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Background: Endurance exercise has the potential to affect reproductive function, with amenorrhea in female athletes. However, most studies focus on women. Evidence on the association between endurance exercise and male fertility is limited. Objective: To synthesise existing literature on exercise-induced alterations in semen parameters and to assess the clinical impact on male fertility. Methods: Studies reporting on the association between semen parameters and endurance exercise in healthy men were eligible. Men attending fertility clinics were excluded. We searched MEDLINE (PubMed), Embase, SPORTDiscus, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) from their inception to May 28th 2022. JBI Critical Appraisal Tool was used to assess the potential risk of bias. Results: Thirteen studies met inclusion criteria, reporting on 280 subjects. Eight articles reported on endurance runners, three on cyclists and four on triathletes. Four studies did not find any statistically significant sperm alterations. Five reported significant changes in semen parameters, but these were not clinically relevant, as semen parameters remained well above World Health Organisation (WHO) thresholds. Four articles reported a decrease in semen quality with potential clinical consequences as they found a reduced number of sperm cells exhibiting normal morphology in cyclists and triathletes and a greater amount of DNA fragmentation in triathletes. Conclusion: Endurance exercise can have a negative effect on semen quality, although rarely with a clinically relevant impact on male fertility. Evidence is however limited, with poor quality of the included studies. Registration: PROSPERO International prospective register of systematic reviews (CRD42022336753). Key Points: Results suggest that endurance exercise can decrease semen quality, although without a clinically relevant impact on male fertility potential. The available evidence is limited and lacks comparability due to poor methodology. High quality studies are necessary to further assess the relationship between endurance exercise and semen quality. [ABSTRACT FROM AUTHOR]

Osteoporosis does not only affect postmenopausal women, but also ageing men. The burden of disease is projected to increase with higher life expectancy both in females and males. Importantly, osteoporotic men remain more often undiagnosed and untreated compared to women. Sex steroid deficiency is associated with bone loss and increased fracture risk, and circulating sex steroid levels have been shown to be associated both with bone mineral density and fracture risk in elderly men. However, in contrast to postmenopausal osteoporosis, the contribution of relatively small decrease of circulating sex steroid concentrations in the ageing male to the development of osteoporosis and related fractures, is probably only minor. In this review we provide several clinical and preclinical arguments in favor of a 'bone threshold' for occurrence of hypogonadal osteoporosis, corresponding to a grade of sex steroid deficiency that in general will not occur in many elderly men. Testosterone replacement therapy has been shown to increase bone mineral density in men, however data in osteoporotic ageing males are scarce, and evidence on fracture risk reduction is lacking. We conclude that testosterone replacement therapy should not be used as a sole bone-specific treatment in osteoporotic elderly men. [ABSTRACT FROM AUTHOR]

