Alendronate enhances osseointegration in a murine implant model

Vertesich, Klemens; Sosa, Branden R.; Niu, Yingzhen; Ji, Gang; Suhardi, V; Turajane, Kathleen; Mun, Se-Hwan; Xu, Ren; Windhager, Reinhard; Park-Min, Kyung Hyun; Greenblatt, Matthew B.; Bostrom, Mathias P.; Yang, Xu

doi:10.1002/jor.24853

Cited by 15 publications

(18 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in contrast to human knee implantation, there is no joint load applied through the cement plug and there is no mechanical interlock between cement and trabecular bone. To explore biomaterial interfaces with joint loading, tibial hemiarthroplasty models have been developed for the mouse, 11,12 rat, 13 and rabbit. 14 The goal of these studies was not to assess functional total joint replacement per se, but rather to develop a model that could address specific questions with regard to bony ingrowth, fibrous tissue formation, or influence of debris or infection on the bone-implant interface.…”

Section: Rationale For Use Of a Peek Hemiarthroplasty Modelmentioning

confidence: 99%

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty

Mann

Miller

Rossow

et al. 2021

Journal Orthopaedic Research

View full text Add to dashboard Cite

Aseptic loosening of total knee arthroplasty continues to be a challenging clinical problem. The progression of the loosening process, from the initial well-fixed component, is not fully understood. In this study, loss of fixation of cemented hemiarthroplasty was explored using 9-month-old Sprague-Dawley rats with 0, 2, 6, 12, 26 week end points. Morphological and cellular changes of cement-bone fixation were determined for regions directly below the tibial tray (epiphysis) and distal to the tray (metaphysis). Loss of fixation, with a progressive increase in cement-bone gap volume was found in the epiphysis (0.162 mm 3 /week), but did not progress appreciably in the metaphysis (0.007 mm 3 /week). In the epiphysis, there was an early and sustained elevation of osteoclasts adjacent to the cement border and development of a fibrous tissue layer between the cement and bone. There was early formation of bone around the cement in the metaphysis, resulting in a condensed bone layer without osteoclastic bone resorption or development of a fibrous tissue layer. Implant positioning was also an important factor in the cement-bone gap formation, with greater gap formation for implants that were placed medially on the tibial articular surface. Loss of fixation in the rat model mimicked patterns found in human arthroplasty where cement-bone gaps initiate under the tibial tray, at the periphery of the implant. This preclinical model could be used to study early biological response to cemented fixation and associated contributions of mechanical instability, component alignment, and periprosthetic inflammation.

show abstract

Section: Rationale For Use Of a Peek Hemiarthroplasty Modelmentioning

confidence: 99%

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty

Mann

Miller

Rossow

et al. 2021

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…To gain insight into how aging affects osseointegration at the bone-implant interface, we performed RNA-seq of implant-associated tissue from old versus young mice one week after implantation. This time point corresponds to early osseointegration where deposition of woven bone overlaps with a resolving inflammatory response (15,19,23,33,35,40) .…”

Section: Resultsmentioning

confidence: 99%

“…We performed our studies one week post-implantation, when the initial inflammatory response to injury is subsiding and the bone formation phase is underway (15,19,23,33,35) . At this phase, increased and sustained inflammation in aged mice mediated by innate immune cytokines such as TNF and IL-1 can suppress osseointegration by augmenting osteoclastogenesis, suppressing osteoblasts directly or via increased production of Wnt pathway inhibitors such as DKK1 (32,64) , and compromising the emergence of a pre-resolution immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Using an IACUC-approved protocol, 16-week-old (young) and 91-week-old (aged) female C57BL/6 mice (n=10 per group) were purchased from Jackson Laboratory (Bar Harbor, Maine). A porous titanium (Ti6Al4V) implant (Eosint M 270; Eos Electro Optical Systems, Munich, Germany) was inserted into the right proximal tibia of the mice as previously described (Figure 1) (15,19,23) . Mice started weight-bearing with the implanted knee immediately after recovering from anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…We and others have developed animal models to analyze the process of orthopaedic implant integration (12–24) . In our mouse model, load-bearing titanium implants inserted into the proximal tibia become integrated with the surrounding bone over a 4-week period (15,19,23) . Little is known about molecular pathways that regulate this process.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Age-related Impairment of Implant Osseointegration is Associated with Immune Activation and Suppression of Angiogenic, Notch, and Wnt Pathways

Turajane

Chinenov

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri-implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone-implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone-implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri-implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri-implant site may enhance osseointegration and improve the outcome of joint replacement in older patients.

show abstract

RNA‐seqAnalysis ofPeri‐ImplantTissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice

Turajane

Chinenov

et al. 2021

JBMR Plus

Self Cite

View full text Add to dashboard Cite

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri‐implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone‐implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone‐implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri‐implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri‐implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

show abstract

Alendronate enhances osseointegration in a murine implant model

Cited by 15 publications

References 48 publications

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty

Age-related Impairment of Implant Osseointegration is Associated with Immune Activation and Suppression of Angiogenic, Notch, and Wnt Pathways

RNA‐seqAnalysis ofPeri‐ImplantTissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice

Contact Info

Product

Resources

About