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Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis

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Abstract

Introduction

The aim was to analyse data on the use of biochemical bone turnover markers (BTM) in postmenopausal osteoporosis.

Methods

We carried out a comparative analysis of the most important papers concerning BTM in postmenopausal osteoporosis that have been published recently.

Results

The BTM levels are influenced by several factors. They are moderately correlated with BMD and subsequent bone loss. Increased levels of bone resorption markers are associated with a higher risk of fracture. Changes in the BTM during the anti-osteoporotic treatment (including combination therapy) reflect the mechanisms of action of the drugs and help to establish their effective doses. Changes in the BTM during the anti-resorptive treatment are correlated with their anti-fracture efficacy.

Conclusion

Biological samples should be obtained in a standardised way. BTM cannot be used for prediction of the accelerated bone loss at the level of the individual. BTM help to detect postmenopausal women who are at high risk of fracture; however, adequate practical guidelines are lacking. BTM measurements taken during the anti-resorptive therapy help to identify non-compliers. They may improve adherence to the anti-resorptive therapy and the fall in the BTM levels that exceeds the predefined threshold improves patients’ persistence with the treatment. There are no guidelines concerning the use of BTM in monitoring anti-osteoporotic therapy in postmenopausal women.

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References

  1. Dempster DW (2006) Anatomy and functions of the adult skeleton. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism. American Society for Bone and Mineral Research, Washington, DC, pp 7–11

    Google Scholar 

  2. Garnero P, Delmas PD (2001) Biochemical markers of bone turnover in osteoporosis. In: Marcus M, Feldman D, Kelsey J (eds) Osteoporosis, vol 2. Academic Press, New York, pp 459–477

    Google Scholar 

  3. Delmas PD, Demiaux B, Malaval L, Chapuy MC, Edouard C, Meunier PJ (1986) Serum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia comparison with bone histomorphometry. J Clin Invest 77:985–991

    Article  PubMed  CAS  Google Scholar 

  4. Ureña P, Hruby M, Ferreira A, Ang KS, de Vernejoul MC (1996) Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. J Am Soc Nephrol 7:506–512

    PubMed  Google Scholar 

  5. Eriksen EF, Charles P, Melsen F, Mosekilde L, Risteli L, Risteli J (1993) Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. J Bone Miner Res 8:127–132

    PubMed  CAS  Google Scholar 

  6. Eastell R, Delmas PD, Hodgson SF, Eriksen EF, Mann KG, Riggs BL (1988) Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers. J Clin Endocrinol Metab 67:741–748

    Article  PubMed  CAS  Google Scholar 

  7. Charles P, Poser JW, Mosekilde L, Jense FT (1985) Estimation of bone turnover evaluated by 47Ca-kinetics. Efficiency of serum bone gamma-carboxyglutamic acid-containing protein, serum alkaline phosphatase, and urinary hydroxyproline excretion. J Clin Invest 76:2254–2258

    Article  PubMed  CAS  Google Scholar 

  8. Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänänen HK (2006) Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab 52:499–509

    PubMed  CAS  Google Scholar 

  9. Roux JP, Arlot ME, Gineyts E, Meunier PJ, Delmas PD (1995) Automatic-interactive measurement of resorption cavities in transiliac bone biopsies and correlation with deoxypyridinoline. Bone 17:153–156

    Article  PubMed  CAS  Google Scholar 

  10. Eastell R, Colwell A, Hampton L, Reeve J (1997) Biochemical markers of bone resorption compared with estimates of bone resorption from radiotracer kinetic studies in osteoporosis. J Bone Miner Res 12:59–65

    Article  PubMed  CAS  Google Scholar 

  11. Denk E, Hillegonds D, Hurrell RF et al (2007) Evaluation of 41calcium as a new approach to assess changes in bone metabolism: effect of a bisphosphonate intervention in postmenopausal women with low bone mass. J Bone Miner Res 22:1518–1525

    Article  PubMed  CAS  Google Scholar 

  12. Qvist P, Christgau S, Pedersen BJ, Schlemmer A, Christiansen C (2002) 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 31:57–61

    Article  PubMed  CAS  Google Scholar 

  13. Eastell R, Simmons PS, Colwell A et al (1992) Nyctohemeral changes in bone turnover assessed by serum bone Gla-protein concentration and urinary deoxypyridinoline excretion: effects of growth and ageing. Clin Sci 83:375–382

    PubMed  CAS  Google Scholar 

  14. Wichers M, Schmidt E, Bidlingmaier F, Klingmüller D (1999) Diurnal rhythm of crosslaps in human serum. Clin Chem 45:1858–1860

    PubMed  CAS  Google Scholar 

  15. Gertz BJ, Clemens JD, Holland SD, Yuan W, Greenspan S (1998) Application of a new serum assay for type I collagen cross-linked N-telopeptides: assessment of diurnal changes in bone turnover with and without alendronate treatment. Calcif Tissue Int 63:102–106

    Article  PubMed  CAS  Google Scholar 

  16. Aoshima H, Kushida K, Takahashi M et al (1998) Circadian variation of urinary type I collagen crosslinked C-telopeptide and free and peptide-bound forms of pyridinium crosslinks. Bone 22:73–78

    Article  PubMed  CAS  Google Scholar 

  17. Bollen AM, Martin MD, Leroux BG, Eyre DR (1995) Circadian variation in urinary excretion of bone collagen cross-links. J Bone Miner Res 10:1885–1890

    PubMed  CAS  Google Scholar 

  18. Schlemmer A, Hassager C (1999) Acute fasting diminishes the circadian rhythm of biochemical markers of bone resorption. Eur J Endocrinol 140:332–337

    Article  PubMed  CAS  Google Scholar 

  19. Clowes JA, Hannon RA, Yap TS, Hoyle NR, Blumsohn A, Eastell R (2002) Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone 30:886–890

    Article  PubMed  CAS  Google Scholar 

  20. Henriksen DB, Alexandersen P, Bjarnason NH et al (2003) Role of gastrointestinal hormones in postprandial reduction of bone resorption. J Bone Miner Res 18:2180–2189

    Article  PubMed  CAS  Google Scholar 

  21. Brooke-Wavell K, Jones PRM, Hardman AE, Tsuritani I, Yamada Y (2001) Commencing, continuing and stopping brisk walking: effects on bone mineral density, quantitative ultrasound of bone and markers of bone metabolism in postmenopausal women. Osteoporos Int 12:581–587

    Article  PubMed  CAS  Google Scholar 

  22. Hla MM, Davis JW, Ross PD, Yates AJ, Wasnich RD (2001) The relation between lifestyle factors and biochemical markers of bone turnover among early postmenopausal women. Calcif Tissue Int 68:291–296

    Article  PubMed  CAS  Google Scholar 

  23. Suleiman S, Nelson M, Li F, Buxton-Thomas M, Moniz C (1997) Effect of calcium intake and physical activity level on bone mass and turnover in healthy, white, postmenopausal women. Am J Clin Nutr 66:937–943

    PubMed  CAS  Google Scholar 

  24. Seibel MJ, Gartenberg F, Silverberg SJ, Ratcliffe A, Robins SP, Bilezikian JP (1992) Urinary hydroxypyridinium cross-links of collagen in primary hyperparathyroidism. J Clin Endocrinol Metab 74:481–486

    Article  PubMed  CAS  Google Scholar 

  25. Alvarez L, Guanabens N, Peris P et al (1995) Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease. J Bone Miner Res 10:458–463

    PubMed  CAS  Google Scholar 

  26. Garnero P, Gineyts E, Schaffer AV, Seaman J, Delmas PD (1998) Measurement of urinary excretion of nonisomerized and beta-isomerized forms of type I collagen breakdown products to monitor the effects of the bisphosphonate zoledronate in Paget's disease. Arthritis Rheum 41:354–360

    Article  PubMed  CAS  Google Scholar 

  27. Pantazi H, Papapetrou PD (2000) Changes in parameters of bone and mineral metabolism during therapy for hyperthyroidism. J Clin Endocrinol Metab 85:1099–1106

    Article  PubMed  CAS  Google Scholar 

  28. Siddiqi A, Burrin JM, Noonan K et al (1997) A longitudinal study of markers of bone turnover in Graves’ disease and their value in predicting bone mineral density. J Clin Endocrinol Metab 82:753–759

    Article  PubMed  CAS  Google Scholar 

  29. Parkinson C, Kassem M, Heickendorff L, Flyvbjerg A, Trainer PJ (2003) Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal. J Clin Endocrinol Metab 88:5650–5655

    Article  PubMed  CAS  Google Scholar 

  30. Kristo C, Jemtland R, Ueland T, Godang K, Bollerslev J (2006) Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: a prospective, long-term study. Eur J Endocrinol 154:109–118

    Article  PubMed  CAS  Google Scholar 

  31. Chiodini I, Carnevale V, Torlontano M et al (1998) Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing’s syndrome. J Clin Endocrinol Metab 83:1863–1867

    Article  PubMed  CAS  Google Scholar 

  32. Alaxandrakis MG, Passam FH, Malliaraki N, Katachanakis C, Kyriakou DS, Margioris N (2002) Evaluation of bone disease in multiple myeloma: a correlation between biochemical markers of bone metabolism and other clinical parameters in untreated multiple myeloma patients. Clin Chim Acta 325:51–57

    Article  Google Scholar 

  33. Corso A, Arcaini L, Mangiacavalli S et al (2001) Biochemical markers of bone disease in asymptomatic early stage multiple myeloma. A study on their role in identifying high risk patients. Haematologica 86:394–398

    PubMed  CAS  Google Scholar 

  34. Colao A, di Somma C, Pivonello R et al (1999) Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 84:1919–1924

    Article  PubMed  CAS  Google Scholar 

  35. Mizunashi K, Furukawa Y, Miura R, Yumita S, Sohn HE, Yoshinaga K (1988) Effects of active vitamin D3 and parathyroid hormone on the serum osteocalcin in idiopathic hypoparathyroidism and pseudohypoparathyroidism. J Clin Invest 82:861–865

    Article  PubMed  CAS  Google Scholar 

  36. Engler H, Oettli RE, Riesen WF (1999) Biochemical markers of bone turnover in patients with thyroid dysfunctions and in euthyroid controls: a cross-sectional study. Clin Chim Acta 289:159–172

    Article  PubMed  CAS  Google Scholar 

  37. White HD, Ahmad AM, Durham BH et al (2006) Effect of active acromegaly and its treatment on parathyroid circadian rhythmicity and parathyroid target-organ sensitivity. J Clin Endocrinol Metab 91:913–919

    Article  PubMed  CAS  Google Scholar 

  38. Voorzanger-Rousselot N, Juillet F, Mareau E, Zimmermann J, Kalebic T, Garnero P (2006) Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a cross-sectional and longitudinal evaluation. Br J Cancer 95:506–514

    Article  PubMed  CAS  Google Scholar 

  39. Leeming DJ, Koizumi M, Byrjalsen I, Li B, Qvist P, Tanko LB (2006) The relative use of eight collagenous and noncollagenous markers for diagnosis of skeletal metastases in breast, prostate, or lung cancer patients. Cancer Epidemiol Biomarkers Prev 15:32–38

    Article  PubMed  CAS  Google Scholar 

  40. Cloos PA, Lyubimova N, Solberg H et al (2004) An immunoassay for measuring fragments of newly synthesized collagen type I produced during metastatic invasion of bone. Clin Lab 50:279–289

    PubMed  CAS  Google Scholar 

  41. Costa L, Demers LM, Gouveia-Oliveira A et al (2002) Prospective evaluation of the peptide-bound collagen type I cross-links N-telopeptide and C-telopeptide in predicting bone metastases status. J Clin Oncol 20:850–856

    Article  PubMed  CAS  Google Scholar 

  42. Coleman RE, Major P, Lipton A et al (2005) Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J Clin Oncol 23:4925–4935

    Article  PubMed  CAS  Google Scholar 

  43. Chen JS, Cameron ID, Cumming RG et al (2006) Effect of age-related chronic immobility on markers of bone turnover. J Bone Miner Res 21:324–331

    Article  PubMed  CAS  Google Scholar 

  44. Nilsson K, Gustafson L, Isaksson A, Hultberg B (2005) Plasma homocysteine and markers of bone metabolism in psychogeriatric patients. Scand J Clin Lab Invest 65:671–680

    Article  PubMed  CAS  Google Scholar 

  45. Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K (2005) Abnormal bone and calcium metabolism in immobilized Parkinson’s disease patients. Mov Disord 20:1598–1603

    Article  PubMed  Google Scholar 

  46. Sato Y, Asoh T, Oizumi K (1998) High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer’s disease. Bone 23:555–557

    Article  PubMed  CAS  Google Scholar 

  47. Sato Y, Oizumi K, Kuno H, Kaji M (1999) Effect of immobilization upon renal synthesis of 1,25-dihydroxyvitamin D in disabled elderly stroke patients. Bone 24:271–275

    Article  PubMed  CAS  Google Scholar 

  48. Sato Y, Kuno H, Kaji M, Ohshima Y, Asoh T, Oizumi K (1998) Increased bone resorption during the first year after stroke. Stroke 29:1373–1377

    PubMed  CAS  Google Scholar 

  49. Iwamoto J, Takeda T, Ichimura S (2001) Relationships between physical activity and metacarpal cortical bone mass and bone resorption in hemiplegic patients. J Orthop Sci 6:227–233

    Article  PubMed  CAS  Google Scholar 

  50. Ivaska KK, Gerdhem P, Akesson K, Garnero P, Obrant KJ (2007) Effect of fracture on bone turnover markers: a longitudinal study comparing marker levels before and after injury in 113 elderly women. J Bone Miner Res 22:1155–1164

    Article  PubMed  CAS  Google Scholar 

  51. Stoffel K, Engler H, Kuster M, Riesen W (2007) Changes in biochemical markers after lower limb fractures. Clin Chem 53:131–134

    Article  PubMed  CAS  Google Scholar 

  52. Obrant KJ, Ivaska KK, Gerdhem P, Alantalo SL, Pettersson K, Väänänen HK (2005) Biochemical markers of bone turnover are influenced by recently sustained fracture. Bone 36:786–792

    Article  PubMed  CAS  Google Scholar 

  53. Lems WF, van Veen GJM, Gerrits MI et al (1998) Effect of low-dose prednisone (with calcium and calcitriol supplementation) on calcium and bone metabolism in healthy volunteers. Br J Rheumat 37:27–33

    Article  CAS  Google Scholar 

  54. Ton FJ, Gunawardene SC, Lee H, Neer RM (2005) Effects of low-dose prednisone on bone metabolism. J Bone Miner Res 20:464–470

    Article  PubMed  CAS  Google Scholar 

  55. Richy F, Bousquet J, Ehrlich GE et al (2003) Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int 14:179–190

    PubMed  CAS  Google Scholar 

  56. Scanlon PD, Connett JE, Wise RA et al (2004) Loss of bone density with inhaled triamcinolone in Lung Health Study. Am J Resp Crit Care Med 170:1302–1309

    Article  PubMed  Google Scholar 

  57. Fardon TC, Lee DKC, Haggart K, McFarlane LC, Lipworth BJ (2004) Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate. Am J Resp Crit Care Med 170:960–966

    Article  PubMed  Google Scholar 

  58. Martin RJ, Szefler SJ, Chinchilli VM et al (2002) Systemic effect comparisons of six inhaled corticosteroid preparations. Am J Resp Crit Care Med 165:1377–1383

    Article  PubMed  Google Scholar 

  59. Egan JJ, Maden C, Kalra S, Adams JE, Eastell R, Woodcock AA (1999) A randomized, double-blind study comparing the effects of beclomethasone and fluticasone on bone density over two years. Eur Resp J 13:1267–1275

    CAS  Google Scholar 

  60. Malerba M, Bossoni S, Radaeli A et al (2005) Growth hormone response to growth hormone-releasing hormone is reduced in adult asthmatic patients receiving long-term inhaled corticosteroid treatment. Chest 127:515–521

    Article  PubMed  CAS  Google Scholar 

  61. Fujita K, Kasayama S, Hashimoto J et al (2001) Inhaled corticosteroids reduce bone mineral density in early postmenopausal but not premenopausal asthmatic women. J Bone Miner Res 16:782–787

    Article  PubMed  CAS  Google Scholar 

  62. Hall GM, Spector TD, Delmas PD (1995) Markers of bone metabolism in postmenopausal women with rheumatoid arthritis. Arthritis Rheum 38:902–906

    Article  PubMed  CAS  Google Scholar 

  63. Pearce G, Ryan PFJ, Delmas PD, Tabensky DA, Seeman E (1998) The deleterious effects of low-dose corticosteroids on bone density in patients with polymyalgia rheumatica. Br J Rheum 37:292–299

    Article  CAS  Google Scholar 

  64. Brufsky A, Harker WG, Beck JT et al (2007) Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol 25:829–836

    Article  PubMed  CAS  Google Scholar 

  65. Gonnelli S, Cadirni A, Caffarelli C et al (2007) Changes in bone turnover and in bone mass in women with breast cancer switched from tamoxifen to exemestane. Bone 40:205–210

    Article  PubMed  CAS  Google Scholar 

  66. Confavreux CB, Fontana A, Guastalla JP, Munoz F, Brun J, Delmas PD (2007) Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates. Bone 41:346–352

    Article  PubMed  CAS  Google Scholar 

  67. Eastell R, Hannon RA, Cuzick J, Dowsett M, Clack G, Adams JE (2006) Effect of an aromatase inhibitor on BMD and bone turnover markers: 2-year results of the anastrozole, tamoxifen, alone or in combination (ATAC) trial (18233230). J Bone Miner Res 21:1215–1223

    Article  PubMed  CAS  Google Scholar 

  68. Fitzpatrick LA (2004) Pathophysiology of bone loss in patients receiving anticonvulsant therapy. Epilepsy Behav 5:S3–S15

    Article  PubMed  Google Scholar 

  69. Pack AM, Morrell MJ (2004) Epilepsy and bone health in adults. Epilepsy Behav 5:S24–S29

    Article  PubMed  Google Scholar 

  70. Pack A, Shane E, McMahon D, Randall A, Morell M (2007) Antiepileptic drugs affect bone loss via reproductive hormones. J Bone Miner Res 22 [Suppl 1]:S467, Abstract W415

    Google Scholar 

  71. Mintzer S, Boppana P, Toguri J, DeSantis A (2006) Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine and oxcarbazepine. Epilepsia 47:510–515

    Article  PubMed  CAS  Google Scholar 

  72. Pack AM, Morrell MJ, Marcus R et al (2005) Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol 57:252–257

    Article  PubMed  CAS  Google Scholar 

  73. Verrotti A, Greco R, Morgese G, Chiarelli F (2000) Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol 47:385–388

    Article  PubMed  CAS  Google Scholar 

  74. Lau KHW, Nakade O, Barr B, Taylor AK, Houchin K, Baylink DJ (1995) Phenytoin increases markers of osteogenesis for human species in vitro and in vivo. J Clin Endocrinol Metab 80:2347–2353

    Article  PubMed  CAS  Google Scholar 

  75. Kim SH, Lee JW, Choi KG, Chung HW, Lee HW (2007) A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy. Epilepsy Behav 10:291–295

    Article  PubMed  Google Scholar 

  76. Sato Y, Kondo I, Ishida S et al (2001) Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology 57:445–449

    PubMed  CAS  Google Scholar 

  77. Toh S, Hernandez-Diaz S (2007) Statins and fracture risk. A systematic review. Pharmacoepidemiol Drug Saf 16(6):627–640

    Article  PubMed  CAS  Google Scholar 

  78. Bone HG, Kiel DP, Lindsay RS et al (2007) Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial. J Clin Endocrinol Metab 92:4671–4677

    Article  PubMed  CAS  Google Scholar 

  79. Berthold HK, Unverdorben S, Zittermann A et al (2004) Age-dependent effects of atorvastatin on biochemical bone turnover markers: a randomized controlled trial in postmenopausal women. Osteoporos Int 15:459–467

    Article  PubMed  CAS  Google Scholar 

  80. Braatvedt GD, Bagg W, Gamble G, Davidson J, Reid IR (2004) The effect of atorvastatin on markers of bone turnover in patients with type 2 diabetes. Bone 35:766–770

