鍶的成骨效應及其在骨科中應用的研究進展_《中國修復重建外科雜志》

作者：

李蕾 , 雷云坤 , 孟增東

云南省第一人民醫院骨科（昆明，650001）;

關鍵詞：

鍶成骨效應骨組織工程

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的綜述鍶（Sr）的成骨效應及其在骨科中應用的研究進展。方法廣泛查閱近年國內外有關Sr成骨效應及其在骨科中應用的文獻，并對其進行分析。結果體內外研究表明Sr具有促進骨生成和抑制骨重吸收的雙重作用。臨床上，Sr被應用于骨質疏松的治療，組織工程生物材料的復合及骨腫瘤、骨轉移瘤的治療。結論Sr是骨組織工程替代材料的重要復合元素之一，能增強骨替代材料的機械性能和生物學性能，在骨組織工程中有一定發展潛力。

引用本文： 李蕾,雷云坤,孟增東. 鍶的成骨效應及其在骨科中應用的研究進展. 中國修復重建外科雜志, 2012, 26(11): 1398-1402. doi: 復制

1.	Langer R, Vacanti P. Tissue engineering. Science, 1993, 260(5110): 920-926.
2.	Dahl SG, Allain P, Marie PJ, et al. Incorporation and distribution of strontium in bone. Bone, 2001, 28(4): 446-453.
3.	Reginster JY, Deroisy R, Jupsin I. Strontium ranelate: a new paradigm in the treatment of osteoporosis. Drugs Today (Barc), 2003, 39(2): 89-101.
4.	Jupsin I, Collette J, Henrotin Y, et al. Strontium ranelate (Fujisawa/Servier). Curr Opin Investig Drugs, 2005, 6(4): 435-444.
5.	Marie PJ. Strontium ranelate: a novel mode of action optimizing bone formation and resorption. Osteoporos Int, 2005, 16 Suppl 1: S7-10.
6.	Bonnelye E, Chabadel A, Saltel F, et al. Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone, 2008, 42(1): 129-138.
7.	Reginster JY, Deroisy R, Neuprez A, et al. Strontium ranelate: new data on fracture prevention and mechanisms of action. Curr Osteoporos Rep, 2009, 7(3): 96-102.
8.	Fromigué O, Haÿ E, Barbara AE, et al. Essential role of nuclear factor of activated T cells (NFAT)-mediated Wnt signaling in osteoblast differentiation induced by strontium ranelate. J Biol Chem, 2010, 285(33): 25251-25258.
9.	Trouvin AP, Goëb V. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss. Clin Interv Aging, 2010, 5: 345-354.
10.	Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. Semin Nucl Med, 2010, 40(2): 89-104.
11.	Das T, Chakraborty S, Sarma HD, et al. (170)Tm-EDTMP: a potential cost-effective alternative to (89)SrCl(2) for bone pain palliation. Nucl Med Biol, 2009, 36(5): 561-568.
12.	Römer P, Behr M, Proff P, et al. Effect of strontium on human Runx2+/- osteoblasts from a patient with cleidocranial dysplasia. Eur J Pharmacol, 2011, 654(3): 195-199.
13.	Peng S, Liu XS, Huang S, et al. The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: involvement of osteoprotegerin. Bone, 2011, 49(6): 1290-1298.
14.	Yamaguchi M, Weitzmann MN. The intact strontium ranelate complex stimulates osteoblastogenesis and suppresses osteoclastogenesis by antagonizing NF-κB activation. Mol Cell Biochem, 2011, 359(1-2): 399-407.
15.	Rybchyn MS, Slater M, Conigrave AD, et al. An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. J Biol Chem, 2011, 286(27): 23771-23779.
