Relationship of sex steroid hormones with bone mineral density (BMD) in a nationally representative sample of men (original) (raw)

Determinants of Bone Density in Healthy Older Men With Low Testosterone Levels

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2000

Background. Osteoporosis is a significant problem in older men; 30% of all hip fractures occur in men and the mortality rate following hip fracture exceeds that of women. Testosterone is thought to be important in the development of peak bone mass but its role in age-related bone loss is not established. The purpose of this study was to define the predictors of bone mass in healthy older men with low testosterone levels but without symptomatic osteoporosis. Methods. Eighty-three community-dwelling white men, aged more than 65 years old, selected for low bioavailable testosterone levels (Յ 4.44 nmol/l) participated in a cross-sectional study located at a university general clinical research center. Sex hormone concentrations and markers of bone turnover were assayed in serum and urine. Risk factors for osteoporosis and physical activity were ascertained by physical examination and questionnaire, including the Physical Activity Scale in the Elderly (PASE) questionnaire. Bone mineral densities of the femoral neck (FN BMD), spine, and whole body were measured by dual x-ray absorptiometry. Lower extremity muscle strength (1 repetition maximum) was measured using a leg press machine. Results. Mean bone mineral density values were 0.93 Ϯ 0.14 g/cm 2 for femoral neck, 1.31 Ϯ 0.23 g/cm 2 for spine, and 1.22 Ϯ 0.12 g/cm 2 for whole body. Thirty-one of the 82 subjects (37%) had t scores Ͻ-1 and 12 of 82 subjects (15%) had t scores Ͻ-2.5 at the femoral neck. Multiple linear regression analysis demonstrated that bioavailable testosterone, body mass index (BMI), and PASE scores were positively correlated with, and significant predictors of, femoral neck BMD, accounting for 34.4% of the variance in FN BMD (F ϭ 10.10, p ϭ .001). Examining each variable independently, bioavailable testosterone accounted for 20.7%, physical activity score for 9.0%, and BMI for 6.5% of FN BMD. Using analysis of variance, mean values for FN BMD were significantly different between men grouped by tertile of bioavailable testosterone (F ϭ 6.192, p ϭ .003). FN BMD mean values were 0.86 Ϯ 0.14 g/cm 2 for the lowest tertile, 0.94 Ϯ 0.16 for the middle tertile, and 0.99 Ϯ 0.14 for the highest tertile. Markers of bone turnover were inversely correlated, and strength directly correlated with BMD, but did not contribute to the multiple regression model. Conclusions. Fifty-two percent of older men with low bioavailable testosterone levels had BMD levels below the young adult normal range and are likely at an increased risk of fracture. Bioavailable testosterone, BMI, and physical activity scores were significant determinants of FN BMD in these men. These variables are potentially modifiable and, therefore, amenable to intervention. Hence, our results suggest the need for testosterone replacement and physical activity intervention trials in men at risk for osteoporotic fractures.

Bioavailable Estradiol May Be an Important Determinant of Osteoporosis in Men: The MINOS Study 1

The Journal of Clinical Endocrinology & Metabolism, 2001

During recent years, experimental data, case reports, and epidemiological studies have suggested an important role for estradiol in bone metabolism in men. In a cohort of 596 men, aged 51-85 yr, we measured bone mineral density (BMD) of the lumbar spine, hip, total body, and forearm; serum levels of sex steroid hormones [total and free testosterone, total estradiol (17␤E 2), bioavailable estradiol (bio-17␤E 2), androstenedione, and sex hormone-binding globulin]; and markers of bone turnover [serum osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I collagen, and ␤-isomerized C-terminal telopeptide of collagen type I (␤CTX)], as well as urinary excretion of ␤CTX and deoxypyridinoline (DPyr). An age-related decrease was found for bio-17␤E 2 (r ϭ Ϫ0.16; P Ͻ 0.001), free testosterone (r ϭ Ϫ0.25; P Ͻ 0.001), free testosterone index (r ϭ Ϫ0.32; P Ͻ 0.001), and androstenedione (r ϭ Ϫ0.22; P Ͻ 0.001), but not for total 17␤E 2 or total testosterone. 17␤E 2 and bio-17␤E 2 , but not other hormones, were correlated with BMD after adjustment for age and body weight. In men with a bio-17␤E 2 level in the lowest quartile, the average BMD was lower than in men having a bio-17␤E 2 level in the highest quartile by 6.6-8.7% according to the site of measure

Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study

The Aging Male, 2012

We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm 2 ; femoral BMD= 0.847 ± 0.117 g/cm 2 ). TU induced a significant improvement of bone mass after 36 months (lumbar BMD = 1.053 ± 0.145 g/cm 2 ; p < 0.002; femoral BMD = 0.989 ± 0.109; p < 0.003 g/cm 2 ) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r 2 = 0.66, p < 0.0001) and femoral (r 2 = 0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middleaged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.

