DOI QR코드

DOI QR Code

Strategies of Spinal Fusion on Osteoporotic Spine

  • Park, Sung-Bae (Department of Neurosurgery, Inje University College of Medicine, Seoul Paik Hospital) ;
  • Chung, Chun-Kee (Department of Neurosurgery, Seoul National University College of Medicine, Clinical Research institute, Seoul National University Hospital)
  • Received : 2011.02.02
  • Accepted : 2011.05.30
  • Published : 2011.06.28

Abstract

The prevalence of osteoporosis has been increasing globally. Recently surgical indications for elderly patients with osteoporosis have been increasing. However, only few strategies are available for osteoporotic patients who need spinal fusion. Osteoporosis is a result of negative bone remodeling from enhanced function of the osteoclasts. Because bone formation is the result of coupling between osteoblasts and osteoclasts, anti-resorptive agents that induce osteoclast apoptosis may not be effective in spinal fusion surgery, necessitating new bone formation. Therefore, anabolic agents may be more suitable for osteoporotic patients who undergo spinal fusion surgery. The instrumentations and techniques with increased pullout strength may increase fusion rate through rigid fixation. Studies on new osteoinductive materials, methods to increase osteogenic cells, strengthened and biocompatible osteoconductive scaffolds are necessary to enable osteoporotic patients to undergo spinal fusion. When osteoporotic patients undergo spinal fusion, surgeons should consider appropriate osteoporosis medication, instrumentation and technique.

Keywords

References

  1. Abe Y, Takahata M, Ito M, Irie K, Abumi K, Minami A : Enhancement of graft bone healing by intermittent administration of human parathyroid hormone (1-34) in a rat spinal arthrodesis model. Bone 41 : 775-785, 2007 https://doi.org/10.1016/j.bone.2007.06.025
  2. Aebi M : The scoliosis. Eur Spine J 14 : 925-948, 2005 https://doi.org/10.1007/s00586-005-1053-9
  3. Aldini NN, Fini M, Giavaresi G, Giardino R, Greggi T, Parisini P : Pedicular fixation in the osteoporotic spine : a pilot in vivo study on long-term ovariectomized sheep. J Orthop Res 20 : 1217-1224, 2002 https://doi.org/10.1016/S0736-0266(02)00069-4
  4. Alkhiary YM, Gerstenfeld LC, Krall E, Westmore M, Sato M, Mitlak BH, et al. : Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg Am 87 : 731-734, 2005 https://doi.org/10.2106/JBJS.D.02115
  5. Aydogan M, Ozturk C, Karatoprak O, Tezer M, Aksu N, Hamzaoglu A : The pedicle screw fixation with vertebroplasty augmentation in the surgical treatment of the severe osteoporotic spines. J Spinal Disord Tech 22 : 444-447, 2009 https://doi.org/10.1097/BSD.0b013e31818e0945
  6. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, et al. : A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 20 : 2275-2282, 2005
  7. Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, et al. : PaTH Study Investigators. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med 353 : 555-565, 2005 https://doi.org/10.1056/NEJMoa050336
  8. Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, et al. : PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 349 : 1207-1215, 2003 https://doi.org/10.1056/NEJMoa031975
  9. Boden SD : Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute. Spine (Phila Pa 1976) 15 : S26-S31, 2002
  10. Boden SD : The biology of posterolateral lumbar spinal fusion. Orthop Clin North Am 29 : 603-619, 1998 https://doi.org/10.1016/S0030-5898(05)70034-1
  11. Boden SD, Schimandle JH, Hutton WC, Chen MI : The use of an osteoondary-inductive growth factor for lumbar spinal fusion. Part I : Biology of spine fusion. Spine (Phila Pa 1976) 20 : 2626-2632, 1995 https://doi.org/10.1097/00007632-199512150-00003
  12. Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, et al. : Odanacatib, a cathesin-K inhibitor for osteoporosis : a two-year study in postmenopausal women with low bone density. J Bone Miner Res 25 : 937-947, 2010
  13. Brantigan JW, Steffee AD : A carbon fiber implant to aid interbody lumbar fusion. Two-year clinical results in the first 26 patients. Spine (Phila Pa 1976) 18 : 2106-2107, 1991
  14. Bridwell KH, Sedgewick TA, O'Brien MF, Lenke LG, Baldus C : The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis. J Spinal Disord 6 : 461-472, 1993 https://doi.org/10.1097/00002517-199306060-00001
  15. Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, et al. : Comparison of the effect of denosumab and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mass : a randomized, blinded, phase 3 trial. J Bone Miner Res 14 : 1-34, 2009
  16. Burkus JK, Gornet MF, Schuler TC, Kleeman TJ, Zdeblick TA : Six-year outcomes of anterior lumbar interbody arthrodesis with use of interbody fusion cages and recombinant human bone morphogenetic protein-2. J Bone Joint Surg Am 91 : 1181-1189, 2009 https://doi.org/10.2106/JBJS.G.01485
  17. Burval DJ, McLain RF, Milks R, Inceoglu S : Primary pedicle screw augmentation in osteoporotic lumbar vertebrae : biomechanical analysis of pedicle fixation strength. Spine (Phila Pa 1976) 32 : 1077-1083, 2007 https://doi.org/10.1097/01.brs.0000261566.38422.40
  18. Carreon LY, Puno RM, Dimar JR 2nd, Glassman SD, Johnson JR : Perioperative complications of posterior lumbar decompression and arthrodesis in older adults. J Bone Joint Surg Am 85 : 2089-2092, 2003
  19. Cauley JA, Fullman RL, Stone KL, Zmuda JM, Bauer DC, Barrett-Connor E, et al. : Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int 16 : 1525-1537, 2005 https://doi.org/10.1007/s00198-005-1866-8
  20. Cavagna R, Tournier C, Aunoble S, Bouler JM, Antonietti P, Ronai M, et al. : Lumbar decompression and fusion in elderly osteoporotic patients : a prospective study using less rigid titanium rod fixation. J Spinal Disord Tech 21 : 86-91, 2008 https://doi.org/10.1097/BSD.0b013e3180590c23
  21. Chin DK, Park JY, Yoon YS, Kuh SU, Jin BH, Kim KS, et al. : Prevalence of osteoporosis in patients requiring spine surgery : incidence and significance of osteoporosis in spine disease. Osteoporos Int 18 : 1219-1224, 2007 https://doi.org/10.1007/s00198-007-0370-8
  22. Coe JD, Warden KE, Herzig MA, McAfee PC : Influence of bone mineral density on the fixation of thoracolumbar implants. A comparative study of transpedicular screws, laminar hooks, and spinous process wires. Spine (Phila Pa 1976) 15 : 902-907, 1990 https://doi.org/10.1097/00007632-199009000-00012
  23. Conaty JP, Mongan ES : Cervical fusion in rheumatoid arthritis. J Bone Joint Surg Am 63 : 1218-1227, 1981
  24. Cook SD, Barbera J, Rubi M, Salkeld SL, Whitecloud TS 3rd : Lumbosacral fixation using expandable pedicle screws : an alternative in reoperation and osteoporosis. Spine J 1 : 109-114, 2001 https://doi.org/10.1016/S1529-9430(01)00020-1
