In 1989, a prospective randomized multicenter study was initiated in order to determine the safety and efficacy of oral
clodronate in myeloma patients. The primary objective of this long-term trial is to evaluate whether supportive
clodronate is able to prevent or retard the progression of
bone disease and reduce the occurrence of characteristic complications:
pain,
pathologic fractures, and
hypercalcemia. We now report first results as an interim analysis, including data obtained from 26 patients (total number of Tübingen patients n = 36) who entered the study at the Medizinische Universitätsklinik Tübingen. Patients were randomized to receive either
chemotherapy alone (
melphalan 15 mg/m2 i.v. on day 1 and
prednisolone 60 mg/m2 orally on days 1-4 every 4 weeks (control group) or in combination with 1600 mg
clodronate/day orally as a single dose for a period of at least 1 year. Repeated radiologic examinations in addition to hematologic and biochemical analysis were performed in order to evaluate the skeletal status with respect to lytic bone lesions and
osteoporosis and the course of serum M
protein and light chain excretion into urine.
Clodronate treatment resulted in a significant decrease of serum
calcium concentrations and of biochemical indices for
bone resorption. No
clodronate-related toxicity or
hypocalcemia was observed. In patients treated with
chemotherapy alone, this effect was less marked and discontinuous.
Clodronate-treated patients developed fewer progressive bone lesions (significant for lytic, not for osteoporotic lesions). No hypercalcemic episodes occurred in the
clodronate-treated patients, but there were six episodes in the control group. Whereas the number of vertebral fractures was evidently less is
clodronate-treated patients, three of those patients suffered from
multiple fractures of long bones and ribs. All together, 12
pathologic fractures occurred in five
clodronate-treated patients, whereas in the control group 23
pathologic fractures occurred in the same number of patients during the whole observation period. The final analysis of all multicenter included patients should clarify these findings. There was a significant finding that
clodronate proved to have an
analgesic effect.