Bone turnover markers: use in osteoporosis (original) (raw)

• Eriksen, E. F., Axelrod, D. W. & Melsen, F. Skeletal growth, modeling and remodeling in Bone Histomorphometry 1–2 (Raven Press, New York, 1994).
  Google Scholar
• Delmas, P. D., Eastell, R., Garnero, P., Seibel, M. J. & Stepan, J. The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos. Int. 11 (Suppl. 6), S2–S17 (2000).
  Article PubMed Google Scholar
• Singer, F. R. & Eyre, D. R. Using biochemical markers of bone turnover in clinical practice. Cleve. Clin. J. Med. 75, 739–750 (2008).
  Article PubMed Google Scholar
• Brown, J. P. et al. Bone turnover markers in the management of postmenopausal osteoporosis. Clin. Biochem. 42, 929–942 (2009).
  Article CAS PubMed Google Scholar
• Kucharz, E. J. The Collagens: Biochemistry and Pathophysiology (Springer-Verlag, Heidelberg, 1992).
  Book Google Scholar
• Black, D., Duncan, A. & Robins, S. P. Quantitative analysis of the pyridinium crosslinks of collagen in urine using ion-paired reversed-phase high performance chromatography. Anal. Biochem. 169, 197–203 (1988).
  Article CAS PubMed Google Scholar
• Colwell, A., Russell, R. G. G. & Eastell, R. Factors affecting the assay of urinary 3-hydroxy pyridinium cross-links of collagen as markers of bone resorption. Eur. J. Clin. Invest. 23, 341–349 (1993).
  Article CAS PubMed Google Scholar
• Fujimoto, D., Suzuki, M., Uchiyama, A., Miayamoto, S. & Inoue, T. Analysis of pyridinoline, a crosslinking compound of collagen fibres, in human urine. J. Biochem. 94, 1133–1136 (1983).
  Article CAS PubMed Google Scholar
• Eyre, D. R., Koob, T. J. & Van Ness, K. P. Quantitation of hydroxypyridinium crosslinks in collagen by high-performance liquid chromatography. Anal. Biochem. 137, 380–388 (1984).
  Article CAS PubMed Google Scholar
• Robins, S. P. et al. Direct enzyme linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption Direct, enzyme-linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption. J. Bone Miner. Res. 9, 1643–1649 (1994).
  Article CAS PubMed Google Scholar
• Fledelius, C., Johansen, J. S., Cloos, P. A. C., Bonde, M. & Qvist, P. Characterization of urinary degradation products derived from type I collagen: identification of a β isomerized ASP-GLY sequence within the C-terminal telopeptide(α-I) region. J. Biol. Chem. 272, 9755–9763 (1997).
  Article CAS PubMed Google Scholar
• Hanson, D. A. et al. A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen crosslinked N-telopeptides in urine. J. Bone Miner. Res. 7, 1251–1258 (1992).
  Article CAS PubMed Google Scholar
• Clemens, J. D., Herrick, M. V., Singer, F. R. & Eyre, D. R. Evidence that serum NTx (collagen-type I N-telopeptides) can act as an immunochemical marker of bone resorption. Clin. Chem. 43, 2058–2063 (1997).
  CAS PubMed Google Scholar
• Bonde, M., Qvist, P., Fledelius, C., Riis, B. J. & Christiansen, C. Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin. Chem. 40, 2022–2025 (1994).
  CAS PubMed Google Scholar
• Risteli, J., Elomaa, I., Niemi, S., Novamo, A. & Risteli, L. Radioimmunoassay for the pyridinoline cross-linked carboxy- terminal telopeptide of Type I collagen degradation. Clin. Chem. 39, 635–640 (1993).
  CAS PubMed Google Scholar
• Garnero, P. et al. Decreased β-isomerization of the C-terminal telopeptide of type I collagen αI chain in Paget's disease of bone. J. Bone Miner. Res. 12, 1407–1415 (1997).
  Article CAS PubMed Google Scholar
• Garnero, P. et al. Effects of PTH and alendronate on type I collagen isomerization in postmenopausal women with osteoporosis: the PaTH study. J. Bone Miner. Res. 23, 1442–1448 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Vasikaran, S. et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine Position on bone marker standards in osteoporosis. Clin. Chem. Lab Med. 49, 1271–1274 (2011).
  Article CAS PubMed Google Scholar
• Vasikaran, S. 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. 22, 391–420 (2011).
