DIAGNOSTICS OF BONE METABOLISM DISORDERS IN ONCOLOGICAL DISEASES
https://doi.org/10.17709/2409-2231-2015-2-4-88-97
Abstract
Osteoporosis is one of the most significant bone complications of cancer. About 1.5 million cancer patients worldwide have bone metastases. Patients with myeloma, breast cancer, prostate, thyroid, bladder and lung have very high risk of development of bone lesions and related complications. Currently, osteodensitometry is the gold standard for the diagnosis of osteoporosis. In recent years we frequently use the innovative imaging techniques for bone metastases, such as CT, MRI, PET/CT. Unfortunately, the diagnostic value of these methods is that it is not always possible to identify abnormalities of bone metabolism in cancer, especially in the early stages. This review shows the world experience of usage of biochemical markers of bone resorption (calcium, hydroxyproline, NTX, CTX, PYD, DPD, TRAP-5b, bone sialoprotein - BSP) and markers of bone synthesis (osteocalcin, CSF, ACF, Karlovy vary IFF), their advantages and disadvantages. The level of these markers is increased in most patients with osteoporosis and bone metastases, it is suggesting a potential role in early diagnosis of bone metastases.
About the Authors
O. I. ApolikhinRussian Federation
Phd, MD, professor, director of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
B. Y. Alekseev
Russian Federation
Phd, MD, professor, vice director on science, N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
A. V. Sivkov
Russian Federation
PhD, first vice director, N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
N. G. Keshishev
Russian Federation
PhD, head of innovation division, N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
A. A. Trudov
Russian Federation
junior researcher of innovation division of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
E. Z. Rabinovich
Russian Federation
PhD, senior researcher of innovation division of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
A. A. Kachmazov
Russian Federation
PhD, head of oncological department of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
References
1. Kobayashi S., Takahashi H. E., Ito A., Saito N., Nawata M., Horiuchi H., Ohta H., Ito A., Iorio R., Yamamoto N., Takaoka K. Trabecular minimodeling in human iliac bone. Bone. 2003; 32 (2): 163–169.
2. Alekseev B.Ia., Niushko K. M., Kaprin A. D. The pathogenesis, predictors, and prevention of bone complications in patients with castration-resistant metastatic prostate cancer. Onkologiia. Zhurnal imeni P. A. Gerzena 2013; 1 (4): 81–85. (Russian).
3. Nushko K. M., Kalpinskiy A. S., Kaprin A. D. Prevention of complications in castrate-refractory prostate cancer patients with bone metastases. Research’n Practical Medicine Journal. 2015; 2 (3): 76–81. (Russian).
4. Coleman RE. Skeletal complications of malignancy. Cancer. 1997; 80 Suppl: 1588–1594.
5. Lipton A. Pathophysiology of bone metastases: how this knowledge may lead to therapeutic intervention. J Support Oncol. 2004; 2 (3): 205–13.
6. Lipton A., Theriault R. L., Hortobagyi G. N., Simeone J., Knight R. D., Mellars K., Reitsma D. J., Heffernan M., Seaman J. J. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000; 88 (5): 1082–1090.
7. Abildgaard N., Brixen K., Kristensen J. E., Vejlgaard T., Charles P., Nielsen J. L. Assessment of bone involvement in patients with multiple myeloma using bone densitometry. Eur J Haematol. 1996; 57 (5): 370–376.
8. Volodina G. I., Vakhitov V. I., Sevast’yanova G. D., Sadykov M. R. Otdalennye metastazy raka legkikh. Kazan Medical Journal. 2001; 82 (6): 428–430. (Russian).
9. Akhadov T. A., Panov V. O., Aikhkhoff U. Magnitno-rezonansnaya tomografiya spinnogo mozga i pozvonochnika. Moscow, 2000. (Russian).
10. Karmazanovskii G. G. Spiral’naya komp’yuternaya tomografiya: bolyusnoe kontrastnoe usilenie. Moscow: “Vidar” Publ., 2005. (Russian).
