For decades, multiple attempts to fully understand knee osteoarthritis pathophysiology and natural history have been attempted. Despite the extensive amount of research regarding this topic, there are still marked controversies. This multifactorial condition gets influenced by local, systemic, and external factors and its progression and/or response to treatments widely varies from patient to patient. Multiple therapies have been studied in the past, low impact physical activity seems to be supported by all the current medical societies while other interventions have shown conflicting findings. Newer therapies and routes of administration are under investigation and some of them have shown promising preliminary reports. This review intends to give an overview of the current knowledge of pathophysiology and non-surgical therapies available for knee osteoarthritis.

A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structure of essential organs. The massive release of cytokines is implicated in this hypermetabolic response. The aim of the present study was to compare cytokine expression profiles from severely burned children without signs of infections or inhalation injury (n = 19) to the cytokine profiles from normal, noninfected, nonburned children (n = 14). The Bio-Plex suspension array system was used to measure the concentration of 17 cytokines. The expression of proinflammatory and anti-inflammatory cytokines was maximal during the first week after thermal injury. Significant increases were measured for 15 mediators during the first week after thermal injury: interleukin (IL) 1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 p70, IL-13, IL-17, interferon gamma, monocyte chemoattractant protein 1, macrophage inflammatory protein 1beta, and granulocyte colony-stimulating factor (P < 0.05). Granulocyte-macrophage colony-stimulating factor was significantly increased during the second week after burn (P < 0.05). Within 5 weeks, the serum concentrations of most cytokines decreased, approaching normal levels. When compared with the cytokine levels measured in normal children, a total of 16 cytokines were significantly altered (P < 0.05). After severe burn, a specific cytokine expression profile is observed in patients without complications such as inhalation injury or sepsis. The cytokine concentrations decrease during 5 weeks after burn but remain elevated over nonburned values. Furthermore, the elevation in most serum cytokine levels during the first week after burn may indicate a potential window of opportunity for therapeutic intervention.

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OBJECTIVES-Severe burns are associated with a significant loss of muscle and strength. Studies have reported that oxandrolone improves lean body mass in muscle-wasting conditions. Also shown previously in burned children is that an exercise program increases lean body mass and muscle strength. We hypothesized that oxandrolone, in combination with exercise, would increase lean body mass and muscle strength in severely burned children more than oxandrolone alone or exercise alone.METHODS AND PATIENTS-Fifty-one burned children (≥40% total body surface area burned) were randomly assigned to receive oxandrolone alone (0.1 mg/kg per day orally; n = 9), oxandrolone and exercise (n = 14), placebo and no exercise (n = 11), or placebo and exercise (n = 17). Administration of oxandrolone was started at discharge and continued until 1 year after burn. The 12-week exercise training program was started 6 months after burn. Serum hormones, lean body mass, muscle strength, and peak cardiopulmonary capacity were assessed at 6 (baseline) and 9 months after burn. Data were analyzed using a 1-way analysis of variance, and significance was set at P < . 05. RESULTS-The mean percentage of change or increase in weight and lean body mass in the oxandrolone and exercise group was significant compared with placebo and exercise, as well as with the oxandrolone alone group or placebo and no exercise group. Furthermore, lean body mass was significantly improved in the oxandrolone and exercise, oxandrolone alone, and placebo and exercise group compared with the group only receiving placebo. Muscle strength significantly increased in oxandrolone and exercise, placebo and exercise, and the oxandrolone alone group when compared with the placebo and no exercise group. The peak cardiopulmonary capacity was significantly higher in both exercise groups. Insulin-like growth factor 1 was significantly increased in the oxandrolone alone group compared with placebo and exercise and placebo and no exercise. Both exercise groups showed significant changes in insulin-like binding-protein-3 when compared with groups without exercise.CONCLUSIONS-Oxandrolone, in combination with exercise, is beneficial in severely burned children, thus improving their rehabilitation. Keywordsburns; exercise; hormones; lean mass; oxandrolone Severe burns are physically and psychologically catastrophic. Severely burned children have an elevated resting energy expenditure, whole body catabolism, and muscle weakness, which are worsened by prolonged bed rest and physical inactivity. 1,2Address correspondence to Oscar E. Suman, PhD, Children's Wellness and Exercise Center, Shriners Hospitals for Children, 815 Market St, Galveston, TX 77550. E-mail: oesuman@utmb.edu. The authors have indicated they have no financial relationships relevant to this article to disclose. NIH Public Access Author ManuscriptPediatrics. Author manuscript; available in PMC 2008 May 5. Published in final edited form as:Pediatrics. 2007 January ; 119(1): e109-e116. NIH-PA Author ManuscriptNIH-PA Autho...

Body composition of severely burned children significantly improved in the second year compared with the first year after injury. This demonstrates a need for long-term rehabilitation in these burn patients.