Bone Loss In Men Research Articles

Ranking prognosis: Future perspective of RANK/RANKL in breast cancer

With over 2.3 million new cases and 685,000 deaths, breast cancer is the most commonly diagnosed cancer worldwide, and its burden has been rising over the past decades. In India, the incidence increased significantly, almost 50%, between 1965 and 1985. As per the 2020 Globocan information, in India, BC accounted for 13.5% of all cancer cases and 10.6% of all deaths. Compared to Western countries, the poor survival of patients with breast cancer in India is due to several contributing factors such as lack of awareness, earlier onset of disease, delayed initiation and late stage of disease at presentation, and lack of consistent treatment regime. Under these circumstances, it is even more imperative to identify novel targets for breast cancer and put them to clinical use. In a recent report by Ciscar et al., the authors reported that RANK and receptor activator of NFκB ligands (RANKL) status might be important predictors in estrogen receptor (ER)-negative breast cancer. In analyses of more than 2,000 breast cancer samples, the authors confirmed that RANK expression was associated with ER− tumors, while RANKL was rarely found in tumor cells. This also let to conclude that RANK expression is an independent poor prognostic factor in breast cancer, particularly in ER− BC postmenopausal women, and is associated with poor survival. This seminal work has enormous outcomes in the clinical management of breast cancer. This also implies that RANK+ ER- breast cancer might benefit from the recently FDA-approved compound “Denosumab.” Denosumab is used to treat bone loss in men treated for prostate cancer and those who have osteoporosis. It is an inhibitor of RANKL, which is an essential factor initiating bone turnover. RANKL inhibition blocks osteoclast maturation, function, and survival, thus reducing bone resorption. The same mechanism might be beneficial in these RANK+ ER- breast cancer. Clinical trials are underway to test if denosumab can be re-purposed for this subset of breast cancer.

Discontinuation of denosumab in men with prostate cancer.

Patients with prostate cancer receiving androgen deprivation therapy (ADT) are treated with denosumab (DMAB) to prevent fractures and preserve bone mass. We wanted to investigate the change in BMD in men with non-metastatic prostate cancer discontinuing DMAB. We conducted a retrospective cohort study based on medical records from patients referred to the Department of Endocrinology from the Department of Urology, Aarhus University Hospital between June 1, 2018, and June 1, 2021. We retrieved information on biochemistry and DXA performed 0-6months after the last DMAB injection and a second DXA performed approximately 12months after the first. In case of a BMD T-score ≤ - 1 at the lumbar spine or total hip at the first DXA, the patients were treated with zoledronate. The primary endpoint was change in lumbar spine BMD. We included 50 patients with non-metastatic prostate cancer. The mean DMAB treatment duration was 5 ± 0.1years. Among the patients treated with zoledronate (n = 9), BMD was maintained at the spine and femoral neck after a mean of 16months. We found a significant decrease in BMD; - 4.9 ± 4.2%, - 1.9 ± 3.5%, and - 2.4 ± 3.6% at the spine, total hip, and femoral neck between the first and second DXA in the patients not treated with zoledronate (n = 24) (p ≤ 0.01 for all). One patient who did not receive ZOL sustained multiple fragility vertebral fractures after DMAB discontinuation. In men with non-metastatic prostate cancer, discontinuation of DMAB after stopping ADT led to an average bone loss of 2-5%. Zoledronate prevented bone loss in men with osteopenia.

LBSAT139 Osteoporosis Screening In Men As Per Endocrine Society Clinical Practice Guidelines: A Cross-sectional Study