11. Kornienko V. N., Pronin I. N. Diagnosticheskaya neiroradiologiya. Moscow, 2006. (Russian).
12. Karyakina U. V. Radiation diagnostic studies and their efficiency in closed injury of the lower cervical spine. Vestnik rentgenologii i radiologii. 2006; 5: 48–53. (Russian).
13. Stegachev S. K. Proskurina M. F., Yudin A. L. Magnitno-rezonansnaya tomografiya — metod vizualizatsii kostnogo mozga. Materialy Nevskogo radiologicheskogo foruma «Iz budushchego v nastoyashchee». Saint Petersburg, 2003. (Russian).
14. Bazhadug O. B., Tupitsin N. N., Tyulyandin S. A. Znachenie vyyavleniya mikrometastazov v krovi i kostnom mozge u bol’nykh rakom molochnoi zhelezy. Sovremennaya onkologiya. Aktual’nye voprosy klinicheskoi onkologii. 2004; 6 (4): 149–150. (Russian).
15. Akberov N. K., Andrienko S. V., Laryukov A. V. Scintigraphy of skeleton in early detection of the lung cancer metastases. Kazan Medical Journal. 2002; 83 (1): 31–32. (Russian).
16. Lin W. Y., Lin C. P., Yeh S. J., Hsieh B. T., Tsai Z. T., Ting G, Yen T. C., Wang S. J., Knapp F. F. Jr, Stabin M. G. Rhenium-188 hydroxyethylidene diphosphonate: a new generator-produced radiotherapeutic drug of potential value for the treatment of bone metastases. Eur J Nucl Med. 1997; 24 (6):590–595.
17. Davydov G. A. K voprosu o metastaticheskom porazhenii pozvonochnika. Materialy s”ezda Rossiiskogo obshchestva yadernoi meditsiny «Sovremennye problemy yadernoi meditsiny i radiofarmatsevtiki». Obninsk, 2000. (Russian).
18. Khmelevsky Ye. V., Bozhenko V. K., Panshin G. A., Dobrenky M. N., Bolshakova S. A. Predictors of the efficiency of radiotherapy for metastatic skeletal lesions. Rossiiskii onkologicheskii zhurnal. 2006; 4: 16–19. (Russian).
19. Roberts M., Hayward J. L. Bone scanning and farly breast cancer five-years follow-up. Lancet. 1983; 3 (8331): 997–998.
20. Demirkan B., Başkan Z., Alacacioğlu A., Görken I. B., Bekiş R., Ada E., Osma E., Alakavuklar M. False negative bone scintigraphy in a patient with primary breast cancer: a possible transient phenomenon of bisphosphonate (alendronate) treatment. Tumori. 2005; 91 (1): 77–80.
21. Ohno Y., Koyama H., Nogami M., Takenaka D., Yoshikawa T., Yoshimura M., Kotani Y., Nishimura Y., Higashino T., Sugimura K. Whole-body MR imaging vs. FDG-PET: comparison of accuracy of M-stage diagnosis for lung cancer patients. J Magn Reson Imaging. 2007; 26 (3): 498–509.
22. Schmidt G. P., Haug A. R., Schoenberg S. O., Reiser M. F. Wholebody MRI and PET-CT in the management of cancer patients. Eur Radiol. 2006; 16 (6): 1216–1225.
23. Regelsberger J., Langer N., Fritzsche E., Westphal M. Intraoperative ultrasound of intra- and extramedullary tumour. Ultraschall Med. 2003; 24 (6): 399–403.
24. Zozulya Yu. A., Slyn’ko E. I. Spinal’nye sosudistye opukholi i mal’formatsii. Kiev: “EksOb” Publ., 2000. (Russian).
25. Maurer F., Ambacher T, Volkmann R, Weller S. Pathologic fractures: diagnostic and therapeutic considerations and results of treatment. Langenbecks Arch Chir. 1995; 380 (4): 207–217.
26. Vinholes J., Coleman R., Eastell R. Effects of bone metastases on bone metabolism: implications for diagnosis, imaging and assessment of response to cancer treatment. Cancer Treat Rev. 1996; 22: 289–331.
