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.     

Clinical Vignettes: Using Non-BMD Measurements in Clinical Practice

Dual-energy X-ray absorptiometry (DXA) is a well-established clinical tool for measuring bone mineral density (BMD) in the assessment of patients at risk of fracture. DXA is commonly used to diagnose osteoporosis, assess fracture risk, and assess the skeletal effects of treatment. Non-BMD DXA measurements, such as vertebral fracture assessment, hip access length, and trabecular score, have clinical applications that can guide patient treatment decisions. Quantitative computed tomography (QCT) measures three-dimensional volumetric BMD that is correlated with fracture risk. QCT measurements of the hip can also be used to generate a two-dimensional DXA-equivalent areal BMD and T-score that can be used for diagnosis of osteoporosis and the assessment of fracture risk in the FRAX algorithm. Opportunistic measurements of BMD obtained with CT scans evaluating non-skeletal conditions have potential clinical utility in identifying patients at high risk of fracture. This is a collection of clinical vignettes that illustrate potential applications of non-BMD DXA measurements and CT scanning in the management of patients at risk of fracture.     

Bone Mineral Density in Chronic Kidney Disease Use and Misuse

Low bone mineral density (BMD) is a strong risk factor for low trauma fractures in the postmenopausal population without known chronic kidney disease (CKD). In stage 1?C3 CKD, low BMD can also be used to predict fracture risk with the gradient of risk similar to patients without CKD even though patients with stage 3 CKD have an approximate doubling of risk compared with age-matched patients without CKD. This greater risk of fracture in stage 3 CKD is not calculated in the current FRAX model. In stage 4?C5 CKD, BMD by dual-energy x-ray absorptiometry (DXA) is a poor predictor of fracture risk probably related to the severe derangements in bone metabolism in severe CKD, which alter bone quality and strength not measured by DXA. Serial BMD by DXA, however, may be useful in all stages of CKD to monitor for potential loss of BMD or effect of pharmacological agents to improve BMD. Newer radiological technologies, particularly high-resolution peripheral quantitative computerized tomography (HRpQcT) of the radius and tibia show promise to define the microstructural changes in bone that explain the greater risk of fracture observed in patients with CKD versus patients without CKD. BMD by DXA may still be of value across the spectrum of CKD, but physicians should realize its limitations and understand the greater risk of fracture in patients in all stages of CKD as compared to age-matched and BMD-matched patients without CKD.     

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.     

Redefining osteoporosis treatment: Who to treat and how long to treat

Osteoporosis is a common disease that is associated with increased risk of fractures and serious clinical consequences. Bone mineral density (BMD) testing is used to diagnose osteoporosis, estimate the risk of fracture, and monitor changes in BMD over time. Combining clinical risk factors for fracture with BMD is a better predictor of fracture risk than BMD or clinical risk factors alone. Methodologies are being developed to use BMD and validated risk factors to estimate the 10-year probability of fracture, and then combine fracture probability with country-specific economic assumptions to determine cost-effective intervention thresholds. The decision to treat is based on factors that also include availability of therapy, patient preferences, and co-morbidities. All patients benefit from nonpharmacological lifestyle treatments such a weight-bearing exercise, adequate intake of calcium and vitamin D, fall prevention, avoidance of cigarette smoking and bone-toxic drugs, and moderation of alcohol intake. Patients at high risk for fracture should be considered for pharmacological therapy, which can reduce fracture risk by about 50%.     

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.     

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).     

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.     

The activity of a Spanish bone densitometry unit revisited under the point of view of FRAX

In March 2008, FRAX, developed by Kanis and collaborators in the University of Sheffield and supported by the World Health Organization, became available online to calculate absolute risk of osteoporotic fracture in the next 10 years.ObjectiveTo analyze the risk of fracture calculated by FRAX and its determinants in the patients sent to a densitometry unit for bone mineral density (BMD) testing.MethodsAll the patients submitted by Primary Care to the Densitometry Unit for BMD testing underwent a self administered questionnaire to assess the clinical risk factors included in FRAX and a bone densitometry of lumbar spine and proximal femur with a DXA densitometer Hologic QDR 4500. They were classified as having a normal BMD, osteopenia or osteoporosis along with the recommendations of the International Society for Clinical Densitometry. As the reference population to calculate the T and Z scores, we used the one from the NHANES III study for femoral neck and total hip and the one from the Study of the Spanish Population for total spine. With the data of the questionnaire, we calculated, by FRAX, the absolute risk in the next ten years of having a major fracture (MFR) or a hip fracture (HFR). Both risks were calculated with or without the inclusion in the algorithm of BMD: MFR+, MFR?, HFR+ and HFR?. The results were recorded in an Access 2003 database and analyzed with the statistical package SPSS 15.0 for Windows.ResultsWe analyzed the data from 853 women with a mean age of 61.9 (8.9) years and a mean body mass index of 27.0 (4.2) kg/m². Mean BMD at lumbar spine was 0.873 (0.127) g/cm²; at femoral neck, 0.704 (0.105) g/cm²; and at total hip, 0.817 (0.107) g/cm². Twenty percent of the patients had a normal BMD, 55% had osteopenia and 25%, osteoporosis. Yet excluding age and body mass index, the number of fracture risk factors seems low: 31% of the patients had no risk of fracture; 40%, had one; 22%, two; 6%, three; 1%, four; and one patient had five. Mean MFR+ was 5.4 (4.8)%; mean MFR?, 6.3 (5.5)%; mean HFR+, 1.5 (2.9)%; and HFR?, 2.1 (3.3)%.When BMD was included in the algorithm for the calculation of the risk of fracture, the risk was statistically lower (p < 0.001), especially in patients with better BMD.ConclusionsThe risk of fracture calculated by FRAX in the patients sent to a densitometry unit for bone BMD testing seems low and, probably, a better selection of the patients would detect a higher risk of fracture population. When the fracture risk is calculated with the introduction of BMD in the algorithm, it is lower than without including BMD.     

