Bisphosphonates, associated with
rehydration, became the treatment of choice of malignant
hypercalcemia when it became apparent that these compounds normalized plasma
calcium in most cases within a few days and with almost no side effects, and that their effect was prolonged. Dichloromethylene
bisphosphonate and aminobisphosphonate, especially APD, were shown to inhibit
bone resorption with no noticeable inhibition of bone formation, and were highly effective in the long-term treatment of Paget's disease. APD was used in almost 300 patients with malignant
hypercalcemia published in the literature and has been used in the medical clinic at Lausanne for several years. When given to 14 patients with malignant
hypercalcemia at the dose of 25 mg/day until plasma
calcium became normal for two consecutive days, APD had to be given for 4-11 days, severe
hypercalcemia needing longer treatment than mild
hypercalcemia (Adami et al. 1982). When given for a fixed period of 6 days, again plasma
calcium normalized in all patients, whether APD was given i.v. (30 mg/day, ten patients) or orally (1200 mg/day, ten patients) (Adami et al. 1985). Further shortening of the treatment to one single infusion given over 24 h did not decrease the efficacy, as long as high enough doses were given (Blomqvist 1986). For severe
hypercalcemia of above 3.5 mmol/liter 60-90 mg had to be given, while 30-45 mg was sufficient in milder cases (Body 1984). Otherwise, mild, transient, and asymptomatic
hypocalcemia could occur. Normalization of plasma
calcium went along with clinical improvement, sometimes even with correction of
coma. Renal function was improved, even when the initial plasma
creatinine levels were up to twice normal.
Hypercalcemia could reoccur, but the duration of the effect of APD (1 week to several months) depended among other things on the dose administered. The decrease in plasma
calcium was accompanied by a decrease in urinary
calcium and
hydroxyproline, both showing inhibition of
bone resorption. In the case of recurrency, the treatment could be repeated with almost unaltered efficacy, except in end-stage
cancer disease. When given to 13 normocalcemic patients with bone
metastases from
breast cancer,
hydroxyproline and urinary
calcium again decreased. Bone pains and radiologic signs of metastatic
bone resorption also showed significant improvement, although these latter effects could also be explained by the antitumoral treatment, in this uncontrolled open trial.(ABSTRACT TRUNCATED AT 400 WORDS)