Calcium in health and disease

Calcium is an essential but controversial nutrient: there is no consensus on the level of human calcium requirement or the significance of calcium deficiency. The explanation for this must be sought in the history of calcium research since Pommer (1885) first established the difference between osteoporosis and osteomalacia. Pommer showed that rickets and osteomalacia represented a failure to mineralize new bone as it was being formed, leading ultimately to a calcium deficit in the bony tissue itself, whereas osteoporosis was a deficit of whole bone tissue without change in its mineral content. Not long afterwards, Miwa and Stoeltzner (1898) demonstrated that calcium deficiency caused osteoporosis, not osteomalacia, in experimental adult animals. It was Mellanby (1918) who finally identified vitamin D as the factor that prevented and cured rickets. Soon after that, Telfer (1926) showed that vitamin D deficiency led to malabsorption of calcium. From this it was assumed that vitamin D deficiency and calcium deficiency must have the same metabolic consequences. Accepting the concept that both calcium and vitamin D deficiencies led to rickets or osteomalacia, Albright et al. (1938) invoked a new pathogenetic mechanism – failure of new bone formation because of sex hormone deficiency and/or negative nitrogen balance – to explain postmenopausal and other forms of osteoporosis. This paradigm prevailed for a generation until a seminal paper from Sweden (Carlsson and Lindquist, 1955) showed that vitamin D not only regulated calcium absorption but also independently regulated plasma calcium homeostasis. This made it possible to distinguish vitamin D deficiency from calcium deficiency (Nordin, 1960) and allowed the reemergence of the concept (Hess, 1929) that calcium deficiency led to osteoporosis and vitamin D deficiency to osteomalacia. Although this concept is increasingly accepted in theory, there is in practice no consensus about the contribution of calcium deficiency to clinical osteoporosis or about the reality of a calcium requirement in humans (Kanis and Passmore, 1989). Clearly the menopause is associated with a rise in bone breakdown rather than a fall in bone formation (Young and Nordin, 1967; Gallagher, Young and Nordin, 1972; Stepan et al., 1987; Nordin and Polley, 1987; Prince et al., 1995). The current issue is whether oestrogens inhibit bone resorption directly or whether they operate through the calcium economy; it is no longer maintained that they promote bone formation. In the meantime, Albright and colleagues’ original ideas about osteoporosis survive in relation to corticosteroid-induced osteoporosis and perhaps as part of the explanation for age-related osteoporosis, particularly in men.