Anabolic Therapy and Optimal Treatment Sequences for Patients With Osteoporosis at High Risk for Fracture

Objective: Provide an update regarding anabolic medications for osteoporosis, which are often considered to be the last resort for patients with osteoporosis, after multiple fractures have already occurred and other medications have already been administered.Methods: Literature review and discussion.Results: Recent pivotal trial data for anabolic agents and randomized trials comparing anabolic and antiresorptive medications suggest that three anabolic agents (teriparatide, abaloparatide, and romosozumab) reduce nonvertebral and vertebral fractures faster and to a greater extent than potent antiresorptive treatments. Furthermore, bone density accrual is maximized when patients are given anabolic agents first, followed by potent antiresorptive therapy. Since total hip bone density during or after osteoporosis treatment has emerged as an excellent surrogate for future fracture risk, attaining a greater hip bone mineral density is a treatment goal for high-risk osteoporosis patients.Conclusion: This review defines the highest-risk patients and summarizes the rationale for the evolving role of anabolic therapy in the management of postmenopausal women at high risk for fracture.Abbreviations: ACTIVE = Abaloparatide Comparator Trial in Vertebral Endpoints; ARCH = Active Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk; BMD = bone mineral density; FRAME = Fracture Study in Postmenopausal Women with Osteoporosis; FRAX = Fracture Risk Assessment Tool; PTH = parathyroid hormone; TBS = trabecular bone score     

Iatrogenic Osteoporosis,Bilateral Hip Osteonecrosis,and Secondary Adrenal Suppression in an Hiv-Infected Man Receiving Inhaled Corticosteroids and Ritonavir-Boosted Highly Active Antiretroviral Therapy

ObjectiveTo report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy.MethodsWe describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature.ResultsA 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy.Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma.ConclusionsGiven the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavirboosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression. (Endocr Pract. 2011;17:74-78)     

Evaluation and Treatment of Osteoporosis in Patients with a Fragility Hip Fracture

ObjectiveTo determine whether patients with fragility hip fractures underwent assessment and treatment of osteoporosis during initial hospitalization or recommendations for such intervention were made to the primary care provider (PCP) at the time of hospital dismissal.MethodsA review of medical records of patients admitted with a low-impact hip fracture to the Royal University Hospital in Saskatoon, Saskatchewan, Canada, was performed to determine whether recommendations were made to evaluate for or treat osteoporosis. In addition, a questionnaire was sent to the orthopedic surgeons practicing at the hospital to help identify barriers to widespread diagnosis and treatment of osteoporosis in such patients.ResultsBetween January and December 2004, 174 patients with fragility hip fractures were admitted to the Royal University Hospital. The mean age of these patients was 82.5 ± 9.8 years. Evaluation for treatment of osteoporosis was recommended in only 9 patients (5%). We found no significant differences in the intervention rates between male and female patients, between patients with and those without a prior history of osteoporosis or fracture, between patients who were previously taking osteoporosis medications and those who were not, and between patients who were seen by a medical consultant and those who were not. Most orthopedic surgeons believed that they were primarily responsible for the surgical care of these patients, and because they did not see these patients in regular follow-up, the management of osteoporosis was considered the responsibility of the PCP.Conclusion: The results of this study indicate that only a small number of patients with fragility hip fractures receive appropriate evaluation or treatment for underlying osteoporosis either during initial hospitalization or at the time of dismissal from the hospital. In this study, most orthopedic surgeons believed that evaluation and treatment of osteoporosis were the responsibility of the PCP. Because these patients have an increased risk for future fractures, barriers to the diagnosis and treatment of osteoporosis need to be removed, and health-care professionals need to be educated about appropriate risk factor modification in these patients. (Endocr Pract. 2005;11:370-375)     

A Simple Intervention for Improving the Implementation Rate of a Recommended Osteoporosis Treatment After Hip Fracture

