Bone In Men Research Articles

Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial.

In men, many effects of testosterone (T) on the skeleton are thought to be mediated by estradiol (E2), but trial evidence is largely lacking. This study aimed to determine the effects of E2 on bone health in men in the absence of endogenous T. This study is a 6-month randomized, placebo-controlled trial with the hypothesis that E2 would slow the decline of volumetric bone mineral density (vBMD) and bone microstructure, maintain areal bone mineral density (aBMD), and reduce bone remodelling. 78 participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel daily or matched placebo. The outcome measures were vBMD and microarchitecture at the distal tibia and distal radius by high-resolution peripheral quantitative CT, aBMD at the spine and hip by dual-energy x-ray absorptiometry, and serum bone remodelling markers. For the primary endpoint, total vBMD at the distal tibia, there was no significant difference between groups, mean adjusted difference (MAD) 2.0 mgHA/cm3 (95% CI: -0.8 to 4.8), P = 0.17. Cortical vBMD at the distal radius increased in the E2 group relative to placebo, MAD 14.8 mgHA/cm3 (95% CI: 4.5 to 25.0), P = 0.005. Relative to placebo, E2 increased estimated failure load at tibia, MAD 250 N (95% CI: 36 to 465), P = 0.02, and radius, MAD 193 N (95% CI: 65 to 320), P = 0.003. Relative to placebo, E2 increased aBMD at the lumbar spine, MAD 0.02 g/cm2 (95% CI: 0.01 to 0.03), P = 0.01, and ultra-distal radius, MAD 0.01 g/cm2 (95% CI: 0.00 to 0.02), P = 0.01, and reduced serum bone remodelling markers. Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.

Similarities and Differences in Bone Mineral Density between Multiple Sites in the Same Individual: An Elderly Cadaveric Study.

Bone mineral density (BMD) is known to vary based on various factors, and the degree of variation is site-specific. However, few studies have investigated the relationship between bone density at trabecular bone-rich and cortical bone-rich sites in the same individual. In this study, we attempted to measure BMD at multiple sites using whole-body computed tomography images taken immediately after death and to clarify the similarities and differences between skeletal sites. Additionally, we aimed to examine the factors that influence changes in BMD, such as the loading environment, bone microstructure, and the ossification process of each skeletal region. A 3D model containing BMD data of the skull, clavicle, lumbar vertebrae, and femur (neck and diaphysis) was created using computed tomography images taken immediately after the death of 60 individuals (28 men and 32 women, average age: 84.0 years) who consented to participate in the study before death. Arbitrary measurement sites were defined, and bone density was measured at each site. We found that the BMDs of all regions were negatively correlated with age, but this correlation was weaker in the skull than in other regions. The negative correlation was especially pronounced in areas with more trabecular bones in men and in areas with more cortical bones in women. Furthermore, these findings suggest that factors, such as the loading environment, bone microstructure, and the ossification process of the skeletal sites, affect the BMD. Furthermore, our results suggest that it is important to assess the BMD of cortical bone in older women.

Direct bone marrow injection of human bone marrow-derived stromal cells into mouse femurs results in greater prostate cancer PC-3 cell proliferation, but not specifically proliferation within the injected femurs

