Abstract
Levormeloxifene, a nonsteroidal selective estrogen receptor modulator (SERM), has been evaluated for its effects on bone in cynomolgus monkeys ( Macaca fascicularis). Adult female monkeys were imported from Indonesia and randomized into six groups of 25–28 animals each (n = 158). Animals in one group were sham ovariectomized (sham) and received vehicle. Animals in the remaining five groups were ovariectomized and received either vehicle (ovx); 17β-estradiol at 0.016 mg/kg (est); or levormeloxifene at 0.5 (L1), 1 (L2), or 5 (L3) mg/kg. Lumbar spine and whole body bone mass were measured by dual-energy X-ray absorptiometry (DXA) pretreatment and at 6 and 12 months following the initiation of treatment. Bone mass at the femoral neck was measured by peripheral quantitative computed tomography (pQCT) at 0 and 12 months. Serum markers of bone turnover, including bone-specific alkaline phosphatase (BSAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary collagen C-terminal extension peptides (CrossLaps), were measured at 0, 6, and 12 months. Ovariectomy resulted in an increase in these markers; the increase was prevented by estradiol or levormeloxifene. Estradiol or levormeloxifene inhibited loss of lumbar spine bone mineral density (BMD) following ovariectomy compared with untreated monkeys (ovx −5.0%; sham −0.4%; est +0.2%; L1 −3.6%, L2 −2.0%, L3 −2.5%). Estradiol, but not levormeloxifene, prevented loss of BMD at the femoral neck (ovx −7.4%; sham −3.1%; est −3.6%; L1 −8.0%, L2 −6.5%, L3 −7.8%), and whole body bone mineral content (BMC) (ovx −7.6%; sham −1.9%, est −2.9%; L1 −6.2%, L2 −6.1%, L3 −6.7%). Bone loss at each site was correlated with bone turnover as measured by serum and urine biomarkers. There was no dose effect of levormeloxifene.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have