Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion

Wermelin, Karin; Tengvall, Pentti; Aspenberg, Per

doi:10.1080/17453670710013979

Cited by 62 publications

(74 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous experiments, we have repeatedly seen an increase in screw pull-out force over time in control animals [21,39], whereas this time there was a slight decrease in spite of the fact the procedures were identical, and the surgeon the same (FA). This hampers comparison with previous experiments with the pull-out screws.…”

Section: Discussionmentioning

confidence: 77%

The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions

Agholme

Isaksson

Kuhstoss

et al. 2011

Bone

Self Cite

View full text Add to dashboard Cite

The secreted protein Dickkopf-1 (Dkk1) is an antagonist of canonical Wnt signaling, expressed during fracture healing. It is unknown if 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 10 mg/kg Dkk1-ab or saline every 14 days for 14, 28, or 42 days. Antibody treatment increased bone formation around the screws and improved their fixation. After 28 days, 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 Botullinum 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.

show abstract

Section: Discussionmentioning

confidence: 77%

The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions

Agholme

Isaksson

Kuhstoss

et al. 2011

Bone

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bisphosphonates represent the largest group of these anti-resorptive drugs currently in clinical use (Rachner et al, 2011). Accordingly, coating of implant surfaces with bisphosphonates has been explored for its ability to improve implant osseointegration and testing in animal studies yielded positive results (Wermelin et al, 2007;Wermelin et al, 2008a). Another approach is to improve osseointegration by stimulation of bone formation.…”

Section: Modified Implants In An Osteoporosis Modelmentioning

confidence: 99%

Osseointegration of biochemically modified implants in an osteoporosis rodent model

Stadlinger

Korn

Tödtmann

et al. 2013

eCM

View full text Add to dashboard Cite

The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control) or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX) osteoporotic rats (n = 32/group). In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout). Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC), periimplant bone area (BA), bone volume/tissue volume (BV/ TV) and bone-mineral density (BMD) in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

show abstract

“…The trauma of drilling and inserting the screw leads to a healing response that initiates new bone formation in the vicinity of the screw. 2,3 As this leads to increasing strength of the bony threads holding the screw, the pull-out force increases over time, and reflects the efficacy of the healing response.…”

mentioning

confidence: 99%

Efficacy of a sclerostin antibody compared to a low dose of PTH on metaphyseal bone healing

et al. 2013

Self Cite

View full text Add to dashboard Cite

ABSTRACT:We compared the effect of a sclerostin antibody to that of a clinically relevant dose of parathyroid hormone (PTH) in a rat model for metaphyseal bone healing. Screws of steel or poly methyl methacrylate (PMMA) were inserted bilaterally into the proximal tibia of young male rats. During 4 weeks the animals then received injections of either phosphate buffered saline (control), sclerostin antibody (25 mg/kg, twice weekly) or PTH (5 mg/kg, daily). The healing response around the screws was then assessed by mechanical testing and X-ray microtomography (mCT). To distinguish between effects on healing and general effects on the skeleton, other untraumatized bone sites and serum biomarkers were also assessed. After 4 weeks of treatment, PTH yielded a 48% increase in screw pull-out force compared to control (p ¼ 0.03), while the antibody had no significant effect. In contrast, the antibody increased femoral cortical and vertebral strength where PTH had no significant effect. mCT showed only slight changes that were statistically significant for the antibody mainly at cortical sites. The results suggest that a relatively low dose of PTH stimulates metaphyseal repair (screw fixation) specifically, whereas the sclerostin antibody has wide-spread effects, mainly on cortical bone, with less influence on metaphyseal healing. ß

show abstract

Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion

Cited by 62 publications

References 17 publications

The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions

The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions

Osseointegration of biochemically modified implants in an osteoporosis rodent model

Efficacy of a sclerostin antibody compared to a low dose of PTH on metaphyseal bone healing

Contact Info

Product

Resources

About