27. Woitge H. W., Pecherstorfer M., Li Y., Keck A. V., Horn E., Ziegler R., Seibel M. J. Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices. J Bone Miner Res. 1999;14 (5): 792–801.
28. Vinholes J. J. F., Purohit O. P., Abbey M. E., Eastell R., Coleman R. E. Relationships between biochemical and symptomatic response in a double-blind randomised trial of pamidronate for metastatic bone disease. Ann Oncol. 1997; 8: 1243–1250.
29. Miura H., Yamamoto I., Takada M., Kigami Y., Ohta T., Yuu I., Hamanaka Y., Matsushita R., Morita R. Diagnostic validity of bone metabolic markers for bone metastasis. Endocr J. 1997; 44 (5): 751–757.
30. Peacock M., Robertson W. G., Nordin B. E. Relation between serum and urinary calcium with particular reference to parathyroid activity. Lancet. 1969; 1: 384–386.
31. Coleman R. E., Whitaker K. B., Moss D. W., Mashiter G., Fogelman I., Rubens R. D. Biochemical prediction of response of bone metastases to treatment. Br J Cancer. 1988; 58: 205–210.
32. Campbell F. C., Blamey R. W., Woolfson A. M., Elston C. W., Hosking D. J. Calcium excretion (CaE) in metastatic breast cancer. Br J Surg. 1983; 70: 202–204.
33. Coleman R. E. Assessment of response to treatment. In: Rubens R. D., Fogelman I., eds. Bone metastases: diagnosis and treatment. London: Springer-Verlag, 1991.
34. Deacon A. C., Hulme P., Hesp R., Green J. R., Tellez M., Reeve J. Estimation of whole body bone resorption rate: a comparison of urinary total hydroxyproline excretion with two radioisotopic tracer methods in osteoporosis. Clin Chim Acta. 1987; 166: 297–306.
35. Gasser A., Celada A., Courvoisier B., Depierre D., Hulme.PM., Rinsler M., Williams D., Wootton R. The clinical measurement of urinary total hydroxyproline excretion. Clin Chim Acta. 1979; 95 (3): 487–491.
36. Mautalen C. A. Circadian rhythm of urinary total and free hydroxyproline excretion and its relation to creatinine excretion. J Lab Clin Med. 1970; 75: 11–18.
37. Robins S. P., Woitge H., Hesley R., Ju J., Seyedin S., Seibel M. J. Direct, enzyme-linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption. J Bone Miner Res. 1994; 9: 1643–1649.
38. Eastell R., Hampton L., Colwell A., et al. Urinary collagen crosslinks are highly correlated with radioisotopic measurements of bone resorption [abstract]. Osteoporosis. 1990; 2: 469–470.
39. Delmas P. D., Schlemmer A., Gineyts E., Riis B., Christiansen C. Urinary excretion of pyridinoline crosslinks correlates with bone turnover measured on iliac crest biopsy in patients with vertebral osteoporosis. J Bone Miner Res. 1991; 6: 639–644.
40. Bonde M., Qvist P., Fledelius C., Riis B. J., Christiansen C. Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin Chem. 1994; 40: 2022–2025.
41. Hanson D. A., Weis M. A., Bollen A. M., Maslan S. L., Singer F. R., Eyre D. R. A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine. J Bone Miner Res. 1992; 7: 1251–1258.
42. Vasikaran S., Eastell R., Bruyère O., Foldes A. J., Garnero P., Griesmacher A., McClung M., Morris H. A., Silverman S., Trenti T., Wahl D. A., Cooper C., Kanis J. A., for the IOF-IFCC Bone Marker Standards Working Group: Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011; 22: 391–420.
43. Bergmann P., Body J. J., Boonen S., Boutsen Y., Devogelaer J. P., Goemaere S., Kaufman J. M., Reginster J. Y., Gangji V., Members of the Advisory Board on Bone Markers. Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian bone club. Int J Clin Pract. 2009; 63 (1): 19–26.
44. Bjarnason N. H., Henriksen E. E. G., Alexandersen P., Christgau S., Henriksen D. B., Christiansen C. Mechanism of circadian variation in bone resorption. Bone. 2002; 30 (1): 307–313.
