Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men.

Androgens are important regulators of bone and prostate health in elderly men. The role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in men is unclear. We show that specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. INTRODUCTION: Androgens are important regulators of bone and prostate health in elderly men. Local synthesis and degradation of androgens are likely to be important parameters of biological action of androgens in androgen-responsive tissues. The aim of this study was to determine the role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in elderly men. MATERIALS AND METHODS: A subsample of the population-based Swedish part of the MrOS study (n = 631, average age = 75.9 years) was investigated. Bone parameters were measured using DXA. Serum levels of total testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography/mass spectroscopy (GC-MS); androstane-3alpha,17beta-diol-3glucuronide (3G) and androstane-3alpha,17beta-diol-17glucuronide (17G) were measured by liquid chromatography/mass spectroscopy. Prostate volume (n = 159) was measured by transrectal ultrasound. RESULTS: The general pattern is that two of the glucuronidated androgen metabolites, namely 17G and 3G, are stronger positive predictors of BMD than the bioactive androgens (T and DHT). In addition, 17G is a clear positive predictor of prostate volume, explaining 4.5% of the variance in prostate volume, whereas the bioactive androgens do not display any association with prostate volume. CONCLUSIONS: Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Future studies should determine if the glucuronidated androgen metabolites also reflect other biological correlates of androgenic activity, including prostate cancer, and if low levels might be a marker of general androgen deficiency in men.     

Gallstones and previous cholecystectomy in 77- to 78-year-old women in an urban population in Sweden

A randomly selected sample of 120 women, born in 1906-1907 and living in the city of Gothenburg, were invited to an ultrasound examination for gallstone disease. One hundred and nine subjects participated in the study, and among these, 24% gave a history of a previous cholecystectomy, 27% had gallstones, and 49% had no stones in the gallbladder. Among the women with stones in the gallbladder only 35% had associated symptoms. The design of the study enabled a comparison among women with no stones in the gallbladder, with gallstones, and with a previous cholecystectomy. Women with gallstones, previous or present, had a higher body weight, body mass index, skinfold thickness, and serum triglyceride level than subjects without gallstones.     

Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX®, Falls,and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height² (ALM/ht²) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX^®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht² only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht²), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Sport-specific association between exercise loading and the density, geometry, and microstructure of weight-bearing bone in young adult men

Summary

In this population-based study of 24-year-old men, we have investigated the association between sport-specific exercise loading and different bone parameters. We reveal that the association between exercise loading and bone parameters is sport-specific, indicating that nonspecific resistance exercise does not impact bone density, geometry, or microstructure in young men.

Introduction

In this cross-sectional study, the association between nonspecific resistive exercise and areal and volumetric bone density, bone geometry, or bone microstructure was investigated in young adult men.

Methods

A total of 184 male athletes, 24.0?±?0.6 years of age (mean?±?SD), representing nonspecific resistive exercise and soccer (proportion of recreational athletes, 93.4 and 7.7 %, respectively), and 177 nonathletic age-matched controls were measured with dual-energy X-ray absorptiometry. Radius and tibia were measured by peripheral quantitative computed tomography (pQCT) at the diaphysis and by three-dimensional pQCT at the metaphysis.

Results

Men in the nonspecific resistive exercise group had higher grip strength(9.1 % or 0.4 SD) and higher lean mass(5.6 % or 0.5 SD) than those in the nonathletic group(p?<?0.01 and p?<?0.001, respectively). However, men who participated in nonspecific resistive exercise did not have higher bone density or a more favorable bone microstructure or geometry than their nonathletic referents. In contrast, men playing soccer had higher areal bone mineral density (aBMD) at the femoral neck (19.5 % or 1.2 SD) and lumbar spine (12.6 % or 1.0 SD), as well as larger cortical cross-sectional area (16.4 % or 1.1 SD) and higher trabecular bone volume fraction (14.5 % or 0.9 SD), as a result of increased trabecular number (8.7 % or 0.6 SD) and thickness (5.7 % or 0.4 SD) at the tibia than men in the nonathletic group(p?<?0.001).

Conclusions

Weight-bearing exercise with impacts from varying directions (playing soccer) is associated with aBMD and volumetric BMD, cortical bone geometry, as well as trabecular microstructure of weight-bearing bone. Nonspecific recreational resistance exercise does not appear to be a strong determinant of bone density, geometry, or microstructure in young adult men.     

A Meta‐Analysis of the Association of Fracture Risk and Body Mass Index in Women

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person‐years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m²) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non‐obese women. Compared to a BMI of 25 kg/m², the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m² was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.     