BackgroundWhile prostate cancer (PCa) cells most often metastasize to bone in men, species-specific differences between human and mouse bone marrow mean that this pattern is not faithfully replicated in mice. Herein we evaluated the impact of partially humanizing mouse bone marrow with human bone marrow-derived stromal cells (BMSC, also known as "mesenchymal stem cells") on human PCa cell behaviour.MethodsBMSC are key cellular constituents of marrow. We used intrafemoral injection to transplant 5 × 105 luciferase (Luc) and green fluorescence protein (GFP) expressing human BMSC (hBMSC-Luc/GFP) into the right femur of non-obese diabetic (NOD)-severe combined immunodeficiency (scid) interleukin (IL)-2γ−/− (NSG) mice. Two weeks later, 2.5 × 106 PC-3 prostate cancer cells expressing DsRed (PC-3-DsRed) were delivered into the mice via intracardiac injection. PC-3-DsRed cells were tracked over time using an In Vivo Imaging System (IVIS) live animal imaging system, X-ray and IVIS imaging performed on harvested organs, and PC-3 cell numbers in femurs quantified using flow cytometry and histology.ResultsFlow cytometry analysis revealed greater PC-3-DsRed cell numbers within femurs of the mice that received hBMSC-Luc/GFP. However, while there were overall greater PC-3-DsRed cell numbers in these animals, there were not more PC-3-DsRed in the femurs injected with hBMSC-Luc/GFP than in contralateral femurs. A similar proportion of mice in with or without hBMSC-Luc/GFP had bone lessions, but the absolute number of bone lesions was greater in mice that had received hBMSC-Luc/GFP.ConclusionPC-3-DsRed cells preferentially populated bones in mice that had received hBMSC-Luc/GFP, although PC-3-DsRed cells not specifically localize in the bone marrow cavity where hBMSC-Luc/GFP had been transplanted. hBMSC-Luc/GFP appear to modify mouse biology in a manner that supports PC-3-DsRed tumor development, rather than specifically influencing PC-3-DsRed cell homing. This study provides useful insights into the role of humanizing murine bone marrow with hBMSC to study human PCa cell biology.

Microstructural alterations of superolateral femoral neck cortical bone in men with diabetes as a possible basis for fragility fractures: a cadaveric study

Microstructural alterations of superolateral femoral neck cortical bone in men with diabetes as a possible basis for fragility fractures: a cadaveric study

The Short-Term Effect of Prunes in Improving Bone in Men.

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between −0.1 and −2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.

Gender dimorphism in survival of patients with lymph node metastasis of bladder cancer

Background:The effect of gender on the prognosis of bladder cancer (BCa) in different metastatic sites is insufficiently understood. We aimed to assess the impact and potential mechanisms of a combination of gender dimorphism and BCa metastasis sites on the risk of death.Methods:Independent predictors of overall survival and cancer-specific survival were analyzed after stratification by gender and metastasis sites from the Surveillance, Epidemiology, and End Results database. Furthermore, gender-differentially expressed genes (DEGs) and function-enriched annotations for patients with lymph node metastasis (LNM) were identified from The Cancer Genome Atlas (TCGA) database. A gender-associated signature was constructed in TCGA and validated in the IMvigor210 trial, and the magnetic resonance imaging-based radiomics signature was developed in our center to predict the gender-associated signature.Results:In patients with metastatic BCa, the most common site of metastasis is bone in men and lung in women. Moreover, stratified by sex, LNM had a better prognosis in men than visceral metastasis, which was not observed in female. Similarly, stratified by the metastasis site, the prognosis of men in patients with LNM is better than that of women, which was not observed in visceral metastasis patients. Enrichment of DEGs between sexes in patients with LNM may be related to metastasis and tumor immunity, especially the role of neutrophils. Moreover, the gender-associated signature is related to the clinicopathological characteristics of patients, and patients in the high-risk group had worse survival outcomes, and higher susceptibility to cisplatin, docetaxel, camptothecin, and paclitaxel. A nomogram combined with the signature and clinical staging showed significant predictive power in survival prediction. Furthermore, patients with high radiomics scores had a strong tendency for high-risk group.Conclusion:These results may improve the understanding of the differences in tumor biology between sexes and thus provide additional evidence for individualized treatment in BCa.

The impact of anti-androgen therapy on bone in men treated for paraphilia: a retrospective cohort study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Men's Bones Matter Too, a Cross Sectional Study Examining Bone Health among Men with Intellectual Disability in Ireland.

