Effects of chloroquine and hydroxychloroquine on bone health (Review).

Chloroquine (CQ) and hydroxychloroquine (HCQ), which were initially used to treat malaria, are now also used to treat autoimmune and inflammatory diseases, which have gained notoriety during the coronavirus‑19 pandemic. The emerging uses of CQ and HCQ in cancer therapy, metabolic syndrome and bone disorders highlight their broad clinical potential. Patients with autoimmune and inflammatory conditions have a higher risk of suboptimal bone health because of chronic inflammation, immune dysregulation and medication use. In the present review, the use of CQ and HCQ in bone research was explored, particularly in terms of their effectiveness and mechanism in modulating bone homeostasis. CQ and HCQ inhibit osteoblastic activity by suppressing autophagy, inducing oxidative stress and promoting osteoblast apoptosis. CQ suppresses osteoclastic activity by blocking the receptor activator of nuclear factor κ‑β/receptor activator of nuclear factor κ‑β ligand interaction, autophagy and inflammation. HCQ inhibits osteoclastogenesis by increasing the expression levels of osteoprotegerin, inducing osteoclast apoptosis and reducing cytokines without affecting autophagy. With regard to the molecular machineries, CQ and HCQ inhibit bone formation and bone resorption. Variations in dose, frequency and duration of CQ and HCQ treatment result in heterogenous outcomes. Further research is necessary to clarify the net effects of CQ and HCQ on bone through studies specifically designed to explore their direct impact as the primary objective. The use of these medications is broadening particularly in patients with autoimmune diseases who are at risk of skeletal disorders. However, their safety profiles, adverse effects and contraindications must be carefully monitored when administered for long‑term use and in combination.