Diabetes association with self-reported health,resource utilization,and prognosis post-myocardial infarction

BackgroundDiabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health‐related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post‐myocardial infarction (MI) patients with and without DM.HypothesisIn post‐MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes.MethodsThe prospective, observational long‐term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post‐MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and <60 mL/min, and DM treated with medication. Self‐reported health status was assessed at baseline, 1 and 2 years and converted to EQ‐5D scores. The main outcome measures were baseline HRQoL and HRU during follow‐up.ResultsDM at enrollment was 33% (2959 patients, 869 insulin treated). Mean baseline EQ‐5D score (0.86 vs 0.82; P < .0001) was higher; mean number of hospitalizations (0.38 vs 0.50, P < .0001) and mean length of stay (LoS; 9.3 vs 11.5; P = .001) were lower in patients without vs with DM. All‐cause death and the composite of CV death, MI, and stroke were significantly higher in DM patients, with adjusted 2‐year rate ratios of 1.43 (P < .01) and 1.55 (P < .001), respectively.ConclusionsStable post‐MI patients with DM (especially insulin treated) had poorer EQ‐5D scores, higher hospitalization rates and LoS, and worse clinical outcomes vs those without DM. Strategies focusing specifically on this high‐risk population should be developed to improve outcomes.Trial registration ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01866904","term_id":"NCT01866904"}}NCT01866904 (https://clinicaltrials.gov).     

Loss of total body potassium during rapid weight loss does not depend on the decrease of potassium concentration in muscles. Different methods to evaluate body composition during a low energy diet

OBJECTIVE: The aim of the study was to elucidate whether combustion of skeletal muscle glycogen during a very low calorie diet (VLCD) was associated with decreased muscle potassium content. A comparison between different methods was also performed to evaluate body composition during a VLCD and a low calorie diet (LCD). DESIGN: Dietary treatment of obese women by VLCD and LCD. Measurements after 1 and 2 weeks of VLCD and 6 months of LCD. SUBJECTS: Fifteen perimenopausal obese women aged 46.5+/-1.3 y and 15 of 48.0+/-0.7 y of age. MEASUREMENTS: Skeletal muscle biopsies under local anaesthesia. Body composition measurements by means of deal-energy X-ray absorptiometry (DEXA), and measurements of total body potassium (40K) and total body nitrogen (TBN). Measurements of electrolytes and glycogen concentration in muscle samples. RESULTS: In the first study (1 week of VLCD) skeletal muscle glycogen decreased (P<0.01), but muscle potassium increased (P<0.01). Muscle sodium decreased (P<0.01), while muscle magnesium was unaltered. Body weight decreased by 2.9+/-0.5 kg and 40K decreased. Fat-free mass (FFM) calculated from 40K and DEXA decreased by 2.7 vs 1.9 kg (P<0.001). Body fat measured with DEXA decreased by 1.1 kg (P<0.01), but not body fat calculated from 40K. TBN decreased by 0.03+/-0.01 kg (P<0.05) and FFM calculated from TBN by 2.9+/-0.5 kg (P<0.002). In the second study, 6 months on the LCD resulted in 17.0+/-2.0 kg weight reduction and this was mainly due to reduced body fat, 14. 0+/-2.0 kg measured with DEXA and from 40K (P<0.001). The decrease in FFM was slight. CONCLUSION: One week of VLCD resulted in muscle glycogen depletion but increased muscle potassium content in spite of decreased total body potassium. FFM contributed to the main part of body weight loss during short periods of severe energy restriction, but remained unchanged during long-term dietary treatment. Body fat became mostly responsible for the body weight loss during long-term LCD. Calculations of changes of FFM from 40K and TBN seem to overestimate the FFM decrease associated with short-term VLCD. International Journal of Obesity (2000)24, 101-107     

Seven Years of Treatment with Risedronate in Women with Postmenopausal Osteoporosis

The effects of 7 years of risedronate treatment were evaluated in a second 2-year extension of a 3-year vertebral fracture study in women with osteoporosis. For the first 5 years of the study, women received risedronate 5 mg/day or placebo according to the original randomization, with maintenance of blinding. All the women who entered into the 6–7 years extension study received risedronate 5 mg/day. Endpoints included vertebral and nonvertebral fracture assessments, changes in biochemical markers of bone turnover, and bone mineral density (BMD) measurements. A total of 164 women (placebo/risedronate group, 81; risedronate group, 83) entered the 6–7 years extension study and 136 (83%) completed the study. Annualized incidence of new vertebral fractures during the 6–7 years was similar between the 2 treatment groups (3.8%). The incidence of vertebral fractures did not change in the 7-year risedronate group during the 6–7 years as compared to 4–5 years, while a significant reduction was observed in the placebo group that switched to risedronate treatment during years 6–7. The incidence of nonvertebral fractures was 7.4% and 6.0% in the placebo/risedronate and risedronate groups, respectively, during years 6–7. Urinary N-telopeptide decreased from baseline by 54% and 63% at 3 months and 7 years, respectively, in the risedronate group. The increases in BMD from baseline after 5 years of risedronate treatment were maintained or increased further during years 6–7; lumbar spine BMD after 5 and 7 years of risedronate treatment increased from baseline by 8.8% and 11.5%, respectively, for this extension study population. Risedronate was well tolerated and the occurrence of upper gastrointestinal adverse events was low. After 7 years of continuous risedronate treatment there were significant increases in BMD and decreases in bone turnover to within premenopausal levels and there was no indication of any loss of anti-fracture efficacy.