title: A single dose of zoledronic acid reverses the deleterious effects of glucocorticoids on titanium implant osseointegration.
abstract: This study evaluates the effect of zoledronic acid (ZOL) on the osseointegration of titanium implants in rabbits with glucocorticoid (GC)-induced bone loss, and our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of GCs on the osseointegration of titanium implants.
  
  
  BACKGROUND
  The purpose of this study is to evaluate the effect of ZOL on the osseointegration of titanium implants in rabbits with GC-induced bone loss.
  
  
  METHODS
  Three groups of six NZW rabbits were treated for 18 weeks with saline (SALINE), GC (methylprednisolone, 0.35 mg/kg three times a week), or GC + ZOL (methylprednisolone + single dose of ZOL, 0.1 mg/kg). The animals received a titanium implant in the left tibia after 6 weeks and were killed at the 18th week. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at baseline, eighth week (W8), and 18th week (W18) after treatment to determine the change upon treatment (BMD). Histomorphometric and serum bone alkaline phosphatase analysis (BAP) were also performed.
  
  
  RESULTS
  At W8, GC group had a significant reduction in lumbar spine and tibia BMD compared with SALINE (p = 0.003 and p = 0.000), as also observed for GC + ZOL group (p = 0.014 and p = 0.003) just 2 weeks after ZOL treatment. In contrast, at W18, the GC + ZOL had an evident BMD rescue with similar lumbar spine and tibia BMD compared with SALINE (0.043 +/- 0.006 vs. 0.055 +/- 0.009 g/cm(2), p = 0.457 and 0.027 +/- 0.003 vs. 0.041 +/- 0.011 g/cm(2), p = 0.232) and a significantly higher BMD compared with the GC (p = 0.024 and p = 0.001). Histomorphometry revealed that osseointegration was significantly reduced in GC (tibia cortical thickness and diameter, bone-implant contact, total and peri-implant bone area) whereas GC + ZOL had these parameters similar to SALINE (p > 0.05). Likewise, ZOL reversed the BAP alteration induced by GC.
  
  
  CONCLUSIONS
  Our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of glucocorticoids on the osseointegration of titanium implants, suggesting that ZOL therapy may improve the outcome of bone implants in patients with glucocorticoid-induced osteoporosis.
authors.affiliation: Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, 3 masculine andar, Reumatologia, São Paulo, SP, 0124-6903, Brazil.
authors.forename: J S B
authors.initials: JS
authors.lastname: Carvas
authors.forename: R M R
authors.initials: RM
authors.lastname: Pereira
authors.forename: V F
authors.initials: VF
authors.lastname: Caparbo
authors.forename: P
authors.initials: P
authors.lastname: Fuller
authors.forename: C A
authors.initials: CA
authors.lastname: Silveira
authors.forename: L A P
authors.initials: LA
authors.lastname: Lima
authors.forename: E
authors.initials: E
authors.lastname: Bonfa
authors.forename: S B V
authors.initials: SB
authors.lastname: Mello
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005938:Glucocorticoids / Q000633:toxicity*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008775:Methylprednisolone / Q000633:toxicity; D009984:Orthopedic Fixation Devices; D016348:Osseointegration / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D019736:Prostheses and Implants; D011817:Rabbits; D013977:Tibia / Q000503:physiopathology; D014025:Titanium; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005938:Glucocorticoids; D007093:Imidazoles; D000077211:Zoledronic Acid; D014025:Titanium; D008775:Methylprednisolone