Skip to main content

Advertisement

Log in

Management of malignancy-associated hypercalcemia

  • Published:
Clinical Reviews in Bone and Mineral Metabolism Aims and scope Submit manuscript

Conclusion

Rehydration and bisphosphonates represent the mainstay of the management of hypercalcemia associated with malignancy with successful achievement of normocalcemia in some 90% of patients. New experimental approaches are currently being tested. and the antiosteoclastic potential of osteoprotegrin appars to be promising.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ralston SH, Gallagher SJ, Patel U, Campbell J, Boyle IT. 1990 Cancer-associated hypercalcemia: morbidity and mortality. Clinical exprience in 126 treated patients. Ann Intern Med 112:499–504.

    PubMed  CAS  Google Scholar 

  2. Vassilopoulous-Sellin R, Mewman BM, Taylor SH, Guinee VF. 1993 Incidence of hypercalcaemia in patients with malignancy referred to a comprehensive cancer center. Cancer 71:1309–1312.

    Google Scholar 

  3. Mundy GR. 1988 Hypercalcemia of malignancy revisited. J Clin Invest 82:1–6.

    PubMed  CAS  Google Scholar 

  4. Martin TJ, Grill V. 1992 Hypercalcaemia in cancer. J Steroid Biochem Mol Biol 43:123–129.

    PubMed  CAS  Google Scholar 

  5. Watters J, Gerrand G, Dodwell D. 1996 The management of malignant hypercalcaemia. Drugs 52:837–848.

    PubMed  CAS  Google Scholar 

  6. Guise TA, Mundy GR. 1998 Cancer and Bone. Endocr Rev 19:18–15.

    PubMed  CAS  Google Scholar 

  7. Ralston SH, Fogelman I, Gardiner MD, Boyle IT, 1984 Relative contribution of humoral and metastatic factors to the pathogenesis of hypercalcemia in malignancy. Br Med J 288:1405–1408.

    CAS  Google Scholar 

  8. Harinck HIJ, Bijvoet OLM, Plantingh AST, et al. 1987 Role of bone and kidney in tumor-induced hypercalcaemia and its treatment with bisphosphonate and sodium chloride. Am J Med 82:1133–1142.

    PubMed  CAS  Google Scholar 

  9. Bonjour JP, Rizzoli R. 1989 Pathophysiological aspects and therapeutic approaches to tumoral osteolysis and hypercalcemia. Recent Results Cancer Res 116:29–39.

    PubMed  CAS  Google Scholar 

  10. Buchs B, Rizzoli R, Bonjour JP. 1991 Evaluation of bone resorption and renal tubular reabsorption of calcium and phosphate in malignant and non-malignant hypercalcemia. Bone 12:47–56.

    PubMed  CAS  Google Scholar 

  11. Ralston SH. 1994 Pathogenesis and management of cancer associated hypercalcaemia. Cancer Surv 21:179–196.

    PubMed  CAS  Google Scholar 

  12. Walls J, Ratcliffe WA, Howell A, Bundred NJ. 1994 Response to intravenous bisphosphonate therapy in hypercalcaemic patients with or without bone metastases: the role of parathyroid hormone-related protein. Br J Cancer 70:169–172.

    PubMed  CAS  Google Scholar 

  13. Walls J, Ratcliffe WA, Howell A, Bundred NJ, 1994 Parathyroid hormone and parathyroid hormone-related protein in the investigation of hypercalcaemia in two hospital populations. Clin Endocrinol 41:407–413.

    CAS  Google Scholar 

  14. Wysolmerski JJ, Broadus AE. 1994 Hypercalcaemia of malignancy: the central role of parathyroid-related protein. Annu Rev Med 45:189–200.

    PubMed  CAS  Google Scholar 

  15. Duffy JL, Suzuky Y, Churg J, 1971 Acute calcium nephropathy. Arch Pathol 91:340–350.

    PubMed  CAS  Google Scholar 

  16. Lins LE. 1978 Reversible renal failure caused by hypercalcaemia. A retrospective study. Acta Med Scand 203:309.

    PubMed  CAS  Google Scholar 

  17. Ganote CE, Philipsborn DS, Chen E, Carone FA. 1975 Acute calcium nephrotoxicity. An electromicroscopical and semiquantitative light microscopical study. Arch Pathol 99:650–657.