  Article CAS PubMed Google Scholar
• Garnero, P. et al. The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J. Bone Miner. Res. 18, 859–867 (2003).
  Article CAS PubMed Google Scholar
• Halleen, J. M., Tiitinen, S. L., Ylipahkala, H., Fagerlund, K. M. & Vaananen, H. K. Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin. Lab 52, 499–509 (2006).
  CAS PubMed Google Scholar
• Hannon, R. A. et al. Clinical performance of immunoreactive tartrate-resistant acid phosphatase isoform 5b as a marker of bone resorption. Bone 34, 187–194 (2004).
  Article CAS PubMed Google Scholar
• Meier, C. et al. Serum cathepsin K concentrations reflect osteoclastic activity in women with postmenopausal osteoporosis and patients with Paget's disease. Clin. Lab 52, 1–10 (2006).
  CAS PubMed Google Scholar
• Melkko, J., Niemi, S., Risteli, L. & Risteli, J. Radioimmunoassay for the carboxyterminal propeptide of human type I procollagen (PICP). Clin. Chem. 36, 1328–1332 (1990).
  CAS PubMed Google Scholar
• Melkko, J. et al. Immunoassay for intact amino-terminal propeptide of human type I procollagen. Clin. Chem. 42, 947–954 (1996).
  CAS PubMed Google Scholar
• Calvo, M. S., Eyre, D. R. & Gundberg, C. M. Molecular basis and clinical application of biological markers of bone turnover. Endocrine Rev. 17, 333–368 (1996).
  CAS Google Scholar
• Seibel, M. J. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin. Biochem. Rev. 26, 97–122 (2005).
  PubMed PubMed Central Google Scholar
• Price, P. A. & Nishimoto, S. K. Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. Proc. Natl Acad. Sci. USA 77, 2234–2238 (1980).
  Article CAS PubMed PubMed Central Google Scholar
• Cloos, P. A. & Christgau, S. Characterization of aged osteocalcin fragments derived from bone resorption. Clin. Lab. 50, 585–598 (2004).
  CAS PubMed Google Scholar
• Mokuda, S. et al. Postmenopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin (ucOC) levels. J. Endocrinol. Invest. (2011).
• Vergnaud, P. et al. Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS study. J. Clin. Endocrinol. Metab. 82, 719–724 (1997).
  CAS PubMed Google Scholar
• Clemens, T. L. & Karsenty, G. The osteoblast: an insulin target cell controlling glucose homeostasis. J. Bone Miner. Res. 26, 677–680 (2011).
  Article CAS PubMed Google Scholar
• Vesper, H. W. et al. Assessment and recommendations on factors contributing to preanalytical variability of urinary pyridinoline and deoxypyridinoline. Clin. Chem. 48, 220–235 (2002).
  CAS PubMed Google Scholar
• Hannon, R. & Eastell, R. Preanalytical variability of biochemical markers of bone turnover. Osteoporos. Int. 11 (Suppl. 6), S30–S44 (2000).
  Article PubMed Google Scholar
• Jensen, J.-E. B., Kollerup, G., Sorensen, H. A. & Sorensen, O. H. Intraindividual variability in bone markers in urine. Scand. J. Clin. Lab. Invest. 57, 29–34 (1997).
  Article Google Scholar
• Garnero, P., Borel, O. & Delmas, P. D. Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis. Clin. Chem. 47, 694–702 (2001).
  CAS PubMed Google Scholar
• Garnero, P., Vergnaud, P. & Hoyle, N. Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin. Chem. 54, 188–196 (2008).
  Article CAS PubMed Google Scholar
• Bergmann, P. et al. Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club. Int. J. Clin. Pract. 63, 19–26 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, A. J., Hodges, S. & Eastell, R. Measurement of osteocalcin. Ann. Clin. Biochem. 37, 432–446 (2000).
  Article PubMed Google Scholar
• Wichers, M., Schmidt, E., Bidlingmaier, F. & Klingmuller, D. Diurnal rhythm of CrossLaps in human serum. Clin. Chem. 45, 1858–1860 (1999).
  CAS PubMed Google Scholar
• Qvist, P., Christgau, S., Pedersen, B. J., Schlemmer, A. & Christiansen, C. 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 (2002).
  Article CAS PubMed Google Scholar
• Clowes, J. A. et al. Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone 30, 886–890 (2002).
