Hypocalcaemia after denosumab in older people following fracture.

Hypocalcaemia following denosumab therapy can be observed in older adults. This is more common if their pre-treatment corrected serum calcium concentrations are less than 2.28 mmol/L. Denosumab remains a safe treatment in older people but we recommend a cautious approach in people at risk.

INTRODUCTION: Previous studies have indicated that denosumab, an anti-RANK ligand (RANKL) monoclonal antibody, for treatment of osteoporosis is well-tolerated. There is little data specifically regarding its adverse effect profile in a hospitalised older person. Primarily, this study wished to determine the frequency of hypocalcaemia following denosumab administration in older people admitted to hospital following fracture. Secondarily, this study wished to determine any associations that may predict the development of hypocalcaemia.

METHODS: This was a prospective study of 33 participants using a paired study design aged 70 years old or more with fragility fractures who were given denosumab in a rehabilitation hospital in Sydney. The primary outcome was the frequency of hypocalcaemia. Hypocalcaemia was defined as corrected serum concentration of less than 2.20 mmol/L on day 14 after denosumab administration.

RESULTS: Of the 33 participants with a mean age of 84.6 ± 1.2 years old, 5 participants (15.2 %) developed hypocalcaemia post injection. A paired t test showed a mean difference between the baseline and post injection calcium concentrations to be 0.059 mmol/L (95 %CI 0.020-0.098; t = 3.080, p = 0.004). Regression analysis showed that pre-denosumab serum calcium concentration correlated with the post-denosumab injection calcium concentration (R = 0.631, 95 %CI 0.288-0.977; p = 0.001). No other variables were significant. Further, a baseline serum calcium concentration of 2.28 mmol/L was able to predict post-denosumab hypocalcaemia with a sensitivity of 80 % and specificity of 86 %.

CONCLUSIONS: Denosumab is a relatively safe treatment of osteoporosis. This study shows that hypocalcaemia following denosumab therapy can be observed in older adults. Clinicians should be aware of this adverse effect when using denosumab in the older people.