    PubMed  CAS  Google Scholar 

  18. Levi M, Peterson L, Berl T. 1983 Mechanism of concentrating defect in hypercalcaemia. Role of polydypsia and prostaglandins. Kidney Int 23:489–497.

    PubMed  CAS  Google Scholar 

  19. Humes HD. 1986 Role of calcium in pathogenesis of acute renal failure. Am J Physiol 250:579–589.

    Google Scholar 

  20. Hosking DJ, Cowley AJ, Bucknall CA. 1981 Rehydration in the treatment of severe hypercalcaemia. Q J Med 50:473–481.

    PubMed  CAS  Google Scholar 

  21. Bilezikian JP. 1992 Management of acute hypercalcemia. N Engl J Med 326:1196–1203.

    PubMed  CAS  Google Scholar 

  22. Sleeboom HP, Bijvoet OLM, van Oosterom AT, Gleed JH, O'Riordan JLH. 1983 Comparison of intravenous (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate and volume repletion in tumour-induced hypercalcaemia. Lancet 1:239–244.

    Google Scholar 

  23. Miach PJ, Dawborne JK, Martin TJ, et al. 1975 Management of hypercalcaemia of malignancy by peritoneal dialysis. Med J Aust 1:782–784.

    PubMed  CAS  Google Scholar 

  24. Kyle RA. 1975 Multiple myeloma: review of 869 cases. Mayo Clin Proc 50:29–40.

    PubMed  CAS  Google Scholar 

  25. Mundy GR, Bertoline DR. 1986 Bone destruction and hypercalcemia in plasma cell myeloma. Semin Oncol 13:291–299.

    PubMed  CAS  Google Scholar 

  26. Stashenko P, Dewhirst FE, Peros WJ, et al. 1987 Synergistic interactions between interleukin 1, tumor necrosis factor and lymphotoxin in bone resorption. J Immunol 138:1464–1468.

    PubMed  CAS  Google Scholar 

  27. Mundy GR, 1991 Mechanisms of osteolytic bone destruction. Bone 12(Suppl 1):1–6.

    Google Scholar 

  28. Taube T, Elomaa I, Blomqvist C, et al. 1994 Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer. Bone 15:161–166.

    PubMed  CAS  Google Scholar 

  29. Bataille R, Chappard D, Basle M. 1995 Excessive bone resorption in human plasmacytomas: direct induction by tumor cells in vivo. Br J Haematol 90:721–724.

    PubMed  CAS  Google Scholar 

  30. Croucher PI, Apperley JF. 1998 Bone disease in multiple myeloma. Br J Haematol 103:902–910.

    PubMed  CAS  Google Scholar 

  31. Fleisch H. 1991 Bisphosphonates. Pharmacology and use in the treatment of tumour-induced hypercalcaemia and metastatic bone disease. Drugs 42:919–944.

    PubMed  CAS  Google Scholar 

  32. Kanis JA, McCloskey EV, Taube T, et al. 1991 Rationale for the use of bisphosphonates in bone metastases. Bone 12(Suppl 1):13–18.

    Google Scholar 

  33. Bonjour JP, Rizzoli R. 1992 Antioteolytic agents in the management of hypercalcaemia. Ann Oncol 3:589–590.

    PubMed  CAS  Google Scholar 

  34. Coleman RE, Purohit OP. 1993 Osteoclast inhibition for the treatment of bone metastases. Cancer Treat Rev 19:79–103.

    PubMed  CAS  Google Scholar 

  35. Fleisch H. 1998 Bisphosphonates: mechanism of action. Endocr Rev 19:80–100.

    PubMed  CAS  Google Scholar 

  36. Rodan GA. 1998 Mechanism of action of bisphosphonates. Annu Rev Toxicol 38:375–388.

    CAS  Google Scholar 

  37. Russell RGG, Rogers MJ, Frith JC, et al. 1999 The pharmacology of bisphosphonates and new insights into their mechanism of action. J Bone Miner Res 14(Suppl 2):56–65.

    Google Scholar 

  38. van Beek E, Pieterman E, Cohen L, Lowik C, Papapoulos S. 1999 Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun 264:108–111.

    PubMed  Google Scholar 

  39. Bergstrom JD, Bostedor RG, Masarachia PJ, Reszka AA, Rodan G. 2000 Alendronate is a specific nanomolar inhibitor of farnesyldiphosphate synthase. Arch Biochem Biophys 373:231–241.

    PubMed  CAS  Google Scholar 

  40. Shipman CM, Rogers MJ, Apperley JF, Russell RGG, Croucher PI. 1997 Bisphosphonate induces apoptosis in human myeloma cell lines: a novel anti-tumour activity. Br J Haematol 98:665–672.

    PubMed  CAS  Google Scholar 

  41. Aparicio A, Gardner A, Tu Y, Savage A, Berenson J, Lichtenstein A. 1998 In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates. Leukemia 12:220–229.

    PubMed  CAS  Google Scholar 

  42. Yoneda T, Michigami T, Yi B, et al. 2000 Actions of bisphosphonates on bone metastasis in animal models of breast carcinoma. Cancer 88:2979–2988.

    PubMed  CAS  Google Scholar 

  43. van der Pluijm G, Vloedgraven H, van Beek E, van der Wee-Pals L, Lowik C, Papapoulos S. 1996 Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 98:698–705.

    PubMed  Google Scholar 

  44. Boissier S, Magnetto S, Frappart L, et al. 1997 Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 57:3890–3894.

    PubMed  CAS  Google Scholar 

  45. Boissier S, Ferreras M, Peyruchaud O, et al. 2000 Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res 60:2949–2954.

    PubMed  CAS  Google Scholar 

  46. Kanis JA, Percival RC, Yates AJP, Urwin GH, Hamdy NAT. 1986 Effects of diphosphonates in hypercalcaemia due to neoplasia. Lancet 1:615–616.

    PubMed  CAS  Google Scholar 

  47. Hoekman K, Tjandra YI, Papapoulos SE. 1991 The role of 1,25-dihydroxyvitamin D in the maintenance of hypercalcemia in a patient with an ovarian carcinoma producing parathyroid hormone-related protein. Cancer 68:642–647.

    PubMed  CAS  Google Scholar 

  48. Body JJ, Dumon JC. 1994 Treatment of tumor-induced hypercalcaemia with the bisphosphonate pamidronate: dose-response relationship and influence of the tumour type. Ann Oncol 5:359–363.

    PubMed  CAS  Google Scholar 

  49. Chapuy MC, Meunier PJ, Alexandre CM, Vignon EP, 1980 Effects of disodium dichloromethylene diphosphonate on hypercalcaemia produced by bone metastases. J Clin Invest 65:1243–1247.

    PubMed  CAS  Google Scholar 

  50. Jacobs TP, Sins ES, Bilezikian JP, et al. 1981 Hypercalcemia of malignancy: treatment with intravenous dichloromethylene diphosphonate. Ann Intern Med 94:312–316.

    PubMed  CAS  Google Scholar 

  51. Paterson AD, Kanis JA, Cameron EC, et al. 1983 The use of dichloromethylene diphosphonate for the management of hypercalcaemia in multiple myeloma. Br J Haematol 54:121–132.

    PubMed  CAS  Google Scholar 

  52. Percival RC, Paterson AD, Yates AJP, et al. 1985 Treatment of malignant hypercalcaemia with clodronate. Br J Cancer 51:665–669.

    PubMed  CAS  Google Scholar 

  53. Canfield RE, Siris ES, Jacobs TP, 1987 Dichloromethylene diphosphonate action in hematologic and other malignancies. Bone 8(Suppl 1):S57-S62.

    PubMed  Google Scholar 

  54. Urwin GH, Yates AJP, Gray RES, et al. 1987 Treatment of the hypercalcaemia of malignancy with intravenous clodronate. Bone 8(Suppl 1):S43-S51.

    PubMed  Google Scholar 

  55. Ralston SH, Gallagher SJ, Patel U, et al. 1989 Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia. Lancet 2:1180–1182.

    PubMed  CAS  Google Scholar 

  56. O'Rourke NP, McCloskey EV, Vasikaran S, Eyres K, Fern D, Kanis JA, 1993 Effective treatment of malignant hypercalcaemia with a single intravenous infusion of clodronate. Br J Cancer 67:560–563.

