Khalil, Rougin, Antonio, Leen, Laurent, Michaël R, David, Karel, Kim, Na Ri, Evenepoel, Pieter, Eisenhauer, Anton , Heuser, Alexander , Cavalier, Etienne, Khosla, Sundeep, Claessens, Frank, Vanderschueren, Dirk and Decallonne, Brigitte (2020) Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study. European Journal of Endocrinology, 183 (2). pp. 181-189. DOI 10.1530/EJE-20-0348.

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Text [1479683X - European Journal of Endocrinology] Early effects of androgen deprivation on bone and mineral homeostasis in adult men_ a prospective cohort study.pdf - Accepted Version Download (4MB) | Preview

Abstract

Objective: Long-term androgen deprivation therapy (ADT) negatively influences 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/phosphate
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) weeks. 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 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 osteocalcin 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
(TRAcP5b, CTX) were unaltered.

Conclusions: In adult men, calcium release from the skeleton occurs early following 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.

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