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 stu dy, two bone-modulating compounds, an NSAID (flurbiprofen: FBP) and a chemically modified nonantimicrobial tetracycline (CMT), were tested e ither individually or in combination in this model, Ninety days after OVX, 6-month-old female rats were distributed into the following group s: sham-operated controls, untreated OVX, CMT-treated OVX (5 mg P.O./d ay), 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 p retreatment group, After 21 days of therapy, the dissected distal femu rs were processed for Light and fluorescence microscopic and backscatt ered electron microscopic examinations, Net trabecular bone values sho wed that all the treatment groups lost trabecular bone over the 111 da y protocol compared to pretreatment group, In the untreated OVX rats, trabecular bone volume/unit area was reduced by 56% compared to that i n 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 thera py 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 in crease bone deposition (p < 0.01) at the endosteal surfaces of cortica l bone, These results suggest that, in this animal model, (a) cortical bone volume increases by CMT; (b) FBP inhibits osteoclastic bone reso rption in the trabecular area, and (c) a combination of these drugs ma y synergistically prevent bone loss. (C) 1996 by Elsevier Science Inc.