title: Long-term therapy with a new chemically modified tetracycline (CMT-8) inhibits bone loss in femurs of ovariectomized rats.
abstract: The effect of a new non-antimicrobial analog of tetracycline (CMT-8) on bone loss in ovariectomized (OVX) rats was examined. Three-month-old female rats were ovariectomized, and one week later, were distributed into 3 groups: sham-operated non-OVX controls, vehicle-treated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily CMT-8 administration, the intact femurs were dissected and examined by several histological and histomorphometric techniques. OVX significantly (p < 0.01) decreased trabecular bone volume by 53.4% in the metaphyses compared with sham-operated controls. CMT-8 therapy produced a significant (p < 0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats. Of interest, the newly synthesized bone in the CMT-treated OVX rats was found to increase the "connectivity" of the trabecular "struts" by bridging the adjacent longitudinal bone trabeculae, forming dense, plate-like bone trabeculae. These results strongly suggest that long-term CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones.
authors.affiliation: Department of Anatomy, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: N S
authors.initials: NS
authors.lastname: Ramamurthy
authors.forename: L M
authors.initials: LM
authors.lastname: Golub
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy*; D005260:Female; D005269:Femur; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013754:Tetracyclines / Q000494:pharmacology / Q000627:therapeutic use*