Hypocalcaemia in patients with metastatic bone disease treated with denosumab

Jean Jacques Body, Henry G. Bone, Richard H. De Boer, Alison T Stopeck, Catherine Van Poznak, Ronaldo Damião, Karim Fizazi, David H. Henry, Toni Ibrahim, Allan Lipton, Fred Saad, Neal Shore, Toshimi Takano, Adam J. Shaywitz, Huei Wang, Oswaldo L. Bracco, Ada Braun, Paul J. Kostenuik

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Abstract Background This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. Methods Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). Results The overall incidence of laboratory events of hypocalcaemia grade ≥2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; >50 versus ≤50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; >20.77 μg/L [median] versus ≤20.77 μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had >2 bone metastases at baseline versus those with >2 bone metastases at baseline. Conclusion Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia.

Original languageEnglish (US)
Article number9488
Pages (from-to)1812-1821
Number of pages10
JournalEuropean Journal of Cancer
Volume51
Issue number13
DOIs
StatePublished - Aug 8 2015
Externally publishedYes

Fingerprint

Hypocalcemia
Bone Diseases
zoledronic acid
Calcium
Bone and Bones
Neoplasm Metastasis
Vitamin D
Vitamin D Deficiency
Denosumab
Bone Remodeling
Incidence
Small Cell Lung Carcinoma
Osteoclasts
Therapeutics
Collagen Type I
Serum
Alkaline Phosphatase
Creatinine
Prostatic Neoplasms

Keywords

  • Bone metastasis
  • Denosumab
  • Hypocalcaemia
  • Risk factors
  • Zoledronic acid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Body, J. J., Bone, H. G., De Boer, R. H., Stopeck, A. T., Van Poznak, C., Damião, R., ... Kostenuik, P. J. (2015). Hypocalcaemia in patients with metastatic bone disease treated with denosumab. European Journal of Cancer, 51(13), 1812-1821. [9488]. https://doi.org/10.1016/j.ejca.2015.05.016

Hypocalcaemia in patients with metastatic bone disease treated with denosumab. / Body, Jean Jacques; Bone, Henry G.; De Boer, Richard H.; Stopeck, Alison T; Van Poznak, Catherine; Damião, Ronaldo; Fizazi, Karim; Henry, David H.; Ibrahim, Toni; Lipton, Allan; Saad, Fred; Shore, Neal; Takano, Toshimi; Shaywitz, Adam J.; Wang, Huei; Bracco, Oswaldo L.; Braun, Ada; Kostenuik, Paul J.

In: European Journal of Cancer, Vol. 51, No. 13, 9488, 08.08.2015, p. 1812-1821.

Research output: Contribution to journalArticle

Body, JJ, Bone, HG, De Boer, RH, Stopeck, AT, Van Poznak, C, Damião, R, Fizazi, K, Henry, DH, Ibrahim, T, Lipton, A, Saad, F, Shore, N, Takano, T, Shaywitz, AJ, Wang, H, Bracco, OL, Braun, A & Kostenuik, PJ 2015, 'Hypocalcaemia in patients with metastatic bone disease treated with denosumab', European Journal of Cancer, vol. 51, no. 13, 9488, pp. 1812-1821. https://doi.org/10.1016/j.ejca.2015.05.016
Body, Jean Jacques ; Bone, Henry G. ; De Boer, Richard H. ; Stopeck, Alison T ; Van Poznak, Catherine ; Damião, Ronaldo ; Fizazi, Karim ; Henry, David H. ; Ibrahim, Toni ; Lipton, Allan ; Saad, Fred ; Shore, Neal ; Takano, Toshimi ; Shaywitz, Adam J. ; Wang, Huei ; Bracco, Oswaldo L. ; Braun, Ada ; Kostenuik, Paul J. / Hypocalcaemia in patients with metastatic bone disease treated with denosumab. In: European Journal of Cancer. 2015 ; Vol. 51, No. 13. pp. 1812-1821.
@article{108a7b89d3844a75a23ff1177e698406,
title = "Hypocalcaemia in patients with metastatic bone disease treated with denosumab",
abstract = "Abstract Background This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. Methods Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). Results The overall incidence of laboratory events of hypocalcaemia grade ≥2 was higher with denosumab (12.4{\%}) than with zoledronic acid (5.3{\%}). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; >50 versus ≤50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; >20.77 μg/L [median] versus ≤20.77 μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had >2 bone metastases at baseline versus those with >2 bone metastases at baseline. Conclusion Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia.",
keywords = "Bone metastasis, Denosumab, Hypocalcaemia, Risk factors, Zoledronic acid",
author = "Body, {Jean Jacques} and Bone, {Henry G.} and {De Boer}, {Richard H.} and Stopeck, {Alison T} and {Van Poznak}, Catherine and Ronaldo Dami{\~a}o and Karim Fizazi and Henry, {David H.} and Toni Ibrahim and Allan Lipton and Fred Saad and Neal Shore and Toshimi Takano and Shaywitz, {Adam J.} and Huei Wang and Bracco, {Oswaldo L.} and Ada Braun and Kostenuik, {Paul J.}",
year = "2015",
month = "8",
day = "8",
doi = "10.1016/j.ejca.2015.05.016",
language = "English (US)",
volume = "51",
pages = "1812--1821",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "13",

}

TY - JOUR

T1 - Hypocalcaemia in patients with metastatic bone disease treated with denosumab

AU - Body, Jean Jacques

AU - Bone, Henry G.

AU - De Boer, Richard H.

AU - Stopeck, Alison T

AU - Van Poznak, Catherine

AU - Damião, Ronaldo

AU - Fizazi, Karim

AU - Henry, David H.

AU - Ibrahim, Toni

AU - Lipton, Allan

AU - Saad, Fred

AU - Shore, Neal

AU - Takano, Toshimi

AU - Shaywitz, Adam J.

AU - Wang, Huei

AU - Bracco, Oswaldo L.

AU - Braun, Ada

AU - Kostenuik, Paul J.

PY - 2015/8/8

Y1 - 2015/8/8

N2 - Abstract Background This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. Methods Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). Results The overall incidence of laboratory events of hypocalcaemia grade ≥2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; >50 versus ≤50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; >20.77 μg/L [median] versus ≤20.77 μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had >2 bone metastases at baseline versus those with >2 bone metastases at baseline. Conclusion Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia.

AB - Abstract Background This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. Methods Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). Results The overall incidence of laboratory events of hypocalcaemia grade ≥2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; >50 versus ≤50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; >20.77 μg/L [median] versus ≤20.77 μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had >2 bone metastases at baseline versus those with >2 bone metastases at baseline. Conclusion Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia.

KW - Bone metastasis

KW - Denosumab

KW - Hypocalcaemia

KW - Risk factors

KW - Zoledronic acid

UR - http://www.scopus.com/inward/record.url?scp=84938740077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938740077&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2015.05.016

DO - 10.1016/j.ejca.2015.05.016

M3 - Article

C2 - 26093811

AN - SCOPUS:84938740077

VL - 51

SP - 1812

EP - 1821

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 13

M1 - 9488

ER -