Abstract Introduction With the aging of the population, osteoporosis in men is a significant public health problem. Both hip and vertebral fractures are associated with increased mortality in men, as compared to women. One out of every five men experiences fragility fractures at least once in their lifetime. Declining sex steroid levels and bioavailable estradiol levels contributes to age-related bone loss in men. The objective of this study was to identify the underdiagnosis and the lack of guideline-based screening for osteoporosis in men. Method: Endocrine Society Clinical Practice Guidelines published in June 2012 recommends screening for osteoporosis in all men aged ≥70y, and all men aged between 50-69y who have risk factors including delayed puberty, hypogonadism, hyperparathyroidism, hyperthyroidism, chronic obstructive pulmonary disease; drugs such as glucocorticoids or GnRH agonists; life choices such as alcohol abuse or smoking; or other causes of secondary osteoporosis, using a dual-energy x-ray absorptiometry (DXA) of the spine and hip. The National Osteoporosis Foundation has similar recommendations. | Using a cross-sectional study design, charts of male patients eligible for osteoporosis screening, between the period of September 2020 to December 2021, were reviewed. Patients seen in the internal medicine residents’ clinic, family medicine residents’ clinic and endocrinology clinic were included in the study. Results A total of 90 out of the 1120 male patients aged ≥70y had ever undergone a DXA scan. Of these 90 patients, on reviewing their problem list from the electronic health record, 15 had osteoporosis listed and 9 had fragility fracture/compression fracture/fracture listed. Of the 135 patients aged ≥50y with ho HIV, only 21 received a DXA scan. Additionally, it was observed that only 20% (23/120) of the patients on testosterone therapy were screened for osteoporosis. As compared to this, almost 40% (1012 out of 2479) of all women aged ≥65y received screening DXA scan. Conclusion This project highlighted the inconsistencies in ordering screening DXA scans for male patients at risk for osteoporosis. Fewer than 10% of the at-risk males had a DXA. Additionally, 10% of the patients who underwent DXA had already suffered from a fracture, further emphasizing the burden of this disease. Although osteoporosis is appreciated in post-menopausal women, we must not overlook our male patients, who have 2-3 times higher morbidity and mortality associated with a hip fracture. Based on this data, we plan to initiate a quality improvement project with an aim to improve guideline directed screening for osteoporosis. Enhanced DXA screening for at risk patients will not only reduce rates of fragility fracture but will also help reduce healthcare cost. For a sustainable and broader impact, we are working further on EPIC Best Practice Alert to prompt providers to order DXA scans for these patients. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Men’s health and osteoporosis: modern treatment and prevention options

Osteoporosis (OP) has traditionally been seen as a pathology that mainly occurs in postmenopausal women and elderly men, and until recently, the problem of this disease among males has not been given sufficient priority. At the moment, however, OP in men is widely acknowledged to be an important issue of modern health care. Given the etiological and pathogenetic characteristics, two categories of OP have been identified: primary and secondary. In the structure of male OP, the secondary category of OP accounts for up to 40-60 % of all cases. Hypogonadism is one of the common causes of bone loss in men. Initially, males develop a larger bone mass compared to women and, accordingly, greater bone strength. Men over the age of 50 do not undergo rapid bone mass loss, as women do after menopause, and the bone mass decreases more gradually, in a linear manner. With ageing, the trabecular number (Tb.N) in men are relatively maintained with underlying more pronounced thinning of Tb. N associated with decreased osteoblast-forming activity. Although the prevalence of OP among men is significantly lower than among women, the clinical consequences of OP in men are of a great importance. The primary strategy of the anti-osteoporotic therapy is to prevent OP and low-traumatic fractures. According to the current guidelines for the treatment of OP in men, bisphosphonates (BP) are the drugs of choice. Zoledronic acid is a highly effective nitrogen-containing BP, the first drug to be injected once a year. Intravenous injection of zoledronic acid is as effective in reducing the risk of fractures in men as in women.

Study of the relationship between FT3, FT4, and TSH with bone resorption indices in men with hypothyroidism.

This study aimed to find the effect of hypothyroidism in men on metabolism and bone mineral density. The study included a patients group of 90 men suffering from hypothyroidism and 120 healthy subjects as a control group. The study comprised the estimation of the concentration of Blood free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid stimulating hormone (TSH), bone resorption index type I collagen C-terminal peptide (CTX-1), the serum calcium (Ca2+), serum phosphorus (Pi3+), the bone mineral density of the lumbar spine and femoral neck. In the hypothyroidism men group: (1) the bone mass was lower than the control group with significant differences, (2) the bone resorption index CTX-1 was significantly higher than that in the control group and calcium and phosphorus were not different from those in healthy control subjects, and (3) TSH was positively correlated with CTX-1. Male TSH and CTX-1 levels were positively correlated. There is bone loss in men with hypothyroidism, which may be related to increased bone resorption.