45. Seibel M. J., Woitge H. W., Pecherstorfer M., Karmatschek M., Horn E., Ludwig H., Armbruster F. P., Ziegler R. Serum immunoreactive bone sialoprotein as a new marker of bone turnover in metabolic and malignant bone disease. J Clin Endocrinol Metab. 1996; 81 (9): 3289–4.
46. Garnero P. New biochemical markers of bone turnover. IBMS Bone KEy. 2008; 5 (3): 84–102.
47. Halleen J. M., Alatalo S. L., Janckila A. J., Woitge H. W., Seibel M. J., Väänänen H. K. Serum tartrate-resistant acid phosphatase is a specifi c and sensitive marker of bone resorption. Clin Chem. 2001; 47: 597–600.
48. Lyubimova N. V., Pashkov M. V., Tyulandin S. A., Goldberg V. E., Kushlinskiy N. E. Tartrat-resistant phosphatase is the biochemical criterion of metastases in bones. Sibirskiy onkologicheskiy zhurnal. 2004; 4 (12): 23–5. (Russian).
49. Chao T. Y., Ho C. L., Lee S. H., Chen M. M., Janckila A., Yam L. T. Tartrate-resistant acid phosphatase 5b as a serum marker of bone metastasis in breast cancer patients. J Biomed Sci. 2004; 11: 511–6.
50. Gerdhem P., Ivaska K. K., Alatalo S. L., Halleen J. M., Hellman J., Isaksson A., Pettersson K., Vddndnen H. K., Еkesson K., Obrant K. J. Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res. 2004; 19: 386–93.
51. Terpos E., Samarkos M., Meletis C., Apostolidou E., Tsironi M., Korovesis K, Mavrogianni D., Viniou N., Meletis J. Unusual association between increased bone resorption and presence of paroxysmalnocturnal hemoglobinuria phenotype in multiple myeloma. Int J Hematol. 2003; 7: 344–8.
52. Blumsohn A., Hannon R. A., Eastell R. Apparent instability of osteocalcin in serum as measured with different commercially available immunoassays. Clin Chem. 1995; 41: 318–319.
53. Halleen J. M., Alatalo S. L., Suominen H., Cheng S., Janckila A. J., Väänänen H. K. Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res. 2000; 15 (7): 1337–1345.
54. Rogers R. S., Dawson A. W., Wang Z., Thyfault J. P., Hinton P. S. Acute response of plasma markers of bone turnover to a single bout of resistance training or plyometrics. J Appl Physiol. 2011; 111: 1353–1360.
55. Brown J. P., Delmas P. D., Malaval L., Edouard C., Chapuy M. C., Meunier P. J. Serum bone Glaprotein: a specifi c marker for bone formation in postmenopausal osteoporosis. Lancet. 1984; 1: 1091–3.
56. Delmas P. D. Biochemical markers of bone turnover. Acta Orthop. 1995; 66: 176–82.
57. Taylor A. K., Linkhart S., Mohan S., Christenson R. A., Singer F. R., Baylink D. J. Multiple osteocalcin fragments in human urine and serum as detected by a midmolecule osteocalcin radioimmunoassay. J Clin Endocrinol Metab. 1990; 70 (2): 467–72.
58. Page A. E., Hayman A. R., Andersson L. M. B., Chambers T. J., Warburton M. J. Degradation of bone matrix proteins by osteoclast cathepsins. Int J Biochem. 1993; 25 (4): 545–50.
59. Denisov-Nikol’skii Yu. I., Mironov S. P., Omel’yanenko N. P., Matveichuk I. A. Aktual’nye problemy teoreticheskoi i klinicheskoi osteoartrologii. Moscow: “Novosti” Publ.; 2005. (Russian).
60. Stokes F. J., Ivanov P., Bailey L. M., Fraser W. D. The effects of sampling procedures and storage conditions on short-term stability of blood-based biochemical markers of bone metabolism. Clin Chem. 2011; 57 (1): 138–140.