Introduction: The phase 2 MANTA and MANTA-RAy studies were developed in consultation with global regulatory authorities to investigate potential impacts of filgotinib, a Janus kinase 1 preferential inhibitor, on semen parameters in men with active inflammatory diseases. Here we describe the methods and rationale for these studies. Methods and Rationale: The MANTA and MANTA-RAy studies included men (aged 21–65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases, respectively. Participants had no history of reproductive health issues, and the following semen parameter values (≥ 5th percentile of World Health Organization reference values) at baseline: semen volume ≥ 1.5 mL, total sperm/ejaculate ≥ 39 million, sperm concentration ≥ 15 million/mL, sperm total motility ≥ 40% and normal sperm morphology ≥ 30%. Each trial included a 13-week, randomized, double-blind, placebo-controlled period (filgotinib 200 mg vs placebo, up to N = 125 per arm), for pooled analysis of the week-13 primary endpoint (proportion of participants with ≥ 50% decrease from baseline in sperm concentration). All semen assessments were based on two samples (≤ 14 days apart) to minimize effects of physiological variation; stringent standardization processes were applied across assessment sites. From week 13, MANTA and MANTA-RAy study designs deviated owing to disease-specific considerations. All subjects with a ≥ 50% decrease in sperm parameters continued the study in the monitoring phase until reversibility, or up to a maximum of 52 weeks, with standard of care as treatment. Overall conclusions from MANTA and MANTA-RAy will be based on the totality of the data, including secondary/exploratory measures (e.g. sperm motility/morphology, sex hormones, reversibility of any effects on semen parameters). Conclusions: Despite the complexities, the MANTA and MANTA-RAy studies form a robust trial programme that is the first large-scale, placebo-controlled evaluation of potential impacts of an advanced IBD and rheumatic disease therapy on semen parameters. Trial Registration: EudraCT numbers 2017-000402-38 and 2018-003933-14; ClinicalTrials.gov identifiers NCT03201445 and NCT03926195. Plain Language Summary: Filgotinib is a treatment for patients with ulcerative colitis and rheumatoid arthritis, and is being studied in other inflammatory diseases. Filgotinib works by blocking Janus kinase 1, an intracellular protein involved in inflammatory signalling processes. We designed the MANTA and MANTA-RAy trials with global health agencies to find out if filgotinib decreases the quality of semen in men with active inflammatory bowel disease (ulcerative colitis or Crohn's disease) (MANTA) or rheumatic disease (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or non-radiographic axial spondylitis) (MANTA-RAy). This paper describes the design of the two trials. Patients had normal sperm measurements and could not have had previous reproductive health issues. Nearly 250 patients were included in each trial. In both MANTA and MANTA-RAy, half of the patients were treated with 200 mg of filgotinib once a day for 13 weeks, and the other half with placebo. We determined if any patients had a decrease in number of sperm cells per millilitre (sperm concentration) by at least half after 13 weeks of treatment. We then monitored any patients who had such a decrease in sperm concentration for up to 52 weeks (while they received standard of care treatment) or until the decrease was reversed. The conclusions from the trials will be in a different paper and will be based on all the final data, including changes in sex hormones. This is the first large-scale clinical trial programme to measure the effect of a treatment on sperm in men with inflammatory bowel disease or rheumatic diseases. [ABSTRACT FROM AUTHOR]

Diversity in lifestyles and socioeconomic status among European populations, and recent socio-political and economic changes in transitional countries, may affect changes in adiposity. We aimed to determine whether change in the prevalence of obesity varies between the socio-politically transitional North-East European (Łódź, Poland; Szeged, Hungary; Tartu, Estonia), and the non-transitional Mediterranean (Santiago de Compostela, Spain; Florence, Italy) and North-West European (Leuven, Belgium; Malmö, Sweden; Manchester, UK) cities. This prospective observational cohort survey was performed between 2003 and 2005 at baseline and followed up between 2008 and 2010 of 3369 community-dwelling men aged 40-79 years. Main outcome measures in the present paper included waist circumference, body mass index and mid-upper arm muscle area. Baseline prevalence of waist circumference ≥ 102 cm and body mass index ≥ 30 kg/m, respectively, were 39.0, 29.5 % in North-East European cities, 32.4, 21.9 % in Mediterranean cities, and 30.0, 20.1 % in North-West European cities. After median 4.3 years, men living in cities from transitional countries had mean gains in waist circumference (1.1 cm) and body mass index (0.2 kg/m), which were greater than men in cities from non-transitional countries ( P = 0.005). North-East European cities had greater gains in waist circumference (1.5 cm) than in Mediterranean cities ( P < 0.001). Over 4.3 years, the prevalence of waist circumference ≥ 102 cm had increased by 13.1 % in North-East European cities, 5.8 % in the Mediterranean cities, 10.0 % in North-West European cities. Odds ratios (95 % confidence intervals), adjusted for lifestyle factors, for developing waist circumference ≥ 102 cm, compared with men from Mediterranean cities, were 2.3 (1.5-3.5) in North-East European cities and 1.6 (1.1-2.4) in North-West European cities, and 1.6 (1.2-2.1) in men living in cities from transitional, compared with cities from non-transitional countries. These regional differences in increased prevalence of waist circumference ≥ 102 cm were more pronounced in men aged 60-79 years than in those aged 40-59 years. Overall there was an increase in the prevalence of obesity (body mass index ≥ 30 kg/m) over 4.3 years (between 5.3 and 6.1 %) with no significant regional differences at any age. Mid-upper arm muscle area declined during follow-up with the greatest decline among men from North-East European cities. In conclusion, increasing waist circumference is dissociated from change in body mass index and most rapid among men living in cities from transitional North-East European countries, presumably driven by economic and socio-political changes. Information on women would also be of value and it would be of interest to relate the changes in adiposity to dietary and other behavioural habits. [ABSTRACT FROM AUTHOR]