Integrative analysis of genetic and clinical risk factors for bone loss in a Korean population.

The relative contribution of genetic and clinical factors for bone loss is not well known. This study aimed to investigate the annualized percentage change in total hip bone mineral density (BMD) and the genetic and clinical risk factors for bone loss in a Korean prospective cohort study over a 6-year period. We included 645 men aged ≥50years and 683 postmenopausal women who had repeated BMD testing between 2007 and 2014. The association between covariates and annualized percentage change in hip BMD was analyzed through the multivariate linear regression analysis. A total of 2614 single-nucleotide polymorphisms (SNPs) from 23 known BMD-related candidate genes and genome-wise association study were investigated. Hip bone loss increased more rapidly in women than in men with advancing age. Hip bone loss in men increased with lean mass (LM) loss (%/year) (P<0.001) and current smoking (P=0.024) and decreased with increasing waist circumference (WC) (P<0.001), alcohol consumption (P=0.049), and increase in red blood cell counts (P=0.031). Decreasing WC (P=0.009), LM loss (%/year) (P<0.001), and years since menopause ≤ 3years (P=0.003) significantly correlated with hip bone loss in women aged 45-59years. Hip bone loss in women aged ≥60years increased with advancing age (P=0.012), alcohol consumption (P=0.028), LM loss (%/year) (P=0.031), and fat mass loss (%/year) (P<0.001) and decreased with increasing WC (P=0.025). LRP5 rs498830 (β=0.127, P=0.007) and TNFSF11 rs7325635 (β=0.146, P=0.001) were the top SNPs related to hip bone loss in men and postmenopausal women, respectively. However, none of the SNPs were associated with hip bone loss after Benjamini-Hochberg adjustment. In this study, decreasing WC and LM were significant risk factors for hip bone loss in both men and women. Those factors were also identified that had sex-specific or age-specific effects on hip bone loss. None of the SNPs were associated with hip bone loss after multiple testing adjustments. The understanding of the modifiable factors contributing to bone loss has been broadened, and this may have implications such as in developing individualized preventive strategy. Further studies are needed to better predict the risk for bone loss in men and women.

Persistent bone impairment despite long-term control of hyperprolactinemia and hypogonadism in men and women with prolactinomas

While prolactinoma patients have high bone turnover, current data are inconclusive when it comes to determining whether correction of hyperprolactinemia and associated hypogandism improves osteodensitometric data in men and women over the long term. In a large cohort of including 40 men and 60 women, we studied the long-term impact of prolactinoma treatment on bone mineral density (BMD) in men versus women, assessed adverse effects of a primary surgical or medical approach, and evaluated data for risk factors for impaired BMD at last follow-up using multivariate regression analyses. Median duration of follow-up was 79 months (range 13–408 months). Our data indicate that the prevalence of impaired BMD remained significantly higher in men (37%) than in women (7%, p < 0.001), despite the fact that hyperprolactinemia and hypogonadism are under control in the majority of men. We found that persistent hyperprolactinemia and male sex were independent risk factors for long-term bone impairment. Currently, osteoporosis prevention and treatment focus primarily on women, yet special attention to bone loss in men with prolactinomas is advised. Bone impairment as “end organ” reflects the full range of the disease and could become a surrogate marker for the severity of long-lasting hyperprolactinemia and associated hypogonadism.

