Ananthila Anandacoomarasamy

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 musculosketelal 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.

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/m2; 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 (β=0.006, r2=0.19, p=0.029). This association was not detected in the lateral compartment (r2=0.12, p=0.745). Percentage weight loss was associated with an increase in medial dGEMRIC in multiple regression analysis (β=3.9, r2=0.26; p=0.008) but not the lateral compartment (r2=0.14, p=0.34). For every 10% weight loss there was a gain in the medial dGEMRIC index of 39 ms (r2=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.

Influence of BMI on Health‐related Quality of Life: Comparison Between an Obese Adult Cohort and Age‐matched Population Norms

The aim of this study was to determine health‐related quality of life and fatigue measures in obese subjects and to compare scores with age‐ and gender‐matched population norms. A total of 163 obese subjects were recruited from laparoscopic‐adjustable gastric banding or exercise and diet weight loss programs between March 2006 and December 2007. All subjects completed the Medical Outcomes Study Short Form 36 (SF‐36), Assessment of Quality of Life (AQoL), and Multidimensional Assessment of Fatigue (MAF) questionnaires. One‐sample t‐tests were used to compare transformed scores with age‐ and gender‐matched population norms and controls. Obese subjects have significantly lower SF‐36 physical and emotional component scores, significantly lower AQoL utility scores and significantly higher fatigue scores compared to age‐matched population norms. Within the study cohort, the SF‐36 physical functioning, role physical and bodily pain scores, and AQoL utility index were even lower in subjects with clinical knee osteoarthritis (OA). However, obese individuals without OA still had significantly lower scores compared to population norms. Obesity is associated with impaired health‐related quality of life and disability as measured by the SF‐36, AQoL, and fatigue score (MAF) compared to matched population norms.

Cartilage defects are associated with physical disability in obese adults

OBJECTIVE To describe the associations between physical disability measures and knee cartilage defects in obese adults. METHODS One hundred and eleven obese subjects were recruited from laparoscopic adjustable gastric banding or exercise/diet weight loss programmes. All subjects completed disease-specific (WOMAC) and general health status (SF-36) questionnaires, and were assessed for range of knee motion, tibiofemoral alignment and quadriceps strength. Knee cartilage defects were graded on MRI according to established protocol. Regression analysis was adjusted for age, gender, BMI and presence of clinical knee OA. RESULTS The association between higher whole compartment cartilage defect scores and increasing BMI, age and clinical knee OA was confirmed in this obese cohort (r = 0.27, P = 0.01; r = 0.26, P = 0.007; P < 0.0001, respectively), whereas new associations were found with reduced knee range of motion (r = 0.5, P < 0.0001). No associations were found between defect scores and quadriceps strength. Varus malalignment was associated with higher medial cartilage defect scores (r = 0.33, P = 0.013). Higher levels of pain, stiffness and physical disability (WOMAC, SF-36) were associated with higher medial compartment and patella cartilage defect scores. CONCLUSIONS Knee cartilage defects increase with increasing obesity and are associated with both objective and self-reported measures of physical disability. Longitudinal studies are required to assess the potential for change or improvement in cartilage defects with weight loss.

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.

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage: clinical associations in obese adults.

Objective. Delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) is used to assess cartilage glycosaminoglycan distribution. Our aim was to determine the relationships between self-reported pain and disability, clinical variables, and serum leptin, and dGEMRIC indices in obese subjects with and without clinical knee osteoarthritis (OA). Methods. Seventy-seven subjects were recruited from laparoscopic adjustable gastric banding or exercise and diet-weight loss programs. The dGEMRIC index was assessed on MRI according to established protocol. Regression analysis adjusted for age, sex, body mass index (BMI), and presence of clinical knee OA. Results. Mean age and BMI were 51 ± 12.7 years and 39.6 ± 6.2 kg/m2. Twenty-three subjects (30%) had clinical knee OA (American College of Rheumatology criteria). The medial and lateral dGEMRIC indices were 538 ± 80 ms and 539 ± 86 ms. Age correlated negatively with medial (r = −0.40, p < 0.001) and lateral (r = −0.29, p = 0.012) dGEMRIC index. Subjects with clinical knee OA had significantly lower medial dGEMRIC index; however, no association was found for BMI. Varus alignment correlated with lower medial dGEMRIC index (r = −0.43, p < 0.006), while quadriceps strength correlated positively with lateral dGEMRIC index (r = 0.32, p = 0.008). There was also a negative correlation between serum leptin and lateral dGEMRIC index in women (r = −0.39, p = 0.035), with a trend in men (r = −0.52, p = 0.08). There were weak associations with physical disability, as self-reported on the WOMAC questionnaire. Conclusion. In obese subjects, knee dGEMRIC index was associated with age, clinical knee OA, abnormal tibiofemoral alignment, and quadriceps strength. Longitudinal studies are required to assess the potential for improvement in dGEMRIC index with interventions such as strength training.

