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Resume Objectif Verifier l’importance de l’alignement du plateau tibial interne (PTI), determine par la distance entre le bord anterieur et posterieur du plateau (distance inter-bords [DIB]), pour la mesure de l’epaisseur de l’interligne articulaire (EIA) sur les radiographies de genoux normaux. Methodes L’EIA et la DIB ont ete mesurees sur des radiographies de genoux appariees (au debut de l’etude et apres 12 mois) chez 122 patients de l’osteoarthritis initiative (OAI). Les relations entre l’EIA et la DIB, et entre la variation de l’EIA et la variation de la DIB, ont ete evaluees. Resultats Dans une analyse transversale, une relation non lineaire a ete mise en evidence entre l’EIA et la DIB. Avec un mauvais alignement du PTI (DIB > 1,7 mm), une augmentation de 1,0 mm de la DIB entrainait une augmentation de 0,16 mm de l’EIA (IC 95 % : 0,11–0,21) ( p p Initiale et le DIB 12 mois a ete associee a une variation de 0,10 mm de l’EIA (IC 95 % : 0,06–0,13), avec des variations de l’EIA et de la DIB evoluant dans le meme sens. La variation acceptable de la DIB pour une evaluation precise de l’EIA sur des series radiographiques a ete determinee inferieure ou egale a 1,0 mm. Conclusion L’erreur de mesure de l’EIA causee par une variation de la DIB sur des series radiographiques de genoux normaux peut etre aussi importante, voir plus importante, que la variation du pincement de l’interligne articulaire a 12 mois de genoux arthrosiques. L’alignement du PTI et la reproduction de cet alignement dans des series de radiographies de genoux sont necessaires pour une evaluation precise du pincement de l’interligne articulaire des genoux arthrosiques.

Objective To explore whether the risk of incident tibiofemoral (TF) osteoarthritis (OA) in the radiographically normal contralateral knee of overweight/obese women with unilateral knee OA is mediated by malalignment and/or preceded by increased turnover of subchondral bone. Methods We used data of post hoc analyses from a randomized controlled trial. Cross-sectional analyses evaluated the baseline association between frontal plane alignment and bone turnover in the medial TF compartment in 78 radiographically normal contralateral knees. Longitudinal analyses ascertained whether incident radiographic OA (TF osteophyte formation within 30 months) was associated with malalignment and/or increased bone turnover at baseline. Alignment subcategories (varus/neutral/valgus) were based on the anatomic axis angle. 99mTc–methylene diphosphonate uptake in a late-phase bone scan was quantified in regions of interest in the medial tibia (MT) and medial femur (MF) and adjusted for uptake in a reference segment of the ipsilateral tibial shaft (TS). Results MF and MT uptake in varus contralateral knees was 50–55% greater than in the TS. Adjusted MT uptake in varus contralateral knees was significantly greater than that in neutral and valgus contralateral knees (mean 1.55 versus 1.38 and 1.43, respectively; P < 0.05). Among 69 contralateral knees followed longitudinally, 22 (32%) developed TF OA. Varus angulation was associated with a marginally significant increase in the odds of incident OA (adjusted odds ratio 3.98, P = 0.067). Conclusion While the small sample size limited our ability to detect statistically significant risk factors, these data suggest that the risk of developing bilateral TF OA in overweight/obese women may be mediated by varus malalignment.

Summary Objective To respond to a pre-specified set of questions posed by the United States Food and Drug Administration (FDA) on defining the disease state to inform the clinical development of drugs, biological products, and medical devices for the prevention and treatment of osteoarthritis (OA). Methods An Osteoarthritis Research Society International (OARSI) Disease State working group was established, comprised of representatives from academia and industry. The Working Group met in person and by teleconference on several occasions from the Spring of 2008 through the Autumn of 2009 to develop consensus-based, evidence-informed responses to these questions. A report was presented at a public forum in December 2009 and accepted by the OARSI Board of Directors in the Summer of 2010. Results An operational definition of OA was developed incorporating current understanding of the condition. The structural changes that characterize OA at the joint level were distinguished from the patients' experience of OA as the ‘disease' and ‘illness', respectively. Recommendations were made regarding the evaluation of both in future OA clinical trials. The current poor understanding of the phenotypes that characterize OA was identified as an important area for future research. Conclusions The design and conduct of clinical trials for new OA treatments should address the heterogeneity of the disease, treatment-associated structural changes in target joints and patient-reported outcomes.

Objective: To investigate how different types of meniscal tears predispose to different patterns of meniscal position in subjects with and without symptomatic knee osteoarthritis (OA). Methods: A cross-sectional analysis of 161 women participating in an observational study to evaluate knee OA progression was performed using baseline MRI data. Meniscal morphologic features were scored in three separate locations. Meniscal position measures were determined for extrusion and proportion of coverage. Analysis was performed using multiple linear regression models treating each tear type as an individual variable with a binary response. Results: Complex tears, cysts and maceration of the medial meniscus were associated with more medial ( p = 0.0004, p = 0.004, p < 0.0001, respectively) and anterior extrusion ( p = 0.03, p = 0.03, p < 0.0001, respectively) than normal menisci. Horizontal tears of the lateral meniscus had more lateral ( p = 0.005) and anterior extrusion ( p < 0.0001) than normal menisci. Anterior and body tears of the medial meniscus were associated with more anterior extrusion ( p = 0.0006, p = 0.01, respectively), whereas meniscal body tears alone had more medial extrusion than normal menisci ( p = 0.0002). Meniscal body tears of the lateral meniscus had more lateral extrusion than normal menisci ( p = 0.01). Conclusion: Anterior horn and meniscal body tears and the more severe macerated and complex tear types predisposed to more medial meniscal extrusion. Laterally, only meniscal body and horizontal tears significantly affected extrusion, potentially reflecting a lower overall prevalence of lateral meniscal tears. These results may have important implications in identifying tear types associated with more meniscal dysfunction, with the ultimate goal of identifying those at greatest risk for knee OA progression.

summary Objective: To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009. Methods: A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence. Results: Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for selfmanagement, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) � 0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES ¼ 0.77, 95% CI 0.36, 1.17) was no longer significant (ES ¼ 0.16, 95% CI � 0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES ¼ 0.10, 95% CI � 0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3 g/day have been published (HR ¼ 1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo. Conclusion: Publication of a large amount of new research evidence has resulted in changes in the calculated risk–benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.

Summary Objective To identify subregional differences in femorotibial cartilage morphology between healthy controls and women with different grades of radiographic knee osteoarthritis (OA). Design 158 women aged ≥40 years were studied. Weight-bearing extended anterior-posterior (AP) and Lyon schuss radiographs were obtained and the Kellgren Lawrence grade (KLG) determined. 97 women had a body mass index (BMI)≤28, no symptoms, and were AP KLG0. 61 women had a BMI≥30, symptoms in the target knee, and mild (KLG2=31) to moderate (KLG3=30) medial femorotibial radiographic OA in the AP views. Coronal spoiled gradient echo water excitation sequences were acquired at 3.0 Tesla. Total plate and regional measures of cartilage morphology of the weight-bearing femorotibial joint were quantified. Results KLG2 participants displayed, on average, thicker cartilage than healthy controls in the medial femorotibial compartment (particularly anterior subregion of the medial tibia (MT) and peripheral [external, internal] subregions of the medial femur), and in the lateral femur. KLG3 participants displayed significantly thinner cartilage than KLG0 participants in the medial weight-bearing femur (central subregion), in the external subregion of the MT, and in the internal subregion of the lateral tibia. These differences were generally unaffected when possible effects of demographic covariates were considered. Conclusions The results indicate that in femorotibial OA regional cartilage thickening and thinning may occur, dependent on the (radiographic) disease status of the joint. These changes appear to display a heterogeneous spatial pattern, where certain subregions are more strongly affected than others.