  25. Cummings SR, Melton LJ : Epidemiology and outcomes of osteoporotic fractures. Lancet 359 : 1761-1767, 2002 https://doi.org/10.1016/S0140-6736(02)08657-9
  26. Deal C : Future therapeutic targets in osteoporosis. Curr Opin Rheumatol 21 : 380-385, 2009 https://doi.org/10.1097/BOR.0b013e32832cbc2a
  27. Eriksen EF, Landgdahl B, Vesterby A, Rungby J, Kassem M : Hormone replacement therapy prevents osteoclastic hyperactivity : a histomorphometric study in early postmenopausal women. J Bone Miner Res 14 : 1217-1221, 1999 https://doi.org/10.1359/jbmr.1999.14.7.1217
  28. Fraizer DD, Lipson SJ, Fossel AH, Katz JN : Associations between spinal deformity and outcomes after decompression for spinal stenosis. Spine (Phila Pa 1976) 22 : 2025-2029, 1997 https://doi.org/10.1097/00007632-199709010-00017
  29. Ferguson SJ, Winkler F, Nolte LP : Anterior fixation in the osteoporotic spine : cut-out and pullout characteristics of implant. Eur Spine J 11 : 527-534, 2002 https://doi.org/10.1007/s00586-002-0449-z
  30. Farey ID, McAfee PC, Gurr KR, Randolph MA : Quantitative histologic study of the influence of spinal instrumentation on lumbar fusions : a canine model. J Orthop Res 7 : 709-722, 1989 https://doi.org/10.1002/jor.1100070512
  31. Gauthier JY, Chauret N, Cromlish W, Desmarais S, Duong le T, Falgueyret JP, et al. : The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett 18 : 923-928, 2008 https://doi.org/10.1016/j.bmcl.2007.12.047
  32. Glassman SD, Polly DW, Bono CM, Burkus K, Dimar JR : Outcome of lumbar arthrodesis in patients sixty-five years of age or older. J Bone Joint Surg Am 91 : 783-790, 2009 https://doi.org/10.2106/JBJS.H.00288
  33. Greenfield RT 3rd, Capen DA, Thomas JC Jr, Nelson R, Nagelberg S, Rimoldi RL, et al. : Pedicle screw fixation for arthrodesis of the lumbosacral spine in the elderly : an outcome study. Spine (Phila Pa 1976) 23 : 1470-1475, 1998 https://doi.org/10.1097/00007632-199807010-00008
  34. Hart RA, Prendergast MA : Spine surgery for lumbar degenerative disease in elderly and osteoporotic patients. Instr Course Lect 56 : 257-272, 2007
  35. Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, et al. : Parathyroid hormone and teriparatide for the treatment of osteoporosis : a review of the evidence and suggested guidelines for its use. Endocr Rev 26 : 688-703, 2005 https://doi.org/10.1210/er.2004-0006
  36. Horwitz M, Stewart A, Greenspan SL : Sequential parathyroid hormone/alendronate therapy for osteoporosis-robbing Peter to pay Paul? J Clin Endocrinol Metab 85 : 2127-2128, 2000 https://doi.org/10.1210/jc.85.6.2127
  37. Huang RC, Khan SN, Sandhu HS, Metzl JA, Cammisa FP Jr, Zheng F, et al. : Alendronate inhibits spine fusion in a rat model. Spine (Phila Pa 1976) 30 : 2516-2522, 2005 https://doi.org/10.1097/01.brs.0000186470.28070.7b
  38. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, et al. : Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10 : 1478-1487, 1995
  39. Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC : Increased bone formation by prevention of osteoblast apoptosis with PTH. J Clin Invest 104 : 439-446, 1999 https://doi.org/10.1172/JCI6610
  40. Johnsson KE, Willner S, Johnsson K : Postoperative instability after decompression for lumbar spinal stenosis. Spine (Phila Pa 1976) 11 : 107-110, 1986 https://doi.org/10.1097/00007632-198603000-00001
  41. Khosla S, Westendorf JJ, Oursler MJ : Building bone to reverse osteoporosis and repair fracture. J Clin Invest 118 : 421-428, 2008 https://doi.org/10.1172/JCI33612
  42. Kim CH, Kim YI, Choi CS, Park JY, Lee MS, Lee SI, et al. : Prevalence and risk factors of low quantitative ultrasound values of calcaneus in Korean elderly women. Ultrasound Med Biol 26 : 35-40, 2000 https://doi.org/10.1016/S0301-5629(99)00126-X
  43. Kim KH, Lee SH, Lee DY, Shim CS, Maeng DH : Anterior bone cement augmentation in anterior lumbar interbody fusion and percutaneous pedicle screw fixation in patients with osteoporosis. J Neurosurg Spine 12 : 525-532, 2010 https://doi.org/10.3171/2009.11.SPINE09264
  44. Kitchel SH : A preliminary comparative study of radiographic results using mineralized collagen and bone marrow aspirate versus autologous bone in the same patients undergoing posterior lumbar interbody fusion with instrumented posterolateral lumbar fusion. Spine J 6 : 405-411, 2006 https://doi.org/10.1016/j.spinee.2005.09.013
  45. Lehman RA Jr, Kuklo TR, Freedman BA, Cowart JR, Mense MG, Riew KD : The effect of alendronate sodium on spinal fusion : a rabbit model. Spine J 4 : 36-43, 2004 https://doi.org/10.1016/S1529-9430(03)00427-3
  46. Lindsay R : Sex steroids in the pathogenesis and prevention of osteoporosis in Riggs BL (ed) : Osteoporosis : Etiology, Diagnosis and Management. New York : Raven Press, 1988, pp333-358
  47. Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, et al. : Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24 : 578-588, 2009 https://doi.org/10.1359/jbmr.081206
  48. Looker AC, Johnston CC Jr, Wahner HW, Dunn WL, Calvo MS, Harris TB, et al. : Prevalence of low femoral bone density in older U.S. women from NHANES III. J Bone Miner Res 10 : 796-802, 1995
  49. Lu J, Bhargav D, Wei AQ, Diwan A : Posterolateral intertransverse spinal fusion possible in osteoporotic rats with BMP-7 in a higher dose delivered on a composite carrier. Spine (Phila Pa 1976) 33 : 242-249, 2008 https://doi.org/10.1097/BRS.0b013e318162451b
  50. Manolagas SC : Birth and death of bone cells : basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21 : 115-137, 2000 https://doi.org/10.1210/er.21.2.115
  51. Manolagas SC, Jilka RL : Bone marrow, cytokines, and bone remodeling-emerging insights into the pathophysiology of osteoporosis. N Engl J Med 332 : 305-311, 1995 https://doi.org/10.1056/NEJM199502023320506
  52. Manolagas SC, Weinstein RS, Bellido T, Bodenner DL : Opposite effects of estrogen on the life span of osteoblasts / osteocytes vs. ostoclasts in vivo and in vitro : an explanation of the imbalance between formation and resorption in estrogen deficiency. J Bone Miner Res 14 : S169, 1999
  53. Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, et al. : Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy : a randomized blinded phase 2 clinical trial. Bone 43 : 222-229, 2008 https://doi.org/10.1016/j.bone.2008.04.007
  54. Murphy MG, Cerchio K, Stoch SA, Gottesdiener K, Wu M, Recker R : Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 90 : 2022-2028, 2005 https://doi.org/10.1210/jc.2004-2126
  55. Nakamura Y, Hayashi K, Abu-Ali S, Naito M, Fotovati A : Effect of preoperative combined treatment with alendronate and calcitriol on fixation of hydroxyapatite-coated implants in ovariectomized rat. J Bone Joint Surg Am 90 : 824-832, 2008 https://doi.org/10.2106/JBJS.G.00635
