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Erschienen in: Annals of Hematology 7/2016

27.04.2016 | Original Article

Clinical significance of osteoblast precursors and osteoclast precursors in earlier diagnosis and monitoring of myeloma bone disease

verfasst von: Rong Fu, Fengping Peng, Hui Liu, Yihao Wang, Lijuan Li, Guojin Wang, Jia Song, Zonghong Shao

Erschienen in: Annals of Hematology | Ausgabe 7/2016

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Abstract

Bone disease is the most common complication of multiple myeloma (MM). In order to diagnose and monitor the bone damages earlier, we detected circulating osteoclast precursors (OCPs) and osteoblast precursors (OBPs) by flow cytometry, comparing with special biochemical markers, such as tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), carboxy-terminal cross-linking telopeptide of type I collagen (CTX), osteocalcin (OCN), and procollagen I amino-terminal propeptide (PINP). The results showed that the circulating OBPs in the newly diagnosed MM patients significantly decreased compared with the normal controls (7.14 vs 12.82 %, P = 0.045), while circulating OCPs in the newly diagnosed patients and remission patients were significantly increased than the normal controls (2.46 vs 0.17 %, P = 0.000; 1.87 vs 0.17 %, P = 0.000, respectively). According to X-ray, newly diagnosed patients were divided into stages A and B (without and with osteolytic lesions). Compared with the normal controls, the circulating OBPs in stages A and B reduced (12.82 vs 7.47 %, P = 0.041; 12.82 vs 7.14 %, P = 0.010, respectively), while the circulating OCPs elevated (0.17 vs 2.31 %, P=0.010; 0.17 % vs 2.71 %, P=0.001, respectively). The levels of TRACP-5b and CTX in the newly diagnosed patients were higher than the normal controls (P = 0.014, P = 0.037) and remission patients (P = 0.025, P = 0.003), and they were significantly higher in stage B than the normal controls (P = 0.015, P = 0.002). However, the PINP and OCN levels had no significant changes in different stages. In conclusion, abnormal circulating OBPs and OCPs were found earlier before X-ray in MM and still existed in remission patients, indicating that they may be novel predictive markers for early diagnosing and monitoring bone disease.
Literatur
1.
Zurück zum Zitat Kyle RA, Gertz MA, Witzig TE et al (2003) Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clinic Proceedings 78(1):21–33CrossRefPubMed Kyle RA, Gertz MA, Witzig TE et al (2003) Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clinic Proceedings 78(1):21–33CrossRefPubMed
2.
Zurück zum Zitat Dimopoulos M, Terpos E, Comenzo RL et al (2009) International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple myeloma. Leukemia 23(9):1545–1556CrossRefPubMed Dimopoulos M, Terpos E, Comenzo RL et al (2009) International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple myeloma. Leukemia 23(9):1545–1556CrossRefPubMed
3.
Zurück zum Zitat Terpos E, de la Fuente J, Szydlo R et al (2003) Tartrate-resistant acid phosphatase isoform 5b: a novel serum marker for monitoring bone disease in multiple myeloma. Int J Cancer 106(3):455–457CrossRefPubMed Terpos E, de la Fuente J, Szydlo R et al (2003) Tartrate-resistant acid phosphatase isoform 5b: a novel serum marker for monitoring bone disease in multiple myeloma. Int J Cancer 106(3):455–457CrossRefPubMed
4.
Zurück zum Zitat Lund T, Abildgaard N, Andersen TL et al (2010) Multiple myeloma: changes in serum C-terminal telopeptide of collagen type I and bone-specific alkaline phosphatase can be used in daily practice to detect imminent osteolysis*. Eur J Haematol 84(5):412–420CrossRefPubMedPubMedCentral Lund T, Abildgaard N, Andersen TL et al (2010) Multiple myeloma: changes in serum C-terminal telopeptide of collagen type I and bone-specific alkaline phosphatase can be used in daily practice to detect imminent osteolysis*. Eur J Haematol 84(5):412–420CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Woitge HW, Horn E, Keck AV et al (2001) Biochemical markers of bone formation in patients with plasma cell dyscrasias and benign osteoporosis. Clin Chem 47(4):686–693PubMed Woitge HW, Horn E, Keck AV et al (2001) Biochemical markers of bone formation in patients with plasma cell dyscrasias and benign osteoporosis. Clin Chem 47(4):686–693PubMed