Summary Background Joint space width (JSW) evaluated in millimeters on plain X-rays is the currently optimal recognized technique to evaluate osteoarthritis (OA) structural progression. Data obtained can be presented at the group level (e.g., mean±standard deviation of the changes). Such presentation makes difficult the interpretation of the clinical relevance of the reported results. Therefore, a presentation at the individual level (e.g., % progressors) seems more attractive but requires to determining a cut-off. Several methodologies have been proposed to define cut-offs in JSW: arbitrary chosen cut-off, cut-off based on the validity to predict a relevant end-point such as the requirement of total articular replacement or cut-off based on the measurement error such as smallest detectable difference (SDD). Objectives The objective of this OARSI–OMERACT initiative was to define a cut-off evaluated in millimeters on plain X-rays above which a change in JSW could be considered as relevant in patients with hip and knee OA. Methods The first step consisted in a systematic literature research performed using Medline database up to July 2007 to obtain all manuscripts published between 1990 and 2007 reporting a cut-off value in JSW evaluated in millimeters at either the knee or hip level. The second step consisted in a consensus based on the best knowledge of the 11 experts with the support of the available evidence. Results Among the 506 articles selected by the search, 47 articles reported cut-off of JSW in millimeters. There was a broad heterogeneity in cut-off values, whatever the methodologies or the OA localization considered (e.g., from 0.12 to 0.84mm and from 0.22 to 0.78mm for Knee (seven studies) and hip (seven studies), respectively when considering the data obtained based on the reliability). Based on the data extracted in the literature, the expert committee proposed a definition of relevant change in JSW based on plain X-rays, on an absolute change of JSW in millimeters and on the measurement error e.g., calculation of the SDD using the Bland and Altman technique. The results of the analysis of JSW should be expressed in terms of a dichotomous variable (e.g., progressors yes/no): a patient with a change in JSW during the study over such SDD will fulfill the definition of "progressor". Moreover, the pilot study aimed at evaluating the measurement error should be designed to reflect the different characteristics of the primary study in which the analysis of the radiological findings will be based on (patient's characteristics, centers characteristics, readers). Conclusion This initiative based on both an Evidence Based Medicine (Systematic Literature Research) and Expert Opinion approach resulted in a proposal of definition of relevant radiological progression in OA to be used as end-point in clinical trials and also recommendations on the conduct of the reliability study allowing such definition.

To evaluate the validity of using the conventional anteroposterior (AP) radiograph of the knee in order to identify joint space narrowing (JSN) at an early stage of osteoarthritis (OA).Grading of JSN using a 0-5 score and quantitative measurement of joint space width (JSW) of the medial and lateral compartments of the tibiofemoral joint in AP and fluoroscopically assisted posteroanterior Lyon schuss (LS) radiographs of 202 patients with knee OA.Knees without definite JSN (score2) were twice as common in AP than in LS radiographs (36.1% vs 18.8%). The number of knees showing definite medial JSN was identical in both views but four knees showing a medial OA in AP view were classified differently in the LS radiographs (three bicompartmental OA and one lateral OA). The frequency of lateral JSN was approximately twice as great in the LS view as in the AP view. JSN score was significantly higher (p0.001) and JSW was significantly smaller (p0.01) in the LS view than in the AP view. In knees with definite JSN, JSW of the compartment with no narrowing was significantly (p0.04) larger than in knees that did not exhibit definite JSN. Medial JSW and lateral JSW were inversely correlated (p0.001).The standing AP radiograph performed poorly in identifying both the location of JSN in patients with early tibiofemoral OA (especially, lateral OA) and the severity of JSN. The LS radiographs are preferable to standing AP views for the selection of patients for therapeutic trials of structure-modifying OA drugs.

Objective. To determine the extent to which treatment of patients with symptomatic knee osteoarthritis (OA) with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (ACET) reduces total effusion volume and synovial tissue volume, as quantified by magnetic resonance imaging (MRI). Methods. Sequential pilot studies used subjects whose knee OA was treated with NSAIDs (n=10) or with ACET ≤4 g/day (n=20), respectively. After a five half-lives washout of their pain medication, the OA knee with the higher pain score >15 of 25 on the Western Ontario and McMaster Universities' pain scale underwent 1.5T MRI. Effusion was quantified in axial short tau inversion recovery images; to measure synovial tissue volume, fat-suppressed T1-weighted axial images were obtained 3min after i.v. injection of gadolinium contrast. After the initial MRI examination, patients resumed their customary pain medications until the severity of knee pain returned to baseline, when pain was again measured and the MRI was repeated. Results. Pain severity after washout was similar in subjects taking ACET and NSAIDs. Reinstitution of ACET resulted in a 50% decrease in the mean of pain scores (P= 1.7 × 10 -12 ) that was comparable with that seen after the reinstitution of NSAID (49%, P=6.0 × 10 -7 ). The mean total effusion volume measured during the flare of knee pain induced by the withdrawal of the two drugs was comparable (ACET 16.9 ml, NSAID 16.2 ml; P= 0.884). Significant decreases in mean total effusion volume were observed after reinstitution of both ACET (-4.5 ml, P=0.009) and NSAID (-3.3 ml, P=0.013); the difference between drugs was not significant. Analyses of synovial volume yielded similar results. Conclusion. While uncontrolled and derived from small samples, these data suggest that ACET may have a significant anti-inflammatory effect in patients with knee OA, comparable with that achieved with NSAIDs, possibly through an effect on neurogenic inflammation. Joint pain is the clinical feature of OA that most often leads the affected individual to seek medical attention. Because many patients with OA improve symptomatically with the use of NSAIDs, it has been widely assumed that the pain of OA is due to synovial inflammation. However, the origins of OA pain are numerous and may vary from patient to patient and, within the same subject, from visit to visit. Although the articular cartilage is usually the site of the most obvious pathological changes in this disease, it is aneural and, therefore, is not the source of joint pain. However, in addition to the synovium, the subchondral bone, joint capsule, osteophytes, menisci, ligaments, periarticular tendons, entheses and bursae all contain nociceptive nerve endings, stimulation of which by chemical or physical mediators may be a basis for OA pain.

