Hypocalcaemia is a known side effect of denosumab therapy. The risk increases as renal function decline, with incidence of up to 50% in CKD-4 patients (1). Since osteoporosis affects older population disproportionately, low eGFR is common amongst treated patients since eGFR declines with age (2). In acute renal failure, denosumab may be withheld to mitigate the risk of hypocalcaemia. However, its cessation can lead to high bone turnover and increased fracture risk (3). This poses a conundrum as to whether to continue denosumab and monitor for hypocalcaemia, or to discontinue and monitor for rebound high bone turnover.
We describe an 81-year-old female who presented with acute renal failure (eGFR = 12) from sepsis due to renal calculi. She was on denosumab 6-monthly since 2017 for osteoporosis and L4 fracture. Her inpatient ionized calcium was normal at 1.17 mmol/L (total calcium 2.06 mmol/L, albumin 22g/L). Denosumab was ceased post discharge due to hypocalcemic concerns. Eight months after last dose of denosumab, her bone specific alkaline phosphatase (bsALP) was elevated at 35.2 ug/L reflective of high bone turnover.
Hypocalcaemia is common in the elderly population during severe acute illness (4). It is uncertain whether patients on denosumab may be more prone to hypocalcaemia in the setting of concurrent acute illness. In an Austin Health audit of 108 subjects on established denosumab (≥ 2 doses), 27 (25%) subjects had hypocalcemia in routine or inpatient blood tests, only 3 subjects had eGFR < 35. Whilst subjects on established denosumab were reported to be less prone to hypocalcaemia in the setting of suppressed bone turnover (5), more studies are required in this area whereby age related hypoalbuminemia, differential protein binding with renal impairment, acidaemia during sepsis all pose challenges to calcium interpretation and management of ongoing denosumab treatment.