Hyperparathyroidism secondary to zoledronic acid infusion: case report

Abstract

Dear Editor, Bisphosphonates are analogs of inorganic pyrophosphate. They are potent inhibitors of osteoclast-mediated bone resorption, and are shown to be effective in reducing skeletal complications such as bone pain, pathologic fracture, bone surgery, and hypercalcemia [1–5]. Zoledronic acid is a new long-acting and highly potent biphosphonate. We report a patient who developed hyperparathyroidism secondary to zoledronic acid treatment. A 57-year-old female patient was referred to the hospital with abdominal pain in 1997. Subtotal gastrectomy and splenectomy were performed with a diagnosis of stomach cancer. The pathological examination revealed that she had intermediate-grade lymphoma. Following the surgery, six cycles of CHOP and nine cycles of POCEF chemotherapy were administrated. She was then followed-up without any intervention until 2006 when she complained of leg pain. Multiple lytic lesions in fifth, sixth, ninth, tenth costae, and bilateral femurs were observed in scintigraphic examination. Thoracic and abdominal computed tomographies were reported to be normal. In the bone scintigraphy performed in January 2007, there was progression in lytic lesions. A single dose of 800 cGy radiotherapy was applied to femurs to reduce her pain, and zoledronic acid 4 mg, every 4 weeks was initiated. Calcium was also started with zoledronic acid but experienced gastric side effects. After the fourth administration of zoledronic acid, she complained of cramps in the legs. The biochemical examinations revealed that the blood calcium level was 7.5 mg/dl and the corrected calcium level was 7.91 mg/dl (8.8−10.5 mg/dl). Upon these findings, calcium carbonate (2,500 mg) and vitamin D3 (880 IU) were started. She used the prescribed drug for 1 month and the serum calcium level increased to 8.7 mg/dl (corrected calcium level, 9.1 mg/ dl), however, she complained of diffuse bone pain. Vitamin D3 and parathormone levels were found to be 457 pg/ml (4.7−114 pg/ml), and 13.2μg/L (20−120μg/ L), respectively. The renal and liver function tests were in normal limits. Parathyroid scintigraphy was normal. It was thought that the hyperparathyroidism could be secondary to the D hypovitaminosis and calcitriol (0.5 mcg, 2×1) treatment was started. After 3 weeks of calcitriol treatment, the parathormone level decreased to 312 pg/ml (4.7−114 pg/ml). She continued using calcitriol and zoledronic acid. However, after 3 months of calcitriol and zoledronic acid treatment, the parathormone level again increased and was found to be 526 pg/ml (4.7−114 pg/ml). Considering that hyperparathyroidism might be secondary to zoledronic acid treatment, we discontinued its application. Two months after the cessation of zoledronic acid treatment, the parathormone level decreased to 176 pg/ml (4.7−114 pg/ml). The most common electrolyte abnormality associated with zoledronic acid infusion is hypocalcemia [6]. Among breast cancer patients treated in a phase III study of zoledronic acid, hypocalcemia was observed in 39% of patients compared to 7% in the placebo arm [7]. Risk factors for hypocalcemia include pre-existing hypovitaminosis D, hypoparathyroidism, and hypomagnesemia [8–12]. Following zoledronic acid treatment, an increase in parathormone level secondary to hypocalcemia is also reported in the literature [13, 14]. Our patient had several risk factors for developing hypocalcemia such as previous gastric surgery which may Support Care Cancer (2009) 17:469–470 DOI 10.1007/s00520-009-0591-9