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Horm Metab Res 2010; 42(3): 153-164
DOI: 10.1055/s-0029-1241821
Review

© Georg Thieme Verlag KG Stuttgart · New York

Hypercalcemia in Cancer Patients: Pathobiology and Management

L. Santarpia1 , 2 , C. A. Koch3 , N. J. Sarlis4
  • 1Translational Research Unit, Department of Oncology Hospital of Prato and Istituto Toscana Tumori, Florence, Italy
  • 2Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas – M. D. Anderson Cancer Center, Houston, Texas, USA
  • 3Division of Endocrinology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA
  • 4Department of Medical Affairs – Oncology, Sanofi-Aventis U.S., Bridgewater, New Jersey, USA
Further Information

Publication History

received 15.06.2009

accepted 07.10.2009

Publication Date:
03 December 2009 (online)

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Abstract

Hypercalcemia is the most common life-threatening metabolic disorder associated with cancer, occurring in approximately 10–30% of all patients with neoplastic disease, although it occurs much less often in the pediatric setting. Hypercalcemia can emerge in hematologic malignancies, particularly multiple myeloma, as well as assorted solid tumors, primarily lung and breast cancers, and can even dominate the clinical picture in select patients. Early diagnosis and treatment with fluids and drugs that lower calcium levels in the blood can improve symptoms in a few days, ameliorate the quality of life of these patients, and avoid delays in the implementation of further anticancer treatments. Occasionally, the symptoms of hypercalcemia can appear gradually, and may be non-specific, resembling symptoms of many cancers and other comorbidities, especially in the elderly, thus resulting in an underestimated incidence of hypercalcemia in cancer patients. Of note, there is an increasing number of antineoplastic compounds that can interfere with calcium metabolism. Taking into consideration both the severity of hypercalcemia and the tumor status, health care providers should determine and apply appropriate treatment measures. We provide a comprehensive subjective synthesis of peer-reviewed evidence on the pathophysiology and treatment of hypercalcemia in cancer patients.

