Basic fibroblast growth factor improves trabecular bone connectivity and bone strength in the lumbar vertebral body of osteopenic rats.
Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass and connectivity in the proximal tibial metaphyses (PTM) in osteopenic rats. The purpose of this study was to determine the bone anabolic effects of bFGF in the lumbar vertebral body (LVB), a less loaded skeletal site with a lower rate of bone turnover than the PTM. Six-month old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and untreated for 8 weeks to induce osteopenia. Then group 1 (sham) and group 2 (OVX) were treated subcutaneously (s.c.) with vehicle, and OVXed groups 3 and 4 were treated s.c. with PTH [hPTH (1-34) at 40 microg/kg, 5x/week] and bFGF (1 mg/kg, 5x/week), respectively, for 8 weeks. At sacrifice, the fifth LVB was removed, subjected to micro-CT for determination of trabecular bone structure and then processed for histomorphometry to assess bone turnover. The sixth LVB was used for mechanical compression testing (MTS, Bionix 858). The data were analyzed with the Kruskal-Wallis test followed by post-hoc testing as needed. After 16 weeks of estrogen deficiency, there were significant reductions in vertebral trabecular bone volume and trabecular thickness. Treatment with either bFGF or hPTH (1-34) increased BV/TV in OVX animals. Human PTH (1-34)-treated animals had significant increases in trabecular (48%) and cortical thickness (30%) and bone strength [maximum load (53%) and work to failure (175%)] compared to OVX + Vehicle animals. Treatment of osteopenic rats with bFGF increased bone volume (15%), trabecular thickness (13%), maximum load (45%) and work to failure (140%) compared to OVX + Vehicle animals (all P <0.05). Basic FGF increased trabecular bone volume in the lumbar vertebral body of osteopenic rats by restoring trabecular number, thickness and connectivity density. Also, bFGF improved bone mechanical properties (maximum force and work to failure) compared to the OVX + Vehicle group. Therefore, increasing the number, thickness and connections of the trabeculae contributes to increased bone strength in this small animal model of osteoporosis.
Yao
Wei
W
Department of Medicine, Orthopedics and Radiology, University of California at San Francisco, San Francisco, CA, USA.
Hadi
Tamer
T
Jiang
Yebin
Y
Lotz
Jeff
J
Wronski
Thomas J
TJ
Lane
Nancy E
NE
D000818:Animals; D001696:Biomechanical Phenomena; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004548:Elasticity; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000000981:diagnostic imaging / Q000187:drug effects; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014057:Tomography, X-Ray Computed / Q000379:methods
D010281:Parathyroid Hormone; D016222:Fibroblast Growth Factor 2