engleski

Systemically available bone morphogenetic protein two and seven affect bone metabolism

Bone morphogenetic protein (BMP)2 and 7 are used in patients with long bone fractures and non- unions, and spinal fusions. It is unknown whether their potential systemic bioavailability following an local bone administration might effect the skeleton metabolism. To answer this question we examined effects of systemically administered BMP2 and 7 on bone in a newly developed rat model with low level of calciotropic hormones. Removal of thyroid and parathyroid glands (TPTx) in rats resulted in decreased level of calciotropic hormones and a subsequent bone loss assessed by microCT and measurement of serum bone formation and resorption markers, including osteocalcin, C- telopeptide, osteoprotegerin and RANKL. Results were complemented with in vitro studies on osteoblast and osteoclast activity by both BMP2 and 7. The doses used have been calculated from published pharmacodynamic (PD) and bioavailability results from pre-clinical BMP2 and 7 studies. TPTx resulted in bone loss which was restored by systemic administration of 10-70 µg/kg of BMP2 and 10-250 µg/kg of BMP7. BMP2 showed a higher capacity for enhancing trabecular microarchitecture, while BMP7 augmented trabecular thickness. In vitro experiments revealed that BMP2 and 7, when uncoupled, increased the number and activity of both osteoblasts and osteoclasts. Surprisingly, both BMP2 and 7 showed an increased bone volume in an in vivo environment of low calciotropic hormones. Locally administered BMP2 and 7 from bone devices might become partially available in circulation but will not mediate a systemic bone loss.

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

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