Bone turnover markers correlate with implant fixation in a rat model using LPS‐doped particles to induced implant loosening

Abstract

Revision surgery for particle-induced implant loosening in total joint replacement is expected to increase dramatically over the next few decades. This study was designed to investigate if local tissue and serum markers of bone remodeling reflect implant fixation following administration of lipopolysaccharide (LPS)-doped polyethylene (PE) particles in a rat model. 24 rats received bilateral implantation of intramedullary titanium rods in the distal femur, followed by weekly bilateral intra-articular injection of either LPS-doped PE particles (n = 12) or vehicle which contained no particles (n= 12) for 12 weeks. The group in which the particles were injected had increased serum C-terminal telopeptide of type I collagen, decreased serum osteocalcin, increased peri-implant eroded surface, decreased peri-implant bone volume, and decreased mechanical pull-out strength compared to the controls. Implant fixation strength was positively correlated with peri-implant bone volume and serum osteocalcin and inversely correlated with serum C-terminal telopeptide of type I collagen, while energy to yield was positively correlated with serum osteocalcin and inversely correlated with the number of tartrate resistant acid phosphatase positive cells at the interface and the amount of peri-implant eroded surface. There was no effect on trabecular bone volume at a remote site. Thus, the particle-induced impaired fixation in this rat model was directly associated with local and serum markers of elevated bone resorption and depressed bone formation, supporting the rationale of exploring both anti-catabolic and anabolic strategies to treat and prevent particle-related implant osteolysis and loosening and indicating that serum markers may prove useful in tracking implant fixation.

Are There Biological Markers for Wear or Corrosion? A Systematic Review

“…A second limitation is that we did not include animal studies in which biomarkers of aseptic loosening/osteolysis were studied [14,18,21,27] because only two of these studies included stable and loosened implants [18,27]. These two studies showed dramatic increases in serum CTX-1, OPG, cathepsin K, and PINP and depression of serum OC.…”

Intramembranous bone regeneration and implant placement using mechanical femoral marrow ablation: rodent models

“…19 A third scenario uses a larger hand drill with a 2.0 mm drill bit to widen the distal 5 mm of the ablation site, followed by implant placement. 20 This widened portion of the canal and the lack of bone wax allow for exposure of the ablation site to the joint space and is used in a model where particles are introduced into the joint space to mimic particle-induced peri-implant osteolysis. 20 Suturing and surgical staple placement are completed in the same manner as in the mouse surgery.…”

“…4,17,20,21,37,38 To assess the reproducibility of the model, we re-analyzed outcome data from the mouse marrow ablation model and the rat implant fixation model in which the animal strain, age, sex and experimental end points were comparable. Both mouse studies included females from FVB/NJ and BALB/cJ strains of the same age (10-11 weeks) with the same end point (bone volume/tissue volume, BV/TV) at 7 days post-marrow ablation.…”

“…Similarly, we compared comparable groups from two studies using the rat implant model, 20,21 in which 6-month old male Sprague-Dawley rats had implants in place for 12 weeks. In this case, we examined the mechanical strength of implant fixation within the host bone.…”

“…14,15 Model choice depends upon the type of bone formation to be studied, as well as the importance of loadbearing, skeletal region and ability to translate to the clinic. The marrow ablation model is primarily used for two main purposes: (1) as a model for intramembranous bone regeneration 3,4,16,17 and (2) as a model to study implant fixation in orthopedics 9,[18][19][20][21] and dentistry. 22,23 Therefore, the model is of interest to orthopedic and dental research, including biomaterial specialists, implant designers and molecular biologists as well as the field of regenerative medicine.…”