ASBMR 27th Annual Meeting M001–M525

Abstract

Abstractsaromatisable androgen 5α-dihydrotestosterone (DHT) was administered (45µg/day via subcutaneous implants) to orchidectomized male P6 and R1 mice at week 4 (start of puberty). Both bone resorption and formation markers (urinary deoxypyridinoline [DPD] and serum osteocalcin [oc]) and tibial bone mass (by in vivo pQCT) were measured every 4 weeks between 4-20 weeks of age. At baseline and endpoint serum osteoprotegerin (OPG) was evaluated. At the tibial diaphysis, DHT had similar bone anabolic effects in P6 and R1. DHT increased periosteal expansion more than endocortical expansion, resulting in thickening of the cortex (+7% in P6 and +4% in R1, respectively; P<0.001). At the tibial metaphysis, DHT also induced a sustained increase of trabecular bone mineral density during the entire experimental period; this increase was significantly greater in P6 (+150% in P6 versus +68% in R1, P<0.001), despite similar action of DHT on seminal vesicles in P6 and R1. In accordance with its bone sparing action on cancellous bone, DHT lowered oc and DPD in P6 (-47% and -59%, respectively, P<0.001) and R1 (-53% and -60%, respectively, P<0.001) during the entire experimental period. Moreover, DHT increased serum OPG (which was already higher in P6 than R1) in P6 (+63%, P<0.05) but not in R1.In conclusion, DHT action on the skeleton is not impaired in growing P6. DHT has similar anabolic action on cortical bone in P6 compared to controls. In cancellous bone, on the other hand, DHT shows a stronger bone sparing effect in P6; this effect is consistent with an increase of OPG in this animal model of senile osteoporosis. The longitudinal follow-up of bone markers in combination with in vivo pQCT appears an interesting tool for the combined evaluation of cortical and cancellous bone acquisition during growth in animal models. Orthopaedic Surgery, University of Arkansas, Little Rock, AR, USA, 3 Jackson Laboratory, Bar Harbor, ME, USA. DisclosuresAromatase inhibitors (AIs), effective treatment for breast cancer, block estrogen synthesis by inhibiting the conversion of testosterone and androstenedione to estradiol and estrone. Increased bone resorption and decreased bone mineral density (BMD) are predicted consequences. We hypothesized that bisphosphonates (BPs) may prevent bone loss from AI therapy. We studied the effect of estrogen deficiency on bone remodeling in 4-week-old female nude mice that underwent ovariectomy (ovx) or sham surgery. Ovx and sham mice did not differ in BMD (assessed by DXA) or in histomorphometric assessment of trabecular bone volume. Next, to study the effect of AIs +/-BPs on bone remodeling, 4-week-old female nude mice were treated with letrozole (10 mcg/d), zoledronic acid (ZA) (5 mcg/kg twice weekly), letrozole (10 mcg/d) + ZA (5 mcg/kg twice weekly) or control. Mice treated with letrozole alone had lower BMD compared to control mice (p<0.0001; total body, spine, femur and tibia). Mice treated with ZA alone had higher BMD compared to control mice (p<0.0001; total body, spine, femur and tibia). Mice tre...