The direct role for 1,25(OH)2D activity and metabolism in growth plate has been previously shown, using both chondrocyte-specific VDR and CYP27B1 knockout mouse models, and indicate that chondrocytic RANKL-mediated osteclastogenesis is impaired without vitamin D activity. The reduction in bone resorption in these conditional deletion models was associated with increased bone volume albeit only in the period of neonatal through to 15 days of age, suggesting that the effects of vitamin D in chondrocytes is transient and non-essential. It is less clear, however, whether elevated endogenous 1,25(OH)2D activity plays a greater role in growth plate chondrocytes. To model enhanced local 1,25(OH)2D activity in chondrocytes, we inactivated the CYP24A1 gene in chondrocytes (Ch-CYP24A1KO) using Type 2a1-Cre mice and compared to littermate floxed-CYP24A1 mice. 8-week-old female Ch-CYP24A1KO mice (n=6/gp) exhibited 46% increase in distal femoral hypertrophic chondrocyte zone width (P<0.01) and a converse albeit, minimal decrease in proliferative chondrocyte zone width, which is indicative of enhanced growth plate maturation. Consistent with this, Ch-CYP24A1KO exhibited a 22% increase in primary spongiosa width (P<0.05) and 26% increase in upper metaphysis BV/TV% (P<0.01) due to increased Tb.N (P<0.01). In contrast, the lower metaphysis bone volume in Ch-CYP24A1KO mice was unchanged. Interestingly, Ch-CYP24A1KO mice exhibited increased osteoclastogenesis both in the primary spongiosa (38%, P<0.01) and metaphyseal trabecular bone (3.2-fold, P<0.05), which is consistent with reports of 1,25(OH)2D activity on chondrocytes promoting bone resorption and may explain the absent increased bone phenotype in the lower metaphysis. Collectively, these data indicate that despite elevated osteoclastogenesis, the absence of chondrocytic 1,25(OH)2D catabolism results in enhanced growth plate maturation which leads to increased metaphyseal trabecular bone accrual well beyond the age that had hitherto be recognised. Enhancing 1,25(OH)2D activity in the growth plate may be important in rectifying pathologies of impaired growth plate maturation.