Key words

cancer - hypercalcemia - malignancy - therapy

References

  • 1 Chan FK, Koberle LM, Thys-Jacobs S, Bilezikian JP. Differential diagnosis, causes, and management of hypercalcemia.  Curr Probl Surg. 1997;  34 445-523
    Search in Google Scholar
  • 2 Diercks DB, Shumaik GM, Harrigan RA, Brady WJ, Chan TC. Electrocardiographic manifestations: electrolyte abnormalities.  J Emerg Med. 2004;  27 153-160
    Search in Google Scholar
  • 3 Nishi S, Barbagelata N, Atar S, Birnbaum Y, Tuero E. Hypercalcemia-induced ST-segment elevation mimicking acute myocardial infarction.  J Electrocardiol. 2006;  39 298-300
    Search in Google Scholar
  • 4 Edelson GW, Kleerekoper M. Hypercalcemic crisis.  Med Clin North Am. 1995;  79 79-92
    Search in Google Scholar
  • 5 Falk S, Kratzsch J, Paschke R, Koch CA. Hypercalcemia as a result of sarcoidosis with normal serum concentrations of vitamin D.  Med Sci Monit. 2007;  13 133-136
    Search in Google Scholar
  • 6 Suda T, Kobayashi K, Jimi E, Udagawa N, Takahashi N. The molecular basis of osteoclast differentiation and activation.  Novartis Found Symp. 2001;  232 235-247 discussion 247–250 
    Search in Google Scholar
  • 7 Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption.  J Bone Miner Res. 2000;  15 2-12
    Search in Google Scholar
  • 8 Schett G, Hayer S, Zwerina J, Redlich K, Smolen JS. Mechanisms of Disease: the link between RANKL and arthritic bone disease.  Nat Clin Pract Rheumatol. 2005;  1 47-54
    Search in Google Scholar
  • 9 McCollum CR, Pitman K, Bigler SA, Vijayakumar V, Flessner M, Jenkins J, Horn M, Arnold A, Koch CA. Hypercalcemia of 26.5 mg: Isolated parathyroid malignancy or hereditary syndrome?.  J Invest Med. 2009;  57 S327
    Search in Google Scholar
  • 10 Fernandez-Ranvier GG, Khanafshar E, Jensen K, Zarnegar R, Lee J, Kebebew E, Duh QY, Clark OH. Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis?.  Cancer. 2007;  110 255-264
    Search in Google Scholar
  • 11 Robert JH, Trombetti A, Garcia A, Pache JC, Herrmann F, Spiliopoulos A, Rizzoli R. Primary hyperparathyroidism: can parathyroid carcinoma be anticipated on clinical and biochemical grounds? Report of 9 cases and review of the literature.  Ann Surg Oncol. 2005;  12 1-7
    Search in Google Scholar
  • 12 Wysolmerski JJ, Broadus AE. Hypercalcemia of malignancy: the central role of parathyroid hormone-related protein.  Annu Rev Med. 1994;  45 189-200
    Search in Google Scholar
  • 13 Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE. Biochemical evaluation of patients with cancer associated hypercalcemia: evidence for humoral and nonhumoral groups.  N Engl J Med. 1980;  303 1377-1383
    Search in Google Scholar
  • 14 Dunbar ME, Wysolmerski JJ, Broadus AE. Parathyroid hormone-related protein: from hypercalcemia of malignancy to developmental regulatory molecule.  Am J Med Sci. 1996;  312 287-294
    Search in Google Scholar
  • 15 Strewler GJ. Mechanisms of disease – The physiology of parathyroid hormone-related protein.  N Engl J Med. 2000;  342 177-185
    Search in Google Scholar
  • 16 Chorev M. Parathyroid hormone 1 receptor: Insights into structure and function. Receptors Channels.  2002;  8 219-242
    Search in Google Scholar
  • 17 Philbrick WM, Wysolmerski JJ, Galbraith S, Holt E, Orloff JJ, Yang KH, Vasavada RC, Weir EC, Broadus AE, Stewart AF. Defining the roles of parathyroid hormone-related protein in normal physiology.  Physiol Rev. 1996;  76 127-173
    Search in Google Scholar
  • 18 Kronenberg HM, Chung U. The parathyroid hormone-related protein and Indian hedgehog feedback loop in the growth plate.  Novartis Found Symp. 2001;  232 144-152 discussion 152–157 
    Search in Google Scholar
  • 19 Kimura S, Nishimura Y, Yamaguchi K, Nagasaki K, Shimada K, Uchida H. A case of pheochromocytoma producing parathyroid hormone-related protein and presenting with hypercalcemia.  J Clin Endocrinol Metab. 1990;  70 1559-1563
    Search in Google Scholar
