title: Zinc has insulin-mimetic properties which enhance spinal fusion in a rat model.
abstract: Previous studies have found that insulin or insulin-like growth factor treatment can stimulate fracture healing in diabetic and normal animal models, and increase fusion rates in a rat spinal fusion model. Insulin-mimetic agents, such as zinc, have demonstrated antidiabetic effects in animal and human studies, and these agents that mimic the effects of insulin could produce the same beneficial effects on bone regeneration and spinal fusion.
  
  
  
  The purpose of this study was to analyze the effects of locally applied zinc on spinal fusion in a rat model.
  
  
  
  Institutional Animal Care and Use Committee-approved animal study using Sprague-Dawley rats was used as the study design.
  
  
  
  Thirty Sprague-Dawley rats (450-500 g) underwent L4-L5 posterolateral lumbar fusion (PLF). After decortication and application of approximately 0.3 g of autograft per side, one of three pellets were added to each site: high-dose zinc calcium sulfate (ZnCaSO4), low-dose ZnCaSO4 (half of the high dose), or a control palmitic acid pellet (no Zn dose). Systemic blood glucose levels were measured 24 hours postoperatively. Rats were sacrificed after 8weeks and the PLFs analyzed qualitatively by manual palpation and radiograph review, and quantitatively by micro-computed tomography (CT) analysis of bone volume and trabecular thickness. Statistical analyses with p-values set at .05 were accomplished with analysis of variance, followed by posthoc tests for quantitative data, or Mann-Whitney rank tests for qualitative assessments.
  
  
  
  Compared with controls, the low-dose zinc group demonstrated a significantly higher manual palpation grade (p=.011), radiographic score (p=.045), and bone formation on micro-CT (172.9 mm(3) vs. 126.7 mm(3) for controls) (p<.01). The high-dose zinc also demonstrated a significantly higher radiographic score (p=.017) and bone formation on micro-CT (172.7 mm(3) vs. 126.7 mm(3)) (p<.01) versus controls, and was trending toward higher manual palpation scores (p=.058).
  
  
  
  This study demonstrates the potential benefit of a locally applied insulin-mimetic agent, such as zinc, in a rat lumbar fusion model. Previous studies have demonstrated the benefits of local insulin application in the same model, and it appears that zinc has similar effects.
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA. Electronic address: johndkoerner@gmail.com.
authors: John D
authors: JD
authors: Koerner
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: Michael J
authors: MJ
authors: Vives
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: J Patrick
authors: JP
authors: O'Connor
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: Paul
authors: P
authors: Chirichella
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: Eric A
authors: EA
authors: Breitbart
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: Saad B
authors: SB
authors: Chaudhary
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: Linda
authors: L
authors: Uko
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: Sangeeta
authors: S
authors: Subramanian
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: J C
authors: JC
authors: Fritton
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: Joseph
authors: J
authors: Benevenia
authors: Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.
authors: Sheldon S
authors: SS
authors: Lin
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000601:surgery; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion / Q000379:methods*; D015032:Zinc / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D007328:Insulin; D015032:Zinc