The effects of PTH, loading and surgical insult on cancellous bone at the bone–implant interface in the rabbit

Abstract

Enhancing the quantity and quality of cancellous bone with anabolic pharmacologic agents may lead to more successful outcomes of non-cemented joint replacements. Using a novel rabbit model of cancellous bone loading, we examined two specific questions regarding bone formation at the bone-implant interface: (1) does the administration of intermittent PTH, a potent anabolic agent, and mechanical loading individually and combined enhance the peri-implant cancellous bone volume fraction; and, (2) does surgical trauma enhance the anabolic effect of PTH on peri-implant bone volume fraction. In this model, PTH enhanced peri-implant bone volume fraction by 30% in loaded bone, while mechanical loading alone increased bone volume fraction modestly (+10%). Combined mechanical loading and PTH treatment had no synergistic effect on any cancellous parameters. However, a strong combined effect was found in bone volume fraction with combined surgery and PTH treatment (+34%) compared to intact control limbs. Adaptive changes in the cancellous bone tissue included increased ultimate stress and enhanced remodeling activity. The number of proliferative osteoblasts increased as did their expression of pro-collagen 1 and PTH receptor 1, and the number of TRAP positive osteoclasts also increased. In summary, both loading and intermittent PTH treatment enhanced peri-implant bone volume, and surgery and PTH treatment had a strong combined effect. This finding is of clinical importance since enhancing early osseointegration in the post-surgical period has numerous potential benefits.

Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant

“…The finding that iPTH enhanced bone formation within our titanium implant is consistent with the beneficial effects of iPTH therapy on osseointegration seen in other models [17][18][19][20][21][22][23]35 . In our study, an increase in trabecular number, as opposed to trabecular thickness, appeared to be the primary structural change resulting from iPTH in the peri-implant region compared with the distal region.…”

“…In previous animal models, iPTH enhanced implant osseointegration of nonphysiologically loaded cortical and cancellous bone in rabbits and rats [17][18][19][20][21][22][23] . These models fail to simulate the intra-articular environment and physiologic loading that accompany tibial cancellous fixation in total knee arthroplasty.…”

“…Previous studies of in vivo models suggested that iPTH improves osseointegration [17][18][19][20][21][22][23][29][30][31][32][33][34] . Previous studies on osseointegration, however, had substantial limitations, including (1) use of large animals (rabbits, sheep, and dogs) with accompanying high cost, lower throughput 17,19,30,31,[35][36][37][38] , and greater humanitarian concerns compared with those related to small-animal models; (2) nonphysiologic implant placement such as in the medullary canal or extra-articular locations 18,[20][21][22]32,39 ; and (3) reliance on cortical bone support for stability 18,[20][21][22]40 . In the present study, we used a newly developed murine model with an intra-articular titanium implant that was loaded through the knee joint and supported by the cancellous bone bed of the proximal part of the tibia.…”

“…The implants were then removed gently from the tibiae with minimal loss of tissue at the bone-implant interface 19 , and the bone was embedded in paraffin. Transverse sections beginning 1 mm distal to the surface of the trimmed tibial plateau were cut serially.…”

“…As previously described 19 , sections were deparaffinized and rehydrated, endogenous peroxidase activity was blocked with 3% H 2 O 2 for thirty minutes, and then a protein block solution (X0909; Dako, Carpinteria, California) was used for twenty minutes. Primary antibodies diluted in antibody diluent (S3022; Dako) were allowed to react overnight; this was followed by incubation with a biotinylated secondary antibody (1:200 E0464 [Dako] for procollagen I and 1:400 E0432 [Dako] for cathepsin K) for one hour.…”