In patients with
multiple myeloma, despite a major reduction of bone
pain achieved with
chemotherapy, skeletal disease continues to progress. The effects of
clodronate, an inhibitor of osteoclastic
bone resorption, are evaluated on the natural history of skeletal disease in patients with newly diagnosed
multiple myeloma. Within the framework of the VIth MRC
Multiple Myeloma Trial, 536 patients (218 women, 318 men) with recently diagnosed
multiple myeloma were randomized to receive either
clodronate 1600 mg daily (n=264) or an outwardly identical placebo (n=272) in addition to
chemotherapy. Treatment with
clodronate was associated with a 50% decrease in the proportion of patients with severe hypercalcaemia (5.1% v 10.1%, P=0.06) and a similar reduction in reported non-vertebral fractures (6.8% v 13.2%, P=0.04). Fewer patients receiving
clodronate sustained vertebral fractures after entry to the trial (38% v 55%, P=0.01) and patients also lost less height over 3 years compared to those receiving placebo (2.0 v 3.4 cm, P=0.01). Biochemical indices of bone turnover were significantly lower in patients receiving concomitant
clodronate, both at plateau and at disease relapse. The frequencies of
back pain and poor performance status were significantly lower at 24 months in
clodronate than in placebo-treated patients (10.9% v 19.9%, P=0.05, and 18.3% v 30.5% P=0.03 respectively.) There was no statistically significant difference in survival between the
clodronate and placebo treated patients. The study indicates that long-term oral
clodronate slows the progression of skeletal disease in
multiple myeloma and decreases the associated morbidity. Patients without overt skeletal disease at diagnosis were also found to benefit from
clodronate, indicating that this treatment should be initiated as early in the course of the disease as possible.