Osteoporosis Diagnosis, Management, and Referral Practice After Fragility Fractures.

PURPOSE OF REVIEW: The purpose of this manuscript is to review the current diagnosis, management, and referral practices of patients with osteoporosis after a fragility fracture from the orthopedic surgeon's perspective. RECENT FINDINGS: Effective treatments are available for osteoporosis that significantly decrease the risk of additional fractures. Despite recommendations for improved post-fragility fracture osteoporosis management, the rate of diagnosis and treatment is still unacceptably low. Patients sustaining a low-energy fracture should be evaluated for osteoporosis with discussion of beginning pharmacological treatment. Antiresorptive and anabolic agents are available treatment options. Fracture Liaison Services can help to coordinate the care of these patients and improve the rate of diagnosis and initiation of therapy. Dartmouth-Hitchcock is working to improve the bone health for our patients utilizing a multidisciplinary team-based approach. This process is intended to lead to increased recognition of osteoporosis within our institution and close the capture gap between hospital discharge and initiation of osteoporosis pharmacotherapy.

Androgen Deprivation Therapy for Prostate Cancer: Specialty Clinic Collaboration and the Electronic Medical Record Can Improve Bone Health Monitoring.

INTRODUCTION: Patients with prostate cancer on androgen deprivation therapy are at increased risk for iatrogenic osteoporosis, minimal trauma fractures and reduced bone density. We created a high risk osteoporosis clinic to manage patients at risk for these complications. A quality improvement initiative involving a best practice advisory and provider education program was implemented to enhance care of patients with prostate cancer. METHODS: Fishbone diagrams were constructed to reveal causes of suboptimal bone health management. A best practice advisory was created for gonadotropin-releasing hormone agonist orders in the Epic electronic medical record to encourage referrals to the high risk osteoporosis clinic. Discussions were held with urology clinic staff regarding fracture risk. Referral rates were assessed via periodic chart reviews. RESULTS: Baseline referral rate to the high risk osteoporosis clinic was 4%. Final review indicated that 113 patients with prostate cancer were seen in the urology clinic from March 2017 to April 2018, of whom 67 were referred to the high risk osteoporosis clinic. At the end of the study period the referral rate had increased to 59%. Among the 113 patients 32 received antiresorptive therapy, 75% of whom had been referred to the high risk osteoporosis clinic. Of 67 patients referred to the clinic 48 had dual energy x-ray absorptiometry completed or pending and 50 had vitamin D levels obtained or pending. Of 46 patients not referred to the clinic 7 had dual energy x-ray absorptiometry completed and 3 had vitamin D levels obtained or pending. CONCLUSIONS: Use of a best practice advisory and urology nursing staff education program increased high risk osteoporosis clinic referrals. A higher proportion of patients referred to the clinic had bone health monitored compared to patients without this referral.

Traditional signs and symptoms commonly attributed to hypogonadism do not correlate with testosterone levels: the Cooper Center Longitudinal Study Experience.

Evidence suggests that substantial testosterone therapy is occurring without checking levels of testosterone, presumably based on the presence of symptoms alone. We sought to explore the relationship between total testosterone level and non-specific symptoms, metabolic abnormalities, and sexual dysfunction associated with hypogonadism. This cross-sectional study included 2994 generally healthy men aged 50-79 years examined at a preventive medicine clinic in Dallas, TX from January 2012 to March 2016. Symptoms of hypogonadism were assessed. Screening morning total testosterone levels were measured and categorized into low (<250 ng/dL), low normal (250-399 ng/dL), and normal (≥400 ng/dL). Multiple logistic regression models were used to test the associations between total testosterone and signs and symptoms of hypogonadism. When considering symptoms and signs of hypogonadism, only decreased libido (OR 1.31, 95% CI 1.00 to 1.70), fasting glucose ≥100 mg/dL (OR 1.47, CI 1.15 to 1.88), and hemoglobin A1c over 6% (OR 1.47, 95% CI 1.06 to 2.03) were associated with increased odds of low testosterone after adjustment for age, body mass index, and cardiorespiratory fitness. Testosterone levels were not associated with fatigue, depression, or erectile dysfunction in our study (p>0.6). In this preventive medicine cohort, symptoms commonly attributed to testosterone deficiency were not associated with low total testosterone levels.

The association of cardiorespiratory fitness, body mass index, and age with testosterone levels at screening of healthy men undergoing preventive medical examinations: The Cooper Center Longitudinal Study.