Objective: To compare quantitative estimates of change in joint space width (JSW) with semiquantitative ratings of the progression of joint space narrowing (JSN) with respect to sensitivity to change over time. Methods: 431 obese women 45 to 64 years old with unilateral radiographic knee osteoarthritis were randomised to 30 months’ treatment with doxycycline 100 mg twice daily or placebo. Quantitative estimates of change in JSW in the medial tibiofemoral compartment from fluoroscopically assisted semiflexed AP radiographs were obtained at baseline and 16 and 30 months after randomisation. Radiographic JSN was rated (0–3 scale) in the same images by two readers using a standard atlas. Changes in overall severity of knee osteoarthritis were derived from gradings of conventional standing AP radiographs at baseline and 30 months, with blinding to treatment group and chronological order of examination. Results: Follow up radiographs were obtained from 381 subjects (88%) at 16 months and from 367 (85%) at 30 months. The treatment groups did not differ in the frequency of significant loss of JSW by dichotomous criteria (⩾0.5 mm, ⩾1.0 mm, ⩾20%, or ⩾50% of baseline JSW). Progressors and non-progressors, as defined by each of the dichotomous outcomes, differed significantly in mean value for quantitative measurement of change in JSW at 30 months (p⩽0.001). Conclusions: Quantitative and semiquantitative indicators of progression of osteoarthritis in fluoroscopically standardised radiographs of osteoarthritic knees are highly related, but the effect of doxycycline on articular cartilage thickness was more easily detected with quantitative measurements of change in JSW than with semiquantitative ratings of JSN.

Objective To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment. Methods In this placebo-controlled trial, obese women (n = 431) ages 45–64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6-month intervals. Results Seventy-one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean ± SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 ± 0.42 mm versus 0.24 ± 0.54 mm); after 30 months, it was 33% less (0.30 ± 0.60 mm versus 0.45 ± 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a ≥20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a ≥20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase. Conclusion Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee.

Objective To determine whether baseline or serial plasma concentrations of stromelysin (matrix metalloproteinase 3 [MMP-3]) protein might distinguish subjects with progressive radiographic knee osteoarthritis (OA) from those with stable disease. Methods Subjects were 120 women with unilateral knee OA who participated in a 30-month randomized, placebo-controlled trial of structure modification with doxycycline. Anteroposterior views of both knees in a semiflexed position were obtained at baseline, 16 months, and 30 months. Subjects were selected to obtain comparisons of plasma MMP-3 levels between 60 progressors (21 taking doxycycline, 39 taking placebo) and 60 nonprogressors (30 taking doxycycline, 30 taking placebo) with respect to medial joint space narrowing (JSN) in the index knee. Each group consisted of 30 subjects who exhibited significant increases in knee pain. Blood samples were obtained semiannually for MMP-3 assay. Results Subjects in the placebo group whose MMP-3 concentration was in the upper tertile of the baseline distribution showed a 4-fold increase in the odds of progression of JSN as compared with the lower tertile (odds ratio 4.12, P = 0.037). Baseline MMP-3 levels were unrelated to knee pain. The within-subject mean of serial MMP-3 concentrations was associated with concurrent JSN in the placebo group over the 0–16-month interval (b = 0.18 mm/SD increase in the mean MMP-3, P < 0.01) and over the 16–30-month interval (b = 0.15, P < 0.05). Similar evidence of concurrent validity was found in the placebo group for the maximum of intercurrent MMP-3 values. Conclusion The baseline MMP-3 level was a significant predictor of JSN in this pilot study. Moreover, serial plasma MMP-3 levels reflected concurrent JSN in the placebo group over the 30-month period of observation.

Drugs should be used as adjuncts to non-pharmacological measures In the 1950s and early 60s Sir John Charnley succeeded in developing components for total hip arthroplasty and demonstrated the remarkable success that could be achieved with this procedure in patients with osteoarthritis (OA). Charnley’s adaptation of polymethylmethacylate as a fixation interface between the metallic or plastic implant and the bone served as a major advance in the surgical treatment of severe OA.1,2 Development of total knee arthroplasty followed. The materials and surgical techniques have improved steadily so that both of these procedures are associated with a high level of patient satisfaction. Most patients with OA of the hip or knee who undergo total joint arthroplasty experience clinically significant improvement in joint pain, function, and quality of life.3,4 Recommendation of total joint arthroplasty for the patient with OA, however, is tantamount to an acknowledgement of the failure of medical management. The surgical procedure is often performed after the patient has experienced years, or even decades, of pain and disability. Among all the pharmacological and non-pharmacological interventions promoted for treatment of OA in the half century since Charnley directed his attention to replacement of the arthritic hip, none approximates the effectiveness of arthroplasty. The 1963 edition of the Cecil-Loeb textbook of medicine,5 in discussing the treatment of OA, noted: “Analgesics, particularly salicylates, are useful in controlling the symptoms of osteoarthritis. Phenylbutazone is sometimes helpful when salicylates have failed, but the potential toxic reactions rarely justify its use in such a mild disorder. Systemic corticosteroid treatment is not recommended for osteoarthritis. Intra-articular injections of hydrocortisone acetate ... may be helpful for joints which fail to respond to simpler measures.” Despite enormous increases in our understanding of pain mechanisms and of the metabolism, biochemistry, and molecular biology of articular …

Objective Computerized measurement of changes in joint space width (JSW) on serial radiographs of the knee in the semiflexed, anteroposterior (SF-AP) view has been used recently as a primary outcome measure in clinical trials of disease-modifying osteoarthritis drugs (DMOADs). In the use of fluoroscopy to achieve reproducible alignment of the medial tibial plateau and x-ray beam, the SF-AP radiographic protocol affords greater sensitivity in the detection of joint space narrowing (JSN) than that achieved by conventional radiographic positioning techniques. However, the utility of the SF-AP view is compromised by the variation in x-ray penetration in each examination, which may confound the correction of the automated measurement of JSW for the radiographic magnification inherent in an AP view of the knee. A recent DMOAD trial using the SF-AP protocol showed an improbable increase in JSW of ≥0.50 mm (i.e., greater than the measurement error). The present report provides an analysis of this problem, and the study aim was to demonstrate that substitution of the automated estimates of JSW with precise manual measurements can markedly reduce the problem attributable to radiographic magnification. Methods SF-AP radiographs were obtained at baseline and at 16 months and 30 months thereafter from subjects enrolled in a 6-center DMOAD trial. For each examination, a 6.35-mm steel ball was affixed to the skin over the head of the fibula to permit estimation of the percentage of radiographic magnification (%Mag) and correction of JSW measurements. Measurements of the minimum interbone distance (IBD) in the medial tibiofemoral compartment and the %Mag were obtained by an automated method (edge detection) and manually. Combinations of automated and manual measurements of the IBD and %Mag in estimates of magnification-corrected JSW were compared with respect to their reproducibility, agreement, and sensitivity to JSN. Results With fully automated measurements, variations in x-ray penetration in analog radiographs and edge enhancement in digital radiographs resulted in the computer “seeing” a metal ball whose diameter was artifactually reduced, resulting in an inflated measurement of JSW. Use of manual measurement of the IBD and %Mag largely eliminated these problems and reduced, from 16% to 2%, the frequency of knees exhibiting an increase in JSW ≥0.50 mm. In 14 of the 15 knees in which a significant increase in JSW was noted with the manual method, this increase in JSW could be explained by the development of significant lateral compartment narrowing during the study or poor alignment of the medial plateau. Conclusion Although automated and manual methods of JSW measurement of the knee in the SF-AP view possess comparable intrareader reproducibility, the manual method is less susceptible to technical factors that affect the correction of raw JSW estimates for radiographic magnification. Until we can identify practical, effective solutions to these technical problems, use of any radiographic protocol involving AP imaging of the knee in a DMOAD trial must be viewed with caution.

Objective To evaluate the effectiveness of tidal irrigation (TI) in comparison with a well-matched sham irrigation (SI) procedure as a treatment for knee osteoarthritis (OA). Methods One hundred eighty subjects with knee OA were randomized to receive TI or SI, with clinical followup over the ensuing 12 months. The primary outcomes of interest were change in pain and function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Subjects and the nurse assessor were blinded, and success of blinding was assessed. Results Although the study groups were otherwise comparable, the baseline WOMAC pain and physical functioning scores were higher (worse) in the SI group. After adjustment for baseline, there were no differences between the effects of SI and TI. Blinding was successful, with ∼90% of SI and TI subjects stating that they had received the TI procedure. Conclusion Most, if not all, of the effect of TI appears to be attributable to a “placebo response.”

Objective To estimate the reproducibility of the semiflexed metatarsophalangeal (MTP) view in repeat radiographic examinations of the knee of subjects with osteoarthritis (OA) with respect to radioanatomic alignment of the medial tibial plateau and the central x-ray beam and the precision of measurements of minimum medial tibiofemoral joint space width (JSW). Methods Thirty-eight subjects with definite knee OA underwent 2 semiflexed MTP examinations on the same day. Radioanatomic alignment of the medial tibial plateau and the x-ray beam (distance between anterior and posterior margins of the plateau) was measured manually (Lequesne method). Manual measurements of the JSW in repeat radiographs also were obtained. The reproducibility of JSW measurements was estimated by the method of Bland and Altman. Results Only 29% of the initial semiflexed MTP radiographs exhibited satisfactory radioanatomic alignment (intermargin distance ≤1 mm). However, intermargin distances in initial and repeat radiographs were highly correlated (r = 0.86, P< 0.01). In 89% of knees, the intermargin distance in the first examination was reproduced (±1 mm) in the second examination. The standard error of measurement (mean of within-knee standard deviations of repeat JSW values) was 0.30 mm. The magnitude of discrepancy between repeat measurements of JSW was related positively to overall radiographic severity of knee OA (P< 0.05). Conclusion The semiflexed MTP protocol affords highly reproducible radioanatomic positioning of the knee, although misalignment of the medial tibial plateau and the x-ray beam occurs in >70% of cases. Precision of measurement of JSW in the semiflexed MTP view approaches that associated with fluoroscopically assisted positioning protocols. However, the consequences of poor, albeit reproducible, alignment of the knee in serial semiflexed MTP radiographs in longitudinal studies of OA progression are currently unknown.

In patients with knee osteoarthritis (OA) the real problem, for the clinician and the patient, is not radiographic OA but painful OA. As noted by Liang, ‘x-rays don't weep'.1 Patients weep. In this issue of the Annals , Snijders et al 2 report results of a randomised controlled (RCT), placebo-controlled trial of doxycycline (doxy) in patients with symptomatic knee OA. Their primary end point was the difference in the proportion of subjects in the two treatment groups who achieved a clinical response at 24 weeks, as judged by OMERACT-OARSI responder criteria. Secondary outcomes included joint pain, stiffness, function, quality of life, OA-related medication use and side effects of treatment. The results showed no difference between doxy and placebo with respect to symptomatic benefit; about one-third of each treatment group met the responder criteria. The authors conclude that doxy is ineffective in reducing symptoms of knee OA over 24 weeks. The study was prompted by our 2005 report that doxy slowed the rate of joint space narrowing (JSN) over 30 months in patients with knee OA; significant differences from placebo were seen as early as 16 months.3 In contrast to the study by Snijders et al ,2 our primary outcome measure was the effect of doxy on radiographic progression of OA, not on symptoms. Specifically, our intent was to ascertain whether a fluoroscopically assisted semiflexed radiographic view of the knee4 was suitable for use in a multicentre clinical trial of a putative structure-modifying OA drug (SMOAD). Subjects enrolled in the study, which was implemented in 1997, were recruited chiefly from the community, rather than from clinics for patients with joint pain. Our inclusion criteria did not contain a threshold for severity of joint pain and levels of knee pain at entry were low. Post hoc comparison showed …

Objective Previous studies of knee osteoarthritis (OA) have yielded variable estimates of the rate of joint space narrowing (JSN) in the standing anteroposterior (AP) radiograph, due largely to longitudinal changes in the alignment of the medial tibial plateau (MTP) and x-ray beam. To characterize this bias, we examined serial radiographs of subjects with knee OA in population-based and clinical OA cohorts from 3 locations in the United States and the United Kingdom. Methods Radiographic features of knee OA (e.g., osteophytosis, JSN) and MTP alignment in 428 OA knees were evaluated by consensus of 2 readers. Alignment was considered satisfactory if the anterior and posterior margins of the MTP were superimposed within 1 mm. Readers were blinded to subject identity, and films were read in random order. The minimum medial joint space width was also measured manually (standard error of repeated measurements 0.20 mm) in serial knee images. Results Only 14% of serial radiographs exhibited alignment of the MTP in both images. In OA knees with satisfactory alignment in both images, the mean rate of JSN over 2–3 years (0.26 mm/year) was significantly larger (P = 0.004) than that in OA knees with misalignment in 1 or both radiographs and was 86% more rapid than the mean JSN in all OA knees. Moreover, the within-group standard deviation of JSN was significantly smaller among knees with reproduced alignment of the MTP than in knees in which misalignment occurred in 1 or both images (P = 0.006). Conclusion Poor standardization of knee positioning in serial standing AP radiographs in previous studies of OA progression has obscured the rate and variability of articular cartilage loss in subjects with knee OA. True JSN (i.e., JSN that is not attributable to longitudinal changes in the alignment of the MTP with the x-ray beam in serial radiographic examinations) may occur more rapidly, and with less between-subject variability, than that previously thought to be characteristic of knee OA.

Objective To investigate the inhibition of matrix metalloproteinase 1 (MMP-1), MMP-8, and MMP-13 by doxycycline, and to determine whether the variable hemopexin-like domain of each MMP was responsible for the differences in susceptibility to doxycycline inhibition among these collagenases. Methods Recombinant human MMP-1 (collagenase 1), MMP-8 (collagenase 2), and MMP-13 (collagenase 3), truncated forms of MMP-8 and MMP-13 lacking the hemopexin-like domain, and a mutant form of truncated MMP-13 were used in these studies. The activity of the full-length MMP in the presence of doxycycline was tested against type II collagen, a natural substrate for the enzymes. A small peptolide substrate was used to determine which structural features of the MMPs were related to sensitivity to doxycycline inhibition. Results The activity of MMP-13 and MMP-8 against type II collagen was inhibited by 50-60% by 30 microM doxycycline, while that of MMP-1 was inhibited only 18% by 50 microM doxycycline. In contrast, in experiments with the peptolide substrate, neither full-length nor truncated MMP-13 was inhibited until the concentration of the drug exceeded 90 microM. MMP-8 and truncated MMP-8 were sensitive to inhibition by 30 microM doxycycline, while MMP-1 was slightly inhibited (14%) by 90 microM doxycycline. For MMP-8, inhibition was reversible upon dilution and was independent of the order in which the reagents were added. Kinetic analysis of the inhibition constant (K(i)) of MMP-8 (K(i) = 36 microM) and truncated MMP-8 (K(i) = 77 microM) indicated that inhibition was noncompetitive. Conclusion Significant inhibition of MMP-13 and MMP-8 activity against collagen occurred in vitro at concentrations that were near the concentrations achieved in serum after oral dosing. Studies with truncated enzymes and 2 substrates suggest that doxycycline disrupts the conformation of the hemopexin-like domain of MMP-13 and the catalytic domain of MMP-8.

