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骨转换生化标志物在骨质疏松中的应用

Author
Harold N Rosen, MD
Section Editor
Clifford J Rosen, MD
Deputy Editor
Jean E Mulder, MD
Translators
何畏, 主任医师

引言

成人的骨骼在不断重构，即破坏(骨质吸收)之后重建(骨形成)。骨质吸收和再形成对微小骨折的修复，以及骨骼结构在压力及其他生物机械力下的改变具有重要意义。骨形成在正常情况下与骨质吸收紧密偶联，因此骨量不会改变。骨形成与骨质吸收失偶联时就会发生骨骼疾病。

目前已有数种测定骨转换标志物(bone turnover marker, BTM)的检查方法，它们可测定胶原分解产物以及破骨细胞和成骨细胞在骨质吸收和形成过程中释放出的其他分子。骨形成的特异性标志物包括：骨特异性碱性磷酸酶(bone-specific alkaline phosphatase, BALP)、骨钙素和Ⅰ型前胶原N端前肽(N-terminal propeptide of type 1 procollagen, P1NP)；骨质吸收的特异性标志物包括：Ⅰ型胶原N端肽(N-telopeptide of type 1 collagen, NTX)、Ⅰ型胶原C端肽(C-terminal telopeptide of type 1 collagen, CTX)和吡啶啉交联(表 1)。

BTM在临床试验中可帮助研究者了解治疗药物的作用机制。然而，尚未充分确定它们在患者治疗中的作用。BTM值的生物学差异和实验室检查差异使它们难以在临床实践中广泛应用(表 2)。BTM可以在一定程度上提示未来的骨丢失和骨折风险。更重要的是，其有助于为骨质疏松患者人群监测抗骨质吸收治疗的效果。

本专题将总结生化BTM的临床应用，BTM的生理学、它们与骨重塑过程的关系及在其他骨病中的应用见其他专题。 (参见“骨生理学和骨转换的生化标志物”和“慢性肾脏病患者骨质疏松的诊断、评估与治疗”，关于‘骨转换的生化标志物’一节和“研究中的生物标志物在类风湿关节炎诊断和评估中的作用”，关于‘骨特异性标志物’一节和“Paget骨病的临床表现与诊断”，关于‘生化检查的作用’一节)

一般原则

下述因素可致使BTM的检测变得复杂：患者自身的巨大随机差异、生物学差异[年龄、性别、体质指数(body mass index, BMI)、昼夜节律和月经周期的差异]，以及大多数检测方法的标准化程度都较低(表 2)[1,2]。这些问题使BTM难以在临床实践中广泛应用。不过一些临床检测现已实现自动化。2012年，美国国家骨质健康联盟(National Bone Health Alliance, NBHA)启动了一个项目，旨在使美国的BTM样本采集操作标准化，以及为血清P1NP(骨形成指标)和血清CTX(骨质吸收指标)设立参考范围。NBHA、国际骨质疏松基金会(International Osteoporosis Foundation, IOF)及国际临床化学和实验室医学联盟(International Federation of Clinical Chemistry and Laboratory Medicine, IFCC)认为这两个指标最有临床应用前景[3,4]；该项目仍在进行中。

         