BACKGROUND: Currently, exogenous hormone replacement is used in many men with hypogonadism without clear organic cause. This study examines the contribution of modifiable health behaviors, i.e., physical activity and weight control, to the maintenance of testosterone levels with aging. METHODS: In a cross-sectional study of 2994 healthy men aged 50-79 years examined at a preventive medicine clinic from January 2012 to March 2016, screening morning total testosterone levels were measured and categorized as low (<250 ng/dL), low normal (250-399 ng/dL), and normal (>400 ng/dL). Cardiorespiratory fitness (fitness) was estimated from a maximal exercise treadmill test. Multiple logistic regression models were used to test the associations between low testosterone levels and age, body mass index (BMI), and fitness. FINDINGS: Mean testosterone levels were in the normal range for each age group (50-59, 60-69, and 70-79). There was a similar prevalence of low testosterone in each age group (11·3%, 10%, and 10·5%, respectively). The prevalence of low testosterone was positively associated with BMI and negatively associated with fitness but was not associated with age. INTERPRETATION: This study found no evidence that low testosterone is an inevitable consequence of aging. Maintenance of healthy weight and fitness may help maintain normal testosterone levels.

Corrigendum to "Predictors of Fracture Risk and Bone Mineral Density in Men with Prostate Cancer on Androgen Deprivation Therapy".

[This corrects the article DOI: 10.4061/2011/924595.].

The Relationship Between Cardiorespiratory Fitness and Bone Mineral Density in Men: A Cross-sectional Study.

OBJECTIVE: To determine the relationship between estimated cardiorespiratory fitness (CRF) and femoral neck (FN) bone mineral density (BMD) in men. PATIENTS AND METHODS: This cross-sectional study included 2569 men aged 50 to 90 years (mean, 63.5 years) who had at least 1 health examination at a preventive medicine clinic between January 27, 1998, and February 24, 2015. Maximal treadmill tests were conducted using the Balke protocol and were used to estimate CRF. We stratified patients into low, moderate, and high CRF categories. The FN BMD was measured by dual-energy x-ray absorptiometry. Odds ratios (ORs) for T-scores of -2.5 or less (osteoporosis) and -1.0 or less (low BMD) were calculated for categorical CRF and were adjusted for weight, age, and days per week of resistance activity. RESULTS: The sample prevalence of osteoporosis in the FN was 4.1% and of low BMD was 49.4%. There was a significant inverse association between higher CRF category and osteoporosis measured at the FN (moderate vs low: OR=0.34; 95% CI, 0.16-0.74; high vs low: OR=0.19; 95% CI, 0.09-0.42) and low BMD (moderate vs low: OR=0.64; 95% CI, 0.43-0.96; high vs low: OR=0.43; 95% CI, 0.29-0.65). CONCLUSION: In men, CRF is directly associated with BMD. These results suggest that moderate-to-high CRF levels attained through regular physical activity may attenuate age-related decline in BMD. Further studies are needed to determine whether this translates to a lower risk of osteoporotic fracture in more fit men.

A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial.

CONTEXT: One in 4 men in the United States aged >50 years will have an osteoporosis-related fracture. Fewer data are available on osteoporosis treatment in men than in women. OBJECTIVE: The purpose of this study was to evaluate denosumab therapy in men with low bone mineral density (BMD). DESIGN: This was a phase 3 study with 2 treatment periods: a previously reported 12-month double-blind, placebo-controlled phase and a 12-month open-label phase. SETTING: This was a multicenter study conducted in North America and Europe. PARTICIPANTS: A total of 228 men entered the open-label phase and 219 completed the study. INTERVENTION: Men from the original denosumab (long-term) and placebo (crossover) groups received 60 mg of denosumab sc every 6 months. MAIN OUTCOME MEASURES: BMD, serum collagen type I C-telopeptide, and safety were measured. RESULTS: During the open-label phase, continued BMD increases occurred with long-term denosumab treatment (2.2% lumbar spine, 0.9% total hip, 1.3% femoral neck, 1.3% trochanter, and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P < .01). The crossover group showed BMD gains after 12 months of denosumab treatment similar to those of the long-term denosumab group during the first treatment year. Significant reductions in serum collagen type I C-teleopeptide were observed after denosumab administration. Adverse event rates were similar between groups, and no new safety signals were identified. CONCLUSIONS: In men with low BMD, denosumab treatment for a second year continued to increase BMD, maintained reductions in bone resorption, and was well tolerated. BMD increased in men initiating denosumab during the second year. These effects were similar to those previously seen in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy.

A cross-sectional survey of urinary iodine status in Latvia.