  56. Okuda S, Miyauchi A, Oda T, Haku T, Yamamoto T, Iwasaki M : Surgical complications of posterior lumbar interbody fusion with total laminectomy in 251 patients. J Neurosurg Spine 4 : 304-309, 2006 https://doi.org/10.3171/spi.2006.4.4.304
  57. Okuda S, Oda T, Miyauchi A , Haku T, Yamamoto T, Iwasaki M : Surgical outcomes of posterior lumbar interbody fusion in elderly patients. J Bone Joint Surg Am 88 : 2714-2720, 2006 https://doi.org/10.2106/JBJS.F.00186
  58. Orwoll ES, Klein RF : Osteoporosis in men. Endocr Rev 16 : 87-116, 1995
  59. Palmer M, Adami HO, Krusemo UB, Ljunghall S : Increased risk of malignant disease after surgery for primary hyperparathyroidism : a nation-wide cohort study. Am J Epidemiol 127 : 1031-1040, 1988
  60. Parfitt AM, Mundy GR, Roodman GD, Hughes DE, Boyce BF : A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J Bone Miner Res 11 : 150-159, 1996
  61. Peter CP, Cook WO, Nunamaker DM, Provost MT, Seedor JG, Rodan GA : Effect of alendronate on fracture healing and bone remodeling in dogs. J Orthop Res 14 : 74-79, 1996 https://doi.org/10.1002/jor.1100140113
  62. Reinhold M, Schwieger K, Goldhahn J, Linke B, Knop C, Blauth M : Influence of screw positioning in a new anterior spine fixator on implant loosening in osteoporotic vertebrae. Spine (Phila Pa 1976) 31 : 406-413, 2006 https://doi.org/10.1097/01.brs.0000199894.63450.70
  63. Rihn JA, Makda J, Hong J, Patel R, Hilibrand AS, Anderson DG, et al. : The use of RhBMP-2 in single-level transforaminal lumbar interbody fusion : a clinical and radiographic analysis. Eur Spine J 18 : 1629-1636, 2009 https://doi.org/10.1007/s00586-009-1046-1
  64. Roux B : New treatment targets in osteoporosis. Joint Bone Spine 77 : 222-228, 2010 https://doi.org/10.1016/j.jbspin.2010.02.004
  65. Sienkiewicz PJ, Flatley TJ : Postoperative spondylolisthesis. Clin Orthop Relat Res 221 : 172-180, 1987
  66. Sims NA, Gooi JH : Bone remodeling : multiple cellular interactions required for coupling of bone formation and resorption. Semin Cell Dev Biol 19 : 444-451, 2008 https://doi.org/10.1016/j.semcdb.2008.07.016
  67. Szpalski M, Gunzburg R : Lumbar spinal stenosis in the elderly : an overview. Eur Spine J 12 : S170-S175, 2003 https://doi.org/10.1007/s00586-003-0612-1
  68. Takahata M, Ito M, Abe Y, Abumi K, Minami A : The effect of anti-resorptive therapies on bone graft healing in an ovariectomized rat spinal arthrodesis model. Bone 43 : 1057-1066, 2008 https://doi.org/10.1016/j.bone.2008.08.124
  69. Toribatake Y, Hutton WC, Tomita K, Boden SD : Vascularization of the fusion mass in a posterolateral intertransverse process fusion. Spine (Phila Pa 1976) 23 : 1149-1154, 1998 https://doi.org/10.1097/00007632-199805150-00015
  70. Wermers RA, Khosla S, Atkinson EJ, Grant CS, Hodgson SF, O'Fallon WM, et al. : Survival after the diagnosis of hyperparathyroidism : a population-based study. Am J Med 104 : 115-122, 1998 https://doi.org/10.1016/S0002-9343(97)00270-2
  71. Yamamoto T, Ohkohchi T, Ohwada T, Kotoku H, Harada N : Clinical and radiological results of PLIF for degenerative spondylolisthesis. J Musculoskelet Res 2 : 181-195, 1998 https://doi.org/10.1142/S0218957798000184
  72. Yone K, Sakou T, Kawauchi Y, Yamaguchi M, Yanase M : Indication of fusion for lumbar spinal stenosis in elderly patients and its significance. Spine (Phila Pa 1976) 15 : 242-248, 1996