Globally between 30-40% of all osteoporotic fractures occur among men, with a quarter of all hip fractures, the most serious complication of osteoporosis, occurring in men. Among men of 50 years of age or older, osteoporotic fracture risk reaches an alarming 20%. What is of great concern is that associated mortality is greater among men when compared with women. For hip fractures specifically, mortality for men is two to three times that in women which may be attributed to the fact that osteoporosis is often considered a “women’s disease”. Of great concern is that there is a paucity of bone health investigation among men with intellectual disability. In the Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing, objective bone status of 244 men was measured using a quantitative ultrasound. Participant’s also self-reported doctor’s diagnosis of health conditions including osteoporosis, medication and fracture history with the assistance of key workers/family. Ethical approval for the study was obtained from the Faculty of Health Sciences Trinity College and all participating service providers. Overall, 70.9% of men presented with poor bone health, with 57.8% taking at least one medication that contributed to osteoporosis/osteopenia. Men had a high prevalence of fracture (21.7%) despite this less than 18% had attended bone health screening. In light of these findings, it is time for the spotlight to focus on men’s bone health and for healthcare professionals to realise how ‘at risk’ of osteoporosis are men with intellectual disability. Projections place men on a trajectory of continuous increased risk of fracture in comparison to women.

Sex- and Age-Related Differences in the Distribution of Metastases in Patients With Upper Urinary Tract Urothelial Carcinoma.

The distribution of metastatic sites in upper tract urothelial carcinoma (UTUC) is not well-known. Consequently, the effects of sex and age on the location of metastases is also unknown. This study sought to investigate age- and sex-related differences in the distribution of metastases in patients with UTUC. Within the Nationwide Inpatient Sample database (2000-2015), we identified 1,340 patients with metastatic UTUC. Sites of metastasis were assessed according to age (≤63, 64-72, 73-79, and ≥80 years) and sex. Comparison was performed with trend and chi-square tests. Of 1,340 patients with metastatic UTUC, 790 (59.0%) were men (median age, 71 years) and 550 (41.0%) were women (median age, 74 years). The lung was the most common site of metastases in men and women (28.2% and 26.4%, respectively), followed by bone in men (22.3% vs 18.0% of women) and liver in women (24.4% vs 20.5% of men). Increasing age was associated with decreasing rates of brain metastasis in men (from 6.5% to 2.9%; P=.03) and women (from 5.9% to 0.7%; P=.01). Moreover, increasing age in women, but not in men, was associated with decreasing rates of lung (from 33.3% to 24.3%; P=.02), lymph node (from 28.9% to 15.8%; P=.01), and bone metastases (from 22.2% to 10.5%; P=.02). Finally, rates of metastases in multiple organs did not vary with age or sex (65.2% in men vs 66.5% in women). Lung, bone, and liver metastases are the most common metastatic sites in both sexes. However, the distribution of metastases varies according to sex and age. These observations apply to everyday clinical practice and may be used, for example, to advocate for universal bone imaging in patients with UTUC. Moreover, our findings may also be used for design considerations of randomized trials.

Association of Vitamin D and Parathyroid Hormone Status With the Aging-Related Decline of Bone Microarchitecture in Older Men: The Prospective Structure of Aging Men's Bones (STRAMBO) Study.

Poor vitamin D status and high parathyroid hormone (PTH) level are associated with impaired bone microarchitecture, but these data are mainly cross-sectional. We studied the association of the baseline PTH and 25-hydroxycholecalciferol (25OHD) levels with the prospectively assessed deterioration of bone microarchitecture and in estimated bone strength in older men. Distal radius and tibia bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, then after 4 and 8 years in 826 men aged 60-87 years. At distal radius, total bone mineral density (Tt.BMD), cortical thickness (Ct.Thd ), cortical area (Ct.Ar), cortical BMD (Ct.BMD), and trabecular BMD (Tb.BMD) decreased, whereas trabecular area (Tb.Ar) increased more rapidly in men with 25OHD ≤20 ng/mL versus the reference group (>30 ng/mL). Men with 25OHD ≤10 ng/mL had faster decrease in reaction force and failure load than men with 25OHD >30 ng/mL. At the distal tibia, Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, failure load, and reaction force decreased, whereas Tb.Ar increased more rapidly in men with 25OHD between 10 and 20 ng/mL versus the reference group. The results were similar when 12 ng/mL was used as a threshold of severe vitamin D deficiency. At distal radius, men with PTH levels above the median (>44 pg/mL) had more rapid decrease in Tt.BMD, Ct.Ar, Ct.BMD, Ct.Thd , reaction force, and failure load, and more rapid increase in Tb.Ar versus the lowest quartile (≤34 pg/mL). At the distal tibia, men in the highest PTH quartile had faster decrease in Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, reaction force, and failure load and faster increase in Tb.Ar versus the lowest quartile. The results were similar in men with glomerular filtration rate >60 mL/min. The results were similar in men who took no vitamin D or calcium supplements for 8 years. In summary, vitamin D deficiency and secondary hyperparathyroidism are associated with more rapid prospectively assessed cortical and trabecular bone decline in older men. © 2022 American Society for Bone and Mineral Research (ASBMR).

