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Influence of aromatase inhibition on the bone-protective effects of testosterone.

ABSTRACT: The influence of the aromatase enzyme in androgen-induced bone maintenance after skeletal maturity remains somewhat unclear. Our purpose was to determine whether aromatase activity is essential to androgen-induced bone maintenance. Ten-month-old male Fisher 344 rats (n = 73) were randomly assigned to receive Sham surgery, orchiectomy (ORX), ORX + anastrozole (AN; aromatase inhibitor), ORX + testosterone-enanthate (TE, 7.0 mg/wk), ORX + TE + AN, ORX + trenbolone-enanthate (TREN; nonaromatizable, nonestrogenic testosterone analogue; 1.0 mg/wk), or ORX + TREN + AN. ORX animals exhibited histomorphometric indices of high-turnover osteopenia and reduced cancellous bone volume compared with Shams. Both TE and TREN administration suppressed cancellous bone turnover similarly and fully prevented ORX-induced cancellous bone loss. TE- and TREN-treated animals also exhibited greater femoral neck shear strength than ORX animals. AN co-administration slightly inhibited the suppression of bone resorption in TE-treated animals but did not alter TE-induced suppression of bone formation or the osteogenic effects of this androgen. In TREN-treated animals, AN co-administration produced no discernible effects on cancellous bone turnover or bone volume. ORX animals also exhibited reduced levator ani/bulbocavernosus (LABC) muscle mass and elevated visceral adiposity. In contrast, TE and TREN produced potent myotrophic effects in the LABC muscle and maintained fat mass at the level of Shams. AN co-administration did not alter androgen-induced effects on muscle or fat. In conclusion, androgens are able to induce direct effects on musculoskeletal and adipose tissue, independent of aromatase activity.

SUBMITTER: Beck DT

PROVIDER: S-EPMC8366408 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Influence of aromatase inhibition on the bone-protective effects of testosterone.

Beck Darren T DT Yarrow Joshua F JF Beggs Luke A LA Otzel Dana M DM Ye Fan F Conover Christine F CF Miller Julie R JR Balaez Alexander A Combs Sarah M SM Leeper Alicia M AM Williams Alyssa A AA Lachacz Stephanie A SA Zheng Nigel N Wronski Thomas J TJ Borst Stephen E SE

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20141101 11

The influence of the aromatase enzyme in androgen-induced bone maintenance after skeletal maturity remains somewhat unclear. Our purpose was to determine whether aromatase activity is essential to androgen-induced bone maintenance. Ten-month-old male Fisher 344 rats (n = 73) were randomly assigned to receive Sham surgery, orchiectomy (ORX), ORX + anastrozole (AN; aromatase inhibitor), ORX + testosterone-enanthate (TE, 7.0 mg/wk), ORX + TE + AN, ORX + trenbolone-enanthate (TREN; nonaromatizable, ...[more]

PMID: 24764121

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Project description:BACKGROUND:Testosterone deficiency (TD) may induce a series of clinical symptoms. Studies have shown that testosterone supplementation may prevent these unfavourable symptoms and improve patients' quality of life. Given the conflicting findings across studies, this systematic review aims to evaluate the effects and risks associated with testosterone supplementation in middle-aged or aging males with TD. METHODS:Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane. Library were searched to December 2019. The risk of bias of individual included studies and the quality of the aggregate evidence were assessed using the GRADE approach. Our primary outcome was bone mineral density (BMD). Meta-analyses were performed. This systematic review was reported according to the PRISMA statement. RESULTS:A total of 52 randomized controlled trials (RCTs) were included. When compared with placebo, testosterone supplementation did not increase total BMD (short-term: 1081 participants, MD - 0.01 g/cm2, 95% CI - 0.02 g/cm2 to 0.01 g/cm2; long-term: 156 participants, MD 0.04 g/cm2, 95% CI - 0.07 g/cm2 to 0.14 g/cm2), lumbar spine, hip, or femur neck BMD. Furthermore, testosterone supplementation did not decrease the risk of falling or fracture. Lastly, it was found that testosterone supplementation did not increase the risk of cardiovascular events (1374 participants, RR 1.28, 95% CI 0.62 to 2.64), all-cause mortality (729 participants, RR 0.55, 95% CI 0.29 to 1.04), or prostatic events. However, testosterone supplementation may improve sexual function and quality of life (1328 participants, MD -1.32, 95% CI - 2.11 to - 0.52). CONCLUSIONS:The effect of testosterone supplementation on BMD and the risk of falls or fracture remains inconclusive. However, supplementation may benefit patients in the areas of sexual function and quality of life without increasing the risk of cardiovascular events, all-cause mortality, or prostatic events. RCTs with a longer follow-up period are still required. TRIAL REGISTRATION:We registered our protocol in PROSPERO (CRD42018109738).

Project description:Aromatase inhibitor treatment in breast cancer is associated with accelerated bone loss and an increased risk of fracture. Bisphosphonates (BPs) are the mainstay treatment of aromatase inhibitor-associated bone loss (AIBL), which might improve femoral bone at key locations prone to fracture. To test this hypothesis, we performed three-dimensional cortical bone mapping based on quantitative computed tomography (QCT) scans in postmenopausal women with early breast cancer who were receiving aromatase inhibitors. Data of subjects who had both baseline and at least one follow-up QCT at Severance Hospital (South Korea) between 2005 and 2015 were analyzed (BP users, n = 93; BP non-users, n = 203). After exclusion of BP users with low medication persistence (proportion of days covered: <50%), BP users and non-users were 1:1 matched (n = 54 for each group) in terms of age, lumbar spine volumetric bone mineral density (LSvBMD), femoral neck areal BMD (FNaBMD), and total hip areal BMD (THaBMD). During a median follow-up of 2.1 years, BP use attenuated bone loss in LSvBMD (+7.2% vs. -3.8%, p < 0.001), FNaBMD (+1.3% vs. -2.7%, p < 0.001), and THaBMD (-0.3% vs. -2.5%, p = 0.024). BP had a protective effect on cortical parameters of femoral bone: estimated cortical thickness (CTh) (+3.3% vs. + 0.1%, p = 0.007) and cortical mass surface density (CMSD, cortical mass per unit surface area was calculated by multiplying cortical BMD with CTh) (+3.4% vs. -0.3%, p < 0.001). CMSD increased by up to 15% at key locations such as the superior part of the femoral neck and greater trochanter. BP prevented the thinning of average CTh of the femoral neck (-1.4% vs. -6.1%, p < 0.001), particularly at the superior anterior quadrant of femoral neck (absolute difference: +12.8% point vs. non-users). Compared to BP non-users, BP users had improved cross-sectional moment of inertia (+4.4% vs. -0.7%, p = 0.001) and less increase in buckling ratio (+1.3% vs. + 7.5%, p < 0.001). In summary, BP use prevented cortical bone deficits observed in AIBL at key locations of the proximal femur.

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Dataset Information

Influence of aromatase inhibition on the bone-protective effects of testosterone.

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Influence of aromatase inhibition on the bone-protective effects of testosterone.

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