SUN-487 The Effects of Nandrolone on Muscle Wasting in a Mouse Model of Glucocorticoid-Treated Exacerbations of COPD

Abstract Disclosure: S.J. van Krimpen: None. J.M. Webster: None. P. Qiu: None. P. Henrot: None. B. Rezaeifar: None. S.O. Simons: None. A.M. Schols: None. H.R. Gosker: None. R.C. Langen: None. Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease worldwide. Muscle wasting is a well-known, extrapulmonary complication of COPD that negatively affects clinical outcomes. It is accelerated by exacerbations of COPD (ECOPD), which are defined as an acute worsening in respiratory symptoms that worsens over ≤ 14 days and is often associated with increased local and systemic inflammation. Synthetic glucocorticoids (GCs) are administered as standard-of-care (SOC) anti-inflammatory treatment to prevent clinical deterioration in individuals with an ECOPD. However, GCs may aggravate the ECOPD-associated muscle wasting through their catabolic and anti-anabolic actions. In contrast, anabolic steroids stimulate muscle growth and have safely been applied in individuals with stable COPD. We therefore aim to improve the overall therapeutic efficacy of GCs and hypothesized that the anabolic steroid nandrolone attenuates muscle wasting in our mouse model of GC-treated ECOPD. Emphysema was induced in male C57BL/6J mice (n=12/group) by three weekly intratracheal (IT) instillations of elastase to model COPD, followed by IT-LPS (or vehicle) administration to evoke pulmonary inflammation and mimic ECOPD. Dexamethasone (DEX, a GC) or vehicle was injected subcutaneously daily as SOC treatment in ECOPD, starting 4 hours after LPS. Nandrolone decanoate (ND, 5mg/kg bw) or vehicle (90% corn oil in 10% ethanol) was injected subcutaneously at the same time as the first DEX dose. Micro cone beam CT scans were obtained weekly and at study endpoint 48 hours after LPS to verify emphysema development and measure muscle volume changes. After sacrifice, hindlimb muscles were weighed separately and snap-frozen for gene expression analysis. Compared to control, body weight of GC-ECOPD was reduced (-6.4%, p<0.001) whereas GC-ECOPD/ND was not (-3.2%, p=0.076). GC-ECOPD was not different from GC-ECOPD/ND (p=0.072). Muscle weight was reduced in GC-ECOPD and GC-ECOPD/ND compared to control (-6.7%, p<0.001 and -4.4%, p<0.05, respectively). Compared to control, preliminary analysis of (right hindlimb) muscle volume change showed no significant differences for GC-ECOPD or GC-ECOPD/ND (-6.6%, p=0.057 and -5.0% respectively, compared to -1.8%). Atrogene expression (Atrogin-1 and MuRF1) was not affected. In conclusion, in this model of GC-ECOPD, co-treatment with ND did not significantly attenuate loss of body weight, muscle weight or right hindlimb muscle volume. Further and additional analyses of the collected CT scans and tissues will be performed and might reveal underlying processes that provide more information on the effects of nandrolone in this mouse model of GC-treated ECOPD. Presentation: Sunday, July 13, 2025