A study on drill machining for Magnesium alloy using Taguchi method

Magnesium is one the very important material light weight, especially in the field of the vehicle component, and the field of biomedical. Application of material magnesium and its alloy in the field of biomedical based on the magnesium characteristics which look very much like the nature of biocompatibility of bones in man and melted down within the body. Application material magnesium are also many developed by means of grown (implant). Magnesium alloy material has some of the more in the chemical nature and physics, but in the machining process a magnesium alloy known as combustible metal material type, especially during the machining process at high speed. The optimizing of machining process is necessary in order to maintain for not chip burning. In this research, the point angle, lubricant and drilling parameter were analysed to know their influence on the value of surface roughness, cylindricity and perpendicularity. On this research analysis support for new carried out using a Taguchi Method L18 consisting of 3 factors with 3 levels and 1 factors with 2 levels. The research results show that surface roughness is influenced by the significant contributions from the point angle 18.9 % and lubricant 14.5 %, where the point angle is 650 with lubricant of synthetic oil. The emergence of a nose radius tendency resulting in the increasing level subtlety. Cylindricity is influenced by an point angle 450 of the drilling process however, especially if there is an interactions of the feeding of 0.2 mm/rev and synthetic lubricant. The cutting edge accuracy led to a tangential force so that had an impact on their rotation stability and the cylindricity of drilling results. The value of perpendicularity of magnesium AZ31 in the drilling process however also carried out similar procedures are very much influenced by the cutting parameter of feeding that produces the significance of p = 0,044, while the strongest significance will be happened if there were an interaction between feeding of 0,1 mm and synthetic lubricant to p = 0.041.

Osteometric Study of the Batalnoe Necropolis of the Crimean Peninsula

Skeletons of 9 women and 13 men were measured and a number of indices were calculated during the study of burials from the Crimean Tatar Batalnoe necropolis. The ratio of the lengths of the upper and lower extremities was found to be average or lower than average, the shoulder is relatively long. In men, the forearm was often long relative to the shoulder; in women, on the contrary, it was often shorter. Both men and women had short tibia according to the crural index. Women are characterized by very narrow shoulders. The degree of massiveness of long bones in men varies, with the exception of usually massive radius and tibia. Women are characterized by medium-massive and gracile long bones, with the exception of the bones of the forearm. The body length in men was estimated as 162.1–175.1 cm. The reconstructed body length of women is 146.4 –160.0 cm.

Age-related peculiarities of some linear parameters of metacarpal bones in men of Tajikistan