Objective To determine the extent to which the cost of an effective self-care intervention for primary care patients with knee osteoarthritis (OA) was offset by savings resulting from reduced utilization of ambulatory medical services. Methods In an attention-controlled clinical trial, 211 patients with knee OA from the general medicine clinic of a municipal hospital were assigned arbitrarily to conditions of self-care education (group E) or attention control (group AC). Group E (n = 105) received individualized instruction and followup emphasizing nonpharmacologic management of joint pain. Group AC (n = 106) received a standard public education presentation and attention-controlling followup. A comprehensive clinical database provided data concerning utilization and cost of health services during the following year. Results Only 25 subjects (12%) were lost to followup. The 94 subjects remaining in group E made 528 primary care visits during the year following intervention, compared with 616 visits by the 92 patients remaining in group AC (median visits 5 versus 6, respectively; P < 0.05). Fewer visits translated directly into reduced clinic costs in group E, relative to controls (median costs [1996 dollars] $229 versus $305, respectively; P < 0.05). However, self-care education had no significant effects on utilization and costs of outpatient pharmacy, laboratory, or radiology services over the ensuing year. The cost per patient to deliver the self-care intervention was estimated to be $58.70. Conclusion Eighty percent of the cost of delivering effective self-care education to the knee OA patients in this study was offset within 1 year by the reduced frequency and costs of primary care visits. For >50% of patients receiving the intervention, the savings associated with fewer primary care visits exceeded the cost of self-care education.

Objective To determine if diacerhein protects against the early stages of joint damage in a canine model of osteoarthritis (OA). Methods OA was induced in 20 adult mongrel dogs by transection of the anterior cruciate ligament of the left knee. Beginning the day after surgery, dogs in the active treatment group were dosed twice a day with capsules of diacerhein, providing a total daily dose of 40 mg/kg, for 32 weeks. Dogs in the control group received placebo capsules on the same schedule. Pathology in the unstable knee was assessed arthroscopically 16 weeks after surgery and by direct observation when the dogs were killed 32 weeks after surgery. The severity of gross joint pathology was recorded, and samples of the medial femoral condyle cartilage and the synovial tissue adjacent to the central portion of the medial meniscus were collected for histologic evaluation. Water content and uronic acid concentration of the articular cartilage from the femoral condyle were determined, and collagenolytic activity in extracts of cartilage pooled from the medial and lateral tibial plateaus was assayed against 14C-labeled collagen fibers. Results Diacerhein treatment slowed the progression of OA, as measured by grading of gross changes in the unstable knee at arthroscopy 16 weeks after cruciate ligament transection (P = 0.04) and at the time the animals were killed, 32 weeks after surgery (P = 0.05). However, 32 weeks after ACL transection, the mean proteoglycan concentration and water content of the OA cartilage and the level of collagenolytic activity in extracts of the cartilage were not significantly different in the diacerhein treatment group than in the placebo treatment group. Conclusion Diacerhein treatment significantly reduced the severity of morphologic changes of OA compared with placebo. These findings support the view that diacerhein may be a disease-modifying drug for OA.

Objective To determine whether baseline lower extremity muscle weakness is a risk factor for incident radiographic osteoarthritis (OA) of the knee. Methods This prospective study involved 342 elderly community-dwelling subjects (178 women, 164 men) from central Indiana, for whom baseline and followup (mean interval 31.3 months) knee radiographs were available. Lower extremity muscle strength was measured by isokinetic dynamometry and lean tissue (i.e., muscle) mass in the lower extremities by dual x-ray absorptiometry. Results Knee OA was associated with an increase in body weight in women (P = 0.0014), but not in men. In both sexes, lower extremity muscle mass exhibited a strong positive correlation with body weight. In women, after adjustment for body weight, knee extensor strength was 18% lower at baseline among subjects who developed incident knee OA than among the controls (P = 0.053), whereas after adjustment for lower extremity muscle mass, knee extensor strength was 15% lower than in the controls (P not significant). In men, in contrast, adjusted knee extensor strength at baseline was comparable to that in the controls. Among the 13 women who developed incident OA, there was a strong, highly significant negative correlation between body weight and extensor strength (r = -0.740, P = 0.003), that is, the more obese the subject, the greater the reduction of quadriceps strength. In contrast, among the 14 men who developed incident OA, a modest positive correlation existed between weight and quadriceps strength (r = 0.455, P = 0.058). No correlation between knee flexor (hamstring) strength and knee OA was seen in either sex. Conclusion Reduced quadriceps strength relative to body weight may be a risk factor for knee OA in women.

Objective To determine if intraarticular injections of hyaluronan (HA) protect against the early stages of joint damage in a canine model of osteoarthritis (OA). Methods OA was induced in adult mongrel dogs by transection of the anterior cruciate ligament of the left knee. One group of dogs (n = 7) was treated with 5 weekly injections of HA (MW 1,500,000) into the operated knee beginning 1 day after ligament transection. The control group (n = 6) was injected with saline on the same schedule. Twelve weeks after surgery, all dogs were killed, the severity of pathologic changes of OA was graded, and composition of the cartilage and extent of aggregation of proteoglycans (PGs) synthesized in vitro by cartilage slices were determined. Results All dogs showed gross morphologic changes typical of OA in the unstable knee. The severity of joint pathology in HA-treated dogs was comparable with that in the saline-injected controls. In OA cartilage from the saline-treated group, the mean uronic acid concentration was 30-60% greater than that in the contralateral knee. In sharp contrast, the uronic acid concentration in OA cartilage from the HA-treated dogs was 10-30% lower than that in cartilage from the contralateral knee (P = 0.02 and P = 0.03, respectively, for samples from the medial and lateral femoral condyle). The extent of aggregation of PG synthesized in vitro by cartilage from HA-injected animals was similar to that synthesized by cartilage from the saline-injected dogs. Conclusion In this canine model of OA, the series of intraarticular injections of HA did not alter development of osteophytosis or fibrillation. However, the PG concentration of cartilage in the OA knee was significantly reduced by this treatment, suggesting that HA therapy might adversely affect the biomechanical properties of the cartilage.

Objective. To characterize, for the first time, periosteal new bone formation in a well-established canine model of accelerated osteoarthritis (OA) with features of neuropathic arthropathy. Methods. Seven dogs underwent left L4-S1 dorsal root ganglionectomy (DRG), followed 3 weeks later by transection of the anterior cruciate ligament of the ipsilateral knee (ACLT). Eight weeks thereafter, a postmortem examination was performed to assess the severity of cartilage changes of OA and the formation of new bone on the distal femur and proximal tibia in the cruciate-deficient limb. Results. As described previously, extensive fullthickness ulceration of the articular cartilage was present in the unstable knee of every dog. The femoral shaft immediately proximal to the condyles in the unstable limb was consistently wider (mean ± SD diameter 22.4 ± 2.2 mm) than that in the contralateral limb (19.9 ± 1.3 mm; P = 0.01). Xeroradiography and histologic examination of the distal femur revealed extensive formation of woven bone on the periosteal surfaces of the medial, lateral, and anterior aspects of the femoral shaft in the OA limb of every dog. These bony changes were not seen in radiographs of dogs that underwent DRG with the cruciate ligament left intact (n = 8) or of neurologically intact dogs that underwent ACLT (n = 7) and were examined 24 weeks after surgery. Conclusion. Formation of new periosteal bone on the distal femur and tibia is a feature of this model of accelerated OA that is not seen in the conventional ACLT model of OA in the neurologically intact dog. This observation suggests that interruption of sensory input from the limb may affect the regulation of osteogenesis in the mechanically unstable joint.

