engleski

Systemic effect on the skeleton of locally administered BMP2 and BMP 7 containing bone devices

Local application of BMP2 and 7 bone devices have been approved by FDA for long bone fractures, non-unions, and spinal fusions. It is unknown whether systemic release of BMP2 and 7 following a local implantation could impact systemically the bone volume. Also, it is not understood whether systemic their effects on bone require calciotropic hormones. To addresse these questions we explored the effect of systemically administered BMP2 and 7 on bone using our newly developed rat model with a low level of calciotropic hormones. Surgical removal of thyroid and parathyroid glands (TPTx) in rats resulted in low level of thyroid hormones, PTH, calcitonin and 1, 25(OH)2D3, followed by the bone loss evaluated by microCT and serum markers of bone formation and resorption, including osteocalcin, C-telopeptide, osteoprotegerin and receptor activator of nuclear factor kappa-B ligand. Also, BMP2 and 7 were tested in vitro to estimate their influence on bone cell activity. The administered doses were calculated according to published bioavailability results from pre-clinical BMP2 and 7 studies. TPTx caused bone loss which was restored by systemic administration of 10-70 µg/kg of BMP2 and BMP7. BMP2 showed a higher capacity for enhancing trabecular microarchitecture, including increased trabecular number and diminished trabecular separation. On the contrary, BMP7 increased the trabecular thickness. In vitro assays revealed that BMP2 and 7 increased the number and activity of both osteoblasts and osteoclasts. In summary, both BMP2 and 7 showed the ability to increase in vivo the bone volume in a rat model of low calciotropic hormones. Thus, locally administered BMP2 and 7 bone devices will not systemically influence the bone metabolism, even if in treated patients an amount of BMP enters their circulation.

bone morphogenetic protein 2; bone morphogenetic protein 7; bone volume; microCT

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