ObjectiveOsteoporosis is often under-treated, and hip fracture is frequently its first manifestation. Hospitalization for a hip fracture is an opportunity to initiate osteoporosis treatment. The aim of this study was to investigate whether a simple intervention improves the implementation rate of a recommended osteoporosis treatment.MethodsOne hundred elderly patients admitted with low-impact hip fracture were given a 10 minute explanation about osteoporosis and its treatment during their postoperative hospital stay. In addition, the patients received an explanatory brochure and a letter to their primary care physician that included an article on fracture rate reduction with osteoporosis treatment. Implementation of therapy was assessed by a telephone survey 3 and 6 months postoperatively. The patients who had not received treatment at 3 months were given a repeated explanation. The historical control group was comprised of 100 hip fracture patients with similar demographic characteristics, who were operated on and discharged with the standard care recommendations for osteoporosis prevention.ResultsAt the 3 month follow-up, the therapy rate in both groups was similar (19%). Fifty-eight percent of the patients in the study group had no recollection of the intervention. However, after a repeated explanation, at the 6 month follow-up, 39% of the intervention group had received drug therapy for fracture prevention (P<.001).ConclusionA simple intervention enlisting the patients' help to involve their primary care physician can increase treatment rates for osteoporosis following a hip fracture. During the immediate postoperative period, the patients and their families have difficulty implementing the recommendations. Therefore, repeated communications are recommended. (Endocr Pract. 2013;19:46-50)     

The determinants of fracture in men

Osteoporosis represents an increasingly important clinical and public health problem among older men. Estimates indicated that 1-2 million (3-6%) men aged 50 years and over in the United States have osteoporosis and 8-13 million (28- 47%) have osteopenia. The lifetime risk of suffering a hip, spine or forearm fracture for a 50-year-old man is 13%, similar to the risk for prostate cancer. The number of osteoporotic fractures in men is expected to increase dramatically due to aging of the population and secular increases in fracture rates. Identification of men who are at greatest risk of osteoporosis and the risk factors, which predispose men to fracture, are essential so that preventive steps can be taken. Data on risk factors are emerging but many questions remain. Men may fracture at a higher bone mineral density (BMD) level than women. However, estimates of volumetric BMD, which correct in part for gender differences in bone size, and risk of fracture, may actually show similar relationships in men and women. Fracture rates are similar in older African American women and Caucasian men. Improved understanding of ethnic differences in fracture could identify potential reasons for gender differences. Family history and genetic factors are also important risk factors for fractures but the specific candidate genes are not known and whether gender modifies the effects of these genetic polymorphisms on BMD and the risk of fracture is also not known. In general, lifestyle factors and anthropometric measurements show similar relationships with fractures in men and women although few comprehensive prospective studies have been conducted. Current data will be reviewed on the relationships between markers of skeletal health, genetic polymorphisms, lifestyle and anthropometric factors and fracture.     

Treatment of Osteoporosis and Prevention of New Fractures: Role of Intravenously Administered Bisphosphonates

ObjectiveTo evaluate the usefulness of intravenously administered bisphosphonates for improving absorption, tolerability, adherence, and outcomes in the treatment and prevention of osteoporosis.MethodsData published from 1996 to 2009 relevant to the treatment of osteoporosis, with emphasis on bisphosphonates, fracture risk, adherence to therapy, frequency of dosing, intravenous treatment, tolerability, cost-effectiveness, and quality of life, were reviewed.ResultsAlthough bisphosphonates are currently the standard of care for treatment of postmenopausal osteoporosis and osteoporosis in men, oral formulations are associated with poor absorption and potential irritation of the upper gastrointestinal tract. These issues necessitate complicated and restrictive dosing regimens, which in turn lead to poor compliance and persistence. Intravenous formulations such as 3 mg of ibandronate given quarterly and 5 mg of zoledronic acid administered once yearly avoid problems relating to absorption and tolerability by bypassing the gastrointestinal tract. Intravenously administered ibandronate is presumed (by virtue of similar or superior improvements in bone mineral density) to have antifracture efficacy similar to that of orally administered ibandronate given daily, which has been shown to produce significant reductions in vertebral fractures during a 3-year period in comparison with placebo. Zoledronic acid, 5 mg once yearly, has been shown to produce a significant reduction in the risk of morphometric vertebral fractures, clinical vertebral fractures, hip fractures, and nonvertebral fractures versus placebo during a 3-year interval in patients with postmenopausal osteoporosis and also to yield a significantly decreased risk for new clinical fractures versus placebo in patients with recent low-trauma hip fracture. Both agents have favorable safety and tolerability profiles.ConclusionIntravenously administered bisphosphonates have the potential to increase compliance and persistence with therapy in patients with osteoporosis and to improve patient outcomes. (Endocr Pract. 2009;15:483-493)     