Results of study of biochemical markers of bone metabolism in men with coronary heart disease

The development of atherosclerosis is closely related to the calcification of the vessel intima and fibrous plaques, being a complex and multifactorial process, in which the markers of bone formation and resorption play an important role. Objective. To study the biochemical markers of bone metabolism in men with stable coronary heart disease (CHD). Material and methods. The study included 102 men with verified CHD. Data were evaluated by densitometry, coronary angiography, multispiral computed tomography, color duplex scanning of brachiocephalic arteries, serum lipids (total cholesterol, triglycerides [TG], high-density [LHD] and low-density lipoprotein cholesterol), concentrationsin the blood of osteocalcin (OC), bone alkaline phosphatase (BAP), cathepsin K and C-telopeptides (CTx). Results. Concentrations of BAP, cathepsin K and CTx in patients with CHD were significantly higher than in men without CHD. The concentration of OC in men with normal bone mineral density was significantly lower than in patients with osteopenic syndrome. There was a direct correlation between OC and antiatherogenic HDL cholesterol and the inverse correlation between OC and TG, CTx and TG. There was no correlation between the level of bone remodeling markers and coronary artery (CA) lesion variant and the severity of coronary atherosclerosis on SYNTAX scale. The correlation analysis did not reveal the connection of biochemical markers of bone metabolism with the severity of coronary atherosclerosis and calcification and thickness of intima-media complex of carotid arteries. Absolute values of bone formation indices (BAP, OC) were significantly higher in patients with severe СA calcification than in patients without signs of calcification. Summary. Increased rates of osteogenesis and osteoresorption characterize the accelerated process of bone metabolism and indicate in favor of high rates of bone loss in men with CHD, which confirms the likelihood of common pathophysiological mechanisms of bone resorption and arterial calcification.

Late-onset Hypogonadism: Bone health.

Bone health is underdiagnosed and undermanaged in men. Bone loss occurs in men with hypogonadism and in aging men. Thus, patients with a diagnosis of late-onset hypogonadism (LOH) are at risk of osteoporosis and osteoporotic fractures. To provide an update on research data and clinical implications regarding bone health in men with LOH by reviewing literature articles on this issue. A thorough search of listed publications in PubMed on bone health in older men with hypogonadism was performed, and other articles derived from these publications were further identified. Late-onset Hypogonadism may be associated with reduced bone mineral density (BMD). In a pathophysiological perspective, the detrimental effects of testosterone (T) deficiency on BMD are partly ascribed to relative estrogen deficiency and both serum T and serum estradiol (E2) need to be above 200ng/dL and 20pg/mL to prevent bone loss. The effects of exogenous T on BMD are controversial, but most of the studies confirm that testosterone replacement therapy (TRT) increases BMD and prevents further bone loss in men with hypogonadism. No data are available on TRT and the prevention of fractures. In men with documented LOH, a specific clinical workup should be addressed to the diagnosis of osteoporosis in order to program subsequent follow-up and consider specific bone active therapy. TRT should be started according to guidelines of male hypogonadism while keeping in mind that it may also have positive effects also on bone health in men with LOH.

Clinical Manifestations and Factors Associated with Osteosarcopenic Obesity Syndrome: A Cross-Sectional Study in Koreans with Obesity.

Demonstrating the clinical consequences of osteosarcopenic obesity (OSO) is complex. This study evaluated clinical manifestations and factors associated with bone and muscle loss in Koreans with obesity. This cross-sectional observational study enrolled Koreans with obesity aged ≥ 50years from the Korea National Health and Nutrition Examination Survey. Clinical manifestations were compared among four groups: obesity (O), sarcopenic obesity (SO), osteopenic obesity (OO), and OSO. Factors associated with appendicular skeletal muscle mass (ASM) or bone mineral density (BMD) were evaluated. OSO increases with age in both sexes. Men with SO and OSO had increased cardiometabolic diseases and markers, percentages of body fat (BF%), and trunk fat (TF%), and decreased limb fat percentage (LF%). Women with SO and OSO had increased metabolic markers, BF%, and TF% but those with OSO had increased cardiometabolic diseases and lower LF%. Both sexes with OSO had decreased ASM and vitamin D, and higher vitamin D deficiency. BF% was negatively associated with ASM and femur BMD in both sexes. TF% was negatively and LF% was positively associated with ASM in both sexes and with femur BMD in women. Vitamin D was positively associated with femur BMD in men and with ASM and BMD at all sites in women. ASM and BMD were positively associated with each other. Appendicular muscle loss is metabolically significant regardless of bone loss in men; however, appendicular muscle loss with bone loss is metabolically more significant in women. Regional body composition, fat distribution, and vitamin D deficiency were associated with OSO phenotype in both sexes.