6.
Zurück zum Zitat Kowalska M, Druzd-Sitek A, Fuksiewicz M et al (2010) Procollagen I amino-terminal propeptide as a potential marker for multiple myeloma. Clin Biochem 43(6):604–608CrossRefPubMed Kowalska M, Druzd-Sitek A, Fuksiewicz M et al (2010) Procollagen I amino-terminal propeptide as a potential marker for multiple myeloma. Clin Biochem 43(6):604–608CrossRefPubMed
7.
Zurück zum Zitat Terpos E, Dimopoulos MA, Sezer O et al (2010) The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group. Leukemia 24(10):1700–1712CrossRefPubMed Terpos E, Dimopoulos MA, Sezer O et al (2010) The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group. Leukemia 24(10):1700–1712CrossRefPubMed
8.
Zurück zum Zitat Durie BGM, Harousseau JL, Miguel JS et al (2006) International uniform response criteria for multiple myeloma. Leukemia 20(9):1467–1473CrossRefPubMed Durie BGM, Harousseau JL, Miguel JS et al (2006) International uniform response criteria for multiple myeloma. Leukemia 20(9):1467–1473CrossRefPubMed
9.
Zurück zum Zitat Terpos E, Heath DJ, Rahemtulla A et al (2006) Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-κB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. Br J Haematol 135(5):688–692CrossRefPubMed Terpos E, Heath DJ, Rahemtulla A et al (2006) Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-κB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. Br J Haematol 135(5):688–692CrossRefPubMed
10.
Zurück zum Zitat Rubin MR, Manavalan JS, Dempster DW et al (2011) Parathyroid hormone stimulates circulating osteogenic cells in hypoparathyroidism. J Clin Endocrinol Metabol 96(1):176–186CrossRef Rubin MR, Manavalan JS, Dempster DW et al (2011) Parathyroid hormone stimulates circulating osteogenic cells in hypoparathyroidism. J Clin Endocrinol Metabol 96(1):176–186CrossRef
11.
Zurück zum Zitat Manavalan JS, Cremers S, Dempster DW et al (2012) Circulating osteogenic precursor cells in type 2 diabetes mellitus. J Clin Endocrinol Metabol 97(9):3240–3250CrossRef Manavalan JS, Cremers S, Dempster DW et al (2012) Circulating osteogenic precursor cells in type 2 diabetes mellitus. J Clin Endocrinol Metabol 97(9):3240–3250CrossRef
12.
Zurück zum Zitat Petitprez V, Royer B, Desoutter J et al (2015) CD14+ CD16+ monocytes rather than CD14+ CD51/61+ monocytes are a potential cytological marker of circulating osteoclast precursors in multiple myeloma. A preliminary study. Int J Lab Hematol 37(1):29–35CrossRefPubMed Petitprez V, Royer B, Desoutter J et al (2015) CD14+ CD16+ monocytes rather than CD14+ CD51/61+ monocytes are a potential cytological marker of circulating osteoclast precursors in multiple myeloma. A preliminary study. Int J Lab Hematol 37(1):29–35CrossRefPubMed
13.
Zurück zum Zitat Komano Y, Nanki T, Hayashida K et al (2006) Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts. Arthritis Res Ther 8(5):R152CrossRefPubMedPubMedCentral Komano Y, Nanki T, Hayashida K et al (2006) Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts. Arthritis Res Ther 8(5):R152CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Roato I, Grano M, Brunetti G et al (2005) Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement. FASEB J 19(2):228–230PubMed Roato I, Grano M, Brunetti G et al (2005) Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement. FASEB J 19(2):228–230PubMed
15.
Zurück zum Zitat Eghbali-Fatourechi GZ, Lamsam J, Fraser D et al (2005) Circulating osteoblast-lineage cells in humans. N Engl J Med 352(19):1959–1966CrossRefPubMed Eghbali-Fatourechi GZ, Lamsam J, Fraser D et al (2005) Circulating osteoblast-lineage cells in humans. N Engl J Med 352(19):1959–1966CrossRefPubMed
16.