    PubMed  Google Scholar 

  57. Purohit OP, Radstone CR, Anthony C, Kanis JA, Coleman RE, 1995 A randomised double-blind comparison of intravenous pamidronate and clodronate in the hypercalcaemia of malignancy. Br J Cancer 72:1289–1293.

    PubMed  CAS  Google Scholar 

  58. Ralston SH, Dryburgh FJ, Cowan RA, Gardner MD, Jenkins AS, Boyle IT. 1985 Comparison of aminopropylidene diphosphonate, mythramycin and corticosteroids/calcitonin in treatment of cancer-associated hypercalcaemia. Lancet 2:907–910.

    PubMed  CAS  Google Scholar 

  59. Thiebaud D, Jaeger PH, Burckhardt, P. 1986 A single day treatment of tumor-induced hypercalcemia by amino-hydroxypropylidene bisphosphonate. J Bone Miner Res 1:555–562.

    PubMed  CAS  Google Scholar 

  60. Thiebaud D, Portmann L, Jaeger P, Jaquet AF, Burckhardt P, 1986 Oral versus intravenous AHBP (APD) in the treatment of hypercalcaemia of malignancy. Bone 7:247–253.

    PubMed  CAS  Google Scholar 

  61. Man Z, Otero AB, Rendo P, et al. 1990 Use of pamidronate for multiple myeloma osteolytic lesions. Lancet 335:663.

    PubMed  CAS  Google Scholar 

  62. Nussbaum SR, Younger J, Vandepol CJ, et al. 1993 Single-dose intravenous pamidronate for the treatment of hypercalcaemia of malignancy: comparison of 30-, 60-, 90-mg doses. Am J Med 95:297–304.

    PubMed  CAS  Google Scholar 

  63. Body JJ, Magritte A, Seraj F, Sculier JP, Borkowski A. 1989 Aminohydroxypropylidene biphosphonate (APD) treatment for tumour-associated hypercalcaemia: a randomized comparison between a 3-day treatment and single 24-hour infusions. J Bone Miner Res 4:923–928.

    PubMed  CAS  Google Scholar 

  64. Morton AR, Cantrill JA, Craig AE, et al. 1988 Single dose versus daily intravenous aminohydroxypropylidene bisphosphonate (APD) for the hypercalcaemia of malignancy. Br Med J 296:811–814.

    CAS  Google Scholar 

  65. Sawyer N, Newstead CH, Drummond A, Cummingham J. 1990 Fast (4-h) or slow (24-h) infusions of pamidronate disodium (aminohydroxypropylidene disphosphonate APD) as single shot treatment of hypercalcaemia. Bone Miner 9:121–128.

    PubMed  CAS  Google Scholar 

  66. Pecherstorfer M, Herrmann Z, Body JJ, et al. 1996 Randomised phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcaemia of malignancy. J Clin Oncol 14:268–276.

    PubMed  CAS  Google Scholar 

  67. Ralston SH, Thiebaud D, Herrmann Z, et al. 1997 Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia. Br J Cancer 75:295–300.

    PubMed  CAS  Google Scholar 

  68. Body JJ, Lothoraly A, Romieu G, Vigneron AM, Ford J. 1999 A dose-finding study of zoledronate in hypercalcemic cancer patients. J Bone Miner Res 14:1557–1561.

    PubMed  CAS  Google Scholar 

  69. Major P, Lortholary A, Hon J, et al. 2001 Zoledronic acid is superior to pamidronate in the treatment of hypercalcaemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 19:558–567.

    PubMed  CAS  Google Scholar 

  70. Bickerstaff DR, O'Doherty DP, McCloskey EV, Hamdy NAT, Mian M, Kanis JA. 1991 Effects of amino-butylidene diphosphonate in hypercalcaemia due to malignancy. Bone 1:17–20.

    Google Scholar 

  71. Nussbaum SR, Warrell RP, Jude R, Glusman J, Bilezikian JP, 1993 Dose response study of alendronate sodium for the treatment of cancer-associated hypercalcaemia. J Clin Oncol 11:1618–1623.

    PubMed  CAS  Google Scholar 

  72. Dumon JC, Magritte A, Body JJ. 1991 Efficacy and safety of the bisphosphonate tiludronate for the treatment of tumour-associated hypercalcemia. Bone Miner 15:257–266.

