Parathyroid hormone-related protein (PTHrP) does not regulate 1,25-dihydroxyvitamin D serum levels in hypercalcemia of malignancy

We investigated in humoral hypercalcemia of malignancy whether parathyroid hormone-related protein (PTHrP) elevation causes a rise in 1,25-dihydroxyvitamin D (1,25-(OH)2 D) serum levels. We assessed 41 patients with hypercalcemia of malignancy in a prospective study. There were 19 patients who had serum PTHrP levels in the normal range; 22 patients had elevated serum PTHrP levels. All patients were treated with the bisphosphonate pamidronate resulting in a drop of serum calcium (p < 0.0001) and serum phosphate (p < 0.0023) within 12 days, independent of the group. Parathyroid hormone (PTH) was suppressed at the start of therapy and rose to within the normal range during therapy (p < 0.0001), regardless of the PTHrP levels. PTHrP levels were not influenced by calcium lowering therapy. The serum levels of 1,25-(OH)2 D were either suppressed or in the low normal range at the beginning of the study, without any significant difference between both groups. All patients showed a rise in 1,25-(OH)2 D during bisphosphonate therapy (p < 0.0001), independent of their PTHrP levels. Thus PTHrP did not influence the calcium, phosphate-, or PTH-dependent regulation of 1,25-(OH)2 D during calcium lowering therapy. We conclude, that PTHrP does not stimulate renal 1-hydroxylase activity in humoral hypercalcemia of malignancy.