61. Moss D. W. Diagnostic aspects of alkaline phosphatase and its isoenzymes. Clin Biochem. 1987; 20 (4): 225–30.
62. Hooper N. M. Glycosyl-phosphatidylinositol anchored membrane enzymes. Clin Chim Acta. 1997; 266 (1): 3–12.
63. Wennberg C., Hessle L., Lundberg P., Mauro S., Narisawa S., Lerner U. H., Millán J. L. Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice. J Bone Miner Res. 2000; 15 (10): 1879–88.
64. Dobnig H., Sipos A., Jiang Y., Fahrleitner-Pammer A., Ste-Marie L. G., Gallagher J. C., Pavo I., Wang J., Eriksen E. F. Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. J Clin Endocrinol Metab. 2005; 90 (7): 3970–7.
65. Fohr B., Dunstan C. R., Seibel M. J. Markers of bone remodeling in metastatic bone disease. J Clin Endocrinol Metab. 2003; 88 (11): 5059–75.
66. Wallach J. Interpretation of diagnosis tests. Boston: Little Brown and Co.; 1986.
67. Magnusson P., Degerblad M., Saaf M., Larsson L., Thoren M. Diff erent responses of bone alkaline phosphatase isoforms during recombinant insulin-like growth factor-I (IGF-I) and during growth hormone therapy in adults with growth hormone deficiency. J Bone Miner Res. 1997; 12: 210–220.
68. Bettica P., Moro L. Biochemical markers of bone metabolism in the assessment ofosteoporosis. J Int Fed Clin Chem. 1995; 7 (1): 16–22.
69. Berruti A., Dogliotti L., Gorzegno G., Torta M., Tampellini M., Tucci M., Cerutti S., Frezet M. M., Stivanello M., Sacchetto G., Angeli A. Diff erential patterns of bone turnover in relation to bone pain and disease extent in bone in cancer patients with skeletal metastases. Clin Chem. 1999; 45 (8): 1240–7.
70. Wymenga L. F., Groenier K., Schuurman J., Boomsma J. H., Elferink R. O., Mensink H. J. Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis. Br J Urol. 2001; 88: 231–5.
71. Bramer J. A. M., Abudu A. A., Tillman R. M., Carter S. R., Sumathi V. P., Grimer RJ. Pre-and post-chemotherapy alkaline phosphatase levels as prognostic indicators in adults with localised osteosarcoma. Eur J Cancer. 2005; 41 (18): 2846–52.
72. Stokkel M. P., Linthorst M. F., Borm J. J., Taminiau A. H., Pauwels E. K. A reassessment of bone scintigraphy and commonly tested pretreatment biochemical parameters in newly diagnosed osteosarcoma. J Cancer Res Clin Oncol. 2002; 128 (7): 393–9.
73. Wang J., Pei F., Tu C., Zhang H., Qiu X. Serum bone turnover markers in patients with primary bone tumors. Oncology. 2007; 72: 338–42.
74. Lipton A., Demers L., Curley E., Chinchilli V., Gaydos L., Hortobagyi G., Theriault R., Clemens D., Costa L., Seaman J., Knight R. Markers of bone resorption in patients treated with pamidronate. Eur J Cancer. 1998; 34 (13): 2021–2026.
75. Souberbielle J. C., Cormier C., Kindermans C. Bone markers in clinical practice. Curr Opin Rheumatol. 1999; 11 (4): 312–319.
76. Ross P. D., Kress B. C., Parson R. E., Wasnich R. D., Armour K. A., Mizrahi I. A. Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study. Osteoporos Int. 2000; 11 (1): 76–82.
77. Wheater G., Elshahaly M., Tuck S. P., Datta H. K., van Laar J. M. The clinical utility of bone marker measurements in osteoporosis. J Trans Med. 2013, 11: 201.
Review
For citations:
Apolikhin O.I., Alekseev B.Y., Sivkov A.V., Keshishev N.G., Trudov A.A., Rabinovich E.Z., Kachmazov A.A. DIAGNOSTICS OF BONE METABOLISM DISORDERS IN ONCOLOGICAL DISEASES. Research and Practical Medicine Journal. 2015;2(4):88-97. (In Russ.) https://doi.org/10.17709/2409-2231-2015-2-4-88-97