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Bone union after spinal fusion surgery using local bone in long-term bisphosphonate users: a prospective comparative study

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Abstract

Summary

Bisphosphonates are the most commonly used drugs for osteoporosis and long-term use of bisphosphonates may affect fusion rate after spinal fusion surgery. There was significant delayed union after 6 months in long-term bisphosphonates users; however, there were no significant difference in fusion rate of long-term bisphosphonate users. Therefore, spinal fusion surgery should not be hesitated in long-term bisphosphonates users.

Purpose

Bisphosphonates (BPs) are the most popular class of drugs for treatment of postmenopausal osteoporosis. Long-term use of BPs may also inhibit the spinal fusion process after posterior lumbar interbody fusion (PLIF). We compared bone fusion rates of long-term BPs users and non-users after undergoing spinal fusion surgery.

Methods

A total of 97 postmenopausal women who were candidates for single-level PLIF were recruited from 2015 to 2016. Participants were divided into two groups, with 63 patients in a long-term BPs user group and 34 patients in a non-user group. Serum C-terminal cross-linking telopeptide (CTX) levels were checked for bone resorption markers. Bone fusion rates were calculated at 6 months and 1 and 2 years after the surgery. Clinical outcomes were measured using the Oswestry Disability Index (ODI) and visual analog scale (VAS).

Results

Serum CTX level was dramatically decreased in the long-term BPs user group (p < 0.05). Fusion rates at 6 months after surgery were 42% in the non-user group and 26% in the long-term BPs user group (p = 0.035). However, fusion rates were 82% in the long-term BPs user group and 87% in the non-user group at 2 years after surgery (p > 0.05). There was no significant difference between the two groups in ODI or VAS.

Conclusions

Even though there was significant delayed union after 6 months in long-term BPs users, at the 2-year postoperative follow-up, there was no significant difference in bone fusion rate between the two groups. Long-term BPs users showed fusion rates greater than 80% and clinical outcome improvements that were comparable to those in non-users. No significant effect on fusion rate after PLIF was found in long-term BPs users.

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References

  1. Chan CW, Peng P (2011) Failed back surgery syndrome. Pain Med 12(4):577–606. https://doi.org/10.1111/j.1526-4637.2011.01089.x

    Article  PubMed  Google Scholar 

  2. McGuire RA, Amundson GM (1993) The use of primary internal fixation in spondylolisthesis. Spine (Phila Pa 1976) 18(12):1662–1672

    Article  CAS  Google Scholar 

  3. West JL 3rd, Bradford DS, Ogilvie JW (1991) Results of spinal arthrodesis with pedicle screw-plate fixation. J Bone Joint Surg Am 73(8):1179–1184

    Article  PubMed  Google Scholar 

  4. Harris BM, Hilibrand AS, Savas PE, Pellegrino A, Vaccaro AR, Siegler S, Albert TJ (2004) Transforaminal lumbar interbody fusion: the effect of various instrumentation techniques on the flexibility of the lumbar spine. Spine (Phila Pa 1976) 29(4):E65–E70

    Article  Google Scholar 

  5. Hirsch BP, Unnanuntana A, Cunningham ME, Lane JM (2013) The effect of therapies for osteoporosis on spine fusion: a systematic review. Spine J 13(2):190–199. https://doi.org/10.1016/j.spinee.2012.03.035

    Article  PubMed  Google Scholar 

  6. Boden SD (1998) The biology of posterolateral lumbar spinal fusion. Orthop Clin North Am 29(4):603–619

    Article  CAS  PubMed  Google Scholar 

  7. Steinmann JC, Herkowitz HN (1992) Pseudarthrosis of the spine. Clin Orthop Relat Res (284):80–90

  8. Brown CW, Orme TJ, Richardson HD (1986) The rate of pseudarthrosis (surgical nonunion) in patients who are smokers and patients who are nonsmokers: a comparison study. Spine (Phila Pa 1976) 11(9):942–943

    Article  CAS  Google Scholar 

  9. Huang RC, Khan SN, Sandhu HS, Metzl JA, Cammisa FP Jr, Zheng F, Sama AA, Lane JM (2005) Alendronate inhibits spine fusion in a rat model. Spine (Phila Pa 1976) 30(22):2516–2522

    Article  Google Scholar 

  10. Goodman SB, Jiranek W, Petrow E, Yasko AW (2007) The effects of medications on bone. J Am Acad Orthop Surg 15(8):450–460