The aim of the study was to study the linear parameters (length and width of the diaphysis) of metacarpals (MB) in males of Tajik nationality permanently residing in Tajikistan in the age aspect, as well as establishing the possibility of using linear MB parameters to determine the age of the examined. Material and methods . An examination of 117 X-rays was carried out in males of Tajik nationality aged 6-17 years living in Kanibadam in Tajikistan. The length of the MB, the width of the diaphysis of the MB were studied on the radiographs. The relationship between the length and width of the MB diaphysis with age was determined using the Pearson's parametric correlation coefficient - «r» and the nonparametric correlation coefficient - «rs». Comparison of the results with the size of MB in St. Petersburg residents was made. Results. Morphometric examination showed that in boys in Tajikistan, the length of the MB and the width of the diaphysis of the MB significantly increased with age, which is confirmed by the data of the correlation analysis. Dependence of the length and width of the MB on age is described by the linear regression equation, which is an analytical solution to the question of the nature of the dependence of the length and width of the MB diaphysis and the age of the examined. The presence of differences in the size of MB in different age periods was found in boys in Russia and Tajikistan, especially at the age of 14 years. Ethno-territorial differences are more often expressed in the width of the MB than in the length. Conclusions. It was established, that the correlation between the age of the examined and the length of the MB is closer than between the age and the width of the MB diaphysis. To determine the age of the examinee, it is better to use the MB length parameters than the width of the MB. The highest reliability in determining the age of males in Tajikistan from the data obtained was determined according to the length of MB II, and the lowest index was the width of the MB V diaphysis.

Circulating tumor cells correlate with patterns of recurrence in patients with hormone-sensitive prostate cancer.

The aim of this study was to evaluate the correlation between circulating tumor cells (CTCs) and patterns of recurrence in patients with hormone-sensitive prostate cancer. The study involved patients with histologically confirmed, advanced prostatic adenocarcinoma, who were tested for CTCs (Veridex®) when they developed recurrence after radical prostatectomy or external beam radiation between 2008 and 2014. Forty-two prostate cancer patients were evaluated. CTCs were detected in 14 out of 42 (33.3%) patients (Group A), while the remaining 28 (66.7%) showed undetectable levels of CTCs (Group B). The mean prostate-specific antigen value was higher in Group A in comparison to Group B (6.2 vs 3.3 ng/dL) (P=0.48). Presence of bone metastases alone or along with nodal metastases was more common in Group A (57.1%) in comparison to Group B (25%) (P=0.04). In a univariate analysis, the presence of CTCs at diagnosis correlated with the development of bone recurrence (OR: 4; 95% CI: 1.0–15.9; P=0.05). Even if the study enrolled only a small number of patients, the detection of CTCs in the blood appears to correlate with the pattern of progression in patients with hormone-sensitive prostate cancer, suggesting a possible role in anticipating recurrence at the bone in men with higher tumor load. Further prospective studies are warranted in this setting.

Long bone robustness during growth: A cross-sectional pQCT examination of children and young adults aged 5–29 years

Skeletal robustness (cross-section size relative to length) is associated with stress fractures in adults, and appears to explain the high incidence of distal radius fractures in adolescents. However, little is known about the ontogeny of long bone robustness during the first three decades of life. Therefore, we explored the ontogeny of tibial, fibular, ulnar and radial robustness in a cross-sectional sample of 5 to 29year-old volunteers of both sexes. Peripheral quantitative computed tomography (pQCT) was used to evaluate cross-sections of the leg (4%, 14%, 38% and 66%), and forearm (4%, and 66%) in N=432 individuals. Robustness was evaluated as the total bone area divided by bone length. Differences between age-groups, sexes, and age-group×sex interactions were evaluated with ANOVA with Tukey's post hocs where appropriate. Most bone sites exhibited more robust bones in men than women (P<0.001 to 0.02), and in older age-groups than younger (P<0.001). Sex×age-group interaction was observed at the 66% and 38% tibia sites with robustness increasing more with age in men than in women (P=0.006 to 0.042). Post-hoc analyses indicated no sex differences prior to 13years-of-age, and notable exceptions to increasing robustness with age at the 4% radial and 66% tibial sites, which exhibited reduced robustness in age groups close to peak height velocity. In conclusion, the present results suggest that very little sexual dimorphism in long bone robustness exists prior to puberty, and that divergence occurs primarily after cessation of longitudinal growth. A period of relative diaphyseal slenderness was identified at age-groups coinciding with the adolescent growth spurt, which may be related to the relatively high incidence of frank and stress fracture in adolescents.