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Literature review current through: 2017-06 . | This topic last updated: 2016-03-31.
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References
Top
  1. Hlaing TT, Compston JE. Biochemical markers of bone turnover - uses and limitations. Ann Clin Biochem 2014; 51:189.
  2. Bell KJ, Hayen A, Irwig L, et al. The potential value of monitoring bone turnover markers among women on alendronate. J Bone Miner Res 2012; 27:195.
  3. Bauer D, Krege J, Lane N, et al. National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges. Osteoporos Int 2012; 23:2425.
  4. Vasikaran S, Eastell R, Bruyère O, et al. 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.
  5. González-Calvin JL, Mundi JL, Casado-Caballero FJ, et al. Bone mineral density and serum levels of soluble tumor necrosis factors, estradiol, and osteoprotegerin in postmenopausal women with cirrhosis after viral hepatitis. J Clin Endocrinol Metab 2009; 94:4844.
  6. Qvist P, Christgau S, Pedersen BJ, et al. Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. Bone 2002; 31:57.
  7. Schlemmer A, Hassager C. Acute fasting diminishes the circadian rhythm of biochemical markers of bone resorption. Eur J Endocrinol 1999; 140:332.
  8. Eastell R, Barton I, Hannon RA, et al. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 2003; 18:1051.
  9. Ravn P, Hosking D, Thompson D, et al. Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study. J Clin Endocrinol Metab 1999; 84:2363.
  10. Rosen HN, Moses AC, Garber J, et al. Utility of biochemical markers of bone turnover in the follow-up of patients treated with bisphosphonates. Calcif Tissue Int 1998; 63:363.
  11. Bauer DC, Black DM, Garnero P, et al. Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 2004; 19:1250.
  12. Rosen HN, Moses AC, Garber J, et al. Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 2000; 66:100.
  13. Christgau S, Rosenquist C, Alexandersen P, et al. Clinical evaluation of the Serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides. Clin Chem 1998; 44:2290.
  14. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254.
  15. Johansen JS, Riis BJ, Delmas PD, Christiansen C. Plasma BGP: an indicator of spontaneous bone loss and of the effect of oestrogen treatment in postmenopausal women. Eur J Clin Invest 1988; 18:191.
  16. Bonde M, Qvist P, Fledelius C, et al. Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment. J Clin Endocrinol Metab 1995; 80:864.
  17. Chesnut CH 3rd, Bell NH, Clark GS, et al. Hormone replacement therapy in postmenopausal women: urinary N-telopeptide of type I collagen monitors therapeutic effect and predicts response of bone mineral density. Am J Med 1997; 102:29.
  18. Bauer DC, Sklarin PM, Stone KL, et al. Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures. J Bone Miner Res 1999; 14:1404.
  19. Ross PD, Knowlton W. Rapid bone loss is associated with increased levels of biochemical markers. J Bone Miner Res 1998; 13:297.
  20. Chaki O, Yoshikata I, Kikuchi R, et al. The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women. J Bone Miner Res 2000; 15:1537.
  21. Ivaska KK, Lenora J, Gerdhem P, et al. Serial assessment of serum bone metabolism markers identifies women with the highest rate of bone loss and osteoporosis risk. J Clin Endocrinol Metab 2008; 93:2622.
  22. Bauer DC, Garnero P, Harrison SL, et al. Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study. J Bone Miner Res 2009; 24:2032.
  23. van Daele PL, Seibel MJ, Burger H, et al. Case-control analysis of bone resorption markers, disability, and hip fracture risk: the Rotterdam study. BMJ 1996; 312:482.
  24. Garnero P, Hausherr E, Chapuy MC, et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 1996; 11:1531.
  25. Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 2000; 15:1526.
  26. Gerdhem P, Ivaska KK, Alatalo SL, et al. Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res 2004; 19:386.
  27. Delmas PD, Licata AA, Reginster JY, et al. Fracture risk reduction during treatment with teriparatide is independent of pretreatment bone turnover. Bone 2006; 39:237.
  28. Sornay-Rendu E, Munoz F, Garnero P, et al. Identification of osteopenic women at high risk of fracture: the OFELY study. J Bone Miner Res 2005; 20:1813.
  29. Meier C, Nguyen TV, Center JR, et al. Bone resorption and osteoporotic fractures in elderly men: the dubbo osteoporosis epidemiology study. J Bone Miner Res 2005; 20:579.
  30. Ivaska KK, Gerdhem P, Väänänen HK, et al. Bone turnover markers and prediction of fracture: a prospective follow-up study of 1040 elderly women for a mean of 9 years. J Bone Miner Res 2010; 25:393.
  31. Johnell O, Kanis JA, Black DM, et al. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19:764.
  32. Melton LJ 3rd, Crowson CS, O'Fallon WM, et al. Relative contributions of bone density, bone turnover, and clinical risk factors to long-term fracture prediction. J Bone Miner Res 2003; 18:312.
  33. Bjarnason NH, Sarkar S, Duong T, et al. Six and twelve month changes in bone turnover are related to reduction in vertebral fracture risk during 3 years of raloxifene treatment in postmenopausal osteoporosis. Osteoporos Int 2001; 12:922.
  34. Sarkar S, Reginster JY, Crans GG, et al. Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk. J Bone Miner Res 2004; 19:394.
  35. Eastell R, Hannon RA, Garnero P, et al. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate: review of statistical analysis. J Bone Miner Res 2007; 22:1656.
  36. Reginster JY, Sarkar S, Zegels B, et al. Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk. Bone 2004; 34:344.
  37. Dobnig H, Sipos A, Jiang Y, et al. Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. J Clin Endocrinol Metab 2005; 90:3970.
  38. Clowes JA, Peel NF, Eastell R. The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 2004; 89:1117.
  39. Delmas PD, Vrijens B, Eastell R, et al. Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 2007; 92:1296.
  40. Khosla S, Bilezikian JP, Dempster DW, et al. Benefits and risks of bisphosphonate therapy for osteoporosis. J Clin Endocrinol Metab 2012; 97:2272.
  41. Singer FR, Eyre DR. Using biochemical markers of bone turnover in clinical practice. Cleve Clin J Med 2008; 75:739.
  42. Marx RE, Cillo JE Jr, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 2007; 65:2397.
  43. American Society for Bone and Mineral Research Task Force on Osteonecrosis of the Jaw, Khosla S, Burr D, et al. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 2008; 66:1320.
  44. Baim S, Miller PD. Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res 2009; 24:561.
  45. 2013 Clinician's Guide to Prevention and Treatment of Osteoporosis http://nof.org/files/nof/public/content/resource/913/files/580.pdf (Accessed on February 14, 2014).
  46. Lee J, Vasikaran S. Current recommendations for laboratory testing and use of bone turnover markers in management of osteoporosis. Ann Lab Med 2012; 32:105.