BACKGROUND AND OBJECTIVE: A nationwide survey of schoolchildren was conducted to detect regional differences in urinary iodine excretion in Latvia and to compare the results with data from the newborn thyroid-stimulating hormone (TSH) screening database as well with the results of a similar study performed in Latvia 10 years ago. MATERIALS AND METHODS: We conducted a cross-sectional school-based cluster survey of 915 children aged 9-12 years in 46 randomly selected schools in all regions of Latvia. Urine samples, questionnaires on the consumption of iodized salt and information on socioeconomic status were collected. TSH levels in newborns were also measured. RESULTS: The median creatinine-standardized urinary iodine concentration (UIC) in our study was 107.3µg/g Cr. UIC measurements indicative of mild iodine deficiency were present in 31.6%, moderate deficiency in 11.9% and severe deficiency in 2.8% of the participants. The prevalence of iodine deficiency was the highest in the southeastern region of Latgale and the northeastern region of Vidzeme. The prevalence of TSH values >5mIU/L followed a similar pattern. The self-reported prevalence of regular iodized salt consumption was 10.2%. Children from urban schools had a significantly lower UIC than children from rural schools. CONCLUSIONS: Our findings suggest that although the overall median UIC in Latvian schoolchildren falls within the lower normal range, almost 50% of the schoolchildren are iodine deficient, especially in urban schools and in the eastern part of Latvia. The absence of a mandatory salt iodization program puts a significant number of children and pregnant women at risk.

Clinical experience with intravenous zoledronic acid in the treatment of male osteoporosis: evidence and opinions.

Osteoporosis frequently remains underrecognized and undertreated in men. Most osteoporosis-related fractures could be prevented if men at risk would be diagnosed, treated, and remained compliant with therapy. Bisphosphonates, the mainstay of osteoporosis treatment, are potent antiresorptive agents that inhibit osteoclast activity, suppress in vivo markers of bone turnover, increase bone mineral density, decrease fractures, and likely improve survival in men with osteoporosis. The focus of the article is on intravenous zoledronic acid, which may be a preferable alternative to oral bisphosphonate therapy in patients with cognitive dysfunction, the inability to sit upright, polypharmacy, significant gastrointestinal pathology or suspected medication noncompliance. Zoledronic acid is approved in the United States (US) and European Union (EU) as an annual 5 mg intravenous infusion to treat osteoporosis in men. The zoledronic acid 4 mg intravenous dose has been studied in the prevention of bone loss associated with androgen deprivation therapy. This article reviews the evidence for zoledronic acid, currently the most potent bisphosphonate available for clinical use, and its therapeutic effects in the treatment of men with osteoporosis.

Risk factors for diminished bone mineral density among male hemodialysis patients--a cross-sectional study.

UNLABELLED: This cross-sectional study was performed to characterize the factors affecting bone mass in male hemodialysis subjects. We found that of all the factors analyzed, the strongest correlation was with body mass index. In fact, after adjusting for body weight, the correlations with bone turnover markers and sex hormones were no longer significant. PURPOSE: Abnormalities in bone and mineral metabolism are commonly seen in patients with end-stage renal disease, reducing bone quality and raising the risk of fracture. This cross-sectional study was performed to characterize risk factors affecting bone mass among male hemodialysis subjects. METHODS: For this cross-sectional study, we recruited 66 men from three local hemodialysis units. Subjects received dual emission X-ray absorptiometry assessment of three sites (lumbar spine, hip, and distal radius) and the values were correlated with the levels of sex hormones, non-renally excreted bone turnover markers, and mineral metabolism markers. RESULTS: Subjects were found to have bone mineral density (BMD) reduced predominantly at the distal radius, with Z score < −2 seen in 15.4 % and T score < −2.5 in 21 % of men. Independent predictors of bone density included levels of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b, which were inversely correlated with the femoral neck Z score. Factors positively associated with an increased Z score included body mass index at all sites and free estradiol levels at the hip and distal radius. Markers of mineral metabolism (e.g., calcium, phosphate, and 25-hydroxyvitamin D) were not correlated with Z scores of any site or with bone turnover markers. After adjusting for body weight, the associations between BMD, sex hormones, and bone turnover markers were no longer significant. CONCLUSION: We recommend that future studies seeking to assess the factors affecting bone strength among male hemodialysis subjects incorporate a weight-adjusted analysis. Additionally, dialysis-dependent men receiving dual emission X-ray absorptiometry should have the distal radius site added to the standard assessment.

A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density.

CONTEXT: Men with low bone mineral density (BMD) were treated with denosumab. OBJECTIVE: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. DESIGN, SUBJECTS, AND INTERVENTION: This was a placebo-controlled, phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD. MAIN OUTCOME MEASURE: The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at month 12. RESULTS: Of the 242 randomized subjects (mean age 65 yr), 228 (94.2%) completed 1 yr of denosumab therapy. After 12 months, denosumab resulted in BMD increases of 5.7% at the LS, 2.4% at the total hip, 2.1% at the femoral neck, 3.1% at the trochanter, and 0.6% at the one third radius (adjusted P ≤ 0.0144 for BMD percent differences at all sites compared with placebo). Sensitivity analyses done by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations. Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P < 0.0001). The incidence of adverse events was similar between groups. CONCLUSIONS: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed.