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Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition)

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Abstract

Recently the clinical application of bone metabolic markers has achieved significant progress and the measurements of these indices give us a better understanding of the pathogenesis of osteoporosis. Bone metabolic markers were adapted to select drug treatment for osteoporosis and to evaluate drug efficacy. Therefore, the proper application and assessment of bone metabolic markers in clinical practice is very important. To achieve these aims, the committee on the guidelines for the use of biochemical markers of bone turnover in osteoporosis authorized by the Japan Osteoporosis Society has summarized recent progress in bone markers and proposed the proper utilization of bone markers. Although the use of bone metabolic markers now has an important role in the daily management of osteoporosis, their use in Japan is still insufficient because of insurance coverage limitations. Since the Japan Osteoporosis Society first created the 2001 guidelines, new bone metabolic markers have been introduced into clinical practice. The availability of new osteoporosis treatments that promote bone formation has changed the clinical application of bone metabolic markers in current practice. Therefore, revisions to the current clinical practice are needed which led to the proposal to create these new 2012 guidelines.

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References

  1. Braithwaite RS, Col NF, Wong JB (2003) Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc 51:364–370

    Article  PubMed  Google Scholar 

  2. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

    Article  Google Scholar 

  3. Blake GM, Fogelman I (2007) Role of dual-energy X-ray absorptiometry in the diagnosis and treatment of osteoporosis. J Clin Densitom 10:102–110

    Article  PubMed  Google Scholar 

  4. Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara S, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-Hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H, Osteoporosis Diagnostic Criteria Review Committee: Japanese Society for Bone and Mineral Research (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19:331–337

    Article  PubMed  CAS  Google Scholar 

  5. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397

    Article  PubMed  CAS  Google Scholar 

  6. Cummings SR, Palermo L, Browner W, Marcus R, Wallace R, Pearson J, Blackwell T, Eckert S, Black D (2000) Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group. JAMA 283:1318–1321

    Article  PubMed  CAS  Google Scholar 

  7. Weinstein RS (2000) True strength. J Bone Miner Res 15:621–625

    Article  PubMed  CAS  Google Scholar 

  8. Chesnut CH III, Rosen CJ, For the Bone Quality Discussion Group (2001) Reconsidering the effects of antiresorptive therapies in reducing osteoporotic fracture. J Bone Miner Res 16:2163–2172

    Article  PubMed  CAS  Google Scholar 

  9. Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 11:S2–S17

    Article  PubMed  Google Scholar 

  10. Nishizawa Y, Nakamura T, Ohta H, Kushida K, Gorai I, Shiraki M, Fukunaga M, Hosoi T, Miki T, Chaki O, Ichimura S, Nakatsuka K, Miura M, For the Committee on the Guidelines for the Use of Biochemical Markers of Bone Turnover in Osteoporosis, Japan Osteoporosis Society (2004) Guidelines for the use of biochemical makers of bone turnover in osteoporosis. J Bone Miner Metab 23:97–104

    Article  Google Scholar 

  11. Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujieara S, Schiraki M, Kushida K, Miyamoto S, Sone S, Nishimura J, Oh-hashi Y, Hosoi T, Gorai I, Tanaka H, Iga T, Kishimoto H (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19:331–337

    Article  PubMed  CAS  Google Scholar 

  12. Cummings SR, Karpf DB, Harris F, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM (2002) Improvement of spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:282–289

    Article  Google Scholar 

  13. Heaney RP (2003) Is the paradigm shifting? Bone 33:457–465

    Article  PubMed  Google Scholar 

  14. Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Breart G, Meunier PJ, Delmas PD (1996) Markers of bone resorption predict hip fracture in elderly women; EPIDOS prospective study. J Bone Mineral Res 11:1531–1538

    Article  CAS  Google Scholar 

  15. Garnero P, Sornay-Rendu E, Claustrar B, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fracture in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536

    Article  PubMed  CAS  Google Scholar 

  16. Ross PD, Kress BC, Parson RE, Wasnich RD, Armour KA, Mizrahi IA (2000) Serum bone alkaline phosphatase and calcaneus bone density predict fractures; a prospective study. Osteoporos Int 11:76–82

    Article  PubMed  CAS  Google Scholar 

  17. Shiraki M, Kushida K, Fukunaga M, For the Alendronate Phase III Osteoporosis Research Group (1999) A double-masked multicenter comparative study between alendronate and alfacalcidol in Japanese patients with osteoporosis. Osteoporos Int 10:183–192

    Article  PubMed  CAS  Google Scholar 

  18. Morii H, Ohashi Y, Taketani Y, Fukunaga M, Nakamura T, Itabashi A, Sarkar S, Harper K (2003) Effect of raloxifene on bone mineral density and biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis: results from a randomized placebo-controlled trial. Osteoporos Int 14:793–800

    Article  PubMed  CAS  Google Scholar 

  19. Nishizawa Y (2011) A survey of diagnosis and treatment in Japan (in Japanese). Osteoporos Jpn 19:33–47

    Google Scholar 

  20. Committee of Use of Biochemical Markers of Bone Turnover in Osteoporosis, Japan Osteoporosis Society (2001) Guidelines on the use of biochemical markers of bone turnover in osteoporosis (in Japanese). Osteoporos Jpn 9:255–271

    Google Scholar 

  21. Committee of Use of Biochemical Markers of Bone Turnover in Osteoporosis, Japan Osteoporosis Society (2002) Guidelines on the use of biochemical markers of bone turnover in osteoporosis (in Japanese). Osteoporos Jpn 10:251–261

    Google Scholar 

  22. Bell KJ, Hayen A, Macaskill P, Irwig L, Craig JC, Ensrud K, Bauer DC (2009) Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data. Br Med J 338:b2266

    Article  Google Scholar 

  23. Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261

    Article  PubMed  CAS  Google Scholar 

  24. Eriksen EF, Hodgson SF, Eastell R, Cedel SL, O’Fallon WM, Riggs BL (1990) Cancellous bone remodeling in type I (postmenopausal) osteoporosis: quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular level. J Bone Miner Res 5:311–319

    Article  PubMed  CAS  Google Scholar 

  25. Saito M, Marumo K (2010) Collagen-crosslinks as a determinant of bone quality: possible explanation for bone fragility in aging, osteoporosis and diabetes mellitus. Osteoporos Int 21:195–214

    Article  PubMed  CAS  Google Scholar 

  26. Saito M, Fujii K, Mori Y, Marumo K (2006) Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 17:1514–1523

    Article  PubMed  CAS  Google Scholar 

  27. Nagaoka H, Mochida Y, Atsawasuwan P, Kaku M, Kondoh T, Yamauchi M (2008) 1,25(OH)2D3 regulates collagen quality in an osteoblastic cell culture system. Biochem Biophys Res Commun 377:674–678

    Article  PubMed  CAS  Google Scholar 

  28. Raposo B, Rodríguez C, Martínez-González J, Badimon L (2004) High levels of homocysteine inhibit lysyl oxidase (LOX) and down regulate LOX expression in vascular endothelial cells. Atherosclerosis 177:1–8

    Article  PubMed  CAS  Google Scholar 

  29. Liu G, Nellaiappan K, Kagan HM (1997) Irreversible inhibition of lysyl oxidase by homocysteine thiolactone and its selenium and oxygen analogues. Implications for homocystinuria. J Biol Chem 272:32370–32377

    Article  PubMed  CAS  Google Scholar 

  30. van Meurs JB, Dhonukshe-Rutten RA, Pluijim SM, van der Klift M, de Jonge R, Lindemans J, de Groot LC, Hofman A, Witteman JC, van Leeuwen JP, Breteler MM, Lips P, Pols HA, Uitterlinden AG (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350:2033–2041

