Endocrine Abstracts

Introduction: Denosumab is an important treatment option for osteoporosis. Rebound hypercalcemia on discontinuation of denosumab is well documented. Denosumab can increase PTH, peaking within 2-4 weeks of administration and subsiding thereafter, therefore making diagnosis of primary hyperparathyroidism (pHPT) difficult. The aim of our case series is to review the calcium fluctuations in relationship to timing of denosumab administration and identify the possibility of rebound hypercalcemia during denosumab treatment.

Methods: A retrospective case-series analysis of patients discussed at metabolic bone multidisciplinary meeting due to elevated calcium on denosumab treatment (2019-2022) was conducted. Calcium was checked as part of standard care during denosumab treatment, and if elevated led to subsequent PTH measurement. Based on the timing of calcium measurement to denosumab administration, the hypercalcemia was classified as pre-denosumab (taken preceding denosumab administration), post-denosumab (within 3 weeks of administration of denosumab) or mid-denosumab (typically between 3 weeks post administration and 2 weeks before next injection)

Results: n=16; all patients had normal calcium preceding denosumab initiation. The patterns identified were:A. One-off pre-denosumab hypercalcemia: (n=3): Elevated calcium noted only once; all were on a pre-denosumab sample. 2 of these had a high PTH on post-denosumab both of which normalized on subsequent pre-denosumab sample; one had persistent PTH throughout.B. Persistent pre-denosumab hypercalcemia: (n=2). These patients had elevated calcium on more than one occasion on pre-denosumab samples. One patient had elevated PTH, but on post-denosumab sample.C. Likely pHPT: (n=5): These patients had high calcium not only in pre but also in the post denosumab samples. 4 had elevated PTH.D. Inconclusive: (n=6). These patients had documented hypercalcemia in pre and mid-denosumab samples but normal readings post-denosumab, therefore likely pointing towards calcium lowering effect of denosumab. 4 had documented high PTH.

Conclusion: Incidental hypercalcemia can be commonly encountered during denosumab treatment. A significant proportion of these patients may represent ‘rebound’ hypercalcemia and less likely to be true pHPT (groups A, B). The normal calcium readings preceding denosumab initiation, timing of the elevated reading (pre-denosumab being elevated) and a lack of consistent PTH raise (normal PTH despite being on Denosumab) may support the likelihood of this phenomenon during denosumab treatment. The possibility of pHPT being unmasked or incidentally idenfied needs to be considered too (groups C, D). This case series depicts the complexities and uncertainties of identifying an aetiology for high calcium during denosumab treatment and hence the need for multi-disciplinary approach and long term prospective studies.