16.	Yang F, Yang D, Tu J, et al. Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling. Stem Cells, 2011, 29(6): 981-991.
17.	Caverzasio J, Thouverey C. Activation of FGF receptors is a new mechanism by which strontium ranelate induces osteoblastic cell growth. Cell Physiol Biochem, 2011, 27(3-4): 243-250.
18.	Braux J, Velard F, Guillaume C, et al. A new insight into the dissociating effect of strontium on bone resorption and formation. Acta Biomater, 2011, 7(6): 2593-2603.
19.	Ma HT, Peng Z, Hiragun T, et al. Canonical transient receptor potential 5 channel in conjunction with Orai1 and STIM1 allows Sr2+ entry, optimal influx of Ca2+, and degranulation in a rat mast cell line. J Immunol, 2008, 180(4): 2233-2239.
20.	Caudrillier A, Hurtel-Lemaire AS, Wattel A, et al. Strontium ranelate decreases receptor activator of nuclear factor-κB ligand-induced osteoclastic differentiation in vitro: involvement of the calcium-sensing receptor. Mol Pharmacol, 2010, 78(4): 569-576.
21.	Takaoka S, Yamaguchi T, Yano S, et al. The Calcium-sensing Receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization. Horm Metab Res, 2010, 42(9): 627-631.
22.	Coulombe J, Fauren H, Robin B, et al. In vitro effects of strontium ranelate on the extracellular calcium-sensing receptor. Biochem Biophys Res Commun, 2004, 323(4): 1184-1190.
23.	Verberckmoes SC, De Broe ME, D’Haese PC. Dose-dependent effects of strontium on osteoblast function and mineralization. Kidney Int, 2003, 64(2): 534-543.
24.	謝玲, 裴志東, 薛琪. 89鍶治療骨轉移性癌痛的臨床觀察. 中國鄉村醫藥, 2008, 15(5): 19-20.
25.	祁崗, 于梅花, 朱艷媚, 等. 90鍶敷貼器治療皮膚血管瘤療效觀察. 新醫學, 2011, 42(4): 260-262.
26.	MacDonald NS, Nusbaum RE, Stcarns R, et al. The skeletal deposition of non-radioactivc strontium. J Biol Chem, 1951, 188(1): 137-143.
27.	Boivin G, Deloffre P, Perrat B, et al. Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J Bone Miner Res, 1996, 11(9): 1302-1311.
28.	Brennan TC, Rybchyn MS, Green W, et al. Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol, 2009, 157(7): 1291-1300.
29.	Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell, 1998, 93(2): 165-176.
30.	Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol, 2002, 22(4): 549-553.
31.	Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature, 1999, 397(6717): 315-323.
32.	Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology, 2001, 142(12): 5050-5055.
33.	Ali MM, Yoshizawa T, Ishibashi O. PIASxbeta is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts. J Cell Sci, 2007, 120(Pt 15): 2565-2573.
34.	Aliprantis AO, Ueki Y, Sulyanto R, et al. NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism. J Clin Invest, 2008, 118(11): 3775-3789.
