Effects of nandrolone decanoate on forearm mineral density and calcium metabolism in osteoporotic postmenopausal women

Need, A. G.; Morris, Howard A.; Hartley, T. F.; Horowitz, Michael; Nordin, B. E. C.

doi:10.1007/bf02555124

Cited by 44 publications

(16 citation statements)

References 18 publications

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“…In early studies, Lafferty et al (91) found that calcium absorption transiently increased following short-term treatment (2 to 3 months) with testosterone. Consistent with this, a significant increase in the hourly fractional rate of radiocalcium absorption was found in 27 women with postmenopausal osteoporosis following 3 months of therapy with the anabolic steroid, nandrolone decanoate (92). However, since androgens may affect serum levels of vitamin D-binding protein, thus altering the levels of free 1,25-dihydroxyvitamin D 3 (93), it remains unclear whether androgens might exert their effects on intestinal calcium absorption directly or indirectly through effects on the vitamin D-endocrine system.…”

Section: Extraskeletal Effects Of Androgens On Calcium Metabolismsupporting

confidence: 62%

“…Therapy with the anabolic steroid, stanozolol, for 8 to 32 months in 23 women with postmenopausal osteoporosis decreased urinary calcium excretion by 32% (97). In addition, treatment with nandrolone decanoate for 3 months significantly increased renal tubular calcium reabsorption in 27 women with postmenopausal osteoporosis (92).…”

Section: Extraskeletal Effects Of Androgens On Calcium Metabolismmentioning

confidence: 97%

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Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

122

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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: Extraskeletal Effects Of Androgens On Calcium Metabolismsupporting

confidence: 62%

Section: Extraskeletal Effects Of Androgens On Calcium Metabolismmentioning

confidence: 97%

Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

122

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“…Therefore, while estrogen is the main sex steroid regulating bone accrual and maintenance in females, we have provided evidence that androgens also play a physiological role in bone in females via the genomic AR pathway. Supportive evidence for this is provided by observations of increased bone mineral density in hirsute women with increased circulating levels of testosterone (Buchanan et al 1988), in woman following treatment with the synthetic non-aromatizable androgen nandrolone decanoate (Need et al 1987, Johansen et al 1989, and in female ovariectomized rats treated with the non-aromatizable androgen, DHT (Tobias et al 1994). …”

Section: Discussionmentioning

confidence: 89%

DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females

MacLean¹,

Moore²,

Sastra³

et al. 2010

Journal of Endocrinology

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We used our genomic androgen receptor (AR) knockout (ARKO) mouse model, in which the AR is unable to bind DNA to: 1) document gender differences between males and females; 2) identify the genomic (DNA-binding-dependent) AR-mediated actions in males; 3) determine the contribution of genomic AR-mediated actions to these gender differences; and 4) identify physiological genomic AR-mediated actions in females. At 9 weeks of age, control males had higher body, heart and kidney mass, lower spleen mass, and longer and larger bones compared to control females. Compared to control males, ARKO males had lower body and kidney mass, higher splenic mass, and reductions in cortical and trabecular bone. Deletion of the AR in ARKO males abolished the gender differences in heart and cortical bone.Compared with control females, ARKO females had normal body weight, but 14% lower heart mass and heart weight/ body weight ratio. Relative kidney mass was also reduced, and relative spleen mass was increased. ARKO females had a significant reduction in cortical bone growth and changes in trabecular architecture, although with no net change in trabecular bone volume. In conclusion, we have shown that androgens acting via the genomic AR signaling pathway mediate, at least in part, the gender differences in body mass, heart, kidney, spleen, and bone, and play a physiological role in the regulation of cardiac, kidney and splenic size, cortical bone growth, and trabecular bone architecture in females.

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“…40) In addition, OVX rats of about the same age were used in evaluating commercial anti-osteoporosis drugs, and they showed positive effects. 37,41,42) Androgenic compounds such as anabolic steroids have positive effects on osteoporosis, 43,44) and long-term treatment with anti-androgen bicaltamide decreased BMD in prostate cancer patients. 45) S-101479 could be beneficial in treating osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

The Novel Non-steroidal Selective Androgen Receptor Modulator S-101479 Has Additive Effects with Bisphosphonate, Selective Estrogen Receptor Modulator, and Parathyroid Hormone on the Bones of Osteoporotic Female Rats

Furuya

Yamamoto

Ohyabu

et al. 2012

Biological & Pharmaceutical Bulletin

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We have studied non-steroidal selective androgen receptor modulators (SARMs) to develop anti-osteoporosis drugs for males and females. Many SARMs have been studied for their anabolic effects on bone or muscle with reduced virilizing effects in male animals. However, the tissue selectivities of these agents in female animals have not been fully evaluated. We evaluated the novel SARM S-101479 from tetrahydroquinoline libraries in ovariectomized (OVX) rats. S-101479 preferentially bound to the androgen receptor with nanomolar affinity among nuclear receptors. It increased the bone mineral density (BMD) of femurs and diminished the effects on the uterus and clitoral gland in OVX rats. We then compared the effect of S-101479 on bone with those of commercial anti-osteoporosis drugs such as alendronate, raloxifene, and teriparatide. Furthermore, we evaluated the effects of combination treatments with these agents in OVX rats. After 16-week treatment, all agents significantly increased BMD, but the magnitude of bone mineral content (BMC) and/or bone size (projected bone area) were different. Alendronate, raloxifene, and teriparatide maintained BMC and bone size in this experimental dose. Only S-101479 increased BMC with bone size on single treatments. In combination treatment, S-101479 significantly increased BMC and bone size compared with single treatments of other agents. S-101479, like natural androgen, may have showed periosteal bone formation of the cortical area and indicated additive effects with commercial anti-osteoporosis drugs. These results indicate that S-101479 may be a useful anti-osteoporosis drug, particularly for patients with established severe osteoporosis.Key words selective androgen receptor modulator; bone anabolic; additive effect Androgens are known to have beneficial anabolic effects on various tissues such as bone, muscle, and red blood cells (RBCs).1-4) However, the clinical use of androgens has been limited because of their undesirable virilizing and metabolic actions. Their effect on the prostate gland is an extremely serious side effect because the risk of prostate cancer or benign prostate hyperplasia may increase. 5,6) The side effects of androgens are not lethal in women, but many virilizing effects (e.g., hirsutism, voice change, and acne) have been observed. 7,8) Anabolic steroids were developed to reduce the side effects of androgens and treat osteoporosis. However, their actions were not sufficient to reduce virilizing effects, and they exhibited hepatotoxic actions. [9][10][11][12] Recently, the actions of non-steroidal selective androgen receptor modulators (SARMs) have been investigated in many laboratories. [13][14][15][16][17] Typically, they were observed to be more tissue-selective than anabolic steroids and were orally available in preclinical models. We have focused on bone anabolic SARMs to develop anti-osteoporosis agents without serious virilizing effects.

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Effects of nandrolone decanoate on forearm mineral density and calcium metabolism in osteoporotic postmenopausal women

Cited by 44 publications

References 18 publications

Androgen effects on bone metabolism: recent progress and controversies

Androgen effects on bone metabolism: recent progress and controversies

DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females

The Novel Non-steroidal Selective Androgen Receptor Modulator S-101479 Has Additive Effects with Bisphosphonate, Selective Estrogen Receptor Modulator, and Parathyroid Hormone on the Bones of Osteoporotic Female Rats

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