  Article CAS PubMed Google Scholar
• Henriksen, D. B. et al. Role of gastrointestinal hormones in postprandial reduction of bone resorption. J. Bone Miner. Res. 18, 2180–2189 (2003).
  Article CAS PubMed Google Scholar
• Sato, J., Hasegawa, K., Tanaka, H. & Morishima, T. Urinary N-telopeptides of type I collagen in healthy children. Pediatr. Int. 52, 398–401 (2010).
  Article CAS PubMed Google Scholar
• Lapillonne, A., Travers, R., Dimaio, M., Salle, B. L. & Glorieux, F. H. Urinary excretion of cross-linked N-telopeptides of type 1 collagen to assess bone resorption in infants from birth to 1 year of age. Pediatrics 110, 105–109 (2002).
  Article PubMed Google Scholar
• Naylor, K. E., Iqbal, P., Fledelius, C., Fraser, R. B. & Eastell, R. The effect of pregnancy on bone density and bone turnover. J. Bone Miner. Res. 15, 129–137 (2000).
  Article CAS PubMed Google Scholar
• Veitch, S. W. et al. Changes in bone mass and bone turnover following tibial shaft fracture. Osteoporos. Int. 17, 364–372 (2006).
  Article CAS PubMed Google Scholar
• Ivaska, K. K., Gerdhem, P., Akesson, K., Garnero, P. & Obrant, K. J. 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 (2007).
  Article CAS PubMed Google Scholar
• Bahar, S. et al. Comparison of the acute alterations in serum bone turnover markers and bone mineral density among women with surgical menopause. Eur. J. Obstet. Gynecol. Reprod. Biol. 159, 194–197. (2011).
  Article PubMed Google Scholar
• Prior, J. C. et al. Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate. J. Bone Miner. Res. 12, 1851–1863 (1997).
  Article CAS PubMed Google Scholar
• Glover, S. J., Garnero, P., Naylor, K., Rogers, A. & Eastell, R. Establishing a reference range for bone turnover markers in young, healthy women. Bone 42, 623–630 (2008).
  Article CAS PubMed Google Scholar
• Adami, S. et al. Determinants of bone turnover markers in healthy premenopausal women. Calcif. Tissue Int. 82, 341–347 (2008).
  Article CAS PubMed Google Scholar
• Horowitz, G. L. Estimating reference intervals. Am. J. Clin. Pathol. 133, 175–177 (2010).
  Article PubMed Google Scholar
• Glover, S. J. et al. Establishing a reference interval for bone turnover markers in 637 healthy, young, premenopausal women from the United Kingdom, France, Belgium, and the United States. J. Bone Miner. Res. 24, 389–397 (2009).
  Article PubMed Google Scholar
• Seibel, M. J., Lang, M. & Geilenkeuser, W. J. Interlaboratory variation of biochemical markers of bone turnover. Clin. Chem. 47, 1443–1450 (2001).
  CAS PubMed Google Scholar
• United Kingdom National External Quality Assessment Service (online) (2010).
• Walsh, L. J., Wong, C. A., Pringle, M. & Tattersfield, A. E. Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study. BMJ 313, 344–346 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Osteoporosis prevention, diagnosis, and therapy. JAMA 285, 785–795 (2001).
• Van Staa, T. P. et al. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum. 48, 3224–3229 (2003).
  Article CAS PubMed Google Scholar
• Dovio, A. et al. Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis. J. Clin. Endocrinol. Metab. 89, 4923–4928 (2004).
  Article CAS PubMed Google Scholar
• Heuck, C. & Wolthers, O. D. A placebo-controlled study of three osteocalcin assays for assessment of prednisolone-induced suppression of bone turnover. J. Endocrinol. 159, 127–131 (1998).
  Article CAS PubMed Google Scholar
• KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int. Suppl. S1–S130 (2009).
• Seiler, S., Heine, G. H. & Fliser, D. Clinical relevance of FGF-23 in chronic kidney disease. Kidney Int. Suppl. S34–S42 (2009).
• Fliser, D. et al. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J. Am. Soc. Nephrol. 18, 2600–2608 (2007).
  Article CAS PubMed Google Scholar
• Garnero, P., Sornay-Rendu, E., Chapuy, M. C. & Delmas, P. D. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J. Bone Miner. Res. 11, 337–349 (1996).
  Article CAS PubMed Google Scholar
• Lofman, O., Magnusson, P., Toss, G. & Larsson, L. Common biochemical markers of bone turnover predict future bone loss: a 5-year follow-up study. Clin. Chim. Acta 356, 67–75 (2005).