Objective. To evaluate a concise program of self-care education delivered by an arthritis nurse specialist as an adjunct to primary care for inner-city patients with knee osteoarthritis (OA). Methods. An attention-controlled clinical trial; 211 inner-city patients with knee OA were assigned arbitrarily to education (E) or attention-control (AC) conditions. Group E received an individualized 30-60-minute educational intervention that emphasized non-pharmacologic management of joint pain, preservation of function by problem-solving, and practice of principles of joint protection. Brief telephone contacts 1 week and 4 weeks later monitored and reinforced new self-care activities. Group AC viewed a 20-minute standardized public education presentation on arthritis and received followup telephone calls (only to encourage continued participation in the study). Outcomes included the Health Assessment Questionnaire (HAQ) Disability and Discomfort Scales, 10-cm visual analog scales measuring knee pain at rest and while walking, and the Quality of Well-Being (QWB) scale. Assessments were made at baseline and at 4-month intervals for 1 year. Results. A total of 165 subjects (78%) completed all assessments. After control for baseline status, group E had significantly lower scores for disability and resting knee pain throughout the year of postintervention followup (P < 0.05 for both). Effects were somewhat discordant. By 12 months, functional benefits had begun to wane, while the effect on resting knee pain had grown. The overall effects of education on walking knee pain, overall joint pain (by HAQ), and general health status (by QWB) were not significant. Conclusion. Self-care education for inner-city patients with knee OA, delivered as an adjunct to primary care, was found to result in notable preservation of function and control of resting knee pain. The magnitude of the observed effects compares well with those of more labor-intensive and time-consuming intervention models. However, more sustained preservation of function and consistent effects on pain may require prolonged, more proactive followup, either by the patient educator or by a trained clinical assistant dedicated to the task of supporting self-care by patients with knee OA.

Treatment of patients with OA of the knee should be individualized and tailored to the severity of the symptoms. In individuals with mild symptomatic OA, treatment may be limited to patient education, physical and occupational therapy and other nonpharmacologic modalities, and pharmacologic therapy including non-opioid oral and topical analgesics. In patients who are unresponsive to this treatment regimen, the use of NSAIDs in addition to nonpharmacologic therapy is appropriate unless medically contraindicated. Judicious use of intraarticular steroid injections has a role either as monotherapy or an adjunct to systemic therapy in patients with knee OA who have symptomatic effusions. The role of joint lavage and arthroscopic debridement in patients with OA of the knee who are unresponsive to conservative medical therapy needs further study, and these procedures cannot be routinely recommended for all patients at this time. Patients with severe symptomatic OA of the knee require an aggressive approach to decreasing pain, increasing mobility, and decreasing functional impairment; such patients may benefit from orthopedic consultation and evaluation for osteotomy or total joint arthroplasty.

OBJECTIVE In recent studies, the synovial fluid concentration of molecules derived from the extracellular matrix of articular cartilage has been used to deduce the magnitude of cartilage destruction or repair in osteoarthritic (OA) joints. Because low-grade synovitis is often present in such joints, we assessed the effect of synovial inflammation on the clearance of a prototypical protein, albumin, from synovial fluid. METHODS 131I-labeled albumin (RISA) was injected into 1 (control) knee of each of 14 dogs. The concentration of RISA in synovial fluid aspirated 7 hours after the injection and serial measurements of surface radioactivity were used to calculate the volume of distribution (Vd) and clearance of RISA. One week later, synovitis was induced in the contralateral knee by intraarticular injection of various quantities of calcium pyrophosphate dihydrate (CPPD) crystals, after which RISA was injected into that joint and these measurements were repeated. RESULTS Intraarticular injection of 500 micrograms of CPPD crystals produced intense synovitis, with a mean synovial fluid white blood cell (WBC) count of 43,200 cells/mm3, and values for RISA Vd and RISA clearance (36.5 ml and 33.7 microliters/minute) were much higher than those for saline-injected control knees (2.7 ml and 1.5 microliters/minute, respectively). Injection of 0.5 microgram of CPPD also produced marked synovitis and values for Vd and RISA clearance that were 2-3-fold greater than those in the contralateral knee. The low-grade synovitis produced by only 0.05 microgram of CPPD, which resulted in synovial fluid WBC counts as low as 1,000-2,000 cells/mm3, was accompanied by increases in the clearance and Vd of RISA to levels approximately 40% and approximately 80% higher, respectively, than those for the contralateral knee. CONCLUSION Even mild synovitis, as seen in OA, may significantly increase the clearance of a protein from the joint. Synovitis is a significant variable which must be considered in studies of putative chondroprotective drugs if conclusions about the effects of drugs on cartilage metabolism are to be drawn from changes in the synovial fluid concentration of a "marker" protein.

Transection of the anterior cruciate ligament in the dog leads to osteoarthritis. This study defines the kinematic changes in the unstable knee after transection of the cruciate ligament (six dogs) and after a sham operation (four dogs). In the dogs that were anterior cruciate ligament-deficient (ACL-D), the duration of stance 1 week postoperatively decreased 38% from the preoperative value, but only a 4% decrease was seen at 6 weeks. The duration of double hindlimb support increased from 6 to 19% of the entire cycle 1 week after surgery but returned to the baseline value by 18 weeks. As the unstable limb contacted the treadmill belt, the initial flexion (yield) and subsequent extension (propulsive) phases were not evident or were markedly attenuated in every ACL-D dog throughout the 26-week period of observation. The angular velocity patterns were characterized by a slight extension velocity at touchdown (compared with a zero value preoperatively) and a decrease in the peak velocities (both flexion and extension) during the remainder of the stance phase. None of these changes was observed in the animals that had a sham operation. These data indicate that, in the dog, the nervous system compensates for instability of the knee by altering angular, but not temporal, parameters. The extension velocity at touchdown and the reduction in peak flexion velocity during the yield component of the stance phase may reduce the ability of the limb to absorb impact forces and lead to the development of osteoarthritis of the knee. Alternatively, the reductions in flexion and extension of the knee during the stance phase and in the values for peak velocity presumably reflect protective muscular reflexes that may slow the rate of progression of joint breakdown.

OBJECTIVE To estimate among recent and current rheumatology fellows the appeal of a 3-year rheumatology fellowship emphasizing musculoskeletal medicine. METHODS A survey of 348 trainee members of the American College of Rheumatology during 1990-1993, by mailed questionnaire. RESULTS The response rate was 77.8% (n = 271). Both recent and current fellows indicated that they desired more experience in musculoskeletal medicine. Most notably, 50% of current fellows, and a significantly higher proportion of recent fellows (70%; P < 0.005), indicated that they would have opted for a 3-year fellowship in musculoskeletal medicine had one been available to them at the completion of their residency. CONCLUSION Expertise in musculoskeletal medicine is desired by a sufficient proportion of recent and current rheumatology fellows to warrant the investment in another year of training.