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the method of choice for quantifying small molecules in research and clinical setting. Although there is a large toolkit to increase quantification levels for LC-MS/MS, these techniques are sometimes insufficient to attain the needed limits of quantification (LOQs) or the method becomes too impractical for routine use. We examined the possibilities and limitations of signal summing, an under-utilized, easy-to-apply practice to increase LOQs for an immunosuppressant LC-MS/MS method. The limits of signal summing for everolimus were tested by running samples of everolimus at three concentrations in triplicate programming, increasing amounts of identical transitions in a constant cycle time up to the maximum number the software permitted to sum. The increase in peak area and the signal-to-noise ratio were determined. The effect on imprecision of peak areas and response ratios was evaluated by injection of a low concentration of everolimus tenfold using respectively one and five identical transitions, retaining an identical ion counting time. We compared the imprecision, LOQ, and recovery for our routine everolimus method (using one transition for everolimus and one for d3-everolimus) and an adapted method summing three identical transitions for everolimus (and one for d3-everolimus). The increase in signal was close to the theoretically expected one with a larger experimental spread for everolimus once more than five transitions were used. There was no clear beneficial effect of summing on imprecision. The adapted everolimus method showed a lower LOQ, but comparable imprecision and recovery as the routine method. Quantification levels can be improved by signal summing. No clear effect on imprecision was observed. [ABSTRACT FROM AUTHOR]

The need for a routinely applicable assay to measure low estradiol levels in adult men, postmenopausal women, and young adolescents was recently discussed in an Endocrine Society position statement. Our aim was to develop a sensitive liquid chromatography-tandem mass spectrometry method for estradiol and estrone in human serum without the need for derivatization or extended extraction protocols. After protein precipitation of serum with a mixture of methanol/acetonitrile (85/15) ( v/ v) containing isotopic internal standards (17β-estradiol-16,16,17- d and estrone-2,3,4-C), we quantified estradiol and estrone by two-dimensional liquid chromatography-tandem mass spectrometry with electrospray ionization in the negative mode monitoring 5 × 271.20→145.00 (17β-estradiol) and 269.20→145.00 (estrone). Sensitivity was increased by using fluoride and summation of 5 identical transitions for estradiol. Our method was analytically validated, compared against direct immunoassays using serum of 25 adult men, and clinically tested by measuring samples of 3 men at baseline and after chemical castration, 30 postmenopausal women and 15 patients receiving aromatase inhibitors. Total imprecision was below 20 % for the low quality controls. Limit of quantification was 1.3 ng/L (4.8 pmol/L) for estradiol and 1.2 ng/L (4.4 pmol/L) for estrone. Estradiol in Certified Reference Material BCR-576 was within specified uncertainty limits. No significant ion suppression or interference was observed. Our method showed modest correlation with direct immunoassay for estradiol ( r = 0.64) but no correlation for estrone ( r = 0.12). Patient sample results were within expected ranges. In conclusion, we developed a routinely applicable liquid chromatography-tandem mass spectrometry method for estradiol and estrone measurement which is sensitive enough for use in men, postmenopausal women, and young adolescents. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Androgens increase both the size and strength of skeletal muscle via diverse mechanisms. The aim of this review is to discuss the different cellular targets of androgens in skeletal muscle as well as the respective androgen actions in these cells leading to changes in proliferation, myogenic differentiation, and protein metabolism. Androgens bind and activate a specific nuclear receptor which will directly affect the transcription of target genes. These genes encode muscle-specific transcription factors, enzymes, structural proteins, as well as microRNAs. In addition, anabolic action of androgens is partly established through crosstalk with other signaling molecules such as Akt, myostatin, IGF-I, and Notch. Finally, androgens may also exert non-genomic effects in muscle by increasing Ca uptake and modulating kinase activities. In conclusion, the anabolic effect of androgens on skeletal muscle is not only explained by activation of the myocyte androgen receptor but is also the combined result of many genomic and non-genomic actions. [ABSTRACT FROM AUTHOR]