New Insights Into Androgen and Estrogen Receptor Regulation of the Male Skeleton.

Beginning with the report in 1994 that an adult male with homozygous loss of estrogen receptor α (ERα) had unfused epiphyses and osteopenia,(1) there is now considerable evidence from observational and interventional studies (summarized in Khosla and colleagues(2)) that estrogen is the dominant regulator of bone metabolism in men. Indeed, a legitimate argument can be made that testosterone is largely a prohormone for the skeleton, with its effects on bone mediated principally via aromatization to estrogen, although it remains likely that testosterone contributes to bone size via effects on periosteal apposition and perhaps indirectly to bone mass by increasing muscle mass.

On the mark? Is alkaline phosphatase a surrogate for bone density in men with hypogonadism?

The current issue of the BJUI contains a paper by Dubaja et al. 1 that may be of interest to physicians who have patients with hypogonadism. The authors speak to an unappreciated aspect of low testosterone; namely, the loss of bone in men and the possible recovery with treatment. Their retrospective study looked at 140 men with hypogonadism treated with exogenous testosterone replacement or clomiphene citrate testosterone enhancement. These men were also assessed for bone mineral density (BMD) markers at 6, 12 and 24 months after initial treatment. Importantly, dual-energy X-ray absorptiometry (DEXA) was performed a second time after 2 treatment years for a subset of these men. DEXA showed that there was a gain in BMD and a loss of serum alkaline phosphatase (AP) for all the men over time. The loss of AP was rapid but stabilized at 6 months. Testosterone and free testosterone increased as expected but there were no changes in vitamin D, calcium, parathyroid hormone or sex hormone-binding globulin. There was a correlation between AP and testosterone. The authors recognized poor bone density at baseline in those men with testosterone levels <250 ng/dl. Bone mineral density is the best way to predict osteoporosis and fragility fractures 2. Women loose BMD after menopause and that is accompanied by many changes, including gains in AP 3. The decline in serum oestrogens is a factor for women, and oestrogen replacement therapy historically has been used to prevent that loss. Not all men undergo a similar loss, i.e. andropause is not recognized in the same way as menopause. Even though osteoporosis is less common in men, the associated comorbidity may be more significant. There is an age-related decline in testosterone and an acute loss for some men such that they approach their physicians with symptoms. The underlying cause of bone loss in men and women may be the same: serum oestrogen loss. Men who lose testosterone are also losing oestrogen because testosterone is the precursor via aromatase. Repros Therapeutics is developing a way to treat men with secondary hypogonadism. An ongoing 1-year DEXA study recruited eligible men. Key inclusion factors were age < 60 years and body mass index > 25 kg/m2. Remarkably 24% of men failed the screening test because of osteopenia, despite the fact that few of them were old or underweight. The present paper by Dubaja et al. suggests that a readily available serum test may be able to monitor men on testosterone therapies for gain in BMD. Given the relatively low incidence of osteoporosis, screening every man by DEXA is not cost-efficient. The 1 year or more needed to find BMD loss by DEXA also wastes time and resources. Quantitative CT is more costly and is accompanied by high radiation exposure. The use of AP, as suggested in the present study, may represent a reasonable alternative. The paper is not without its weaknesses. There was no indication of whether these men had primary or secondary hypogonadism. Transdermal testosterone should raise testosterone and oestrogen in both groups of men whereas clomiphene citrate works through changes in LH and FSH and requires an intact hypothalamic-pituitary-gonadal axis (useful in men with secondary hypogonadism only). Indeed, the two kinds of treatment will have the opposite effect on LH and FSH 4. The authors recognized the importance of Leydig cells in producing testosterone, yet the effects of a transdermal testosterone would be to shut down testosterone production. We commend their suggestion that other factors that contribute to both bone and Leydig cell function, insulin-like 3 5 and osteocalcin 6 should be studied in relation to AP. The loss of subjects throughout the 2 years was troubling, but it is known that men on transdermal treatments discontinue with disturbing frequency despite satisfaction 7. If those who stayed in the present study were those with the best outcomes in terms of testosterone and BMD, potential bias may exist. If men can be encouraged to continue therapy through positive effects on BMD being detected as early as 6 months, AP monitoring may improve patient compliance. Only DEXA can give that assurance now. The authors noted the need for a larger prospective trial. Nevertheless, their paper provides a rationale for monitoring men on testosterone therapies that can be implemented with minimal cost or the need for new diagnostics. Authors are employees and/or stockholders in Repros Therapeutics.

