Trolox, r‑irisin and resveratrol cocktail to counteract osteoblast metabolism alterations in osteoarthritis and osteoporosis

Introduction Osteoarthritis and osteoporosis are age-related musculoskeletal disorders characterized by increased oxidative stress and cellular senescence, which contribute to altered metabolism and disease progression. Although research in this field is constantly evolving, the discovery of new molecular targets and drug combinations to counteract musculoskeletal disorders remains a goal of great interest. This study aimed to evaluate the efficacy of a cocktail of trolox, recombinant irisin (r-irisin) and resveratrol in modulation of osteoblastic metabolism by investigating the expression of NADPH oxidase 4 (NOX4), sirtuin 1 (SIRT1) and pentraxin 3 (PTX3). Materials and methods 20 male patients undergoing hip arthroplasty were enrolled, including ten patients with coxarthrosis and ten patients with osteoporosis. Femoral head biopsies were taken from each patient to isolate primary osteoblast cultures, which were treated with the cocktail for 6 days. Results The cocktail of trolox, r-irisin and resveratrol increased cell viability, and reduced ROS and senescence β-galactosidase activity (SA-β-Gal) levels. In addition, western blotting analysis showed reduced expression of NOX4 and increased expression of SIRT1 and PTX3 in both experimental groups, although with more pronounced effects in osteoarthritic patients, highlighting lower treatment efficacy in the presence of osteoporosis. Conclusions The improvement in cell viability and reduction in oxidative stress and cellular senescence observed through treatment-induced modulation of the NOX4–SIRT1 axis and PTX3 suggests a protective role for these biomarkers in bone metabolism. These findings could offer new perspectives in counteracting the effects of aging on the skeletal system by improving bone health and mitigating metabolic alterations.