The effect of bone morphogenic protein-7 on bone healing and formation in an osteoporotic environment

Abstract

Osteoporosis is major public health problem which is characterised by low bone mass, bone fragility and increased susceptibility to fracture. Fracture healing in osteoporosis is delayed; rates of implant failure are high. There is limited understanding of fracture healing in osteoporosis and no biological treatment options are available.

The work described herein is to investigate whether bone morphogenic protein-7 (BMP-7) can enhance fracture healing in osteoporosis from two perspectives.

The first study examined the effect of using a single dose of BMP-7 in a collagen/CMC composite (OP-1 putty, OP1) in femoral fracture healing in an ovarectomy rat model at 12, 20, and 31 days post surgery. Callus cross sectional area, bone mineral density, biomechanical stiffness and maximum torque, radiographic bony union and histological callus maturity were evaluated at each time point. There were statistically significant increases in bone mineral density and cross section area of callus at all time points in the OP-1 group compared to controls (CMC only), and biomechanical readings showed stronger bones at day 31 in the OP1 group. Histological and radiographic evaluation indicated acceleration of bony union in the OP1 group when compared with the control. These results suggested that BMP-7 accelerates fracture healing in an oestrogen deficient state in a rat femoral fracture healing model.

The second, an in vitro, study investigated the effect of BMP-7 on bone formation in an oestrogen-deficient environment in rat callus explant cultures at 24 and 48 hours. Osteogenic activity was evaluated by examining alkaline phosphatase activity, histological analysis and nitric oxide. Supplementation cultures with BMP-7, Oestrogen (E2) or in combination induced cell proliferation, increased AP activity and calcium mineralisation, with the greatest effect observed when BMP-7 and E2 were combined. Nitrite concentrations were increased by E2 but not by BMP-7 stimulation.

Together, the results of these studies may help to develop biological therapies (specifically BMP-7) for increasing the efficacy of bone fracture healing in osteoporosis in future.