Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model

Kanezaki, Shozo; Miyazaki, Masashi; Ishihara, Toshinobu; Notani, Naoki; Abe, Tetsutaro; Tsubouchi, Yuhta; Kataoka, Masashi; Tsumura, Hiroshi

doi:10.1186/s13018-019-1470-9

Cited by 8 publications

(8 citation statements)

References 26 publications

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“…Fourth, we did not perform biomechanical testing that could quantify the degree of bony union. Instead, we evaluated bony union by the manual palpation method [13,21,22,23].…”

Section: Discussionmentioning

confidence: 99%

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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

Moon¹,

Jeong²,

Lee³

2021

Preprint

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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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“…Fourth, we did not perform biomechanical testing that could quantify the degree of bony union. Instead, we evaluated bony union by the manual palpation method [13,21,22,23].…”

Section: Discussionmentioning

confidence: 99%

“…Manual palpation is a sensitive and speci c method of assessing bone fusion [13,21,22,23]. Manual palpation with varus/valgus and anterior/posterior angulated force was performed for all harvested specimens with a particular focus at the defect region.…”

Section: Manual Palpation and Manipulationmentioning

confidence: 99%

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

Moon¹,

Jeong²,

Lee³

2021

Preprint

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“…We previously reported that the synergistic effect of rhBMP-2 and PTH 1-34 administered systemically as a single dose at the optimal time was e cacious for fracture repair and signi cantly enhanced bone fusion in a rat femoral fracture model [22]. The purpose of this study was to clarify the optimal dosing interval and administration method for the combination of rhBMP-2 and PTH 1-34 in a rat spinal fusion model.…”

Section: Introductionmentioning

confidence: 98%

Optimal Intermittent Administration Interval of Parathyroid Hormone 1-34 for Bone Morphogenetic Protein-induced Bone Formation in a Rat Spinal Fusion Model

Abe

Miyazaki

Ishihara

et al. 2020

Preprint

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Background: Both bone morphogenetic protein 2 (BMP-2) and teriparatide (parathyroid hormone [PTH] 1-34) are used to enhance bone healing. There is still no established opinion regarding the optimum dose and administration method. We investigated the optimal dose and administration method for the combination of BMP-2 and PTH 1-34 in a rat spinal fusion model. Methods: Group I was implanted with a control carrier. Groups II, III, and IV were implanted with a carrier containing 3μg of recombinant human BMP-2 (rhBMP-2). In addition, following implantation, PTH 1-34 injections were administered to Group III thrice a week (total, 180 μg/kg/week) and Group IV six times a week (total, 180 µg/kg/week). The rats were euthanized after 8 weeks, and their spines were explanted; assessed by manual palpation, radiographs, and high-resolution micro-computed tomography (micro-CT); and subjected to histological analysis. Serum markers of bone metabolism were also analyzed. Results: Manual palpation tests showed that the fusion rates in Groups III and IV were considerably higher than those in Group I. They also had higher radiographic scores than Group I. Micro-CT analysis revealed enhanced bone marrow density expressed as bone volume/tissue volume in Group IV versus Group I. Serum marker analysis revealed that Group IV had higher osteocalcin and lower tartrate-resistant acid phosphatase-5b than Group III. Histological analysis indicated that Group IV had enhanced remodeling. Conclusions: The rhBMP-2 and PTH combination enhanced bone fusion and remodeling of newly formed bone in the rat spinal fusion model. More frequent administration may be superior in terms of bone fusion and bone metabolism.

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“…Bone healing is accelerated upon treatment with the parathyroid hormone in animal models 10 11 12) . Some studies also report the bone-healing potential of teriparatide, when used in human subjects who have vertebral or lower limb fractures 13 14 15 16 17) .…”

Section: Introductionmentioning

confidence: 99%

Effects of Teriparatide on Treatment Outcomes in Osteoporotic Hip and Pelvic Bone Fractures: Meta-analysis and Systematic Review of Randomized Controlled Trials

et al. 2020

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The primary objective of this study was to evaluate randomized controlled trials (RCTs) that have reported the effects of teriparatide on bone-healing in osteoporotic hip and pelvic bone fractures to determine the efficacy of teriparatide in lowering the rate of treatment failure. A total of 2,809 studies were identified using a comprehensive literature search (MEDLINE [n=1,061], Embase [n=1,395], and Cochrane Library n=353]). Five RCTs were included in the final analysis. Treatment failure rates at the last follow-up of osteoporotic hip and pelvic bone fractures between the teriparatide and control groups was the primary outcome. Treatment failure was defined as non-union, varus collapse of the proximal fragment, perforation of the lag screw, and any revision in cases due to mechanical failure of the implant during the follow-up period. The number of treatment failures in the teriparatide and placebo groups were 11.0% (n=20 out of 181) and 17.6% (n=36 out of 205), respectively. Although the rate of treatment failure in the teriparatide group was lower than that in the control group, this difference was not significant (odds ratio, 0.81 [95% confidence interval, 0.42–1.53]; P=0.16; I 2 =42%). This meta-analysis did not identify any significant differences in the rate of treatment failure between the teriparatide and control groups at final follow-up. Based on these results, we believe that there is a lack of evidence to confirm efficacy of teriparatide in reducing treatment failures in osteoporotic hip and pelvic bone fractures.

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Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model

Cited by 8 publications

References 26 publications

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

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

Optimal Intermittent Administration Interval of Parathyroid Hormone 1-34 for Bone Morphogenetic Protein-induced Bone Formation in a Rat Spinal Fusion Model

Effects of Teriparatide on Treatment Outcomes in Osteoporotic Hip and Pelvic Bone Fractures: Meta-analysis and Systematic Review of Randomized Controlled Trials

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