MONITORING THE ACTION OF CLODRONATE WITH TYPE-I COLLAGEN METABOLITES IN MULTIPLE-MYELOMA

In our previous double-blind trial, we reported that clodronate reduce d the incidence of bone lesions, fractures, pain and hypercalcaemia in multiple myeloma. Recently, it has been assumed that the antiresorpti ve effect of bisphosphonates on the osteoclasts is mediated through th e osteoblasts. We therefore determined, in 244 patients of the same tr ial, serum assays of aminoterminal propeptide of type I procollagen (P INP) and type I collagen degradation product (ICTP). PINP is an early synthesis product of proliferating osteoblasts, in comparison to the a lkaline phosphatase (AP) which is secreted by differentiated osteoblas ts during the maturation phase of collagen. ICTP circulates in serum w hen old bone is resorbed. Our results indicate that after 25 months, t he PINP levels decreased in the clodronate group (from 68.9 +/- 4.4 mu g/l to 37.2 +/- 3.5 mu g/l; P < 0.001) but not in the control group ( from 61.5 +/- 3.2 mu g/l to 69.3 +/- 7.5 mu g/l; P < NS). The fall in the ICTP levels was markedly steeper in the patients receiving clodron ate (from 8.38 +/- 0.80 mu g/l to 4.58 +/- 0.32 mu g/l; P < 0.01) than placebo (from 7.84 +/- 0.53 mu g/l to 6.45 +/- 0.95 mu g/l; P = NS). A significant difference between the study groups was seen at 4 months in the PINP, at 7 months in the ICTP and at 13 months in the AP level s, suggesting that clodronate affected through the proliferating osteo blasts, the osteoclasts, and through the osteoclasts, the differentiat ed osteoblasts. High baseline ICTP, PINP and AP levels indicated a poo r prognosis. The decrease of the markers by clodronate was more marked in survivors than in non-survivors. Copyright (C) 1996 Elsevier Scien ce Ltd