THE EFFECT OF SYSTEMICALLY ADMINISTERED PDGF-BB ON THE RODENT SKELETON

Platelet-derived growth factor (PDGF), an osteoblast mitogen, has been demonstrated to accelerate fracture healing and periodontal bone repa ir when applied locally in vivo. To explore whether PDGF could stimula te bone formation in intact bone, we administered it systemically to r ats rendered acutely estrogen-deficient, Because PDGF map stimulate bo ne resorption in vitro, PDGF was administered with and without an anti resorptive agent (alendronate). All treatments were given by intraveno us injection 3 times a week for 6 weeks, Spinal bone mineral density ( BMD) decreased by 5% in the vehicle-treated ovariectomized (OVX) rats by the end of the study as determined by DXA. Treatment with PDGF prev ented this bone loss and significantly (p < 0.05) increased the bone d ensity in the spine (9%) and whole skeleton (5.8%), Combined treatment with PDGF and alendronate resulted in a greater increase at the spine (18%) and whole skeleton (12.8%) than either agent alone, Histomorpho metric analysis demonstrated that treatment with PDGF increased the os teoblast number and osteoblast perimeter without consistent changes in osteoclast estimates, Biomechanical testing demonstrated that PDGF ad ministration increased the vertebral body compressive strength and fem oral shaft torsional stiffness and resulted in a trend for enhanced fe moral head shearing strength, Coadministration of alendronate further increased these indices of bone strength, PDGF administration also cau sed premature closure of the growth plate, decreased body fat, and res ulted in extraskeletal collagen deposition, We therefore demonstrate, for the first time, that systemic administration of PDGF can increase bone density and strength throughout the skeleton.