    Article  PubMed  Google Scholar 

  11. Gehrig L, Lane J, O’Connor MI (2008) Osteoporosis: management and treatment strategies for orthopaedic surgeons. J Bone Joint Surg Am 90(6):1362–1374

    Article  PubMed  Google Scholar 

  12. Lehman RA Jr, Kuklo TR, Freedman BA, Cowart JR, Mense MG, Riew KD (2004) The effect of alendronate sodium on spinal fusion: a rabbit model. Spine J 4(1):36–43

    Article  PubMed  Google Scholar 

  13. Xue Q, Li H, Zou X, Bunger M, Egund N, Lind M, Christensen FB, Bunger C (2005) The influence of alendronate treatment and bone graft volume on posterior lateral spine fusion in a porcine model. Spine (Phila Pa 1976) 30(10):1116–1121

    Article  Google Scholar 

  14. Rodan GA, Fleisch HA (1996) Bisphosphonates: mechanisms of action. J Clin Invest 97(12):2692–2696. https://doi.org/10.1172/JCI118722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lin JT, Lane JM (2003) Bisphosphonates. J Am Acad Orthop Surg 11(1):1–4

    Article  PubMed  Google Scholar 

  16. Xu XL, Gou WL, Wang AY, Wang Y, Guo QY, Lu Q, Lu SB, Peng J (2013) Basic research and clinical applications of bisphosphonates in bone disease: what have we learned over the last 40 years? J Transl Med 11:303. https://doi.org/10.1186/1479-5876-11-303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li C, Wang HR, Li XL, Zhou XG, Dong J (2012) The relation between zoledronic acid infusion and interbody fusion in patients undergoing transforaminal lumbar interbody fusion surgery. Acta Neurochir 154(4):731–738. https://doi.org/10.1007/s00701-012-1283-7

    Article  PubMed  Google Scholar 

  18. Nagahama K, Kanayama M, Togawa D, Hashimoto T, Minami A (2011) Does alendronate disturb the healing process of posterior lumbar interbody fusion? A prospective randomized trial. J Neurosurg Spine 14(4):500–507. https://doi.org/10.3171/2010.11.SPINE10245

    Article  PubMed  Google Scholar 

  19. Glassman SD, Polly DW, Bono CM, Burkus K, Dimar JR (2009) Outcome of lumbar arthrodesis in patients sixty-five years of age or older. J Bone Joint Surg Am 91(4):783–790. https://doi.org/10.2106/JBJS.H.00288

    Article  PubMed  Google Scholar 

  20. Okuda S, Oda T, Miyauchi A, Haku T, Yamamoto T, Iwasaki M (2006) Surgical outcomes of posterior lumbar interbody fusion in elderly patients. J Bone Joint Surg Am 88(12):2714–2720. https://doi.org/10.2106/JBJS.F.00186

    Article  PubMed  Google Scholar 

  21. Garnero P, Delmas PD (1998) Biochemical markers of bone turnover. Applications for osteoporosis. Endocrinol Metab Clin N Am 27(2):303–323

    Article  CAS  Google Scholar 

  22. Rosen HN, Moses AC, Garber J, Ross DS, Lee SL, Greenspan SL (1998) Utility of biochemical markers of bone turnover in the follow-up of patients treated with bisphosphonates. Calcif Tissue Int 63(5):363–368

    Article  CAS  PubMed  Google Scholar 

  23. Rosen HN, Moses AC, Garber J, Iloputaife ID, Ross DS, Lee SL, Greenspan SL (2000) Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 66(2):100–103

    Article  CAS  PubMed  Google Scholar 

  24. Gong HS, Song CH, Lee YH, Rhee SH, Lee HJ, Baek GH (2012) Early initiation of bisphosphonate does not affect healing and outcomes of volar plate fixation of osteoporotic distal radial fractures. J Bone Joint Surg Am 94(19):1729–1736. https://doi.org/10.2106/JBJS.K.01434

    Article  PubMed  Google Scholar 

  25. Manabe T, Mori S, Mashiba T, Cao Y, Kaji Y, Iwata K, Komatsubara S, Yamamoto T, Seki A, Norimatsu H (2009) Eel calcitonin (elcatonin) suppressed callus remodeling but did not interfere with fracture healing in the femoral fracture model of cynomolgus monkeys. J Bone Miner Metab 27(3):295–302. https://doi.org/10.1007/s00774-009-0046-x

