Sex Steroid Actions in Male Bone

Vanderschueren, Dirk; Laurent, Michaël; Claessens, Frank; Gielen, Evelien; Lagerquist, Marie K; Vandenput, Liesbeth; Börjesson, Anna; Ohlsson, Claes

doi:10.1210/er.2014-1024

Cited by 255 publications

(275 citation statements)

References 444 publications

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“…Bone mass is reduced in male mice with null mutations in either the ER-α gene or the aromatase gene, demonstrating a clear effect of estrogens on bone (21)(22)(23). Bone mass is also reduced in male mice with null mutations in the AR gene, indicating that androgens also exert effects on bone (24).…”

Section: Discussionmentioning

confidence: 99%

Gonadal steroid–dependent effects on bone turnover and bone mineral density in men

Finkelstein¹,

Lee²,

Leder³

et al. 2016

Journal of Clinical Investigation

161

119

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METHODS.One hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men. 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.FUNDING. AbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.

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Section: Discussionmentioning

confidence: 99%

Gonadal steroid–dependent effects on bone turnover and bone mineral density in men

Finkelstein¹,

Lee²,

Leder³

et al. 2016

Journal of Clinical Investigation

161

119

View full text Add to dashboard Cite

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“…The substantial hypoestrogenism induced by adjuvant hormonal therapy with aromatase inhibitors or tamoxifene + LHRH analogues in women with breast cancer, and the androgen deprivation induced by GnRH agonists and/or antiandrogens in men with prostate cancer, lead to an accelerated bone loss and rapidly increase fracture risk (50)(51)(52)(53). There is a substantial difference in the rate of bone turnover, and thereby in the rate of bone loss, among different patient populations (men, premenopausal and postmenopausal women at diagnosis) and with different types of antihormonal therapy (chemotherapy-induced menopause, GnRH with or without tamoxifen, or aromatase inhibitors from oils, androgen deprivation therapy).…”

Section: Adjuvant Hormonal Therapymentioning

confidence: 99%

Guidelines for the diagnosis, prevention and management of osteoporosis

et al. 2016

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Osteoporosis poses a significant public health issue. National Societies have developed Guidelines for the diagnosis and treatment of this disorder with an effort of adapting specific tools for risk assessment on the peculiar characteristics of a given population. The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has recently revised the previously published Guidelines on the diagnosis, riskassessment, prevention and management of primary and secondary osteoporosis. The guidelines were first drafted by a working group and then approved by the board of SIOMMMS. Subsequently they received also the endorsement of other major Scientific Societies that deal with bone metabolic disease. These recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on leading experts' experience and opinion, and on good clinical practice. The osteoporosis prevention should be based on the elimination of specific risk factors. The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk, and this is the case only when the risk of fracture is rather high as measured with variables susceptible to pharmacological effect. DeFRA (FRAX® derived fracture risk assessment) is recognized as a useful tool for easily estimate the long-term fracture risk. Several secondary forms of osteoporosis require a specific diagnostic and therapeutic management

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“…In addition, an indirect contribution of androgen deficiency to fracture risk in men due to reduced muscle mass and increased fall risk is also plausible. Finally, it is important to mention the potential contribution of nongenomic and ligand-independent effects of both testosterone and estrogen on bone health, although existing in vivo animal data indicate that such factors do not generally compensate for the negative skeletal effects of frank sex-steroid deficiency (32).…”

Section: Current and Previous Findingsmentioning

confidence: 99%