    Article  PubMed  CAS  Google Scholar 

  81. Rejnmark L, Buus NH, Vestergaard P et al (2004) Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women. J Bone Miner Res 19:737–744

    Article  PubMed  CAS  Google Scholar 

  82. Rosenson RS, Tangney CC, Langman CB, Parker TS, Mevine DM, Gordon BR (2005) Short-term reduction in bone markers with high-dose simvastatin. Osteoporos Int 16:1272–1276

    Article  PubMed  Google Scholar 

  83. Montagnani A, Gonnelli S, Cepollaro C et al (2003) Effect of simvastatin treatment on bone mineral density and bone turnover in hypercholesterolemic postmenopausal women: a 1-year longitudinal study. Bone 32:427–433

    Article  PubMed  CAS  Google Scholar 

  84. Mostaza JM, de la Piedra C, Curiel MD, Pena R, Lahoz C (2001) Pravastatin therapy increases procollagen I N-terminal propeptide (PINP), a marker of bone formation in post-menopausal women. Clin Chim Acta 308:133–137

    Article  PubMed  CAS  Google Scholar 

  85. Ho-Ming Chan M, Wing-Lai M, Wai-Kwun Chiu R, Chow CC, Hiu-Shuen I, Wai-Kei Lam C (2001) Simvastatin increases serum osteocalcin concentration in patients treated for hypercholesterolaemia. J Clin Endocrinol Metab 86:4556–4559

    Article  Google Scholar 

  86. Yki-Jarvinen H (2004) Thiazolidinediones. N Engl J Med 351:1106–1118

    Article  PubMed  Google Scholar 

  87. Grey A, Bolland M, Gamble G et al (2007) The peroxisome proliferator-activated receptor-γ agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 92:1305–1310

    Article  PubMed  CAS  Google Scholar 

  88. Berberoglu Z, Gursoy A, Bayraktar N, Yazici AC, Tutuncu NB, Demirag NG (2007) Rosiglitazone decreases serum bone-specific alkaline phosphatase activity in postmenopausal diabetic women. J Clin Endocrinol Metab 92:3523–3530

    Article  PubMed  CAS  Google Scholar 

  89. Watanabe S, Takeuchi Y, Fukumoto S, Fujita H, Nakano T, Fujita T (2003) Decrease in serum leptin by troglitazone is associated with preventing bone loss in type 2 diabetic patients. J Bone Miner Metab 21:166–171

    Article  PubMed  CAS  Google Scholar 

  90. Okazaki R, Miura M, Toriumi M et al (1999) Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus. Endocr J 46:795–801

    Article  PubMed  CAS  Google Scholar 

  91. Rajgopal R, Bear MK, Butcher MK, Shaugnessy SG (2007) The effects of heparin and low molecular weight heparins on bone. Thromb Res http://dx.doi.org/10.1016/j.thromres.2006.10.025

  92. Knapen MHJ, Hellemons-Boode BSP, Langenberg-Ledeboer M et al (2000) Effect of oral anticoagulant treatment on markers for calcium and bone metabolism. Haemostasis 30:290–297

    Article  PubMed  CAS  Google Scholar 

  93. Obrant KJ, Käkönen SM, Astermark J et al (1999) The proportion of carboxylated to total or intact osteocalcin in serum discriminates warfarin-treated patients from control subjects. J Bone Miner Res 14:555–560

    Article  PubMed  CAS  Google Scholar 

  94. Menon RK, Gill DS, Thomas M, Kernoff PBA, Dandona P (1987) Impaired carboxylation of osteocalcin in warfarin-treated patients. J Clin Endocrinol Metab 64:59–61

    Article  PubMed  CAS  Google Scholar 

  95. Pietschmann P, Woloszczuk W, Panzer S, Kyrle P, Smolen J (1988) Decreased serum osteocalcin levels in phenprocoumon-treated patients. J Clin Endocrinol Metab 66:1071–1074

    PubMed  CAS  Google Scholar 

  96. Chapuy MC, Schott AM, Garnero P, Hans D, Delmas PD, Meunier PJ (1996) Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. J Clin Endocrinol Metab 81:1129–1133

    Article  PubMed  CAS  Google Scholar 

  97. Theiler R, Stähelin HB, Kräzlin M, Tyndall A, Bischoff HA (1999) High bone turnover in the elderly. Arch Phys Med Rehabil 80:485–489

    Article  PubMed  CAS  Google Scholar 

  98. Theiler R, Stähelin HB, Kräzlin M et al (2000) Influence of physical mobility and season on 25-hydroxyvitamin D-parathyroid hormone interaction and bone remodelling in the elderly. Eur J Endocrinol 143:673–679

    Article  PubMed  CAS  Google Scholar 

  99. Rapuri PB, Kinaymu HK, Gallagher JC, Haynatzka V (2002) Seasonal changes in calciotropic hormones, bone markers, and bone mineral density in elderly women. J Clin Endocrinol Metab 87:2024–2032

    Article  PubMed  CAS  Google Scholar 

  100. Hannon R, Eastell R (2000) Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 11 [Suppl 6]:30–44

    Article  CAS  Google Scholar 

  101. Smith SM, Dillon EL, DeKerlagand DE, Davis-Street JE (2004) Variablity of collagen crosslinks: impact of sample collection period. Calcif Tissue Int 74:336–341

    Article  PubMed  CAS  Google Scholar 

  102. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD (1996) Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 11:337–349

    PubMed  CAS  Google Scholar 

  103. Garnero P, Mulleman D, Munoz F, Sornay-Rendu E, Delmas PD (2003) Long-term variability of markers of bone turnover in postmenopausal women and implications for their clinical use: the OFELY study. J Bone Miner Res 18:1789–1794

    Article  PubMed  Google Scholar 

  104. Chaki O, Yoshikata I, Kikuchi R et al (2000) The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women. J Bone Miner Res 15:1537–1544

    Article  PubMed  CAS  Google Scholar 

  105. Löfman O, Magnusson P, Toss G, Larsson L (2005) Common biochemical markers of bone turnover predict future bone loss: a 5-year follow-up study. Clin Chim Acta 356:67–75

    Article  PubMed  CAS  Google Scholar 

  106. Schneider DL, Barrett-Connor EL (1997) Urinary N-telopeptide levels discriminate normal, osteopenic, and osteoporotic bone mineral density. Arch Intern Med 157:1241–1245

    Article  PubMed  CAS  Google Scholar 

  107. Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC (1992) Biochemical parameters associated with low bone density in healthy men and women. J Bone Miner Res 7:1123–1130

    PubMed  CAS  Google Scholar 

  108. Stepan JJ (2000) Prediction of bone loss in premenopausal women. Osteoporos Int 11 [Suppl 6]:S45–S54

    Article  PubMed  Google Scholar 

  109. Iki M, Morita A, Ikeda Y et al (2006) Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women—the Japanese Population-based Osteoporosis (JPOS) cohort study. Osteoporosis Int 17:1086–1095

    Article  CAS  Google Scholar 

  110. Chapurlat RD, Garnero P, Sprnay-Rendu E, Arlot ME, Claustrat B, Delmas PD (2000) Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women. Osteoporos Int 11:493–498

    Article  PubMed  CAS  Google Scholar 

  111. Garnero P, Sornay-Rendu E, Duboeuf F, Delmas PD (1999) Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study. J Bone Miner Res 14:1614–1621

    Article  PubMed  CAS  Google Scholar 

  112. Rogers A, Hannon RA, Eastell R (2000) Biochemical markers as predictors of rates of bone loss after menopause. J Bone Miner Res 15:1398–1404

    Article  PubMed  CAS  Google Scholar 

  113. Cheng S, Suominen H, Väänänen K, Käkönen SM, Pettersson K, Heikkinen E (2002) Serum osteocalcin in relation to calcaneal bone mineral density in elderly men and women: a 5-year follow-up. J Bone Miner Metab 20:49–56

    Article  PubMed  CAS  Google Scholar 

  114. Melton LJ III, Atkinson EJ, O’Connor MK, O’Fallon W, Riggs BL (2000) Determinants of bone loss from the femoral neck in women of different ages. J Bone Miner Res 15:24–31

    Article  PubMed  Google Scholar 

  115. Yoshimura N, Hashimoto T, Sakata K, Morioka S, Kasamatsu T, Copper C (1999) Biochemical markers of bone turnover and bone loss at the lumbar spine and femoral neck: the Taiji study. Osteoporos Int 65:198–202

    CAS  Google Scholar 

  116. Dennison E, Eastell R, Fall CHD, Kellingray S, Wood PJ, Cooper C (1999) Determinants of bone loss in elderly men and women: a prospective population-based study. Osteoporos Int 10:384–391

    Article  PubMed  CAS  Google Scholar 

  117. Bauer DC, Sklarin PM, Stone KL et al (1999) Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures. J Bone Miner Res 14:1404–1410

    Article  PubMed  CAS  Google Scholar 

  118. Slemenda C, Longcope C, Peacock M, Hui S, Johston CC (1996) Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women. J Clin Invest 97:14–21

    Article  PubMed  CAS  Google Scholar 

  119. Keen RW, Nguyen T, Sobnack R, Perry LA, Thompson PW, Spector TD (1996) Can biochemical markers predict bone loss at the hip and spine ? A 4-year prospective study of 141 early postmenopausal women. Osteoporos Int 6:399–406

    Article  PubMed  CAS  Google Scholar 

  120. Cummings SR, Palermo L, Browner W (2000) Monitoring osteoporosis therapy with bone densitometry. Misleading changes and regression to the mean. JAMA 283:1318–1321

    Article  PubMed  CAS  Google Scholar 

  121. Christiansen C, Riis BJ, Rodbro P (1987) Prediction of rapid bone loss in postmenopausal women. Lancet I:1105–1108

    Article  Google Scholar 

  122. Ross PD, Knowlton W (1998) Rapid bone loss is associated with increased levels of biochemical markers. J Bone Miner Res 13:297–302

    Article  PubMed  CAS  Google Scholar 

  123. Akesson K, Ljunghall S, Jonsson B et al (1995) Assessment of biochemical markers of bone metabolism in relation to the occurrence of fracture: a retrospective and prospective population-based study of women. J Bone Miner Res 10:1823–1829

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  125. 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 

  126. Tromp AM, Ooms ME, Popp-Snijders C, Roos JC, Lips P (2000) Predictors of fractures in elderly women. Osteoporos Int 11:134–140

    Article  PubMed  CAS  Google Scholar 

  127. Garnero P, Cloos P, Sornay-Rendu E, Qvist P, Delmas PD (2002) Type I collagen racemization and isomerization and the risk of fracture in postmenopausal women: the OFELY prospective study. J Bone Miner Res 17:826–833

    Article  PubMed  CAS  Google Scholar 

  128. Bruyère O, Collette J, Delmas P et al (2003) Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal women. Maturitas 44:259–265

    Article  PubMed  CAS  Google Scholar 

  129. Melton LJ III, Crowson CS, O’Fallon WM, Wahner HW, Riggs BL (2003) Relative contribution of bone density, bone turnover, and clinical risk factors to long-term fracture prediction. J Bone Miner Res 18:312–318

    Article  PubMed  Google Scholar 

  130. Gerdhem P, Ivaska KK, Alatalo SL et al (2004) Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res 19:386–393

    Article  PubMed  CAS  Google Scholar 

  131. Sornay-Rendu E, Munoz F, Garnero P, Duboeuf F, Delmas PD (2005) Identification of osteopenic women at high risk of fracture: the OFELY study. J Bone Miner Res 20:1813–1819

    Article  PubMed  Google Scholar 

  132. Ivaska KK, Gerdhem P, Akesson K, Obrant KJ (2007) Bone turnover markers and prediction of fracture: nine-year follow-up study of 1040 elderly women. J Bone Miner Res 22 [Suppl 1]:S21, Abstract 1073

    Google Scholar 

  133. Garnero P, Hausher E, Chapuy MC et al (1996) Markers of bone resorption predict hip fracture in elderly women: the Epidos prospective study. J Bone Miner Res 11:1531–1538

    PubMed  CAS  Google Scholar 

  134. Chapurlat RD, Garnero P, Bréart G, Meunier PJ, Delmas PD (2000) Serum type I collagen breakdown product (serum CTX) predicts hip fracture risk in elderly women: the EPIDOS study. Bone 27:283–286

    Article  PubMed  CAS  Google Scholar 

  135. Chen JS, Seibel MJ, Zochling J et al (2006) Calcaneal ultrasound but not bone turnover predicts fractures in vitamin D deficient frail elderly at high risk of falls. Calcif Tissue Int 79:37–42

    Article  PubMed  CAS  Google Scholar 

  136. Garnero P, Dargent-Molina P, Hans D et al (1998) Do markers of bone resorption add to bone mineral density and ultrasonographic heel measurement for the prediction of hip fracture in elderly women? The EPIDOS prospective study. Osteoporos Int 8:563–569

    Article  PubMed  CAS  Google Scholar 

  137. Weel AEAM, Seibel MJ, Hofman A, Leeuwen JPTM, Pols HAP (1999) Which fractures are associated with high bone resorption in elderly women: the Rotterdam study. J Bone Miner Res 14 [Suppl 1]:S160, Abstract 1110

    Google Scholar 

  138. Dobnig H, Piswanger-Sölkner JC, Obermayer-Pietsch B et al (2007) Hip and nonvertebral fracture prediction in nursing home patients: role of bone ultrasound and bone marker measurements. J Clin Endocrinol Metab 92:1678–1686

