Diagnosing hypovitaminosis D: serum measurements of calcium, phosphate, and alkaline phosphatase are unreliable, even in the presence of secondary hyperparathyroidism.

OBJECTIVE: To ascertain the ability of routine biochemical markers of bone turnover to predict vitamin D insufficiency.

METHODS: Receiver operating characteristic (ROC) analysis was used to assess the value of serum alkaline phosphatase, calcium, and phosphate concentrations in the detection of hypovitaminosis D (< 20 nmol/l) in 467 patients between 1998 and 2000 (Cohort 1). The same analysis was repeated in a subsequent group of 719 patients between 2001 and 2003 (Cohort 2), in whom values of parathyroid hormone (PTH) were also available. Samples with elevated parathyroid levels from Cohort 2 were also analyzed to determine whether, in this subset, serum levels of calcium, phosphate, and alkaline phosphatase could reliably predict hypovitaminosis D. A subset of 50 patients from Cohort 1, with serum Vitamin D < 12 nmol/l, were reviewed by case note and telephone interview to determine demographic characteristics and the prevalence of risk factors for severe hypovitaminosis D.

RESULTS: The areas under the ROC curves for alkaline phosphatase, calcium, and phosphate were all less than 0.7 (the criterion for a useful test) in both Cohorts 1 and 2. In the subset of Cohort 2 with elevated serum PTH levels (n = 337), the area under the ROC curve for calcium was 0.701 (95% confidence interval 0.643-0.758), and less than 0.7 for alkaline phosphatase and phosphate. In the 50 patients from Cohort 1 with severe hypovitaminosis D, risk factors were prevalent: 66% were vegetarian or vegan, clothing was partially or completely occlusive of sunlight (veiling) in 72%, and 60% of this cohort went outdoors less than 5 times per week. Symptoms were non-specific in the majority.

CONCLUSION: Routine measurements of calcium, phosphate, and alkaline phosphatase are not reliable predictors of hypovitaminosis D, even when vitamin D insufficiency has been sufficient to produce a PTH response. Clinical suspicion based upon history and an awareness of risk factors should remain the gold standard for requesting serum vitamin D measurements. Inadequate sunlight exposure (through veiling and poor outdoor exposure) and poor dietary intake are highly prevalent features of hypovitaminosis D in severely affected patients.