Summary Objective Marked differences exist between human knee and ankle joints regarding risks and progression of osteoarthritis (OA). Pathomechanisms of degenerative joint disease may therefore ...differ in these joints, due to differences in tissue structure and function. Focusing on structural issues, which are design goals for tissue engineering, we compared cell and matrix morphologies in different anatomical sites of adult human knee and ankle joints. Methods Osteochondral explants were acquired from knee and ankle joints of deceased persons aged 20–40 years and analyzed for cell, matrix and tissue morphology using confocal and electron microscopy (EM) and unbiased stereological methods. Morphological variations disclosing an association between joint type (knee vs ankle) and biomechanical role (convex vs concave articular surfaces) were identified by a 2-way analysis of variance (ANOVA) and a post-hoc analysis. Results Knee cartilage exhibited higher cell densities in the superficial zone than ankle cartilage. In the transitional zone, higher cell densities were observed in association with convex vs concave articular surfaces, without significant differences between knee and ankle cartilage. Highly uniform cell and matrix morphologies were evident throughout the radial zone in the knee and ankle, regardless of tissue biomechanical role. Throughout the knee and ankle cartilage sampled, chondron density was remarkably constant at approximately 4.2 × 106 chondrons/cm3. Conclusion Variation in cartilage cell and matrix morphologies with changing joint and biomechanical environments suggests that tissue structural adaptations are performed primarily by the superficial and transitional zones. Data may aid the development of site-specific cartilage tissue engineering, and help to identify conditions where OA is likely to occur.
Objectives: To develop evidence based recommendations for the management of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group comprised 16 rheumatologists, one ...physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. Results: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. Conclusion: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.
Objective Data pertaining to the quantitative structural features and organization of normal articular cartilage are of great importance in understanding its biomechanical properties and in ...attempting to establish this tissue's counterpart by engineering in vitro. A comprehensive set of such baseline data is, however, not available for humans. It was the purpose of the present study to furnish the necessary information.
Design The articular cartilage layer covering the medial femoral condyle of deceased persons aged between 23 and 49 years was chosen for the morphometric analysis of cell parameters using confocal microscopy in conjunction with unbiased stereological methods. The height of the hyaline articular cartilage layer, as well as that of the calcified cartilage layer and the subchondral bone plate, were also measured.
Results The mean height of the hyaline articular cartilage layer was found to be 2.4mm, the volume density of chondrocytes therein being 1.65%, the number of cells per mm3 of tissue 9626 and the mean cell diameter 13μm. Other estimators (including matrix mass per cell and cell profile density) were also determined.
Conclusions A comparison of these normal human quantitative data with those published for experimental animals commonly used in orthopaedic research reveals substantial differences, consideration of which in tissue engineering strategies destined for human application are of paramount importance for successful repair. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.
The aim of this review is to assess the efficacy of treatments for postmenopausal osteoporosis in women with low bone mass or with an existing vertebral fracture. We searched the literature for ...studies (randomized, double-masked, placebo-controlled and prospective) that reported on drugs registered in Europe or North America. We included 41 reports on 12 agents. To assess the consistency among the studies for each drug, we plotted the percent change in bone mineral density (BMD) for the control group against the percent change in BMD for the treated group for lumbar spine and femoral neck. We used methods of cluster analysis to determine consistency among the studies. For each agent we summarized the relative risk for vertebral fracture (patients with new fracture) and for hip fractures. The duration of the studies ranged from 1 to 4.3 years. The proportion of patients who discontinued treatment ranged from 4% to 80%. Most of the studies reported on change in BMD. Twenty-six studies (10 drugs) provided data on new vertebral fractures and 12 (6 drugs) on hip fractures. Apart from fluoride effects on spine BMD, increases in BMD with bisphosphonates were greater than those seen with the remaining treatments. Generally, for each agent the changes in BMD (relative to placebo) were consistent among the studies. The exceptions were calcitriol and calcitonin for changes in BMD of the spine and of the femoral neck. Alendronate, calcitonin, risedronate and raloxifene caused significant reductions in the risk of vertebral fractures. Alendronate, risedronate or the combination of calcium plus vitamin D had a significant effect on the risk of hip fracture. Most therapies are effective in increasing BMD; some decrease the risk of vertebral fracture. For hip fracture, alendronate and risedronate reduce the risk in women with osteoporosis, and calcium and vitamin D reduce the risk in institutionalized patients.
