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Additive Protective Effects of Estrogen and Androgen Treatment on Trabecular Bone in Ovariectomized Rats
Author(s) -
Tivesten Åsa,
MovérareSkrtic Sofia,
Chagin Andrei,
Venken Katrien,
Salmon Phil,
Vanderschueren Dirk,
Sävendahl Lars,
Holmäng Agneta,
Ohlsson Claes
Publication year - 2004
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.040819
Subject(s) - endocrinology , medicine , ovariectomized rat , bone resorption , estrogen , androgen , dihydrotestosterone , androgen receptor , chemistry , bone remodeling , osteoporosis , osteocalcin , osteoblast , estrogen receptor , hormone , alkaline phosphatase , in vitro , biochemistry , prostate cancer , cancer , breast cancer , enzyme
Both ER and AR activation regulates trabecular bone mass. We show that combined estrogen and androgen treatment results in additive protection of trabecular bone in OVX rats. This may in part be attributable to the effect of AR activation to attenuate the inhibitory effect of ER activation on bone formation. Introduction: Sex steroids are important regulators of trabecular bone mass. Both estrogen receptor (ER) and androgen receptor (AR) activation results in increased trabecular bone mass. The aim of this study was to investigate if combined estrogen and androgen treatment might be beneficial in the treatment of trabecular bone loss. Materials and Methods: Twelve‐week‐old female rats were ovariectomized (OVX) and treated with vehicle (V), 17β‐estradiol (E 2 ; ER activation), dihydrotestosterone (DHT; AR activation), or the combination (E 2 + DHT) for 6 weeks. The skeletal phenotype was analyzed by pQCT, μCT, histomorphometry of growth plates, and serum levels of biochemical bone markers. Results: Both E 2 (+121% over V) and DHT (+34%) preserved the trabecular volumetric BMD (tvBMD) in OVX rats. The effect of E 2 and DHT on tvBMD was additive, resulting in a 182% increase over V in the rats given E 2 + DHT. μCT analyses of the trabecular bone microstructure revealed that the effect of E 2 and DHT was additive on the number of trabeculae. E 2 treatment reduced serum markers of both bone resorption (collagen C‐terminal telopeptide) and bone formation (osteocalcin), indicating reduced bone turnover. Addition of DHT to E 2 treatment did not modulate the effects of E 2 on the marker of bone resorption, whereas it attenuated the inhibitory effect of E 2 on the bone formation marker, which might explain the additive protective effect of E 2 and DHT on trabecular bone mass. In contrast, DHT partially counteracted the suppressive effect of E 2 on longitudinal bone growth and the E 2 ‐induced alterations in growth plate morphology. Conclusions: These findings show that combined estrogen and androgen treatment results in additive protective effects on trabecular bone in OVX rats. Our data suggest that a combined treatment with selective ER and AR modulators might be beneficial in the treatment of osteoporosis.