Management of Male Osteoporosis: an Update

Osteoporosis is a major health concern for men in our aging population. The incidence of osteoporotic fractures in men is expected to rise as life expectancy increases. When adjusted for age, one half of all hip fractures occur in men and of all osteoporotic fractures; hip fractures account for the highest morbidity and mortality. Several factors contribute to bone loss in men. Sex steroid deficiency plays an important role in male age-related bone loss. Careful evaluation for secondary causes of bone loss (including lifestyle factors, comorbidities, and risk medications) is warranted. Osteoporosis guidelines recommend bone mineral density (BMD) testing in men over age 70, earlier in men with other risk factors. As in women, adequate calcium and vitamin D intake, regular weight-bearing exercise, smoking cessation, limiting excessive alcohol, and fall prevention strategies are recommended. Available clinical data support efficacy of bisphosphonates (alendronate, risedronate, zoledronic acid), denosumab, and anabolic therapy (teriparatide) in men with osteoporosis as well as in women. Abaloparatide, a parathyroid hormone-related peptide analog with demonstrated anti-fracture efficacy in women, awaits the conclusion of clinical trials in men. Romosozumab shows similar BMD and bone turnover marker effects in osteoporotic men compared to women; evaluation of safety concerns is ongoing. Recent insights into osteoporosis pathophysiology and bone cell biology provide promising direction for effective therapeutic strategies for the management of male osteoporosis.

Recent Update on RANKL Inhibitor

The prevalence of osteoporosis is continuing to increase with growing elderly population. A variety of anti-osteoporotic agents have been used for the prevention and treatment of osteoporosis and osteoporotic fractures. Novel therapeutic agents based on the newly discovered mechanisms in bone biology have been recently introduced. Denosmab, a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand, is a new therapeutic agent that inhibits osteoclast differentiation, activity, and survival. In the fracture reduction evaluation of denosumab in osteoporosis every 6 months (FREEDOM) trial, denosumab treatment for 36 months significantly increased bone mineral density at all skeletal sites evaluated, thereby resulting in a significant reduction in the risk of vertebral, nonvertebral, and hip fractures. In the FREEDOM Extension study, in which denosumab treatment was continued for up to 10 years, denosumab showed a continued improvement in bone mineral density and a consistently low fracture risk similar to rates observed in the denosumab group during the FREEDOM trial. Denosumab also offered a favorable safety profile with generally low and stable adverse event rates. Denosumab was indicated for treatment of postmenopausal women with osteoporosis at high risk for fracture, treatment to increase bone mass in men with osteoporosis, treatment of bone loss in men receiving androgen deprivation therapy for prostate cancer, and treatment of bone loss in women receiving adjuvant aromatase inhibitor therapy for breast cancer. For these patients, denosumab is an important option for the prevention and treatment of osteoporosis and osteoporotic fractures. (Korean J Med 2018;93:252-259)

Effects of tocotrienol from Bixa orellana (annatto) on bone histomorphometry in a male osteoporosis model induced by buserelin