Bone Mineral Density of the 1/3 Radius Refines Osteoporosis Diagnosis,Correlates With Prevalent Fractures,and Enhances Fracture Risk Estimates

ObjectiveTo investigate the added value of 1/3 radius (1/3R) for the diagnosis of osteoporosis by spine and hip sites and its correlation with prevalent fractures and predicted fracture risk.MethodsFracture Risk Assessment Tool (FRAX) scores for hip and major osteoporotic fractures (MOF) with/without trabecular bone score were considered proxy for fracture risk. The contribution of 1/3R to risk prediction was depicted via linear regression models with FRAX score as the dependent variable—first only with central and then with radius T-score as an additional covariate. Significance of change in the explained variance was compared by F-test.ResultsThe study included 1453 patients, 86% women, aged 66 ± 10 years. A total of 32% (n = 471) were osteoporotic by spine/hip and 8% (n = 115) by radius only, constituting a 24.4% increase in the number of subjects defined as osteoporotic (n = 586, 40%). Prior fracture prevalence was similar among patients with osteoporosis by spine/hip (17.4%) and radius only (19.1%) (P = .77).FRAX prediction by a regression model using spine/hip T-score yielded explained variance of 51.8% and 49.9% for MOF and 39.8% and 36.4% for hip (with/without trabecular bone score adjustment, respectively). The contribution of 1/3R was statistically significant (P < .001) and slightly increased the explained variance to 52.3% and 50.4% for MOF and 40.9% and 37.4% for hip, respectively.ConclusionReclassification of BMD results according to radius measurements results in higher diagnostic output. Prior fractures were equally prevalent among patients with radius-only and classic-site osteoporosis. FRAX tool performance slightly improved by incorporating radius BMD. Whether this approach may lead to a better fracture prediction warrants further prospective evaluation.     

Orthopedic-Metabolic Collaborative Management for Osteoporotic Hip Fracture

Objective: Osteoporotic hip fractures are associated with increased morbidity, mortality, and secondary fractures. Although osteoporosis treatment can reduce future fracture risk, patients often do not receive it. We report results of a coordinator-less fracture liaison service in Israel addressing hip fracture patients. The primary endpoint was attending the Metabolic Clinic. Secondary endpoints included vitamin D measurement, calcium and vitamin D recommendations, initiation of osteoporosis treatment, and mortality 1-year post-fracture.Methods: This prospective study included 219 hip fracture patients who were compared with historical controls. Data on hospitalized patients were collected before and after implementation of a structured protocol for hip fracture patients, led by a multidisciplinary team, without a coordinator.Results: The study included 219 and 218 patients ≥60 years old who were operated on in 2013 and 2012, respectively. Metabolic Clinic visits increased from 6.4 to 40.2% after the intervention (P<.001). Among 14 patients who attended the Clinic in 2012, 85.7% began osteoporosis therapy; among 88 who attended in 2013, 45.5% were treated at the first visit. Vitamin D measurements and calcium and vitamin D supplementation increased postintervention (0.5–80.1%, P<.001; 30.8–84.7%, P<.001, respectively). Patients receiving osteoporosis medications had lower mortality rates than untreated patients (4.3% vs. 21.8%).Conclusion: An Orthopedic-Metabolic team implemented by existing staff without a coordinator can improve osteoporosis care for hip fracture patients. Yet, gaps remain as only 40% had Metabolic Clinic follow-up postintervention, and of these, only half received specific treatment recommendations. Hospitals are encouraged to adopt secondary fracture prevention protocols and continuously improve them to close the gaps between current management and appropriate metabolic assessment and treatment.Abbreviations: CHS = Clalit Health Services; CI = confidence interval; FLS = fracture liaison service; HMO = health maintenance organization; OR = odds ratio     

A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men

ObjectiveBone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men.MethodsThis cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men.ResultsThe mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS.ConclusionIn older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS.     

