Fracture Risk In Men Research Articles

Sex hormone–binding globulin is a biomarker associated with nonvertebral fracture in men on dialysis therapy

Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation. Results of serum biochemistry, SHBG, gonadal steroids (total testosterone, calculated free testosterone and estradiol), BMD by dual-energy X-ray absorptiometry and thoracolumbar X-rays were obtained. Multivariable regression models were used to examine associations between SHBG, gonadal steroids, BMD and fracture of 321 men with a mean age of 47 years. Diabetes mellitus was present in 45% and their median dialysis vintage was 24 months. Prior fractures occurred in 42%, 18% had vertebral fracture on lateral spine X-ray, 17% had non-vertebral fragility fracture within 10 years and 7% had both. After adjustment for age, body mass index and dialysis vintage, higher SHBG levels were significantly associated with nonvertebral fractures [odds ratio 1.81 (1.30-2.53)] and remained significant after adjustment for BMD. Calculated free testosterone and estradiol values were not associated with fracture. Prevalent fracture rates were high in relatively young men on dialysis awaiting transplantation. Thus, SHBG is a novel biomarker associated with fracture, which warrants investigation in prospective studies.

EAA clinical guideline on management of bone health in the andrological outpatient clinic.

Male osteoporosis is now a well-recognized medical disorder with established clinical guidelines for both diagnosis and management. Prevention as well as management of osteoporosis in men consulting the andrological outpatient clinic because of low testosterone, however, is not well established. This gap of knowledge is-at least partly-explained by the controversy with respect to the threshold of testosterone needed for skeletal maintenance. However, testosterone deficiency may be clearly associated with bone loss as well as frailty in men. If anything, andrologists should therefore be aware of the potential silent presence of osteoporosis in men with confirmed hypogonadism. Therefore, the management of patients with potential hypogonadism should include a complete bone health assessment, besides clinical and biochemical evaluation of gonadal status. Such bone health assessment should include specific items in medical history and physical examination related to fracture risk. Furthermore, dual-energy absorptiometry is indicated to evaluate fracture risk in men with confirmed clinical hypogonadism. Regarding treatment, besides general measures to prevent or manage male osteoporosis testosterone replacement can be initiated (as described in guidelines for hypogonadism), but data on its efficacy in preventing fractures are lacking. Thus, additional anti-osteoporotic may be needed, especially in men with very low testosterone who are at high risk of bone loss and/or in men not able to receive testosterone replacement.

Sports Participation in High School and College Leads to High Bone Density and Greater Rates of Bone Loss in Young Men: Results from a Population-Based Study.

Estimated lifetime risk of an osteoporotic fracture in men over the age of 50years is substantial and lifestyle factors such as physical activity may explain variation in bone mass and bone loss associated with aging. Men (n = 253) aged 20-66years were followed for 7.5years and factors that influence changes in means and rates of change in bone mass, density, and size using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) were investigated; in particular, seasons of sports participation during high school and college. Men with greater sports participation had higher total hip bone mineral content (BMC) (48.4 ± 0.9 and 48.6 ± 0.9g for 7-12 and 13+ seasons vs. 45.6 ± 0.8 and 45.4 ± 0.7g for 0 and 1-6 seasons, respectively p < 0.05) and areal bone mineral density (aBMD) (1.082 ± 0.015 and 1.087 ± 0.015g/cm2 for 7-12 and 13+ seasons vs. 1.011 ± 0.015 and 1.029 ± 0.013g/cm2 for 0 and 1-6 seasons, respectively p < 0.05) than men who participated in less sport-seasons. However, men with higher sports participation also had greater rates of bone loss in their mid-twenties at the hip (BMC - 0.8 and - 1.2% and aBMD - 0.8 and - 0.9% for 7-12 and 13+ seasons of sport participation, respectively) compared to those with 0 seasons of sport participation (BMC - 0.6% and aBMD - 0.6%) (all p < 0.05). Similar results were observed for femoral neck aBMD. Men with 7+ seasons of sport participation had higher cross-sectional area at the 20% distal radius site than those with no sports participation (all p < 0.05). These findings support significant effects of high school and/or college sports participation on bone mass and geometry in men throughout adulthood.

