Figure 6.

Skeletal effects of 1,25(OH)₂D₃ signaling. During a negative calcium balance, when VDR action in the intestine is impaired or dietary calcium intake is low, intestinal calcium absorption is decreased. Normal serum calcium levels can however be maintained by increased 1,25(OH)₂D₃ and PTH levels, which will increase bone resorption and reduce bone matrix mineralization. During a normal or positive calcium balance, normal serum 1,25(OH)₂D₃ levels promote intestinal calcium absorption. This pathway will deliver sufficient calcium for adequate bone matrix mineralization. VDR signaling in osteoprogenitors increases RANKL expression and stimulates osteoclastogenesis, whereas VDR action in mature osteoblasts has anticatabolic actions, by decreasing RANKL expression, and anabolic effects by stimulating LRP-5 signaling.