IntroductionOsteoporosis is a debilitating skeletal side effect of androgen deprivation therapy based on gonadotropin-releasing hormone (GnRH) agonist in men. Tocotrienol from Bixa orellana (annatto) has been demonstrated to offer protection against osteoporosis by exerting anabolic effects on bone. Thus, it may prevent osteoporosis among GnRH agonist users. ObjectiveThis study aimed to determine the effectiveness of annatto-tocotrienol on the bone turnover markers and bone histomorphometry in a model of male osteoporosis induced by buserelin (a GnRH agonist). MethodsForty-six three-months-old male Sprague-Dawley rats (three months old; 300–350 g) were randomly divided into six groups. The baseline control group (n = 6) was sacrificed at the onset of the study. The normal control group (n = 8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n = 8) received corn oil orally daily and subcutaneous buserelin injection 75 μg/kg/day daily. The calcium control (n = 8) received 1% calcium in drinking water and subcutaneous buserelin injection 75 μg/kg/day. The remaining rats were treated with two different treatments, i.e., (1) oral annatto tocotrienol at 60 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8); (2) oral annatto tocotrienol at 100 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8). The rats were injected with calcein twice before being sacrificed to label the bones. The rats were euthanized, and their blood and right femur were harvested at the end of the treatment for bone turnover markers and bone histomorphometry examination. ResultsBoth serum osteocalcin and C-telopeptide of type 1 collagen were not significantly different between treated groups and buserelin control (P > 0.05). The buserelin control group had a significantly lower bone volume and higher eroded surface compared with the normal control group (P < 0.05). Both groups treated with annatto tocotrienol (60 mg/kg/day and 100 mg/kg/day) had significantly higher bone volume, trabecular thickness and osteoblast number, as well as a significantly lower single-labelled surface compared with the buserelin control (P < 0.05). Only rats treated with annatto tocotrienol 60 mg/kg/day had a significantly higher double-labelled surface compared with buserelin control (P < 0.05). ConclusionAnnatto tocotrienol can prevent trabecular bone loss by increasing the mineralising surface and osteoblasts number. Thus, it has a potential role in preventing bone loss in men using GnRH agonist.

Association Between Dietary Fiber Intake and Bone Loss in the Framingham Offspring Study.

Dietary fiber may increase calcium absorption, but its role in bone mineralization is unclear. Furthermore, the health effect of dietary fiber may be different between sexes. We examined the association between dietary fiber (total fiber and fiber from cereal, fruits, vegetables, nuts, and legumes) and bone loss at the femoral neck, trochanter, and lumbar spine (L2 to L4 ) in older men and women. In the Framingham Offspring Study, at baseline (1996-2001), diet was assessed using the Willett food-frequency questionnaire, and bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Follow-up BMD was measured in 2001-2005 and 2005-2008 among 792 men (mean age 58.1 years; BMI 28.6 kg/m2 ) and 1065 women (mean age 57.3 years; BMI 27.2 kg/m2 ). We used sex-specific generalized estimating equations in multivariable regressions to estimate the difference (β) of annualized BMD change in percent (%ΔBMD) at each skeletal site per 5 g/d increase in dietary fiber. We further estimated the adjusted mean for bone loss (annualized %ΔBMD) among participants in each higher quartile (Q2, Q3, or Q4) compared with those in the lowest quartile (Q1) of fiber intake. Higher dietary total fiber (β = 0.06, p = 0.003) and fruit fiber (β = 0.10, p = 0.008) was protective against bone loss at the femoral neck in men but not in women. When examined in quartiles, men in Q2-Q4 of total fiber had significantly less bone loss at the femoral neck versus those in Q1 (all p < 0.04). For women, we did not observe associations with hip bone loss, although fiber from vegetables appeared to be protective against spine bone loss in women but not men. There were no associations with cereal fiber or nut and legume fiber and bone loss in men or women. Our findings suggest that higher dietary fiber may modestly reduce bone loss in men at the hip. © 2017 American Society for Bone and Mineral Research.

Dietary calcium intake and rate of bone loss in men.

