Local Administration of Ibandronate and Bone Morphogenetic Protein-2 After Ischemic Osteonecrosis of the Immature Femoral Head

Vandermeer, Jacob S.; Kamiya, Nobuhiro; Aya-ay, James; Garces, Amanda; Browne, Richard; Kim, Harry K. W.
May 2011
Journal of Bone & Joint Surgery, American Volume;5/18/2011, Vol. 93-A Issue 10, p905
Academic Journal
Background: Bisphosphonate therapy has been shown to preserve the osteonecrotic femoral head in experimental and short-term clinical studies. However, a lack of new bone formation within the preserved femoral head due to the inhibition of bone remodeling is a concern. The purpose of this investigation was to determine if combined therapy consisting of ibandronate and bone mprphogenetic protein-2 (BMP-2) can preserve the shape of the femoral head and stimulate new bone formation in an immature animal model of ischemic osteonecrosis. Methods: lschemic osteonecrosis was surgically induced in immature pigs. Four groups were studied: normal, treated with saline solution, treated with ibandronate, and treated with both ibandronate and BMP-2 (the ibandronate + BMP-2 group). The animals were killed eight weeks after surgery. Radiographic, histological, and histomorphometric assessments were performed. Results: Radiographic assessment showed better preservation of the femoral head shape-i.e., a 54% (Cl [95% confidence interval]: 22%, 86%) higher mean epiphyseal quotient-in the ibandronate + BMP-2 group than in the saline group. Histological assessment showed increased trabecular bone in the bandronate + BMP-2 group as compared with that in the saline group. The mean values for trabecular bone volume, thickness, and number and for osteoblast surface were an average of 400% (Cl: 242%; 558%), 212% (Cl: 166%, 259%), 71% (Cl: 6%, 137%), and 2402% (Cl: 2113%, 2693%) higher, respectively, in the ibandronate + BMP-2 group than in the saline group. The osteoclast number was significantly reduced in the ibandronate + BMP-2 group compared with that in the saline group (-59% [Cl: -75%, -42%]). The mean osteoblast surface value in the ibandronate + BMP-2 group was significantly higher (2567% [Cl: 2258%, 2877%]) than that in the ibandronate group. Heterotopic ossifications were present in the capsule of the hip joint in the ibandronate + BMP-2 group. Conclusions: A combination of ibandronate and BMP-2 decreased femoral head deformity while stimulating bone formation in an immature animal model of ischemic osteonecrosis. Clinical Relevance: The findings provide a proof of concept that a combination of antiresorptive and anabolic agents can significantly improve bone healing and decrease deformity following ischemic osteonecrosis in the immature femoral head of a pig. Additional studies are needed to investigate whether heterotopic ossification can be prevented.


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