Treatment of Paget's disease of bone with (4-chloro-phenyl) thiomethylene bisphosphonate

Introduction of antiosteoclastic drugs, calcitonin and etidronate, has profoundly changed the treatment of active Paget's disease of bone. Nevertheless, the use of these drugs is limited in some patients by the occurrence of side-effects or by a resistance to therapy. We report the results of an open, nonrandomized study with a new bisphosphonate, (chloro-4 phenyl) thiomethylene bisphosphonate (Cl-TMBP), given orally to 35 patients with active Paget's disease of bone. At two different dosages this new bisphosphonate induced a significant decrease in disease activity. Patients receiving a mean dosage of 5 mg/kg/d (n = 14) showed a significant reduction of serum alkaline phosphatase levels to 43% of pretherapeutic values (from 499 +/- 91 to 214 +/- 41 IU/l) while hydroxyproline/creatinine ratio decreased to 43% of baseline (from 93 +/- 21 to 40 +/- 11). A second group of patients (n = 21) receiving a mean dosage of 11 mg/kg/d exhibited a similar response: serum alkaline phosphatase activity was reduced to 42% of initial values (from 1384 +/- 209 to 584 +/- 111 IU/l) while hydroxyproline/creatinine ratio fell to 48% of baseline (from 144 +/- 27 to 69 +/- 15). This was accompanied by a reduction in radionuclide uptake in pagetic areas. A prolonged beneficial effect was observed in most patients. In patients receiving the highest dosage significant reduction in serum calcium and rise in parathyroid hormone were observed. Otherwise no clinical or biological side-effect occurred throughout the study.