    PubMed  CAS  Google Scholar 

  73. O'Rourke NP, McCloskey EV, Rosini S, Coleman RE, Kanis JA. 1991 Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate). Br J Cancer 69:914–917.

    Google Scholar 

  74. Fukumoto S, Matumoto T, Takebe K, et al. 1994 Treatment of malignancy-associated hypercalcemia with YM 175, a new bisphosphonate: elevated threshold for parathyroid hormone secretion in hypercalcemic patients. J Clin Endocrinol Metab 79:165–170.

    PubMed  CAS  Google Scholar 

  75. Grill V, Ho P, Body JJ, et al. 1991 Parathyroid hormone-related protein: elevated levels in both humoral hypercalcaemia of malignancy and hypercalcaemia complicating metastatic breast cancer. J Clin Endocrinol Metab 73:1309–1315.

    PubMed  CAS  Google Scholar 

  76. Jung A. 1982 Comparison of two parenteral diphosphonates in hypercalcemia of malignancy. Am J Med 72:221–226.

    PubMed  CAS  Google Scholar 

  77. Dodwell DJ, Abbas SK, Morton AR, Howell A. 1991 Parathyroid hormone-related protein and response to pamidronate therapy for tumour-induced hypercalcaemia. Eur J Cancer 27:1629–1633.

    PubMed  CAS  Google Scholar 

  78. Wimalawansa SJ. 1994 Significance of plasma PTHrP in patients with hypercalcaemia of malignancy treated with bisphosphonate. Cancer 73:2223–2230.

    PubMed  CAS  Google Scholar 

  79. Gurney H, Grill V, Martin TJ. 1993 Parathyroid hormone-related protein and response to pamidronate in tumour-induced hypercalcaemia. Lancet 341:1611–1613.

    PubMed  CAS  Google Scholar 

  80. Bloomfield DJ. 1998 Should bisphosphonates be part of the standard therapy of patients with multiple myeloma or bone metastases from other cancers? An evidence-based review. J Clin Oncol 16:1218–1225.

    PubMed  CAS  Google Scholar 

  81. McCloskey EV, Guest JF, Kanis JA. 2001 The clinical and cost considerations of bisphosphonates in preventing bone complications in patients with metastatic breast cancer or multiple myeloma. Drugs 61:1253–1274.

    PubMed  CAS  Google Scholar 

  82. Paterson AHG, Powles TJ, Kanis JA, McCloskey EV, Hanson J, Ashley S. 1993 Double-blind trial of oral clodronate in patients with bone metastases from breast cancer. J Clin Oncol 11:59–65.

    PubMed  CAS  Google Scholar 

  83. Diel IJ, Solomayer EF, Costa SD, et al. 1998 Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 339:357–363.

    PubMed  CAS  Google Scholar 

  84. Van Holten-Verzantvoort ATM, Kroon HM, Bijvoet OLM, et al. 1993 Palliative pamidronate (APD) treatment in patients with bone metastases from breast cancer. J Clin Oncol 11:491–498.

    PubMed  Google Scholar 

  85. Hortobagyi GN, Theriault RL, Porter L, et al. 1996 Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. N Engl J Med 335:1785–1791.

    PubMed  CAS  Google Scholar 

  86. Hortobagyi GN, Theriault RL, Lipton A, Porter L, Blayney D, Sinoff C. 1998 Long-term prevention of skeletal complications of metastatic breast carcinoma with pamidronate. J Clin Oncol 16:2038–2044.

    PubMed  CAS  Google Scholar 

  87. Theriault RL, Lipton A, Hortobagyi GN, et al. 1999 Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomised, placebo-controlled trial. J Clin Oncol 17:846–855.

    PubMed  CAS  Google Scholar 

  88. Hultborn R, Gundesen S, Ryden S, et al. 1999 Efficacy of pamidronate in breast cancer with bone metastases: a randomised double-blind placebo-controlled multicenter study. Anticancer Res 19:3383–3392.

    PubMed  CAS  Google Scholar 

  89. Lahtinen R, Laakso M, Palva I, et al. 1992 Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Lancet 340:1049–1052.

    PubMed  CAS  Google Scholar 

  90. Heim ME, Clemens MR, Queisser W, et al. 1995 Prospective randomized trial of dichloromethylene bisphosphonate (clodronate) in patients with multiple myeloma requiring treatment: a multicentre study. Onkologie 18:439–448.

    Google Scholar 

  91. McCloskey EV, MacLennan ICM, Drayson M, et al. 1998 A randomised trial of the effect of clodronate on skeletal morbidity in myelomatosis. Br J Haematol 100:317–325.

    PubMed  CAS  Google Scholar 

  92. Brincker H, Westin J, Abildgaard N, et al. for the Danish-Swedish Co-operative Study Group. 1998 Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double-blind placebo-controlled trial. Br J Haematol 101:280–286.

    PubMed  CAS  Google Scholar 

  93. Berenson JR, Lichtenstein A, Porter L, et al. 1996 Efficacy of pamidronate in reducing the skeletal events in patients with advanced multiple myeloma. N Engl J Med 334:488–493.

    PubMed  CAS  Google Scholar 

  94. Berenson JR, Lichtenstein A, Porter L, et al. for the Myeloma Aredia Study Group. 1998. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Clin Oncol 16:593–602.

    CAS  Google Scholar 

  95. Singer FR, Keutmann HT, Neer AM, Potts JT Jr, Bloch KJ. 1972. Pharmacologic effects of salmon calcitonin in man. In: Calcium, Parathyroid Hormone and the Calcitonins. Excerpta Medica. Amsterdam, 89–96.

    Google Scholar 

  96. Galante L, Joplin JF, MacIntyre I, Woodhouse NJY. 1973 The calcium lowering effect of salmon calcitonin in patients with Paget's disease. Clin Sci 44:605–610.

    PubMed  CAS  Google Scholar 

  97. Fillastre JP, Humbert G, Leroy J, Maitrot J, Deshayes P, Canonne MA. 1975 Furosemide, mythramycine and salmon calcitonin in hypercalcaemia. Eur J Intens Care Med 1:185–188.

    Google Scholar 

  98. Hosking DJ. 1980 Treatment of severe hypercalcaemia with calcitonin. Metab Bone Dis Related Res 2:207–212.

    Google Scholar 

  99. Ralston SH, Alzaid AA, Gardner MD, Boyle IT. 1986 Treatment of cancer-associated hypercalcaemia with combined aminohydroxypropylidene disphosphonate and calcitonin. Br Med J 292:1549–1550.

    CAS  Google Scholar 

  100. Thiebaud D, Jacquet AF, Burckhardt P. 1990 Fast and effective treatment of malignant hypercalcaemia. Arch Intern Med 151:2125–2128.

    Google Scholar 

  101. Perlia CP, Gubisch NJ, Cootter J, Edelberg D, Dederick MM, Taylor SG. 1970. Mithramycin treatment of hypercalcaemia. Cancer 25:389–394.

    PubMed  CAS  Google Scholar 

  102. Stewart AF, 1983 Therapy of malignancy-associated hypercalcaemia. Am J Med 74:475–479.

    PubMed  CAS  Google Scholar 

  103. Mundy GR, Wilkinson R, Heath DA. 1983 Comparative study of available medical therapy for hypercalcaemia of malignancy, Am Med J 74:421–432.

    CAS  Google Scholar 

  104. Slayton RE, Shnider BI, Elias E, Horton J, Perlia CP. 1971 New approach to the treatment of hypercalcaemia. Clin Pharmacol Ther 12:833–837.

    PubMed  CAS  Google Scholar 

  105. Warrell RP Jr, Bockman RS, Coonley CJ, Isaacs M, Staszewski H, 1984 Gallium nitrate inhibits calcium resorption from bone and is effective treatment for cancer-related hypercalcaemia. J Clin Invest 73:1487–1490.

    PubMed  CAS  Google Scholar 

  106. Strumpf M, Kowalski MA, Mundy GR. 1978 Effects of glucocorticoids on osteoclast-activing factor. J Lab Clin Med 92:772–778.

    PubMed  CAS  Google Scholar 

  107. Ishikawa H, Tanaka H, Iwato K, et al. 1990 Effect of glucocorticoids on the biological activities of myeloma cells: inhibition of interleukin-1 beta osteoclast-acytivating factor-induced bone resorption. Blood 75:715–720.

    PubMed  CAS  Google Scholar 

  108. Goodwin JS, Atluru D, Sierakowski S, Lianos EA. 1986 Mechanism of action of glucocorticosteroids: inhibition of T-cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B. J Clin Invest 77:1244–1250.

    PubMed  CAS  Google Scholar 

  109. Kimberg DV, Baerg RD, Gershon E, Graudius RT, 1971 Effect of cortisone treatment on the active transport of calcium by the small intestine. J Clin Invest 50:1309–1321

    PubMed  CAS  Google Scholar 

  110. Carre M, Ayigbede O, Miravet L, Rasmussen H, 1974 The efect of prednisolone upon the metabolism and action of 25-hydroxy- and 1,25-dihydroxy vitamin D3. Proc Natl Acad Sci USA. 71:2996–3000.

    PubMed  CAS  Google Scholar 

  111. Heyburn PJ, Francis RM, Peacock M. 1979 Acute effects of saline, calcitonin and hydrocortisone on plasma calcium in vitamin D intoxication. Br Med J 1:232–233.

    PubMed  CAS  Google Scholar 

  112. Breslau NA, McGuire JL, Zerwekh JE, et al. 1984 Hypercalcaemia associated with increased serum calcitriol levels in three patients with lymphoma. Ann Intern Med 100:1–7.

    PubMed  CAS  Google Scholar 

  113. Percival RC, Yates AJP, Gray RES, Neal FE, Forrest AR, Kanis JA. 1984 The role of glucocorticoids in the management of malignant hypercalcaemia. Br Med J 289–287.

  114. Carey RW, Schmitt GW, Kopaid HH, 1968 Massive extraskeletal calcification during phosphate treatment of hypercalcaemia. Arch Intern Med 122:150–155.

    PubMed  CAS  Google Scholar 

  115. Shackney S, Hasson J. 1967 Precipitous fall in serum calcium, hypotension and acute renal failure after intravenous phosphate therapy for hypercalcaemia. Ann Intern Med 66:906–916.

    PubMed  CAS  Google Scholar 

  116. Kong YY, Yoshida H, Sarosi I, et al. 1999 OPLG is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis. Nature 397:315–323.

    PubMed  CAS  Google Scholar 

  117. Hofbauer LC, 1999 Osteoprotegerin ligand and osteoprotegerin: novel implications for osteoclast biology and bone metabolism. Eur J Endocrinol 141:195–210.

    PubMed  CAS  Google Scholar 

  118. Hofbauer LC, Neubauer A, Heufelder AE. 2001 Receptor activator of nuclear factor-kB ligand and osteoporotegerin. Potential implications for the pathogenesis and treatment of malignant bone diseases. Cancer 92:460–470.

    PubMed  CAS  Google Scholar 

  119. Caparelli C, Kostenuik PJ, Morony S, et al. 1999 Comparison of osteoprotegerin and pamidronate in a murine model of humoral hypercalcemia of malignancy. J Bone Miner Res 14(Suppl 1):S163.

    Google Scholar 

  120. Goltzman D, Karaplis AC, Kremer R, Rabbani SA. 2000 Molecular basis of the spectrum of skeletal complications of neoplasia. Cancer 88(Suppl):2903–2908.

    PubMed  CAS  Google Scholar 

  121. Ogata E. 2000 Parathyroid hormone-related protein as a potential target of therapy for cancer-associated morbidity. Cancer 88(Suppl):2909–2911.

    PubMed  CAS  Google Scholar 

  122. El Abdaimi K, Papavasiliou V, Rabbani SA, Rhim JS, Goltzman D, Kremer S. 1999 Reversal of hypercalcemia with the vitamin D analoue EB 1089 in a human model of squamous cancer. Cancer Res 59:3325–3328.

    PubMed  Google Scholar 

  123. Aklilu F, Park M, Goltzman D, Rabbani SA. 1997 Induction of parathyroid hormone-related peptide by the Ras oncogene: role of Ras farnesylation inhibitors as potential therapeutic agents for hypercalcemia of malignancy. Cancer Res 57:4517–4522.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Neveen A. T. Hamdy MD, MRCP.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hamdy, N.A.T., Papapoulos, S.E. Management of malignancy-associated hypercalcemia. Clinic Rev Bone Miner Metab 1, 65–76 (2002). https://doi.org/10.1385/BMM:1:1:65

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/BMM:1:1:65

Keywords

Navigation