Long Term Effects of Dichloromethylene Diphosphonate in Paget's Disease of Bone

Abstract

Dichloromethylene diphosphonate (C12MDP) is a diphosphonate which markedly inhibits bone resorption. We have tested CUMDP in Paget's disease, a disorder characterized by increased bone remodeling. Sixty-three patients with progressive Paget's disease were treated for 6 months with Cl₂MDP at daily oral doses of 400, 800, 1600, or 2400 mg. Thirty-nine patients received calcium and vitamin D supplements during treatment. Patients in all treatment groups had significant reduction in serum alkaline phosphatase, urinary hydroxyproline, skeletal uptake of ^99mtechnetium-diphosphonate scintiscans, and resorption parameters on iliac crest biopsy samples as assessed by quantitative histomorphometry. Treatment was well tolerated and did not induce a skeletal mineralization defect. The reduction in alkaline phosphatase and urinary hydroxyproline persisted 1 yr after withdrawal of treatment. The biochemical remission was sustained in half of the patients 2 yr after the end of treatment and was accompanied by a marked reduction of bone pain. A daily dose of 800 mg is recommended as the best for control of clinical and biochemical symptoms. The transient increase in iPTH levels observed in patients treated with CI2MDP alone did not occur when calcium and vitamin D were added. We conclude that Cl₂MDP is effective in the treatment of Paget's disease of bone and provides a prolonged response. Dietary supplementation with calcium and vitamin D is desirable to prevent secondary hyperparathyroidism.