Hypocalcemia Associated with Strontium-89 Administration in a Patient with Diffuse Bone Metastases from Neuroendocrine Carcinoma  Masanori Mori, MD, Nada A. Fadul, MD, Eduardo Bruera, MD, Shalini Dalal, MD  Journal of Pain and Symptom Management  Volume 37, Issue 5, Pages 923-929 (May 2009) DOI: 10.1016/j.jpainsymman.2008.05.010 Copyright © 2009 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 1 A positron emission tomography/computed tomography scan showing widespread, metabolically active bone metastases. Journal of Pain and Symptom Management 2009 37, 923-929DOI: (10.1016/j.jpainsymman.2008.05.010) Copyright © 2009 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 2 (a) An electrocardiogram on the day following strontium-89 administration, showing a QTc interval of 453 ms. (b) An electrocardiogram after calcium repletion on the 4th day of strontium-89 administration, showing a normal QT interval. Journal of Pain and Symptom Management 2009 37, 923-929DOI: (10.1016/j.jpainsymman.2008.05.010) Copyright © 2009 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 3 Theoretical model for strontium (Sr2+)-induced hypocalcemia. We hypothesized that Sr2+ affects calcium (Ca2+) homeostasis by stimulating the calcium-sensing receptors (CasRs), which are located in the parathyroid glands, kidneys, and bones. Activation of CasR suppresses parathyroid hormone (PTH) production in the parathyroid glands, leading to increased urinary excretion of Ca2+, decreased production of 1,25-dihydroxyvitamin D3 by the kidneys, and inhibition of Ca2+ release from the bones. Further, Sr2+ also may have direct effects on the kidneys and possibly bones via its agonistic effects on CasR. Low 1,25-dihydroxyvitamin D3 decreases the absorption of Ca2+ from the intestines. These Sr2+ effects may induce or worsen hypocalcemia. Journal of Pain and Symptom Management 2009 37, 923-929DOI: (10.1016/j.jpainsymman.2008.05.010) Copyright © 2009 U.S. Cancer Pain Relief Committee Terms and Conditions