  • 20 Al-Rashid RA, Cress C. Hypercalcemia associated with neuroblastoma.  Am J Dis Child. 1979;  133 838-341
    Search in Google Scholar
  • 21 Mitlak BH, Hutchison JS, Kaufman SD, Nussbaum SR. Parathyroid hormone related peptide mediates hypercalcemia in an islet cell tumor of the pancreas.  Horm Metab Res. 1991;  23 344-346
    Search in Google Scholar
  • 22 Prager D, Rosenblatt JD, Ejima E. Hypercalcemia, parathyroid hormone-related protein expression and human T-cell leukemia virus infection.  Leuk Lymphoma. 1994;  14 395-400
    Search in Google Scholar
  • 23 Ikeda K, Ogata E. Humoral hypercalcemia of malignancy: some enigmas on the clinical features.  J Cell Biochem. 1995;  57 384-391
    Search in Google Scholar
  • 24 Goldring SR, Goldring MB. Cytokines and skeletal physiology.  Clin Orthop. 1996;  324 13-23
    Search in Google Scholar
  • 25 Uy HL, Mundy GR, Boyce BF, Story BM, Dunstan CR, Yin JJ, Roodman GD, Guise TA. Tumor necrosis factor enhances parathyroid hormone-related protein-induced hypercalcemia and bone resorption without inhibiting bone formation in vivo.  Cancer Res. 1997;  57 3194-3199
    Search in Google Scholar
  • 26 de la Mata J, Uy HL, Guise TA, Story B, Boyce BF, Mundy GR, Roodman GD. Interleukin-6 enhances hypercalcemia and bone resorption mediated by parathyroid hormone-related protein in vivo.  J Clin Invest. 1995;  95 2846-2852
    Search in Google Scholar
  • 27 Hewison M, Kantorovich V, Liker HR, Van Herle AJ, Cohan P, Zehnder D, Adams JS. Vitamin D-mediated hypercalcemia in lymphoma: Evidence for hormone production by tumor-adjacent macrophages.  J Bone Miner Res. 2003;  18 ((3)) 579-582
    Search in Google Scholar
  • 28 Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, O’Keefe PF, Ramnaraine ML, Clohisy DR, Mntyh PW. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord.  Nature Med. 2000;  6 521-528
    Search in Google Scholar
  • 29 Budayr AA, Nissenson RA, Klein RF, Pun KK, Clark OH, Diep D, Arnaud CD, Strewler GJ. Increased serum levels of a parathyroid hormone-like protein in malignancy-associated hypercalcemia.  Ann Intern Med. 1989;  111 807-812
    Search in Google Scholar
  • 30 Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell  Jr  RP, Olson BR, Wu TL, Mitnick ME, Broadus AE, Stewart AF. Immunochemical characterization of circulating parathyroid hormone- related protein in patients with humoral hypercalcemia of cancer.  N Engl J Med. 1990;  322 1106-1112
    Search in Google Scholar
  • 31 Croucher PI, Shipman CM, Lippitt J, Perry M, Asosingh K, Hijzen A, Brabbs AC, van Beek EJ, Holen I, Skerry TM, Dunstan CR, Russell GR, Van Camp B, Vanderkerken K. Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.  Blood. 2001;  13 3534-3540
    Search in Google Scholar
  • 32 Kostenuik PJ. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength.  Curr Opin Pharmacol. 2005;  5 618-625
    Search in Google Scholar
  • 33 Chirgwin JM, Guise TA. Molecular mechanisms of tumor-bone interactions in osteolytic metastases.  Crit Rev Eukaryot Gene Expr. 2000;  2 159-178
    Search in Google Scholar
  • 34 Fisher G, Skillern PG. Hypercalcemia due to hypervitaminosis A.  JAMA. 1974;  227 1413-1414
    Search in Google Scholar
  • 35 Mugishima H, Chin M, Suga M, Schichino H, Ryo N, Nakamura M, Harada K. Hypercalcemia induced by 13 cis-retinoic acid in patients with neuroblastoma.  Pediatr Int. 2008;  50 235-237
    Search in Google Scholar
  • 36 Lawrence JA, Adamson PC, Caruso R, Chow C, Kleiner D, Murphy RF, Venzon DJ, Shovlin M, Noone M, Merino M, Cowan KH, Kaiser M, O’Shaughnessy J, Zujewski J, Phase I. clinical trial of alitretinoin and tamoxifen in breast cancer patients: toxicity, pharmacokinetic, and biomarker evaluations.  J Clin Oncol. 2001;  19 2754-2763
    Search in Google Scholar
  • 37 Bergman SM, O’Mailia J, Krane NK, Wallin JD. Vitamin-A-induced hypercalcemia: response to corticosteroids.  Nephron. 1988;  50 362-364
    Search in Google Scholar
