Relationship between serum 25-hydroxyvitamin D and parathyroid hormone in the search for a biochemical definition of vitamin D deficiency in children

BACKGROUND: Current guidelines use differing definitions of vitamin D deficiency based on serum 25-hydroxyvitamin D (25OHD) levels, which complicates clinical decision making on vitamin D doses used for the prevention and treatment. This study examined the natural relationship between serum 25OHD, parathyroid hormone (PTH), calcium, phosphate, and alkaline phosphatase. METHODS: Two-hundred and fourteen children routinely admitted without conditions affecting the natural relationship among metabolites, including 17 with radiologically confirmed vitamin D deficiency rickets, were studied. The frequency of abnormal bone metabolites was examined for different 25OHD thresholds. RESULTS: The best fitting intersection point where PTH levels increased was a 25OHD level of 34 nmol/l (R-2 = 0.454; 95% confidence interval: 27-41 nmol/l). Seventy-three and 86% of the children demonstrated some biochemical abnormality below 25OHD levels of 41 and 27 nmol/l, respectively. All patients with rickets had 25OHD levels < 34 nmol/l. The vast majority of children with abnormal bone metabolites had 25OHD levels < 34 nmol/l and PTH levels > 50 ng/l. CONCLUSION: Vitamin D deficiency, based on PTH elevation, was best defined by a 25OHD level of < 34 nmol/l. Because deficient calcium supply often coexists with vitamin D deficiency and both can independently cause nutritional rickets, a threshold for the skeletal effects of vitamin D should not be based purely on 25OHD levels.