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.

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.

The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone increases bone resorption in women with type 2 diabetes: a randomized, controlled trial.

In previous studies, with up to 16 weeks of exposure to rosiglitazone or pioglitazone, circulating markers of bone formation [procollagen I N-terminal propeptide (P1NP), osteocalcin, and bone-specific alkaline phosphatase] decreased but no change in bone resorption markers was found. We examined the effect of rosiglitazone on bone resorption and formation markers when used for 24 weeks. This post-hoc analysis of a double-blind, placebo-controlled, randomized trial evaluated the effects of 6 months of rosiglitazone use versus placebo on circulating markers of bone turnover in 111 patients with type 2 diabetes and cardiovascular disease or additional cardiac risk factors. The principal end points for analysis were changes in bone formation and resorption markers, measured by P1NP and carboxy-terminal cross-links (CTX), respectively. There were 111 subjects who completed the study and had baseline and 6-month data; mean age was 56, including 41% women and 67% nonwhite (50 black, 18 Hispanic, and six other), and subjects were evenly distributed between placebo and rosiglitazone groups. Women treated with rosiglitazone had higher CTX levels (0.43 ng/mL) than those who received placebo (0.23 ng/mL) (P = 0.007), with no significant differences in P1NP or OPG. Overall, in stratified analyses of men and in stratified analyses among different ethnicities, there were no statistically significant differences observed in CTX, P1NP, OPG, PTH, or 25-OHD between the treatment groups. Women taking rosiglitazone had higher circulating markers of bone resorption, which is contrary to prior studies of shorter duration, where the principal observation was a decrease in markers of bone formation.

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.

Relation of osteoprotegerin to coronary calcium and aortic plaque (from the Dallas Heart Study).

Circulating osteoprotegerin (OPG) has been shown to be elevated in patients with vascular disease. The role of OPG as a biomarker for atherosclerosis in a large, unselected population is not well known. Plasma OPG levels were measured in 3,386 subjects in the Dallas Heart Study, a multiethnic, population-based probability sample of adults aged 30 to 65 years. Coronary artery calcium (CAC) was measured by electron beam computed tomography. Aortic plaque was assessed by magnetic resonance imaging. Multivariable logistic regression was used to assess associations among OPG, cardiovascular risk factors, CAC, and aortic plaque. Age, female gender, black race, smoking, personal and family history of coronary artery disease (CAD), diabetes mellitus, hyperlipidemia, CAC, and aortic plaque were significantly associated with higher plasma OPG levels (p <0.01) in univariable analyses. The prevalence of CAC and aortic plaque increased across OPG quartiles (p <0.001 for each). An OPG level in the fourth quartile was independently associated with CAC (RR 1.39, 95% confidence interval 1.01 to 1.93) and aortic plaque (RR 1.42, 95% confidence interval 1.09 to 1.86) after adjustment for age, gender, smoking, diabetes, hyperlipidemia, and family history of premature CAD. In conclusion, plasma OPG is independently associated with CAC and aortic plaque in an unselected population, suggesting it may be a novel biomarker for atherosclerosis in humans.

Comparison of testosterone, alendronate, and a combination of both therapies in men with low bone mineral density.

BACKGROUND: Both bisphosphonates and testosterone are known to improve bone mineral density (BMD) in men with low bone mass, but whether combination therapy is superior to these agents used alone is not clear. We compared the changes in lumbar spine BMD when men with low bone mass were treated with each agent alone or as combination therapy. METHODS: In a retrospective study, we analyzed serum and BMD data from 149 men who had been evaluated in the Endocrinology Clinic at the Dallas Veterans Affairs Medical Center, Dallas, Texas. The subjects were divided into three cohorts: 59 men receiving testosterone therapy alone, 68 men receiving alendronate therapy alone, and 22 receiving combination therapy. RESULTS: Compared with the baseline values, the lumbar spine and BMD increased significantly in each of the testosterone, alendronate, and combination therapy cohorts (median annualized rate of change: 2.1% [p < .001], 2.6% [p < .001], and 2.5% [p = .04], respectively). The combination therapy group did not demonstrate any additional increase in BMD at the lumbar spine or total hip compared with either agent alone. The results did not change after adjusting for differences in baseline weight, age, BMD, or baseline testosterone level. CONCLUSION: The results suggest that the combination of testosterone and alendronate does not appear to be superior to single-drug therapy in our patient population.

Male osteoporosis: deadly, but ignored.

Male osteoporosis is a relatively unknown condition for many physicians. Yet about 500,000 fractures happen in men every year. For comparison, prostate cancer is diagnosed in 200,000 men annually. Mortality rate during the first year of hip fracture is higher than 30%, and 50% of patients do not regain their previous mobility and independence. This review focuses on epidemiology, underling causes, diagnostic tools, and treatment of male osteoporosis and prevention of fractures.

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.].

Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds.

In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a K(i) value of 6 micro M. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.

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.

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.