Short-term supplementation of COX-2 inhibitor suppresses bone turnover in gonad-intact middle-aged male rats.
There is an increasing body of evidence supporting the idea that nonsteroidal antiinflammatory drugs can effectively suppress ovariectomy-induced bone loss in adult rats. The present study investigated the effects of supplementation of selective cyclooxygenase-2 inhibitor [5,5-dimethyl-3-(3 flurophenyl)-4-(4 methylsulphonal) phenyl-2 (6H) furanone, DFU] to diets on bone metabolism, bone mineral density (BMD), and histomorphometry in middle-aged male rats. Forty 16-month-old male rats (n = 8/group) were fed diets containing 0 (control), 5, 10, 15, or 20 mg/kg DFU body weight/day for 4 weeks. Supplementation of DFU resulted in higher plasma levels of pyridinoline, insulin-like growth factor I, and parathyroid hormone, but lower bone-specific alkaline phosphatase activity, prostaglandin E(2,) and 1,25-(OH)(2) vitamin D(3). Compared to the control, DFU supplementation at 20 mg/kg did not affect total scanned area, BMD, and bone mineral content as determined by DEXA. Histomorphometric data showed that rats fed DFU at 20 mg/kg had lower values of mineralizing surface, eroded surface, mineral apposition rate, and bone formation rate, but no difference in trabecular thickness, number, and separation compared to the control. The present data demonstrate that the short-term supplementation of selective COX-2 inhibitor to gonad-intact middle-aged male rats resulted in suppression of bone formation and increased bone resorption, and thereby suppressed bone turnover rate, without significant loss of bone. Such action was through modulating local factors and systemic hormones.
Shen
Chwan-Li
CL
Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430-9790, USA. Leslie.Shen@ttuhsc.edu
Yeh
James K
JK
Wang
Xingjia
X
D000375:Aging / Q000502:physiology*; D000821:Animal Feed; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D008297:Male; D051381:Rats; D013737:Testis / Q000502:physiology*; D013997:Time Factors
C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D005663:Furans