Progressive Temporal Change in Serum SHBG, But Not in Serum Testosterone or Estradiol, Is Associated With Bone Loss and Incident Fractures in Older Men: The Concord Health and Ageing in Men Project

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2016

This study aimed to examine progressive temporal relationships between changes in major reproductive hormones across three waves of a cohort study of older men and (1) changes in bone mineral density (BMD) and (2) incident fractures (any, hip or non-vertebral) over an average of 6 years of follow-up. The CHAMP cohort of men aged 70 years and older were assessed at baseline (2005 to 2007, n = 1705), 2-year follow-up (n = 1367), and 5-year follow-up (n = 958). Serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) (by liquid chromatography-tandem mass spectrometry [LC-MS/MS]), and sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) (by immunoassay) were measured at all time-points, whereas free testosterone (cFT) was calculated using a well-validated formula. Hip BMD was measured by dual-energy X-ray absorptiometry (DXA) at all three time-points, and fracture data were verified radiographically. Statistical...

Are Bioactive and Free Sex Steroids Associated with Bone Mineral Density and Bone Turnover Markers in Middle Aged Men?

osteoporozdunyasindan.com

Aim: To investigate whether bioactive and free sex steroids are associated with bone mineral density (BMD) and bone turnover markers in middle aged men. Material and Methods: One hundred and fifteen out of 165 volunteers aged 35-65 years presenting to our outpatient clinic were included in the study. Serum albumin, total testosterone (T), total estradiol (E2), SHBG, osteocalcin (OC) and C-terminal telopeptide (CTx) levels were measured. Free and bioactive sex steroids, free androgen index (FAI) and free estrogen index (FEI) were calculated. BMD in the lumbar spine and the hip was measured in all participants and effects of sex steroids on BMD and bone turnover markers were investigated. Results: The mean age and the mean body mass index (BMI) in all participants were 52.4±7.8 years and 26.1±3.4 kg/m 2 respectively. There was no significant difference in sex hormone levels and bone turnover markers between the individuals with osteoporosis and osteopenia and the individuals with normal BMD (p>0.05). There was a significant relation between age and FAI (r=-0.23, p=0.01), but there was no significant relation between age and bioactive and free sex steroids, FEI and SHBG. However, there was a positive correlation between BMI and bioactive E2 (r=0.35, p:0001), free E2 (r=0.29, p:0.002) and FEI (r=0.39, p=0.0001). After an adjustment for variables effective on BMD was made; no relation was found between BMD measures from the lumbar spine and the hip and serum bioactive sex steroids, free sex steroids, FAI, FEI and SHBG (p>0.05). However, there was a weak positive relation between serum bioactive T, FEI and OC, CTx levels (p=0.05). Conclusion: We think that bioactive and free sex steroids are not independent variables effective on BMD in the spine and the hip in middle aged men and that further studies are needed to elucidate the pathophysiology of idiopathic male osteoporosis.

Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis

CLINICAL …, 2005

Objectives Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. Data source A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. Review methods Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. Results Overall, 1083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64·5 years (range 49·9 -77·6) and mean serum testosterone was 10·9 nmol / l (range 7·8 -19). Testosterone treatment produced: (i) a reduction of 1·6 kg (CI: 2·5 -0·6) of total body fat, corresponding to − 6·2% (CI: 9·2 -3·3) variation of initial body fat, (ii) an increase in fat free mass of 1·6 kg (CI: 0·6 -2·6), corresponding to +2·7% (CI: 1·1 -4·4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size = 0·3 standard mean difference (SMD), CI: − 0·0 to 0·6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3·7% (CI: 1·0 -6·4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = − 0·6 SMD, CI: − 1·0 to − 0·2). Testosterone also reduced total cholesterol by 0·23 mmol / l (CI: − 0·37 to − 0·10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline ( − 0·085 mmol/l, CI: − 0·017 to − 0·003). Sensitivity and meta-regression analysis revealed that the dose / type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. Conclusion The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems. studies linking androgen decline with the frailty of old age, and the ADAM syndrome has not been universally accepted as a true clinical entity. An alternative approach would be to evaluate whether increasing serum testosterone concentration of ageing men to the level found in young adults improves or reverses these symptoms. Despite much recent interest by physicians, the media and the general population, and the publication of several studies examining the effects of testosterone treatment on body composition, 7-25 strength, bone density and metabolism and lipid

Testosterone is an independent determinant of bone mineral density in men with type 2 diabetes mellitus

Clinical Chemistry and Laboratory Medicine, 2000

List of abbreviations body mass index (BMI); bone mineral density (BMD); C-reactive protein (CRP); type 2 diabetes mellitus (DT2); follicle-stimulating hormone (FSH); hemoglobin A 1c (HbA 1c); high-density lipoprotein cholesterol (HDL-C); immunoreactive insulin (IRI); lowdensity lipoprotein cholesterol (LDL-C); luteinizing hormone (LH); sex hormonebinding globulin (SHBG); total cholesterol (TC); triglyceride (TG); very low-density lipoprotein cholesterol (VLDL-C); qualitative ultrasound (QUS)

Are Bioactive and Free Sex Steroids Associated with Bone Mineral Density and Bone Turnover Markers in Middle Aged Men? - Original Investigation

DOAJ (DOAJ: Directory of Open Access Journals), 2009

Faculty of 1000 evaluation for Gonadal steroid-dependent effects on bone turnover and bone mineral density in men

F1000 - Post-publication peer review of the biomedical literature, 2016

RESULTS. As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men. CONCLUSIONS. Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton. TRIAL REGISTRATION. ClinicalTrials.gov, NCT00114114.

Relationship of sex steroid hormones with bone mineral density (BMD) in a nationally representative sample of men (original) (raw)

Related papers