Vitamin D deficiency and monitoring

What it is

Vitamin D deficiency is a common cause of secondary osteoporosis, diagnosed by a suboptimal serum 25,OH vitamin D level. Vitamin D deficiency leads to impaired intestinal absorption of calcium and lower serum calcium levels; the low serum calcium causes elevated iPTH, and to maintain serum calcium homeostasis calcium is sacrificed from the skeleton, leading to low bone density. In children the same deficiency causes rickets, through defective mineralization of osteoid and growth plates.

The synthesis runs in three steps. In the skin, UV-B light at 290-315 nm turns 7-dehydrocholesterol into cholecalciferol, vitamin D3, while ergosterol from plants or fungus gives ergocalciferol, vitamin D2; dietary sources are few, the natural ones such as fish, and supplementation (in US) is by ergocalciferol. In the liver, microsomal 25-hydroxylase turns both into 25(OH) cholecalciferol, calcidiol. In the kidney, at the renal tubular epithelium, mitochondrial 1alpha-hydroxylase turns calcidiol into 1,25(OH)2 cholecalciferol, calcitriol, which is the active vitamin D. That last enzyme is the regulated step: PTH and a low serum phosphate push it on, while a high serum phosphate and FGF23 hold it back.

Calcitriol then acts on intestinal calcium absorption. The arrow into calcium absorption at the renal distal convoluted tubule comes from parathyroid hormone, not from calcitriol, and both routes feed the calcium pool. On the bone side, osteoclasts give calcium resorption from bone while osteoblasts give increased calcium deposition stored in the bone matrix, and the skeletal system holds 98% of body calcium.