Is there a place for bone turnover markers in the assessment of osteoporosis and its treatment?

As populations age, the number of osteoporotic fractures will increase. Bone mineral density (BMD) measurement remains the major way to diagnose osteoporosis and to indicate therapy. The FRAX tool, based on clinical risk factors, estimates the 10-year risk of hip and major osteoporotic fractures. The association of BMD and FRAX measurements has improved the identification of patients who are most at risk. However, some patients can still be overlooked and denied therapy. It is sound that adding the measure of bone turnover markers to the former risk factors and their follow-up during therapy could best address the efficacy of treatment of osteoporosis. Whether this behavior is cost-effective remains to be settled.     

Skeletal health among African Americans with recent‐onset rheumatoid arthritis

Objective

African Americans with rheumatoid arthritis (RA) may be at increased fracture risk. We applied the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Foundation (NOF) guidelines to a cohort of African Americans with early RA to identify which patients were recommended for osteoporosis treatment.

Methods

Risk factors and bone mineral density (BMD) were assessed in a cohort of African Americans with RA. The WHO FRAX tool estimated 10‐year fracture risk. Patients were risk stratified using FRAX without BMD to identify which individuals might be most efficiently targeted for BMD testing.

Results

Participants (n = 324) had a mean age of 51 years and included 81% women. There were no associations of RA disease characteristics with BMD. The proportion of patients recommended for osteoporosis treatment varied from 3–86%, depending on age and body mass index (BMI). Ten‐year fracture risk calculated with BMI only was generally the same or higher than fracture risk calculated with BMD; adding BMD data provided the most incremental value to risk assessment in patients 55–69 years of age with low/normal BMI, and in those ≥70 years of age with BMI ≥30 kg/m².

Conclusion

A high proportion of African Americans with RA were recommended for treatment under the 2008 NOF guidelines. FRAX without BMD identified low‐risk patients accurately. Systematic application of FRAX to screen high‐risk groups such as patients with RA may be used to target individuals for BMD testing and reduce the use of unnecessary tests and treatments.     

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世界卫生组织(WHO)推荐使用双能X线BMD测量仪(DXA)测定的骨密度诊断骨质疏松,以T≤-2.5为骨质疏松。对没有发生过骨折又有低骨量的人群(T>-2.5),采用骨折风险评估模型(FRAX)工具可以计算出每位个体发生骨折的绝对风险。面对每位"骨质疏松"患者,医师都应该做到低骨量的鉴别诊断、原发性或继发性骨质疏松的鉴别诊断、未来骨折风险的评估。     

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.     

Treatment of osteopenia

The majority of osteoporotic fractures happen in individuals with BMD t-scores in the osteopenic range (?2, 5< t-score <?1). However, widespread use of anti-osteoporotic medication in this group based on t-score alone is not advisable because: 1) the number needed to treat is much higher (NNT?>?100) than in patients with fractured and t-score below ?2,5 (NNT 10?C20); 2)while specific osteoporosis treatments have demonstrated significant reductions of the fracture risk in patients with t-score <?2, 5, the efficacy in patients in the osteopenic range is less well established. Therefore, an osteopenic t-score does not in itself constitute a treatment imperative. Generally, osteopenia has to be associated with either low energy fracture(s) or very high risk for future fracture as assessed with risk calculators like FRAX to warrant specific osteoporosis therapy. Vertebral fractures are now conveniently assessed using lateral x-rays from DXA machines. In the vast majority of cases antiresorptive treatments (mainly hormone replacement therapy and SERMS in younger and bisphosphonates or Denosumab in older women) are the treatments of choice in this group of patients,??only rarely is anabolic therapy indicated.     