Consensus and Controversy Regarding Osteoporosis in the Pediatric Population

ObjectiveTo review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence.MethodsThe medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis.ResultsChildhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass—variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients.ConclusionBone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood. (Endocr Pract. 2007;13:513-520)     

Frax Prediction without BMD for Assessment of Osteoporotic Fracture Risk

ObjectiveTo compare Fracture Risk Assessment Tool (FRAX) calculations with and without bone mineral density (BMD) in predicting the 10-year probability of hip and major osteoporotic fractures (MOF).MethodsA cross-sectional review of patients requiring screening for osteoporosis as part of their routine medical care was conducted. Postmenopausal women and men over 50 years of age who were never diagnosed with osteoporosis or treated with U.S. Food and Drug Administration-approved agents for osteoporosis were included. Height, weight, FRAX questionnaire, femoral neck BMD, and T-score data were obtained. FRAX scores with BMD (FRAX/BMD) and without BMD (FRAX) were calculated. Subjects were separated on the basis of identical and different treatment recommendations. Fracture risk factors were compared between groups using simple Student’s t test analysis of numerical variables and Fisher’s exact test analysis of binary variables.ResultsOf 151 total subjects, 127 (84%) had identical fracture risk predictions with or without BMD included in the FRAX calculation. Thirty subjects met treatment criteria and 97 did not, but the FRAX prediction was the same with risk factors alone or with risk factors plus BMD. Age was the only risk factor that was significantly different between those with identical and different predictions (median age, 64.42 and 76.25 years, respectively; P&#x003C;.001).ConclusionIn most cases, FRAX alone provides the same prediction as FRAX with BMD. Younger age is more indicative of an identical prediction. (Endocr Pract. 2013;19:780-784)     

AN 18-Month Open-Label Trial of Teriparatide in Patients with Previous Parathyroidectomy at Continued Risk for Osteoporotic Fractures: An Exploratory Study

ObjectiveTo determine whether teriparatide increases lumbar spine bone mineral density (BMD) in patients who have undergone parathyroidectomy for primary hyperparathyroidism (PHPT) and are at continued risk for fracture.MethodsThis open-label, nonrandomized, uncontrolled exploratory design study included patients who had undergone parathyroidectomy for PHPT and were judged to be at continued risk for fracture according to National Osteoporosis Foundation criteria. Patients were administered teriparatide subcutaneously, 20 mcg daily, for 18 months after they satisfactorily completed the screening period to ensure their eligibility for study participation. BMD was assessed by dual-energy x-ray absorptiometry at baseline, 6 months, 12 months, and 18 months. Secondary objectives included efficacy of teriparatide on increasing hip BMD, incidence of fractures, and safety measurements.ResultsSeven women and 3 men were included. Change in mean lumbar spine BMD was 0.059 gm/cm², which is a 7.1% increase (P = .005). Change in mean femoral neck BMD was 0.019 gm/cm², which is a nonsignificant increase of 3.3% (P = .49). There was no incidence of fractures. There were no significant changes in the safety measurements.ConclusionsThe use of teriparatide in patients with PHPT who have undergone parathyroidectomy and are still at risk for fracture is effective in improving lumbar spine BMD without deleterious effects on safety. Teriparatide should therefore be considered as a viable alternative for the treatment of these patients, as it may help in the prevention of fractures and their complications. (Endocr Pract. 2011;17:377-383)     

