The quantitative ADAM questionnaire: a new tool in quantifying the severity of hypogonadism

Androgen deficiency is a pervasive problem in the older male population and is thought to be responsible for many symptoms once considered to be the result of normal aging. Numerous methods have been proposed to facilitate the detection of men at risk for androgen deficiency. In this article, we propose a novel screening tool, the quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire and report its successful use in quantifying the severity of androgen deficiency in a group of older men. Fifty-seven males scheduled to undergo radical prostatectomy for prostate cancer completed the qADAM as well as the Sexual Health Inventory for Men (SHIM) and the Expanded Prostate Cancer Index Composite hormonal/sexual (EPICh/EPICs) questionnaires. Thirty-four men also had serum testosterone levels measured for comparison. The qADAM showed statistically significant correlation to the SHIM (P=0.001), EPICh (P=0.016), EPICs (P=<0.001), and serum testosterone (P=0.046). The qADAM represents a viable alternative to existing questionnaires used to detect androgen deficiency and to assess response to treatment

Non-invasive muscle contraction assay to study rodent models of sarcopenia

<p>Abstract</p> <p>Background</p> <p>Age-related sarcopenia is a disease state of loss of muscle mass and strength that affects physical function and mobility leading to falls, fractures, and disability. The need for therapies to treat age-related sarcopenia has attracted intensive preclinical research. To facilitate the discovery of these therapies, we have developed a non-invasive rat muscle functional assay system to efficiently measure muscle force and evaluate the efficacy of drug candidates.</p> <p>Methods</p> <p>The lower leg muscles of anesthetized rats are artificially stimulated with surface electrodes on the knee holders and the heel support, causing the lower leg muscles to push isometric pedals that are attached to force transducers. We developed a stimulation protocol to perform a fatigability test that reveals functional muscle parameters like maximal force, the rate of fatigue, fatigue-resistant force, as well as a fatigable muscle force index. The system is evaluated in a rat aging model and a rat glucocorticoid-induced muscle loss model</p> <p>Results</p> <p>The aged rats were generally weaker than adult rats and showed a greater reduction in their fatigable force when compared to their fatigue-resistant force. Glucocorticoid treated rats mostly lost fatigable force and fatigued at a higher rate, indicating reduced force from glycolytic fibers with reduced energy reserves.</p> <p>Conclusions</p> <p>The involuntary contraction assay is a reliable system to assess muscle function in rodents and can be applied in preclinical research, including age-related sarcopenia and other myopathy.</p

Morning vs evening dosing of the cathepsin K inhibitor ONO-5334: effects on bone resorption in postmenopausal women in a randomized, phase 1 trial

SUMMARY: The cathepsin K inhibitor, ONO-5334, improves bone mineral density in postmenopausal women with osteoporosis. The effects of morning versus evening administration of ONO-5334 were investigated by measuring bone turnover marker levels in healthy postmenopausal women. Morning administration of ONO-5334 showed a more consistent suppressive effect on bone resorption than evening administration. INTRODUCTION: Bone turnover is thought to be subject to circadian variation, and the efficacy of osteoporosis treatments may be optimized by regulating the time of dosing. This study assessed whether evening administration of the cathepsin K inhibitor, ONO-5334, had a differential effect on the bone turnover marker, C-terminal telopeptide of type I collagen (CTX-I), compared with morning administration. METHODS: This was a single-center, single blind crossover study. Fourteen healthy postmenopausal women were assigned to receive ONO-5334 150 mg once daily for 5 days in each period; they were randomized to receive either evening doses in the first period and morning doses in the second or vice versa. Serum and urinary levels of CTX-I were measured throughout the study. RESULTS: Both regimens showed similar patterns of reduction in serum and urinary CTX-I; however, CTX-I suppression was more consistently >60% over 24 h following morning administration. Morning administration led to 6% greater suppression of 24-h serum CTX-I area under the effect curve (AUE; 69 vs 63%; P < .05) and 7% greater suppression of urinary CTX-I/creatinine AUE (93 vs 86%; P < .01) than evening administration. Higher plasma ONO-5334 concentrations were observed between 12 and 24 h postdose following morning administration, with mean trough concentrations for the morning and evening regimens at 9.4 and 4.0 ng/mL, respectively. There were no safety findings of concern. CONCLUSION: Morning dosing of ONO-5334 is more efficacious at reducing markers of bone turnover in healthy postmenopausal women than evening dosing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01384188, registered on June 27, 2011 EudraCT: 2008-006284-37 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-015-3342-4) contains supplementary material, which is available to authorized users

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

<p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

Advances in Glucocorticoid-Induced Osteoporosis

Glucocorticoid-induced osteoporosis (GIOP) is one of the most important side effects of glucocorticoid use, as it leads to an increased risk of fractures. Recently, many published studies have focused on the cellular and molecular mechanisms of bone metabolism, the pathophysiology of GIOP, and the intervention options to prevent GIOP. In this review, recent advances in GIOP are summarized, particularly recent progress in our understanding of the mechanisms of GIOP resulting in improved insight that might result in the development of new treatment options in the near future

A systematic review and meta-analysis of bone metabolism in prostate adenocarcinoma

<p/> <p>Background</p> <p>Osteoporosis could be associated with the hormone therapy for metastatic prostate carcinoma (PCa) and with PCa <it>per se</it>. The objective of this review is to determine the incidence of bone loss and osteoporosis in patients with PCa who are or are not treated with hormone therapy (ADT).</p> <p>Methods</p> <p>The Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published studies on prostate cancer and bone metabolism. The outcomes assessed were: fracture, osteoporosis and osteopenia.</p> <p>Results</p> <p>Thirty-two articles (116,911 participants) were included in the meta-analysis. PCa patients under ADT had a higher risk of osteoporosis (RR, 1.30; <it>p </it>< 0.00001) and a higher risk of fractures (RR, 1.17; <it>p </it>< 0.00001) as compared to patients not under ADT. The total bone mineral density was lower in patients under ADT when compared with patients not under ADT (<it>p </it>= 0.031) but it was similar to bone mineral density found in healthy controls (<it>p </it>= 0.895). The time of androgen deprivation therapy correlated negatively with lumbar spine and total hip bone mineral density (Spearman's rho = -0.490 and -0.773; <it>p </it>= 0.028 and 0.001, respectively) and with total hip <it>t </it>score (Spearman's rho = -0.900; <it>p </it>= 0.037).</p> <p>Conclusion</p> <p>We found consistent evidence that the use of androgen deprivation therapy in patients with PCa reduces bone mineral density, increasing the risk of fractures in these patients.</p