Association between metabolic syndrome and bone fracture risk

Osteoporosis and metabolic syndrome (MS) share similar risk factors. Previous studies of association between bone marrow density (BMD) and MS are controversial. Moreover, some studies revealed that MS is associated with BMD but not with bone fracture. In clinical practice, patients pay more attention to bone fracture risk than BMD values. Hence, this study aimed to evaluate the association between MS and the 10-year bone fracture risk probability using a fracture risk assessment tool (FRAX) from community-based data. From March 2014 to August 2015, 2689 participants (897 men and 1792 women) were enrolled in this study. Inflammatory cytokines, such as tumor necrosis factor alpha and C-reactive protein, and adipokines were included for analysis.The mean age was 60.2 ± 10.7 years in men and 58.9 ± 9.6 years in women. The percentage of MS was 27.6% in men and 27.9% in women. Participants were divided into 2 groups, those with or without MS. Compared with women without MS, women with MS had a higher rate of fracture risk (22.8% vs 16.3%, P = .001). In contrast, men with MS had a lower rate of fracture risk then men without MS (5.6% vs 12.3%, P = .004). However, MS loss the association with a high bone fracture risk in men based on multivariate logistical regression analysis, after adjusting for confounding factor of body mass index (BMI). Conclusively, the result of regression analysis between MS and the bone fracture risk may be different in men and women, and BMI was an important confounding factor to interfere with the regression analysis.

Trabecular Bone Score in Men and Women with Impaired Fasting Glucose and Diabetes.

Diabetes is associated with increased skeletal fragility, despite higher bone mineral density (BMD). Alternative measures are necessary to more accurately determine fracture risk in individuals with diabetes. Therefore, we aimed to describe the relationship between trabecular bone score (TBS) and normoglycaemia, impaired fasting glucose (IFG) and diabetes and determine whether TBS-adjusted FRAX (Aus) score differed between these groups. This study included 555 men (68.7±12.2years) and 514 women (62.0±12.0years), enrolled in the observational Geelong Osteoporosis Study. IFG was considered as fasting plasma glucose (FPG) ≥5.5mmol/L and diabetes as FPG ≥7.0mmol/L, with the use of antihyperglycaemic medication and/or self-report. Using multivariable regression, the relationship between groups and TBS was determined. Men and women (all ages) with diabetes had lower mean TBS compared to those with normoglycaemia, in models adjusted for age, height and weight/waist circumference (all p<0.05). Men with IFG had lower mean TBS in the age-adjusted models only (all p<0.05). The addition of TBS to the FRAX score improved the discrimination between glycaemia groups, particularly for younger women (<65years). There was no difference in TBS detected between normoglycaemia and IFG; however, those with diabetes had lower TBS. Thus, the increased fracture risk in men and women with diabetes may be a result of BMD-independent bone deterioration. TBS adjustment of FRAX scores may be useful for younger women (<65years) with diabetes. This suggests that halting or reversing progression from IFG to diabetes could be important to prevent skeletal fragility in diabetes.

Carotenoid dietary intakes and plasma concentrations are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort.

Carotenoids are found in abundance in fruit and vegetables, and may be involved in the positive association of these foods with bone health. This study aimed to explore the associations of dietary carotenoid intakes and plasma concentrations with bone density status and osteoporotic fracture risk in a European population. Cross-sectional analyses (n 14 803) of bone density status, using calcaneal broadband ultrasound attenuation (BUA) and longitudinal analyses (n 25 439) of fracture cases were conducted on data from the prospective European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of middle-aged and older men and women. Health and lifestyle questionnaires were completed, and dietary nutrient intakes were derived from 7-d food diaries. Multiple regression demonstrated significant positive trends in BUA for women across quintiles of dietary α-carotene intake (P=0·029), β-carotene intake (P=0·003), β-cryptoxanthin intake (P=0·031), combined lutein and zeaxanthin intake (P=0·010) and lycopene intake (P=0·005). No significant trends across plasma carotenoid concentration quintiles were apparent (n 4570). The Prentice-weighted Cox regression showed no trends in fracture risk across dietary carotenoid intake quintiles (mean follow-up time 12·5 years), except for a lower risk for wrist fracture in women with higher lutein and zeaxanthin intake (P=0·022); nevertheless, inter-quintile differences in fracture risk were found for both sexes. Analysis of plasma carotenoid data (mean follow-up time 11·9 years) showed lower hip fracture risk in men across higher plasma α-carotene (P=0·026) and β-carotene (P=0·027) quintiles. This study provides novel evidence that dietary carotenoid intake is relevant to bone health in men and women, demonstrating that associations with bone density status and fracture risk exist for dietary intake of specific carotenoids and their plasma concentrations.

The prevention of fragility fractures in patients with non-metastatic prostate cancer: a position statement by the international osteoporosis foundation.