  Article CAS PubMed Google Scholar
• Rosen, C. J., Chesnut III, C. H. & Mallinak, N. J. S. The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation. J. Clin. Endocrinol. Metab. 82, 1904–1910 (1997).
  CAS PubMed Google Scholar
• Rogers, A., Hannon, R. A. & Eastell, R. Biochemical markers as predictors of rates of bone loss after menopause. J. Bone Miner. Res. 15, 1398–1404 (2000).
  Article CAS PubMed Google Scholar
• Eastell, R. et al. Bone turnover markers and bone mineral density response with risedronate therapy: relationship with fracture risk and patient adherence. J. Bone Miner. Res. 26, 1662–1669 (2011).
  Article CAS PubMed Google Scholar
• Bauer, D. C. et al. 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 (2006).
  Article CAS PubMed Google Scholar
• Garnero, P. et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J. Bone Miner. Res. 11, 1531–1538 (1996).
  Article CAS PubMed Google Scholar
• van Daele, P. L. et al. Case-control analysis of bone resorption markers, disability, and hip fracture risk: the Rotterdam study. BMJ 312, 482–483 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Garnero, P., Sornay-Rendu, E., Claustrat, B. & Delmas, P. D. 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 (2000).
  Article CAS PubMed Google Scholar
• Gerdhem, P. et al. Biochemical markers of bone metabolism and prediction of fracture in elderly women. J. Bone Miner. Res. 19, 386–393 (2004).
  Article CAS PubMed Google Scholar
• Ivaska, K. K., Gerdhem, P., Vaananen, H. K., Akesson, K. & Obrant, K. J. 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. 25, 393–403 (2010).
  Article CAS PubMed Google Scholar
• Garnero, P., Cloos, P., Sornay-Rendu, E., Qvist, P. & Delmas, P. D. 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 (2002).
  Article CAS PubMed Google Scholar
• Johnell, O. et al. Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J. Clin. Endocrinol. Metab. 87, 985–992 (2002).
  Article CAS PubMed Google Scholar
• Ross, P. D. et al. Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study. Osteoporos. Int. 11, 76–82 (2000).
  Article CAS PubMed Google Scholar
• Bjarnason, N. H. 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. 12, 922–930 (2001).
  Article CAS PubMed Google Scholar
• Bauer, D. C. 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. 19, 1250–1258 (2004).
  Article PubMed Google Scholar
• Delmas, P. D. et al. Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis. J. Bone Miner. Res. 24, 1544–1551 (2009).
  Article CAS PubMed Google Scholar
• Reginster, J. Y. et al. Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk. Bone 34, 344–351 (2004).
  Article CAS PubMed Google Scholar
• Sarkar, S. et al. Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk. J. Bone Miner. Res. 19, 394–401 (2004).
  Article PubMed Google Scholar
• Bauer, D. C. et al. Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study. J. Bone Miner. Res. 24, 2032–2038 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Riis, B. J., Hansen, M. A., Jensen, A. M., Overgaard, K. & Christiansen, C. Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study. Bone 19, 9–12 (1996).
  Article CAS PubMed Google Scholar
• Johnell, O. et al. Biochemical indices of bone turnover and the assessment of fracture probability. Osteoporos. Int. 13, 523–526 (2002).
  Article CAS PubMed Google Scholar
• Christiansen, C. et al. Dose dependent effects on bone resorption and formation of intermittently administered intravenous ibandronate. Osteoporos. Int. 14, 609–613 (2003).
  Article CAS PubMed Google Scholar
• Hodsman, A. B. et al. Efficacy and safety of human parathyroid hormone-(1–84) in increasing bone mineral density in postmenopausal osteoporosis. J. Clin. Endocrinol. Metab 88, 5212–5220 (2003).
  Article CAS PubMed Google Scholar
• Eastell, R. et al. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study. J. Bone Miner. Res. 26, 1303–1312 (2011).
  Article CAS PubMed Google Scholar
• Lewiecki, E. M. New targets for intervention in the treatment of postmenopausal osteoporosis. Nat. Rev. Rheumatol. 7, 631–638 (2011).
  Article CAS PubMed Google Scholar
• Bouxsein, M. L. & Delmas, P. D. Considerations for development of surrogate endpoints for antifracture efficacy of new treatments in osteoporosis: a perspective. J. Bone Miner. Res. 23, 1155–1167 (2008).