    Article  PubMed  CAS  Google Scholar 

  139. Johnell O, Oden A, de Laet C, Garnero P, Delmas PD, Kanis JA (2002) Biochemical indices of bone turnover and the assessment of fracture probability. Osteoporos Int 13:523–526

    Article  PubMed  CAS  Google Scholar 

  140. Robbins JA, Schott AM, Garnero P, Delmas PD, Hans D, Meunier PJ (2005) Risk factors for hip fracture in women with high BMD: EPIDOS study. Osteoporos Int 16:149–154

    Article  PubMed  CAS  Google Scholar 

  141. Delmas PD, Licata AA, Reginster JY et al (2006) Fracture risk reduction during treatment with teriparatide is independent of pretreatment bone turnover. Bone 39:237–243

    Article  PubMed  CAS  Google Scholar 

  142. Bauer DC, Garnero P, Hochberg MC et al DM (2006) Pretreatment levels of bone turnover and the antifracture efficacy of alendronate: the fracture intervention trial. J Bone Miner Res 21:292–299

    Article  PubMed  CAS  Google Scholar 

  143. Schousboe JT, Bauer DC, Nyman JA, Kane RL, Melton LJ, Ensrud KE (2007) Potential for bone turnover markers to cost-effectively identify and select post-menopausal osteopenic women at high risk of fracture for bisphosphonate therapy. Osteoporos Int 18:201–210

    Article  PubMed  CAS  Google Scholar 

  144. Garnero P (2000) Markers of bone turnover for the prediction of fracture risk. Osteoporos Int 11 [Suppl 6]:S55–S65

    Article  PubMed  Google Scholar 

  145. Borah B, Dufresne TE, Chmielewski PA, Johnson TD, Chines A, Manhart MD (2004) Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. Bone 34:736–746

    Article  PubMed  CAS  Google Scholar 

  146. Szulc P, Seeman E, Dubeouf F, Sornay-Rendu E, Delmas PD (2006) Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J Bone Miner Res 21:1856–1863

    Article  PubMed  Google Scholar 

  147. 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 

  148. Dempster DW (2000) The contribution of trabecular architecture to cancellous bone quality. J Bone Miner Res 15:20–23

    Article  PubMed  CAS  Google Scholar 

  149. Follet H, Boivin G, Rumelhart C, Meunier PJ (2004) The degree of mineralization is a determinant of bone strength: a study on human calcanei. Bone 34:783–789

    Article  PubMed  CAS  Google Scholar 

  150. Viguet-Carin S, Roux JP, Arlot ME et al (2006) Contribution of the advanced glycation end product pentosidine and of maturation of type I collagen to compressive biomechanical properties of human lumbar vertebrae. Bone 39:1073–1079

    Article  CAS  Google Scholar 

  151. Oxlund H, Barckman M, Ortoft G, Andreassen TT (1995) Reduced concentrations of collagen cross-links are associated with reduced strength of bone. Bone 17 [Suppl 4]:365S–371S

    PubMed  CAS  Google Scholar 

  152. Banse X, Sims TJ, Bailey AJ (2002) Mechanical properties of adult vertebral cancellous bone: correlation with collagen intermollecular cross-links. J Bone Miner Res 17:1621–1628

    Article  PubMed  CAS  Google Scholar 

  153. Garnero P, Gineyts E, Arbault P, Christiansen C, Delmas PD (1995) Different effects of bisphosphonate and estrogen therapy on free and peptide-bound cross-links excretion. J Bone Miner Res 10:641–649

    Article  PubMed  CAS  Google Scholar 

  154. Colwell A, Eastell R (1996) The renal clearance of free and conjugated pyridinium cross-links of collagen. J Bone Miner Res 11:1976–1980

    PubMed  CAS  Google Scholar 

  155. Bonnick S, Saag KG, Kiel DP et al (2006) Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years. J Clin Endcrinol Metab 91:2631–1637

    Article  CAS  Google Scholar 

  156. Reszka AA, Rodan GA (2003) Mechanism of action of bisphosphonates. Curr Osteoporos Rep 1:45–52

    Article  PubMed  Google Scholar 

  157. Liberman UM, Weiss SR, Broll J (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The alendronate phase III osteoporosis treatment study group. N Engl J Med 333:1437–1443

    Article  PubMed  CAS  Google Scholar 

  158. Harris ST, Watts NB, Genant HK (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. A randomized controlled trial. JAMA 282:1344–1352

    Article  PubMed  CAS  Google Scholar 

  159. Roodman D (2006) Regulation of osteoclast differentiation. Ann N Y Acad Sci 1068:100–109

    Article  PubMed  CAS  Google Scholar 

  160. Kim MK, Kim HD, Park JH et al (2006) An orally active cathepsin K inhibitor, furan-2-carboxylic acid, 1-{1-[4-flouro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide (OST-4077), inhibits osteoclast activity in vitro and bone loss in ovariectomized rats. J Pharmacol Exp Ther 318:555–562

    Article  PubMed  CAS  Google Scholar 

  161. McClung MR, Lewiecki EM, Cohen SB et al (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354:821–831

    Article  PubMed  CAS  Google Scholar 

  162. Papanastasiou P, Ortmann CE, Olson M, Vigneron A, Trechsel U (2006) Effect of three month treatment with the cathepsin K inhibitor, balicatib, on biochemical markers of bone turnover in postmenopausal women. Evidence for uncoupling of bone resorption and bone formation. J Bone Miner Res 21 [Suppl 1]:S59, Abstract 1223

    Google Scholar 

  163. Delmas PD, Bjarnason NH, Mitlak BH (1997) Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 337:1641–1647

    Article  PubMed  CAS  Google Scholar 

  164. Ravn P, Clemmesen B, Riis BJ, Christiansen C (1996) The effect on bone mass and bone markers of different doses of ibandronate: a new bisphosphonate for prevention and treatment of postmenopausal osteoporosis: a 1-year, randomized, double-blind, placebo-controlled dose-finding study. Bone 19:527–533

    Article  PubMed  CAS  Google Scholar 

  165. Thiébaud D, Burckhardt P, Kriegbaum H et al (1997) Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis. Am J Med 103:298–307

    Article  PubMed  Google Scholar 

  166. Christiansen C, Tanko LB, Warming L et al (2003) Dose dependent effects on bone resorption and formation of intermittently administered intravenous ibandronate. Osteoporos Int 14:609–613

    Article  PubMed  CAS  Google Scholar 

  167. Greenspan SL, Bone HG, Ettinger MP et al (2007) Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis. Ann Intern Med 146:326–339

    PubMed  Google Scholar 

  168. Chen P, Satterwhite JH, Licata AA et al (2005) Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 20:962–970

    Article  PubMed  CAS  Google Scholar 

  169. Dobnig H, Sipos A, Jiang Y et al (2005) Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. J Clin Endocrinol Metab 90:3970–3977

