ABSTRACT

Calcium homeostasis is achieved through a hormone-driven balance of physiological adaptations, including alterations in intestinal absorption, bone formation, and kidney reabsorption. The principle regulators of this process include parathyroid hormone (PTH) and calcitriol, whereby calcitriol is synthesized in response to low serum calcium through the calcium-PTH-vitamin D axis. Low serum calcium stimulates release of PTH from parathyroid chief cells, which subsequently enhances synthesis of calcitriol from 25OHD in the kidney. Calcitriol then activates VDR in the intestine to enhance calcium absorption, in the kidney to enhance calcium retention, and in osteoclast cells to release calcium from the bone mineral matrix. Randomized controlled trials (RCTs) and animal models indicate that vitamin D is not required to maintain bone health if calcium intake is sufficient (Reid et al., 2013). Bone loss by VDR null mice was reversed with calcium + phosphorus supplementation (Masuyama et  al., 2003), and mice with intestine-specific VDR expression (otherwise VDR null in other tissues including bone and kidney) had normal serum calcium levels and greater bone mineral density (BMD) than control mice (Xue and Fleet, 2009). These experiments, in addition to the observation that VDR is expressed by osteosclasts (absorptive bone cells) and not osteoblasts (mineralizing bone cells), suggest that the function of vitamin D is to maintain serum calcium, not to maintain bone health directly. Severe vitamin D deficiency affects bone health when serum 25OHD concentration is too low (<25 nmol/L) for adequate production of calcitriol, thereby preventing upregulation of intestinal calcium absorption (Need et al., 2008).