Bone Abstracts

Background: Denosumab is a highly effective treatment for osteoporosis but poses a substantial risk of profound hypocalcaemia in patients with advanced chronic kidney disease (CKD), driven by a rapid shift in skeletal calcium flux following the abrupt suppression of osteoclast-mediated bone resorption. We hypothesised that an off-label 30 mg "bridging dose" would provide an attenuated depth and duration of RANKL inhibition compared to the licensed 60 mg dose, thereby limiting the magnitude of the calcium nadir. This study evaluates the safety and biochemical efficacy of this initiation strategy in a high-risk cohort.

Methods: A retrospective service evaluation was conducted on patients receiving 30 mg denosumab at a tertiary metabolic bone centre between January 2021 and December 2025. All patients underwent pre-treatment Vitamin D optimisation and a mandatory two-week post-dose biochemical review. Hypocalcaemia was defined as adjusted calcium 2.20 mmol/L. Demographic, biochemical and outcome data were reviewed, including renal function, calcium, vitamin D, post-dose hypocalcaemia, and subsequent escalation to standard dose.

Results: Seventy-one patients were included (mean age 84; 81.7% female), of whom 88.7% had sustained prior fragility fractures. A significant proportion (43.7%) had baseline eGFR 30 mL/min/1.73m². Post-dose hypocalcaemia occurred in 19/71 (26.8%) patients. All episodes were biochemically mild, asymptomatic, and none required hospitalisation or led to treatment cessation. Hypocalcaemia was significantly more prevalent in men than women (69.2% vs 17.2%; P 0.001) and more likely in younger patients (75y 60%, 75-84y 29.4%, 84y 18.2%, P 0.025). Specifically, all CKD5 patients developed biochemical hypocalcaemia compared to 21.4% in CKD4 and 23.7% in CKD3 (P 0.012). The mean serum calcium reduction was similarly associated with CKD category (CKD5, 0.577mmol/L vs CKD4, 0.148mmol/L and CKD3, 0.091mmol/L, P 0.005). Overall, 47/71 patients (66.2%) were subsequently escalated to licensed 60 mg dosing, with no further hypocalcaemia reported.

Conclusion: This evaluation demonstrates that a 30 mg denosumab test dose is a viable strategy for initiating therapy in patients at high risk of mineral instability. By facilitating a controlled individual assessment of the biochemical response, this bridging protocol ensures a safe transition to the licensed 60 mg dose for those most vulnerable to hypocalcaemia.