Translational Research
Volume 155, Issue 5 , Pages 247-255 , May 2010

Markers of bone remodeling and skeletal morbidity in patients with solid tumors metastatic to the skeleton receiving the biphosphonate zoledronic acid

  • Giannis Mountzios

      Affiliations

    • Department of Medical Oncology, 251 General Airforce Hospital, University of Athens, Athens, Greece
    • Corresponding Author InformationReprint requests: Giannis Mountzios, PhD, Department of Medical Oncology, Univeristy Hospital Alexandra, 251 General Airforce Hospital, 3 P. Kanellopoulou Avenue, PC 115 25 Athens, Greece
  • ,
  • Evangelos Terpos

      Affiliations

    • Department of Biomedical Research, 251 General Airforce Hospital, University of Athens, Athens, Greece
  • ,
  • Konstantinos Syrigos

      Affiliations

    • “Sotiria” Hospital, 3rd Department of Biomedical Research, University of Athens, Athens, Greece
  • ,
  • Christos Papadimitriou

      Affiliations

    • Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens, Athens, Greece, University of Athens, Athens, Greece
  • ,
  • Giorgos Papadopoulos

      Affiliations

    • Department of Medical Oncology, 251 General Airforce Hospital, University of Athens, Athens, Greece
  • ,
  • Aristotelis Bamias

      Affiliations

    • Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens, Athens, Greece, University of Athens, Athens, Greece
  • ,
  • Myron Mavrikakis

      Affiliations

    • Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens, Athens, Greece, University of Athens, Athens, Greece
  • ,
  • Meletios-Athanassios Dimopoulos

      Affiliations

    • Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens, Athens, Greece, University of Athens, Athens, Greece

Received 18 September 2009 ,Revised 20 December 2009 ,Accepted 9 January 2010.

