CD40 KO mice and CD40L KO mice display decreased baseline BMD and increased bone resorption, concurrent with decreased B-cell OPG production. Decreased BMD was observed by DXA in (A) CD40 KO mice and (B) CD40L KO mice relative to age-matched (24 weeks) WT controls of the same genetic background at multiple anatomic positions including total body, spine, and femurs. P < .01, n = 16 (WT), n = 14 (CD40 KO), n = 12 (WT and CD40 KO). μCT reconstructions showing reduced trabecular and cortical structure of representative femurs in (C) CD40 KO mice and in (D) CD40L KO mice relative to their respective WT controls. Increased biochemical indices of bone resorption (CTx) were observed in the serum of (E) CD40 KO mice and (F) CD40L KO mice. Decreased OPG production by IgM⁺ BM B cells derived from (G) CD40 KO mice and (H) CD40L KO mice compared with WT (ELISA). *P ≤ .001. Real-time RT-PCR quantitation of OPG and RANKL mRNA expression in (I) CD40 KO and (J) CD40L KO mice. Mean ± SD of 3 independent WT and CD40 KO mice. *P ≤ .01.