Bone Mineral Density and Androgen Levels in Elderly Males

Rapado, A; Hawkins, Federico; Sobrinho, L. G.; Díaz-Curiel, Manuel; Galvao-Telles, A.; Arver, Stefan; Gomes, José Melo; Mazer, Norman A.; Costa, Joaquim Garcia e; Horcajada, C; López-Gavilanes, E.; Mascarenhas, Mário Rui; Papapietro, K.; Alvarez, MA; Pereira, Ma C.; Martínez, Guillermo; Valverde, Isabel; García, Javier de Santiago; Carballal, J. J.; García, Irene

doi:10.1007/s002239900726

Cited by 59 publications

(23 citation statements)

References 19 publications

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“…Low testosterone levels may be a risk factor for cardiovascular disease [21] and the low BMD might reflect its association with BMD and risk of mortality. Low testosterone may also be involved in the stimulation of biologic response to vitamin D in the target organs, such as intestine and bone [22], although a more recent study has shown that sex male hormones are not correlated with the decrease in hip BMD [23]. The findings raise questions regarding the role of androgens in cardiovascular risk and lipid profile and their possible association with BMD.…”

Section: Discussionmentioning

confidence: 95%

Bone Mineral Density at the Hip Predicts Mortality in Elderly Men

2001

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Low bone density as assessed by calcaneal ultrasound has been associated with mortality in elderly men and women. We examined the relationship between bone density measured at the hip and all cause and cardiovascular mortality in elderly men. Men aged 65-76 years from the general community were recruited from general practices in Cambridge between 1991 and 1995. At baseline survey, data collection included health questionnaires, measures of anthropometry and cardiovascular risk factors, as well as bone mineral density (BMD) measured using dual energy X-ray absorptiometry. All men have been followed up for vital status up to December 1999. BMD was significantly inversely related to mortality from all causes and cardiovascular disease, with decreasing rates with increasing bone density quartile, and an approximate halving of risk between the bottom and top quartile (p < 0.002, test for trend all causes and p < 0.025, test for trend for cardiovascular deaths). In multivariate analyses using the Cox proportional hazards model, an increase of 1 standard deviation (0.144 g/cm2) in total hip bone density was significantly associated with an age-adjusted 0.77 relative risk (95% CI 0.66-0.91) for all-cause mortality and 0.76 relative risk (95% CI 0.62-0.93) for cardiovascular disease mortality. The association remained significant after adjusting for age, body mass index, cigarette smoking status, serum cholesterol, systolic blood pressure, past history of heart attack, stroke or cancer and other lifestyle factors which included use of alcohol, physical activity and general health status. Low bone density at the hip is thus a strong and independent predictor of all-cause and cardiovascular mortality in older men.

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Section: Discussionmentioning

confidence: 95%

Bone Mineral Density at the Hip Predicts Mortality in Elderly Men

2001

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“…Numerous studies investigated the putative physiological relationship between circulating levels of 25OHD 3 /1,25(OH) 2 D, the activity of VDR and VD metabolizing enzymes, and serum testosterone and estradiol levels in both animals and humans (Tanaka et al 1976, Hyldstrup et al 1984, Small et al 1984, Hochberg et al 1985, Krabbe et al 1986, Sonnenberg et al 1986, Hagenfeldt et al 1992, Morley et al 1993, Inpanbutr et al 1996, Otremski et al 1997, Rapado et al 1999, Kinuta et al 2000, van Abel et al 2002, Braga et al 2002, Van Cromphaut et al 2003, Echchgadda et al 2004, Valimaki et al 2004, Kastelan et al 2009, Fleet & Schoch 2010, Krishnan et al 2010a, 2010b, Meng et al 2010, Pilz et al 2011, Ramlau-Hansen et al 2010, Wehr et al 2010, Ceglia et al 2011, Foresta et al 2011, Lundqvist et al 2011, Lee et al 2012. It has been shown that estrogen promotes the two-step activation of cholecalciferol to 1,25(OH) 2 D 3 and reinforces a positive effect on calcium homeostasis through a direct stimulatory effect on intestinal calcium absorption.…”

Section: Vd Regulates Biosynthesis Of Estradiol and Testosteronementioning

confidence: 99%

Vitamin D metabolism, sex hormones, and male reproductive function

Jensen¹

2012

Reproduction

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The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

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“…In general, correlations between bone mass and serum androgen concentrations in adult men have been either weak or insignificant [17,42,48]. Furthermore, many of the various clinical trials examining androgen therapy have been unable to demonstrate robust effects on bone mass, including treatment with anabolic steroids [11].…”

Section: Introductionmentioning

confidence: 99%

Targeting of androgen receptor in bone reveals a lack of androgen anabolic action and inhibition of osteogenesis

Wiren

Semirale

Zhang

et al. 2008

Bone

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Androgens are anabolic hormones that affect many tissues, including bone. However, an anabolic effect of androgen treatment on bone in eugonadal subjects has not been observed and clinical trials have been disappointing. The androgen receptor (AR) mediates biological responses to androgens. In bone tissue, both AR and the estrogen receptor (ER) are expressed. Since androgens can be converted into estrogen, the specific role of the AR in maintenance of skeletal homoeostasis remains controversial. The goal of this study was to use skeletally targeted overexpression of AR in differentiated osteoblasts as a means of elucidating the specific role(s) for AR transactivation in the mature bone compartment. Transgenic mice overexpressing AR under the control of the 2.3-kb α1 (I)-collagen promoter fragment showed no difference in body composition, testosterone, or 17β-estradiol levels. However, transgenic males have reduced serum osteocalcin, CTx and TRAPC5b levels, and a bone phenotype was observed. In cortical bone, high-resolution micro-computed tomography revealed no difference in periosteal perimeter but a significant reduction in cortical bone area due to an enlarged marrow cavity. Endocortical bone formation rate was also significantly inhibited. Biomechanical analyses showed decreased whole bone strength and quality, with significant reductions in all parameters tested. Trabecular morphology was altered, with increased bone volume comprised of more trabeculae that were closer together but not thicker. Expression of genes involved in bone formation and bone resorption was significantly reduced. The consequences of androgen action are compartment-specific; anabolic effects are exhibited exclusively at periosteal surfaces, but in mature osteoblasts androgens inhibited osteogenesis with detrimental effects on matrix quality, bone fragility and whole bone strength. Thus, the present data demonstrate that enhanced androgen signaling targeted to bone results in low bone turnover and inhibition of bone formation by differentiated osteoblasts. These results indicate that direct androgen action in mature osteoblasts is not anabolic, and raise concerns regarding anabolic steroid abuse in the developing skeleton or high-dose treatment in eugonadal adults.

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Bone Mineral Density and Androgen Levels in Elderly Males

Cited by 59 publications

References 19 publications

Bone Mineral Density at the Hip Predicts Mortality in Elderly Men

Bone Mineral Density at the Hip Predicts Mortality in Elderly Men

Vitamin D metabolism, sex hormones, and male reproductive function

Targeting of androgen receptor in bone reveals a lack of androgen anabolic action and inhibition of osteogenesis

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