THE EFFECT OF SYSTEMICALLY ADMINISTERED RHIGF-I/IGFBP-3 COMPLEX ON CORTICAL BONE STRENGTH AND STRUCTURE IN OVARIECTOMIZED RATS

The action of systematically administered recombinant human insulinlike growth factor-I (rhIGF-I) complexed to its natural binding protein-3 (rhIGFBP-3) on cortical bone dynamic, structural, and mechanical properties was tested in previously ovariectomized (Ovx) rats, Bilateral ovariectomy or sham surgery was performed on 16-week-old female Sprague-Dawley rats. Eight weeks after surgery basal Sham and Ovx rats were killed to establish baseline cortical bone values before the initiation of treatment with rhIGF-I/IGFBP-3 complex. At that time, Ovx rats had increased body weight and body fat mass with reduced femoral BMC and BMD relative to basal Shams, Bone formation rates in Ovx rats were increased on both cortical envelopes relative to time-matched controls. The thickness of the inner lamellar bone layer and average cortical width were reduced due to increased endocortical erosion. A similar ratio between Sham and Ovx rats in body mass and composition and femoral BMC and BMD continued throughout the experiment. Sixteen weeks after surgery bone formation rates at both cortical envelopes in Ovx rats were reduced relative to Shams, but endocortical erosion remained high causing a further decrease in thickness of the inner lamellar layer. As a result of periosteal bone modeling, Ovx rats exhibited a larger femoral cross-sectional area and periosteal perimeter, as well as a thicker outer lamellar layer. Newly deposited periosteal bone increased ultimate torque values in the Ovx rats relative to Shams at 16 weeks. Treatment of Ovx rats with the rhIGF-I/IGFBP-3 complex increased body weight, lean body mass, and femoral BMC and BMD, Bone formation was increased at both cortical envelopes resulting in a deposition of normal lamellar bone layers. Endocortical erosion remained similar to values seen in Sham rats. Envelope-specific changes following rhIGF-I/IGFBP-3 treatment resulted in a thicker cortex, higher polar moment of inertia and torque to failure relative to Ovx and Sham values, suggesting that this formulation may be of benefit in the treatment of various ostopenias.