BMP2

Material properties of bone in the femoral head treated with ibandronate and BMP-2 following ischemic osteonecrosis

Bone morphogenetic protein (BMP)-2 and ibandronate (IB) decrease the femoral head deformity following ischemic osteonecrosis of the femoral head (ONFH). The purpose of this study was to determine the effects of BMP-2 and IB on the mineral content and nanoindentation properties of the bone following ONFH. ONFH was surgically induced in a femoral head of piglets.

BMP Signaling is Required for Adult Skeletal Homeostasis and Mediates Bone Anabolic Action of Parathyroid Hormone

Bmp2 and Bmp4 genes were ablated in adult mice (KO) using a conditional gene knockout technology. Bones were evaluated by microcomputed tomography (μCT), bone strength tester, histomorphometry and serum biochemical markers of bone turnover. Drill-hole was made at femur metaphysis and bone regeneration in the hole site was measured by calcein binding and μCT.

A novel nonviral gene delivery tool of BMP-2 for the reconstitution of critical-size bone defects in rats

The osseointegration of bone implants, implant failure, and the bridging of critical-size bone defects are frequent clinical challenges. Deficiencies in endogenous bone healing can be resolved through the local administration of suitable recombinant growth factors (GFs).

Local Administration of Bone Morphogenetic Protein-2 and Bisphosphonate During Non-Weight-Bearing Treatment of Ischemic Osteonecrosis of the Femoral Head

Authors

Harry K.W. Kim, MD, MS; Olumide Aruwajoye, MS; Justin Du ; Nobuhiro Kamiya, MD, PhD

Abstract

Background: Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calvé-Perthes disease. We sought to determine if local administration of bone morphogenetic protein (BMP)-2 with or without bisphosphonate can increase the bone formation during the non-weight-bearing treatment in the large animal model of Legg-Calvé-Perthes disease.

Methods: Eighteen piglets were surgically induced with femoral head ischemia. Immediately following the surgery, all animals received an above-the-knee amputation to enforce local non-weight-bearing (NWB). One to two weeks later, six animals received local BMP-2 to the necrotic head (BMP group), six received local BMP-2 and ibandronate (BMP+IB group), and the remaining six received no treatment (NWB group). All animals were killed at eight weeks after the induction of ischemia. Radiographic, microcomputed tomography (micro-CT), and histomorphometric assessments were performed.

Results: Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP+IB groups had a decrease of 20%, 14%, and 10%, respectively, in their mean epiphyseal quotient in comparison with the normal control group. Micro-CT analyses showed significantly higher femoral head bone volume in the BMP+IB group than in the BMP group (p = 0.02) and the NWB group (p < 0.001). BMP+IB and BMP groups had a significantly higher trabecular number (p < 0.01) and lower trabecular separation (p < 0.02) than the NWB group. In addition, the osteoclast number per bone surface was significantly lower in the BMP+IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP+IB groups than in the NWB group (p < 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP+IB group but not in the BMP group.

Conclusions: Administration of BMP-2 with bisphosphonate best decreased bone resorption and increased new bone formation during non-weight-bearing treatment of ischemic osteonecrosis in a pig model, but heterotopic ossification is a concern.

Clinical Relevance: This preclinical study provides new evidence that BMP-2 with bisphosphonate can effectively prevent the extreme bone loss associated with the non-weight-bearing treatment and increase new bone formation in the femoral head in this animal model of ischemic osteonecrosis.

Link To Article

http://dx.doi.org/10.2106/JBJS.M.01361