Rickets and osteomalacia

Although the relationship between rickets and vitamin D was recognized over 60 years ago it is only relatively recently that the metabolic pathway leading to the active form of vitamin D was recognized. We now understand that vitamin D in the form of one of its active metabolites is necessary for the maintenance of calcium homeostasis and we appreciate in part the mechanisms by which this is brought about. However, much still remains to be discovered about the aetiology of rickets and the role of vitamin D metabolites in bone development. In this article I would like briefly to review our understanding of some aspects of the aetiology of rickets and the research we have carried out into this still unsolved problem. From the earliest days of vitamin D research it was appreciated that animals had two potential sources of this substance, namely the diet and the action of ultraviolet light (UVL) on skin 7-dehydrocholesterol. UVL of wavelength <315 nm breaks the C,-C,, bond with varying efficiency according to the particular wavelength, to form pre-vitamin D (Fig. I). The latter molecule undergoes a temperature-dependent isomerization to yield vitamin D. It also undergoes other intermolecular rearrangements to yield tachysterol and lumisterol. Factors such as the wavelength of the UVL employed, temperature and solvent affect the nature of the products of this photoisomerization but at 37’ about 7% is pre-vitamin D, 15% is lumisterol and tachysterol and about 78% is vitamin D. Pre-vitamin D is always present in any sample of vitamin D. In solution at room temperature about 20% may be pre-vitamin D with the percentage reducing to 5-10 at 37O. Vitamin D is sparsely distributed in food (Table I ) so that without a national fortification policy dietary vitamin D intake would be less than 2 . 0 pg/d. Because the diet of most people contains only small amounts of vitamin D, and as rickets is