Denosumab-induced hypocalcemia in patients with osteoporosis:​ can you know who will get low?

Tsvetov, G.; Amitai, O.; Shochat, T.; Shimon, I.; Akirov, A.; Diker-Cohen, T.

Affiliations

¹Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel

²Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

³Clalit Healthcare Services, Petah-Tikva, Israel

⁴Statistical Consulting Unit, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel

⁵Department of Medicine A, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel

Abstract and keywords

Summary: Hypocalcemia was reported at low rates (0.05–1.7%) in denosumab-treated postmenopausal women with osteoporosis. This real-life study shows a 7.4% rate of denosumab-induced hypocalcemia in community-dwelling osteoporotic men and women. Pretreatment serum calcium and creatinine levels are major predictors for this complication. Serum-calcium monitoring may help to identify and prevent severe hypocalcemia.

Purpose: RCTs have reported a 0.05–1.7% rate of hypocalcemia in denosumab-treated postmenopausal women with osteoporosis, but long-term real-life data are lacking. We assessed the rate of hypocalcemia in osteoporotic community-dwelling patients treated with denosumab.

Methods: A retrospective analysis was conducted based on medical records (2010–2018) from a large HMO. An albumin-adjusted serum calcium concentration lower than 8.5 mg/dL was defined as hypocalcemia.

Results: We included 2005 patients (93% women, mean age 76 ± 9 years). Hypocalcemia developed during treatment in 149 patients (7.4%; 1% less than 8 mg/dL): in 66 after 0.5–1 years; 48 after 1–2 years; 35 after > 2 years. On comparison of the hypocalcemic and normocalcemic patients, the strongest predictors of hypocalcemia were pretreatment levels of albumin-adjusted serum calcium (9.1 ± 0.4 vs. 9.4 ± 0.5 mg/dL, respectively; p < 0.05) and creatinine (0.9 ± 0.5 vs. 0.8 ± 0.3 mg/dL, respectively; p < 0.05). The hypocalcemia rate increased in parallel to a decrease in eGFR (p = 0.032 for the difference between eGFR ranges). Baseline calcium level ≤ 9.31 mg/dL predicted hypocalcemia with a sensitivity of 77% and specificity of 56%. A model of (− 2)*calcium + creatinine predicted hypocalcemia (3.7% when lower and 17.1% when higher than − 17.4). Gender, age, 25-hydroxyvitamin-D, parathyroid hormone, alkaline phosphatase, and whether denosumab was given as first or advanced line of osteoporotic therapy had no predictive value.

Conclusion: Real-life rates of denosumab-induced hypocalcemia are higher than previously reported. Hypocalcemia might develop after each dose of denosumab in ongoing treatment. Adequate calcium and vitamin D supplementation are needed. Serum calcium monitoring is advised in high-risk patients for early detection of severe hypocalcemia.

Keywords: Adverse event; Denosumab; Hypocalcemia; Osteoporosis; Safety

Links

DOI: 10.1007/s00198-019-05261-7

PubMed: 31838550

WoS: 000519860300006

History

Received: 2019-06-27

Accepted: 2019-12-05

Online: 2019-12-14

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Cited By (3)

Year	Entry
2020	Kim KJ, Hong N, Lee S, Kim M, Rhee Y. A simple-to-use score for identifying individuals at high risk of denosumab-associated hypocalcemia in postmenopausal osteoporosis: a real-world cohort study. Calcif Tiss Int. December 2020;107(6):567-575.
2023	Cowan A, Jeyakumar N, McArthur E, Fleet JL, Kanagalingam T, Karp I, Khan T, Muanda FT, Nash DM, Silver SA, Thain J, Weir MA, Garg AX, Clemens KK. Hypocalcemia risk of denosumab across the spectrum of kidney disease: a population-based cohort study. J Bone Miner Res. May 2023;38(5):650-658.
2020	Ho P, Tan EF, Su S, Mallya J. Correspondence to "Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?" Osteoporos Int. August 2020;31(8):1597-1597.