Local Administration of Bone Morphogenetic Protein-2 and Bisphosphonate During Non-Weight-Bearing Treatment of Ischemic Osteonecrosis of the Femoral Head

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

doi:10.2106/jbjs.m.01361

Cited by 52 publications

(46 citation statements)

References 24 publications

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“…One budding solution to this increased activity of osteoclasts is to inhibit osteoclast function or number, thus effectively eliminating that particular side effect. 119 Bisphosphonates are a class of drugs directed at preventing loss of bone mass and are clinically relevant by treating osteoporosis. [120][121][122] Use of bisphosphonates in conjunction with BMP-2 proved to significantly decrease the number of osteoclasts per bone surface area.…”

Section: Addition Of Bisphosphonatesmentioning

confidence: 99%

“…In an experiment conducted on piglets with Legg-Calvé-Perthes disease, BMP-2 administered with bisphosphonate decreased bone resorption while maintaining increased new bone formation compared with BMP-2 alone. 119 With this decrease, extreme bone loss associated with BMP-2 that could lead to osteolysis and subsidence can be avoided. Conversely, with a decreased quantity of osteoclasts, osteoblastic differentiation and functionality are much less regulated, and side effects such as heterotopic ossification are found much more frequently than with BMP-2 use alone.…”

Section: Addition Of Bisphosphonatesmentioning

confidence: 99%

“…Conversely, with a decreased quantity of osteoclasts, osteoblastic differentiation and functionality are much less regulated, and side effects such as heterotopic ossification are found much more frequently than with BMP-2 use alone. 119 …”

Section: Addition Of Bisphosphonatesmentioning

confidence: 99%

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A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

James

LaChaud

Shen

et al. 2016

Tissue Engineering Part B: Reviews

852

769

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Bone morphogenetic protein-2 (BMP-2) is currently the only Food and Drug Administration (FDA)-approved osteoinductive growth factor used as a bone graft substitute. However, with increasing clinical use of BMP-2, a growing and well-documented side effect profile has emerged. This includes postoperative inflammation and associated adverse effects, ectopic bone formation, osteoclast-mediated bone resorption, and inappropriate adipogenesis. Several large-scale studies have confirmed the relative frequency of adverse events associated with the clinical use of BMP-2, including life-threatening cervical spine swelling. In fact, the FDA has issued a warning of the potential life-threatening complications of BMP-2. This review summarizes the known adverse effects of BMP-2, including controversial areas such as tumorigenesis. Next, select animal models that replicate BMP-2's adverse clinical effects are discussed. Finally, potential molecules to mitigate the adverse effects of BMP-2 are reviewed. In summary, BMP-2 is a potent osteoinductive cytokine that has indeed revolutionized the bone graft substitute market; however, it simultaneously has accrued a worrisome side effect profile. Better understanding of these adverse effects among both translational scientists and clinicians will help determine the most appropriate and safe use of BMP-2 in the clinical setting.

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Section: Addition Of Bisphosphonatesmentioning

confidence: 99%

Section: Addition Of Bisphosphonatesmentioning

confidence: 99%

See 1 more Smart Citation

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

James

LaChaud

Shen

et al. 2016

Tissue Engineering Part B: Reviews

852

769

View full text Add to dashboard Cite

show abstract

“…While the use of ibandronate alone maintains bone volume after the induction of ischemic osteonecrosis by decreasing bone resorption, the trabecular bone treated with ibandronate lacks remodeling of the necrotic bone and new bone formation. The trabecular microstructure of the BMP + IB‐treated group showed thicker trabeculae due to the appositional bone formation on the surface of the necrotic bone maintained by IB treatment, thus, yielding a mixed distribution of mineral from newer and older trabecular bone. Decreased remodeling has been shown previously to increase the mineral content of bone treated with bisphosphonate in normal beagles and osteoporotic patients .…”

Section: Discussionmentioning

confidence: 99%

“…Bisphosphonates and bone morphogenetic proteins (BMPs) have previously been used as treatment in experimental models of femoral head osteonecrosis . Bone morphogenic proteins are potential therapeutic options that play a pivotal role in bone formation during bone development and fracture healing .…”

mentioning

confidence: 99%

Material properties of bone in the femoral head treated with ibandronate and BMP-2 following ischemic osteonecrosis

2016

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Bone morphogenetic protein (BMP)-2 and ibandronate (IB) decrease the femoral head deformity following ischemic osteonecrosis of the femoral head (ONFH). The purpose of this study was to determine the effects of BMP-2 and IB on the mineral content and nanoindentation properties of the bone following ONFH. ONFH was surgically induced in the femoral head of piglets. There were five groups: normal control, untreated, IB, BMP, and BMP + IB (n = 5/group). Backscattered electron imaging, Raman spectroscopy, and nanoindentation testing were performed. Both BMP and BMP + IB groups showed calcium content in the trabecular bone similar to the normal group, while the IB and no-treatment groups showed a significant increase in the calcium content compared to the normal group. The carbonate content relative to phosphate was significantly increased in the IB and BMP + IB groups (p < 0.01) compared to the normal group. No significant difference was found between the BMP and the normal group. The nanoindentation modulus of the bone in the IB group was significantly increased compared to the normal group (p < 0.05). No significant differences were observed between the BMP and BMP + IB groups compared to the normal group. The nanoindentation hardness measurements in the IB group were also significantly increased compared to the BMP and BMP + IB groups (p < 0.05). In summary, trabecular bone treated with BMP or BMP + IB had material properties comparable to normal bone whereas the bone in the IB group retained the increased mineral content and the nanoindentation hardness found in the necrotic bone. Hence, BMP or BMP + IB better restores the normal mineral content and nanomechanical properties after ONFH than IB treatment alone. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1453-1460, 2017.

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Patient‐Specific Bone Particles Bioprinting for Bone Tissue Engineering

Ratheesh

Vaquette

Xiao

2020

Adv Healthcare Materials

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Although bioinks with both high printability and shape fidelity while maintaining high cell viability are developed, the biofunctionality of the resulting bioprinted construct is often overlooked. To address this, a methacrylated gelatin (GelMA)-based bioink biofunctionalized with bone particles (BPs) is developed as a personalized treatment strategy for bone regeneration. The bioink consists of incorporating BPs of various sizes (0-500 µm) in GelMA at various concentrations (ranging from 5 to 15% w/v). The printability of the bioink is systematically investigated and it is demonstrated that a 15% w/v BP-loading results in high print quality for 10% and 12.5% GelMA concentrations. Rheological evaluation reveals a strong shear thinning behavior essential for printing and a high gel strength in bioink with 15% w/v 0-500 µm BPs for both GelMA concentrations. In addition, the printability of the bioink and the metabolic activity of the resulting scaffolds are dependent on both the concentration of hydrogel and size of the BPs. Importantly, the cells initially contained in the BPs are able to migrate and colonize the bioprinted scaffold while maintaining their capacity to express early osteogenic markers. This study demonstrates the feasibility of bioprinted viable BPs and may have some potential for chairside clinical translation.

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Local Administration of Bone Morphogenetic Protein-2 and Bisphosphonate During Non-Weight-Bearing Treatment of Ischemic Osteonecrosis of the Femoral Head

Abstract: 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.

Cited by 52 publications

References 24 publications

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

Material properties of bone in the femoral head treated with ibandronate and BMP-2 following ischemic osteonecrosis

Patient‐Specific Bone Particles Bioprinting for Bone Tissue Engineering

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