Local Alendronic Acid Elution Increases Net Periimplant Bone Formation: A Micro-CT Analysis

Bobyn, J. D.; Thompson, Rebecca; Lim, Letitia; Pura, Jenny Ann; Bobyn, Kristian; Tänzer, Michael

doi:10.1007/s11999-013-3120-6

Cited by 39 publications

(42 citation statements)

References 20 publications

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“…Local application is of particular interest in cases where existing bone needs to be preserved and augmented whilst avoiding the known side effects related to systemic administration [14,15]. Several in vivo studies have shown that a local delivery of BPs can enhance peri-implant bone density [16,17], implant fixation [18e22], and the repair of bony defects [23,24] in animal models and humans. Furthermore BPs have been shown to preserve bone allografts [25,26] as well as bone sites affected by osteonecrosis [27].…”

Section: Introductionmentioning

confidence: 99%

Does locally delivered Zoledronate influence peri-implant bone formation? – Spatio-temporal monitoring of bone remodeling in vivo

Kettenberger

Ston

Thein³

et al. 2014

Biomaterials

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a b s t r a c tBisphosphonates are known for their strong inhibitory effect on bone resorption. Their influence on bone formation however is less clear. In this study we investigated the spatio-temporal effect of locally delivered Zoledronate on peri-implant bone formation and resorption in an ovariectomized rat femoral model. A cross-linked hyaluronic acid hydrogel was loaded with the drug and applied bilaterally in predrilled holes before inserting polymer screws. Static and dynamic bone parameters were analyzed based on in vivo microCT scans performed first weekly and then biweekly. The results showed that the locally released Zoledronate boosted bone formation rate up to 100% during the first 17 days after implantation and reduced the bone resorption rate up to 1000% later on. This shift in bone remodeling resulted in an increase in bone volume fraction (BV/TV) by 300% close to the screw and 100% further away. The double effect on bone formation and resorption indicates a great potential of Zoledronateloaded hydrogel for enhancement of peri-implant bone volume which is directly linked to improved implant fixation.

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Section: Introductionmentioning

confidence: 99%

Does locally delivered Zoledronate influence peri-implant bone formation? – Spatio-temporal monitoring of bone remodeling in vivo

Kettenberger

Ston

Thein³

et al. 2014

Biomaterials

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“…Alendronate was dissolved in aliquots of distilled deionized water to produce doses of 0.02 mg/cm 2 , 0.06 mg/cm 2 , and 0.18 mg/cm 2 . The 0.06 mg/cm 2 alendronate dose was chosen based on the previous successful results using a similar implant [5]. To find the lowest effective dose, a dose 1 .…”

Section: Implant Structurementioning

confidence: 99%

“…Periimplant bone was defined as the area surrounding the implant. A radius of 2.5 mm from the implant was specified based on a previous study that showed that bone formation that resulted from local bisphosphonate elution was localized to the periimplant region [5]. Periimplant bone was calculated by taking the percentage of bone found in the area of the 2.5 mm radius and dividing this by the total area defined by this medullary space, not including the area of the implant.…”

Section: Sample Preparationmentioning

confidence: 99%

“…Several clinical studies of large patient cohorts have shown that systemic delivery of bisphosphonates can reduce revision rates for total joint replacement implant loosening [2,3,7,20], but systemic treatment exposes the entire skeleton to the drug, thereby subjecting patients to the associated risks of side effects or adverse events such as nausea, vomiting, epigastric pain, and dypsepsia [17]. This potentially can be avoided by locally releasing the bisphosphonate directly from the implant to the surrounding bone as seen in our previous radioactive studies showing insignificant levels of the drug outside the direct periimplant region exposed to the bisphosphonate [5]. Prior studies in animal models with various bisphosphonates have shown that locally administered or released bisphosphonates enhanced bone formation around implants [4, 8-11, 13, 15, 19, 24, 25, 30].…”

Section: Introductionmentioning

confidence: 99%

“…In a previous pilot study in dogs, using two different alendronate doses on porous implants, the efficacy of alendronate on periimplant formation was seen with the higher dose resulting in greater local bone formation 12 weeks after surgery [5]. Expanding from the pilot study, it also was necessary to determine the therapeutic dose range of contemporary implants similar to those available today.…”

Section: Introductionmentioning

confidence: 99%

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Implant-delivered Alendronate Causes a Dose-dependent Response on Net Bone Formation Around Porous Titanium Implants in Canines

