Abstract
BackgroundInflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp.MethodsConsecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation.ResultsEMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group.ConclusionsPiroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may include modifications in the cytokine network and increases in monocytic expression of cytoprotective Hsp27.Trial registration numberISRCTN: ISRCTN96340690
Highlights
Inflammation is the main cause of disease-associated muscle wasting
We have previously demonstrated a better recovery of muscle endurance following treatment with celecoxib, a cyclooxygenase(COX)-2 selective drug, in hospitalized geriatric patients with acute infection [5]
In the present placebo-controlled randomized controlled trial (RCT) we investigated the effect of piroxicam on the evolution of muscle performance and mobility in hospitalized geriatric patients with acute infection
Summary
Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp. Sarcopenia, the age-related loss of muscle mass and performance, is a major component of frailty [1]. We have previously demonstrated a better recovery of muscle endurance following treatment with celecoxib, a cyclooxygenase(COX)-2 selective drug, in hospitalized geriatric patients with acute infection [5]. We hypothesized that NSAID treatment would preserve muscle performance by reducing infection-induced inflammation faster than antibiotics alone, and possibly by increasing expression of Hsp. Our results show improvements in muscle performance and basic mobility with piroxicam, but not with placebo
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