Cathepsin K is the protease that is primarily responsible for the degradation of bone matrix by osteoclasts. Inhibitors of cathepsin K are in development for treatment of osteoporosis. Currently available antiresorptive drugs interfere with osteoclast function. They inhibit both bone resorption and formation, due to the coupling between these processes. Cathepsin K inhibitors, conversely, target the resorption process itself and may not interfere with osteoclast stimulation of bone formation. In fact, when cathepsin K is absent or inhibited in mice, rabbits, or monkeys, bone formation is maintained or increased. In humans, inhibition of cathepsin K is associated with sustained reductions in bone resorption markers but with smaller and transient reductions in bone formation markers. The usefulness of cathepsin K inhibitors in osteoporosis is now being examined in phase 2 and phase 3 clinical trials of postmenopausal osteoporotic women. [ABSTRACT FROM AUTHOR]

We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (β [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (β [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (β [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (β [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (β [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the influence of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, and IGF-I on calcaneal ultrasound parameters in middle-aged and elderly European men. Men aged 40-79 years were recruited from population registers for participation in the European Male Ageing Study (EMAS). Subjects were invited by letter to complete a postal questionnaire and to attend for an interviewer-assisted questionnaire, quantitative ultrasound (QUS) of the calcaneus, and a fasting blood sample from which serum levels of IGFBP-1, IGFBP-3, IGF-I, estradiol (E(2)), and SHBG were assayed. The questionnaires included the Physical Activity Scale for the Elderly (PASE) and questions about smoking and alcohol consumption. Estimated bone mineral density (eBMD) was derived as a function of the QUS parameters speed of sound and broadband ultrasound attenuation. Height and weight were measured in all subjects. 3057 men, mean age 59.7 years (standard deviation 11.0) were included in the analysis. After adjusting for age, center, and BMI, higher levels of IGFBP-1 were associated with lower eBMD. Higher levels of both IGFBP-3 and IGF-I were associated with higher eBMD. After further adjustment for PASE score, current smoking, alcohol consumption, free E(2), and SHBG, IGFBP-3 and IGF-I, though not IGFBP-1, remained significantly associated with eBMD. IGFBP-1 was associated with bone health, though the effect could be explained by other factors. IGFBP-3 and IGF-I were independent determinants of bone health in middle-aged and elderly European men. [ABSTRACT FROM AUTHOR]

We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79 years were recruited from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance, and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight men, mean age 60.0 years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with a higher BUA (beta coefficient = 2.44 dB/ Mhz), SOS (beta = 6.83 m/s), and QUI (beta = 3.87). Compared to those who were inactive, those who walked or cycled more than an hour per day had a higher BUA (beta = 3.71 dB/Mhz), SOS (beta = 6.97 m/s), and QUI (beta = 4.50). A longer time to walk 50 ft was linked with a lower BUA (beta = -0.62 dB/ Mhz), SOS (beta = -1.06 m/s), and QUI (beta = -0.69). Smoking was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption. Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and reduce the risk of fracture in middle-aged and elderly European men. [ABSTRACT FROM AUTHOR]

Osteoporosis is a major cause of morbidity, mortality, and healthcare costs. The socioeconomic burden of osteoporosis is likely to increase dramatically if improvements in prevention are not made. Calcium supplementation effectively reduces the rate of bone loss in postmenopausal women, yet most women do not achieve an adequate calcium intake. In fact, use of calcium supplementation appears to have declined as the more effective antiresorptive therapies, such as bisphosphonates, have become available. Among patients prescribed bisphosphonates, calcium intake is often insufficient, despite the fact that adequate calcium intake may be necessary to gain the maximum benefits from antiresorptive therapy. In addition, because calcium interferes with bisphosphonate absorption, incorrect use of calcium may limit the efficacy of bisphosphonate therapy. This underscores the need for new initiatives to reduce the confusion surrounding appropriate calcium use during antiresorptive therapy. Co-packaging of bisphosphonates with calcium supplements is one strategy to help ensure that patients taking bisphosphonates not only achieve adequate calcium intake but also gain the maximum benefit from bisphosphonate therapy. [ABSTRACT FROM AUTHOR]

