Dietary calcium versus vitamin D in rickets: A response to Vlok et al.

The role of dietary calcium deficiency in rickets' causation was recently discussed in this journal (Vlok et al., 2022). Reviewing some of the biomedical literature, that paper concluded that low dietary calcium might play a prime role. We recently published a review that, in contrast, concluded that the evidence supporting a major role for dietary deficiency of calcium is weak (Mays & Brickley, 2022). In this letter, we argue that failure to engage with key aspects of the literature, including those we highlighted in our paper, and inaccurate citation of sources, have combined to result in the Vlok et al. publication greatly exaggerating the likely role of dietary calcium in rickets in communities both today and in the past. Although Vlok et al. attempt a critique of our review, they do not engage with its core aspect. This was a systematic overview of modern epidemiological studies where it was claimed that rickets was due to dietary calcium deficiency. We emphasized studies with data on serum vitamin D levels (25-OHD) and dietary calcium intake of individuals with active skeletal rickets. Six of the 15 studies we reviewed compared calcium intake in cases and controls; in three, intake was lower in cases. Levels of dietary calcium intake below which rickets lesions occur are unknown. However, data from controls without rickets, and those who have recovered from it, show that ca. 180–200 mg/day do not appear to be associated with bone lesions. In two of the three studies, mean intake of cases was above this level; in one, it was less (156 mg/day). But in two of these three, vitamin D levels were also below (Ahmed et al., 2020) or around (Aggarwal et al., 2012) the threshold associated with rickets (Atapattu et al., 2013), clouding the picture. Fourteen reviewed studies measured serum 25-OHD; in eight, it was similar to or below the threshold for bone lesions. Given the half-life of 25-OHD and the time taken for radiographic healing, perhaps more pertinent than the exact 25-OHD levels is that in eight of 11 studies with cases and controls, active rickets cases showed significantly lower serum 25-OHD. Thus we concluded that evidence from well-conducted epidemiological studies for a role for low dietary calcium, rather than vitamin D deficiency, in rickets in communities was weak. Secondly, Vlok et al. claim that one can distinguish rickets caused by low dietary calcium rather than low vitamin D on the basis of ‘low or no’ urinary calcium “secretion” (sic), low serum calcium, cure of rickets by calcium supplementation, in combination with non-deficient levels of serum 25-OHD and 1,25(OH)2D. This is erroneous. The first two criteria are completely non-specific as to cause. We deal with the difficulties of identifying cause using response to treatments in our publication, but in essence, even if low vitamin D was the cause, an improvement may be elicited by calcium supplementation. As stated above, in epidemiological studies, cases of purported calcium deficiency rickets in fact consistently showed low mean 25-OHD. Raised (not non-deficient) serum 1,25(OH)2D was once considered an indication of dietary calcium deficiency but is now acknowledged also to occur in vitamin D deficiency (refs. in Mays & Brickley, 2022). Thirdly, we emphasized epidemiological over case studies because they are more suited to evaluating the importance of dietary calcium in rickets in communities, our prime interest. Nevertheless, Vlok et al. (2022: 11) reprimand us for this, arguing that case reports provide some of the strongest evidence for the role of dietary calcium. However, the three case studies they cite here comprise one where the causes of rickets were unclear and the authors highlight a need to investigate genetic factors (Afrand & Modaresi, 2014). Another (Sodri et al., 2021) describes a child excluded from adequate sunlight during a covid lockdown. The third (Davidovits et al., 1993) had adequate vitamin D but this was only measured after moving from Russia, with minimal exposure to sunlight/UVB, to sunny Israel. In no case was calcium intake (mg/day) before treatment accurately measured, although in one instance (Davidovits et al., 1993) it was “roughly estimated”. We concluded that, at a community level, rickets is essentially an indication of low vitamin D status, but that occasionally, in very low calcium intake groups, dietary calcium deficiency may play a role by accentuating the need for vitamin D (Mays & Brickley, 2022). This is in tune with physiological expectations (Patel et al., 2016), and is in accord with recent reconsiderations of epidemiological evidence (e.g., Sempos et al., 2021). The authors have identified no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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