Arthritic diseases cause enormous burdens in terms of pain, crippling, and disability. Osteoarthritis (OA), the most common form of arthritis, is characterized by a slow progressive degeneration of ...articular cartilage. The exact etiology of OA is not known, but the degradation of cartilage matrix components is generally agreed to be due to an increased synthesis and activation of extracellular proteinases, mainly matrix metalloproteinases. Insufficient synthesis of new matrix macromolecules is also thought to be involved, possibly as a consequence of deficient stimulation by growth factors. Although OA is defined as a noninflammatory arthropathy, proinflammatory cytokines such as interleukin-1 have been implicated as important mediators in the disease. In response to interleukin-1, chondrocytes upregulate the production of nitric oxide and prostaglandin E2, two factors that have been shown to induce a number of the cellular changes associated with OA. The generation of these key signal molecules depends on inducible enzymes and can be suppressed by pharmacological inhibitors.
Objective: To develop evidence based recommendations for the management of hip osteoarthritis (OA). Methods: The multidisciplinary guideline development group comprised 18 rheumatologists, 4 ...orthopaedic surgeons, and 1 epidemiologist, representing 14 European countries. Each participant contributed up to 10 propositions describing key clinical aspects of hip OA management. Ten final recommendations were agreed using a Delphi consensus approach. Medline, Embase, CINAHL, Cochrane Library, and HTA reports were searched systematically to obtain research evidence for each proposition. Where possible, outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. Effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation was assessed using the traditional A–D grading scale and a visual analogue scale. Results: Ten key treatment propositions were generated through three Delphi rounds. They included 21 interventions, such as paracetamol, NSAIDs, symptomatic slow acting disease modifying drugs, opioids, intra-articular steroids, non-pharmacological treatment, total hip replacement, osteotomy, and two general propositions. 461 studies were identified from the literature search for the proposed interventions of efficacy, side effects, and cost effectiveness. Research evidence supported 15 interventions in the treatment of hip OA. Evidence specific for the hip was strikingly lacking. Strength of recommendation varied according to category of research evidence and expert opinion. Conclusion: Ten key recommendations for the treatment of hip OA were developed based on research evidence and expert consensus. The effectiveness and cost effectiveness of these recommendations were evaluated and the strength of recommendation was scored.
Bone ultrasound measures (QUSs) can assess fracture risk in the elderly. We compared three QUSs and their association with nonvertebral fracture history in 7562 Swiss women 70–80 years of age. The ...association between nonvertebral fracture was higher for heel than phalangeal QUS.
Introduction: Because of the high morbidity and mortality associated with osteoporotic fractures, it is essential to detect subjects at risk for such fractures with screening methods. Because quantitative bone ultrasound (QUS) discriminated subjects with osteoporotic fractures from controls in several cross‐sectional studies and predicted fractures in prospective studies, QUS could be more practical than DXA for screening.
Material and Methods: This cross‐sectional and retrospective multicenter (10 centers) study was performed to compare three QUSs (two heel ultrasounds: Achilles+ GE‐Lunar and Sahara Hologic; the phalanges: ultrasound DBM sonic 1200 IGEA) for determining by logistic regression nonvertebral fracture odds ratio (OR) in a sample of 7562 Swiss women, 75.3 ± 3.1 years of age. The two heel QUSs measured the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). In addition, Achilles+ calculated the stiffness index (SI) and the Sahara calculated the quantitative ultrasound index (QUI) from BUA and SOS. The DBM sonic 1200 measured the amplitude‐dependent SOS (AD‐SOS).
Results: Eighty‐six women had a history of atraumatic hip fracture after the age of 50, 1594 had a history of forearm fracture, and 2016 had other nonvertebral fractures. No fracture history was reported by 3866 women. Discrimination for hip fracture was higher than for the other nonvertebral fractures. The two heel QUSs had a significantly higher discrimination power than the QUSs of the phalanges, with standardized ORs, adjusted for age and body mass index, ranging from 2.1 to 2.7 (95% CI = 1.6, 3.5) compared with 1.4 (95% CI = 1.1, 1.7) for the AD‐SOS of DBM sonic 1200.
Conclusion: This study showed a high association between heel QUS and hip fracture history in elderly Swiss women. This could justify integration of QUS among screening strategies for identifying elderly women at risk for osteoporotic fractures.
To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA).
The multidisciplinary guideline development group, representing 15 European countries, generated 10 key ...propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale.
Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint.
Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
Objective Marathon runners have an increased risk of developing joint disease. During and after a 42-km run, elevation of multiple cytokines occurs in the blood, reflecting inflammatory processes. We ...compared this cytokine response with serum levels of cartilage oligomeric matrix protein (COMP) and melanoma inhibitory activity (MIA), two markers for joint metabolism and/or damage.
Methods Serum from eight endurance-trained runners was collected shortly before the start of a marathon run, after 31km, 42km, 2h after the end, on the first and on the second morning after the run. For comparison, serum was obtained from 35 healthy controls and 80 patients with knee joint injury, rheumatoid arthritis or osteoarthritis. Serum levels of C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble interleukin-6 receptor (sIL-6R, gp80), soluble tumor necrosis factor receptor II (sTNFRII, p75), COMP and MIA were measured by ELISA.
Results Compared with healthy controls, the runner's baseline serum levels of TNF-α, sIL-6R, COMP and MIA were significantly increased. COMP and MIA levels, higher than the upper normal limits of 5μg/ml and 6ng/ml respectively, were found in seven and five of eight runners. The elevated levels of COMP were similar to those found in joint injury or osteoarthritis, and the elevated levels of MIA were comparable to those reported in rheumatoid arthritis. During the run, the serum levels of IL-1RA, IL-6, TNF-α and COMP rose significantly, and gradually returned to baseline within 24h. Only modest changes of CRP, sIL-6R, sTNFRII and MIA occurred during the run. Late elevations of CRP and MIA were observed after 24 and 48h. The correlation analysis suggests associations between COMP, sIL-6R, TNF-α, IL-1RA on one hand and sTNFRII, and MIA and CRP on the other hand.
Conclusions Elevated baseline levels of COMP and MIA might reflect increased joint matrix turnover and/or damage due to prior extreme physical training. During the run, COMP was increasing possibly due to the severe physical strain on joint structures, associated with the early inflammation. After the run, MIA and CRP increased within 24h, suggesting a correlation with later inflammatory processes. Thus, our data suggest that COMP and MIA are markers for distinct aspects of joint metabolism and/or damage in both disease and sport.
BACKGROUND Osteoarthritis (OA) is the most common joint disease encountered throughout Europe. A task force for the EULAR Standing Committee for Clinical Trials met in 1998 to determine the ...methodological and logistical approach required for the development of evidence based guidelines for treatment of knee OA. The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinically and/or radiographically affecting any compartment of the knee. METHODS The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the electronic databases Medline and Embase using a combination of subject headings and keywords. All European language publications in the form of systematic reviews, meta-analyses, randomised controlled trials, controlled trials, and observational studies were included. During stage three all the relevant studies were quality scored. The summary statistics for validated outcome measures, when available, were recorded and, where practical, the numbers needed to treat and the effect size for each treatment were calculated. In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach. The final stage ranked these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach. RESULTS Over 2400 English language publications and 400 non-English language publications were identified. Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. CONCLUSIONS These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities. It is apparent that certain clinical propositions are supported by substantial research based evidence, while others are not. There is thus an urgent need for future well designed trials to consider key clinical questions.
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