Effects of indomethacin on biologic fixation of porous-coated titanium implants

Cook, Stephen D.; Barrack, Robert L.; Dalton, Jeanette E.; Thomas, Kevin A.; Brown, Theresa C.

doi:10.1016/s0883-5403(05)80184-6

Cited by 40 publications

(26 citation statements)

References 28 publications

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“…In a later study, they observed a stress of 18.8 ± 3.7 MPa (12 weeks, n = 12) for a bilayered titanium porous beaded coating with a pore size of 275 um. 16 Another study by Cook's group also demonstrated stresses similar to what was observed in this study. 18 At 6 months, 50% porous Ti alloy surfaces, with an average pore size of approximately 200 um, failed at an average stress of 21.9 ± 4.6 MPa.…”

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

Three-dimensional printing and porous metallic surfaces: A new orthopedic application

Melican

Zimmerman

Dhillon³

et al. 2001

J. Biomed. Mater. Res.

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As-cast, porous surfaced CoCr implants were tested for bone interfacial shear strength in a canine transcortical model. Three-dimensional printing (3DP) was used to create complex molds with a dimensional resolution of 175 microm. 3DP is a solid freeform fabrication technique that can generate ceramic pieces by printing binder onto a bed of ceramic powder. A printhead is rastered across the powder, building a monolithic mold, layer by layer. Using these 3DP molds, surfaces can be textured "as-cast," eliminating the need for additional processing as with commercially available sintered beads or wire mesh surfaces. Three experimental textures were fabricated, each consisting of a surface layer and deep layer with distinct individual porosities. The surface layer ranged from a porosity of 38% (Surface Y) to 67% (Surface Z), whereas the deep layer ranged from 39% (Surface Z) to 63% (Surface Y). An intermediate texture was fabricated that consisted of 43% porosity in both surface and deep layers (Surface X). Control surfaces were commercial sintered beaded coatings with a nominal porosity of 37%. A well-documented canine transcortical implant model was utilized to evaluate these experimental surfaces. In this model, five cylindrical implants were placed in transverse bicortical defects in each femur of purpose bred coonhounds. A Latin Square technique was used to randomize the experimental implants left to right and proximal to distal within a given animal and among animals. Each experimental site was paired with a porous coated control site located at the same level in the contralateral limb. Thus, for each of the three time periods (6, 12, and 26 weeks) five dogs were utilized, yielding a total of 24 experimental sites and 24 matched pair control sites. At each time period, mechanical push-out tests were used to evaluate interfacial shear strength. Other specimens were subjected to histomorphometric analysis. Macrotexture Z, with the highest surface porosity, failed at a significantly higher shear stress (p = 0.05) than the porous coated controls at 26 weeks. It is postulated that an increased volume of ingrown bone, resulting from a combination of high surface porosity and a high percentage of ingrowth, was responsible for the observed improvement in strength. Macrotextures X and Y also had significantly greater bone ingrowth than the controls (p = 0.05 at 26 weeks), and displayed, on average, greater interfacial shear strengths than controls, although they were not statistically significant.

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Section: Discussionsupporting

confidence: 88%

“…7,15 Cook et al 16 tested a twolayer beaded CPTi porous surface made from −30/+45 sieve size powder resulting in an average pore size of 275 um and approximately 39% porosity. Cook et al's 6 week bone ingrowth of 77.3% (n = 12) was higher than the range we measured, 44 ±18.3%.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional printing and porous metallic surfaces: A new orthopedic application

Melican

Zimmerman

Dhillon³

et al. 2001

J. Biomed. Mater. Res.

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“…Others have shown a decrease in pullout strength of transcortical plugs after 3 weeks of treatment with indomethacin. 8 Treatment with indomethacin had a time-dependent inhibitory effect on bone ingrowth in porous-coated implants. 7 Our in vitro data also indicate a downregulation of osteoblast function by general cyclooxygenase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to the nonsteroid anti-inflammatory agent for less than 3 weeks reduced bone formation and the pullout strength of transcortical plugs whereas longer exposures were without effect. 8 The studies described above indicate that arachidonic acid metabolism is important to optimal bone formation around implants and suggest that periimplant osteogenesis is sensitive to the rate and extent of prostaglandin production. In vitro studies support this hypothesis.…”

