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

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Abstract

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.

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Author notes

  1. G. Tsvetov and O. Amitai contributed equally to this work.

Authors and Affiliations

  1. Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center - Beilinson Hospital, 39 Jabotinski St., 4941492, Petah Tikva, Israel

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

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

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

  3. Clalit Healthcare Services, Petah-Tikva, Israel

    O. Amitai

  4. Statistical Consulting Unit, Rabin Medical Center - Beilinson Hospital, 39 Jabotinski St., 4941492, Petah Tikva, Israel

    T. Shochat

  5. Department of Medicine A, Rabin Medical Center - Beilinson Hospital, 39 Jabotinski St., 4941492, Petah Tikva, Israel

    T. Diker-Cohen

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  1. G. Tsvetov
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Correspondence to T. Diker-Cohen.

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The study was approved by the Clalit Helsinki Ethics Committee.

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Tsvetov, G., Amitai, O., Shochat, T. et al. Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?. Osteoporos Int 31, 655–665 (2020). https://doi.org/10.1007/s00198-019-05261-7

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