Androgen deprivation therapy is commonly employed for the treatment of non-metastatic prostate cancer as primary or adjuvant treatment. The skeleton is greatly compromised in men with prostate cancer during androgen deprivation therapy because of the lack of androgens and estrogens, which are trophic factors for bone. Men receiving androgen deprivation therapy sustain variable degrees of bone loss with an increased risk of fragility fractures. Several bone antiresorptive agents have been tested in randomized controlled trials in these patients. Oral bisphosphonates, such as alendronate and risedronate, and intravenous bisphosphonates, such as pamidronate and zoledronic acid, have been shown to increase bone density and decrease the risk of fractures in men receiving androgen deprivation therapy. Denosumab, a fully monoclonal antibody that inhibits osteoclastic-mediated bone resorption, is also effective in increasing bone mineral density and reducing fracture rates in these patients. The assessment of fracture risk, T-score and/or the evaluation of prevalent fragility fractures are mandatory for the selection of patients who will benefit from antiresorptive therapy. In the future, new agents modulating bone turnover and skeletal muscle metabolism will be available for testing in these subjects.

Serum Phosphate Is Associated With Fracture Risk: The Rotterdam Study and MrOS.

Extreme phosphate levels (P) have been associated with mineralization defects and increased fracture risk. Whether P within normal range is related to bone health in the general population is not well understood. To investigate the association of P with bone mineral density (BMD) and fracture risk, we assessed two population-based cohorts: the Dutch Rotterdam Study (RS-I, RS-II, RS-III; n = 6791) and the US Osteoporotic Fractures in Men (MrOS; n = 5425) study. The relationship of P with lumbar spine (LS) and femoral neck (FN) BMD was tested in all cohorts via linear models; fracture risk was tested in RS-I, RS-II, and MrOS through Cox models, after follow-up of 8.6, 6.6, and 10.9 years, respectively. Adjustments were made for age, body mass index, smoking, serum levels of calcium, potassium, 25-hydroxyvitamin D, estimated glomerular filtration rate (eGFR), FN-BMD, prevalent diabetes, and cardiovascular disease. Additional adjustments were made for phosphate intake, parathyroid hormone, and fibroblast growth factor 23 levels in MrOS. We further stratified by eGFR. Results were pooled through study-level meta-analyses. Hazard ratios (HR) and betas (β) (from meta-analyses) are expressed per 1 mg/dL P increase. P was positively associated with fracture risk in men and women from RS, and findings were replicated in MrOS (pooled HR all [95% CI]: 1.47 [1.31-1.65]). P was associated with fracture risk in subjects without chronic kidney disease (CKD): all (1.44 [1.26-1.63]) and in men with CKD (1.93 [1.42-2.62]). P was inversely related to LS-BMD in men (β: -0.06 [-0.11 to -0.02]) and not to FN-BMD in either sex. In summary, serum P was positively related to fracture risk independently from BMD and phosphate intake after adjustments for potential confounders. P and LS-BMD were negatively related in men. Our findings suggest that increased P levels even within normal range might be deleterious for bone health in the normal population. © 2017 American Society for Bone and Mineral Research.

Association of type 2 diabetes and an inflammatory marker with incident bone fracture among a Japanese cohort.

Aims/IntroductionThere are various causes of incident bone fracture. Not only aging, low bone mineral density and history of previous fracture, but also diabetes mellitus and inflammation are regarded as risk factors for fracture. The purpose of the present study was to verify the association of glycemic control or one inflammatory marker with incident fracture in a large‐scale Japanese cohort.Materials and MethodsThe present study was carried out at the Hiroshima Atomic Bomb Casualty Council and included 6,556 participants (2,785 men and 3,771 women, aged 55–87 years) who underwent annual health examinations and were followed for 7.4 years. Information about incident fractures was collected at interviews. Participants were classified into three groups: normal, borderline and diabetes mellitus according to glycohemoglobin levels (treated diabetes patients were included in the diabetes mellitus group). Furthermore, participants were classified into four additional groups by glycemic control (diabetes mellitus or non‐diabetes mellitus) and C‐reactive protein (CRP) levels (low or high). Hazard ratios (HRs) of diabetes mellitus, CRP and their combined risk of incident fracture were evaluated.ResultsAfter adjusting for age, bone mineral density and previous fracture, CRP was associated with increased fracture risk (in men HR 1.04, 95% confidence interval [CI]: 1.003–1.06; in women HR 1.07, 95% CI: 1.03–1.13), and diabetes mellitus predicted fracture risk in men (HR 1.31, 95% CI: 1.02–1.51). Fracture risk was significantly higher among the diabetes mellitus with high CRP group compared with the non‐diabetes mellitus with low CRP group (in men HR 1.47, 95% CI: 1.02–1.98; in women HR 1.41, 95% CI: 1.04–1.92).ConclusionsAmong a Japanese cohort, CRP measurements were helpful to detect high fracture risk in patients with type 2 diabetes mellitus.