Identifying women with osteoporosis remains a clinical challenge, as it may not be feasible or cost-effective to recommend dual-energy X-ray absorptiometry (DXA) for all postmenopausal women. In this regard, quantitative ultrasound (QUS) has emerged as an attractive screening tool because of the (relatively) low cost and because QUS and DXA-assessed BMD appear to be equally predictive of future (hip) fracture risk. The objective of this study was to compare the ability of calcaneal QUS to identify osteoporosis with two alternative potential screening methods: digital X-ray radiogrammetry (DXR) and radiographic absorptiometry (RA). We enrolled a total of 221 postmenopausal community-dwelling Caucasian women aged 50-75 years. Bone mineral density (BMD) was measured at the lumbar spine and the total hip regions using DXA. Calcaneal ultrasound attenuation and velocity were assessed using QUS and metacarpal and phalangeal bone density were estimated by the use of DXR and RA, respectively. Receiver operating characteristic (ROC) curves were constructed by calculating the specificity and sensitivity of QUS, DXR, and RA at different cut-point values in discriminating osteoporosis, as defined by aT-score below -2.5 at the spine or hip using DXA, and the areas under the curves (AUCs) were computed. The sensitivity for identifying women with osteoporosis was 67.6% [95% confidence interval (CI), 50.2-82.0%] using QUS and was 76.9% (95% CI, 60.7-88.8%) and 82.9% (95% CI, 67.9-92.8%), respectively, using DXR and RA. The negative predictive value (NPV, the proportion of patients with a negative test who have no osteoporosis) was 90% for QUS, compared with an NPV of 94% for both DXR and RA. These data suggest that metacarpal DXR and phalangeal RA may be as effective as calcaneal QUS for targeting DXA testing in high-risk postmenopausal women. [ABSTRACT FROM AUTHOR]

The aim of this prospective study was to document the functional outcome and quality of life (QoL) over 1 year following hip fracture in elderly women. A total of 159 unselected elderly women with a first hip fracture were matched for age and residence with an equal number of control women. Functional status was measured by completing a Rapid Disability Rating Scale version 2 (RDRS-2) questionnaire [score ranging from 0 (best) to 54 (worse)], before hospital discharge and 12 months later. To examine longitudinal change in health-related QoL, fracture subjects and controls completed the Short Form 36 (SF-36) questionnaire. For the 134 women still alive at 1 year, the mean RDRS-2 score before hospital discharge was 16.2 (95% CI: 15.0–18.0) and 3.5 (2.6–4.3) in patients and controls, respectively (P<0.001). During the year following hospital discharge, the mean RDRS-2 score improved to 13.0 (11.1–14.1) in hip-fracture women and worsened to 4.3 (3.3–5.0) in the control group (differences with initial scores: P<0.001 in both groups). After adjustment for potential confounders (including age and comorbidity), the estimated functional decline attributable to a hip fracture was 24% in the first year. Poor functional status upon discharge was the strongest predictor of a poor functional status at 1 year. Overall, similar trends were observed when using SF-36 scores as compared with RDRS-2 scores. However, only 51% of the study population was able to complete the SF-36 questionnaire at discharge and after 1 year, and these subjects were considerably younger (P<0.001), had less cognitive impairment (P<0.001), and had better functional status (P<0.001) than those who were unable to complete the SF-36. For those women able to complete the SF-36 questionnaires, the mean SF-36 score before hospital discharge was 56.4 (95% CI: 51.9–60.9) and 71.1 (67.5–74.8) in patients and controls, respectively (P<0.001). During the year following hospital discharge, the mean SF-36 score improved significantly to 61.1 (56.5–65.7) in hip-fracture patients (P=0.03), but remained unchanged in the control group (P=0.23). Overall, the results of this study indicate that women who sustain a hip fracture continue to suffer from substantial functional impairment and loss in QoL at 1 year, despite a significant recovery during this 12-month period. Function upon hospital discharge is the strongest predictor of functional status 1 year later. Assessing QoL in hip fracture women through self-administered questionnaires is subject to considerable bias due to non-response. [ABSTRACT FROM AUTHOR]

