Androgen Supplementation in Eugonadal Men with Osteoporosis: Effects of Six Months' Treatment on Markers of Bone Formation and Resorption

Anderson, Fiona; Francis, Roger M.; Peaston, R; Wastell, H.

doi:10.1359/jbmr.1997.12.3.472

Cited by 166 publications

(90 citation statements)

References 34 publications

(35 reference statements)

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“…The direct effects of androgens on bone metabolism in vivo have been extensively assessed in animal studies (largely rodents) (59)(60)(61)(62)(63)(64)(65) and clinical or epidemiological studies (5,7,8,(11)(12)(13)(14)(15). The endpoints of these studies were BMD (5, 7, 8, 11-13, 59, 64-66, 68-80), static or dynamic histomorphometry (7, 59-62, 64, 65, 67, 68, 87, 88), measurement of biochemical markers of bone formation and bone resorption (5,12,65,66,69,(81)(82)(83)(84)(85)(86)(87)(88), or biomechanical properties of bone (63).…”

Section: In Vivo Effects Of Androgens On Bone Metabolismmentioning

confidence: 99%

“…The endpoints of these studies were BMD (5, 7, 8, 11-13, 59, 64-66, 68-80), static or dynamic histomorphometry (7, 59-62, 64, 65, 67, 68, 87, 88), measurement of biochemical markers of bone formation and bone resorption (5,12,65,66,69,(81)(82)(83)(84)(85)(86)(87)(88), or biomechanical properties of bone (63). The majority of studies were performed either in spontaneous or orchiectomy-induced hypogonadism with or without subsequent androgen replacement therapy, or androgen treatment of eugonadal male or female subjects.…”

Section: In Vivo Effects Of Androgens On Bone Metabolismmentioning

confidence: 99%

“…However, while several studies have noted significant correlations between either total or free testosterone levels in aging men and BMD at various sites (13,77,78), others have failed to confirm this relationship (79,80). Of interest, a recent report of an open, prospective trial of intramuscular testosterone treatment of eugonadal men with osteoporosis found that spine BMD increased in these men by 5% over 6 months, although hip BMD did not change (5,72).…”

Section: Effects Of Androgens On Bmdmentioning

confidence: 99%

“…Androgen deficiency results in various abnormalities of bone metabolism, including a tall eunuchoid stature due to unfused growth plates and thinner (particularly cortical) bones as well as a lower peak bone mass and accelerated bone loss due to increased bone resorption, resulting in a higher fracture risk (1). While the clinical and biochemical effects of androgens (and androgen deficiency) on bone metabolism are well appreciated (1,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), the cellular and molecular action(s) of androgens on bone cells have remained largely unclear.…”

Section: Introductionmentioning

confidence: 99%

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Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

121

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Androgens have beneficial effects on skeletal development and maintenance in women and men. The detection and functional characterization of androgen receptors in bone cells has implicated bone tissue as a potential target tissue for androgens. Gonadal and adrenal androgens directly regulate various aspects of osteoblastic lineage cells, including proliferation, differentiation, mineralization, and gene expression. These effects may differ depending on the stage of differentiation, the number of androgen receptors, and other inherent characteristics (species, site, cell biology) of the osteoblastic cell system. In addition, recent studies have suggested that some of the anabolic and anti-resorptive effects of androgens on bone may be mediated by regulation of autocrine and paracrine factors in the bone microenvironment, including transforming growth factor-b, insulin-like growth factors (and their binding proteins), and interleukin-6. This review summarizes the recent progress made in our knowledge of androgen receptor action, local androgen metabolism in bone, and direct and indirect effects of gonadal and adrenal androgens as well as androgen receptor antagonists on bone cells.

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Section: In Vivo Effects Of Androgens On Bone Metabolismmentioning

confidence: 99%

Section: In Vivo Effects Of Androgens On Bone Metabolismmentioning

confidence: 99%

Section: Effects Of Androgens On Bmdmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

121

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“…Testosterone and estradiol levels were associated with differing and complementary features on bone histomorphometry such as trabecular thickness and trabecular number [34]. In a therapeutic trial of testosterone supplementation in men with osteoporotic vertebral fracture [35], pharmacological doses of testosterone were associated with proportionate rises in estradiol levels, and increases in LS-BMD during testosterone therapy correlated more closely with changes in serum estradiol than with changes in serum testosterone (Fig. 3).…”

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confidence: 99%

Sex Hormones and Osteoporosis in Men

et al. 1998

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Osteoporosis in men is a common disorder, the incidence of which is increasing. Bone is lost with advancing age in men as well as in women, leading to an increased risk of fracture after minimal trauma. Recent epidemiological data from North America suggests a lifetime risk of fracture of the hip, spine, or forearm of 13.1% in white men aged 50 [1]. Despite the considerable public health burden attributable to these fractures, our understanding of their pathogenesis is incomplete and there is no established treatment for osteoporosis in men.Androgen deficiency is thought to play an important role in many cases of male osteoporosis. Biochemical evidence of hypogonadism is found in about 20% of men with vertebral fractures [2] and up to 50% of men with hip fractures [3,4], often without other clinical features of gonadal failure. In cell culture studies using human osteoblastlike cells from both men and women [5][6][7], specific androgen receptors can be identified by nuclear and cytosolic binding assays (Table 1). Similarly, osteoblasts obtained from fresh femoral bone specimens can also metabolize the circulating androgen androstenedione to testosterone and 5␣-dihydrotestosterone (DHT) in both men and women [8] at rates dependent mainly on androstenedione concentration. Cells of osteoclast lineage may also have these properties, though this is less well established. Androgen receptors have also been directly demonstrated in osteoblasts and osteocytes around the growth plate [9]. Androgens may promote proliferation and differentiation of osteoblasts, inhibit osteoclast recruitment or affect osteoblast-to-osteoclast signaling.Animal studies have mostly been performed in orchiectomized (orch) male rats, though there are reservations about the appropriateness of this model because the rat skeleton grows throughout life. Replacement therapy with either testosterone or 5␣-DHT results in enhanced bone mass, though this remains lower than in control rats [10].In male humans, androgens have a marked effect on bone growth and peak bone mass via the growth hormone/ IGF-I axis; accordingly, androgen deficiency before puberty leads to lower bone mineral density (BMD) in both cortical and trabecular bone. Loss of androgens in later life is associated with increased bone resorption and loss of trabecular bone, but cortical bone mass is not greatly affected [11,12]. In a study of 12 men who had undergone judicial castration for ''sexual delinquency'' [13], bone turnover was increased and lumbar spine BMD fell significantly, with evidence of the most rapid loss in the first 5 years after castration. Rates of bone loss were as high as 7% per year, comparable to loss rates seen in early postmenopausal women. In this study, calcitonin therapy was effective in reducing bone loss, and low calcitonin levels have been reported in another group of young hypogonadal men who had not undergone surgery [14]. Others have found low plasma 1,25 dihydroxyvitamin D levels and impaired calcium absorption in hypogonadal men [15].This combination o...

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