title: Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant.
abstract: BACKGROUND
  Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration.
  
  
  METHODS
  Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 μg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing.
  
  
  RESULTS
  Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher, respectively, in the iPTH-treated mice than in the vehicle-treated mice, and the maximum implant pullout strength was 30.9% greater. iPTH also increased osteoblast and osteoclast density by 65.2% and 47.0%, respectively, relative to the values in the vehicle group, when the data at post-implantation weeks 1 and 2 were averaged.
  
  
  CONCLUSIONS
  iPTH increased osseointegration, cancellous mass, and the strength of the bone-implant interface.
  
  
  CONCLUSIONS
  Our murine model is an excellent platform on which to study biological enhancement of cancellous osseointegration.
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Ricciardi
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Dvorzhinskiy
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Caroline
authors.initials: C
authors.lastname: Brial
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Lane
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Samrath
authors.initials: S
authors.lastname: Bhimani
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Jayme C
authors.initials: JC
authors.lastname: Burket
authors.affiliation: Department of Biomaterials and Biomimetics, New York University College of Dentistry, 345 East 24th Street, New York, NY 10010.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Sarkisian
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: F Patrick
authors.initials: FP
authors.lastname: Ross
authors.affiliation: Cornell University, Ithaca, NY 14853.
authors.forename: Marjolein C H
authors.initials: MC
authors.lastname: van der Meulen
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang: yangx@hss.edu.
authors.forename: Mathias P G
authors.initials: MP
authors.lastname: Bostrom
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D007279:Injections, Subcutaneous; D007595:Joint Prosthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016348:Osseointegration / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D010784:Photomicrography; D011474:Prosthesis Design; D019919:Prosthesis Implantation; D013977:Tibia / Q000187:drug effects* / Q000502:physiology / Q000601:surgery; D014025:Titanium
chemical_list: D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D014025:Titanium