    Article  PubMed  CAS  Google Scholar 

  170. Hodsman AB, Hanley DA, Ettinger MP et al (2003) Efficacy and safety of human parathyroid hormone-(1–84) in increasing bone mienral density in postmenopausal osteoporosis. J Clin Endocrinol Metab 88:5212–5220

    Article  PubMed  CAS  Google Scholar 

  171. Lindsay R, Nieves J, Formica C et al (1997) Randomised controlled study of effect of parathyroid hormone on vertebral bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 350:550–555

    Article  PubMed  CAS  Google Scholar 

  172. Eastell R, McCloskey EV, Glover S et al (2007) Rapid and robust biochemical response to teriparatide therapy for osteoporosis. J Bone Miner Res 22 [Suppl 1]:S322, Abstract T366

    Google Scholar 

  173. Jilka RL (2007) Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 40:1434–1446

    Article  PubMed  CAS  Google Scholar 

  174. Aubin JE, Lian JB, Stein GS (2006) In: Favus M (ed) Bone formation: maturation and functional activities of osteoblast lineage cells. Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th edn. American Society for Bone and Mineral Research, Washington, DC, pp 20–29

    Google Scholar 

  175. Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB (2007) Effects of a one-month treatment with PTH(1–34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res 2007 22:495–502

    Article  PubMed  CAS  Google Scholar 

  176. Meunier PJ, Roux C, Seeman E et al (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468

    Article  PubMed  CAS  Google Scholar 

  177. Delmas PD, Pornel B, Felsenberg D et al (1999) A dose-ranging trial of a matrix transdermal 17β-estradiol for the prevention of bone loss in early postmenopausal women. Bone 24:517–523

    Article  PubMed  CAS  Google Scholar 

  178. McClung M, Clemmensen B, Daifotis A (1998) Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Ann Intern Med 128:253–261

    PubMed  CAS  Google Scholar 

  179. Harris ST, Gertz BJ, Genant HK et al (1993) The effect of short term treatment with alendronate on vertebral density and biochemical markers of bone remodelling in early postmenopausal women. J Clin Endocrinol Metab 76:1399–1406

    Article  PubMed  CAS  Google Scholar 

  180. Reginster JY, Adami S, Lakatos P et al (2006) Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis 65:654–661

    Article  PubMed  CAS  Google Scholar 

  181. McClung M, Wasnich R, Recker R et al (2004) Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis. J Bone Miner Res 19:11–18

    Article  PubMed  CAS  Google Scholar 

  182. Tanko LB, Felsenberg D, Czerwinski E et al (2003) Oral weekly ibandronate prevents bone loss in postmenopausal women. J Intern Med 254:159–167

    Article  PubMed  CAS  Google Scholar 

  183. Reid IR, Brown JP, Burckhardt P (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653–661

    Article  PubMed  CAS  Google Scholar 

  184. Delmas PD (2002) Treatment of postmenopausal osteoporosis. Lancet 359:2018–2026

    Article  PubMed  CAS  Google Scholar 

  185. Prestwood KM, Kenny AM, Unson C, Kulldorff M (2000) The effect of low dose micronized 17β-estradiol on bone turnover, sex hormone levels, and side effects in older women: a randomized, double blind, placebo-controlled study. J Clin Endocrinol Metab 85:4462–4469

    Article  PubMed  CAS  Google Scholar 

  186. Prestwood KM, Kenny AM, Kleppinger A, Kulldorff M (2003) Ultralow-dose micronized 17β-estradiol and bone density and bone metabolism in older women. A randomized controlled trial. JAMA 290:1042–1048

    Article  PubMed  CAS  Google Scholar 

  187. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH (2002) Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 287:2668–2676

    Article  PubMed  CAS  Google Scholar 

  188. 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 

  189. Delmas PD, Li Z, Cooper C (2004) Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses. J Bone Miner Res 19:330–337

    Article  PubMed  CAS  Google Scholar 

  190. Sarkar S, Mitlak BH, Wong M, Stock JL, Black DM, Harper KD (2002) Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 17:1–10

    Article  PubMed  CAS  Google Scholar 

  191. Chapurlat RD, Palermo L, Ramsay P, Cummings SR (2005) Risk of fracture among women who lose bone density during treatment with alendronate. The fracture intervention trial. Osteoporos Int 16:842–848

    Article  PubMed  CAS  Google Scholar 

  192. Bauer DC, Black DM, Garnero P et al (2004) Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 19:1250–1258

    Article  PubMed  Google Scholar 

  193. 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 

  194. Eastell R, Hannon RA, Garnero P, Campbell MJ, Delmas PD (2007) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate: review of statistical analysis. J Bone Miner Res 22:1656–1660

    Article  PubMed  Google Scholar 

  195. Reginster JY, Sarkar S, Zegels B et al (2004) Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk. Bone 34:344–351

    Article  PubMed  CAS  Google Scholar 

  196. Bjarnasson NH, Sarkar 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  Google Scholar 

  197. Finkelstein JS, Klibanski A, Arnold AL, Toth TL, Hornstein MD, Neer RM (1998) Prevention of estrogen deficiency-related bone loss with human parathyroid hormone-(1–34). A randomized control trial. JAMA 280:1067–1073

    Article  PubMed  CAS  Google Scholar 

  198. Bauer DC, Garnero P, Bilezikian JP et al (2006) Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 91:1370–1375

    Article  PubMed  CAS  Google Scholar 

  199. Wasnich RD, Bagger YZ, Hosking DJ et al (2004) Changes in bone density and turnover after alendronate or estrogen withdrawal. Maturitas 11:622–630

    Google Scholar 

  200. Sornay-Rendu E, Garnero P, Munoz F, Duboeuf F, Delmas PD (2003) Effect of withdrawal of hormone replacement therapy on bone mass and bone turnover: the OFELY study. Bone 33:159–166

    Article  PubMed  CAS  Google Scholar 

  201. Greenspan SL, Emkey RD, Bone HG (2002) Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 137:875–883

    PubMed  CAS  Google Scholar 

  202. Gallagher JC, Rapuri PB, Haynatzki G, Detter JR (2002) Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers. J Clin Endocrinol Metab 87:4914–4923

    Article  PubMed  CAS  Google Scholar 

  203. Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black DM, Cummings SR (1995) Estrogen replacement therapy and fractures in older women. Study of osteoporotic fractures research group. Ann Intern Med 122:9–16

    PubMed  CAS  Google Scholar 

  204. Raisz L, Smith JA, Trahiotis M et al (2000) Short-term risedronate treatment in postmenopausal women: effects on biochemical markers of bone turnover. Osteoporos Int 11:615–620

    Article  PubMed  CAS  Google Scholar 

  205. Ravn P, Christensen JO, Baumann M, Clemmensen B (1998) Changes in biochemical markers and bone mass after withdrawal of ibandronate treatment: prediction of bone mass changes during treatment. Bone 22:559–564