    Article  CAS  PubMed  Google Scholar 

  26. Cao Y, Mori S, Mashiba T, Westmore MS, Ma L, Sato M, Akiyama T, Shi L, Komatsubara S, Miyamoto K, Norimatsu H (2002) Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res 17(12):2237–2246. https://doi.org/10.1359/jbmr.2002.17.12.2237

    Article  CAS  PubMed  Google Scholar 

  27. Xue D, Li F, Chen G, Yan S, Pan Z (2014) Do bisphosphonates affect bone healing? A meta-analysis of randomized controlled trials. J Orthop Surg Res 9:45. https://doi.org/10.1186/1749-799X-9-45

    Article  PubMed  PubMed Central  Google Scholar 

  28. Peter CP, Cook WO, Nunamaker DM, Provost MT, Seedor JG, Rodan GA (1996) Effect of alendronate on fracture healing and bone remodeling in dogs. J Orthop Res 14(1):74–79. https://doi.org/10.1002/jor.1100140113

    Article  CAS  PubMed  Google Scholar 

  29. Bauss F, Schenk RK, Hort S, Muller-Beckmann B, Sponer G (2004) New model for simulation of fracture repair in full-grown beagle dogs: model characterization and results from a long-term study with ibandronate. J Pharmacol Toxicol Methods 50(1):25–34. https://doi.org/10.1016/j.vascn.2003.11.003

    Article  CAS  PubMed  Google Scholar 

  30. Munns CF, Rauch F, Zeitlin L, Fassier F, Glorieux FH (2004) Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate. J Bone Miner Res 19(11):1779–1786. https://doi.org/10.1359/JBMR.040814

    Article  CAS  PubMed  Google Scholar 

  31. Li C, Mori S, Li J, Kaji Y, Akiyama T, Kawanishi J, Norimatsu H (2001) Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats. J Bone Miner Res 16(3):429–436. https://doi.org/10.1359/jbmr.2001.16.3.429

    Article  CAS  PubMed  Google Scholar 

  32. Rozental TD, Vazquez MA, Chacko AT, Ayogu N, Bouxsein ML (2009) Comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. J Hand Surg [Am] 34(4):595–602. https://doi.org/10.1016/j.jhsa.2008.12.011

    Article  Google Scholar 

  33. Amanat N, Brown R, Bilston LE, Little DG (2005) A single systemic dose of pamidronate improves bone mineral content and accelerates restoration of strength in a rat model of fracture repair. J Orthop Res 23(5):1029–1034. https://doi.org/10.1016/j.orthres.2005.03.004

    Article  CAS  PubMed  Google Scholar 

  34. Goodship AE, Walker PC, McNally D, Chambers T, Green JR (1994) Use of a bisphosphonate (pamidronate) to modulate fracture repair in ovine bone. Ann Oncol 5(Suppl 7):S53–S55

    PubMed  Google Scholar 

  35. 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(4):557–562. https://doi.org/10.1007/s00586-006-0212-y

    Article  PubMed  Google Scholar 

  36. Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15(4):613–620. https://doi.org/10.1359/jbmr.2000.15.4.613

    Article  CAS  PubMed  Google Scholar 

  37. Yang KH, Park SY, Yoo JH, Kim TH, Park HW, Ryu JH, Choo KS (2005) Effect of the long-term administration of pamidronate on bone strength and fracture healing in a rat model. J Korean Orthop Assoc 40(8):1043–1049

    Google Scholar 

  38. Cocquyt V, Kline WF, Gertz BJ, Van Belle SJ, Holland SD, DeSmet M, Quan H, Vyas KP, Zhang KE, De Greve J, Porras AG (1999) Pharmacokinetics of intravenous alendronate. J Clin Pharmacol 39(4):385–393

    Article  CAS  PubMed  Google Scholar 

  39. Amanat N, McDonald M, Godfrey C, Bilston L, Little D (2007) Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair. J Bone Miner Res 22(6):867–876. https://doi.org/10.1359/jbmr.070318

    Article  CAS  PubMed  Google Scholar 

  40. Little DG, Cornell MS, Briody J, Cowell CT, Arbuckle S, Cooke-Yarborough CM (2001) Intravenous pamidronate reduces osteoporosis and improves formation of the regenerate during distraction osteogenesis. A study in immature rabbits. J Bone Joint Surg (Br) 83(7):1069–1074

