Stimulation of implant fixation by parathyroid hormone (1–34)—A histomorphometric comparison of PMMA cement and stainless steel

Orthopaedic Department, University Hospital Eppendorf, Hamburg, Germany.
Journal of Orthopaedic Research (Impact Factor: 2.99). 12/2005; 23(6):1266-70. DOI: 10.1016/j.orthres.2005.04.006.1100230605
Source: PubMed


Whereas continuous exposure to PTH results in bone resorption, PTH administration at intermittent doses results in bone formation by increasing osteoblast number and activity. PTH leads to faster fracture repair and better fixation of orthopaedic implants in animal models. The present study evaluates if PTH is able to increase the contact surface between bone and implant and whether the effect of PTH is dependent on implant material characteristics. The implants were made as rods, either of stainless steel or Palacos R bone-cement. The steel rods had a surface roughness of R(a) 0.1 microm and the cement rods R(a) 2.2 microm. In 40 adult male rats, one cement rod was inserted in the left tibia and one steel rod in the right tibia. After implantation, the rats were divided into groups by random. One group was injected three times a week with human PTH (1-34) at a dose of 60 microg/kg BW/injection. The second group was injected with the vehicle only. Both groups were then divided into groups for 2 and 4 weeks time till tibial harvest. The tibial segments around the hole of the rods were then prepared by standard histological techniques. The linear tissue surfaces, that had been in contact with the surface of the rod, were analyzed in a blind fashion. PTH increased the bone contact fraction compared with the vehicle in the steel group from 7.4 (SD 7.6) to 21.1 (SD 10.7) % after 2 weeks and from 9.8 (SD 8.1) to 47.1 (SD 13.3) % after 4 weeks. In the cement group PTH increased the contact index again compared with the vehicle from 7.8 (SD 10.2) to 53.6 (SD 26.3) % already after 2 weeks and from 14.3 (SD 15) to 65.6 (SD 15.7) % after 4 weeks. The bone trabeculae adjacent to the implant had become fewer and thicker after the treatment with PTH (1-34), with an increase of the bone mass in the area next to the bone-implant-interface. The earlier onset of PTH effects in the rougher cement group suggests that intermittent PTH treatment might lead to an increased micro-interlock between implant and bone, and might therefore be considered as a possible drug to enhance incorporation of orthopedic implants.

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    • "We have previously used PTH and bisphosphonates to increase bone formation and improve implant fixation in rodents [20] [25] [26]. Improved implant fixation by bisphosphonates has also been shown in patients [40], and PTH appears to accelerate human fracture healing [41- 42]. "
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    ABSTRACT: The secreted protein Dickkopf-1 (Dkk1) is an antagonist of canonical Wnt signaling, expressed during fracture healing. It is unclear how it is involved in the mechanical control of bone maintenance. We investigated the response to administration of a Dkk1 neutralizing antibody (Dkk1-ab) in metaphyseal bone under different loading conditions, with or without trauma. In this three part experiment, 120 rats had a screw or bone chamber inserted either unilaterally or bilaterally in the proximal tibia. Mechanical (pull-out) testing, μCT and histology were used for evaluation. The animals were injected with either 10mg/kg Dkk1-ab or saline every 14days for 14, 28, or 42days. Antibody treatment increased bone formation around the screws and improved their fixation. After 28days, the pull-out force was increased by over 100%. In cancellous bone, the bone volume fraction was increased by 50%. In some animals, one hind limb was paralyzed with Botulinum toxin A (Botox) to create a mechanically unloaded environment. This did not increase the response to antibody treatment with regard to screw fixation, but in cancellous bone, the bone volume fraction increased by 233%. Thus, the response in unloaded, untraumatized bone was proportionally larger, suggesting that Dkk1 may be up-regulated in unloaded bone. There was also an increase in thickness of the metaphyseal cortex. In bone chambers, the antibody treatment increased the bone volume fraction. The results suggest that antibodies blocking Dkk1 might be used to stimulate bone formation especially during implant fixation, fracture repair, or bone disuse. It also seems that Dkk1 is up-regulated both after metaphyseal trauma and after unloading, and that Dkk1 is involved in mechano-transduction.
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    ABSTRACT: Vascularized bone transplantation enables reconstruction of large skeletal defects, but this process needs a long time. Since short-term intermittent parathyroid hormone (PTH) enhances rat fracture healing, we investigated the effects of 4-week intermittent low-dose (10 microg/kg/day) or high-dose (100 microg/kg/day) PTH followed by 4-week vehicle, low-dose or high-dose intermittent PTH, or zoledronic acid (ZOL, 2 micro/kg/week), a potent bisphosphonate, on large skeletal reconstruction by vascularized tibial grafting in rats. Compared to 8-week vehicle, 8-week low-dose PTH did not significantly increase the serum osteocalcin level as well as the urinary deoxypyridinoline level, while 4-week low-dose or high-dose PTH followed by 4-week ZOL decreased both of these levels. Eight-week PTH increased the bone mass of the graft and strength of the reconstructed skeleton in a dose-dependent manner; notably, the reconstructed skeleton showed an obviously higher response to PTH compared to the contralateral nonoperated femur. In contrast, 4-week PTH followed by 4-week vehicle reduced these effects and caused local bone loss at the host-graft junctions. Four-week PTH followed by 4-week ZOL did not induce such bone loss; however, 4-week high-dose PTH followed by 4-week ZOL caused a large callus in the distal cortical junction. Four-week PTH followed by 4-week ZOL increased the bone mass and strength similarly to 8-week PTH. These preliminary findings suggest, for the first time, that sequential treatment with short-term intermittent low-dose PTH and bisphosphonate as well as long-term intermittent low-dose PTH treatment enhance large skeletal reconstruction by vascularized bone transplantation, though early timing of sequential antiresorptive treatment could result in delay of bone repair.
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