Effect of local zoledronic acid administration in a rat model of posterolateral spinal fusion

Strickland, Ashley R; Cavanaugh, Daniel L.; Leatherwood, William H.; Raynor, James; Brown, Alexander; Weinhold, Paul S.

doi:10.1016/j.jor.2019.08.021

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…As seen in systemic ZOL treatment, the topical treatment of ZOL co-administration with rh-BMP-2 also promoted and maintained new bone formation in the bone marrow environment. Topical administration of ZOL has been considered to reduce the associated side effects and limit the effect to a target site [ 22 ]. ZOL is known to cause side effects such as hypocalcemia, renal failure, or osteonecrosis of the jaw.…”

Section: Discussionmentioning

confidence: 99%

Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

Ueyama

Ohta

Imai

et al. 2021

BMC Musculoskelet Disord

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Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

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Section: Discussionmentioning

confidence: 99%

Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

Ueyama

Ohta

Imai

et al. 2021

BMC Musculoskelet Disord

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“…These doses fall within a range where previous studies have demonstrated a clinically significant treatment effect through local administration. 35 , 36 …”

Section: Methodsmentioning

confidence: 99%

Local application of zoledronate inhibits early bone resorption and promotes bone formation

Hsieh,

Wang,

Kao

et al. 2024

JBMR Plus

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Nonunion resulting from early bone resorption is common after bone transplantation surgery. In these patients, instability or osteoporosis causes hyperactive catabolism relative to anabolism, leading to graft resorption instead of fusion. Systemic zoledronate administration inhibits osteoclastogenesis and is widely used to prevent osteoporosis; however, evidence on local zoledronate application is controversial due to osteoblast cytotoxicity, uncontrolled dosing regimens, and local release methods. We investigated the effects of zolendronate on osteoclastogenesis and osteogenesis and explored the corresponding signaling pathways. In vitro cytotoxicity and differentiation of MC3T3E1 cells, rat bone marrow stromal cells (BMSCs) and preosteoclasts (RAW264.7 cells) were evaluated with different zolendronate concentrations. In vivo bone regeneration ability was tested by transplanting different concentrations of zolendronate with β-TCP bone substitute into rat femoral critical-sized bone defects. In vitro, zolendronate concentrations below 2.5 × 10-7 M did not compromise viability in the three cell lines and did not promote osteogenic differentiation in MC3T3E1 cells and BMSCs. In RAW264.7 cells, zoledronate inhibited ERK and JNK signaling, downregulating c-Fos and NFATc1 expression, with reduced expression of fusion-related DC-STAMP and osteoclast-specific Ctsk and TRAP. In vivo, histological staining revealed increased osteoid formation and neovascularization and reduced fibrotic tissue with 500 μM and 2000 μM zolendronate. More osteoclasts were found in the normal saline group after 6 weeks, and sequential osteoclast formation occurred after zoledronate treatment, indicating inhibition of bone resorption during early callus formation without inhibition of late-stage bone remodeling. In vivo, soaking β-TCP artificial bone with 500 μM or 2000 μM zoledronate is a promising approach for bone regeneration, with potential applications in bone transplantation.

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The effect of cannabinoids on single-level lumbar arthrodesis outcomes in a rat model

Fogel,

Yeritsyan,

Momenzadeh

et al. 2024

The Spine Journal

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Effect of local zoledronic acid administration in a rat model of posterolateral spinal fusion

Cited by 3 publications

References 14 publications

Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

Local application of zoledronate inhibits early bone resorption and promotes bone formation

The effect of cannabinoids on single-level lumbar arthrodesis outcomes in a rat model

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