A high Ca intake has been recommended for osteoporosis prevention; however, little research has examined the relationship between dietary Ca and bone health in men. We examined associations between dietary Ca intake, bone mineral density (BMD) and change in BMD at the total body, hip and spine over 2 years in a cohort of men (mean age 57 years, BMI 26 kg/m2) from a trial. Data from the total cohort (n 323) were used in the analysis of Ca intake and BMD at baseline, and data from the placebo group (n 99) were used in the longitudinal analysis of Ca intake and change in BMD. Parathyroid hormone (PTH) and the markers of bone turnover serum total alkaline phosphatase activity, serum C-telopeptide and serum procollagen type-1 N-terminal propeptide were measured in a subset of participants at baseline (n 150), and associations with dietary Ca at baseline were examined. Mean Ca intake was 870 mg/d. Baseline BMD was not related to dietary Ca intake at any site, before or after adjustment for covariables. Similarly, bone loss over 2 years was not related to Ca intake at any site, before or after adjustment. Dietary Ca intake was inversely correlated with PTH at baseline (r -0·19, P=0·02), but was not associated with the markers of bone turnover. BMD and rates of bone loss were unrelated to Ca intake in these men. This suggests that strategies to increase Ca intake are unlikely to impact on the prevalence of and morbidity from male osteoporosis.

Osteoporosis in men.

Osteoporotic fractures are the leading cause of morbidity and mortality among aging men. 30% of all hip fractures occur in men, and mortality resulting from not only the hip fracture, but also the spine and other major osteoporotic fractures, is significantly higher in men than in women. As in women, hypogonadism is the best documented risk factor for developing osteoporosis in men. In older men, testosterone levels are negatively correlated with the risk of fractures, and it seems that this age-related testosterone deficiency should not be considered as one of the many causes of secondary osteoporosis, rather one of the major and most important mechanisms of senile osteoporosis. Acute hypogonadism induced by ablation treatment for prostate cancer (surgical or pharmacological castration, antiandrogen therapy) is associated with an extremely high risk of fracture. Other documented causes of bone loss in men are cigarette smoking and alcohol abuse, and a number of diseases that require corticosteroid treatment. Pharmacotherapy of osteoporosis should be recommended to all men with a diagnosed osteoporotic fracture and all men with a high 10-year absolute fracture risk (FRAXTM). Not all drugs registered for the treatment of postmenopausal osteoporosis have been registered for the treatment of osteoporosis in men, and others have not been the subject of long-term and costly clinical trials required for such registration. The risk reduction of new fractures was documented only for treatment with zoledronic acid. Risedronate, strontium ranelate, teriparatide, and denosumab in men increase in bone mineral density comparable to that seen in postmenopausal women.

The association of testosterone, sex hormone-binding globulin, and insulin-like growth factor-1 with bone parameters in Korean men aged 50years or older.

Testosterone and insulin-like growth factor-1 (IGF-1) are essential factors for the maintenance of bone health in men. However, the results for the association of testosterone and IGF-1 with bone parameters were not consistent in prior studies. We evaluated the relationship of testosterone, sex hormone-binding globulin (SHBG), and IGF-1 with bone mineral density (BMD) and bone turnover markers (BTMs) in Korean men. We enrolled 1227 men aged ≥50years in this cross-sectional study. Serum levels of total testosterone (TT), SHBG, IGF-1, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen (CTX) were measured. Free testosterone (FT) was calculated using Vermeulen's method. BMD was measured by dual-energy X-ray absorptiometry. TT level was not related to BMD or BTMs in the unadjusted model; however, after adjusting for SHBG and IGF-1, the association between TT and BTMs was significant (β=-0.139 for osteocalcin and β=-0.204 for CTX). SHBG levels were negatively associated with lumbar BMD, and positively associated with BTMs in all models. As SHBG level increased, the prevalence of osteopenia or osteoporosis defined by BMD significantly increased (OR of 1SD change, 1.24). IGF-1 levels were significantly related with BMD, but not with BTMs. Meanwhile, FT levels were positively associated with BMD and negatively associated with BTMs. In conclusion, SHBG levels were independently related with bone parameters and osteopenia in men aged ≥50years. IGF-1 levels were positively associated with BMD, but not with BTMs. SHBG may play a role in regulating age-related bone loss in men after middle-age.

DOES OSTEOPOROSIS AFFECT YOUNG MEN?

