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      No deleterious effect of low dose methotrexate on titanium implant osseointegration in a rabbit model

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          Abstract

          OBJECTIVE:

          To evaluate the effect of low dose methotrexate alone or in combination with glucocorticoid treatment on titanium implant osseointegration.

          METHODS:

          Groups of 6–8 adult New Zealand White rabbits were treated for 18 weeks with saline (control), methotrexate, glucocorticoid, or methotrexate plus glucocorticoid. The animals received a titanium implant in the tibia at week 6. Lumbar spine and tibia bone mineral densities were analyzed before and after treatment. Histomorphometric analysis of bone cortical thickness, total bone area around the implant, and % of bone to implant contact was performed.

          RESULTS:

          After 18 weeks, the change in the bone mineral density in the lumbar spines and tibias in the methotrexate group was comparable to the control group (0.035 vs. 0.055 g/cm 2 and 0.021 vs. 0.041 g/cm 2, respectively). In contrast, both the glucocorticoid group and glucocorticoid plus methotrexate group had significant reductions at both sites. Histomorphometric analysis of the tibia in the control and methotrexate groups revealed no significant changes in cortical thickness (133 vs. 126 µm), total bone area around the implant (33 vs. 30%), or bone to implant contact (40 vs. 38%). In contrast, glucocorticoid group had significant reductions compared to controls in tibia cortical thickness (99 vs. 133 µm), total bone area around the implant (24 vs. 33%), and bone to implant contact (27 vs. 40%). Similar reductions were observed in the glucocorticoid plus methotrexate group.

          CONCLUSIONS:

          Our results demonstrate that low dose methotrexate treatment does not affect titanium implant osseointegration, suggesting that this therapy is safe for surgical procedures requiring a titanium implant.

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          Most cited references98

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          Biology of implant osseointegration.

          Osseointegration refers to a direct structural and functional connection between ordered, living bone and the surface of a load-carrying implant. Currently, an implant is considered as osseointegrated when there is no progressive relative movement between the implant and the bone with which it has direct contact. A direct bone contact as observed histologically may be indicative of the lack of a local or systemic biological response to that surface. It is therefore proposed that osseointegration is not the result of an advantageous biological tissue response but rather the lack of a negative tissue response. The rationale of the present review is to evaluate the basic science work performed on the concept of biology of osseointegration, and to discuss the specific factors as they may relate to osseous healing around an implant.
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            Treatment persistence with adalimumab, etanercept, or infliximab in combination with methotrexate and the effects on health care costs in patients with rheumatoid arthritis.

            Anti-tumor necrosis factor (TNF) biologic agents are effective in treating rheumatoid arthritis (RA). Information on patient persistence with biologic anti-TNF therapies is limited, and the effects of persistence on the costs of therapy are unknown. The aims of this study were to compare treatment persistence with adalimumab, etanercept, or infliximab in combination withmethotrexate (MTX) and evaluate the effects of persistence on overall health care costs. This retrospective study used data from the PharMetrics managed care administrative claims database. Data from patients with RA who received combination treatment with an anti-TNF agent plus MTX and had > or = 24 months of continuous plan eligibility were collected. The 3 anti-TNF cohorts were adalimumab + MTX (adalimumab group), etanercept + MTX (etanercept group), and infliximab + MTX (infliximab group). Treatment persistence was defined as the number of days between the first and last anti-TNF treatment and was reported as a percentage of the 1-year period after treatment initiation. Costs were compared between patients with treatment persistence rates > or = 80% or or = 80% had higher mean total health care costs compared with those with treatment persistence or = 80% persistence cohort ($3091 vs $4601; P = 0.015). In this population of patients with RA, overall treatment persistence was high, with patients treated with infliximab + MTX having significantly higher persistence compared with those treated with adalimumab + MTX or etanercept + MTX. While pharmacy costs were higher in patients with > or = 80% persistence, nonpharmacy costs were lower.
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              A longitudinal study of the growth of the New Zealand white rabbit: cumulative and biweekly incremental growth rates for body length, body weight, femoral length, and tibial length.

              This longitudinal study documents cumulative and incremental growth in the New Zealand white rabbit from 2 to 34 weeks of age at biweekly intervals. Body weight, body length, femoral length, and tibial length have been assessed in 17 male and 12 female rabbits, with the data tabulated separately. A specially designed restrainer was used that allowed the sequential clinical measurements and femoral and tibial radiographs to be performed without the use of anesthesia. Skeletal growth was complete at 28 weeks, with the 34-week values thus representing mature adult lengths. The mean body weight at 2 weeks of age was 6% that at 34 weeks, and by 16 weeks, 72% of the weight at 34 weeks was achieved. Weight continued to increase in the adult. The mean body length at 2 weeks was 40% that at 34 weeks, and by 16 weeks, 91% of mature adult length was achieved. The mean femoral length at 2 weeks was 38% of the adult length, and at 16 weeks, it reached 95% of adult length. The mean tibial length at 2 weeks was 38% of the adult length, and 94% of the adult value was achieved by 16 weeks. The longitudinal data document the rate and extent of growth of the New Zealand white rabbit, and allow for more accurate timing and quantitation of physical and systemic interventions on the developing skeleton of the commonly investigated New Zealand white rabbit.
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                Author and article information

                Journal
                Clinics (Sao Paulo)
                Clinics
                Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
                1807-5932
                1980-5322
                June 2011
                : 66
                : 6
                : 1055-1059
                Affiliations
                [I ]Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo.
                [II ]Periodontics, Dental Branch, Universidade de São Paulo, SP, Brazil.
                Author notes
                E-mail: bcarvas@ 123456hotmail.com Tel.: 55 11 3061-7200
                Article
                cln_66p1055
                10.1590/S1807-59322011000600023
                3129966
                21808875
                3b77c518-3c98-418c-8997-967757a3272c
                Copyright © 2011 Hospital das Clínicas da FMUSP

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 February 2011
                : 2 March 2011
                : 15 February 2011
                Page count
                Pages: 5
                Categories
                Basic Research

                Medicine
                glucocorticoid,dental implant,methotrexate,osseointegration
                Medicine
                glucocorticoid, dental implant, methotrexate, osseointegration

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