  • 38 Saunders MP, Salisbury AJ, O’Byrne KJ, Long L, Whitehouse RM, Talbot DC, Mawer EB, Harris AL. A novel cyclic adenosine monophosphate analog induces hypercalcemia via production of 1,25-dihydroxyvitamin D in patients with solid tumors.  J Clin Endocrinol Metab. 1997;  82 4044-4048
    Search in Google Scholar
  • 39 Kawa S, Yoshizawa K, Nikaido T, Kiyosawa K. Inhibitory effect of 22-oxa-1,25-dihydroxyvitamin D3, maxacalcitol, on the proliferation of pancreatic cancer cell lines.  J Steroid Biochem Mol Biol. 2005;  97 173-177
    Search in Google Scholar
  • 40 Morony S, Warmington K, Adamu S, Asuncion F, Geng Z, Grisanti M, Tan HL, Capparelli C, Starnes C, Weimann B, Dunstan CR, Kostenuik PJ. The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared with bisphosphonates in two models of humoral hypercalcemia of malignancy.  Endocrinology. 2005;  146 3235-3243
    Search in Google Scholar
  • 41 Zhang X, Jiang F, Li P, Li C, Ma Q, Nicosia SV, Bai W. Growth suppression of ovarian cancer xenografts in nude mice by vitamin D analogue EB108.  Clin Cancer Res. 2005;  11 323-328
    Search in Google Scholar
  • 42 Kumagai T, O’Kelly J, Said JW, Koeffler HP. Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against leukemia, myeloma, and colon cancer cells.  J Natl Cancer Inst. 2003;  95 896-905
    Search in Google Scholar
  • 43 Funato K, Miyazawa K, Yaguchi M, Gotoh A, Ohyashiki K. Combination of 22-oxa-1,25-dihydroxyvitamin D(3), a vitamin D(3) derivative, with vitamin K(2) (VK2) synergistically enhances cell differentiation but suppresses VK2-inducing apoptosis in HL-60 cells.  Leukemia. 2002;  16 1519-1527
    Search in Google Scholar
  • 44 Hansen CM, Mäenpää PH. EB 1089, a novel vitamin D analog with strong antiproliferative and differentiation-inducing effects on target cells.  Biochem Pharmacol. 1997;  54 1173-1179 (Review) 
    Search in Google Scholar
  • 45 Wang X, Gardner JP, Kheir A, Uskokovic MR, Studzinski GP. Synergistic induction of HL60 cell differentiation by ketoconazole and 1-desoxy analogues of vitamin D.  J Natl Cancer Inst. 1997;  89 1199-1206
    Search in Google Scholar
  • 46 Donnelly J, Hackler RH, Bunts RC. Present urologic status of the World War II paraplegic: 25-year followup. Camparison with status of the 20-year Korean War paraplegic and 5-year Vietnam paraplegic.  J Urol. 1972;  108 558-562
    Search in Google Scholar
  • 47 Hansen MF, Seton M, Merchant A. Osteosarcoma in Paget's disease of bone.  J Bone Miner Res. 2006;  21 ((Suppl 2)) 58-63
    Search in Google Scholar
  • 48 Hallengren B, Spjuth J, Dymling JF. Hypercalcaemia induced by increased thyroxine substitution in a patient treated with dihydrotachysterol.  Acta Endocrinol (Copenh). 1984;  10 28-30
    Search in Google Scholar
  • 49 Meythaler JM, Tuel SM, Cross LL. Successful treatment of immobilization hypercalcemia using calcitonin and etidronate.  Arch Phys Med Rehabil. 1993;  74 316-319
    Search in Google Scholar
  • 50 Kaul S, Sockalosky JJ. Human synthetic calcitonin therapy for hypercalcemia of immobilization.  J Pediatr. 1995;  126 825-827
    Search in Google Scholar
  • 51 Chen JD, Morrison C, Zhang C, Kahnoski K, Carpten JD, Teh BT. Hyperparathyroidism-jaw tumour syndrome.  J Intern Med. 2003;  253 634-642
    Search in Google Scholar
  • 52 Shattuck TM, Välimäki S, Obara T, Gaz RD, Clark OH, Shoback D, Wierman ME, Tojo K, Robbins CM, Carpten JD, Farnebo LO, Larsson C, Arnold A. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma.  N Engl J Med. 2003;  349 1722-1729
    Search in Google Scholar
  • 53 Agha A, Carpenter R, Bhattacharya S, Edmonson SJ, Carlsen E, Monson JP. Parathyroid carcinoma in multiple endocrine neoplasia type 1 (MEN1) syndrome: two case reports of an unrecognised entity.  J Endocrinol Invest. 2007;  30 145-149
    Search in Google Scholar
  • 54 Nussbaum SR, Gaz RD, Arnold A. Hypercalcemia and ectopic secretion of parathyroid hormone by an ovarian carcinoma with rearrangement of the gene for parathyroid hormone.  N Engl J Med. 1990;  323 1324-1328
