EFFECTS OF LATHYRITIC DRUGS AND LATHYRITIC DEMINERALIZED BONE-MATRIX ON INDUCED AND SUSTAINED OSTEOGENESIS

Demineralized bone matrix was implanted in normal and lathyritic rats. At 2 weeks, the bone that formed in the lathyritic animals had an ele vated alkaline phosphatase activity and a reduced calcium content comp ared with the controls. Four weeks after implantation, these biochemic al parameters were reversed, with a decrease in alkaline phosphatase a ctivity and an increase in calcium content to control levels. The hist ology of the recovered implants revealed new bone formation. Lathyriti c demineralized bone matrix was prepared from bones of rats fed beta-a minopropionitrile for 2 weeks (2-week BAPN-DBM) or 4 weeks (4-week BAP N-DBM), and was implanted in normal rats. Two weeks after implantation , both preparations of lathyritic demineralized bone matrix demonstrat ed early bone formation, although alkaline phosphatase activity and ca lcium content were reduced. By 4 weeks after implantation, no biochemi cal or histological evidence of bone formation remained at the site of the 4-week BAPN-DBM implants; continued but reduced bone formation wa s observed at the site of the 2-week BAPN-DBM implants. Reconstitution of inactivated normal demineralized bone matrix with the guanidine-so luble extracts restored the osteoinductive capacity. However, reconsti tution of inactivated lathyritic demineralized bone matrix (4-week BAP N-DBM) failed to restore the osteoinductive capacity. These results in dicate that the degree of crosslinking of the collagen matrix that act s as a carrier for osteoinductive proteins plays a key role in inducin g and sustaining osteogenesis.