Manipulation of the Anabolic and Catabolic Responses With OP-1 and Zoledronic Acid in a Rat Critical Defect Model

Abstract Background: The use of long-term and high-dose bisphosphate is associated with severely suppressed bone turnover and the delayed union of fractures. However, therapeutic methods to overcome the negative effects of bisphosphonate use are lacking. Bone morphogenetic proteins (BMPs) are powerful osteoinductive proteins. We hypothesized that BMPs had similar effects as autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment. The purpose of this study was to compare BMPs with demineralized freeze-dried bone grafts and autografts in a rat femoral bone defect model with long-term and high-dose bisphosphonate treatment. Methods: Forty rats were divided into the following four groups depending upon the materials implanted into the femoral defect after ten weeks of bisphosphonate (zoledronic acid) injections: Group I: absorbable collagen sponge (control); group II: demineralized freeze-dried bone graft; group III: autogenous bone graft; and group IV: rhBMP-2 with an absorbable collagen sponge. Radiographic union, micro computed tomography (CT) analysis, manual palpation, and histologic analysis were evaluated. Results: The radiographic union rate, manual union rate, and micro-CT bone volume in groups III and IV were significantly higher than those in groups I and II. Groups III and IV showed similar results to each other. Although the amount of immature bone in the BMP-treated group was large, the effect was similar to that of autografts in the bone defect model in which bone turnover was severely reduced by bisphosphonate treatment. Conclusion: BMP might be a good substitute for autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment.

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BMP-2 Promotes Bone Formation in Bone Defects in Which Bone Remodeling Is Suppressed by Long-term and High-dose Zoledronic Acid

10.21203/rs.3.rs-684348/v1 ◽

2021 ◽

Author(s):

Young Jae Moon ◽

Seongyup Jeong ◽

Kwang-Bok Lee

Keyword(s):

Zoledronic Acid ◽

Collagen Sponge ◽

High Dose ◽

Bisphosphonate Treatment ◽

Union Rate ◽

Defect Model ◽

Absorbable Collagen Sponge ◽

Freeze Dried ◽

Radiographic Union

Abstract Background: The use of long-term and high-dose bisphosphate is associated with severely suppressed bone turnover and the delayed union of fractures. However, therapeutic methods to overcome the negative effects of bisphosphonate use are lacking. Bone morphogenetic proteins (BMPs) are powerful osteoinductive proteins. We hypothesized that BMPs had similar effects as autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment. The purpose of this study was to compare BMPs with demineralized freeze-dried bone grafts and autografts in a rat femoral bone defect model with long-term and high-dose bisphosphonate treatment. Methods: Forty rats were divided into the following four groups depending upon the materials implanted into the femoral defect after ten weeks of bisphosphonate (zoledronic acid) injections: Group I: absorbable collagen sponge (control); group II: demineralized freeze-dried bone graft; group III: autogenous bone graft; and group IV: rhBMP-2 with an absorbable collagen sponge. Radiographic union, micro computed tomography (CT) analysis, manual palpation, and histologic analysis were evaluated. Results: The radiographic union rate, manual union rate, and micro-CT bone volume in groups III and IV were significantly higher than those in groups I and II. Groups III and IV showed similar results to each other. Although the amount of immature bone in the BMP-treated group was large, the effect was similar to that of autografts in the bone defect model in which bone turnover was severely reduced by bisphosphonate treatment. Conclusion: BMP might be a good substitute for autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment.

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Utilization of the AO LockingRatNail in a Novel Rat Femur Critical Defect Model

Journal of Investigative Surgery ◽

10.3109/08941939.2012.655370 ◽

2012 ◽

Vol 25 (6) ◽

pp. 381-386 ◽

Cited By ~ 6

Author(s):

Harvey E. Montijo ◽

James F. Kellam ◽

F. Keith Gettys ◽

James S. Starman ◽

MAJ Kenneth J. Nelson ◽

...

Keyword(s):

Rat Femur ◽

Defect Model ◽

Critical Defect

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A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein–2 and zoledronic acid

Science Advances ◽

10.1126/sciadv.abc1779 ◽

2020 ◽

Vol 6 (48) ◽

pp. eabc1779

Author(s):

Deepak Bushan Raina ◽

Lucas-Maximilian Matuszewski ◽

Corina Vater ◽

Julia Bolte ◽

Hanna Isaksson ◽

...

Keyword(s):

Zoledronic Acid ◽

Calcium Sulfate ◽

Bone Defects ◽

Bone Morphogenic Proteins ◽

Femoral Defect ◽

Defect Healing ◽

Critical Defect ◽

Delivery Platform ◽

Critical Bone Defects ◽

Bone Morphogenic Protein 2

Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made. We demonstrate that a carrier consisting of a powder of calcium sulfate/hydroxyapatite (CaS/HA) mixed with bone active molecules provides an efficient drug delivery platform for critical femoral defect healing in rats. The bone-active molecules were composed of osteoinductive rhBMP-2 and the bisphosphonate, and zoledronic acid (ZA) was chosen to overcome BMP-2–induced bone resorption. It was demonstrated that delivery of rhBMP-2 was necessary for critical defect healing and restoration of mechanical properties, but codelivery of BMP-2 and ZA led to denser and stronger fracture calluses. Together, the CaS/HA biomaterial with rhBMP-2 and/or ZA can potentially be used as an off-the-shelf alternative to autograft bone.

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Efficacy of silicate-substituted calcium phosphate with enhanced strut porosity as a standalone bone graft substitute and autograft extender in an ovine distal femoral critical defect model

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-015-5559-3 ◽

2015 ◽

Vol 27 (1) ◽

Cited By ~ 8

Author(s):

Stacy A. Hutchens ◽

Charlie Campion ◽

Michel Assad ◽

Madeleine Chagnon ◽

Karin A. Hing

Keyword(s):

Calcium Phosphate ◽

Bone Graft ◽

Bone Graft Substitute ◽

Defect Model ◽

Critical Defect

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Biodegradable Adhesive (LYDEX) with Hydroxyapatite Granules

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.361-363.575 ◽

2007 ◽

Vol 361-363 ◽

pp. 575-578 ◽

Cited By ~ 4

Author(s):

T. Yamamoto ◽

Shunsuke Fujibayashi ◽

Naoki Nakajima ◽

Hajime Sugai ◽

Suong Hyu Hyon ◽

...

Keyword(s):

Bone Substitute ◽

Bone Repair ◽

Setting Time ◽

Risk Of Infection ◽

Defect Model ◽

Critical Defect ◽

Low Cytotoxicity ◽

Schiff Base Formation ◽

Base Formation

A new biodegradable adhesive(LYDEX) which is based on Schiff base formation had developed. LYDEX is easy to control the setting time and degradation speed and it has no risk of infection. In the previous study, LYDEX showed high bonding strength and low cytotoxicity in vitro[1]. In the present study, good bone repair was seen in rat bone defect models, especially in rapidly degrading type. On the other hand, slowly degrading type kept its shape longer without excessive inflammation. In rabbit critical defect model with hydroxyapatite granules (HAs), more newly formed bone was seen in rapidly degrading group and hydroxyapatite group, in 3weeks. In 6weeks, more new bone was seen in slowly degrading type group, whereas, almost no new bone was seen in deep area of the fibrin group, in 12weeks. Direct bonding between HAs and bone was seen in HA group and LYDEX groups. These findings suggest that LYDEX with hydroxyapatite granules can be a promising bone substitute.

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