Secondary Causes of Osteoporosis

ObjectiveTo provide an updated review of several causes of secondary osteoporosis as well as screening recommendations for these disorders.MethodsWe conducted an updated review of the literature published since 2006 on secondary causes of osteoporosis. This information has been added to the relevant data published between 1990 and 2006, which was included in our prior review from 2006. This current review also includes recent clinical guidelines recommendations.ResultsSecondary osteoporosis occurs in almost two thirds of men, more than half of premenopausal women, and about 30% of postmenopausal women. Its causes are vast, and they include hypogonadism, medications, hyperthyroidism, vitamin D deficiency, primary hyperparathyroidism, solid organ transplantation, gastrointestinal diseases, hematologic diseases, Cushing's syndrome, and idiopathic hypercalciuria. These causes have their own pathogenesis, epidemiologic features, and effects on the skeleton.ConclusionThe causes of secondary osteoporosis are numerous, and an understanding of their characteristics with respect to bone density and potential fracture risk is essential in the management of osteoporosis. A heightened awareness of the possibility of their existence is necessary to provide optimal care. (Endocr Pract. 2013;19:120-128)     

Predictors of Short- and Long-Term Mortality in Males and Females with Hip Fracture - A Prospective Observational Cohort Study

Background

Hip fracture is associated with increased mortality. Our aim was to study potential risk factors, including osteoporosis, associated with short- and long-term mortality in a prospectively recruited cohort of fragility hip fracture patients.

Methodology/Principal Findings

Fragility hip fracture patients aged >50 years admitted to a county hospital in Southern Norway in 2004 and 2005 were consecutively identified and invited for assessment. Patients with high energy or pathological fractures, patients with confusion, serious infections or who were non-residents in the catchment area were excluded. As part of a clinical routine, data were collected using questionnaires. Standardized bone density measurements of lumbar spine and hip were performed. Potential predictors of hip fracture mortality were tested using univariate and multivariate logistic regression analysis. A total of 432 hip fracture patients (129 males and 303 females) were prospectively identified. Among them 296 (85 males and 211 females) patients [mean age 80.7 (SD 9.1)] were assessed at the Osteoporosis center. Variables independently associated with short-term mortality (after 1 year) were in females older age [Odds Ratio (OR) 6.95] and in males older age (OR 5.74) and pulmonary disease (OR 3.20), whereas no associations were observed with mortality for 3 months after the fragility hip fracture. Variables independently associated with 5 years mortality in males was osteoporosis (OR 3.91) and older age (OR 6.95), and in females was dementia (OR 4.16) and older age (OR 2.80).

Conclusion

Apart from known predictors as age and comorbidity osteoporosis in our study was identified as a potential independent predictor of long-term hip fracture mortality in males. This is of particular importance as treatment with bisphosphonates after hip fracture has been shown to reduce hip fracture mortality and may be a clinical target to reduce the burden of the disease. Further studies however are needed to confirm the validity of this finding.     

Long-Term Follow-up of patients on Drug Holiday from Bisphosphonates: Real-World Setting

ObjectiveAtypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk.MethodsA retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures.ResultsEleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were −2.225 (±1.779) and −2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (−0.0084 ± 0.03 gm/cm²).ConclusionThe current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy. (Endocr Pract. 2013;19:989-994)     

