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Archives of Orthopaedic and Trauma Surgery

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01-01-2018 | Orthopaedic Surgery

Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model

Authors: Pawel Zwolak, Jan Farei-Campagna, Thorsten Jentzsch, Brigitte von Rechenberg, Clément M. Werner

Published in: Archives of Orthopaedic and Trauma Surgery | Issue 1/2018

Abstract

Background

Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model.

Methods

A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery.

Results

The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1–S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone.

Conclusions

A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our results justify further investigations to potentially use local application of zoledronic acid in future clinical studies.

Omidi-Kashani F, Hasankhani EG, Rahimi MD, Khanzadeh R (2014) Comparison of functional outcomes following surgical decompression and posterolateral instrumented fusion in single level low grade lumbar degenerative versus isthmic spondylolisthesis. Clin Orthop Surg 6:185–189CrossRefPubMedPubMedCentral

Choi KC, Shim HK, Kim JS, Lee SH (2015) Does pre-existing L5–S1 degeneration affect outcomes after isolated L4–5 fusion for spondylolisthesis? J Orthop Surg Res 10:39CrossRefPubMedPubMedCentral

Ajiboye RM, Hamamoto JT, Eckardt MA, Wang JC (2015) Clinical and radiographic outcomes of concentrated bone marrow aspirate with allograft and demineralized bone matrix for posterolateral and interbody lumbar fusion in elderly patients. Eur Spine J 24:2567–2572CrossRefPubMed

Fu TS, Wang IC, Lu ML, Hsieh MK, Chen LH, Chen WJ (2016) The fusion rate of demineralized bone matrix compared with autogenous iliac bone graft for long multi-segment posterolateral spinal fusion. BMC Musculoskelet Disord 17:3CrossRefPubMedPubMedCentral

Feiertag MA, Boden SD, Schimandle JH, Norman JT (1996) A rabbit model for nonunion of lumbar intertransverse process spine arthrodesis. Spine (Phila Pa 1976) 21:27–31CrossRef

McAfee PC, Farey ID, Sutterlin CE, Gurr KR, Warden KE, Cunningham BW (1991) The effect of spinal implant rigidity on vertebral bone density. A canine model. Spine (Phila Pa 1976) 16(6 Suppl):190–197CrossRef

Wing KJ, Fisher CG, O’Connell JX, Wing PC (2000) Stopping nicotine exposure before surgery. The effect on spinal fusion in a rabbit model. Spine (Phila Pa 1976) 25:30–34CrossRef

Kodera R, Miyazaki M, Yoshiiwa T, Kawano M, Kaku N, Tsumura H (2014) Manipulation of anabolic and catabolic responses with bone morphogenetic protein and zoledronic acid in a rat spinal fusion model. Bone 58:26–32CrossRefPubMed

Bransford R, Goergens E, Briody J, Amanat N, Cree A, Little D (2007) Effect of zoledronic acid in an L6–L7 rabbit spine fusion model. Eur Spine J 16:557–562CrossRefPubMed

10.

Deyo RA, Nachemson A, Mirza SK (2004) Spinal-fusion surgery—the case for restraint. N Engl J Med 350:722–726CrossRefPubMed

11.

Aghdasi B, Montgomery SR, Daubs MD, Wang JC (2013) A review of demineralized bone matrices for spinal fusion: the evidence for efficacy. Surgeon 11:39–48CrossRefPubMed

12.

Hoffmann MF, Jones CB, Sietsema DL (2012) Adjuncts in posterior lumbar spine fusion: comparison of complications and efficacy. Arch Orthop Trauma Surg 132:1105–1110CrossRefPubMed

13.

Kang J, An H, Hilibrand A, Yoon ST, Kavanagh E, Boden S (2012) Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions. Spine (Phila Pa 1976) 37:1083–1091CrossRef

14.

Tilkeridis K, Touzopoulos P, Ververidis A, Christodoulou S, Kazakos K, Drosos GI (2014) Use of demineralized bone matrix in spinal fusion. World J Orthop 5:30–37CrossRefPubMedPubMedCentral

15.

Benford HL, McGowan NW, Helfrich MH, Nuttall ME, Rogers MJ (2001) Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone 28:465–473CrossRefPubMed

16.

Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH (2007) Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 1117:209–257CrossRefPubMed

17.

Jobke B, Milovanovic P, Amling M, Busse B (2014) Bisphosphonate-osteoclasts: changes in osteoclast morphology and function induced by antiresorptive nitrogen-containing bisphosphonate treatment in osteoporosis patients. Bone 59:37–43CrossRefPubMed

18.

Zwolak P, Dudek AZ (2013) Antineoplastic activity of zoledronic acid and denosumab. Anticancer Res 33:2981–2988PubMed

19.

