Basic fibroblast growth factor improves trabecular bone connectivity and bone strength in the lumbar vertebral body of osteopenic rats

Abstract

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.

The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of glucocorticoids

“…The scans were initiated in the sagittal plane of the vertebral body and covered the entire cortical and trabecular bone of the vertebral body. Secondary spongiosa was consistently selected for evaluation (20)(21)(22). Three-dimensional (3-D) trabecular structural parameters were measured directly, as previously described (20,21,23).…”

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

“…In OVX rats, PDGF administration increases osteoblast number, resulting in increased bone mass and strength (89). Fibroblast growth factors (FGFs) are other positive regulators of osteoblastogenesis (90), and systemic administration of FGF2 was found to increase bone formation and bone strength in OVX rats (91,92). VEGF can also promote bone formation in vivo (93).…”

The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

“…Bone histomorphometry was performed using a semiautomatic image analysis Bioquant system (Bioquant Image Analysis Corporation, Nashville, TN) linked to a microscope equipped with transmitted and fluorescent light sources [14][15][16].…”

“…These indices were used to calculate mineralizing surface (MS/BS) and mineral apposition rate (MAR), bone formation rate (BFR/BS) and percentage of osteoclast surface (OcS/BS), according to Parfitt et al [17,18]. We have reported similar methodology in other experiments in our laboratory [14][15][16]19].…”

“…Typically the lengths of the samples were twice as large as the diameters; consequently, buckling during the test was not a problem. Maximum load and cross-sectional dimensions were used to calculate the compressive strength [15,16].…”