35.	Ikeda F, Nishimura R, Matsubara T, et al. Activation of NFAT signal in vivo leads to osteopenia associated with increased osteoclastogenesis and bone-resorbing activity. J Immunol, 2006, 177(4): 2384-2390.
36.	Guo J, Jin J, Cooper LF. Dissection of sets of genes that control the character of wnt5a-deficient mouse calvarial cells. Bone, 2008, 43(5): 961-971.
37.	Cheng SL, Shao JS, Cai J, et al. Msx2 exerts bone anabolism via canonical Wnt signaling. J Biol Chem, 2008, 283(29): 20505-20522.
38.	Fromigué O, Haÿ E, Barbara A, et al. Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. J Cell Mol Med, 2009, 13(8B): 2189-2199.
39.	Dong SW, Ying DJ, Duan XJ, et al. Bone regeneration using an acellular extracellular matrix and bone marrow mesenchymal stem cells expressing Cbfα1. Biosci Biotechnol Biochem, 2009, 73(10): 2226-2233.
40.	Hamdy NA. Strontium ranelate improves bone microarchitecture in osteoporosis. Rheumatology (Oxford), 2009, 48 Suppl 4: iv9-13.
41.	Cesareo R, Napolitano C, Iozzino M. Strontium ranelate in postmenopausal osteoporosis treatment: a critical appraisal. Int J Womens Health, 2010, 2: 1-6.
42.	Kay MI, Young RA, Posner AS. Crystal structure of hydroxyapatite. Nature, 1964, 204: 1050-1052.
43.	陳德敏, 傅飛遠. 不同含鍶量的摻鍶羥基磷灰石固溶體機械性能評價. 口腔材料器械雜志, 2001, 10(4): 178-179.
44.	倪國新, 呂維加, 曲廣運, 等. 鍶羥基磷灰石生物活性骨水泥應用于髖關節置換的研究. 中華創傷骨科組織, 2007, 9(8): 708-710.
45.	閆鈞, 張玉梅, 憨勇, 等. 鍶磷灰石涂層鈦種植體骨結合的動物實驗. 中華口腔醫學雜志, 2010, 45(2): 89-93.
46.	廖大鵬, 周正炎, 顧云峰, 等. 鍶磷灰石生物特性的初步研究. 華西口腔醫學雜志, 2002, 20(3): 172-174.
47.	李峰, 趙信義. 含鍶磷酸鈣骨水泥體內降解性能. 生物醫學工程與臨床, 2006, 10(4): 210-213.
48.	陳德敏, 劉雪陽. 鍶磷灰石多孔陶瓷不同孔隙率對成骨細胞生物學行為的影響. 組織工程與重建外科雜志, 2006, 2(3): 123-127.
49.	余喜訊, 陳元維, 史國齊, 等. 摻鍶聚磷酸鈣骨組織工程支架材料與成骨細胞及內皮細胞的相容性研究. 中國組織工程研究與臨床康復, 2007, 11(5): 857-860.
50.	傅飛遠, 陳德敏, 張建中. MTT比色法評價摻鍶羥基磷灰石固溶體細胞毒性. 生物醫學工程雜志, 2001, 18(3): 389-390, 415.
51.	郝瑞然, 王德平. 改性硼硅酸鹽生物玻璃的可控降解性能. 中國組織工程研究與臨床康復, 2008, 12(10): 1962-1965.
52.	Pan HB, Zhao XL, Zhang X, et al. Strontium borate glass: potential biomaterial for bone regeneration. J R Soc Interface, 2010, 7(48): 1025-1031.
53.	Pina S, Vieira SI, Rego P, et al. Biological responses of brushite-forming Zn- and ZnSr-substituted beta-tricalcium phosphate bone cements. Eur Cell Mater, 2010 , 20: 162-177.
54.	余喜訊, 顧志鵬, 任大偉, 等. 新型骨科材料SCPP對成骨細胞促血管化生長因子表達影響的研究. 四川大學學報: 工程科學版, 2011, 43(1): 219-225.
55.	王楠, 郝永強, 何國, 等. 纖維多孔鈦微球復合納米鍶磷灰石修復骨缺損的實驗研究. 中華骨科雜志, 2009, 29(7): 672-676.
56.	朱廣文, 張延軍, 李鍵, 等. 核素Sr-89治療前列腺癌骨轉移臨床價值及血清tPSA變化的研究. 放射免疫學雜志, 2009, 22(1): 6-7.
57.	胥杰, 陳曉. 89Sr治療30例肺癌多發骨轉移的療效觀察. 中國呼吸與危重監護雜志, 2008, 7(2): 104-106.
58.	Logothetis CJ, Navone NM, Lin SH. Understanding the biology of bone metastases: key to the effective treatment of prostate cancer. Clin Cancer Res, 2008, 14(6): 1599-1602.

