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Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion – Lumbar Fusion

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The article discusses the limitations of using recombinant human bone morphogenetic protein-2 (rhBMP-2) for lumbar fusion due to issues with initial burst release and late bone resorption. The study aimed to improve posterolateral spinal fusion (PLF) by delivering rhBMP-2 and zoledronic acid (ZA) using a calcium sulfate/hydroxyapatite (CaS/HA) carrier. The results showed that the combination of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF without inhibiting systemic bone turnover. This treatment regimen could potentially be a safe and cost-effective solution to enhance spinal fusion

Summarised by Mr Mo Akmal – Lead Spinal Surgeon
The London Spine Unit : most established treatment facility in UK

Published article

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this in vivo study was to analyze if…

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Bioact Mater. 2024 Mar 6;36:256-271. doi: 10.1016/j.bioactmat.2024.02.034. eCollection 2024 Jun.ABSTRACTRecombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is,

Bioact Mater. 2024 Mar 6;36:256-271. doi: 10.1016/j.bioactmat.2024.02.034. eCollection 2024 Jun.

ABSTRACT

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this alive study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA). Six groups were allocated (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, and CaS/HA + BMP-2 + local ZA). 10-week-old male Wistar rats, were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds. At 3 and 6 weeks, the animals were euthanized for radiography, μCT, histological staining, or biomechanical testing to evaluate spinal fusion. The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn’t support PLF. However, the delivery of rhBMP-2 significantly promoted PLF. Combining systemic ZA with BMP-2 didn’t enhance spinal fusion. Notably, the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF, without inhibiting systemic bone turnover, and potentially reduced the dose of rhBMP-2. Together, the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.

PMID:38487704 | PMC:PMC10937206 | DOI:10.1016/j.bioactmat.2024.02.034

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Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion

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Bioact Mater. 2024 Mar 6;36:256-271. doi: 10.1016/j.bioactmat.2024.02.034. eCollection 2024 Jun.ABSTRACTRecombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is
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