    Search in Google Scholar
  • 55 Yoshimoto K, Yamasaki R, Sakai H, Tezuka U, Takahashi M, Iizuka M, Sekiya T, Saito S. Ectopic production of parathyroid hormone by small cell lung cancer in a patient with hypercalcemia.  J Clin Endocrinol Metab. 1989;  68 976-981
    Search in Google Scholar
  • 56 Rizzoli R, Pache JC, Didierjean L, Bürger A, Bonjour JP. A thymoma as a cause of true ectopic hyperparathyroidism.  J Clin Endocrinol Metab. 1994;  79 912-915
    Search in Google Scholar
  • 57 Strewler GJ, Budayr AA, Clark OH, Nissenson RA. Production of parathyroid hormone by a malignant nonparathyroid tumor in a hypercalcemic patient.  J Clin Endocrinol Metab. 1993;  1373-1375
    Search in Google Scholar
  • 58 Strodel WE, Thompson NW, Eckhauser FE, Knol JA. Malignancy and concomitant primary hyperparathyroidism.  J Surg Oncol. 1988;  37 10-12
    Search in Google Scholar
  • 59 Stanaway SE, Wilding JP. Hypercalcaemia of hypoadrenal crisis mistaken for hypercalcaemia of malignancy in a patient with known bone metastases: a case report.  Eur J Intern Med. 2000;  11 348-350
    Search in Google Scholar
  • 60 Nelson KA, Walsh D, Abdullah O, McDonnell F, Homsi J, Komurcu S, LeGrand SB, Zhukovsky DS. Common complications of advanced cancer.  Semin Oncol. 2000;  27 34-44
    Search in Google Scholar
  • 61 Hotta M, Sato K, Shibasaki T, Demura H. Hypercalcemia in an euthyroid patient with secondary hypoadrenalism and diabetes insipidus due to hypothalamic tumor.  Endocr J. 1998;  45 773-778
    Search in Google Scholar
  • 62 Gesundheit N, Petrick PA, Nissim M, Dahlberg PA, Doppman JL, Emerson CH, Braverman LE, Oldfield EH, Weintraub BD. Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case reports and follow-up of nine patients.  Ann Intern Med. 1989;  11 827-835
    Search in Google Scholar
  • 63 Salvatori M, Saletnich I, Rufini V, Dottorini ME, Corsello SM, Troncone L, Shapiro B. Severe thyrotoxicosis due to functioning pulmonary metastases of well-differentiated thyroid cancer.  J Nucl Med. 1998;  39 1202-1207
    Search in Google Scholar
  • 64 Skrabanek P. Catecholamines cause the hypercalciuria and hypercalcaemia in phaeochromocytoma and in hyperthyroidism.  Med Hypotheses. 1977;  3 59-62
    Search in Google Scholar
  • 65 Ueda M, Inaba M, Tahara H, Imanishi Y, Goto H, Nishizawa Y. Hypercalcemia in a patient with primary hyperparathyroidism and acromegaly: distinct roles of growth hormone and parathyroid hormone in the development of hypercalcemia.  Intern Med. 2005;  44 307-310
    Search in Google Scholar
  • 66 Koo WS, Jeon DS, Ahn SJ, Kim YS, Yoon YS, Bang BK. Calcium-free hemodialysis for the management of hypercalcemia.  Nephron. 1996;  72 424-428
    Search in Google Scholar
  • 67 Vernava AM, O’Neal LW, Palermo V. Lethal hyperparathyroid crisis: hazards of phosphate administration.  Surgery. 1987;  102 941-948
    Search in Google Scholar
  • 68 Berenson JR, Lipton A. Bisphosphonates in the treatment of malignant bone disease.  Annu Rev Med. 1999;  50 237-248
    Search in Google Scholar
  • 69 Zolendronate (Zometa). . Med Lett Drugs Ther. 2001;  43 110-111
  • 70 Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, Yunus F, Bell R, Body J, Quebe-Fehling E, Seaman J. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials.  J Clin Oncol. 2001;  19 558-567
    Search in Google Scholar
  • 71 Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein M, Coleman RE, Reitsma DJ, Seaman JJ, Chen BL, Ambros Y. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial.  Cancer J. 2001;  7 377-387
    Search in Google Scholar
  • 72 Markowitz GS, Fine PL, Stack JI, Kunis CL, Radhakrishnan J, Palecki W, Park J, Nasr SH, Hoh S, Siegel DS, D’Agati VD. Toxic acute tubular necrosis following treatment with zoledronate (Zometa).  Kidney Int. 2003;  64 281-289
    Search in Google Scholar
  • 73 Machado CE, Flombaum CD. Safety of pamidronate in patients with renal failure and hypercalcemia.  Clin Nephrol. 1996;  45 175-179
