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 repair when applied locally in vivo. To explore whether PDGF could stimulate bone formation in intact bone, we administered it systemically to rats rendered acutely estrogen-deficient. Because PDGF may stimulate bone resorption in vitro, PDGF was administered with and without an antiresorptive agent (alendronate). All treatments were given by intravenous 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 prevented this bone loss and significantly (p < 0.05) increased the bone density 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. Histomorphometric analysis demonstrated that treatment with PDGF increased the osteoblast number and osteoblast perimeter without consistent changes in osteoclast estimates. Biomechanical testing demonstrated that PDGF administration increased the vertebral body compressive strength and femoral shaft torsional stiffness and resulted in a trend for enhanced femoral head shearing strength. Coadministration of alendronate further increased these indices of bone strength. PDGF administration also caused premature closure of the growth plate, decreased body fat, and resulted 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.
Mitlak
B H
BH
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Finkelman
R D
RD
Hill
E L
EL
Li
J
J
Martin
B
B
Smith
T
T
D'Andrea
M
M
Antoniades
H N
HN
Lynch
S E
SE
D015502:Absorptiometry, Photon; D000818:Animals; D000077214:Becaplermin; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D007275:Injections, Intravenous; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012741:Sexual Maturation / Q000502:physiology*; D013131:Spine / Q000187:drug effects; D013977:Tibia / Q000187:drug effects; D014057:Tomography, X-Ray Computed
D004967:Estrogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin