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Perspectives on the future of bone and joint diseases.

The diseases of bones, joints, and muscles are common, chronic, and very costly to society. While the impact of these diseases falls across the age spectrum, the worldwide growth in the percentage of elderly in the population makes attention to musculoskeletal disorders and conditions particularly critical. An effective prevention strategy, driven by an understanding of the fundamental biology of bone and connective tissue, can only result from an upshift in the efforts of many sectors--public and private, academic, scientific, and patient-based--with new opportunities for partnerships and collaborative efforts flourishing. The Decade of the Bone and Joint can serve as a catalyst in this effort. The National Institutes of Health (NIH) are pleased to join with other national and international organizations to promote new activities and initiatives during the next decade. The NIH Osteoarthritis Initiative is highlighted as an example of a public-private partnership to develop resources and information on the natural history of the disease process that can drive new clinical intervention studies in osteoarthritis. Hopefully, this initiative and others will pave the way for important, scientifically driven prevention strategies during the next decade.

Biomedical Research↗

Mandibular asymmetry in adult patients with unilateral degenerative joint disease.

The purpose of this study was to evaluate the association between unilateral degenerative joint disease (UDJD) and lower facial asymmetry. Twenty symptomatic patients and 20 asymptomatic volunteers were studied. Posteroanterior radiographs and bilateral mandibular laminographs were used to evaluate lower face and mandibular asymmetry. The two-way analysis of variance test was used to compare the groups. The posteroanterior radiographs did not reveal vertical asymmetry for the patients. The group with the left side affected exhibited deviation of the mandibular dental midline, the menton, and the antigonion toward the affected side. The laminographs of the same group revealed decreased condylar height and increased antigonial notching in the affected side. The results suggest that subjects with UDJD may manifest lower face asymmetry. This can be of clinical value when adult patients exhibiting asymmetry are to be treated.

Adult↗

A correlative study of clinical and histological findings of revision hip arthroplasty for rheumatoid arthritis and inflammatory joint disease.

OBJECTIVE: Primary hip arthroplasty in rheumatoid arthritis (RA) and other forms of inflammatory joint disease (IJD) is generally thought to be associated with a less favourable outcome in terms of implant survival and other complications. Whether the duration of implant survival correlates with the degree of rheumatoid-like inflammatory changes in periprosthetic tissues is uncertain. METHODS: Histopathological changes in periprosthetic tissues obtained following revision surgery of 34 total hip replacements on 27 patients with IJD (RA 18 cases: ankylosing spondylitis three cases; juvenile chronic arthritis six cases) were examined. RESULTS: A heavy diffuse lymphocyte and plasma cell infiltrate +/- lymphoid aggregates was noted in 29% of cases in whom the mean implant survival was 5.6 years (range: 2-8 years). Where little or no lymphocytic infiltrate was noted in periprosthetic tissues, the mean implant survival was 8.6 years (range: 1-17 years). Revision arthroplasty was not undertaken for early or late infection of a primary hip replacement. CONCLUSIONS: Our findings indicate that implant survival is less in those cases where there is a heavy lymphocyte and plasma-cell infiltrate in periprosthetic tissues. These findings suggest that the presence of a heavy chronic inflammatory-cell infiltrate in periprosthetic tissues is likely to be a contributory factor in causing early implant failure in RA.

Adolescent↗

Application of biomarkers in the clinical development of new drugs for chondroprotection in destructive joint diseases: a review.

Emerging evidence supports the concept that biochemical markers are clinically useful non-invasive diagnostic tools for the monitoring of changes in cartilage turnover in patients with destructive joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Epidemiological studies demonstrated that measurements of different degradation products of proteins in the extracellular matrix of hyaline cartilage in urine or serum samples are (1) increased in OA or RA patients compared with healthy individuals, (2) correlate with disease activity, and (3) are predictive for the rate of changes in radiographic measures of cartilage loss. The present review provides an updated list of available biomarkers and summarize the research data arguing for their clinical utility. In addition, it addresses the question whether or not the monitoring of biomarkers during different treatment modalities could be a useful approach to characterize the chondro-protective effects of approved and candidate drugs. Finally, it briefly reviews the in vitro/ex vivo experimental settings - isolated chondrocyte cultures and articular cartilage explants - that can assist in the verification of novel markers, but also studies assessing direct effects of drug candidates on chondrocytes. Collectively, biomarkers may acquire a function as established efficacy parameters in the clinical development of novel chondro-protective agents.

