Impact of Resistance Exercise and Nitrate Supplementation on Muscle Function and Clinical Outcomes after Knee Osteoarthritis Surgery in Middle-Aged Women with Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: /Objectives: Sarcopenia, defined by reduced muscle mass and strength, is linked to osteoarthritis (OA), particularly in middle-aged women, and may be exacerbated post-operatively. Resistance exercise (RE) helps counteract sarcopenia, but postoperative recovery is often suboptimal. Emerging evidence suggests that nitrate (NO3-) supplementation may enhance muscle recovery and complement RE. This study investigated whether NO3-supplementation combined with RE during postoperative rehabilitation improves thigh muscle mass and strength in middle-aged women with sarcopenia. Methods: We conducted a prospective randomized placebo-controlled double-blind study with thirty-two middle-aged women with sarcopenia and cartilage defects who were scheduled for mesenchymal stem cell implantation. They were randomized to receive RE (24 supervised sessions over 12 weeks) with NO3- supplementation (NG, n=16) or a placebo (PG, n=16). NO3- and placebo supplementation were administered 2 hours before each session. The primary outcomes were thigh muscle cross-sectional area (CSA) and knee extension/flexion strength. The secondary outcomes were Short Physical Performance Battery (SPPB), skeletal muscle index, hand grip strength (HGS), International Knee Documentation Committee (IKDC), and Western Ontario and McMaster Uni-versities (WOMAC) scores. Results: Thigh muscle CSA decreased significantly in PG but not in NG. Knee extension strength increased significantly in NG compared to PG at 6 and 12 weeks after the intervention. The SPPB and IKDC scores improved significantly in NG, while the HGS and WOMAC scores improved similarly in both groups. Conclusions: NO3-supplementation combined with RE effectively prevented muscle atrophy and enhanced muscle strength in middle-aged women with sarcopenia who underwent surgery, indi-cating potential for improving postoperative recovery.