Section: Introductionmentioning

confidence: 98%

Both cyclooxygenase-1 and cyclooxygenase-2 mediate osteoblast response to titanium surface roughness

Boyan

Lohmann

Sisk

et al. 2001

J. Biomed. Mater. Res.

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Previous studies suggest that the enhanced expression of the osteoblastic phenotype exhibited by MG63 osteoblast-like cells on rough Ti surfaces (R(a) 4-5 microm) involves increased production of prostaglandin. Inhibition of prostaglandin synthesis by indomethacin blocks surface-roughness-dependent decreases in cell proliferation and increases in alkaline phosphatase activity and the production of osteocalcin and TGF-beta1. This study examined the hypothesis that the increase in expression of the osteoblastic phenotype noted in MG63 cells cultured on rough Ti surfaces is mediated by inducible cyclooxygenase-2 (Cox-2) whereas Cox-1 modulates prostaglandin production and phenotypic expression of the cells under standard conditions and on smooth Ti surfaces. MG63 cells were cultured on tissue culture plastic, smooth Ti (PT, R(a) = 0.60 microm), and two rough Ti surfaces with differing morphologies (SLA, R(a) = 3.97 microm and TPS, R(a) = 5.21 microm). At 24 h after plating, media were replaced with media containing the general Cox inhibitor indomethacin (10(-7)M), the Cox-1 inhibitor resveratrol (1 or 10 microM), or the Cox-2 inhibitor NS-398 (1 or 10 microM). Media were changed again after 48 h. Five days after plating, osteocalcin, PGE(2), and TGF-beta1 content of the conditioned media were determined. Cell numbers were assessed in the same cultures used for determination of osteocalcin production. Cell layer protein and alkaline phosphatase specific activity were assessed in cultures used to measure PGE(2) and TGF-beta1. Indomethacin, resveratrol, and NS-398 had no effect on cell number. Indomethacin blocked the surface-roughness-dependent increase in PGE(2) production by up to 80%. Similarly, resveratrol inhibited up to 50% of the PGE(2) production on smooth surfaces and up to 80% on rough surfaces. In contrast, NS-398 had no effect on PGE(2) production by cells on smooth surfaces but caused a 60% reduction in cultures on rough surfaces. Indomethacin reduced alkaline phosphatase on all surfaces below basal levels. However, neither resveratrol nor NS-398 had an effect. Indomethacin blocked the stimulatory effect of surface roughness on osteocalcin production while resveratrol only partially reduced osteocalcin production, and NS398 completely blocked the surface-dependent increase. TGF-beta1 production on rough surfaces was blocked by indomethacin. The effects of resveratrol and NS-398 were dose dependent, but neither agent caused total inhibition of the increase noted on SLA, and only resveratrol blocked the increase on TPS. These results indicate that both Cox-1 and Cox-2 are involved in the response of osteoblasts to surface roughness with respect to production of PGE(2), TGF-beta1, and osteocalcin. While prostaglandin mediates the effects of surface roughness on alkaline phosphatase, neither Cox-1 nor Cox-2 appears to be involved, at least with respect to the two inhibitors used.

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“…A doseresponse effect was found for the indomethacin and aspirin groups. In another study, indomethacin decreased the bone-implant interface attachment strength of transcortical plugs in dogs at three weeks, but not at later time periods up to 24 weeks (14).…”

Section: Non-specific Nsaids and Bonementioning

confidence: 92%

Cox-2 Selective Inhibitors and Bone

Goodman

Genovese

et al. 2003

Int J Immunopathol Pharmacol

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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed medications for relief of pain and inflammation. Recent animal studies using models of fracture healing and bone ingrowth suggest that NSAIDs (both non-selective NSAIDs and selective COX-2 inhibitors) adversely affect these bone-related processes. The dose and time-relationships of these medications and their resulting effects on bone have not yet been fully elucidated. Furthermore, whether COX-2 inhibitors and non-selective NSAIDs lead to clinically relevant adverse effects on bone healing in humans is unknown.

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Effects of indomethacin on biologic fixation of porous-coated titanium implants

Cited by 40 publications

References 28 publications

Three-dimensional printing and porous metallic surfaces: A new orthopedic application

Three-dimensional printing and porous metallic surfaces: A new orthopedic application

Both cyclooxygenase-1 and cyclooxygenase-2 mediate osteoblast response to titanium surface roughness

Cox-2 Selective Inhibitors and Bone

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