Bisphosphonate therapy for Paget's disease in a patient with hypoparathyroidism: Profound hypocalcemia, rapid response, and prolonged remission

Bisphosphonate treatment for severe Paget's disease leads to hypocalcemia f ollowed by a secondary hyperparathyroid response to restore normocalcemia. A case is presented of a 60-year-old woman with polyostotic Paget's disease and postsurgical hypoparathyroidism. In 1993 her Paget's disease 91 aline phosphatase (ALP), 1260 U/liter (35-135 U/liter), and fasting urinary hydro xyproline excretion, 13.7 mu mol/liter GF (0.4-1.9 mu mol/liter)was treated with intravenous pamidronate. Symptomatic hypocalcemia followed the first 60-mg dose, requiring large doses of calcium supplementation and calcitriol . Pamidronate therapy to a total dose of 360 mg was followed by rapid and p rolonged remission with indices of bone turnover in the normal range within 2 months and persisting for at least 19 months after treatment. In 1999 re lapse of Paget's disease-ALP, 511 U/liter (35-135 U/liter), and fasting uri nary deoxypyridinoline/creatinine 53.1 mu mol/mol (5-27 mu mol/mol)-was tre ated with alendronate, 10 mg daily. Symptomatic hypocalcemia occurred again , requiring increased calcium and calcitriol therapy. Indices of bone turno ver were within the normal range 9 weeks after the start of therapy. These responses were significantly more rapid and sustained than those observed i n euparathyroid. subjects. This case suggests that the lack of parathyroid response may modify the response to bisphosphonates by: (a) increasing intr insic uptake of bisphosphonate into the pagetic skeleton, allowing response to a smaller dose; (b) increasing duration and severity of hypocalcemia af ter bisphosphonate therapy; and (c) removing the hyperparathyroid drive to reactivation of pagetic osteoclasts, leading to a prolonged remission. Thes e observations have implications for optimizing bisphosphonate therapy both in Paget's disease and in osteoporosis.