What is the role of cyclosporin A in the pathogenesis of organ transplantation-related osteoporosis?

Updated: Jul 02, 2020
  • Author: Carmel M Fratianni, MD, FACE; Chief Editor: George T Griffing, MD  more...
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Like glucocorticoids, CsA causes severe and rapid trabecular bone loss. However, unlike glucocorticoids, CsA results in accelerated bone turnover, with both increased formation and resorption. The bone histomorphology resembles that of the oophorectomized female rat. Antiresorptive agents, such as estrogen, alendronate, and calcitonin, can largely prevent this bone loss. Alendronate specifically prevents CsA-induced osteopenia in rats, maintaining trabecular bone volume at the tibia.

Some investigators have speculated that this effect of cyclosporine may be mediated through testosterone because cyclosporine suppresses the hypothalamic-pituitary-gonadal axis and lowers serum testosterone levels in rats and in human transplant patients. Some evidence suggests that cyclosporine may have a direct testicular effect. Examination of rat testes after CsA exposure has revealed decreased LH-receptor numbers and dramatically decreased serum and intratesticular testosterone. Altered testicular cytochrome P-450 activity is reported due to suppressed heme formation and the steroidogenic activities that rely on it, such as 17-hydroxylase and side-chain cleavage enzymes.

Others have speculated that CsA may have a direct pituitary or hypothalamic effect, inducing hypogonadotrophic hypogonadism and a blunted response of LH/follicle-stimulating hormone (FSH) to gonadotropin-releasing hormone. While CsA may have both central and direct testicular effects, CsA-induced bone loss is not prevented by testosterone administration in the rat model and did not correlate with bone turnover or histomorphometry findings.

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