Secondary hyperparathyroidism associated with dichloromethane diphosphonate treatment of Paget's disease.
Six patients with extensive polyostotic Paget's disease were treated for 3 months with dichloromethane diphosphonate (CL2MDP; 1600 mg/day, orally). Serum alkaline phosphatase and urinary hydroxyproline excretion decreased 60-80% in each patient. Blood ionized calcium (ca++) and immunoreactive PTH (iPTH) were measured weekly during the first month of therapy and monthly thereafter. As an index of parathyroid function, PTH secretory reserve was assessed by EDTA infusions before treatment, at the end of treatment, and 3 months after Cl2 MDP therapy was stopped. Before therapy, iPTH and Ca++ were normal in all patients. During treatment, Ca++ decreased and iPTH increased in all patients; mean iPTH approximately doubled (95% confidence limits, 1.5- to 2.7-fold increase). At the end  of 3 months of treatment, EDTA infusion raised iPTH in each patient to a level higher than that in the control infusion, indicating augmented PTH secretory reserve. Ca++, iPTH, and the iPTH response to EDTA-induced hypocalcemia returned toward baseline by 3 months after the end of CL2MDP treatment. The results indicate that secondary hyperparathyroidism developed as a result of Cl2MDP therapy. The cause of the parathyroid-gland adaptation is not known; the hyperparathyroidism is, however, at least partly reversible. Cl2MDP inhibits bone resorption while allowing bone mineralization to continue; this differential effect could lead to the hypocalcemia and parathyroid hyperfunction.
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D002118:Calcium / Q000097:blood; D004002:Clodronic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects*; D004492:Edetic Acid; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D006962:Hyperparathyroidism, Secondary / Q000139:chemically induced*; D010001:Osteitis Deformans / Q000097:blood / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000097:blood
D004164:Diphosphonates; D010281:Parathyroid Hormone; D004002:Clodronic Acid; D004492:Edetic Acid; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium