Skip to main content

Advertisement

SpringerLink
Log in

Osteoprotegerin and Bone Mass in Squamous Cell Head and Neck Cancer Patients

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Osteoprotegerin (OPG) is considered one of the main regulators of bone remodeling. Various patterns of serum OPG levels have been described in different types of tumors. We undertook this study to determine serum OPG levels in patients with squamous cell head and neck cancer (SCHNC), analyzing their relationship with other metabolic bone parameters and bone mineral density (BMD), as well as the possible influence of chemotherapy. Forty male patients with localized SCHNC were studied, and their results were compared with those of 40 healthy male controls. The type of treatment followed by each patient was noted. Age, weight, height, and lifestyle habits were recorded; and OPG, Ca2+, intact parathyroid hormone (iPTH), 25-Hydroxyvitamin D (25OHD) and 1,25-Dihydroxyvitamin D (1,25(OH)2D), bone alkaline phosphatase, osteocalcin, and serum C-terminal cross-links telopeptide of type I collagen (ICTP) were determined. Dual-energy X-ray absorptiometry BMD at the lumbar spine, femoral neck, and hip was also measured. Serum OPG was higher in patients than in controls (91.7 ± 25.8 vs. 77.2 ± 26.3, P = 0.02). ICTP (a bone resorption marker) was 37% higher in patients (P = 0.007). Bone mass was lower in patients at the lumbar spine, femoral neck, and total hip. Lumbar spine Z-score showed a significant progressive decrease in controls, stage I-III patients, and stage IV patients. Logistic regression analysis showed a significant association between the disease and serum OPG levels, the odds ratio per standard deviation increase of this being 1.9 (95% confidence interval 1.1–3.8, P = 0.04) after adjusting for bone mass and ICTP serum levels, as well as for alcohol and smoking history. Adjustment for alcohol intake and tobacco use did not cancel out BMD differences between patients and controls. Patients with SCHNC show increased OPG serum levels, increased bone resorption, and decreased bone mass. The OPG rise appears to be unrelated to the BMD decrease, and the BMD decrease seems to be, at least in part, independent of smoking and drinking habits. No differences in either OPG or BMD were seen between patients with and without chemotherapy. Further studies are needed to clarify the mechanisms responsible for OPG and BMD changes in SCHNC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Simonet WS, Lacey DL, Dunstan CR, et al. (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319

    Article  PubMed  CAS  Google Scholar 

  2. Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142:5050–5055

    Article  PubMed  CAS  Google Scholar 

  3. Brown JM, Vessella RL, Kostenuik PJ, Dunstan CR, Lange PH, Corey E (2001) Serum osteoprotegerin levels are increased in patients with advanced prostate cancer. Clin Cancer Res 7:2977–2983

    PubMed  CAS  Google Scholar 

  4. Sezer O, Heider U, Zavrski I, Kuhne CA, Hofbauer LC (2003) RANK ligand and osteoprotegerin in myeloma bone disease. Blood 101:2094–2098

    Article  PubMed  CAS  Google Scholar 

  5. Lipton A, Ali SM, Leitzel K, Chinchilli V, Witters L, Engle L, Holloway D, Bekker P, Dunstan CR (2002) Serum osteoprotegerin levels in healthy controls and cancer patients. Clin Cancer Res 8:2306–2310

    PubMed  CAS  Google Scholar 

  6. Clohisy DR, Perkins SL, Ramnaraine ML (2000) Review of cellular mechanisms of tumour osteolysis. Clin Orthop 373:104–114

    Article  PubMed  Google Scholar 

  7. Bruning PF, Pit MJ, de Jong-Bakker M, van den Ende A, Hart A, van Enk A (1990) Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. Br J Cancer 61:308–310

    PubMed  CAS  Google Scholar 

  8. Young DR, Virolainen P, Inoue N, Frassica FJ, Chao EY (1997) The short-term effects of cisplatin chemotherapy on bone turnover. J Bone Miner Res 12:1874–1882

