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The process of the photolytic activation of vitamin D precursor(s) in the skin has been elucidated by a detailed analysis of the products formed after ultraviolet light exposure. The photolytic product isolated from the skin of rats exposed to ultraviolet irradiation was identified as previtamin D3 by several criteria including its (a) characteristic ultraviolet absorption spectrum, (b) mass spectrum, and (c) thermal isomerization to vitamin D3, which itself was identified also by mass spectroscopy. Vitamin D3 per se was not formed by ultraviolet irradiation--vitamin D3 arises exclusively from the thermal conversion of previtamin D3. Detectable amounts of lumisterol3 or tachysterol3 were not seen.

Summary: The cardiovascular system in Paget's disease of bone and the response to therapy withcalcitonin and diphosphonate. J. W. Henley, R. S. Croxson and H. K. Ibbertson, Aust. N.Z. J. Med., 1979, 9, pp. 390–397. The cardiovascular status of 39 patients with Paget's disease of bone was studied before and after treatment with porcine calcitonin or diphosphonate (disodium etidronate). Cardiovascular abnormalities were detected in 32 patients. Systemic hypertension was present in four, ischaemic heart disease in five, cardiac enlargement in ten and evidence of valvular and/or arterial calcification in 14. Before treatment the cardiac index was elevated in 27 of 39 patients (69%) and there was a significant direct correlation with the serum alkaline phosphatase (r = 0·68, P < 0·001), urine total hydroxyproline (r = 0·51, P<0·001) and percentage skeletal involvement (r = 0·51, P<0·001). After 24 weeks' treatment with either diphosphonate or calcitonin, there was a fall in cardiac index in 17 of 18 patients; the mean reduction being 12·7% for the calcitonin group and 27% for the diphosphonate treated patients. There was a rise in mean arterial pressure and peripheral resistance in both groups (P< 0·025) and a fall in cardiothoracic ratio (P<0·005) but no change in heart rate. In 17 patients studied 24 weeks after the end of therapy, similar, though less marked changes were observed. The cardiac index was lower than the pretreatment value in all eight diphosphonate treated patients but cardiac index and biochemical indices were higher than basal levels in three of nine patients who had received calcitonin. This study confirms a high incidence of cardiovascular complications and an increased cardiac output in most patients with moderate or severe Paget's disease of bone. There was a significant correlation between these abnormalities, the biochemical indices of disease activity and the radiological evidence of skeletal disease. Treatment with either diphosphonate or calcitonin caused partial or complete biochemical remission and a reduction in cardiac index in most patients studied.

Cutaneous 7-dehydrocholesterol, exposed to ultraviolet radiation, converts to previtamin D3, which in turn converts in skin to vitamin D3 and is carried into the circulation. We investigated the feasibility of the photochemical conversion in skin of hydroxylated derivatives of 7-dehydrocholesterol - such as 1 alpha, 25-dihydroxy-7-dehydrocholesterol (1 alpha, 25-(OH)2-7-DHC) - to the corresponding hydroxylated previtamin as an alternative method of delivery of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2-D3) to subjects who are deficient in the endogenous metabolite. In human volunteers and in vitamin-D-deficient rats [24-3H] 1 alpha, 25-(OH)2-D3 appeared in blood after [24-3H] 1 alpha, 25-(OH)2-7-DHC was applied to the skin and exposed to ultraviolet radiation. In anephric rats, intestinal calcium absorption and serum calcium levels were elevated after a topical dose of 1 alpha, 25-(OH)2-7-DHC combined with ultraviolet phototherapy. Delivery of equivalent doses of 1 alpha, 25-(OH)2-D3 through the skin and orally showed that there was more prolonged stimulation in intestinal calcium absorption and serum calcium elevation after cutaneous administration. The photochemical conversion of precursors may be useful in the treatment of patients with impaired vitamin-D metabolism.