Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks

Wermelin, Karin; Aspenberg, Per; Linderbäck, Paula; Tengvall, Pentti

doi:10.1002/jbm.a.31583

Cited by 59 publications

(72 citation statements)

References 30 publications

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“…We found an increase in predicted force at pullout of 8% after 10 days and 32% after 17 days as well as an increase in stiffness of 16% after 10 days and 35% after 17 days for the Zoledronate treated animals. Other studies obtained also similar values two weeks after screw implantation and bisphosphonate release (Tengvall et al, 2004;Wermelin et al, 2008). One more study from the Aspenberg group reported a 41% increase in pullout force for BP coated screws after 4 weeks (Agholme et al, 2011) what corresponds again very well with the 42% increase that we found after the same time period.…”

Section: Discussionsupporting

confidence: 89%

Time course of bone screw fixation following a local delivery of Zoledronate in a rat femoral model – A micro-finite element analysis

Kettenberger

Latypova

Terrier

et al. 2015

Journal of the Mechanical Behavior of Biomedical Materials

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Hydrogel BisphosphonateScrew fixation microCT microFE a b s t r a c t A good fixation of osteosynthesis implants is crucial for a successful bone healing but often difficult to achieve in osteoporotic patients. One possible solution to this issue is the local delivery of bisphosphonates in direct proximity to the implants, A critical aspect of this method, that has not yet been well investigated, is the time course of the implant fixation following the drug release. Usual destructive mechanical tests require large numbers of animals to produce meaningful results. Therefore, a micro-finite element (microFE) approach was chosen to analyze implant fixation. In vivo micro computed tomography (microCT) scans were obtained, first weekly and later bi-weekly, after implantation of polymeric screws in the femoral condyles of ovariectomized rats. In one half of the animals, Zoledronate was released from a hydrogel matrix directly in the peri-implant bone stock, the other animals were implanted only with screws as control. The time course of the implant fixation was investigated with linear elastic microFE models that were created based on in vivo microCT scans. The numerical models were validated against experimental pullout-tests measurements in an additional cadaver study. The microFE analysis revealed a significant increase in force at yield of the Zoledronate treated group compared to the control group. The force of the treated group was 28% higher after 17 days of screw implantation, 42% higher after 31 days. The significant difference persisted until the end of the in vivo study at day 58 (po0.01). The early onset and prolonged duration of the implant anchorage improvement that was found in this study indicates the great potential of Zoledronate-loaded hydrogel for an enhancement of osteosynthesis implant fixation in impaired bone.

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Section: Discussionsupporting

confidence: 89%

Time course of bone screw fixation following a local delivery of Zoledronate in a rat femoral model – A micro-finite element analysis

Kettenberger

Latypova

Terrier

et al. 2015

Journal of the Mechanical Behavior of Biomedical Materials

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“…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

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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.

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“…Steel screws were tested for pull-out strength in a computerized materials testing machine (100 R; DDL Inc. Eden Prairie, MN, USA), at a cross-head speed of 0.1 mm/s. These type of measurements have been described in detail earlier [23]. The machine recorded the peak force and the energy uptake until the force had dropped to 90% of maximum.…”

Section: Mechanical Evaluationmentioning

confidence: 99%

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

Agholme

Isaksson

Kuhstoss

et al. 2011

Bone

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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.

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Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks

Cited by 59 publications

References 30 publications

Time course of bone screw fixation following a local delivery of Zoledronate in a rat femoral model – A micro-finite element analysis

Time course of bone screw fixation following a local delivery of Zoledronate in a rat femoral model – A micro-finite element analysis

Osseointegration of biochemically modified implants in an osteoporosis rodent model

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

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