Weight loss in obese people has structure-modifying effects on medial but not on lateral knee articular cartilage.

BACKGROUND: Obesity is an important risk factor for knee osteoarthritis (OA), Weight loss can reduce the symptoms of knee OA. No prospective studies assessing the impact of weight loss on knee cartilage structure and composition have been performed. OBJECTIVES: To assess the impact of weight loss on knee cartilage thickness and composition. METHODS: 111 obese adults were recruited from either laparoscopic adjustable gastric banding or exercise and diet weight loss programmes from two tertiary centres. MRI was performed at baseline and 12-month follow-up to assess cartilage thickness. 78 eligible subjects also underwent delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), an estimate of proteoglycan content. The associations between cartilage outcomes (cartilage thickness and dGEMRIC index) and weight loss were adjusted for age, gender, body mass index (BMI) and presence of clinical knee OA. RESULTS: Mean age was 51.7 ± 11.8 years and mean BMI was 36.6 ± 5.8 kg/m(2); 32% had clinical knee OA. Mean weight loss was 9.3 ± 11.9%. Percentage weight loss was negatively associated with cartilage thickness loss in the medial femoral compartment in multiple regression analysis (ß=0.006, r(2)=0.19, p=0.029). This association was not detected in the lateral compartment (r(2)=0.12, p=0.745). Percentage weight loss was associated with an increase in medial dGEMRIC in multiple regression analysis (ß=3.9, r(2)=0.26; p=0.008) but not the lateral compartment (r(2)=0.14, p=0.34). For every 10% weight loss there was a gain in the medial dGEMRIC index of 39 ms (r(2)=0.28; p=0.014). The lowest weight loss cut-off associated with reduced medial femoral cartilage thickness loss and improved medial dGEMRIC index was 7%. CONCLUSIONS: Weight loss is associated with improvements in the quality (increased proteoglycan content) and quantity (reduced cartilage thickness losses) of medial articular cartilage. This was not observed in the lateral compartment. This could ultimately lead to a reduced need for total joint replacements and is thus a finding with important public health implications.

Use of biological disease-modifying anti-rheumatic drugs in patients with concurrent rheumatic disease and hepatitis B.

BACKGROUND: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are effective in the management of inflammatory arthritides. Reactivation of hepatitis B virus (HBV) is a potential adverse outcome in patients treated with bDMARDs. There is currently no consensus on the approach to identifying and treating these patients with underlying HBV infection. AIM: The aims of this study were to assess the risk of HBV reactivation in patients treated with bDMARDs, and to determine whether HBV screening should be carried out in all patients prior to commencing bDMARDs. METHODS: A literature search was undertaken to identify all reports of patients with inflammatory arthritides and concurrent HBV infection being treated with bDMARDs. RESULTS: Forty-three patients with HBV infection were identified, of whom eight patients developed HBV reactivation after exposure to bDMARDs. Of the patients who experienced reactivation, two had unknown infection that surfaced during bDMARD therapy. Patients who experienced reactivation were promptly treated with antiviral therapy and saw clinical improvement. There are no long-term data on these patients. CONCLUSIONS: HBV reactivation may result in serious consequences, including death. Tuberculosis screening prior to bDMARD treatment is already standard practice, as is HBV screening for patients undergoing cancer chemotherapy. Implementing HBV screening for all patients prior to bDMARD treatment can identify patients with chronic HBV who may require antiviral therapy.

Methotrexate: long-term safety and efficacy in an Australian consultant rheumatology practice.

BACKGROUND: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment. METHODS: A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18-year period. The primary outcome was time to cessation of MTX. RESULTS: Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity-related discontinuation occurred in 93 patients (11.8%) and due to non-adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57-0.96; P = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42-0.74; P < 0.001). Being of the male sex aged more than 60 years and having a non-RA diagnosis predisposed to stopping MTX earlier. CONCLUSION: MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re-evaluate and revise the current monitoring guidelines.

P2X7 gene polymorphisms do not appear to be a susceptibility gene locus in sporadic cases of systemic lupus erythematosus.

The P2X(7) receptor is a ligand-gated cation-selective channel that mediates ATP-induced apoptosis of cells of the immune system. A loss-of-function single nucleotide polymorphism (SNP) at position 1513 (1513 A-->C) of the P2X(7) gene has recently been identified in both healthy and chronic lymphocytic leukemia (CLL) B-cells, translating into a loss of P2X(7)-mediated apoptosis in these cells. This antiapoptotic effect results in increased B-cell numbers, thereby potentially contributing to the survival of B-CLL clones. It was hypothesized that prolonged cell survival may also predispose to induction of autoimmunity. The objective of this study is to analyze the role of the P2X(7) receptor and its loss-of-function 1513 A-->C polymorphism (SNP) in the development of systemic lupus erythematosus (SLE). DNA samples obtained from patients with sporadic SLE were analyzed for the presence of the 1513 A-->C polymorphism using polymerase chain reaction (PCR) amplification and then direct sequencing. No significant difference in allele frequencies (1513 A-->C polymorphism) between sporadic cases of SLE and controls was found. A loss-of-function SNP at position 1513 (1513 A-->C) of the P2X(7) gene does not appear to be a susceptibility gene locus for the development of sporadic SLE.

The impact of obesity on the musculoskeletal system.

Obesity is associated with a range of disabling musculoskeletal conditions in adults. As the prevalence of obesity increases, the societal burden of these chronic musculoskeletal conditions, in terms of disability, health-related quality of life, and health-care costs, also increases. Research exploring the nature and strength of the associations between obesity and musculoskeletal conditions is accumulating, providing a better understanding of underlying mechanisms. Weight reduction is important in ameliorating some of the manifestations of musculoskeletal disease and improving function.

Long term outcomes of inversion ankle injuries.

BACKGROUND: Ankle sprains are common sporting injuries generally believed to be benign and self limiting. However, some studies report a significant proportion of patients with ankle sprains having persistent symptoms for months or even years. AIMS: To determine the proportion of patients presenting to an Australian sports medicine clinic who had long term symptoms after a sports related inversion ankle sprain. METHODS: Consecutive patients referred to the NSW Institute of Sports Medicine from August 1999 to August 2002 with inversion ankle sprain were included. Exclusion criteria were fracture, ankle surgery, or concurrent lower limb problems. A control group, matched for age and sex, was recruited from patients attending the clinic for upper limb injuries in the same time period. Current ankle symptoms, ankle related disability, and current health status were ascertained through a structured telephone interview. RESULTS: Nineteen patients and matched controls were recruited and interviewed. The mean age in the ankle group was 20 (range 13-28). Twelve patients (63%) were male. Average follow up was 29 months. Only five (26%) ankle injured patients had recovered fully, with no pain, swelling, giving way, or weakness at follow up. None of the control group reported these symptoms (p<0.0001). Assessments of quality of life using short form-36 questionnaires (SF36) revealed a difference in the general health subscale between the two groups, favouring the control arm (p<0.05). There were no significant differences in the other SF36 subscales between the two groups. CONCLUSION: Most patients who sustained an inversion ankle injury at sport and who were subsequently referred to a sports medicine clinic had persistent symptoms for at least two years after their injury. This reinforces the importance of prevention and early effective treatment.