    Article  PubMed  CAS  Google Scholar 

  9. ESMO (2003) Minimum clinical recommendations for diagnosis, treatment and follow-up of squamous cell carcinoma of the head and neck. Ann Oncol 14:1014–1015

    Article  Google Scholar 

  10. Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A, Ikeda K, Higashio K, Yamada Y (1999) Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14:518–527

    Article  PubMed  CAS  Google Scholar 

  11. Mezquita-Raya P, de la Higuera M, García DF, Alonso G, Ruiz-Requena ME, de Dios Luna J, Escobar-Jiménez F, Muñoz-Torres M (2005) The contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal women. Osteoporos Int 16:1368–1374

    Article  PubMed  Google Scholar 

  12. Grigorie D, Neacsu E, Marinescu M, Popa O (2003) Circulating osteoprotegerin and leptin levels in postmenopausal women with and without osteoporosis. Rom J Intern Med 41:409–415

    PubMed  CAS  Google Scholar 

  13. Riggs BL, Khosla S, Atkinson EJ, Dunstan CR, Melton LJ 3rd (2003) Evidence that type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency. Osteoporos Int 14:728–733

    Article  PubMed  CAS  Google Scholar 

  14. Takai H, Kanematsu M, Yano K, Tsuda E, Higashio K, Ikeda K, Watanabe K, Yamada Y (1998) Transforming growth factor-beta stimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells. J Biol Chem 273:27091–27096

    Article  PubMed  CAS  Google Scholar 

  15. Janssens K, ten Dijke P, Janssens S, Van Hul W (2005) Transforming growth factor-beta1 to the bone. Endocr Rev 26:743–74

    Article  PubMed  CAS  Google Scholar 

  16. Rosenthal E, McCrory A, Talbert M, Young G, Murphy-Ullrich J, Gladson C (2004) Elevated expression of TGF-beta1 in head and neck cancer-associated fibroblasts. Mol Carcinog 40:116–121

    Article  PubMed  CAS  Google Scholar 

  17. Xian CJ, Howarth GS, Cool JC, Foster BK (2004) Effects of acute 5-fluorouracil chemotherapy and insulin-like growth factor-I pretreatment on growth plate cartilage and metaphyseal bone in rats. Bone 35:739–749

    Article  PubMed  CAS  Google Scholar 

  18. Olszynski WP, Shawn Davison K, Adachi JD, Brown JP, Cummings SR, Hanley DA, Harris SP, Hodsman AB, Kendler D, McClung MR, Miller PD, Yuen CK (2004) Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment. Clin Ther 26:15–28

    Article  PubMed  Google Scholar 

  19. Karlsson KM, Karlsson C, Ahlborg HG, Valdimarsson O, Ljunghall S, Obrant KJ (2003) Bone turnover responses to changed physical activity. Calcif Tissue Int 72:675–680

    Article  PubMed  CAS  Google Scholar 

  20. Morgan H, Tumber A, Hill PA (2004) Breast cancer cells induce osteoclast formation by stimulating host IL-11 production and downregulating granulocyte/macrophage colony-stimulating factor. Int J Cancer 109:653–660

    Article  PubMed  CAS  Google Scholar 

  21. Guise TA (2000) Molecular mechanisms of osteolytic bone metastases. Cancer 88:2892–2898

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University Hospital Marqués de Valdecilla, University of Cantabria, Avenida de Valdecilla s/n, 39008, Santander, Spain

    C. Valero, J. M. Olmos, J. L. Hernández & J. González Macías

  2. Service of Medical Oncology, University Hospital Marqués de Valdecilla, University of Cantabria, 39008, Santander, Spain

    F. Rivera & M. E. Vega

Authors
  1. C. Valero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. M. Olmos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Rivera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. L. Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. E. Vega
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. González Macías
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. González Macías.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Valero, C., Olmos, J.M., Rivera, F. et al. Osteoprotegerin and Bone Mass in Squamous Cell Head and Neck Cancer Patients. Calcif Tissue Int 78, 343–347 (2006). https://doi.org/10.1007/s00223-005-0237-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-005-0237-y

Keywords

Search

Navigation