Of all fractures being linked with osteoporosis, those of the hip are the most important in terms of early death, functional dependence, and costs of care. Reduction of these adverse outcomes depends on preventing hip fractures caused by a fall on a biomechanically compromised proximal femur. In order to allow targeting of preventive care, there is considerable interest in predicting the risk of hip fracture. Bone densitometry is an established method to determine the risk of developing fractures. Recent studies, however, have identified additional factors which contribute to fracture risk independently of bone mass, suggesting that, in addition to taking measures that maintain bone density, risk factor modification may prove to be an effective strategy for preventing hip fracture. The aim of this article is to review current knowledge on clinical risk factors for hip fracture in elderly women. [ABSTRACT FROM AUTHOR]

Effects of androgen deficiency and androgen replacement on bone density, as measured with dual-energy X-ray absorptiometry (DXA) and single photon absorptiometry (SPA), cortical ratio (cortical thickness/outside bone diameter x 100), and biomechanical properties were evaluated in 14-month-old (1 month after orchiectomy (orch) or sham-operation) and in 17-month-old (4 months after orch or sham) male rats. Whole femoral bone mineral content (BMC) and density (BMD) measured with DXA were not significantly decreased 1 month after orch. Whole femoral BMC and BMD were 10% and 8% lower in 4 months after orch (P < 0.01 and P < 0.001, respectively). This decrease was prevented by testosterone replacement. There was an excellent correlation (R = 0.99) between whole femoral BMC and femoral ash weight. Selective scanning of cortical and cancellous sites of the femur showed that both cancellous and cortical BMC and BMD were significantly decreased 4 months after orch. SPA of the right tibia confirmed a 7% decrease in cancellous BMC and BMD 4 months after orch (preventable by testosterone) but not in cortical BMD and BMC. Femoral cortical ratio decreased with age (47 +/- 2 in 14-month-old and 40 +/- 2 in 17-month-old sham rats versus 63 +/- 1 in 6-month-old male rats) due to a continuously enlarging femoral shaft. Androgen deficiency resulted in an even greater decrease of the cortical ratio 4 months after orch (36 +/- 2 in 17-month-old orch rats) that was again prevented by testosterone (47 +/- 3).(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

We investigated the effect of short-term, 1,25-dihydroxyvitamin D3 therapy (4 micrograms/day for 4 days) on calcium metabolism in 27 postmenopausal women (11 cases with osteoporosis and 16 cases with osteoarthritis). Bone mass at the axial and appendicular skeleton was higher in osteoarthritis than in osteoporosis. Initial values of calcium metabolism were similar. Osteoporotic and osteoarthritic patients responded with a similar significant increase in serum osteocalcin (+61% and +54%, respectively), fasting urinary calcium excretion (+178% and +124%, respectively) and 24 hour calcium excretion (+148% and +142%, respectively). Parathyroid hormone (PTH) levels decreased significantly in both groups (-30% and -18%, respectively). Osteoclastic bone resorption, evaluated by urinary hydroxyproline excretion, was not stimulated in either group. We conclude that in osteoporosis and also in osteoarthritis (1) 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) stimulation of osteoblast function is similar in production of osteocalcin; (2) the vitamin D target tissues react adequately to 1,25(OH)2D3 stimulation; (3) short-term high dose of 1,25(OH)2D3 does not stimulate bone resorption; and (4) the differences in bone mass between osteoarthritis and osteoporosis are not related to an alteration of the responsiveness to stimulation by 1,25 (OH)2D3. [ABSTRACT FROM AUTHOR]

Serum vitamin D metabolites and urinary calcium excretion; parameters of bone formation (serum alkaline phosphatase, serum osteocalcin); parameters of bone resorption (24 hour hydroxyprolinuria, 2 hour fasting urinary hydroxyproline/creatinine ratio); and parameters of cortical and trabecular bone density, parathyroid hormone (iPTH, COOH terminal assay), and serum minerals (calcium, phosphorus) were followed serially in 55 young adults (21 women and 34 men) from December 1985 until January 1987 at four different times during the year. The effect of a low-dose cyclooxygenase inhibitor (piroxicam 5 mg daily) on the same parameters of bone density and bone turnover when given from December until May, was also evaluated in this study. At the end of the treatment period parameters of bone turnover and bone density were comparable between placebo and piroxicam-treated groups. Therefore, the results of all subjects were pooled in order to investigate seasonal variation. In both sexes, seasonal variation was found not only for 250HD3 but also for 1,25(OH)2D3, serum calcium and phosphorus, urinary calcium excretion, and for bone density at the lumbar spine. Parameters of bone formation (serum osteocalcin and alkaline phosphatase), bone resorption (24 hour urinary hydroxyprolinuria and fasting urinary hydroxyproline/creatinine ratio) and PTH were influenced by this seasonal variation. We conclude that in young adults, a significant seasonal variation occurs, with low winter and high summer values, for serum 25 and 1,25(OH)2D3 for urinary calcium apparently without important influence on parameters of bone turnover or parathyroid activity and for lumbar spine density. Treatment with a low-dose cyclooxygenase inhibitor was without influence on the observed changes. [ABSTRACT FROM AUTHOR]