Objective. To evaluate the sequence of changes in articular cartilage, trabecular bone, and subchondral plate in dogs with osteoarthritis (OA), 3 months, 18 months, and 54 months after anterior cruciate ligament transection (ACLT). Methods. Specimens of the medial tibial plateau were analyzed with microscopic computed tomography (micro-CT) at a resolution of 60 μm, and biochemical and morphologic changes in the femoral articular cartilage were assessed. Results. At 3 months and 18 months after ACLT, the articular cartilage in the unstable knee showed histologic changes typical of early OA and increased water content and uronic acid concentration; by 54 months, full-thickness ulceration had developed. Micro-CT analysis showed a loss of trabecular bone in the unstable knee, compared with the contralateral knee, at all time points. At both 18 and 54 months, the differences in trabecular thickness and surface-to-volume ratio were greater than at 3 months. Although the mean subchondral plate thickness, especially in the medial aspect of the medial tibial plateau, was greater in the OA knee than in the contralateral knee 18 months and 54 months after ACLT, these differences were not statistically significant; however, the difference was significantly greater at 54 months than at 3 months. Conclusion. Thickening of the subchondral bone is not required for the development of cartilage changes of OA in this model. The bony changes that develop after ACLT, however, could result in abnormal transmission of stress to the overlying cartilage and thereby contribute to the progression of cartilage degeneration.

Objective In vitro studies have indicated that levels of neutral metalloproteinases in osteoarthritic (OA) cartilage are elevated and that doxycycline (doxy) inhibits collagenolytic and gelatinolytic activity in extracts of OA cartilage. The purpose of the present study was to test the effect of oral doxy administration on the severity of cartilage degeneration in OA. Methods OA was induced in 12 adult mongrel dogs by transection of the anterior cruciate ligament (ACL) 2 weeks after dorsal root ganglionectomy. Six dogs received doxy orally from the day after ACL transection until they were killed 8 weeks later; the other 6 served as untreated OA controls. Results The unstable knee of each untreated dog exhibited extensive full-thickness cartilage ulceration of the medial femoral condyle. In sharp contrast, cartilage on the distal aspect of the femoral condyle of the unstable knee was grossly normal in 2 doxy-treated dogs, and exhibited only thinning and/or surface irregularity in the others. Degenerative cartilage lesions on the medial trochlear ridge, superficial fibrillation of the medial tibial plateau, and osteophytosis were, however, unaffected by doxy treatment. Collagenolytic activity and gelatinolytic activity in cartilage extracts from OA knees of untreated dogs were 5-fold and 4-fold greater, respectively, than in extracts from dogs given doxy. Conclusion Prophylactic administration of doxy markedly reduced the severity of OA in weight-bearing regions of the medial femoral condyle. It remains to be determined whether administration of doxy after OA changes have developed is also effective.

Objective We previously reported that monthly telephone contact by lay personnel, to promote self-care for patients with osteoarthritis (OA), was associated with improved joint pain and physical function after 1 year of followup. The present study was a secondary analysis to determine whether improvement was contingent on intensified medical treatment. Methods We reanalyzed control/treatment group differences in all 40 subjects with radiographically confirmed knee OA who had had no changes in antirheumatic drug therapy or institution of physical therapy during the period of observation. Results Group differences in measured pain remained significant (effect size [ES] = 0.65 SD, P less than 0.01). The same trend was observed for physical function (ES = 0.53 SD, P not significant). Conclusion The findings in this reanalysis suggest that periodic telephone support interventions are effective enough to be regarded as an adjunctive treatment for OA.

Clinical criteria for the classification of patients with hip pain associated with osteoarthritis (OA) were developed through a multicenter study. Data from 201 patients who had experienced hip pain for most days of the prior month were analyzed. The comparison group of patients had other causes of hip pain, such as rheumatoid arthritis or spondylarthropathy. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop different sets of criteria to serve different investigative purposes. Multivariate methods included the traditional "number of criteria present" format and "classification tree" techniques. Clinical criteria: A classification tree was developed, without radiographs, for clinical and laboratory criteria or for clinical criteria alone. A patient was classified as having hip OA if pain was present in combination with either 1) hip internal rotation greater than or equal to 15 degrees, pain present on internal rotation of the hip, morning stiffness of the hip for less than or equal to 60 minutes, and age greater than 50 years, or 2) hip internal rotation less than 15 degrees and an erythrocyte sedimentation rate (ESR) less than or equal to 45 mm/hour; if no ESR was obtained, hip flexion less than or equal to 115 degrees was substituted (sensitivity 86%; specificity 75%). Clinical plus radiographic criteria: The traditional format combined pain with at least 2 of the following 3 criteria: osteophytes (femoral or acetabular), joint space narrowing (superior, axial, and/or medial), and ESR less than 20 mm/hour (sensitivity 89%; specificity 91%). The radiographic presence of osteophytes best separated OA patients and controls by the classification tree method (sensitivity 89%; specificity 91%). The "number of criteria present" format yielded criteria and levels of sensitivity and specificity similar to those of the classification tree for the combined clinical and radiographic criteria set. For the clinical criteria set, the classification tree provided much greater specificity. The value of the radiographic presence of an osteophyte in separating patients with OA of the hip from those with hip pain of other causes is emphasized.

We examined the relationship between articular cartilage degeneration, as visualized arthroscopically, and joint space narrowing (JSN) in standing anteroposterior knee radiographs of 161 patients with chronic knee pain. The majority of these patients had radiographic findings of mild osteoarthritis. Twenty-five (33%) of the 76 patients in the series whose radiographs showed tibiofemoral JSN had grossly normal articular cartilage in both tibiofemoral compartments at arthroscopy (false-positive). The specificity of medial JSN for the presence of medial compartment articular cartilage degeneration was 0.61, i.e., only 61% of patients with normal (grade 0) medial compartment cartilage had a normal medial joint space. Of 22 patients with >50% medial JSN, 9 (41%) had normal articular cartilage in the medial compartment at arthroscopy. Of 6 patients with >50% lateral JSN, 3 (50%) had normal lateral compartment articular cartilage at arthroscopy. Among 36 patients with >25% JSN who had neither medial nor lateral compartemnt articular cartilage degeneration, JSN was associated with articular caartilage degeneration, JSN was associated with articular cartilage degeneration in the patellofemoral compartemnt in 8 (22%), with meniseus degeneration in 18 (50%), and with both in 8 (22%). Thus, in these patients with chronic knee pain, radiographic evidence of JSN in the tibiofemoral compartment did not permit confident prediction of the status of the articular cartilage.