Kang CN, Kim CW, Moon JK (2016) The outcomes of instrumented posterolateral lumbar fusion in patients with rheumatoid arthritis. Bone Jt J 98-B:102–108CrossRef

20.

Martin GJ Jr, Boden SD, Titus L, Scarborough NL (1999) New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis. Spine (Phila Pa 1976) 24:637–645CrossRef

21.

Kim MK, Lee SH, Kim ES, Eoh W, Chung SS, Lee CS (2011) The impact of sagittal balance on clinical results after posterior interbody fusion for patients with degenerative spondylolisthesis: a pilot study. BMC Musculoskelet Disord 12:69CrossRefPubMedPubMedCentral

22.

Bobyn J, Rasch A, Little DG, Schindeler A (2013) Posterolateral inter-transverse lumbar fusion in a mouse model. J Orthop Surg Res 8:2CrossRefPubMedPubMedCentral

23.

Kiely PD, Brecevich AT, Taher F, Nguyen JT, Cammisa FP, Abjornson C (2014) Evaluation of a new formulation of demineralized bone matrix putty in a rabbit posterolateral spinal fusion model. Spine J 14:2155–2163CrossRefPubMed

24.

Faucheux C, Verron E, Soueidan A, Josse S, Arshad MD, Janvier P, Pilet P, Bouler JM, Bujoli B, Guicheux J (2009) Controlled release of bisphosphonate from a calcium phosphate biomaterial inhibits osteoclastic resorption in vitro. J Biomed Mater Res Part A 89:46–56CrossRef

25.

Mundy GR, Yoneda T, Hiraga T (2001) Preclinical studies with zoledronic acid and other bisphosphonates: impact on the bone microenvironment. Semin Oncol 28(2 Suppl 6):35–44CrossRefPubMed

26.

Peng H, Sohara Y, Moats RA, Nelson MD Jr, Groshen SG, Ye W, Reynolds CP, DeClerck YA (2007) The activity of zoledronic Acid on neuroblastoma bone metastasis involves inhibition of osteoclasts and tumor cell survival and proliferation. Cancer Res 67:9346–9355CrossRefPubMed

27.

Coscia M, Quaglino E, Iezzi M, Curcio C, Pantaleoni F, Riganti C, Holen I, Monkkonen H, Boccadoro M, Forni G, Musiani P, Bosia A, Cavallo F, Massaia M (2010) Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway. J Cell Mol Med 14:2803–2815CrossRefPubMed

28.

Im GI, Qureshi SA, Kenney J, Rubash HE, Shanbhag AS (2004) Osteoblast proliferation and maturation by bisphosphonates. Biomaterials 25:4105–4115CrossRefPubMed

29.

Reinholz GG, Getz B, Pederson L, Sanders ES, Subramaniam M, Ingle JN, Spelsberg TC (2000) Bisphosphonates directly regulate cell proliferation, differentiation, and gene expression in human osteoblasts. Cancer Res 60:6001–6007PubMed

30.

Back DA, Pauly S, Rommel L, Haas NP, Schmidmaier G, Wildemann B, Greiner SH (2012) Effect of local zoledronate on implant osseointegration in a rat model. BMC Musculoskelet Disord 13:42CrossRefPubMedPubMedCentral

31.

Konnecke I, Serra A, El Khassawna T, Schlundt C, Schell H, Hauser A, Ellinghaus A, Volk HD, Radbruch A, Duda GN, Schmidt-Bleek K (2014) T and B cells participate in bone repair by infiltrating the fracture callus in a two-wave fashion. Bone 64:155–165CrossRefPubMed

32.

Chen F, Dai Z, Kang Y, Lv G, Keller ET, Jiang Y (2016) Effects of zoledronic acid on bone fusion in osteoporotic patients after lumbar fusion. Osteoporos Int 27:1469–1476CrossRefPubMed

33.

Bobyn J, Rasch A, Kathy M, Little DG, Schindeler A (2014) Maximizing bone formation in posterior spine fusion using rhBMP-2 and zoledronic acid in wild type and NF1 deficient mice. J Orthop Res 32:1090–1094CrossRefPubMed

Title: Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model
Authors: Pawel Zwolak
Jan Farei-Campagna
Thorsten Jentzsch
Brigitte von Rechenberg
Clément M. Werner
Publication date: 01-01-2018
Publisher: Springer Berlin Heidelberg
Published in: Archives of Orthopaedic and Trauma Surgery / Issue 1/2018
Print ISSN: 0936-8051
Electronic ISSN: 1434-3916
DOI: https://doi.org/10.1007/s00402-017-2818-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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