1. Langer R, Vacanti P. Tissue engineering. Science, 1993, 260(5110): 920-926.
2. Dahl SG, Allain P, Marie PJ, et al. Incorporation and distribution of strontium in bone. Bone, 2001, 28(4): 446-453.
3. Reginster JY, Deroisy R, Jupsin I. Strontium ranelate: a new paradigm in the treatment of osteoporosis. Drugs Today (Barc), 2003, 39(2): 89-101.
4. Jupsin I, Collette J, Henrotin Y, et al. Strontium ranelate (Fujisawa/Servier). Curr Opin Investig Drugs, 2005, 6(4): 435-444.
5. Marie PJ. Strontium ranelate: a novel mode of action optimizing bone formation and resorption. Osteoporos Int, 2005, 16 Suppl 1: S7-10.
6. Bonnelye E, Chabadel A, Saltel F, et al. Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone, 2008, 42(1): 129-138.
7. Reginster JY, Deroisy R, Neuprez A, et al. Strontium ranelate: new data on fracture prevention and mechanisms of action. Curr Osteoporos Rep, 2009, 7(3): 96-102.
8. Fromigué O, Haÿ E, Barbara AE, et al. Essential role of nuclear factor of activated T cells (NFAT)-mediated Wnt signaling in osteoblast differentiation induced by strontium ranelate. J Biol Chem, 2010, 285(33): 25251-25258.
9. Trouvin AP, Goëb V. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss. Clin Interv Aging, 2010, 5: 345-354.
10. Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. Semin Nucl Med, 2010, 40(2): 89-104.
11. Das T, Chakraborty S, Sarma HD, et al. (170)Tm-EDTMP: a potential cost-effective alternative to (89)SrCl(2) for bone pain palliation. Nucl Med Biol, 2009, 36(5): 561-568.
12. Römer P, Behr M, Proff P, et al. Effect of strontium on human Runx2+/- osteoblasts from a patient with cleidocranial dysplasia. Eur J Pharmacol, 2011, 654(3): 195-199.
13. Peng S, Liu XS, Huang S, et al. The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: involvement of osteoprotegerin. Bone, 2011, 49(6): 1290-1298.
14. Yamaguchi M, Weitzmann MN. The intact strontium ranelate complex stimulates osteoblastogenesis and suppresses osteoclastogenesis by antagonizing NF-κB activation. Mol Cell Biochem, 2011, 359(1-2): 399-407.
15. Rybchyn MS, Slater M, Conigrave AD, et al. An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. J Biol Chem, 2011, 286(27): 23771-23779.
16. Yang F, Yang D, Tu J, et al. Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling. Stem Cells, 2011, 29(6): 981-991.
17. Caverzasio J, Thouverey C. Activation of FGF receptors is a new mechanism by which strontium ranelate induces osteoblastic cell growth. Cell Physiol Biochem, 2011, 27(3-4): 243-250.
18. Braux J, Velard F, Guillaume C, et al. A new insight into the dissociating effect of strontium on bone resorption and formation. Acta Biomater, 2011, 7(6): 2593-2603.
19. Ma HT, Peng Z, Hiragun T, et al. Canonical transient receptor potential 5 channel in conjunction with Orai1 and STIM1 allows Sr2+ entry, optimal influx of Ca2+, and degranulation in a rat mast cell line. J Immunol, 2008, 180(4): 2233-2239.
20. Caudrillier A, Hurtel-Lemaire AS, Wattel A, et al. Strontium ranelate decreases receptor activator of nuclear factor-κB ligand-induced osteoclastic differentiation in vitro: involvement of the calcium-sensing receptor. Mol Pharmacol, 2010, 78(4): 569-576.
21. Takaoka S, Yamaguchi T, Yano S, et al. The Calcium-sensing Receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization. Horm Metab Res, 2010, 42(9): 627-631.
22. Coulombe J, Fauren H, Robin B, et al. In vitro effects of strontium ranelate on the extracellular calcium-sensing receptor. Biochem Biophys Res Commun, 2004, 323(4): 1184-1190.
23. Verberckmoes SC, De Broe ME, D’Haese PC. Dose-dependent effects of strontium on osteoblast function and mineralization. Kidney Int, 2003, 64(2): 534-543.
24. 謝玲, 裴志東, 薛琪. 89鍶治療骨轉移性癌痛的臨床觀察. 中國鄉村醫藥, 2008, 15(5): 19-20.
25. 祁崗, 于梅花, 朱艷媚, 等. 90鍶敷貼器治療皮膚血管瘤療效觀察. 新醫學, 2011, 42(4): 260-262.