Objective: The Lyon Schuss (LS) and fixed flexion (FF) views of the knee are superior to a conventional standing anteroposterior view in evaluating joint space narrowing (JSN) in osteoarthritis (OA). Both position the knee identically but only the LS aligns the medial tibial plateau (MTP) with the x -ray beam fluoroscopically. The present study provides the first head-to-head comparison of the LS and FF views. Methods: At baseline and 12 months, 62 OA and 99 control knees were imaged twice on the same day with LS and FF views. Minimum joint space width (mJSW) was measured by computer and MTP alignment was assessed from the distance between anterior and posterior margins of the MTP (intermargin distance, IMD). Reproducibility of measurements of mJSW and sensitivity to change were evaluated. Results: In normal knees, JSW did not vary over 12 months with either view. In OA knees, 12-month mJSN was 0.22 (0.43) mm with the LS view and −0.01 (0.46) mm with the FF view (p = 0.0002 and p = 0.92, respectively). Mean IMD was only half as large in LS as in FF views (0.9 (0.5) mm vs 1.9 (1.2) mm, p Conclusions: LS and FF radiographs offer similar reproducibility in JSW measurement. However, presumably due to its superiority in aligning the MTP, the LS view is much more sensitive to JSN in OA knees.

Anterior cruciate ligament transection (ACLT) in the dog produces changes in the articular cartilage of the unstable knee that are consistent with those of osteoarthritis (OA). To determine whether the degrees of severity of OA cartilage changes, of synovitis, and of synovial iron deposition were related to adequacy of hemostasis at the time of ACLT, a modified surgical technique was devised, whereby electrocautery was used to obtain meticulous control of bleeding when the ligament was severed and irrigation was used to remove intraarticular blood before closure of the joint. When no particular attention was given to hemostasis, 69% of the dogs showed synovitis in the OA knee 10 weeks after ACLT; when electrocautery and irrigation were used to maintain hemostasis, synovitis was present in only 24% of the OA knees 10 weeks after ACLT (P less than 0.01). Iron deposits were present in 75% of synovial samples obtained after routine ACLT, but in only 6% (P less than 0.001) when attention was given to hemostasis. Hypertrophy of articular cartilage, chondrocyte cloning, fibrillation, and changes in tangential zone chondrocytes were less prominent in the OA knee when electrocautery and irrigation were used. However, the water content, uronic acid concentration, and rate of net 35S-labeled glycosaminoglycan synthesis were similarly increased regardless of the surgical technique used, and presumably, these changes reflect the reaction of joint cartilage to mechanical instability in this model of OA.

Neuropathic (Charcot) arthropathy is a slowly progressive, chronic, destructive form of joint degeneration seen in patients with a neurosensory deficit. Attempts to produce neuropathic joint disease experimentally with a variety of deafferentation procedures have generally been unsuccessful. However, if the knee is rendered unstable by anterior cruciate ligament transection (ACLT), breakdown of the joint occurs rapidly in dogs that have previously undergone dorsal root ganglionectomy (DRG) for deafferentation of the ipsilateral limb. In contrast, ACLT in neurologically intact dogs produces not only nonprogressive changes that are characteristic of mild osteoarthritis. This report describes 3 patients with longstanding insulin-dependent diabetes mellitus in whom neuropathic arthropathy developed within weeks after minor trauma to the foot or ankle. In these patients, diabetic neuropathy served as the functional equivalent of dorsal root ganglionectomy, and the minor trauma served as the functional equivalent of ACLT. Together, they illustrate the phenomenon of neurogenic acceleration of joint degeneration in humans.

We previously reported that intraarticular injections of hyaluronan (HA), administered prophylactically to dogs in whom knee osteoarthritis had been induced by transection of the anterior cruicate ligament, did not significantly modify the intraarticular pathology but decreased the proteogylcan concentration of the articular cartilage by as much as 30%. Because the cartilage proteoglycan concentration is directly related to the stiffness of the tissue, these results raised the possibility that intraarticular HA therapy could exacerbate OA. In the present study, using a different HA formulation, with a longer interval between intraarticular HA injection and examination of joint tissues, we found that neither prophylactic nor therapeutic administration of HA had an effect on the severity of OA pathology, the magnitude of vertical ground reaction forces generated by the unstable hind limb (a surrogate for joint pain), or the cartilage proteoglycan concentration. The data suggest that the suppression of proteoglycan synthesis induced by HA is temporary and fully reversible and that HA injections do not result in overloading of the OA extremity. A significant correlation was noted between the severity of chondropathy and the magnitude of the vertical ground reaction forces generated by the unstable limb.

Objective Although recent protocols for standardized knee radiography afford highly reproducible radioanatomic alignment of the joint and measurement of joint space width (JSW) in repeat radiographs acquired on the same day, the sensitivity of these techniques to joint space narrowing (JSN) over time in subjects with knee osteoarthritis (OA) is unknown. The present study was undertaken to compare the metatarsophalangeal (MTP) view and the semiflexed anteroposterior (AP) view with respect to sensitivity to JSN in knee OA. Methods In 49 subjects with definite knee OA, 2 MTP radiographs and 1 semiflexed AP radiograph were obtained at baseline. Each examination was repeated 14 months later. In MTP views, minimum JSW and the distance between the anterior and posterior margins of the medial tibial plateau (intermargin distance [IMD], an indicator of parallel alignment of the tibial plateau and the x-ray beam) were measured with a pair of calipers and a magnifying lens fitted with a graticule. JSW in semiflexed AP views was measured by digital image analysis. Results The mean of within-knee standard deviations of JSW in the baseline MTP examinations (n = 52 OA knees) was 0.24 mm (coefficient of variation 5.8%). Although IMDs in the 2 baseline MTP views were very highly correlated (+0.88), IMDs in the serial examinations were only moderately correlated (+0.45). Serial MTP views showed a small increase in mean JSW over 14 months that was not significantly greater than zero (mean ± SD +0.09 ± 0.66 mm; P not significant). In contrast, concurrent semiflexed AP examinations showed a marginally significant decrease in mean JSW (−0.09 ± 0.31 mm; P = 0.10). Conclusion These results demonstrate that evidence of the short-term reproducibility of a radiographic protocol is an insufficient basis on which to predict the quality of its longitudinal performance.

Animal models have proved to be of considerable importance in elucidating mechanisms underlying joint damage in osteoarthritis (OA) and providing proof of concept in the development of pharmacologic and biologic agents that may modify structural damage in the OA joint. The utility of animal models in predicting the response to an intervention with a drug or biologic agent in humans, however, can be established only after evidence is obtained of a positive effect of the agent in humans. To date, no agent has been shown unequivocally to have such an effect, although diacerhein and glucosamine have recently been reported to lower the rate of loss of articular cartilage in patients with hip OA and knee OA, respectively, based on measurements of the rate of joint space narrowing in plain radiographs. Furthermore, the predominant manifestation of OA - and the feature that leads people with radiographic changes of the disease to decide to seek medical attention and contributes to the enormous medicoeconomic and socioeconomic burden imposed by the disease - is joint pain. Notably, none of the animal models of OA is a good indicator of the analgesic effects of pharmacologic agents. Indeed, it should not be assumed a priori that reduction in the rate of progression of joint damage in OA will be associated with a reduction in joint pain.

To evaluate the effectiveness of tidal irrigation (TI) in comparison with a well-matched sham irrigation (SI) procedure as a treatment for knee osteoarthritis (OA).One hundred eighty subjects with knee OA were randomized to receive TI or SI, with clinical followup over the ensuing 12 months. The primary outcomes of interest were change in pain and function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Subjects and the nurse assessor were blinded, and success of blinding was assessed.Although the study groups were otherwise comparable, the baseline WOMAC pain and physical functioning scores were higher (worse) in the SI group. After adjustment for baseline, there were no differences between the effects of