Oral citrate supplementation mitigates age-associated pathological intervertebral disc calcification in LG/J mice.

Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. Here, we investigate the efficacy of long-term oral KCitrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. KCitrate successfully reduced the incidence of disc calcification in LG/J mice without deleterious effects on vertebral bone structure, plasma chemistry, and locomotion. Notably, a positive effect on grip strength was evident in treated mice. Spectroscopic investigation of the persisting calcified nodules indicated KCitrate did not alter the mineral composition and revealed that reactivation of an endochondral differentiation program in endplates may drive LG/J disc calcification. Importantly, KCitrate reduced calcification incidence without altering the pathological endplate chondrocyte hypertrophy, suggesting mitigation of disc calcification primarily occurred through Ca chelation, a conclusion supported by chondrogenic differentiation and Seahorse metabolic assays. Overall, this study underscores the therapeutic potential of KCitrate as a systemic intervention strategy for disc calcification.