  Article PubMed PubMed Central Google Scholar
• Lewiecki, E. M. Benefits and limitations of bone mineral density and bone turnover markers to monitor patients treated for osteoporosis. Curr. Osteoporos. Rep. 8, 15–22 (2010).
  Article PubMed Google Scholar
• Hochberg, M. C. et al. Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J. Clin. Endocrinol. Metab. 87, 1586–1592 (2002).
  Article CAS PubMed Google Scholar
• Bell, K. J. et al. The potential value of monitoring bone turnover markers among women on alendronate. J. Bone Miner. Res. http://dx.doi.org/10.1002/jbmr.525 (2011).
• de Papp, A. E. et al. A cross-sectional study of bone turnover markers in healthy premenopausal women. Bone 40, 1222–1230 (2007).
  Article PubMed Google Scholar
• Delmas, P. D. et al. Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J. Clin. Endocrinol. Metab 92, 1296–1304 (2007).
  Article CAS PubMed Google Scholar
• Clowes, J. A., Peel, N. F. & Eastell, R. The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J. Clin. Endocrinol. Metab. 89, 1117–1123 (2004).
  Article CAS PubMed Google Scholar
• Silverman, S. L., Nasser, K., Nattrass, S. & Drinkwater, B. Impact of bone turnover markers and/or educational information on persistence to oral bisphosphonate therapy: a community setting-based trial. Osteoporos. Int. 23, 1069–1074 (2012).
  Article CAS PubMed Google Scholar
• Braga de Castro, M. A., Hannon, R. & Eastell, R. Monitoring alendronate therapy for osteoporosis. J. Bone Miner. Res. 14, 602–608 (1999).
  Article Google Scholar
• Orwoll, E. et al. Alendronate for the treatment of osteoporosis in men. N. Engl. J. Med. 343, 604–610 (2000).
  Article CAS PubMed Google Scholar
• Orwoll, E. S. et al. Efficacy and safety of monthly ibandronate in men with low bone density. Bone 46, 970–976 (2010).
  Article CAS PubMed Google Scholar
• Orwoll, E. S. et al. Efficacy and safety of a once-yearly i.v. Infusion of zoledronic acid 5 mg versus a once-weekly 70-mg oral alendronate in the treatment of male osteoporosis: a randomized, multicenter, double-blind, active-controlled study. J. Bone Miner. Res. 25, 2239–2250 (2010).
  Article CAS PubMed Google Scholar
• Boonen, S. et al. Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebo-controlled, double-blind, multicenter study. J. Bone Miner. Res. 24, 719–725 (2009).
  Article CAS PubMed Google Scholar
• Bolland, M. J. et al. Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial. J. Clin. Endocrinol. Metab 92, 1283–1288 (2007).
  Article CAS PubMed Google Scholar
• Black, D. M. et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N. Engl. J. Med. 356, 1809–1822 (2007).
  Article CAS PubMed Google Scholar
• Delmas, P. D. et al. Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis. J. Bone Miner. Res. 24, 1544–1551 (2009).
  Article CAS PubMed Google Scholar
• Eastell, R. et al. Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J. Bone Miner. Res. 26, 530–537 (2011).
  Article CAS PubMed Google Scholar
• Miller, P. D. et al. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial. J. Clin. Endocrinol. Metab 96, 394–402 (2011).
  Article CAS PubMed Google Scholar
• Grey, A. et al. Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial. J. Bone Miner. Res. 25, 2251–2255 (2010).
  Article CAS PubMed Google Scholar
• Grey, A. et al. Five years of anti-resorptive activity after a single dose of zoledronate—results from a randomized double-blind placebo-controlled trial. Bone http://dx.doi.org/10.1016/j.bone.2012.03.016 (2012).
• Glover, S. J. et al. Rapid and robust response of biochemical markers of bone formation to teriparatide therapy. Bone 45, 1053–1058 (2009).
  Article CAS PubMed Google Scholar
• McClung, M. R. et al. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch. Intern. Med. 165, 1762–1768 (2005).
  Article CAS PubMed Google Scholar
• Tsujimoto, M., Chen, P., Miyauchi, A., Sowa, H. & Krege, J. H. PINP as an aid for monitoring patients treated with teriparatide. Bone 48, 798–803 (2011).
  Article CAS PubMed Google Scholar
• Eastell, R. et al. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J. Bone Miner. Res. 18, 1051–1056 (2003).
