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Several questions concerned Prentice's approach to estimating the adequacy of mineral intakes. Firstly, there is, in some instances, uncertainty about the optimal end point, e.g. optimal bone mineral density at different ages. Secondly, there may be age periods, during which intakes ought to be higher than during others, so that one can perhaps not just divide the mineral content in early adulthood by the time that is available to accumulate them. Thirdly, even though the mineral intake may appear adequate, diets, particularly in developing countries, may contain substances that interfere with their absorption and bioavailability. Fourthly, a series of factors other than mineral intakes (e.g. physical exercise) may influence the efficiency of Ca utilization and bone accretion. In her reply, Prentice emphasized that her intention was not to establish dietary goals or even recommended dietary allowances; she was only trying to gauge if looking at habitual dietary intakes could give a clue as to whether mineral deficiencies could play a role in stunting or not.
A regression equation between height and bone mineral content obtained in a longitudinal study using dual energy X-ray absorptiometry (DEXA) predicted Widdowson's data that were used by Prentice to within 5%, but some caution is still indicated, because DEXA measures are calibrated against inorganic hydroxy-apatite which does not have the same composition as human bone.
Drinking water, as well as special dietary and cultural practices (such as the addition of dried baobab leaves to steamed millet or geophagia) can be important but highly variable sources of Ca and other minerals. Unfortunately they are not always taken into account in assessments of mineral intakes; they seem, however, to have been considered in most of the studies reviewed by Prentice. One of the aims of her review was to make a rough estimate for what mineral intakes appeared plentiful and which marginal, so that more attention and research could then be focused on the ones that are more likely to be limiting. Calcium intakes undoubtedly appear to be marginal because they are close to the theoretical accretion rates.
Several studies have been undertaken to show whether or not undernourished children tend to have low bone mineralization that does not manifest itself clinically; Prentice's data from The Gambia show a mild degree of demineralization, but this has not always been found. This is a subject for future research, which should not be difficult with modern techniques. An effect on linear growth is a different question.
Rats on a Ca deficient diet develop long, thin, demineralized bones, whereas rats on a P deficient diet stop growing. Also in children, a lack of P. as it occurs in some renal diseases and hypophosphataemic rickets, is always associated with linear growth retardation, whereas hypocalcaemia is primarily associated with low bone density and osteopenia, and only in extreme cases, as in those described by Pettifor in South Africa, with linear growth retardation.
It has been argued that Ca is important for linear growth in preterm infants, but it seems very difficult to feed VLBW infants enough Ca. The various high-Ca formulae that have been tried have not had any significant influence on linear growth. More effective seems to be a diet which is initially rich in P and to which Ca is added later, but even this does not result in accretion rates that are comparable to a normal one in utero.
Prentice's paper is concerned with Ca intake and bone mineralization, but it does not deal with ionized and non-ionized Ca in the circulation and their regulation. There is some discussion as to whether this really matters or not. Ionized Ca is involved not only in bone mineralization, but also in neural excitability and other vital functions. It therefore has to be very tightly regulated and independent of dietary intake. The role of the bound Ca is poorly understood.
Ca exchange between the circulation and the skeleton is affected by prostaglandins, parathyroid hormone, oestrogen, physical exercise and probably many other factors. This appears to be an area that is wide open to additional research.