Current evidence for osteoarthritis treatments

Osteoarthritis (OA) is the most common form of arthritis and the leading cause of chronic disability among older people. The burden of the disease is expected to rise with an aging population and the increasing prevalence of obesity. Despite this, there is as yet no cure for OA. However, in recent years, a number of potential therapeutic advances have been made, in part due to improved understanding of the underlying pathophysiology. This review provides the current evidence for symptomatic management of OA including nonpharmacological, pharmacological and surgical approaches. The current state of evidence for disease-modifying therapy in OA is also reviewed.

Magnetic resonance imaging in Löfgren’s syndrome: demonstration of periarthritis

In Löfgren’s syndrome, pain and swelling commonly involves the ankle joints. In this prospective case series, the magnetic resonance imaging findings of ankle joint involvement are described. Extensive subcutaneous and soft tissue oedema was commonly seen around the ankles. Bone, cartilage, ligaments and tendons were typically uninvolved. Small amounts of joint and tenosynovial fluid were present without evidence of synovial thickening or synovitis. The fluid is probably reactive to adjacent inflammation in the para-articular soft tissues and probably not representing a primary site of involvement. These findings demonstrate that the arthritis in Löfgren’s syndrome stems primarily from periarthritis. This is consistent with prior descriptions using ultrasonography.

Cutaneous vasculitis associated with infliximab in the treatment of rheumatoid arthritis

A 62-year-old woman was diagnosed with seropositive rheumatoid arthritis (RA) in 1984. At diagnosis, antinuclear antibody (ANA) titre was 1:40. There were no antibodies to double-stranded DNA (dsDNA) or extractable nuclear antigens (ENA). The erythrocyte sedimentation rate (ESR) was 43 mm/h. Initial therapy was i.m. gold and prednisone. Six years later, methotrexate (MTX) was added for disease control. Intercurrent medical problems included pernicious anaemia, hypertension and hypercholesterolaemia. Her other medications were folic acid, enalapril, simvastatin, alendronate, calcium and i.m. vitamin B 12 . In 2002, she had ongoing active disease. She was enrolled in an infliximab study (full report pending). All patients received infliximab, at varying doses, for the second 6 months of the study. At study entry, she had a positive Mantoux test. Pyridoxine and isoniazid were commenced for chemoprophylaxis against reactivation of possible latent tuberculosis. In March 2003, she received either 3 mg/kg or 10 mg/kg of infliximab by infusion in addition to her usual therapy. Further infusions were programmed for 4 weeks, 8 weeks and 8 weekly thereafter. The patient experienced mild infusion reactions which settled with anti-histamines and her RA improved significantly. In May 2003, she was admitted with a 3-day history of new onset bilateral lower limb rash and swelling, 2 days of mild nausea, vomiting and diarrhoea, and a 1-day history of throbbing frontal headaches. Examination revealed a diffuse palpable, purpuric rash extending from ankles to shins, with associated pitting oedema. (Fig. 1) Livedo reticularis was noted across her back and anterior thighs. There was no active synovitis. She was febrile to 38.3 ° C. The remainder of her examination was unremarkable. Full blood count and serum biochemistry were normal, ESR 64 mm/h, C-reactive protein 108 mg/L, ANA titre 1:640 (homogeneous pattern), dsDNA titre 14 kIU/L (0–7 kIU/L), no anti-ENA or anti-histone antibodies, normal complement levels, positive for antibodies to anti-neutrophil cytoplasm but negative for antibodies to proteinase-3 and myeloperoxidase, ferritin 540 mmol/L (0–200), polyclonal hypergammaglobulinaemia on serum electrophoresis, and negative hepatitis B and C serology. Urinalysis showed proteinuria <0.06 g/L (longstanding) with negative urine cultures. Blood cultures were negative. Chest X-ray, electrocardiogram and trans-thoracic echocardiogram were normal. The gastrointestinal symptoms settled with symptomatic management. Skin biopsy confirmed leucocytoclastic vasculitis (LCV). Direct immunofluorescence was negative. In light of the raised ANA, antidsDNA antibody, elevated inflammatory markers, fever, vasculitic rash and livedo reticularis, LCV due to a lupus-like syndrome was diagnosed. Infliximab, isoniazid and pyridoxine were ceased. MTX and gold were withheld and the prednisone dose increased. One month post-discharge, the cutaneous vasculitis had resolved completely (ANA titre 1:160 and antidsDNA antibody titre 7). Gold and then MTX were reintroduced with impunity. Prednisone was weaned. The patient remains well.

