Abstract
Summary
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.
Similar content being viewed by others
References
Bliuc D et al. (2013) Compound risk of high mortality following osteoporotic fracture and refracture in elderly women and men. J Bone Miner Res 28(11):2317–2324. doi:10.1002/jbmr.1968
Osteoporosis prevention, diagnosis, and therapy. JAMA., 2001. 285(6): p. 785–95
Brown JP et al. (2013) Discontinuation of denosumab and associated fracture incidence: analysis from the fracture reduction evaluation of denosumab in osteoporosis every 6 months (FREEDOM) trial. J Bone Miner Res 28(4):746–752. doi:10.1002/jbmr.1808
Cummings SR et al. (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765. doi:10.1056/NEJMoa0809493
Rizzoli R et al. (2011) Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis. Calcif Tissue Int 89(2):91–104. doi:10.1007/s00223-011-9499-8
Bridgeman MB, Pathak R (2011) Denosumab for the reduction of bone loss in postmenopausal osteoporosis: a review. Clin Ther 33(11):1547–1559. doi:10.1016/j.clinthera.2011.10.008
Ershova OB et al. (2014) Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis. Ter Arkh 86(10):60–64
Qi WX et al. (2013) Incidence and risk of denosumab-related hypocalcemia in cancer patients: a systematic review and pooled analysis of randomized controlled studies. Curr Med Res Opin 29(9):1067–1073. doi:10.1185/03007995.2013.813840
McCormick BB, Davis J, Burns KD (2012) Severe hypocalcemia following denosumab injection in a hemodialysis patient. Am J Kidney Dis 60(4):626–628. doi:10.1053/j.ajkd.2012.06.019
Fujita T et al. (1976) Aging and parathyroid hormone secretion. J Gerontol 31(5):523–526
Sherman SS, Hollis BW, Tobin JD (1990) Vitamin D status and related parameters in a healthy population: the effects of age, sex, and season. J Clin Endocrinol Metab 71(2):405–413
Hill PA (1998) Bone remodelling. Br J Orthod 25(2):101–107
Brown WW et al. (1986) Aging and the kidney. Arch Intern Med 146(9):1790–1796
Chen JS et al. (2006) Effect of age-related chronic immobility on markers of bone turnover. J Bone Miner Res 21(2):324–331
LeBlanc A et al. (1995) Calcium absorption, endogenous excretion, and endocrine changes during and after long-term bed rest. Bone 16(4 Suppl):301S–304S
Sato Y et al. (2001) Changes in bone and calcium metabolism following hip fracture in elderly patients. Osteoporos Int 12(6):445–449
Shigematsu T et al. (1997) Changes in bone and calcium metabolism with space flight. Osteoporos Int 7(Suppl 3):S63–S67
Block GA et al. (2012) A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res 27(7):1471–1479. doi:10.1002/jbmr.1613
Levin A et al. (2007) Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 71(1):31–38
Muqeet Adnan M et al. (2014) Severe hypocalcemia due to denosumab in metastatic prostate cancer. Case Rep Nephrol 2014:565393. doi:10.1155/2014/565393
Bekker PJ et al. (2004) A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Resn 19(7):1059–1066
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was approved by the southeastern Sydney Local Health District Human Research Ethics Committee in June 2015 as a low/negligible risk research project with HREC ref. 15/080 LNR/15/POWH/160.
Conflicts of interest
None.
Rights and permissions
About this article
Cite this article
Chen, J., Smerdely, P. Hypocalcaemia after denosumab in older people following fracture. Osteoporos Int 28, 517–522 (2017). https://doi.org/10.1007/s00198-016-3755-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-016-3755-8