Local administration of ibandronate and bone morphogenetic protein-2 after ischemic osteonecrosis of the immature femoral head: A combined therapy that stimulates bone formation and decreases femoral head deformity

Jacob S. Vandermeer, Nobuhiro Kamiya, James Aya-ay, Amanda Garces, Richard Browne, Harry K W Kim

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 morphogenetic 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: Ischemic 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% (CI [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 ibandronate + 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% (CI: 242%, 558%), 212% (CI: 166%, 259%), 71% (CI: 6%, 137%), and 2402% (CI: 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% [CI: -75%, -42%]). The mean osteoblast surface value in the ibandronate + BMP-2 group was significantly higher (2567% [CI: 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.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalJournal of Bone and Joint Surgery - Series A
Volume93
Issue number10
DOIs
StatePublished - May 18 2011

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Bone Morphogenetic Protein 2
Osteonecrosis
Thigh
Osteogenesis
Therapeutics
Heterotopic Ossification
Osteoblasts
ibandronic acid
Coxa Magna
Swine
Animal Models
Bone Density Conservation Agents
Anabolic Agents
Bone Remodeling
Hip Joint
Diphosphonates
Osteoclasts
Sodium Chloride
Capsules

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

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Local administration of ibandronate and bone morphogenetic protein-2 after ischemic osteonecrosis of the immature femoral head : A combined therapy that stimulates bone formation and decreases femoral head deformity. / Vandermeer, Jacob S.; Kamiya, Nobuhiro; Aya-ay, James; Garces, Amanda; Browne, Richard; Kim, Harry K W.

In: Journal of Bone and Joint Surgery - Series A, Vol. 93, No. 10, 18.05.2011, p. 905-913.

Research output: Contribution to journalArticle

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abstract = "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 morphogenetic 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: Ischemic 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{\%} (CI [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 ibandronate + 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{\%} (CI: 242{\%}, 558{\%}), 212{\%} (CI: 166{\%}, 259{\%}), 71{\%} (CI: 6{\%}, 137{\%}), and 2402{\%} (CI: 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{\%} [CI: -75{\%}, -42{\%}]). The mean osteoblast surface value in the ibandronate + BMP-2 group was significantly higher (2567{\%} [CI: 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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AU - Kamiya, Nobuhiro

AU - Aya-ay, James

AU - Garces, Amanda

AU - Browne, Richard

AU - Kim, Harry K W

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