Body mass index and the risk of low bone mass–related fractures in women compared with men

Background:Body mass index (BMI) is inconsistently associated with the progression of low bone mass–related fractures. We conducted a systematic review and meta-analysis to summarize the evidence regarding the relationship between BMI and the risk of fracture in men and women separately. Furthermore, we analyzed the association between BMI and fracture risk in women compared with men.Methods:PubMed, EmBase, and the Cochrane Library were searched up to November 2015 to identify prospective cohort studies of low bone mass–related fractures. Prospective cohort studies that reported effect estimates of fracture risk for different BMI categories compared to normal weight were included. Relative risk (RR) and the ratio of relative risk (RRR) were calculated using a random-effect model to measure the relationship between BMI and fracture risk.Results:We analyzed 37 cohorts (32 articles), which included a total of 506,004 women and 118,372 men; overall, 38,200 incident cases were reported. Overall, a lower BMI was not associated with fracture risk in men (RR: 1.50, 95% confidence interval [CI]: 1.00–2.26; P = 0.051) or women (RR: 1.25, 95% CI: 0.97–1.62; P = 0.083). Although a higher BMI might play a beneficial impact in men (RR: 0.80, 95% CI: 0.69–0.93; P = 0.003), it has little effect in women (RR: 0.91, 95% CI: 0.74–1.11; P = 0.343). In addition, an increase in BMI by 5 kg/m2 decreased the risk of fractures in men (RR: 0.90, 95% CI: 0.83–0.98; P = 0.017) and women (RR: 0.85, 95% CI: 0.81–0.89; P < 0.001). Finally, there was no evidence of a sex difference in the RR for fractures between participants with different BMI categories compared with those with normal BMI. Finally, gender did not affect the risk of fracture for any category of BMI values.Conclusion:Higher BMI may affect the risk of fractures regardless of the sex. This association may be due to the interaction between the participants’ BMI and their bone mass density.

Bone Health and Bone-targeted Therapies for Prostate Cancer: a Programme in Evidence-based Care — Cancer Care Ontario Clinical Practice Guideline

AimsTo make recommendations with respect to bone health and bone-targeted therapies in men with prostate cancer. Materials and methodsA systematic review was carried out by searching MEDLINE, EMBASE and the Cochrane Library from inception to January 2016. Systematic reviews and randomised-controlled trials were considered for inclusion if they involved therapies directed at improving bone health or outcomes such as skeletal-related events, pain and quality of life in patients with prostate cancer either with or without metastases to bone. Therapies included medications, supplements or lifestyle modifications alone or in combination and were compared with placebo, no treatment or other agents. Disease-targeted agents such as androgen receptor-targeted and chemotherapeutic agents were excluded. Recommendations were reviewed by internal and external review groups. ResultsIn men with prostate cancer receiving androgen deprivation therapy, baseline bone mineral density testing is encouraged. Denosumab should be considered for reducing the risk of fracture in men on androgen deprivation therapy with an increased fracture risk. Bisphosphonates were effective in improving bone mineral density, but the effect on fracture was inconclusive. No medication is recommended to prevent the development of first bone metastasis. Denosumab and zoledronic acid are recommended for preventing or delaying skeletal-related events in men with metastatic castration-resistant prostate cancer. Radium-223 is recommended for reducing symptomatic skeletal events and prolonging survival in men with symptomatic metastatic castration-resistant prostate cancer. ConclusionsThe recommendations represent a current standard of care that is feasible to implement, with outcomes valued by clinicians and patients.

Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma.