Management of osteoporosis

Osteoporosis or osteopenia occurs in about 44 million Americans, resulting in 1.5 million fragility fractures per year. The consequences of these fractures include pain, disability, depression, loss of independence, and increased mortality. The burden to the healthcare system, in terms of cost and resources, is tremendous, with an estimated direct annual USA healthcare expenditure of about $17 billion. With longer life expectancy and the aging of the baby-boomer generation, the number of men and women with osteoporosis or low bone density is expected to rise to over 61 million by 2020. Osteoporosis is a silent disease that causes no symptoms until a fracture occurs. Any fragility fracture greatly increases the risk of future fractures. Most patients with osteoporosis are not being diagnosed or treated. Even those with previous fractures, who are at extremely high risk of future fractures, are often not being treated. It is preferable to diagnose osteoporosis by bone density testing of high risk individuals before the first fracture occurs. If osteoporosis or low bone density is identified, evaluation for contributing factors should be considered. Patients on long-term glucocorticoid therapy are at especially high risk for developing osteoporosis, and may sustain fractures at a lower bone density than those not taking glucocorticoids. All patients should be counseled on the importance of regular weight-bearing exercise and adequate daily intake of calcium and vitamin D. Exposure to medications that cause drowsiness or hypotension should be minimized. Non-pharmacologic therapy to reduce the non-skeletal risk factors for fracture should be considered. These include fall prevention through balance training and muscle strengthening, removal of fall hazards at home, and wearing hip protectors if the risk of falling remains high. Pharmacologic therapy can stabilize or increase bone density in most patients, and reduce fracture risk by about 50%. By selecting high risk patients for bone density testing it is possible to diagnose this disease before the first fracture occurs, and initiate appropriate treatment to reduce the risk of future fractures.     

Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBDs): What the Endocrinologist Needs to Know

ObjectiveChronic kidney disease-mineral and bone disorders (CKD-MBDs) are a spectrum of abnormalities involving skeletal hormones, minerals, and bone turnover and mineralization. This paper focuses on what the endocrinologist should know about the assessment and management of skeletal and metabolic disorders in CKD-MBDs.MethodsRelevant literature was reviewed to (1) define disturbances of minerals and hormones in the course of CKD; (2) identify the variable radiographic and histomorphometric changes of CKD-MBDs; (3) review the association among CKD-MBDs, vascular calcification, cardiovascular disease (CVD), and mortality; and (4) clarify issues in CKD-MBDs therapy.ResultsAssessment and treatment of CKD-MBDs is complicated by progressive changes in bone minerals and skeletal regulatory hormones as kidney function declines. CKD-MBDs are associated with fracture risk, and studies demonstrate that bone mineral density can be used to assess bone loss and fracture risk in these patients. Treatment of CKD-MBDs continues to evolve. Use of calcium, phosphate binders, vitamin D, vitamin D–receptor analogs, and drugs for osteoporosis and CKD-MBDs treatment are discussed in the context of safety and efficacy for patients with CKD.ConclusionThe association of CKD with bone disease, vascular calcification, CVD, and mortality mandates earlier recognition and treatment of CKD-MBDs. Osteoporosis as a distinct entity can be diagnosed and managed in CKD, although assessment of osteoporosis becomes challenging in late (stage 4 to 5) CKD. Diabetes is common in early (stage 1 to 3) CKD. In addition, 96% of all individuals identified as having CKD have early CKD. The endocrinologist is uniquely positioned to address and treat both diabetes and many of the metabolic and skeletal disorders associated with early CKD-MBDs, including osteoporosis. (Endocr Pract. 2014;20:500-516)     

Virtual Orthopedic-Rehabilitation-Metabolic Collaboration for Treating Osteoporotic HIP Fractures

Objective: To evaluate the effectiveness of a virtual, closed-loop protocol that treated hip fracture patients without formal clinic visits.Methods: In this prospective cohort study, an intervention group of 85 hip fracture patients (33.6%) with vitamin D levels ≥65 nmol/L who received recommendations for osteoporosis treatment, was compared to a nonintervention group of 168 (66.4%), with vitamin D <65 nmol/L. Treatment included vitamin D loading in orthopedic and rehabilitation departments for patients from both groups, and virtual, osteoporosis treatment recommendations by Metabolic Clinic physicians to patients from the intervention group upon achieving a vitamin D level ≥65 nmol/L. Recommendations were given without requiring clinic visits. Osteoporosis drug recommendations were relayed to primary care physicians. The primary endpoint was patients receiving osteoporosis drugs within 12-months post-surgery. Secondary endpoints were patients issued drugs within 3- and 6-months post-surgery, and 1-year post-fracture mortality rates.Results: Among 253 hip fracture patients (81.3 ± 10.7 years-of-age, 68.8% women), the postintervention osteoporosis medication issue rate was higher than in the nonintervention group (48.2% versus 22.0%, respectively; P<.001). More intervention group patients received drugs 3 months (18.8% versus 2.9%; P<.001) and 6 months after surgery (40% versus 5.9%; P<.001). One-year mortality was lower among patients who received any osteoporosis medications (either through our intervention or from community physicians) than among untreated patients (5.1% versus 26.3%; P<.001).Conclusion: Virtual orthopedic-rehabilitation-metabolic collaboration increased osteoporosis treatment rates post-hip fracture. Yet, treatment rates remained <50%. Additional research is required to increase treatment rates further, such as providing drug therapy shortly after surgery, perhaps during rehabilitation, or lowering the vita-min D threshold.Abbreviations: CHS = Clalit Health Services; FLS = Fracture liaison service; HMO = Health Maintenance Organization; MMC = Meir Medical Center; PCP = primary care physician     