  Article CAS PubMed Google Scholar
• Ensrud, K. E. et al. 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 (2004).
  Article CAS PubMed Google Scholar
• Naylor, K. E. et al. The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women. Bone 46, 592–597 (2010).
  Article CAS PubMed Google Scholar
• Eastell, R., Hannon, R. A., Wenderoth, D., Rodriguez-Moreno, J. & Sawicki, A. Effect of stopping risedronate after long-term treatment on bone turnover. J. Clin. Endocrinol. Metab 96, 3367–3373 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Miller, P. D. et al. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 43, 222–229 (2008).
  Article CAS PubMed Google Scholar
• Gallagher, J. C., Rapuri, P. B., Haynatzki, G. & Detter, J. R. Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers. J. Clin. Endocrinol. Metab. 87, 4914–4923 (2002).
  Article CAS PubMed Google Scholar
• Greenspan, S. L. et al. 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 (2002).
  Article CAS PubMed Google Scholar
• Wasnich, R. D. et al. Changes in bone density and turnover after alendronate or estrogen withdrawal. Menopause 11, 622–630 (2004).
  Article PubMed Google Scholar
• Sornay-Rendu, E., Garnero, P., Munoz, F., Duboeuf, F. & Delmas, P. D. Effect of withdrawal of hormone replacement therapy on bone mass and bone turnover: the OFELY study. Bone 33, 159–166 (2003).
  Article CAS PubMed Google Scholar
• Rogers, A., Saleh, G., Hannon, R. A., Greenfield, D. & Eastell, R. Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J. Clin. Endocrinol. Metab 87, 4470–4475 (2002).
  Article CAS PubMed Google Scholar
• Naylor, K. E. et al. Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation. J. Clin. Endocrinol. Metab 88, 5361–5365 (2003).
  Article CAS PubMed Google Scholar
• Jabbar, S. et al. Osteoprotegerin, RANKL and bone turnover in postmenopausal osteoporosis. J. Clin. Pathol. 64, 354–357 (2011).
  Article CAS PubMed Google Scholar
• Ardawi, M. S., Al-Kadi, H. A., Rouzi, A. A. & Qari, M. H. Determinants of serum sclerostin in healthy pre- and postmenopausal women. J. Bone Miner. Res. 26, 2812–2822 (2011).
  Article CAS PubMed Google Scholar
• Mirza, F. S., Padhi, I. D., Raisz, L. G. & Lorenzo, J. A. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J. Clin. Endocrinol. Metab 95, 1991–1997 (2010).
  Article PubMed PubMed Central Google Scholar
• Modder, U. I. et al. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J. Bone Miner. Res. 26, 373–379 (2011).
  Article CAS PubMed Google Scholar
• Sridharan, M. et al. Circulating fibroblast growth factor-23 increases following intermittent parathyroid hormone (1–34) in postmenopausal osteoporosis: association with biomarker of bone formation. Calcif. Tissue Int. 87, 398–405 (2010).
  Article CAS PubMed Google Scholar
• Butler, J. S. et al. The role of Dkk1 in bone mass regulation: correlating serum Dkk1 expression with bone mineral density. J. Orthop. Res. 29, 414–418 (2011).
  Article PubMed Google Scholar
• Rosen, C. J. et al. Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study. J. Bone Miner. Res. 20, 141–151 (2005).
  Article CAS PubMed Google Scholar
• Miller, P. D. et al. Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J. Bone Miner. Res. 20, 1315–1322 (2005).
  Article CAS PubMed Google Scholar
• Cummings, S. R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J Med. 361, 756–765 (2009).
  Article CAS PubMed Google Scholar
• Black, D. M. et al. One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N. Engl. J Med. 353, 555–565 (2005).
  Article CAS PubMed Google Scholar
• Ettinger, B. et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282, 637–645 (1999).
  Article CAS PubMed Google Scholar
• Chesnut, C. H., III. et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am. J. Med. 109, 267–276 (2000).
  Article CAS PubMed Google Scholar
• Meunier, P. J. et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N. Engl. J Med. 350, 459–468 (2004).
  Article CAS PubMed Google Scholar
• Kraenzlin, M. E. et al. The effect of intranasal salmon calcitonin on postmenopausal bone turnover as assessed by biochemical markers: evidence of maximal effect after 8 weeks of continuous treatment. Calcif. Tissue Int. 58, 216–220 (1996).
  Article CAS PubMed Google Scholar