The title question explains the newly emerged tendencies of Osteoporosis and its prevalence. As the rates of the incidence of Osteoporosis are growing the myths related to the disease are about to crush. Many years doctors believed that women are much more likely to get osteoporosis than men, but IOF declared 2014 as the year of “Men osteoporosis” Moreover, if previously Osteoporosis was attributed to the conditions of an old age, today it is most apparent, scientists focused on Osteoporosis are evaluating the disease in young population; The information about Peak Bone Mass has a prognostic opportunity for the progression of the bone mass decrease and consequent bone fragility. The question in the article title line: Does Osteoporosis affect young men? the rationale of the question in the title lies in those risk-factors that determine development of OP are most likely uncovered in men rather than in women. Among them are: smoking, alcohol consumption, hypogonadal state. Androgens have vital role in bone formation in both: men and women. It is proved that osteoblasts have androgen receptors. Series of research support the evidence that androgen deficiency lead to retarded skeletal growth in men. Androgen Deficiency is recognized as the most potent reason of Bone Loss in Men. The aim of the study was to assess BMD in young Georgian men, and determine correlations between BMD and basic osteoporosis risk factors. 2800 Young Men with the age 22-50 (median age 38±4.6) years were examined, all patients have filled the questioner Table1 OP Risk-Factors in Young Georgian Males n=2800 Ge netic Factor Spine Defor mities Low Bone Mass &lt;70 Alcohol con sump tion Hypo dynamic Lifestyle Low Cal cium Intake Sexual Potency De crease 15% 420 35% 980 10,7% 299,6 8,5% 238 21% 588 41% 1148 39,8% 1114,4 Bone Mass was measured using DXA Dual Energy Absorbtiometric Technique (Hologic 1000), according to T and Z criteria SD; in particular cases Lumbar Spine X-ray has been performed. Statistical Analysis was made by Excel-Windows Microsoft MedicalExe Statistical Software. Confidence indicators were calculated by the appropriate formula; Results have computed Normal Bone mass in 55% -2800 young men; Osteopenia in 17%; Osteoporosis (T&lt;-2, 5 SD). Measured in 38% of the group. Results Received: 1. Low bone mass detected in 45% of Healthy Young Georgian Men ( more than 1000 men) Therefore, the condition should be followed to avoid progression of bone loss and its complications. 2. Secondary hypogonadotropic hypogonadism and Lumbar spine vertebral deformities were major OP risk -a factor is young Georgian men are: It is apparent that emerging risk-factors are continuing the list of worldwide recognized risk-factor; Consequently evaluation of newly-appearing risks should be spotted and closely monitored. 3. The correlation between Osteoporosis incidence and Hypogonadism is clear. It is recommended to correct hypogonadal state for the prevention of bone loss progression.

Role of Osteoprotegerin and Receptor Activator of Nuclear Factor-κB Ligand in Bone Loss Related to Advanced Chronic Obstructive Pulmonary Disease

Background:Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD. We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD. The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-α) with bone turnover in men with very severe COPD.Methods:Pulmonary function, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor-alpha-I and II (sTNFR-I, sTNFR-II), osteocalcin (OC), and β-CrossLaps (βCL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers. COPD patients and healthy controls were compared using an independent t-test and Mann–Whitney U-test. The Pearson coefficient was used to assess the relationships between variables.Results:OPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum βCL, TNF-α, and its receptors were higher. OPG directly correlated with forced expiratory volume in 1 s (FEV1) % predicted (r = 0.46, P < 0.005), OC (r = 0.34, P < 0.05), LS (r = 0.56, P < 0.001), and FN T-score (r = 0.47, P < 0.01). In contrast, serum RANKL inversely associated with LS and FN T-score (r = −0.62, P < 0.001 and r = −0.48, P < 0.001) but directly correlated with βCL (r = 0.48, P < 0.001). In addition, OPG was inversely correlated with RANKL (r = −0.39, P < 0.01), TNF-α (r = −0.56, P < 0.001), and sTNFR-I (r = −0.40, P < 0.01).Conclusion:Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD.

Tumor necrosis factor superfamily members in bone loss in men with end-stage chronic obstructive lung disease

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