    Search in Google Scholar
  • 74 Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S, Kuhn JA, Dratch AD, D’Agati VD. Collapsing focal segmental glomerulosclerosis ollowing treatment with high-dose pamidronate.  J Am Soc Nephrol. 2001;  12 1164-1172
    Search in Google Scholar
  • 75 Skeel RT. Oncology emergencies and critical care issues. In: Skeel RT, Ed. Handbook of Cancer Chemotherapy, 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2007: 696-699
    Search in Google Scholar
  • 76 Leyland-Jones B. Treating cancer-related hypercalcemia with gallium nitrate.  J Support Oncol. 2004;  2 509-516 discussion 516–520 
    Search in Google Scholar
  • 77 Chitambar CR. Gallium nitrate revisited.  Semin Oncol. 2003;  30 ((2 Suppl 5)) 1-4
    Search in Google Scholar
  • 78 Cvitkovic F, Armand JP, Tubiana-Hulin M, Rossi JF, Warrell  RP. Randomized, double-blind, phase II trial of gallium nitrate compared with pamidronate for acute control of cancer-related hypercalcemia.  Cancer J. 2006;  12 47-53
    Search in Google Scholar
  • 79 Edelson GW, Talpos GB, Bone HG. Hypercalcemia associated with Wegener's granulomatosis and hyperparathyroidism: etiology and management.  Am J Nephrol. 1993;  275-277
    Search in Google Scholar
  • 80 O’Leary TJ, Jones G, Yip A, Lohnes D, Cohanim M, Yendt ER. The effects of chloroquine on serum 1,25-dihydroxyvitamin D and calcium etabolism in sarcoidosis.  N Engl J Med. 1986;  315 727-730
    Search in Google Scholar
  • 81 Barre PE, Gascon-Barré M, Meakins JL, Goltzman D. Hydroxychloroquine treatment of hypercalcemia in a patient with sarcoidosis undergoing hemodialysis.  Am J Med. 1987;  82 1259-1262
    Search in Google Scholar
  • 82 Adams JS, Kantorovich V. Inability of short-term, low-dose hydroxychloroquine to resolve vitamin D-mediated hypercalcemia in patients with B-cell lymphoma.  J Clin Endocrinol Metab. 1999;  84 799-801
    Search in Google Scholar
  • 83 Nemeth EF. Pharmacological regulation of parathyroid hormone secretion.  Curr Pharm Des. 2002;  8 2077-2087
    Search in Google Scholar
  • 84 Nemeth EF, Fox J. Calcimimetic compounds: A direct approach to controlling plasma levels of parathyroid hormone in hyperparathyroidism.  Trends Endocrinol Metab. 1999;  10 66-71
    Search in Google Scholar
  • 85 Collins MT, Skarulis MC, Bilezikian JP, Silverberg SJ, Spiegel AM, Marx SJ. Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent.  J Clin Endocrinol Metab. 1998;  83 1083-1088
    Search in Google Scholar
  • 86 Betea D, Bradwell AR, Harvey TC, Mead GP, Schmidt-Gayk H, Ghaye B, Daly AF, Beckers A. Hormonal and biochemical normalization and tumor shrinkage induced by anti-parathyroid hormone immunotherapy in a patient with metastatic parathyroid carcinoma.  J Clin Endocrinol Metab. 2004;  89 3413-3420
    Search in Google Scholar
  • 87 Sato K, Onuma E, Yocum RC, Ogata E. Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody.  Semin Oncol. 2003;  30 ((5 Suppl 16)) 167-173
    Search in Google Scholar
  • 88 Morony S, Warmington K, Adamu S, Asuncion F, Geng Z, Grisanti M, Tan HL, Capparelli C, Starnes C, Weimann B, Dunstan CR, Kostenuik PJ. The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared to bisphosphonates in two models of humoral hypercalcemia of malignancy.  Endocrinology. 2005;  146 3235-3243
    Search in Google Scholar
  • 89 Kostenuik PJ. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength.  Curr Opin Pharmacol. 2005;  5 618-625
    Search in Google Scholar
  • 90 Rifkin WD. Denosumab in postmenopausal women with low bone mineral density.  N Engl J Med. 2006;  354 2390-2391
    Search in Google Scholar

Correspondence

L. SantarpiaMD, PhD 

Translational Research Unit

Department of Oncology

Hospital of Prato and Istituto

Toscana Tumori

Florence

Italy

Piazza dell' Ospedale

59100 Prato

Italy

Phone: +39 0574 434766

Fax: +39 0574 29798

Email: lsantarp@mdanderson.org