References 

  1. Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2:584–593
  2. Coleman R, Brown J, Terpos E, et al. Bone markers and their prognostic value in metastatic bone disease: clinical evidence and future directions. Cancer Treat Rev. 2008;34:629–639
  3. Vega D, Maalouf NM, Sakhaee K. The role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab. 2007;92:4514–4521
  4. Kwan TS, Padrines M, Theoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15:49–60
  5. Grimaud E, Soubigou L, Couillaud S, et al. Receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis. Am J Pathol. 2003;163:2021–2031
  6. Fohr B, Dunstan CR, Seibel MJ. Clinical review 165: markers of bone remodeling in metastatic bone disease. J Clin Endocrinol Metab. 2003;88:5059–5075
  7. Fedarko NS, Jain A, Karadag A, Van Eman MR, Fisher LW. Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin Cancer Res. 2001;7:4060–4066
  8. Saad F, Gleason DM, Murray R, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004;2:879–882
  9. Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer. 2003;98:1735–1744
  10. Rosen LS, Gordon D, Tchekmedyian NS, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer. 2004;100:2613–2621
  11. Greenspan SL, Bhattacharya RK, Sereika SM, Brufsky A, Vogel VG. Prevention of bone loss in survivors of breast cancer: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2007;92:131–136
  12. Brufsky A, Harker WG, Beck JT, et al. Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol. 2007;25:829–836
  13. Clemons MJ, Dranitsaris G, Ooi WS, et al. Phase II trial evaluating the palliative benefit of second-line zoledronic acid in breast cancer patients with either a skeletal-related event or progressive bone metastases despite first-line bisphosphonate therapy. J Clin Oncol. 2006;24:4895–4900
  14. Smith MR, Cook RJ, Coleman R, et al. Predictors of skeletal complications in men with hormone-refractory metastatic prostate cancer. Urology. 2007;70:315–319
  15. Coleman RE, Major P, Lipton A, et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J Clin Oncol. 2005;23:4925–4935
  16. Mountzios G, Dimopoulos MA, Bamias A, et al. Abnormal bone remodeling process is due to an imbalance in the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) axis in patients with solid tumors metastatic to the skeleton. Acta Oncol. 2007;46:221–229
  17. Terpos E, Mihou D, Szydlo R, et al. The combination of intermediate doses of thalidomide with dexamethasone is an effective treatment for patients with refractory/relapsed multiple myeloma and normalizes abnormal bone remodeling, through the reduction of sRANKL/osteoprotegerin ratio. Leukemia. 2005;19:1969–1976
  18. Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008;29:155–192
  19. Terpos E, Szydlo R, Apperley JF, et al. Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index. Blood. 2003;102:1064–1069
  20. Koizumi M, Takahashi S, Ogata E. Comparison of serum bone resorption markers in the diagnosis of skeletal metastasis. Anticancer Res. 2003;23:4095–4099
  21. Koizumi M, Takahashi S, Ogata E. Bone metabolic markers in bisphosphonate therapy for skeletal metastases in patients with breast cancer. Breast Cancer. 2003;10:21–27
  22. Nakayama K, Fukumoto S, Takeda S, et al. Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia. J Clin Endocrinol Metab. 1996;81:607–611
  23. Body JJ, Delmas PD. Urinary pyridinium cross-links as markers of bone resorption in tumor-associated hypercalcemia. J Clin Endocrinol Metab. 1992;74:471–475
  24. Demers LM, Costa L, Chinchilli VM, Gaydos L, Curley E, Lipton A. Biochemical markers of bone turnover in patients with metastatic bone disease. Clin Chem. 1995;41:1489–1494
  25. Pecherstorfer M, Zimmer-Roth I, Schilling T, et al. The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease. J Clin Endocrinol Metab. 1995;80:97–103
  26. Mack PC, Redman MW, Chansky K, et al. Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J Clin Oncol. 2008;26:4771–4776
  27. Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Vaananen HK. Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab. 2006;52:499–509
  28. Korpela J, Tiitinen SL, Hiekkanen H, et al. Serum TRACP 5b and ICTP as markers of bone metastases in breast cancer. Anticancer Res. 2006;26:3127–3132
  29. Scarnecchia L, Minisola S, Pacitti MT, et al. Clinical usefulness of serum tartrate-resistant acid phosphatase activity determination to evaluate bone turnover. Scand J Clin Lab Invest. 1991;51:517–524
  30. Hirsh V, Major PP, Lipton A, et al. Zoledronic acid and survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity. J Thorac Oncol. 2008;3:228–236
  31. Schneider S, Yochim J, Brabender J, et al. Osteopontin but not osteonectin messenger RNA expression is a prognostic marker in curatively resected non-small cell lung cancer. Clin Cancer Res. 2004;10:1588–1596
  32. Salminen EK, Kallioinen MJ, la-Houhala MA, et al. Survival markers related to bone metastases in prostate cancer. Anticancer Res. 2006;26:4879–4884
  33. Cook RJ, Coleman R, Brown J, et al. Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. Clin Cancer Res. 2006;12:3361–3367
  34. Lonning PE, Geisler J, Krag LE, et al. Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. J Clin Oncol. 2005;23:5126–5137
  35. Coleman RE, Banks LM, Girgis SI, et al. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol. 2007;8:119–127
  36. Ibrahim A, Scher N, Williams G, et al. Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clin Cancer Res. 2003;9:2394–2399
  37. Lipton A, Cook R, Saad F, et al. Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid. Cancer. 2008;113:193–201
  38. Hershman DL, McMahon DJ, Crew KD, et al. Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2008;26:4739–4745
  39. Lipton A, Steger GG, Figueroa J, et al. Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin Cancer Res. 2008;14:6690–6696
  40. Fizazi K, Lipton A, Mariette X, et al. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009;27:1564–1571
  41. Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008;26:4875–4882

 Supported by a Translational Research Fellowship (to G.M.) from the European Society of Medical Oncology (ESMO).

PII: S1931-5244(10)00009-5

doi: 10.1016/j.trsl.2010.01.002

Translational Research
Volume 155, Issue 5 , Pages 247-255 , May 2010