Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head: An experimental investigation in immature pigs

Harry K W Kim, Olumide Aruwajoye, Justin Du, Nobuhiro Kamiya

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19 Citations (Scopus)

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-Calve-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-Calve-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 (BMP1IB 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.

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.

Results: Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP1IB 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 BMP1IB group than in the BMP group (p = 0.02) and the NWB group (p 0.001). BMP1IB 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 BMP1IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP1IB groups than in the NWB group (p 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP1IB group but not in the BMP group.

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.

Original languageEnglish (US)
Pages (from-to)1515-1524
Number of pages10
JournalJournal of Bone and Joint Surgery - American Volume
Volume96
Issue number18
DOIs
StatePublished - Sep 17 2014

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Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Osteonecrosis
Diphosphonates
Thigh
Osteogenesis
Swine
Legg-Calve-Perthes Disease
Heterotopic Ossification
Animal Models
Bone Resorption
Bone and Bones
Therapeutics
Ischemia
X Ray Tomography
X-Ray Microtomography
Osteoclasts
Amputation
Capsules
Hip

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine
  • Medicine(all)

Cite this

@article{c4cfff8afa334e4abef04e5c17218510,
title = "Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head: An experimental investigation in immature pigs",
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-Calve-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-Calve-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 (BMP1IB 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.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.Results: Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP1IB 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 BMP1IB group than in the BMP group (p = 0.02) and the NWB group (p 0.001). BMP1IB 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 BMP1IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP1IB groups than in the NWB group (p 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP1IB group but not in the BMP group.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.",
author = "Kim, {Harry K W} and Olumide Aruwajoye and Justin Du and Nobuhiro Kamiya",
year = "2014",
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day = "17",
doi = "10.2106/JBJS.M.01361",
language = "English (US)",
volume = "96",
pages = "1515--1524",
journal = "Journal of Bone and Joint Surgery - American Volume",
issn = "0021-9355",
publisher = "Journal of Bone and Joint Surgery Inc.",
number = "18",

}

TY - JOUR

T1 - Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head

T2 - An experimental investigation in immature pigs

AU - Kim, Harry K W

AU - Aruwajoye, Olumide

AU - Du, Justin

AU - Kamiya, Nobuhiro

PY - 2014/9/17

Y1 - 2014/9/17

N2 - Background: Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calve-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-Calve-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 (BMP1IB 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.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.Results: Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP1IB 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 BMP1IB group than in the BMP group (p = 0.02) and the NWB group (p 0.001). BMP1IB 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 BMP1IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP1IB groups than in the NWB group (p 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP1IB group but not in the BMP group.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.

AB - Background: Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calve-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-Calve-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 (BMP1IB 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.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.Results: Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP1IB 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 BMP1IB group than in the BMP group (p = 0.02) and the NWB group (p 0.001). BMP1IB 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 BMP1IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP1IB groups than in the NWB group (p 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP1IB group but not in the BMP group.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.

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U2 - 10.2106/JBJS.M.01361

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