fracture assessment tools that use the combination of bone density and clinical risk factors to improve the prediction of low-trauma fractures. These fracture assessment tools quantitatively predict the 10-year probability of hip and major osteoporosis-related fractures, and can be used with various intervention strategies to effectively intervene with cost-effective therapies to prevent future fractures.     

Drug insight: Existing and emerging therapies for osteoporosis

Osteoporosis is a major public health problem that is characterized by microarchitectural deterioration, low bone mass, and increased risk of fractures. Currently, many women and men affected with this disease are not diagnosed or treated. As osteoporosis is often clinically silent, risk-factor assessment and measurement of BMD are needed to identify those who may benefit from osteoporosis therapy. Although adequate daily intake of calcium and vitamin D, and regular weight-bearing exercise are important for skeletal health, they are not adequate treatments for individuals with osteoporosis. Therapies approved for treatment and/or prevention of osteoporosis in the United States include oral bisphosphonates (alendronate, ibandronate and risedronate), calcitonin, estrogens, teriparatide (parathyroid hormone fragment [1-34]), and raloxifene. For most patients, oral bisphosphonates are the treatment of choice, given the large-scale randomized-trial data demonstrating efficacy in fracture reduction, although bisphosphonates that reduce spine and nonspine fractures (e.g. alendronate and risedronate) are preferred. For high-risk patients (those with very low bone density, or with fractures), teriparatide therapy for 2 years should be considered. The treatment paradigm for osteoporosis will evolve further as promising new treatments progress through clinical development.     

Osteoporosis: From concepts to T scores and now absolute fracture risk

The definition of osteoporosis has always been challenging. Historically the clinical definition could only be based on the presence or occurrence of an osteoporotic fracture. However waiting for a fracture to occur before making a diagnosis has limitations, not least that high risk individuals cannot be identified for treatment prior to fracture. With the availability of bone density measurements, the definition moved to the use of T-scores. Whilst widely used, this approach has limitations that include low sensitivity and not taking into account other variables that influence bone strength and extra-skeletal risk factors. In view of the limitations of using T scores in isolation, there has been a move towards assessment of individualised risk that incorporates multiple risk factors (with or without bone density measurement) to help predict future fracture risk. This approach potentially allows identification and treatment of individuals at high risk of fracture, the condition that needs to be treated as opposed to treating low bone density. Indeed bone density (where measured) becomes one of the many risk factors without a threshold interpretation for any given value. Numerous tools are available that have varying sensitivity, specificity, utility, applicability to, and that have been validated for any given population. Of the available tools, the World Health Organisation Fracture Risk Assessment Tool (FRAX) calculator has been extensively studied. It is available more widely, with country specific utility with and without bone density measurements, which is important in regions with scarce access to bone densitometry. FRAX is the only tool available that is India specific.