Significance of plasma PTH-rp in patients with hypercalcemia of malignancy treated with bisphosphonate.
BACKGROUND
Hypercalcemia of malignancy (HM) is one of the commonest metabolic complications associated with cancer. Plasma parathyroid hormone-related peptide (PTH-rp) is known to cause hypercalcemia in the vast majority of patients with HM.


METHODS
Fifty-two patients with HM were treated with a single infusion of 60 mg of pamidronate (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). Serum calcium and plasma PTH-rp levels were measured at the basal and after pamidronate therapy.


RESULTS
Normocalcemia was achieved in 43 (i.e., 83%) of these patients within 3 to 5 days. Eighty-one percent had increased plasma PTH-rp levels. There was no difference in the percentages of patients who had elevated plasma PTH-rp levels compared with those of patients with metastatic bone disease and humoral HM. However, the latter group of patients had significantly higher circulatory PTH-rp levels (P < 0.01). The pretreatment calcium levels were not correlated with the calcium-lowering responses nor with plasma PTH-rp levels. However, there was a significant positive correlation between pretreatment plasma PTH-rp levels and the nadir serum calcium (P < 0.001) and a negative correlation with the changes in serum calcium levels (P < 0.001) after pamidronate therapy. No relationship existed between pretreatment calcium levels or PTH-rp levels with the extent or the severity of the metastatic bone disease. Patients who had the highest PTH-rp levels had the worst prognosis, poorest calcium-lowering effect, shortest duration of normocalcemia, and required higher doses and frequent infusions of pamidronate to maintain normocalcemia. The nonresponders to therapy had a significantly higher mean plasma PTH-rp level (> 75 pg/ml) than the responders (P < 0.01).


CONCLUSIONS
The plasma PTH-rp levels may help to predict the calcium-lowering effect of bisphosphonate and give an indication of the prognosis in patients with HM. They may allow identification of patients who need higher doses and increased frequency of administration of bisphosphonate, thereby expediting the normocalcemic response.
Wimalawansa
S J
SJ
Department of Medicine (Endocrinology), Royal Postgraduate Medical School, London, United Kingdom.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000097:blood; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000150:complications* / Q000652:urine; D000077268:Pamidronate; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism*; D011863:Radioimmunoassay
D004164:Diphosphonates; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D000077268:Pamidronate; D002118:Calcium