Arthritis, Rheumatoid↗

Early contributions to the study of bone and joint disease in Glasgow, Scotland.

Despite the fact that the University of Glasgow had a well-developed medical school founded in the eighteenth century, a modern rheumatology unit was only opened in 1965. However, Glasgow physicians, surgeons, and pathologists contributed to the study of bone and joint disease before this date. This paper is a summary of their contributions.

Bone Diseases↗

Clinical features of adult-onset ankylosing spondylitis in Korean patients: patients with peripheral joint disease (PJD) have less severe spinal disease course than those without PJD.

OBJECTIVE: We investigated the clinical features of Korean patients with adult-onset ankylosing spondylitis (AAS) and examined the differences between AAS patients with and without peripheral joint disease (PJD). METHODS: We studied 67 consecutive patients with primary AAS who visited the rheumatology clinic of a tertiary referral hospital. All patients experienced joint symptoms after the age of 15 and fulfilled the modified New York criteria for ankylosing spondylitis. Hips and shoulders were not considered as peripheral joints. RESULTS: The male-to-female ratio was 8.6:1.0. Mean age at disease onset was 22.3 +/- 5.5 (mean +/- s.d.) yr and disease duration was 10.8 +/- 8.0 yr. Spinal symptoms were the first manifestations in 80.6% of patients. During the disease course, hip, shoulder and peripheral joint involvement were found in about 60% of patients. In patients with PJD, the most commonly affected joints were the knees and ankles. The pattern of PJD, in most cases, was asymmetrical and mono/oligoarticular. AAS patients with PJD had fewer spinal symptoms than those without PJD as a presenting feature (71.8 vs 92.9%, P = 0.035). The modified Schober test showed greater increments in patients with PJD (4.9 +/- 2.4 vs 3.0 +/- 2.4 cm, P = 0.002). Forced vital capacity was better in patients with PJD (79.0 +/- 11.4 vs 70.8 +/- 15.5% of predicted value, P = 0.016). Totally ankylosed sacroiliitis, spinal squaring and syndesmophytes on radiographs were less common in the patients with PJD than in those without PJD (33.3 vs 64.2%, P = 0.012; 20.5 vs 67.9%, P = 0.000; and 38.5 vs 71.4%, P = 0.008, respectively). CONCLUSION: Peripheral joints as well as shoulder and hip joints were more frequently involved during the disease course in Korean AAS patients compared with earlier reports in Caucasians. The general joint involvement pattern of PJD was similar to patterns reported previously. Our data suggest that, clinically and radiographically, AAS patients with PJD have a less severe spinal disease course than those without PJD.

Adolescent↗

Leucocyte migration inhibition with collagen type I and collagen type III in rheumatoid arthritis and degenerative joint diseases.

The leucocytes of 22 patients with classic rheumatoid arthritis were investigated with the direct leucocyte migration inhibition technique in agarose as described by Clausen. The leucocytes of 9 patients with degenerative joint diseases and of 9 healthy persons served as controls. Collagen type I and collagen type III were used as antigens. The leucocytes of 22 patients with rheumatoid arthritis showed in 15 cases a migration inhibition with collagen type III and in 10 cases with collagen type I. The inhibition with collagen type III was stronger and more frequent than with collagen type I. The frequent leucocyte migration inhibition with collagen type III in classic rheumatoid arthritis seems to be an expression of possible cell mediated reactivity against that type of collagen which appears especially in rheumatoid synovial tissue.

Adult↗

[Effects of lower extremity joints' disease on lumbar surgical outcomes].

OBJECTIVE: To study the effects of lumber operation on patients with pathologic changes of the lumbar vertebrae combined with degenerative diseases of lower extremity joints. METHODS: 237 patients with pathologic changes of the lumbar vertebrae combined with pain and/or limited activity of hip or knee joint, 153 (64.56%) with degenerative knee joints and 84 (35.44%) with degenerative hip joints received lumbar surgery. 160 patients with lower extremity joint pain and negative physical examination and imagology before the surgery were used as controls. The joint pain value was assessed on all patients with Visual Analog Scale before and after treatment and the joint pain relief rate was calculated. RESULTS: The average pain relief rate of the control group was 90.54%, significantly higher than those of the degenerative knee joint group (55.20%) and the degenerative hip joint group (46.88%, both P < 0.05). CONCLUSION: Diseases of lower extremity joints influence the lumbar surgical outcomes. It is very important to make a definite diagnosis of the lower extremity joint pain pre-operationally and take appropriate measures to treat the pain according to its pathogenesis.

