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][2][3][4][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 ...

Paget’s Disease of Bone and Calcium Homeostasis: Focus on Bisphosphonate Treatment

“…Interestingly, PTH remained signifi cantly increased by 90 % (range 20-252 %) 3 months after ZOL infusion and returned to baseline levels at 12 months, although calcium was normalized by the 10 th day in all patients ( Avramidis et al, 2008 ). This pattern of sustained PTH increase after BPs treatment, despite serum calcium normalization, has been also reported in other metabolic bone diseases including bone metastases ( Sayin and Yazici, 2009 ). Furthermore, there are 2 more case reports of severe, symptomatic hypocalcemia following BPs treatment in patients with PDB ( Stuckey et al, 2001 ;Whitson et al, 2006 ) and one in juvenile Paget's disease ( Polyzos et al, 2010 ).…”

“…On the contrary, osteomalacia was not seen in bone biopsies of 2 patients who received high-dose PAM for PDB resistant to treatment ( Cundy et al, 1996 ). ( Sayin and Yazici, 2009 ) and bone loss following liver transplantation ( Crawford et al, 2006 ). Even in postmenopausal hemodialysis women, who had established secondary hyperparathyroidism, PAM infusion resulted in aggravation of hypocalcemia and secondary hyperparathyroidism ( Lu et al, 2003 ).…”

Hyperparathyroidism Following Denosumab and Zoledronate Therapy in a Secondary Care Setting

“…Studies of denosumab 7,9,10 have shown that plasma PTH levels rise above the reference range (but tend to return to normal toward the end of the dose interval) in association with reduced albumin-adjusted calcium (which tends to remain in the reference range). Although there has been 1 case report of secondary normocalcemic hyperparathyroidism with zoledronate, 11 to our knowledge, there has been only 1 longitudinal study of the effect of a single dose of zoledronate on biochemical parameters, which found that PTH levels rose and calcium levels reduced following therapy; however, both remained within reference ranges. All previous studies have been longitudinal studies of postmenopausal women over a maximum of 12-month (for denosumab) or 24-month (for zoledronate) periods.…”

Transient secondary hyperparathyroidism following intravenous infusion of zoledronic acid

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Dear Editor, We have read with interest the paper of Sayin and Yazici [1], describing a case of secondary hyperparathyroidism following multiple intravenous zoledronic acid (ZOL) infusions in a patient with stomach lymphoma and bone metastases. The authors supported that serum parathyroid hormone (PTH) continued to increase, despite serum calcium and vitamin D normalization, until ZOL infusions were stopped.

Hypocalcemia has been described after ZOL, as well as after other bisphosphonates (BPs), in various conditions, including bone metastases, Paget's disease of bone (PDB), and osteoporosis.

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