Train High Eat Low for Osteoarthritis study (THE LO study): protocol for a randomized controlled trial.

INTRODUCTION Osteoarthritis (OA) is one of the most prevalent chronic conditions among older adults, with the medial tibio-femoral joint being most frequently affected. The knee adduction moment is recognized as a surrogate measure of the medial tibio-femoral compartment joint load and therefore represents a valid intervention target. This article provides the rationale and methodology for THE LO study (Train High, Eat Low for Osteoarthritis), which is a randomized controlled trial that is investigating the effects of a unique, targeted lifestyle intervention in overweight/obese adults with symptomatic medial knee OA. RESEARCH QUESTION Compared to a control group given only lifestyle advice, do the effects of the following interventions result in significant reductions in the knee adduction moment: (1) gait retraining; and (2) combined intervention (which involves a combination of three interventions: (a) gait retraining, (b) high-intensity progressive resistance training, and (c) high-protein/low-glycaemic-index energy-restricted diet)? It is hypothesized that the combined intervention group will be superior to the isolated interventions of the high-protein/low-glycaemic-index diet group and the progressive resistance training group. Finally, it is hypothesized that the combined intervention will result in a greater range of improvements in secondary outcomes, including: muscle strength, functional status, body composition, metabolic profile, and psychological wellbeing, compared to any of the isolated interventions or control group. DESIGN Single-blinded, randomized controlled trial adhering to the CONSORT guidelines on conduct and reporting of non-pharmacological clinical trials. PARTICIPANTS One hundred and twenty-five community-dwelling people are being recruited. Inclusion criteria include: medial knee OA, low physical activity levels, no current resistance training, body mass index ≥ 25kg/m(2) and age ≥ 40 years. INTERVENTION AND CONTROL The participants are stratified by sex and body mass index, and randomized into one of five groups: (1) gait retraining; (2) progressive resistance training; (3) high-protein/low-glycaemic-index energy-restricted diet (25 to 30% of energy from protein, 45% of energy from carbohydrates, < 30% of energy from fat, and glycaemic index diet value < 50); (4) a combination of these three active interventions; or (5) a lifestyle-advice control group. All participants receive weekly telephone checks for health status, adverse events and optimisation of compliance. MEASUREMENTS Outcomes are measured at baseline, 6 and 12 months. The primary outcome is the peak knee adduction moment during the early stance phase of gait. The secondary outcome measures are both structural (radiological), with longitudinal reduction in medial minimal joint space width at 12 months, and clinical, including: change in body mass index; joint pain, stiffness and function; body composition; muscle strength; physical performance/mobility; nutritional intake; habitual physical activity and sedentary behaviour; sleep quality; psychological wellbeing and quality of life. DISCUSSION THE LO study will provide the first direct comparison of the long-term benefits of gait retraining, progressive resistance training and a high-protein/low-glycaemic-index energy-restricted diet, separately and in combination, on joint load, radiographic progression, symptoms, and associated co-morbidities in overweight/obese adults with OA of the knee.