부산대학교 도서관

Vitamin D deficiency remains the most common cause of nutritional rickets in the UK with considerable rise in reported cases in the last decade, however the true extent of disease burden remains unexplored. The thesis contains three prospective studies investigating the hidden burden of vitamin D deficiency in: 1) infants presenting with symptomatic deficiency and their family members, 2) a large multi-ethnic newborn cohort and 3) Sudden Unexpected Death in Infancy and Childhood (SUDIC). In infants with severe deficiency, significant cardiac dysfunction, growth plate abnormalities and osteomalacia was uncovered in infants with severe deficiency; and biochemical osteomalacia in 77% of their asymptomatic family members. Only a third of the UK newborns (n=919/2999) had sufficient 25 hydroxyvitamin D (25OHD) levels, with babies born in the winter to dark-skinned mothers most affected. At post-mortem examination (n=33, 29 infants) 70% had histological rickets at the growth plate but only 40% manifest biochemical vitamin D deficiency and only 9% radiological rickets. Lower 24,25 dihydroxyvitamin D3 [24,25(OH)2D3] levels and elevated ratio of 25OHD3:24,25(OH)2D3 were better indicators of histological rickets when compared to 25OHD3. Elevated osteoid surface, volume and thickness were noted in roughly 33%, 62% and 14% respectively. On three-point bending test, rib samples with histological rickets displayed disproportionate displacement in response to load indicating increased plasticity and had a tendency towards higher fracture toughness.