Tetracycline/flurbiprofen combination therapy modulates bone remodeling in ovariectomized rats: preliminary observations.
The loss of trabecular bone in the ovariectomized (OVX) rat provides a useful experimental model of postmenopausal osteoporosis. In this study, two bone-modulating compounds, an NSAID (flurbiprofen: FBP) and a chemically modified nonantimicrobial tetracycline (CMT), were tested either individually or in combination in this model. Ninety days after OVX, 6-month-old female rats were distributed into the following groups: sham-operated controls, untreated OVX, CMT-treated OVX (5 mg P.O./day), FBP-treated OVX (0.3 mg P.O./day), and combination (CMT plus FBP)-treated OVX (COMBO) groups. Untreated 3-month-old rats were used as pretreatment group. After 21 days of therapy, the dissected distal femurs were processed for light and fluorescence microscopic and backscattered electron microscopic examinations. Net trabecular bone values showed that all the treatment groups lost trabecular bone over the 111 day protocol compared to pretreatment group. In the untreated OVX rats, trabecular bone volume/unit area was reduced by 56% compared to that in the sham-operated controls, this bone loss associated with increased numbers of osteoclasts (p < 0.05). Cortical bone volume was, however, not significantly reduced in OVX rats. Both FBP-alone and COMBO therapy showed marginal, but significant, (p < 0.05, p < 0.01, respectively) inhibition of trabecular bone loss, and osteoclast numbers were also decreased (p < 0.05). Both CMT alone and COMBO therapy appeared to increase bone deposition (p < 0.01) at the endosteal surfaces of cortical bone. These results suggest that, in this animal model, (a) cortical bone volume increases by CMT; (b) FBP inhibits osteoclastic bone resorption in the trabecular area, and (c) a combination of these drugs may synergistically prevent bone loss.
Aoyagi
M
M
Department of Prosthodontics, School of Dentistry, Showa University, Shinagawa-ku, Tokyo, Japan.
Sasaki
T
T
Ramamurthy
N S
NS
Golub
L M
LM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D005269:Femur / Q000737:chemistry / Q000648:ultrastructure; D005480:Flurbiprofen / Q000627:therapeutic use*; D008855:Microscopy, Electron, Scanning; D010024:Osteoporosis / Q000188:drug therapy; D010052:Ovariectomy; D011500:Protein Synthesis Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013752:Tetracycline / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011500:Protein Synthesis Inhibitors; D005480:Flurbiprofen; D013752:Tetracycline