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Selective estrogen receptor modulators: A possible new treatment of osteoporosis in males
Darko Kastelan1, Zlatko Giljevic, Ivana Kraljevic
1Division of Endocrinology, Department of Internal Medicine, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.
Abstract:
More recently, osteoporosis in men has been recognized as an important public health problem. Bone loss begins in mid life and is associated with the decline of the sex steroids production. Although there is no equivalent of the menopause, gonadal function in men is affected in a slow progressive way leading to hypogonadism. Testosterone, the major androgen in men, exerts its effect on bone by local conversion to 5alpha-dihydrotestosterone or by aromatization to estrogens. Several studies have found that estrogen, rather than testosterone, levels are more closely correlated with BMD in elderly men. Selective estrogen receptor modulator (SERM) raloxifene binds to estrogen receptors and exhibit estrogenic effect in bone, but, contrary to estrogen, without feminizing effect. There are limited numbers of studies investigating the effects of SERMs in males. Animal studies demonstrated that SERMs inhibit bone turnover and prevent bone loss in orchidectomised adult male rats. Raloxifene has been shown to increase bone mineral density of the hip in men receiving androgen deprivation therapy for prostate cancer. Moreover, experimental data demonstrated dramatic increase in cell death in human prostate cancer cell lines after the treatment with raloxifene. All these observations suggest that SERMs may be useful for the prevention and treatment of osteoporosis not only in postmenopausal women but also in elderly men. However, our hypothesis should be tested in a proper designed clinical trial. Several important issues have to be addressed. Does the same drug dose that has been shown to be effective in postmenopausal women should be used in men, too? Does treatment with SERMs reduce the fracture risk in men and is it comparable to that observed in women? Does treatment with SERMs have any beneficial effect on cardiovascular system and prostate cancer? And finally, do men experience adverse events other than women treated with SERMs? Answering to these questions will have great impact in getting the decision of possible SERMs usage in the treatment of osteoporosis in elderly males.
Insights
Selective estrogen receptor modulators (SERMs) show promise for treating osteoporosis in men, potentially offering benefits for bone health and other conditions. Further clinical trials are needed to confirm efficacy and safety in males.
Area of Science:
- Endocrinology
- Gerontology
- Pharmacology
Background:
- Osteoporosis is an emerging public health concern in men, linked to age-related decline in sex steroids.
- Estrogen levels, not testosterone, correlate more strongly with bone mineral density (BMD) in elderly men.
- Selective estrogen receptor modulators (SERMs) mimic estrogen's bone effects without feminization.
Purpose of the Study:
- To explore the potential of SERMs for osteoporosis prevention and treatment in elderly men.
- To identify key questions for future clinical trials on SERM use in men.
Main Methods:
- Review of existing animal and human studies on SERM effects in males.
- Analysis of raloxifene's impact on bone mineral density in men undergoing prostate cancer therapy.
- Examination of experimental data on SERMs and prostate cancer cell lines.
Main Results:
- Animal studies indicate SERMs inhibit bone turnover and prevent bone loss in male rats.
- Raloxifene increased hip BMD in men receiving androgen deprivation therapy.
- Experimental data suggest raloxifene may induce cell death in prostate cancer lines.
Conclusions:
- SERMs show potential for treating osteoporosis in elderly men.
- Further research is required to determine optimal dosing, fracture risk reduction, cardiovascular and prostate cancer effects, and adverse events in men.
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