ObjectiveAndrogen deprivation therapy (ADT) increases fracture risk in men with carcinoma of the prostate, but little is known about the fracture risk for different types of ADT. We studied the fracture risk amongst Chinese patients with carcinoma of the prostate prescribed different ADT regimens.Subjects and methodsThis was a single-centered observational study that involved 741 patients with carcinoma of the prostate from January 2001 to December 2011.ResultsAfter a median follow-up of 5 years, 71.7% of the study cohort received ADT and the incidence rate of fracture was 8.1%. Multivariable Cox regression analysis revealed that use of ADT was significantly associated with risk of incident fracture (Hazard Ratio [HR] 3.60; 95% Confidence Interval [95% CI] 1.41–9.23; p = 0.008), together with aged >75 years and type 2 diabetes. Compared with no ADT, all three types of ADT were independently associated with the risk of incident fracture: anti-androgen monotherapy (HR 4.47; 95% CI 1.47–13.7; p = 0.009), bilateral orchiectomy ± anti-androgens (HR 4.01; 95% CI 1.46–11.1; p = 0.007) and luteinizing hormone-releasing hormone agonists ± anti-androgens (HR 3.16; 95% CI 1.18–8.43; p = 0.022). However, there was no significant difference in the relative risks among the three types of ADT.ConclusionsFracture risk increases among all types of ADT. Clinicians should take into account the risk-benefit ratio when prescribing ADT, especially in elderly patients with type 2 diabetes.

Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health.

It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed.

Osteoporosis Treatment Efficacy for Men: A Systematic Review and Meta-Analysis.

To evaluate the efficacy of treatment options to reduce osteoporotic fracture risk in men. Systematic review and meta-analysis. Randomized clinical trials that evaluated the efficacy of a treatment for osteoporosis or low bone mineral density for adult men and reported fracture outcomes. Men. PubMed, Embase, and the Cochrane Library databases were searched for relevant studies. Information was extracted from included studies on participant sociodemographic characteristics, number of male participants, treatment evaluated, comparator for evaluated treatment, study duration, and fracture outcomes. Risk of bias of individual studies was assessed using measures recommended by the Cochrane Collaboration. Twenty-four articles reporting results for 22 studies (including 4,868 male participants) met strict inclusion criteria. Fixed-effects meta-analyses using the Mantel-Haenszel method demonstrated significantly lower risk of vertebral fractures with alendronate (relative risk (RR) = 0.328, 95% confidence interval (CI) = 0.155-0.692) and risedronate (RR = 0.428, 95% CI = 0.245-0.746) but not with calcitonin (RR = 0.272, 95% CI = 0.046-1.608) or denosumab (RR = 0.256, 95% CI = 0.029-2.238) than in controls. For bisphosphonates as a treatment category, meta-analyses demonstrated significantly lower risk of vertebral fractures (RR = 0.368, 95% CI = 0.252-0.537) and nonvertebral fractures (RR = 0.604, 95% CI = 0.404-0.904) than in controls. The meta-analysis finding that bisphosphonates significantly reduce nonvertebral fracture risk was not robust to sensitivity analysis. Bisphosphonates reduce the risk of vertebral and possibly nonvertebral fractures for men with osteoporosis. Further studies are needed to evaluate the efficacy of bisphosphonates for reducing nonvertebral fracture risk and the efficacy of nonbisphosphonates for reducing vertebral and nonvertebral fracture risk in men with osteoporosis.

Clinical Relevance of Vertebral Fractures in Men.

Clinical Relevance of Vertebral Fractures in Men.

Study of sex differences in the association between hip fracture risk and body parameters by DXA-based biomechanical modeling

There is controversy about whether or not body parameters affect hip fracture in men and women in the same way. In addition, although bone mineral density (BMD) is currently the most important single discriminator of hip fracture, it is unclear if BMD alone is equally effective for men and women. The objective of this study was to quantify and compare the associations of hip fracture risk with BMD and body parameters in men and women using our recently developed two-level biomechanical model that combines a whole-body dynamics model with a proximal-femur finite element model. Sideways fall induced impact force of 130 Chinese clinical cases, including 50 males and 80 females, were determined by subject-specific dynamics modeling. Then, a DXA-based finite element model was used to simulate the femur bone under the fall-induced loading conditions and calculate the hip fracture risk. Body weight, body height, body mass index, trochanteric soft tissue thickness, and hip bone mineral density were determined for each subject and their associations with impact force and hip fracture risk were quantified. Results showed that the association between impact force and hip fracture risk was not strong enough in both men (r=−0.31,p<0.05) and women (r=0.42,p<0.001) to consider the force as a sole indicator of hip fracture risk. The correlation between hip BMD and hip fracture risk in men (r=−0.83,p<0.001) was notably stronger than that in women (r=−0.68,p<0.001). Increased body mass index was not a protective factor against hip fracture in men (r=−0.13,p>0.05), but it can be considered as a protective factor among women (r=−0.28,p<0.05). In contrast to men, trochanteric soft tissue thickness can be considered as a protective factor against hip fracture in women (r=−0.50,p<0.001). This study suggested that the biomechanical risk/protective factors for hip fracture are sex-specific. Therefore, the effect of body parameters should be considered differently for men and women in hip fracture risk assessment tools. These findings support further exploration of sex-specific preventive and protective measurements to reduce the incidence of hip fractures.