We measured bone osteocalcin concentrations in EDTA extracts from iliac crest cortical bone specimens obtained postmortem from 63 men and 71 women (age range 19-90 years), and serum osteocalcin levels in healthy blood donors, 49 men and 49 women (age range 21-65 years). Bone and serum osteocalcin concentrations were higher in men than in women, and an age-related decline was observed in both sexes. In women, however, a temporary increase in serum (P less than 0.05) osteocalcin was seen in the sixth decade. This study shows sex- and age-related changes in bone osteocalcin consistent with changes in serum osteocalcin, confirming that serum measurement of osteocalcin reflects bone levels. As osteocalcin reflects osteoblastic activity and thus bone formation, the overall decline in bone and serum osteocalcin in men and women, and the increase in serum osteocalcin in the sixth decade in women, indicate that aging is associated with a decrease in bone formation and turnover and that osteoblastic activity and bone turnover are stimulated at the menopause. [ABSTRACT FROM AUTHOR]

The vitamin D receptor is highly expressed in the gastrointestinal tract where it transacts gene expression. With current limited understanding of the interactions between the gut microbiome and vitamin D, we conduct a cross-sectional analysis of 567 older men quantifying serum vitamin D metabolites using LC-MSMS and defining stool sub-Operational Taxonomic Units from16S ribosomal RNA gene sequencing data. Faith's Phylogenetic Diversity and non-redundant covariate analyses reveal that the serum 1,25(OH)2D level explains 5% of variance in α-diversity. In β-diversity analyses using unweighted UniFrac, 1,25(OH)2D is the strongest factor assessed, explaining 2% of variance. Random forest analyses identify 12 taxa, 11 in the phylum Firmicutes, eight of which are positively associated with either 1,25(OH)2D and/or the hormone-to-prohormone [1,25(OH)2D/25(OH)D] "activation ratio." Men with higher levels of 1,25(OH)2D and higher activation ratios, but not 25(OH)D itself, are more likely to possess butyrate producing bacteria that are associated with better gut microbial health. Here, the authors investigate associations of vitamin D metabolites with gut microbiome in a cross-sectional analysis of 567 elderly men enrolled in the Osteoporotic Fractures in Men (MrOS) Study and find larger alpha-diversity correlates with high 1,25(OH)2D and high 24,25(OH)2D and higher ratios of activation and catabolism. [ABSTRACT FROM AUTHOR]

A new study has found eight single nucleotide polymorphisms in sex hormone-binding globulin that functionally affect its affinity for androgens or estrogens and other biochemical properties. This finding adds to growing concern about the ‘one size fits all’ approach in formulas to calculate free or bioavailable concentrations of estradiol and testosterone. [ABSTRACT FROM AUTHOR]

The article discusses a study on single nucleotide polymorphisms (SNPs) in sex hormone-binding globulin (SHBG) that affects its affinity for androgens or estrogens. Noted is the structure of each subunit of SHBG, which is consists of two laminin G-like domains. It is said that one of the implications of the findings of the study for clinical chemistry is that it calls for the reassessment of formulas use for calculating free or bioavailable sex steroids.

The authors discuss research on a composite five-year fracture prediction model for older women. They reference the study "Empirically Based Composite Fracture Prediction Model From the Global Longitudinal Study of Osteoporosis in Postmenopausal Women (GLOW)" by G. FitzGerald and colleagues published in the "Journal of Clinical Endocrinology and Metabolism" in 2013. They also discuss the genetic risk of fracture.