Calcium and vitamin D deficiency impairs bone health and may cause rickets in children and osteomalacia in adults. Large animal models are useful to study experimental osteopathies and associated metabolic changes. We intended to modulate vitamin D status and induce nutritional osteomalacia in minipigs. The control group (n = 9) was fed a semisynthetic reference diet with 6？g calcium and 6,500？IU vitamin D3/kg and the experimental group (n = 10) the same diet but with only 2？g calcium/kg and without vitamin D. After 15 months, the deficient animals were in negative calcium balance, having lost bone mineral density significantly (means ± SEM) with ？51.2 ± 14.7？mg/cm3 in contrast to controls (？2.3 ± 11.8？mg/cm3), whose calcium balance remained positive. Their osteoid surface was significantly higher, typical of osteomalacia. Their plasma 25(OH)D dropped significantly from 60.1 ± 11.4？nmol/L to 15.3 ± 3.4？nmol/L within 10 months, whereas that of the control group on the reference diet rose. Urinary phosphorus excretion and plasma 1,25-dihydroxyvitamin D concentrations were significantly higher and final plasma calcium significantly lower than in controls. We conclude that the minipig is a promising large animal model to induce nutritional osteomalacia and to study the time course of hypovitaminosis D and associated functional effects. 1. Introduction Adequate calcium and vitamin D intakes are essential for skeletal health and to minimize the incidence of osteoporosis and of rickets in children and nutritional osteomalacia in adults. Calcium and vitamin D supplementation is also key to the treatment of these diseases [1–3]. Rickets and osteomalacia remain endemic problems in developing countries but show increasing prevalence also in North America and Europe [3, 4] because of changes in life style with an increase of indoor activities and a decrease in sunlight exposure. Incidence of osteomalacia is also increased by the demographic shift, because calcium and vitamin D intakes are often inadequate in the elderly, in whom vitamin D synthesis, calcium absorption, and renal reabsorption tend to diminish [3]. Subjects with darker skin or covering clothing habits are at higher risk because both factors contribute to insufficient dermal vitamin D synthesis, responsible in turn for diminished bone density. Vitamin D combined with calcium has been shown to enhance lower-extremity function when vitamin D intake was sufficient to assure a serum concentration of 25-hydroxyvitamin D [25(OH)D] that exceeds 75？nmol/L [5]. This value is much higher than the current
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