    Article  CAS  Google Scholar 

  41. Smith EJ, McEvoy A, Little DG, Baldock PA, Eisman JA, Gardiner EM (2004) Transient retention of endochondral cartilaginous matrix with bisphosphonate treatment in a long-term rabbit model of distraction osteogenesis. J Bone Miner Res 19(10):1698–1705. https://doi.org/10.1359/JBMR.040709

    Article  CAS  PubMed  Google Scholar 

  42. Fleisch H (1998) Bisphosphonates: mechanisms of action. Endocr Rev 19(1):80–100. https://doi.org/10.1210/edrv.19.1.0325

    Article  CAS  PubMed  Google Scholar 

  43. Bagger YZ, Tanko LB, Alexandersen P, Ravn P, Christiansen C (2003) Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal. Bone 33(3):301–307

    Article  CAS  PubMed  Google Scholar 

  44. Puhaindran ME, Farooki A, Steensma MR, Hameed M, Healey JH, Boland PJ (2011) Atypical subtrochanteric femoral fractures in patients with skeletal malignant involvement treated with intravenous bisphosphonates. J Bone Joint Surg Am 93(13):1235–1242. https://doi.org/10.2106/JBJS.J.01199

    Article  PubMed  Google Scholar 

  45. Thompson RN, Phillips JR, McCauley SH, Elliott JR, Moran CG (2012) Atypical femoral fractures and bisphosphonate treatment: experience in two large United Kingdom teaching hospitals. J Bone Joint Surg (Br) 94(3):385–390. https://doi.org/10.1302/0301-620X.94B3.27999

    Article  CAS  Google Scholar 

  46. Ohtori S, Inoue G, Orita S, Yamauchi K, Eguchi Y, Ochiai N, Kishida S, Kuniyoshi K, Aoki Y, Nakamura J, Ishikawa T, Miyagi M, Kamoda H, Suzuki M, Kubota G, Sakuma Y, Oikawa Y, Inage K, Sainoh T, Takaso M, Ozawa T, Takahashi K, Toyone T (2012) Teriparatide accelerates lumbar posterolateral fusion in women with postmenopausal osteoporosis: prospective study. Spine (Phila Pa 1976) 37(23):E1464–E1468. https://doi.org/10.1097/BRS.0b013e31826ca2a8

    Article  Google Scholar 

  47. Ohtori S, Inoue G, Orita S, Yamauchi K, Eguchi Y, Ochiai N, Kishida S, Kuniyoshi K, Aoki Y, Nakamura J, Ishikawa T, Miyagi M, Kamoda H, Suzuki M, Kubota G, Sakuma Y, Oikawa Y, Inage K, Sainoh T, Takaso M, Toyone T, Takahashi K (2013) Comparison of teriparatide and bisphosphonate treatment to reduce pedicle screw loosening after lumbar spinal fusion surgery in postmenopausal women with osteoporosis from a bone quality perspective. Spine (Phila Pa 1976) 38(8):E487–E492. https://doi.org/10.1097/BRS.0b013e31828826dd

    Article  Google Scholar 

  48. Ohtori S, Orita S, Yamauchi K, Eguchi Y, Ochiai N, Kuniyoshi K, Aoki Y, Nakamura J, Miyagi M, Suzuki M, Kubota G, Inage K, Sainoh T, Sato J, Shiga Y, Abe K, Fujimoto K, Kanamoto H, Inoue G, Takahashi K (2015) More than 6 months of teriparatide treatment was more effective for bone union than shorter treatment following lumbar posterolateral fusion surgery. Asian Spine J 9(4):573–580. https://doi.org/10.4184/asj.2015.9.4.573

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Orthopaedics, Korea University College of Medicine, Anam Hospital, Inchonro 73, Seongbukgu, Seoul, 02841, South Korea

    Taewook Kang, Si Young Park, Seok Ha Hong, Jin Hyeok Lee, Soon Hyuck Lee & Jong Hoon Park

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  1. Taewook Kang
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Correspondence to Si Young Park.

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Kang, T., Park, S.Y., Hong, S.H. et al. Bone union after spinal fusion surgery using local bone in long-term bisphosphonate users: a prospective comparative study. Arch Osteoporos 14, 74 (2019). https://doi.org/10.1007/s11657-019-0628-8

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