    Article  PubMed  CAS  Google Scholar 

  206. Watts NB, Chines A, Olszynski WP et al (2008) Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int 19:365–372

    Article  PubMed  CAS  Google Scholar 

  207. Bone HG, Hosking D, Devolelaer JP et al (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–1199

    Article  PubMed  CAS  Google Scholar 

  208. Tonino RP, Meunier PJ, Emkey R et al (2000) Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. J Clin Endocrinol Metab 85:3109–3115

    Article  PubMed  CAS  Google Scholar 

  209. Ravn P, Bidstrup M, Wasnich RD et al (1999) Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results from the early postmenopausal intervention cohort study. A randomized, controlled trial. Ann Intern Med 131:935–942

    PubMed  CAS  Google Scholar 

  210. Black DM, Schwartz AV, Ensrud KE et al (2006) Effects of continuing or stopping alendronate after 5 years of treatment. The Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296:2927–2938

    Article  PubMed  CAS  Google Scholar 

  211. Bagger YZ, Tanko LB, Alexandersen P, Ravn P, Christiansen C (2003) Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal. Bone 33:301–307

    Article  PubMed  CAS  Google Scholar 

  212. Ensrud KE, Barrett-Connor EL, Schwartz A et al (2004) Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the fracture intervention trial long-term extension. J Bone Miner Res 19:1259–1269

    Article  PubMed  CAS  Google Scholar 

  213. Black DM, Bilezikian JP, Ensrud KE et al (2005) One year alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N Engl J Med 353:555–565

    Article  PubMed  CAS  Google Scholar 

  214. Black DM, Greenspan SL, Ensrud KE et al (2003) The effects of parathyroid hormone and alendronate alone or in comination in postmenopausal osteoporosis. N Engl J Med 349:1207–1215

    Article  PubMed  CAS  Google Scholar 

  215. Ettinger B, San Martin J, Crans G, Pavo I (2004) Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 19:745–751

    Article  PubMed  CAS  Google Scholar 

  216. Delmas PD, Watts N, Miller P, Cahall D, Bilezikian J, Lindsay R (2007) Bone turnover markers demonstrate greater earlier responsiveness to teriparatide following treatment with risedronate compared with alendronate: the OPTAMISE study. J Bone Miner Res 22 [Suppl 1]:S27, Abstract 1092

    Google Scholar 

  217. Rittmaster RS, Bolognese M, Ettinger MP et al (2000) Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab 85:2129–2134

    Article  PubMed  CAS  Google Scholar 

  218. Black DM, Bauer DC, Rosen CJ, Greenspan SL, Bilezikian JP (2007) Prediction of 24 month change in BMD on PTH followed by alendronate: the PaTH study. J Bone Miner Res 22 [Suppl 1]:S26, Abstract 1090

    Google Scholar 

  219. Eviö S, Tiitinen A, Laitinen K, Ylikorkala O, Välimäki MJ (2004) Effects of alendronate and hormone replacement therapy, alone and in combination, on bone mass and markers of bone turnover in elderly women with osteoporosis. J Clin Endocrinol Metab 89:626–631

    Article  PubMed  CAS  Google Scholar 

  220. Lindsay R, Cosman F, Lobo RA et al (1999) Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial. J Clin Endocrinol Metab 84:3076–3081

    Article  PubMed  CAS  Google Scholar 

  221. Harris ST, Eriksen EF, Davidson M et al (2001) Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 86:1890–1897

    Article  PubMed  CAS  Google Scholar 

  222. Warming L, Ravn P, Christiansen C (2005) Levonorgestrel and 17β-estradiol given transdermally for the prevention of postmenopausal osteoporosis. Maturitas 50:78–85

    Article  PubMed  CAS  Google Scholar 

  223. Liu JH, Muse KN (2005) The effects of progestins on bone density and bone metabolism in postmenopausal women: a randomized controlled trial. Am J Obstet Gynecol 192:1316–1324

    Article  PubMed  CAS  Google Scholar 

  224. Tobias JH, Clarke S, Mitchell K, Robins S, Amer H, Fraser WD (2001) Analysis of the contribution of dydrogesterone to bone turnover changes in postmenopausal women commencing hormone replacement therapy. J Clin Endocrinol Metab 86:1194–1198

    Article  PubMed  CAS  Google Scholar 

  225. Raisz LG, Wiita B, Artis A et al (1996) Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. J Clin Endocrinol Metab 81:37–43

    Article  PubMed  CAS  Google Scholar 

  226. Committee for Medicinal Products for Human Use—Guideline on the evaluation of medicinal products in the treatment of primary osteoporosis. European Medicinal Agency CPMP/EWP/552/95 Rev. 2

  227. Rizzoli R, the Alendronate Once-weekly Study Group (2002) Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis. J Bone Miner Res 17:1988–1996

    Article  PubMed  CAS  Google Scholar 

  228. Watts NB, Lindsay R, Li Z, Kasibhatla C, Brown J (2003) Use of matched historical controls to evaluate the anti-fracture efficacy of once-a-week risedronate. Osteoporos Int 14:437–441

    Article  PubMed  CAS  Google Scholar 

  229. Brown JP, Kendler DL, McClung MR et al (2002) The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Calcif Tissue Int 71:103–111

    Article  PubMed  CAS  Google Scholar 

  230. Chesnut CH III, Skag A, Christiansen C et al (2004) Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal women. J Bone Miner Res 19:1241–1249

    Article  CAS  Google Scholar 

  231. Delmas PD, Recker RR, Chesnut CH III et al (2004) Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study. Osteoporos Int 15:792–798

    Article  PubMed  CAS  Google Scholar 

  232. Miller PD, McClung MR, Macovei L et al (2005) Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res 20:1315–1322

    Article  PubMed  CAS  Google Scholar 

  233. Papapoulos S, Schimmer R (2007) Changes in bone remodeling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate. Ann Rheum Dis 66:853–838

    Article  PubMed  CAS  Google Scholar 

  234. Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int 15:1003–1008

    Article  PubMed  Google Scholar 

  235. Eastell R, Garnero P, Vrijens B et al (2003) Influence of patient compliance with risedronate therapy on bone turnover marker and bone mineral density response: the IMPACT study. Calcif Tissue Int 72:408, Abstract P-297

    Google Scholar 

  236. Clowes JA, Peel NFA, Eastell R (2004) The impact of monitoring on adherence and persistence with anti-resorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89:1117–1123

    Article  PubMed  CAS  Google Scholar 

  237. Delmas PD, Vrijens B, Eastell R et al (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 

  238. Delmas PD (2000) Markers of bone turnover for monitoring treatment of osteoporosis with antiresorptive drugs. Osteoporos Int 11 [Suppl 6]:S66–S76

    Article  PubMed  Google Scholar 

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Szulc, P., Delmas, P.D. Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis. Osteoporos Int 19, 1683–1704 (2008). https://doi.org/10.1007/s00198-008-0660-9

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