G Tsvetov1,2, O Amitai1,2,3, T Shochat4, I Shimon1,2, A Akirov1,2, T Diker-Cohen5,6,7. 1. Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center - Beilinson Hospital, 39 Jabotinski St., 4941492, Petah Tikva, Israel. 2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Clalit Healthcare Services, Petah-Tikva, Israel. 4. Statistical Consulting Unit, Rabin Medical Center - Beilinson Hospital, 39 Jabotinski St., 4941492, Petah Tikva, Israel. 5. Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center - Beilinson Hospital, 39 Jabotinski St., 4941492, Petah Tikva, Israel. taliadico@gmail.com. 6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. taliadico@gmail.com. 7. Department of Medicine A, Rabin Medical Center - Beilinson Hospital, 39 Jabotinski St., 4941492, Petah Tikva, Israel. taliadico@gmail.com.
Abstract
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.
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 osteoporoticmen 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-dwellingpatients 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.
Authors: C A Naranjo; U Busto; E M Sellers; P Sandor; I Ruiz; E A Roberts; E Janecek; C Domecq; D J Greenblatt Journal: Clin Pharmacol Ther Date: 1981-08 Impact factor: 6.875
Authors: Alison T Stopeck; Allan Lipton; Jean-Jacques Body; Guenther G Steger; Katia Tonkin; Richard H de Boer; Mikhail Lichinitser; Yasuhiro Fujiwara; Denise A Yardley; María Viniegra; Michelle Fan; Qi Jiang; Roger Dansey; Susie Jun; Ada Braun Journal: J Clin Oncol Date: 2010-11-08 Impact factor: 44.544