Pura

Bobyn

Tänzer

2016

Clinical Orthopaedics &Amp; Related Research

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Background Bony fixation of cementless orthopaedic implants is not always achieved, particularly in challenging scenarios such as revision surgery, trauma, and tumor reconstruction. An adjunct therapy for improving porous implant fixation could improve the reliability and durability of these reconstructive procedures. Questions/purposes In this study, we asked whether there is a positive and dose-dependent effect of the local release of the bisphosphonate alendronate from (1) alendronate/ hydroxyapatite (HA) porous-coated titanium implants compared with bare metal porous controls; and (2) alendronate/HA on porous-coated titanium implants compared with HA-coated porous controls with respect to extent of bone ingrowth, bone apposition, and periimplant bone formation in a canine model? Methods Three-dimensional printed porous-coated cylindrical implants coated with three different doses (0.02, 0.06, and 0.18 mg/cm 2 ) of alendronate were inserted bilaterally in the intramedullary canal of the proximal femora of 15 adult mongrel dogs (age range, 3-9 years; mean, 5 years) weighing between 36 kg and 60 kg (mean, 43 kg). In each dog, an implant coated with HA and one of three different doses of alendronate was inserted on one side while the contralateral femur had a bare metal porous control implant and an identical control implant with a coating of HA. The dose effect of locally released alendronate on the extent of bone ingrowth, bone apposition, and periimplant bone was assessed by backscattered electron microscopy of three pairs of crosssections taken from each implant at 12 weeks after surgery. A linear mixed model was used to perform the statistical analyses to account for the correlation in the data resulting from the multiple measures performed on each dog. Results Compared with paired bare metal controls, periimplant bone increased by 92% (p = 0.007), and 114% (p\ 0.001) in the femora with the alendronate implants with a dose of 0.06 mg/cm 2 , or 0.18 mg/cm 2 , respectively. At a dose of 0.02 mg/cm 2 , there was no difference (46% change; p = 0.184, with the numbers available). The comparison of the alendronate-dosed implants with their HA-coated controls showed that the intermediate dose of 0.06 mg/cm 2 alendronate had the greatest effect on net bone formation. Bone apposition was enhanced with the 0.06-mg/cm 2 alendronate femoral implants (82%; p = 0.008), although there was no change in bone ingrowth Two of the authors certify that they (JDB, MT), or a member of their immediate families, has or may receive payments or benefits, during the study period, an amount of USD 10,000 to USD 100,000 from Pipeline Biotechnology (Cedar Knolls, NJ, USA). (37% change; p = 0.902, with the numbers available). When compared with the HA-coated control implants, the greatest effect of the alendronate-dosed implants was the increased amount of periimplant bone at the intermediate dose of 0.06-mg/cm 2 (108%, p = 0.009). There was no effect of the low (0.02-mg/cm 2 ) and high (0.18-mg/cm 2 ) alendronate-dosed implants (...

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Local delivery of zoledronate from a poly (D,L‐lactide)—Coating increases fixation of press‐fit implants

Jakobsen

Bechtold

Søballe

et al. 2015

Journal Orthopaedic Research

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Early secure fixation of total joint replacements is crucial for long-term survival. Antiresorptive agents such as bisphosphonates have been shown to increase implant fixation. We investigated whether local delivery of zoledronate from poly-D, Llactide (PDLLA)-coated implants could improve implant fixation and osseointegration. Experimental titanium implants were bilaterally inserted press-fit into the proximal tibiae of 10 dogs. On one side the implant was coated with PDLLA containing zoledronate. The contralateral implant was uncoated and used as control. Observation period was 12 weeks. Implant fixation was evaluated with histomorphometry and biomechanical push-out test. We found an approximately twofold increase in all biomechanical parameters when comparing data from the zoledronate group with their respective controls. Histomorphometry showed increased amount of preserved bone and increased bone formation around the zoledronate implants. This study indicates that local delivery of zoledronate from a PDDLA coating has the potential to increase implant fixation. ß

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Local Alendronic Acid Elution Increases Net Periimplant Bone Formation: A Micro-CT Analysis

Abstract: This concept has potential to improve the biologic fixation of porous reconstructive implants.

Cited by 39 publications

References 20 publications

Does locally delivered Zoledronate influence peri-implant bone formation? – Spatio-temporal monitoring of bone remodeling in vivo

Does locally delivered Zoledronate influence peri-implant bone formation? – Spatio-temporal monitoring of bone remodeling in vivo

Implant-delivered Alendronate Causes a Dose-dependent Response on Net Bone Formation Around Porous Titanium Implants in Canines

Local delivery of zoledronate from a poly (D,L‐lactide)—Coating increases fixation of press‐fit implants

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