  73. Zipfel GJ, Guiot BH, Fessler RG : Bone grafting. Neurosurg Focus 14 : e8, 2003

Cited by

  1. A Clinical Result of Pedicle Screw Fixation in Osteoporotic Spine - Complications and Prevention - vol.19, pp.4, 2011, https://doi.org/10.4184/jkss.2012.19.4.131
  2. Adult spinal deformity surgery vol.23, pp.3, 2012, https://doi.org/10.1097/bco.0b013e3182500535
  3. The Impact of Menopause on Bone Fusion after the Single-Level Anterior Cervical Discectomy and Fusion vol.54, pp.6, 2011, https://doi.org/10.3340/jkns.2013.54.6.496
  4. Balancing Rigidity and Safety of Pedicle Screw Fixation via a Novel Expansion Mechanism in a Severely Osteoporotic Model vol.2015, pp.None, 2011, https://doi.org/10.1155/2015/318405
  5. Perioperative Medical Management of Spine Surgery Patients With Osteoporosis : vol.77, pp.suppl4, 2011, https://doi.org/10.1227/neu.0000000000000939
  6. Alendronate Prevents Intervertebral Disc Degeneration Adjacent to a Lumbar Fusion in Ovariectomized Rats : vol.40, pp.20, 2011, https://doi.org/10.1097/brs.0000000000001092
  7. Clinical and Radiographic Outcomes of Transforaminal Lumbar Interbody Fusion in Patients with Osteoporosis vol.6, pp.7, 2016, https://doi.org/10.1055/s-0036-1578804
  8. Efficacy of a Cellular Bone Allograft for Foot and Ankle Arthrodesis and Revision Nonunion Procedures vol.38, pp.3, 2011, https://doi.org/10.1177/1071100716674977
  9. Difference in Spinal Fusion Process in Osteopenic and Nonosteopenic Living Rat Models Using Serial Microcomputed Tomography vol.60, pp.3, 2011, https://doi.org/10.3340/jkns.2016.0707.002
  10. Microstructural properties of trabecular bone autografts: comparison of men and women with and without osteoporosis vol.13, pp.1, 2018, https://doi.org/10.1007/s11657-018-0422-z
  11. Surgical Risk Assessment and Prevention in Elderly Spinal Deformity Patients vol.10, pp.None, 2011, https://doi.org/10.1177/2151459319851681
  12. Surgeon Management of Osteoporosis in Instrumented Spine Surgery: AOSpine Latin America Survey vol.9, pp.2, 2011, https://doi.org/10.1177/2192568218785369
  13. Noninstrumented Lumbar Fusion with Bone Morphogenetic Proteins for Spinal Stenosis with Spondylolisthesis in the Elderly vol.126, pp.None, 2011, https://doi.org/10.1016/j.wneu.2019.02.251
  14. Adult Spinal Deformity Surgery in Patients With Movement Disorders : A Propensity-matched Analysis of Outcomes and Cost vol.45, pp.5, 2011, https://doi.org/10.1097/brs.0000000000003251
  15. Osteoporosis and Spine Surgery : A Critical Analysis Review vol.8, pp.6, 2011, https://doi.org/10.2106/jbjs.rvw.19.00160
  16. A Prospective Study on the Feasibility, Safety, and Efficacy of a Modified Technique to Augment the Strength of Pedicle Screw in Osteoporotic Spine Fixation vol.14, pp.3, 2020, https://doi.org/10.31616/asj.2019.0211
  17. Bisphosphonates and parathyroid hormone analogs for improving bone quality in spinal fusion: State of evidence vol.12, pp.2, 2011, https://doi.org/10.4081/or.2020.8590
  18. Is there a difference in the outcomes of anterior cervical discectomy and fusion among female patients with different menopausal statuses? vol.16, pp.1, 2011, https://doi.org/10.1186/s13018-021-02673-2
  19. Denosumab alleviates intervertebral disc degeneration adjacent to lumbar fusion by inhibiting endplate osteochondral remodeling and vertebral osteoporosis in ovariectomized rats vol.23, pp.1, 2011, https://doi.org/10.1186/s13075-021-02525-8