    Article  PubMed  Google Scholar 

  31. Shiraki M, Urano T, Kuroda T, Saito M, Tanaka S, Miyao-Koshizuka M, Inoue S (2008) The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures. J Bone Miner Metab 26:595–602

    Article  PubMed  CAS  Google Scholar 

  32. Amizuka N, Li M, Hara K, Kobayashi M, de Freitas PH, Ubaidus S, Oda K, Akiyama Y (2009) Warfarin administration disrupts the assembly of mineralized nodules in the osteoid. J Electron Microsc 58:55–65

    Article  CAS  Google Scholar 

  33. Tsugawa N, Shiraki M, Suhara Y, Kamao M, Tanaka K, Okano T (2006) Vitamin K status of healthy Japanese women: age-related vitamin K requirement for gamma-carboxylation of osteocalcin. Am J Clin Nutr 83:380–386

    PubMed  CAS  Google Scholar 

  34. Vergnaud P, Garnero P, Meunier PJ, Bréart G, Kamihagi K, Delmas PD (1997) Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS study. J Clin Endocrinol Metab 82:719–724

    Article  PubMed  CAS  Google Scholar 

  35. Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536

    Article  PubMed  CAS  Google Scholar 

  36. Okabe R, Nakatsuka K, Inaba M, Miki T, Naka H, Masaki H, Moriguchi A, Nishizawa Y (2001) Clinical evaluation of the Elecsys beta-CrossLaps serum assay, a new assay for degradation products of type I collagen C-telopeptides. Clin Chem 47:1410–1414

    PubMed  CAS  Google Scholar 

  37. Nishizawa Y, Inaba M, Ishii M, Yamashita H, Miki T, Goto H, Yamada S, Chaki O, Kurasawa K, Mochizuki Y (2008) Reference intervals of serum tartrate-resistant acid phosphatase type 5b activity measured with a novel assay in Japanese subjects. J Bone Miner Metab 26:265–270

    Article  PubMed  CAS  Google Scholar 

  38. Kress BC, Mizrahi IA, Armour KW, Marcus R, Emkey RD, Santora AC 2nd (1999) Use of bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic women. Clin Chem 45:1009–1017

    PubMed  CAS  Google Scholar 

  39. Melkko J, Kauppila S, Niemi S, Risteli L, Haukipuro K, Jukkola A, Risteli J (1996) Immunoassay for intact amino-terminal propeptide of human type I procollagen. Clin Chem 42:947–954

    PubMed  CAS  Google Scholar 

  40. Iki M, Akiba T, Matsumoto T, Nishino H, Kagamimori S, Kagawa Y, Yoneshima H, JPOS Study Group (2004) Reference database of biochemical markers of bone turnover for the Japanese female population. Japanese Population-based Osteoporosis (JPOS) Study. Osteoporos Int 15:981–991

    Article  PubMed  CAS  Google Scholar 

  41. Bjarnason NH, Sarker S, Duong T, Mitlak B, Delmas PD, Christiansen C (2001) 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 12:922–930

    Article  PubMed  CAS  Google Scholar 

  42. Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD (2003) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 18:1051–1056

    Article  PubMed  CAS  Google Scholar 

  43. Delmas PD, Seeman E (2004) Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Bone 34:599–604

    Article  PubMed  CAS  Google Scholar 

  44. Delmas PD, Vrigens B, Eastell R, Roux C, Pols HA, Ringe JD, Grauer A, Cahall D, Watts NB (2007) Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92:1296–1304

    Article  PubMed  CAS  Google Scholar 

  45. Imai E, Horio M, Watanabe T, Iseki K, Yamagata K, Hara S, Ura N, Kiyohara Y, Moriyama T, Ando Y, Fujimoto S, Konta T, Yokoyama H, Makino H, Hishida A, Matsuo S (2009) Prevalence of chronic kidney disease in the Japanese general population. Clin Exp Nephrol 13:621–630

