IGF-binding protein-5 stimulates osteoblast activity and bone accretion inovariectomized mice

Insulin-like growth factor binding protein-5 (IGFBP-5) is an osteoblast sec retory protein that becomes incorporated into the mineralized bone matrix. In osteoblast cultures, IGFBP-5 stimulates cell proliferation by an IGF-ind ependent mechanism. To evaluate whether IGFBP-5 can stimulate osteoblast ac tivity and enhance bone accretion in a mouse model of osteoblast insufficie ncy, daily subcutaneous injections of either intact [IGFBP-5 (intact)] or c arboxy-truncated IGFBP-5 [IGFBP-5-(1-169)] were given to ovariectomized (OV X) mice for 8 wk. Femur and spine bone mineral density (BMD), measured ever y 2 wk, showed early and sustained increases in response to IGFBP-5. Bone h istomorphometry of cancellous bone showed significant elevations in the bon e formation rate in both the femur metaphysis [IGFBP-5(1-169)] only) and sp ine compared with OVX controls. IGFBP-5 also stimulated osteoblast number i n the femur IGFBP-5-( 1-169) only) and spine. These data indicate that IGFB P-5 effectively enhances bone formation and bone accretion in OVX mice by s timulating osteoblast activity. The finding that IGFBP-5-(1-169) is bioacti ve in vivo indicates that the carboxy-terminal portion is not required for this bone anabolic effect.