Hypercalcemia in Patients Treated with Oral Bisphosphonates for Tumor-Induced Osteolysis


  • MichaÅ‚ Holecki Department of Internal Medicine and Metabolic Diseases, Medical University of Silesia, Katowice
  • Anna Skorupa Department of Anaesthesiology and Intensive Care, Medical University of Silesia, Katowice
  • Jan DuÅ‚awa Department of Internal Medicine and Metabolic Diseases, Medical University of Silesia, Katowice
  • Jerzy Chudek Department of Pathophysiology, Medical University of Silesia, Katowice




bisphosphonates, hypercalcemia, malignancy, osteolysis, bone resorption.


Objective: Hypercalcemia as the consequence of an excessive bone resorption is a common complication in patients with cancer. The aim of the study was to analyze the prevalence of hypercalcemia in patients with tumor-induced osteolysis starting therapy with bisphosphonates.

Methods: The questionnaire-based survey (data collected during three consecutive examinations within a 3-month period) was conducted among 1,450 patients treated with bisphosphonates for tumor-induced osteolysis.

Results: Hypercalcemia was found in 8.7% respondents starting the treatment with bisphosphonates. The most common cause of malignancy-associated hypercalcemia was prostate cancer, multiple myeloma and breast cancer. On the other hand, hypercalcemia was the most prevalent among patients with multiple myeloma, metastatic cancer of an unknown primary origin and bladder cancer. Metastases were reported in 342 patients, while pathological fractures in 37. The normalization of calcium level was obtained in 91.4% of the patients treated with bisphosphonates, mostly clodronate. During the bisphosphonate therapy, pathological fractures occurred in 4.6% of patients and the percentage of the patients reporting bone pain decreased from 79.9% to 30.9%.

Conclusion: Multiple myeloma, prostate and breast cancer are the most common causes of hypercalcemia of malignancy in patients with tumor-induced osteolysis starting therapy with bisphosphonates.


Download data is not yet available.


Metrics Loading ...


Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352:373-9.

Mundy GR. Pathogenesis of hypercalcemia of malignancy. Clin Endocrinol (Oxf). 1985;23:705-4.

Bunn PA Jr, Schechter GP, Jaffe E, et al. Clinical course of retrovirus-associated adult T-cell lymphoma in the United States. N Engl J Med. 1983;309:257-64.

Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer. 1987;55:61-6.

Clines GA, Guise TA. Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. Endocr Relat Cancer. 2005;12:549-83.

Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21-33.

Croucher PI, De Hendrik R, Perry MJ, et al. Bisphosphonates in multiple myeloma. Cochrane Database Syst Rev. 2002;3:CD003188.

Gordon S, Helfrich MH, Sati HI, et al. Pamidronate causes apoptosis of plasma cells in vivo in patients with multiple myeloma. Br J Haematol. 2002;119:475-83.

Coleman RE. Bisphosphonates in breast cancer. Ann Oncol. 2005;16:687-95.

Horwitz MJ, Stewart AF. Hypercalcemia associated with malignancy. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. American Society of Bone and Mineral Research. 2006:195-199.

Francini G, Petrioli R, Maioli E, et al. Hypercalcemia in breast cancer. Clin Exp Metastasis. 1993;11:359-67.

Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2:584-93.

Quinn JM, Matsumura Y, Tarin D, McGee J, Athanasou N. Cellular and hormonal mechanisms associated with malignant bone resorption. Lab Invest. 1994;71:465-71.

Camp NJ, Werner TL, Cannon-Albright LA. Familial myeloma. N Engl J Med. 2008; 359: 1734-5.

Higashi Y, Kawamura J, Kanamaru H, Kakehi Y, Yoshida O. 20 cases of hypercalcemia associated with urogenital malignancies. Hinyokika Kiyo. 1984; 30: 599-607.

Saunders Y, Ross JR, Broadley KE, Edmonds PM, Patel S. Steering Group. Systematic review of bisphosphonates for hypercalcaemia of malignancy. Palliat Med. 2004;18:418-31.

Laakso M, Lahtinen R, Virkkunen P, Elomaa I. Subgroup and cost-benefit analysis of the Finnish multicentre trial of clodronate in multiple myeloma. Br J Haematol. 1994;87:725-9.

Elomaa I, Blomqvist C, Porkka L, Lamberg-Allardt C, Borgström GH. Treatment of skeletal disease in breast cancer: a controlled clodronate trial. Bone. 1987;8(Suppl 1):53-56.

Clemens MR, Fessele K, Heim ME. Multiple myeloma: effect of daily dichloromethylene bisphosphonate on skeletal complications. Ann Hematol. 1993;66:141-6.

Pavlakis N, Schmidt R, Stockler M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev. 2005;3:CD003474.

Terpos E, Dimopoulos MA, Berenson J. Established role of bisphosphonate therapy for prevention of skeletal complications from myeloma bone disease. Crit Rev Oncol Hematol. 2011;77(Suppl 1):13-23.

Mantyh PW, Clohisy DR, Koltzenburg M, Hunt S. Molecular mechanisms of cancer pain. Nature Reviews Cancer. 2002;2:201–9.

Lee YP, Schwarz EM, Davies M, et al. Use of zoledronate to treat osteoblastic versus osteolytic lesions in a severecombined- immunodeficient mouse model. Cancer Research. 2002;62:5564–70.

Derenne S, Amiot M, Barille S, et al. Zoledronate is a potent inhibitor of myeloma cell growth and secretion of IL-6 and MMP-1 by the tumoral environment. Journal of Bone and Mineral Research. 1999;14:2048–56.

Senaratne SG, Pirianov G, Mansi JL, Arnett TR, Colston KW. Bisphosphonates induce apoptosis in human breast cancer cell lines. British Journal of Cancer. 2000;82:1459–68.

Boissier S, Magnetto S, Frappart L, et al. Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Research. 1997;57:3890–4.

Fournier P, Boissier S, Filleur S, et al. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Research. 2002;62:6538–44.

Lahtinen R, Laakso M, Palva I, Virkkunen P, Elomaa I. Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group. Lancet. 1992; 340:1049-52.

Yuen KK, Shelley M, Sze WM, Wilt T, Mason MD. Bisphosphonates for advanced prostate cancer. Cochrane Database Syst Rev. 2006;4:CD006250.




How to Cite

Holecki M, Skorupa A, Duława J, Chudek J. Hypercalcemia in Patients Treated with Oral Bisphosphonates for Tumor-Induced Osteolysis. Open Access Maced J Med Sci [Internet]. 2013 Dec. 15 [cited 2021 Apr. 16];1(1):54-8. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2013.011



B - Clinical Sciences

Most read articles by the same author(s)