Chloroquine ameliorates bone loss induced by d-galactose in male rats via inhibition of ERK associated osteoclastogenesis and antioxidant effect

Chloroquine (CQ); a lysosomotropic agent used for decade ago as anti-malarial, was tested against aging induced osteoporosis. Osteoporosis in male rats was induced using d-galactose (D-gal) as a reducing sugar at a dose of 200 mg/kg/day; i.p. Osteoporotic rats were orally treated with CQ (10 mg/kg/day) for four successive weeks. Bone densitometry of tibia and femur were evaluated. Bone formation biomarkers; osteoprotegrin (OPG), bone specific alkaline phosphatse (BALP), and osteocalcin (OCN), and bone resorption biomarker; receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin-k (CTSK), tartrate-resistant acid phosphatase (TRAP) were estimated. Moreover, the expression of extracellular regulated kinase (ERK) in bone was determined. CQ ameliorated the bone detrimental changes induced by d-galactose. It enhanced bone health as revealed by measurement of bone densitometry, halted the activation of receptor activator of nuclear factor kappa-B ligand (RANKL) and reduced bone manifestation of ERK. Furthermore, CQ treatment abated serum cathepsin-k (CTSK) and serum tartrate-resistant acid phosphatase (TRAP) thus inhibited osteoclastogenesis and consequently restored the RANKL/OPG ratio. CQ demonstrated an antioxidant effect in bone where it increased both Catalase (CAT) and Superoxide dismutase (SOD). These CQ preserving effect in rats treated with d-galactose were confirmed by the histopathological examination. The present study points to the potential therapeutic effect of CQ as anti-osteoporotic agent possibly through its antioxidant effects and suppression of ERK associated osteoclastogenesis.