Symptomatic hypocalcaemia after treatment with zoledronic acid in a patient with multiple myeloma

Zoledronic acid is a long-acting bisphosphonate used to decrease skeletal events in patients with multiple myeloma and bony metastasis. It is known to lead to asymptomatic hypocalcaemia, but symptomatic hypocalcaemia after its use is rarely reported [1Go]. We report a patient with multiple myeloma who developed symptomatic hypocalcaemia with zoledronic acid.

A 52-year-old female presented with 2 months history of low backache. She had pallor 2++. Investigations revealed haemoglobin 6.8 g/dl, total leucocyte count (TLC) 5300/mm3, platelets 99 000/mm3, performance status N72–L23–M3, no atypical cells, blood urea 99 mg/dl, serum creatinine 2.8 mg/dl, serum calcium 12.4 mg/dl, phosphorus 2.5 mg/dl, total serum proteins 12 g/dl and serum albumin 1.6 g/dl. Skeletal survey revealed lytic lesions on clavicles, scapulae and ribs, along with partial collapse of L3 and L5. Bone marrow showed increased plasma cells, including immature forms. Serum ‘M’ spike was 4.5 g/dl IgG{kappa}; urine ‘M’ spike was negative; serum ß2-microglobulin was 4081 µg/dl.

The patient was treated with melphalan and prednisolone along with zoledronate 4 mg intravenously (i.v.). On day 7 she developed carpopedal spasms. Corrected serum calcium was 7 mg/dl. She responded to i.v. calcium. After 3 weeks she received a second dose of zoledronate and was put on prophylactic oral calcium and vitamin D3. After 5 days she became drowsy and incontinent. There was no evidence of infection, and cerebrospinal fluid examination was normal. However, serum calcium was low (corrected 7.2 mg/dl). She again responded to i.v. calcium gluconate.

Zoledronate inhibits osteoclast-mediated bone resorption and lowers serum calcium in both normal and hypercalcaemic individuals. It is more potent than pamidronate in treating hypercalcaemia of malignancy [1Go]. Individuals are less able to counteract hypocalcaemic stimuli after treatment with zoledronate than pamidronate [2Go]. There are reports of asymptomatic hypocalcaemia after treatment with zoledronate [3Go, 4Go], but symptomatic hypocalcaemia has been reported only once in literature after zoledronate, which was in a case of carcinoma prostate with bony metastasis [1Go]. The present case is the first report of symptomatic hypocalcaemia after the use of zoledronate in a patient with multiple myeloma.

This report highlights the need for constant vigil on serum calcium in patients receiving zoledronate so that calcium replacement therapy can be initiated as early as possible and symptomatic hypocalcaemia be prevented.

D. Singh*, N. S. Khaira and J. S. Sekhon

Dayanand Medical College and Hospital, Ludhiana Punjab, India 141 001

* Email: devinderaiims{at}hotmail.com

References

1. Wellington K, Goa KL. Zoledronic acid: a review of its use in the management of bone metastasis and hypercalcaemia of malignancy. Drugs. 2003; 63: 417–437.[ISI][Medline]

2. Breen TL, Shane E. Prolonged hypocalcaemia after treatment with zoledronic acid in a patient with prostate cancer and vitamin D deficiency. J Clin Oncol 2004; 22: 1531–1532.[Free Full Text]

3. Body JJ, Lortholary A, Romieu G et al. A dose finding study of zoledronate in hypercalcaemic cancer patients. J Bone Miner Res 1999; 14: 1557–1561.[ISI][Medline]

4. Major PP, Coleman RE. Zoledronic acid in the treatment of hypercalcaemia of malignancy: Results of the international clinical development program. Semin Oncol 2001; 28: 17–24.[CrossRef]





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