Adult↗

Immune responses to canine distemper virus in joint diseases of dogs.

Measurement of immune complexes, antibodies against canine distemper virus (CDV) and anti-CDV antibodies in immune complexes were made in sera and SF from 'normal' dogs and from dogs with joint diseases. These data were compared with cytological analyses of SF samples. In dogs with canine rheumatoid-like arthritis (CRA) there were correlations between circulating anti-CDV antibody levels and circulating immune complex levels (P < 0.001) and between SF anti-CDV antibody levels and SF immune complex levels (P < 0.01). Furthermore, the SF PMN count in dogs with CRA correlated with both the SF anti-CDV antibody levels (P < 0.001) and the SF immune complex anti-CDV antibody levels (P < 0.001). The results demonstrated a relationship between CDV and ongoing synovial inflammation in dogs with CRA.

Animals↗

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS): definition, semiology, prognosis, pathogenesis, treatment, and place relative to other periodic joint diseases.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant inherited condition of periodic fever and pain. Most patients are of northern European descent. The attacks manifest as fever and pain in the joints, abdomen, muscles, skin, or eyes, with variations across patients. An acute-phase response occurs during the attacks. Patients with TRAPS are at risk for AA amyloidosis, the most common targets being the kidneys and liver. Soluble TNFRSF1A is usually low between the attacks and may be normal during the attacks, when TNF levels are high. TNFRSF1A is found in abnormally high numbers on leukocyte cell membranes. TRAPS is the first condition for which naturally occurring mutations in a TNF receptor were found; the mutations affect the soluble TNFRSF1A gene in the 12p13 region. In some patients, the pathogenesis involves defective TNFRSF1A shedding from cell membranes in response to a given stimulus. Thus, TRAPS is a model for a novel pathogenic concept characterized by failure to shed a cytokine receptor. This review compares TRAPS to other inherited periodic febrile conditions, namely, familial Mediterranean fever, Muckle-Wells syndrome, cold urticaria, and hyper-IgD syndrome. The place of TRAPS relative to other intermittent systemic joint diseases is discussed. Colchicine neither relieves nor prevents the attacks, whereas oral glucocorticoid therapy is effective when used in dosages greater than 20 mg/day. The pathogenic hypothesis involving defective TNFRSF1A shedding suggests that medications targeting TNF may be effective in TRAPS.

Adolescent↗

Dental attrition models predicting temporomandibular joint disease or masticatory muscle pain versus asymptomatic controls.

AIMS: To determine whether patients with temporomandibular joint disease or masticatory muscle pain can be usefully differentiated from asymptomatic controls using multifactorial classification tree models of attrition severity and/or rates. METHODS: Measures of attrition severity and rates in patients diagnosed with disc displacement (n = 52), osteoarthrosis (n = 74), or masticatory muscle pain only (n = 43) were compared against those in asymptomatic controls (n = 132). Cross-validated classification tree models were tested for fit with sensitivity, specificity, accuracy and log likelihood accountability. RESULTS: The model for identifying asymptomatic controls only required the three measures of attrition severity (anterior, mediotrusive and laterotrusive posterior) to be differentiated from the patients with a 74.2 +/- 3.8% cross-validation accuracy. This compared with cross-validation accuracies of 69.7 +/- 3.7% for differentiating disc displacement using anterior and laterotrusive attrition severity, 68.7 +/- 3.9% for differentiating disc displacement using anterior and laterotrusive attrition rates, 70.9 +/- 3.3% for differentiating osteoarthrosis using anterior attrition severity and rates, 94.6 +/- 2.1% for differentiating myofascial pain using mediotrusive and laterotrusive attrition severity, and 92.0 +/- 2.1% for differentiating myofascial pain using mediotrusive and anterior attrition rates. The myofascial pain models exceeded the > or =75% sensitivity and > or =90% specificity thresholds recommended for diagnostic tests, and the asymptomatic control model approached these thresholds. CONCLUSION: Multifactorial models using attrition severity and rates may differentiate masticatory muscle pain patients from asymptomatic controls, and have some predictive value for differentiating intracapsular temporomandibular disorder patients as well.

Adolescent↗