Zurück zum Zitat Matsumoto T, Kawamoto A, Kuroda R et al (2006) Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. Am J Pathol 169(4):1440–1457CrossRefPubMedPubMedCentral Matsumoto T, Kawamoto A, Kuroda R et al (2006) Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. Am J Pathol 169(4):1440–1457CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Massey HM, Flanagan AM (1999) Human osteoclasts derive from CD14-positive monocytes. Br J Haematol 106(1):167–170CrossRefPubMed Massey HM, Flanagan AM (1999) Human osteoclasts derive from CD14-positive monocytes. Br J Haematol 106(1):167–170CrossRefPubMed
18.
Zurück zum Zitat Li P, Schwarz EM, O’Keefe RJ et al (2004) Systemic tumor necrosis factor α mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor α-transgenic mice. Arthritis Rheum 50(1):265–276CrossRefPubMed Li P, Schwarz EM, O’Keefe RJ et al (2004) Systemic tumor necrosis factor α mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor α-transgenic mice. Arthritis Rheum 50(1):265–276CrossRefPubMed
19.
Zurück zum Zitat Gregoretti MG, Bergui L, Aragno M et al (1995) Osteoclast precursors circulate in the peripheral blood of patients with aggressive multiple myeloma. Leukemia 9(8):1392–1397PubMed Gregoretti MG, Bergui L, Aragno M et al (1995) Osteoclast precursors circulate in the peripheral blood of patients with aggressive multiple myeloma. Leukemia 9(8):1392–1397PubMed
20.
Zurück zum Zitat Silvestris F, Cafforio P, Tucci M et al (2003) Upregulation of osteoblast apoptosis by malignant plasma cells: a role in myeloma bone disease. Br J Haematol 122(1):39–52CrossRefPubMed Silvestris F, Cafforio P, Tucci M et al (2003) Upregulation of osteoblast apoptosis by malignant plasma cells: a role in myeloma bone disease. Br J Haematol 122(1):39–52CrossRefPubMed
21.
Zurück zum Zitat Tian E, Zhan F, Walker R et al (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349(26):2483–2494CrossRefPubMed Tian E, Zhan F, Walker R et al (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349(26):2483–2494CrossRefPubMed
22.
Zurück zum Zitat Terpos E, Mihou D, Szydlo R et al (2005) 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 19(11):1969–1976CrossRefPubMed Terpos E, Mihou D, Szydlo R et al (2005) 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 19(11):1969–1976CrossRefPubMed
23.
Zurück zum Zitat Tosi P, Zamagni E, Cellini C et al (2006) First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma. Eur J Haematol 76(5):399–404CrossRefPubMed Tosi P, Zamagni E, Cellini C et al (2006) First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma. Eur J Haematol 76(5):399–404CrossRefPubMed
24.
Zurück zum Zitat Heider U, Kaiser M, Müller C et al (2006) Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment. Eur J Haematol 77(3):233–238CrossRefPubMed Heider U, Kaiser M, Müller C et al (2006) Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment. Eur J Haematol 77(3):233–238CrossRefPubMed
25.
Zurück zum Zitat Eom KS, Kim SJ, Lee JJ et al (2014) Changes in osteoblastic activity in patient who received bortezomib as second line treatment for plasma cell myeloma: a prospective multicenter study. Bio Med Res Int 2014:245247 Eom KS, Kim SJ, Lee JJ et al (2014) Changes in osteoblastic activity in patient who received bortezomib as second line treatment for plasma cell myeloma: a prospective multicenter study. Bio Med Res Int 2014:245247
26.
Zurück zum Zitat Lund T, Søe K, Abildgaard N et al (2010) First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro. Eur J Haematol 85(4):290–299CrossRefPubMedPubMedCentral Lund T, Søe K, Abildgaard N et al (2010) First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro. Eur J Haematol 85(4):290–299CrossRefPubMedPubMedCentral
Metadaten
Titel
Clinical significance of osteoblast precursors and osteoclast precursors in earlier diagnosis and monitoring of myeloma bone disease
verfasst von
Rong Fu
Fengping Peng
Hui Liu
Yihao Wang
Lijuan Li
Guojin Wang
Jia Song
Zonghong Shao
Publikationsdatum
27.04.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 7/2016
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-016-2657-3

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