Systemic intermittent parathyroid hormone treatment improves osseointegration of press-fit inserted implants in cancellous bone

Abstract

Background and purpose Intermittent administration of parathyroid hormone (PTH) has an anabolic effect on bone, as confirmed in human osteoporosis studies, distraction osteogenesis, and fracture healing. PTH in rat models leads to improved fixation of implants in low-density bone or screw insertion transcortically.Material and methods We examined the effect of human PTH (1–34) on the cancellous osseointegration of unloaded implants inserted press-fit in intact bone of higher animal species. 20 dogs were randomized to treatment with human PTH (1–34), 5 μg/kg/day subcutaneously, or placebo for 4 weeks starting on the day after insertion of a cylindrical porous coated plasma-sprayed titanium alloy implant in the proximal metaphyseal cancellous bone of tibia. Osseointegration was evaluated by histomorphometry and fixation by push-out test to failure.Results Surface fraction of woven bone at the implant interface was statistically significantly higher in the PTH group by 1.4 fold with (median (interquartile range) 15% (13–18)) in the PTH group and 11% (7–13) in control. The fraction of lamellar bone was unaltered. No significant difference in bone or fibrous tissue was observed in the circumferential regions of 0–500, 500–1,000, and 1,000–2,000 μm around the implant. Mechanically, the implants treated with PTH showed no significant differences in total energy absorption, maximum shear stiffness, or maximum shear strength.Interpretation Intermittent treatment with PTH (1–34) improved xhistological osseointegration of a prosthesis inserted press-fit at surgery in cancellous bone, with no additional improvement of the initial mechanical fixation at this time point.

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.…”

“…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.…”

Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed

“…However, in a dog study of implant integration, small but significant effects were seen with 5µg/kg [21]. We chose this dose because when we are close to the lowest efficacious dose, the effects of possible contributing factors, such as loading, are more likely to make a difference.…”

Experimental and Numerical Models of Complex Clinical Scenarios; Strategies to Improve Relevance and Reproducibility of Joint Replacement Research

“…Experimental details for these studies are found in the original publications [16][17][18][23][24][25][26][27][28]. In brief, retrieved bone-implant specimens are cut into two pieces.…”

“…Motion or instability is well known to prevent healing of a fractured bone, and to reduce bone-implant fixation by predictably producing a fibrous interfacial membrane around a joint replacement implant [16]. Another fundamental condition is the surgical preparation of the implant site, and whether line-to-line press-fit fixation is achieved, or whether there are localized gaps between the implant and bone [17,18]. These different features can be a main driver of differential results, yet may not be readily possible to include in numerical models [17][18][19][20].…”