Lesser quantities of vitamin D are

found in the diet. It is found in two forms – vitamin D3

and vitamin D2

(ergocalciferol). The latter is derived from yeast that has been irradiated with ultraviolet light.

kidneys

The role of vitamin D Vitamin D has important roles in the intestine, in the kidney and in bone but undoubtedly also has effects on most organs. The most well-known role is in maintaining serum levels of calcium and phosphorus, which it achieves by increasing the efficiency of absorption of both calcium and phosphorus in the intestine, and calcium re-absorption in the kidney (Fig. 2). In the absence of the vitamin, only 10–15 per cent of dietary calcium is absorbed, but when levels are adequate, absorption may double to 30–40 per cent (1) (Fig. 3). How is this brought about? The

vitamin interacts with a specific receptor called a VDR (vitamin D receptor), which together with a number of cofactors enhances the transcription of various proteins (Fig. 4) such as calcium-channel proteins and a calcium-binding protein, calbindin. Within bone, the same

transcriptional mechanism allows the vitamin to stimulate osteoblast cells to express nuclear factor kappa B ligand, or RANKL. RANKL is recognised by pre-osteoclast cells and stimulates them to develop into active osteoclasts. Osteoclasts serve to dissolve the mineralised collagen matrix within bone, and in doing so they release calcium and phosphorus – which complements the vitamin’s other roles in maintaining calcium and phosphorus levels in serum (Fig. 2).

Effects of low vitamin D A deficiency of vitamin D will result in reduced blood levels of calcium, and an increase in the level of parathyroid hormone (PTH) secreted from the parathyroid glands (Fig. 2), – secondary hyperparathyroidism. PTH enhances the synthesis of vitamin D as well as the re-absorption of calcium in the

BOX 1: BIOLOGICAL EFFECTS OF VITAMIN D DEFICIENCY

n Reduced calcium n Increased PTH n Increased RANKL

12

Figure 2: Major interactions

between vitamin D, parathyroid hormone (PTH), calcium and phosphorus

around the body

90 80 70 60 50 40 30 20 10

adequate vitamin D status

absence of vitamin D

Figure 3: Absorption of dietary calcium with different vitamin D status.

PROTEIN FUNCTION mRNA TRANSLATION

vitamin D responsive element (V

element (VDRE) VDR 1, 25(OH)2 D 1, 25(OH)2D

Figure 4: Protein transcription by vitamin D and the vitamin D receptor (VDR) within the cell

in the

kidney, but paradoxically it increases the loss of phosphorus in the kidneys. Like vitamin D, PTH stimulates the production of RANKL (Box 1) and this in turn contributes to increased demineralisation of bones, as part of an attempt to maintain serum calcium levels – at the expense of bone mineral content.

Vitamin D and disease The smoke-filled skies of the industrial revolution meant that children in the 17th century had limited exposure to sunlight, and rickets was the first recognised manifestation of vitamin D deficiency. In adults, deficiencies may manifest as osteopenia, osteoporosis or osteomalacia. Osteomalacia may present as vague and generalised bone pain with weakness and fatigue, and is often implicated in patients with conditions such as fibromyalgia or myofascial pain syndrome. Therefore it should be considered in the diagnosis of anyone presenting with recalcitrant muscle aches and pains, trigger points and whole-body pain. See Box 2 for some of the signs and symptoms of hypovitaminosis D.

sportEX medicine 2010;43(Jan):11-16 CALCIFICATION

serum phosphorus serum calcium

ABSORBTION

other vitamin D receptor organs

1,25(OH)2 D PTH 1,25(OH)2 D PTH bone

parathyroid glands

intestines 1-hydroxylase

phosphate ions

Calcium and

% of absorbed calcium