    Article  PubMed  Google Scholar 

  46. Yamada S, Inaba M, Kurajoh M, Shidara K, Imanishi Y, Ishimura E, Nishizawa Y (2008) Utility of serum tartrate-resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction. Clin Endocrinol (Oxf) 69:189–196

    Article  CAS  Google Scholar 

  47. Inaba M, Kurajoh M, Okuno S, Imanishi Y, Yamada S, Mori K, Ishimura E, Yamakawa T, Nishizawa Y (2010) Poor muscle quality rather than reduced lean body mass is responsible for the lower serum creatinine level in hemodialysis patients with diabetes mellitus. Clin Nephrol 74:266–272

    PubMed  CAS  Google Scholar 

  48. Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD, Grauer A, Cahall D, Watts NB (2003) A reinforcement message based on bone turnover marker response influences long-term persistence with risedronate in osteoporosis: IMPACT study. J Bone Miner Res 18:S374

    Google Scholar 

  49. Kurasawa K, Chaki O, Hirahara F (2006) Evaluation of serum bone-specific alkaline phosphatase using automated chemiluminescent enzyme immunoassay (in Japanese). Jpn J Med Pharm Sci 55:279–285

    CAS  Google Scholar 

  50. Shiraki M, Aoki C, Yamazaki N, Ito Y, Tsugawa N, Sunahara Y, Okano T (2007) Clinical assessment of undercarboxylated osteocalcin measurement in serum using and electrochemiluminescence immunoassay: establishment of cut-off values to determine vitamin K insufficiency in bone and to predict fracture leading to clinical use of vitamin K2 (in Japanese). Jpn J Med Pharm Sci 57:537–546

    CAS  Google Scholar 

  51. Nishizawa Y, Inaba M, Ishi K, Yamashita H, Miki T, Goto H, Yamada S, Chaki O, Karasawa K (2005) Evaluation of newly developed kit for measurement of bone-specific tartrate-resistant acid phosphates in blood (in Japanese). Jpn J Med Pharm Sci 54:709–717

    CAS  Google Scholar 

  52. Sone T, Yoshikawa K, Tamada T, Takeda N, Fukunaga M (2001) Clinical application of radioimmunoassay for determination of serum intact PINP (procollagen type I amino-terminal propeptide) (in Japanese). Clin Endocrinol 49:1133–1138

    Google Scholar 

  53. Greenspan SL, Parker RA, Ferguson L, Rosen HN, Maitland-Ramsey L, Karpf DB (1998) Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial. J Bone Miner Res 13:1431–1438

    Article  PubMed  CAS  Google Scholar 

  54. Miyauchi A, Matsumoto T, Sugimoto T, Tsujimoto M, Warner MR, Nakamura T (2010) Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-months, randomized, placebo-controlled, double-blind and 12-month open-label phases. Bone 47:493–502

    Article  PubMed  CAS  Google Scholar 

  55. Tsujimoto M, Chen P, Miyauchi A, Sowa H, Krege JH (2011) PINP as an aid for monitoring patients treated with teriparatide. Bone 8:798–803

    Article  Google Scholar 

  56. Nakamura T, Matsumoto T, Sugimoto T, Shiraki M (2011) Effect of weekly teriparatide in patients with osteoporosis. J Bone Miner Res 26:S1201

    Google Scholar 

  57. Eastell R, Brainbridge PR (2003) Bone turnover markers: their place in the investigation of osteoporosis. In: Orwoll ES, Bliziotes M (eds) Osteoporosis: pathophysiology and clinical management. Humana Press, Totowa, pp 185–197

    Google Scholar 

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Correspondence to Yoshiki Nishizawa.

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For the Committee on the Guidelines for the Use of Biochemical Markers of Bone Turnover in Osteoporosis, Japan Osteoporosis Society Committee Organization.

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Nishizawa, Y., Ohta, H., Miura, M. et al. Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition). J Bone Miner Metab 31, 1–15 (2013). https://doi.org/10.1007/s00774-012-0392-y

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  • DOI: https://doi.org/10.1007/s00774-012-0392-y

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