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.

CONCLUSIONS

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.