Osteoporosis As The Sole Manifestation of Systemic Mastocytosis In A Young Man

ObjectiveTo highlight the difficulty involved in mak ing a diagnosis of systemic mastocytosis (SM) when it manifests solely as osteoporosis.MethodsWe present a detailed case report and review the literature regarding the work-up of secondary osteopo rosis and the diagnosis and treatment of SM. Other cases of SM presenting as osteoporosis in male patients are also described.ResultsA 35-year-old man presented with back pain after weight lifting and was diagnosed with a T7 vertebral compression fracture. A dual-energy x-ray absorptiom etry scan resulted in a T-score of − 3.2 in the spine and of − 1.9 and − 2.4 in the hip and femoral neck areas, respec tively. Results of standard tests for secondary osteoporo sis including calcium, phosphorus, 25-hydroxyvitamin D, kidney and liver function, thyroid function, testosterone level, and midnight salivary cortisol were normal. Further testing revealed a high serum tryptase level of 26.8 μg/L (reference range, < 11.4) and elevated urinary histamine at 39.1 μg/g creatinine (reference range, < 35). Bone marrow biopsy confirmed the diagnosis of mastocytosis.ConclusionThe rare diagnosis of SM is diffi cult when there is little clinical suspicion and remains a challenge to endocrinologists and other physicians. The condition should be suspected in young male patients with no other obvious cause of osteoporosis. (Endocr Pract. 2012; 18:e158 e161)     

Osteoporosis Treatment After Osteoporotic Fractures: Data From a Single Medical Center

ObjectiveMost patients do not receive osteoporosis treatment after osteoporotic fracture. This study reviewed osteoporosis treatment after osteoporotic fractures in a center without a Fracture Liaison Service.MethodsWe identified all patients with hip, vertebral, humeral or radial fractures, evaluated in Meir Medical Center, in 2017. The exclusion criteria were not a Clalit Health Services member, high-energy fracture or 30-day postoperative mortality. The primary endpoint was osteoporosis drugs issued within 12 months of fracture. Secondary endpoints included bone densitometry and 1-year mortality.ResultsFive-hundred-eighty-two patients (average age 78.6 ± 11.1 years, 75.8% women) were included. There were 321 (55.5%) hip, 84 (14.1%) humeral, 33 (5.6%) vertebral, and 144 (24.7%) radial fractures. Osteoporosis drugs were issued to 26.5% of the patients; those with humeral fractures received the least (21.4%) and vertebral, the most (30.3%; P = .51). Bone densitometry was performed in 23.2% of patients. One-year mortality after hip fracture was 12.1%, followed by humeral (3.6%; P < .05). Logistic regression showed that previous treatment (odds ratio [OR] = 7.4; 95% confidence interval [CI] 3.6–15.2), bone densitometry (OR = 4.4; 95% CI 2.6–7.4) and endocrinology visit (OR = 2.6; 95% CI, 1.4–4.6) were the most important factors associated with treatment.ConclusionFewer than one third of patients received pharmacotherapy within 1 year after fracture. Because pharmacotherapy reduces future fractures and mortality, we recommend that medical staff who care for patients with fracture adopt practical and effective strategies to increase treatment rates among patients with osteoporotic fractures.