Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study
Abstract Background Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether den...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-024-11942-2 |
| _version_ | 1797274302570037248 |
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| author | Kazuyo Nakamura Michihiro Kaya Yuki Yanagisawa Keisuke Yamamoto Nana Takayashiki Hirotoshi Ukita Mariko Nagura Kaori Sugiue Mariko Kitajima Kumi Hirano Hiroki Ishida Chiharu Onoda Yutaka Kobayashi Eiji Nakatani Keiichi Odagiri Takaya Suzuki |
| author_facet | Kazuyo Nakamura Michihiro Kaya Yuki Yanagisawa Keisuke Yamamoto Nana Takayashiki Hirotoshi Ukita Mariko Nagura Kaori Sugiue Mariko Kitajima Kumi Hirano Hiroki Ishida Chiharu Onoda Yutaka Kobayashi Eiji Nakatani Keiichi Odagiri Takaya Suzuki |
| author_sort | Kazuyo Nakamura |
| collection | DOAJ |
| description | Abstract Background Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment. Methods We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis. Results Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia. Conclusions Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk. |
| first_indexed | 2024-03-07T14:56:27Z |
| format | Article |
| id | doaj.art-68653e29483f4025a3d904e57c4852f2 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-07T14:56:27Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-68653e29483f4025a3d904e57c4852f22024-03-05T19:24:10ZengBMCBMC Cancer1471-24072024-02-012411810.1186/s12885-024-11942-2Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational studyKazuyo Nakamura0Michihiro Kaya1Yuki Yanagisawa2Keisuke Yamamoto3Nana Takayashiki4Hirotoshi Ukita5Mariko Nagura6Kaori Sugiue7Mariko Kitajima8Kumi Hirano9Hiroki Ishida10Chiharu Onoda11Yutaka Kobayashi12Eiji Nakatani13Keiichi Odagiri14Takaya Suzuki15Shizuoka General HospitalShizuoka General HospitalShizuoka Cancer CenterSeirei Hamamatsu General HospitalIwata City HospitalIwata City HospitalChutoen General Medical CenterJapanese Red Cross Shizuoka HospitalShizuoka City Shizuoka HospitalHamamatsu Medical CenterJA Shizuoka Kohseiren Enshu HospitalYaizu City HospitalFujinomiya City General HospitalShizuoka Graduate University of Public HealthCenter for Clinical Research, Hamamatsu University HospitalShizuoka General HospitalAbstract Background Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment. Methods We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis. Results Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia. Conclusions Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.https://doi.org/10.1186/s12885-024-11942-2DenosumabBone metastasesRenal insufficiencyHypocalcemia |
| spellingShingle | Kazuyo Nakamura Michihiro Kaya Yuki Yanagisawa Keisuke Yamamoto Nana Takayashiki Hirotoshi Ukita Mariko Nagura Kaori Sugiue Mariko Kitajima Kumi Hirano Hiroki Ishida Chiharu Onoda Yutaka Kobayashi Eiji Nakatani Keiichi Odagiri Takaya Suzuki Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study BMC Cancer Denosumab Bone metastases Renal insufficiency Hypocalcemia |
| title | Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study |
| title_full | Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study |
| title_fullStr | Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study |
| title_full_unstemmed | Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study |
| title_short | Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study |
| title_sort | denosumab induced hypocalcemia in patients with solid tumors and renal dysfunction a multicenter retrospective observational study |
| topic | Denosumab Bone metastases Renal insufficiency Hypocalcemia |
| url | https://doi.org/10.1186/s12885-024-11942-2 |
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