BMP2 and 7 are used locally in FDA approved indications including complicated long bone fractures, non-unions, and spinal fusions. It is unknown whether their systemic release following a local implantation might impact systemically the bone metabolism. Furthermore, it is unknown whether systemic BMP effects on bone are direct or mediated by calciotropic hormones. To answer these questions we examined effects of systemically administered BMP2 and 7 on bone in a newly developed rat model with a low level of calciotropic hormones. Removal of thyroid and parathyroid glands (TPTx) in rats resulted in the decreased level of thyroid hormones, PTH, calcitonin and 1,25(OH)2D3 and a subsequent bone loss assessed by microCT and measurement of serum bone formation and resorption markers, including osteocalcin, C-telopeptide, osteoprotegerin and receptor activator of nuclear factor kappa-B ligand. Additionally, BMP2 and 7 were tested in vitro to estimate their influence on osteoblast and osteoclast activity. The administered doses have been calculated according to published bioavailability data 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 all doses of BMP7. BMP2 showed a higher capacity for enhancing trabecular microarchitecture, i.e. increasing trabecular number and diminishing trabecular spacing. In contrast, BMP7 augmented trabecular thickness. In vitro experiments revealed that BMP2 and 7, when uncoupled, increased the number and activity of both osteoblasts and osteoclasts. Collectively, both BMP2 and 7 showed ability to increase bone volume in an in vivo environment of low calciotropic hormones. Therefore, locally administered BMP2 and 7 from bone devices might become partially available in circulation but will not mediate a systemic bone loss.
Disclosure: The authors declared no competing interests.