26. MacDonald NS, Nusbaum RE, Stcarns R, et al. The skeletal deposition of non-radioactivc strontium. J Biol Chem, 1951, 188(1): 137-143.
27. Boivin G, Deloffre P, Perrat B, et al. Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J Bone Miner Res, 1996, 11(9): 1302-1311.
28. Brennan TC, Rybchyn MS, Green W, et al. Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol, 2009, 157(7): 1291-1300.
29. Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell, 1998, 93(2): 165-176.
30. Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol, 2002, 22(4): 549-553.
31. Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature, 1999, 397(6717): 315-323.
32. Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology, 2001, 142(12): 5050-5055.
33. Ali MM, Yoshizawa T, Ishibashi O. PIASxbeta is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts. J Cell Sci, 2007, 120(Pt 15): 2565-2573.
34. Aliprantis AO, Ueki Y, Sulyanto R, et al. NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism. J Clin Invest, 2008, 118(11): 3775-3789.
35. Ikeda F, Nishimura R, Matsubara T, et al. Activation of NFAT signal in vivo leads to osteopenia associated with increased osteoclastogenesis and bone-resorbing activity. J Immunol, 2006, 177(4): 2384-2390.
36. Guo J, Jin J, Cooper LF. Dissection of sets of genes that control the character of wnt5a-deficient mouse calvarial cells. Bone, 2008, 43(5): 961-971.
37. Cheng SL, Shao JS, Cai J, et al. Msx2 exerts bone anabolism via canonical Wnt signaling. J Biol Chem, 2008, 283(29): 20505-20522.
38. Fromigué O, Haÿ E, Barbara A, et al. Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. J Cell Mol Med, 2009, 13(8B): 2189-2199.
39. Dong SW, Ying DJ, Duan XJ, et al. Bone regeneration using an acellular extracellular matrix and bone marrow mesenchymal stem cells expressing Cbfα1. Biosci Biotechnol Biochem, 2009, 73(10): 2226-2233.
40. Hamdy NA. Strontium ranelate improves bone microarchitecture in osteoporosis. Rheumatology (Oxford), 2009, 48 Suppl 4: iv9-13.
41. Cesareo R, Napolitano C, Iozzino M. Strontium ranelate in postmenopausal osteoporosis treatment: a critical appraisal. Int J Womens Health, 2010, 2: 1-6.
42. Kay MI, Young RA, Posner AS. Crystal structure of hydroxyapatite. Nature, 1964, 204: 1050-1052.
43. 陳德敏, 傅飛遠. 不同含鍶量的摻鍶羥基磷灰石固溶體機械性能評價. 口腔材料器械雜志, 2001, 10(4): 178-179.
44. 倪國新, 呂維加, 曲廣運, 等. 鍶羥基磷灰石生物活性骨水泥應用于髖關節置換的研究. 中華創傷骨科組織, 2007, 9(8): 708-710.
45. 閆鈞, 張玉梅, 憨勇, 等. 鍶磷灰石涂層鈦種植體骨結合的動物實驗. 中華口腔醫學雜志, 2010, 45(2): 89-93.
46. 廖大鵬, 周正炎, 顧云峰, 等. 鍶磷灰石生物特性的初步研究. 華西口腔醫學雜志, 2002, 20(3): 172-174.
47. 李峰, 趙信義. 含鍶磷酸鈣骨水泥體內降解性能. 生物醫學工程與臨床, 2006, 10(4): 210-213.
48. 陳德敏, 劉雪陽. 鍶磷灰石多孔陶瓷不同孔隙率對成骨細胞生物學行為的影響. 組織工程與重建外科雜志, 2006, 2(3): 123-127.
49. 余喜訊, 陳元維, 史國齊, 等. 摻鍶聚磷酸鈣骨組織工程支架材料與成骨細胞及內皮細胞的相容性研究. 中國組織工程研究與臨床康復, 2007, 11(5): 857-860.
50. 傅飛遠, 陳德敏, 張建中. MTT比色法評價摻鍶羥基磷灰石固溶體細胞毒性. 生物醫學工程雜志, 2001, 18(3): 389-390, 415.
51. 郝瑞然, 王德平. 改性硼硅酸鹽生物玻璃的可控降解性能. 中國組織工程研究與臨床康復, 2008, 12(10): 1962-1965.
52. Pan HB, Zhao XL, Zhang X, et al. Strontium borate glass: potential biomaterial for bone regeneration. J R Soc Interface, 2010, 7(48): 1025-1031.
53. Pina S, Vieira SI, Rego P, et al. Biological responses of brushite-forming Zn- and ZnSr-substituted beta-tricalcium phosphate bone cements. Eur Cell Mater, 2010 , 20: 162-177.
54. 余喜訊, 顧志鵬, 任大偉, 等. 新型骨科材料SCPP對成骨細胞促血管化生長因子表達影響的研究. 四川大學學報: 工程科學版, 2011, 43(1): 219-225.
55. 王楠, 郝永強, 何國, 等. 纖維多孔鈦微球復合納米鍶磷灰石修復骨缺損的實驗研究. 中華骨科雜志, 2009, 29(7): 672-676.
56. 朱廣文, 張延軍, 李鍵, 等. 核素Sr-89治療前列腺癌骨轉移臨床價值及血清tPSA變化的研究. 放射免疫學雜志, 2009, 22(1): 6-7.
57. 胥杰, 陳曉. 89Sr治療30例肺癌多發骨轉移的療效觀察. 中國呼吸與危重監護雜志, 2008, 7(2): 104-106.
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《中國修復重建外科雜志》

鍶的成骨效應及其在骨科中應用的研究進展

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《中國修復重建外科雜志》

鍶的成骨效應及其在骨科中應用的研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料