Intermittent PTH administration and mechanical loading are anabolic for periprosthetic cancellous bone

Abstract

The purpose of this study was to determine the individual and combined effects on periprosthetic cancellous bone of intermittent PTH (iPTH) and mechanical loading at the cellular, molecular, and tissue levels. Porous titanium implants were inserted bilaterally on the cancellous bone of adult rabbits beneath a loading device attached to the distal lateral femur. The left femur received a sham loading device. The right femur was loaded daily, and half of the rabbits received daily PTH. Periprosthetic bone was evaluated up to 28 days for gene expression, histology, and µCT analysis. Loading and iPTH increased bone mass by a combination of two mechanisms: 1) altering cell populations in a pro-osteoblastic/anti-adipocytic direction, and 2) controlling bone turnover by modulating the RANKL-OPG ratio. At the tissue level, BV/TV increased with both loading (+53%, p<0.05) and iPTH (+54%, p<0.05). Combined treatment showed only small additional effects at the cellular and molecular levels that corresponded to a small additive effect on bone volume (+13% compared to iPTH alone, p>0.05). This study suggests that iPTH and loading are potential therapies for enhancing periprosthetic bone formation. The elucidation of the cellular and molecular response may help further enhance the combined therapy and related targeted treatment strategies.

Effects of Teriparatide Compared with Risedronate on Recovery After Pertrochanteric Hip Fracture

“…A third possibility would be that risedronate had a negative effect, which appears unlikely, as bisphosphonates have been shown not to impair healing in comparison with placebo [36][37][38] , with the potential exception of distal radial fractures 39 , and likely improve implant fixation 40 . A positive effect of teriparatide on human fracture recovery would not be surprising, considering the positive effect on bone-healing in various animal models [13][14][15][16]21,41 .…”

Effect of Teriparatide or Risedronate in Elderly Patients With a Recent Pertrochanteric Hip Fracture: Final Results of a 78-Week Randomized Clinical Trial

“…Although preclinical studies using PTH in animal models are promising (60)(61)(62)(63)(64)(65) and proof-of-concept clinical trials (66,67) and sporadic case reports in humans (68,69) showed an anecdotal benefit of teriparatide in various fractures, to date there are no well-controlled clinical trials to support the hypothesis that teriparatide improves fracture healing. Huang and colleagues (70) have recently reported that 6 months of teriparatide was associated with faster fracture healing, better quality of life, and lower frequency of lag screw cutout and mortality rates in 189 patients with intertrochanteric fractures.…”

Parathyroid hormone 1-34 and skeletal anabolic action

“…21-24 However, continuous dosing results in increased osteoclast activation and lifespan, and thus enhanced endosteal resorption. In contrast, intermittent dosing results in increased trabecular bone volume.…”