Cluster analysis of bone microarchitecture from high resolution peripheral quantitative computed tomography demonstrates two separate phenotypes associated with high fracture risk in men and women

Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. “Cluster 1” contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. “Cluster 2” contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (p<0.05). Mean femoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p<0.001 for both), and in men, in cluster 2 (p<0.001) but not 1 (p=0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone.

Battle of the sex steroids in the male skeleton: and the winner is....

Male osteoporosis is a multifactorial disease, although it is often in part related to hypogonadism. While testosterone replacement therapy has been shown to improve bone mineral density, studies have also linked bone loss and higher fracture risk in men to low estrogen levels. In this issue of the JCI, Finkelstein and colleagues report the results of a clinical study in a cohort of healthy adult men aimed at further discerning the specific roles of androgen and estrogen deficiency in bone loss. The results of their study support previous findings that estrogen deficiency has a dramatic effect on bone homeostasis in men. Future studies to corroborate and expand on these findings have potential to influence the clinical management of male osteoporosis.

TERIPARATIDE IN CONTEMPORARY TREATMENT OF OSTEOPOROSIS: EVIDENCE FROM RECENT PUBLICATIONS

Osteoporosis - a disease witch relates to both women and men, present a growing global problem due to the aging population. Low bone mass and a deterioration microarchitecture are characteristic features of osteoporosis that can lead to fractures, related pain, physical disability, poor quality of life, increased mortality, and high costs of medical care. Teriparatide (recombinant human parathyroid hormone [rhPTH (1-34), Forsteo], which appeared more than a decade ago, is the only one registered in the Russian Federation anabolic treatment for osteoporosis, which increases the density and strength of bone. Initially, it was approved for the treatment of postmenopausal osteoporosis based on the data from a randomized, controlled phase III study that showed a significant reduction in the incidence of vertebral and nonvertebral fractures. Teriparatide is now also approved for the treatment of osteoporosis at high risk of fractures in men and glucocorticoid osteoporosis. The basis for these new indications were the positive results of randomized controlled studies in corresponding patient populations.

Cross-sectional and prospective associations between dietary and plasma vitamin C, heel bone ultrasound, and fracture risk in men and women in the European Prospective Investigation into Cancer in Norfolk cohort

Vitamin C sufficiency may help prevent osteoporosis and fractures by mediating osteoclastogenesis, osteoblastogenesis, and bone collagen synthesis. We determined whether dietary intakes and plasma concentrations of vitamin C were associated with a heel ultrasound and hip and spine fracture risks in older men and women. Participants were recruited from the European Prospective Investigation into Cancer in Norfolk study with 7-d diet diary estimates of vitamin C intake and plasma concentrations. A random subset (4000 of 25,639 subjects) was available for the cross-sectional (ultrasound) study of broadband ultrasound attenuation (BUA) and velocity of sound (VOS), which were determined during the second health examination. The prospective (fracture) study was a case-cohort sample of all participants with a fracture up to March 2009 and the random subset (n = 5319). ANCOVA-determined associations between quintiles of vitamin C intake and plasma status with adjusted BUA and VOS and adjusted Prentice-weighted Cox proportional HRs were calculated for fracture risk. Women were 58% of the population (39-79 y old), and the median follow-up was 12.6 y (range: 0-16 y). Positive associations across all quintiles of vitamin C intake but not plasma status were significant for VOS in men (β = 2.47 m/s, P = 0.008) and BUA in women (β = 0.82 dB/MHz, P = 0.004). Vitamin C intake was not associated with fracture risk, but there was an inverse association with plasma concentrations in men, with quintile 4 having significantly lower risks of hip fractures (HR: 0.35; 95% CI: 0.16, 0.80) and spine fractures (HR: 0.26; 95% CI: 0.10, 0.69) than quintile 1. Higher vitamin C intake was significantly associated with higher heel ultrasound measures in men and women, and higher plasma vitamin C concentrations were significantly associated with reduced fracture risk in men only. Our findings that vitamin C intake and status were inconsistently associated with bone health variables suggest that additional research is warranted.