Assessment of risk factors for bone fractures in patients with type 2 diabetes mellitus: A study in Saudi Arabia

Background and aimsThis study aimed to estimate the prevalence of bone fractures and analyze their associated risk factors in people with and without type 2 diabetes (T2D) in Saudi Arabia.MethodsThis study was conducted among 1188 people (581 type 2 diabetes) in Prince Sultan Military Medical City, Riyadh, Saudi Arabia. In addition to the demographic variables, glycated hemoglobin (HbA1c), creatinine, estimated glomerular filtration rate (eGFR), use of teriparatide, presence of rheumatoid arthritis, presence of chronic obstructive pulmonary disease (COPD), Bone mineral density (BMD), Trabecular Bone Score (TBS) and Fracture Risk using the Fracture Risk Assessment Tool (FRAX) were also collected.ResultsThere were 1188 people (mean age 66.5 ± 8.7yrs) included in this study, of which 1068 (89.9%) were female, and 120 (10.1%) were male. A total of 112 (9.4%) individuals had a fracture history. Female, use of teriparatide, TBS (partially degraded and degraded), FRAX with TBS (MOF), and FRAX with TBS (Hip fx) were identified as independent risk factors for fracture in the whole study population. Teriparatide use and FRAX with TBS (MOF) were observed as independent risk factors for fracture in the non-diabetic population, whereas age, creatinine, eGFR, teriparatide, osteopenia, osteoporosis, TBS (partially degraded, degraded), FRAX with TBS (MOF), FRAX with TBS (Hip fx) were determined as independent risk factors for fracture among patients with diabetes.ConclusionPatients with T2D were observed to have a higher risk for fractures. The findings of the study highlight the requirement for fracture prevention strategies in patients with diabetes.     

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.     

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.     

应用骨折风险预测简易工具评估太原市部分中老年人骨质疏松性髋部骨折风险的价值

目的评价骨折风险预测简易工具(FRAX)在太原市部分中老年人骨质疏松性髋部骨折风险评估中的应用价值。方法在山西医科大学第一医院治疗的髋部骨质疏松性骨折患者(n=292)为骨折组,以骨折组为标准,按性别、年龄配对,招募相同地域的社区居民为对照组(n=292)。2组均使用双能X线骨密度仪(DXA)检测股骨颈骨密度(BMD),收集骨折危险因素,采用FRAX中国模式分别预测2组受试者在有无BMD条件下10年发生髋部骨质疏松性骨折的概率。结果骨折组在有无BMD的条件下10年发生髋部骨质疏松性骨折的概率均高于对照组(P0.01)。有BMD时FRAX预测髋部骨质疏松性骨折的ROC曲线下面积高于无BMD时(0.905、0.701,P0.01),但有无BMD的FRAX预测ROC曲线下面积均低于BMD测定。结论采用FRAX预测太原市部分中老年人骨质疏松性髋部骨折风险评估有一定价值,但预测骨折风险值较低,需要进一步矫正。     

Dairy calcium intake and lifestyle risk factors for bone loss in hiv-infected and uninfected mediterranean subjects

ABSTRACT: BACKGROUND: Despite the reported high prevalence of osteoporosis in the human immunodeficiency virus (HIV)-population, there have been no previous studies examining dairy calcium intake and bone mineral density (BMD) in HIV-subjects. We assessed the prevalence of low BMD in HIV-infected and uninfected subjects and analyzed the effects of calcium intake, lifestyle and HIV-related risk factors on BMD. METHODS: One hundred and twelve HIV-infected subjects were consecutively enrolled. Seventy- six HIV-uninfected subjects matched for age and sex were enrolled as the control group. The HIV-subjects were interviewed about lifestyle habits and completed a weekly food-frequency questionnaire to estimate calcium intake. HIV-RNA, CD4+ T-cell count and data on antiretroviral therapy were also recorded. Both biochemical bone turnover markers and BMD, assessed by dual-energy radiographic absorptiometry (DXA) were recorded in the HIV-cases and controls. We also calculated the 10-year fracture risks using the WHO FRAX equation. RESULTS: Osteoporosis prevalence was significantly higher in the HIV-cases than controls (p < 0.05). BMI values were positively correlated with BMD (p < 0.05). Vitamin D levels were lower in the HIV-subjects (p < 0.02). No correlation was found with daily calcium intake. BMI values were significantly correlated with dairy intake quartiles (p < 0.003). In HIV-subjects, the mean of FRAX score was 1.2 % for hip and 4.7 % for major osteoporotic fractures. On multivariate analysis of the lumbar spine DXA T-score, age (p < 0.005) and HIV/hepatitis C virus co-infection (p < 0.0001) were negatively correlated with BMD, while yogurt intake was a protective predictor of BMD (p < 0.05). In the femur DXA T-score, age (p < 0.01), nadir CD4 + T-cell count < 200 cells/muL (p < 0.05) and drug addiction ( p < 0.0001) were negatively correlated with BMD. CONCLUSIONS: Among the foods rich in calcium, yogurt was a protective predictor of BMD in HIV-subjects. HIV/HCV co-infection, nadir CD4 + T-cell count < 200 cells/muL and drug addiction were independent predictors of severe BMD. Promoting behavioral changes in food intake and lifestyle, aimed at the primary prevention of bone disease in the chronically-infected subjects seems to be essential for implementing medical intervention in these cases.