title: The effects of the antiresorptive agents calcitonin and pamidronate on spine fusion in a rabbit model.
abstract: BACKGROUND
  As the population ages, the number of individuals undergoing pharmacotherapy to prevent or treat osteoporosis is increasing. Drugs of the bisphosphonate family prevent bone resorption, as does calcitonin, though by different mechanisms. Bisphosphonates are deposited in bone, preventing resorption by osteoclasts. Calcitonin is a direct inhibitor of osteoclasts, but is not itself incorporated in bone. The same late middle-aged and elderly patients who are being treated for osteoporosis frequently come to spine fusion. Bone remodelling is a vital part of graft incorporation. Interventions that interfere with remodelling may have a detrimental effect on the rate, time course, and strength of the fusion mass.
  
  
  OBJECTIVE
  To delineate the effects of these anti-osteoporosis medications on the fusion process.
  
  
  METHODS
  Randomized, prospective, double-blind, animal model.
  
  
  METHODS
  Posterolateral arthrodesis was performed at L5/6 in 60 skeletally mature 4.0-4.5 kg New Zealand white rabbits, using 3 cc of autologous iliac crest graft per side. Rabbits were randomized to one of three groups: PAM--pamidronate 1.2 mg subcutaneously 3 times/week for 4 weeks preoperatively, then 0.6 mg/day via miniosmotic pump for 4 weeks postoperatively; CAL--calcitonin 14 IU/day via pump for 4 weeks postoperatively only; CON--no drug intervention. All animals were killed 5 weeks after surgery. Fusion, defined by absolute lack of intersegmental motion, was assessed by manual palpation by two spine surgeons. Where there was disagreement, a third surgeon made the final determination. Stiffness and peak load to failure were determined by mechanical testing of each operated motion segment, and normalized to the adjacent, unoperated level.
  
  
  RESULTS
  Four rabbits excluded (1 each: death; euthanasia for hind-limb palsy; infection; incorrect level). Number fused at 5 weeks: CON 10/18 (56%), PAM 7/19 (37%), CAL 13/19 (68%). Fisher exact test showed no significant differences between groups. Analysis of variance (ANOVA) showed no significant differences in mechanical testing between CAL and CON, but PAM specimens had significantly less peak load than CON or CAL animals (p<.01) and were less stiff than CON (p<.01) or CAL (p<.05) animals.
  
  
  CONCLUSIONS
  Though one must be careful in extrapolating animal data to humans, this study suggests that calcitonin is not detrimental to spine fusion. Pamidronate, however, does lead to a mechanically less robust fusion. Based on this study, there is no evidence to support a recommendation to stop antiresorptive therapy for osteoporosis in the spine fusion patient.
authors.affiliation: Cleveland Clinic Spine Institute, Spine Research Laboratory, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: L Brett
authors.initials: LB
authors.lastname: Babat
authors.forename: Robert
authors.initials: R
authors.lastname: McLain
authors.forename: Ryan
authors.initials: R
authors.lastname: Milks
authors.forename: Lisa
authors.initials: L
authors.lastname: Ferrara
authors.forename: Moon-Jun
authors.initials: MJ
authors.lastname: Sohn
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D002116:Calcitonin / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D000077268:Pamidronate; D011817:Rabbits; D013123:Spinal Fusion; D013718:Tensile Strength
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D002116:Calcitonin; D000077268:Pamidronate