Early effects of androgen deprivation on bone and mineral homeostasis in adult men: A prospective cohort study

Rougin Khalil, Leen Antonio, Michael R. Laurent, Karel David, Na Ri Kim, Pieter Evenepoel, Anton Eisenhauer, Alexander Heuser, Etienne Cavalier, Sundeep Khosla, Frank Claessens, Dirk Vanderschueren, Brigitte Decallonne

Research output: Contribution to journalArticle

Abstract

Objective: Long-term androgen deprivation therapy (ADT) negatively influen ces bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Design: Prospective cohort study. Methods: Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosph ate homeostasis and bone turnover between baseline and first follow-up visit were studied. Results: Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) week s. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2 ); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and o steocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. Conclusions: In adult men, calcium release from the skeleton occurs early f ollowing sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.

Original languageEnglish (US)
Pages (from-to)181-189
Number of pages9
JournalEuropean journal of endocrinology
Volume183
Issue number2
DOIs
StatePublished - Aug 2020

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Khalil, R., Antonio, L., Laurent, M. R., David, K., Kim, N. R., Evenepoel, P., Eisenhauer, A., Heuser, A., Cavalier, E., Khosla, S., Claessens, F., Vanderschueren, D., & Decallonne, B. (2020). Early effects of androgen deprivation on bone and mineral homeostasis in adult men: A prospective cohort study. European journal of endocrinology, 183(2), 181-189. https://doi.org/10.1530/EJE-20-0348