P138 Real-world incidence and management of hypocalcaemia after denosumab administration in patients with chronic kidney disease: a UK secondary-care based audit
Authors: Hardcastle Sarah A , Alshakh Randa , Webb Jackie , Warren Susan , Ahmed Tehseen 
Published: April 2022

Abstract

Background/Aims
Hypocalcaemia is a recognized complication of denosumab therapy in patients with renal impairment. Our local protocol states that patients with creatinine clearance (CrCl) &lt;35ml/min should have blood tests for calcium and renal function weekly for 4 weeks after each denosumab injection. This audit aimed to assess whether such patients underwent appropriate blood monitoring, and to evaluate the incidence, severity and management of hypocalcaemia in this patient population.

Methods
Patients who commenced denosumab between 2011 and March 2020 were eligible for inclusion if they had CrCl &lt;35ml/min. Data collection was undertaken through retrospective review of clinical records and pathology systems.

Results
53 patients fitting the above criteria were identified. One further patient with eGFR 32ml/min was also included, giving 54 patients in total for analysis. The age range of the patients was 76-97, 9/54 (17%) were male. None were on renal replacement therapy. 29/52 patients (56%) missed one or more post-injection blood tests (incomplete data n = 2). The most commonly missed blood tests were the 1st and 4th weekly checks. 18/54 (33%) developed hypocalcaemia at some point after starting denosumab. In 8/18 this was a one-off episode, but 10/18 experienced recurrent hypocalcaemia. Lowest values for adjusted calcium varied from 1.83-2.18mmol/l. Only 3 patients had a value &lt;2.0mmol/l. Patients who did and did not develop hypocalcaemia had a mean (SD) CrCl of 27.3 (5.03) and 27.8 (5.19) respectively. There was no significant difference in CrCl between these two groups (unpaired t-test, p value 0.7338). Comparing those with &gt;1 episode of hypocalcaemia with the rest of the group, again the mean CrCl was not significantly different (26.6 vs. 27.9, p = 0.47). The three patients who developed more severe hypocalcaemia (adjusted calcium &lt;2.00mmol/l) had CrCl values of 33.2, 24.0 and 21.0ml/min. 17/18 patients who developed hypocalcaemia were on combined calcium and vitamin D supplementation. One patient was on vitamin D3 alone due to intolerance of calcium supplements - they developed mild hypocalcaemia only (nadir 2.13mmol/l) and had CrCl 27ml/min. One patient with CrCl 21ml/min became hypercalcaemic on combined supplementation which was later switched to alfacalcidol by the renal team. Hypocalcaemia was most commonly observed 1-week post-injection, but delayed onset of hypocalcaemia 4-6 weeks post-injection was observed in a few cases. Most episodes resolved within 1-2 weeks, almost all within 4 weeks. One patient died 2 weeks after their 2nd denosumab dose from an unrelated cause - adjusted calcium was 2.16 just prior to death. Additional oral calcium was given in two patients; in one of these, hypocalcaemia recurred after a subsequent injection despite additional supplements, and denosumab was discontinued.

Conclusion
In a real-world setting, hypocalcaemia after denosumab in patients with reduced renal function (not on renal replacement therapy) is generally mild and rarely requires treatment.

Disclosure
S.A. Hardcastle: Other; S.H. received conference fee funding from Lilly (UK) in 2018. R. Alshakh: None. J. Webb: None. S. Warren: None. T. Ahmed: None.