Parathyroid hormone-related protein(50–69) and response to pamidronate therapy for tumour-induced hypercalcaemia

A region-specific radioimmunoassay has been employed to measure levels of immunoreactive parathyroid hormone-related protein^(50–69) (iPTHrP^(50–69)) in patients with tumour-induced hypercalcaemia (TIH). This assay is based on an antiserum raised against synthetic human PTHrP^(50–69). The assay showed no cross-reactivity with human or bovine parathyroid hormone^(1–84). The effect of a single dose (60 mg) of pamidronate was studied in 25 consecutive patients with TIH. All were rehydrated prior to treatment. All but 2 patients (8%) became normocalcaemic after treatment; both of these had very high levels of iPTHrP^(50–69). Time to achieve normocalcaemia, as an index of relative resistance to pamidronate, correlated positively with pretreatment level of iPTHrP^(50–69). Absence of radiological evidence of bone metastases also predicted relative resistance to pamidronate. In this study, iPTHrP^(50–69)-induced osteoclastic bone resorption was a more important mechanism in the causation of TIH than PTHrP-induced renal reabsorption of calcium as assessed by the renal thresholds for calcium and phosphate.