The Effect of Treatment With PTH on Undercarboxylated Osteocalcin and Energy Metabolism in Hypoparathyroidism.

CONTEXT: Undercarboxylated osteocalcin (ucOC) has been shown to affect glucose metabolism in mice. We recently randomized patients with hypoparathyroidism to treatment with PTH or placebo and demonstrated a marked increase in total osteocalcin.

OBJECTIVE

To investigate whether there was a similar increase in ucOC and whether that increase affected glucose metabolism.

DESIGN

A 24-week randomized, placebo-controlled trial.

SETTING

Ambulatory patients in a research facility.

PATIENTS: Sixty-two patients aged 31-78 years with hypoparathyroidism, of which 58 completed the trial.

INTERVENTION: 100 μg/d of PTH (1-84).

MAIN OUTCOME MEASURE: Change in ucOC.

RESULTS

ucOC increased by 1185.0 ± 814.4% (mean ± SD) in the PTH-treated group and by 69.3 ± 79.4% in the placebo group (P < 10(-50)). In addition, body weight decreased by 1.1 ± 4.0% in the treatment group and increased 0.8 ± 2.5% in the placebo group (P = .04). Glucose, adiponectin, leptin, homeostasis model of assessment for insulin resistance, total body fat mass, or truncal fat did not change significantly. In addition, the number of hypercalcemic episodes per patient was 3.7 ± 2.9 (mean ± SD) in the PTH-treated group but only 0.2 ± 0.6 in the placebo group (P < .001). Moreover, there was a significant and negative correlation between the change in ucOC and change in body weight (P = .004) or change in total body fat mass (P = .03), and a negative but nonsignificant correlation between the number of hypercalcemic episodes and percentage change in body weight (r = -0.32; P = .1). Change in ucOC did not significantly correlate with changes in other parameters.

CONCLUSIONS

An explanation for the weight loss may be subtle hypercalcemia in PTH treatment inhibiting appetite. Our data do not support a role for ucOC in energy metabolism in humans.