The endocrine role of estrogens on human male skeleton.

Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men.

Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial.

Metabolic syndrome (MetS) is associated with low-grade inflammation, which may harmfully affect bone. Resveratrol (RSV) possesses anti-inflammatory properties, and rodent studies suggest bone protective effects. This study sought to evaluate effects of RSV treatment on bone in men with MetS. The study was conducted at Aarhus University Hospital as a randomized, double-blinded, placebo-controlled trial assessing changes in bone turnover markers, bone mineral density (BMD), and geometry. The study population comprised 74 middle-aged obese men with MetS recruited from the general community, of which 66 completed all visits. Mean age of participants was 49.3 ± 6.3 years and mean body mass index was 33.7 ± 3.6 kg/m(2). Oral treatment with 1.000 mg RSV (RSV(high)), 150 mg RSV (RSV(low)), or placebo daily for 16 weeks. Prespecified primary endpoint was change in bone alkaline phosphatase (BAP). BAP increased dose dependently with RSV (R = 0.471, P < .001), resulting in a significantly greater increase in BAP in the RSV(high) group compared with placebo at all time-points (week 4, 16.4 ± 4.2%, P < .001; week 8, 16.5 ± 4.1%, P < .001; week 16, 15.2 ± 3.7%, P < .001). Lumbar spine trabecular volumetric bone mineral density (LS vBMD(trab)) also increased dose dependently with RSV (R = 0.268, P = .036), with a significant increase of 2.6 ± 1.3% in the RSV(high) group compared with placebo (P = .043). In addition, changes in BAP and LS vBMD(trab) were positively correlated (R = 0.281, P = .027). No consistent changes were detected in bone density at the hip. Our data suggest that high-dose RSV supplementation positively affects bone, primarily by stimulating formation or mineralization. Future studies of longer duration comprising populations at risk of osteoporosis are needed to confirm these results.

The Effect of Bisphosphonates on Bone Mineral Density in Metastatic Prostate Cancer Patients Who Are Treated with Anti-Androgen Drugs and Radiotherapy

Objective: To evaluate the potential effect of bisphosphonates on bone mineral density (BMD) in patients who are treated with anti-androgen drugs and radiotherapy for metastatic prostate cancer. Materials and Methods: The data of 31 patients with metastatic prostate cancer who were treated with anti-androgen drugs and radiotherapy during a 1-year period were retrospectively reviewed. Patients were divided in 2 groups, in which 17 patients in group 1 were treated with zoledronic acid (4 mg/month, intravenous) and 14 patients in group 2 who did not receive zoledronic acid. BMD was measured before the treatment and at the end of the 1st year by dual energy X-ray absorptiometry. Statistical analyses were performed with the T test. Results: Mean age of the patients was 71.42 ± 6.7(range 59-85) years. A significant increase was noted for pelvic bone, femoral neck, and lumbar vertebrae t scores when pretreatment and 1st year measurements were compared in group 1 (p < 0.05). In group 2 a significant decrease was noted for pelvic bone and femoral neck t scores at the end of the 1st year (p < 0.05). A significant increase was noted for pelvic bone and femoral neck follow-up in BMD values at the end of the 1st year compared to initial measurements in group 1. A significant decrease was noted for lumbar vertebrae follow-up in BMD values at the end of the 1st year when compared to initial values in group 2. Conclusion: Zoledronic acid significantly increases BMD and delays unfavorable outcomes for bones in men who are treated with anti-androgen drugs and radiotherapy for metastatic prostate cancer.