• 1
    Cooper C. Epidemiology of osteoporosis. Osteoporos Int 1999; 2: (9 Suppl. 2): S2S8.
  • 2
    Melton LJ III. How many women have osteoporosis now? J Bone Miner Res 1995; 10: 175177.
  • 3
    Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D, on behalf of the European Foundation for Osteoporosis and Bone Disease. Guidelines for diagnosis and management of osteoporosis. Osteoporos Int 1997; 7: 390406.
  • 4
    Yasuda Y, Kaleta J, Bromme D. The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv Drug Deliv Rev 2005; 57: 973993.
  • 5
    Stoch SA, Wagner JA. Cathepsin K inhibitors: a novel target for osteoporosis therapy. Clin Pharmacol Ther 2008; 83: 172176.
  • 6
    Schilling AF, Mülhausen C, Lehmann W, Santer R, Schinke T, Rueger JM, Amling M. High bone mineral density in pycnodysostotic patients with a novel mutation in the propeptide of cathepsin K. Osteoporos Int 2007; 18: 659669.
  • 7
    Saftig P, Hunziker E, Wehmeyer O, Jones S, Boyde A, Rommerskirch W, Moritz JD, Schu P, von Figura K. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A 1998; 95: 1345313458.
  • 8
    Pennypacker B, Shea M, Liu Q, Masarachia P, Saftig P, Rodan S, Rodan G, Kimmel D. Bone density, strength, and formation in adult cathepsin K (-/-) mice. Bone 2009; 44: 199207.
  • 9
    Masarachia PJ, Pennypacker BL, Pickarski M, Scott KR, Wesolowski GA, Smith SY, Samadfam R, Goetzmann JE, Scott BB, Kimmel DB, Duong le T. Odanacatib reduces bone turnover and increases bone mass in the lumbar spine of skeletally mature ovariectomized rhesus monkeys. J Bone Miner Res 2012; 27: 509523.
  • 10
    Pennypacker BL, Duong le T, Cusick TE, Masarachia PJ, Gentile MA, Gauthier JY, Black WC, Scott BB, Samadfam R, Smith SY, Kimmel DB. Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J Bone Miner Res 2011; 26: 252262.
  • 11
    Cusick T, Chen CM, Pennypacker BL, Pickarski M, Kimmel DB, Scott BB, Duong le T. Odanacatib treatment increases hip bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in the ovariectomized adult rhesus monkey. J Bone Miner Res 2012; 27: 524537.
  • 12
    Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD. Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab 1994; 79: 16931700.
  • 13
    Garnero P, Darte C, Delmas PD. A model to monitor the efficacy of alendronate treatment in women with osteoporosis using a biochemical marker of bone turnover. Bone 1999; 24: 603609.
  • 14
    Seibel MJ, Baylink DJ, Farley JR, Epstein S, Yamauchi M, Eastell R, Pols HA, Raisz LG, Gundberg CM. Basic science and clinical utility of biochemical markers of bone turnover – a Congress report. Exp Clin Endocrinol Diabetes 1997; 105: 125133.
  • 15
    Tesch G, Amur S, Schousboe JT, Siegel JN, Lesko LJ, Bai JP. Successes achieved and challenges ahead in translating biomarkers into clinical applications. AAPS J 2010; 12: 243253.
  • 16
    Cremers S, Garnero P. Biochemical markers of bone turnover in the clinical development of drugs for osteoporosis and metastatic bone disease: potential uses and pitfalls. Drugs 2006; 66: 20312058.
  • 17
    Delaissé JM, Engsig MT, Everts V, del Carmen Ovejero M, Ferreras M, Lund L, Vu TH, Werb Z, Winding B, Lochter A, Karsdal MA, Troen T, Kirkegaard T, Lenhard T, Heegaard AM, Neff L, Baron R, Foged NT. Proteinases in bone resorption: obvious and less obvious roles. Clin Chim Acta 2000; 291: 223234.
  • 18
    Everts V, Delaissé JM, Korper W, Jansen DC, Tigchelaar-Gutter W, Saftig P, Beertsen W. The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation. J Bone Miner Res 2002; 17: 7790.
  • 19
    Garnero P, Borel O, Byrjalsen I, Ferreras M, Drake FH, McQueney MS, Foged NT, Delmas PD, Delaissé JM. The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J Biol Chem 1998; 273: 3234732352.
  • 20
    Sassi ML, Eriksen H, Risteli L, Niemi S, Mansell J, Gowen M, Risteli J. Immunochemical characterization of assay for carboxyterminal telopeptide of human type I collagen: loss of antigenicity by treatment with cathepsin K. Bone 2000; 26: 367373.
  • 21
    Adami S, Supronik J, Haha T, Brown JP, Garnero P, Haemmerle S, Ortmann CE, Bousset F, Trechel U. Effect of one Year treatment with the cathepsin-K inhibitor, balicatib, on bone mineral density (BMD) in postmenopausal women with osteopenia/osteoporosis. J Bone Miner Res 2006; 24: (Suppl 1).
  • 22
    Eastell R, Nagase S, Ohyama M, Small M, Sawyer J, Boonen S, Spector T, Kuwayama T, Deacon S. Safety and efficacy of the Cathepsin K inhibitor, ONO-5334, in postmenopausal osteoporosis – the OCEAN study. J Bone Miner Res 2011; 26: 13031312.
  • 23
    Stoch SA, Zajic S, Stone J, Miller DL, Van Dyck K, Gutierrez MJ, De Decker M, Liu L, Liu Q, Scott BB, Panebianco D, Jin B, Duong LT, Gottesdiener K, Wagner JA. Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clin Pharmacol Ther 2009; 86: 175182.
  • 24
    U.S.Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for industry food-effect bioavailability and fed bioequivalence studies. 2002. Available at (last accessed 15 September 2012).
  • 25
    Sun L, Forni S, Schwartz MS, Breidinger S, Woolf EJ. Quantitative determination of odanacatib in human plasma using liquid-liquid extraction followed by liquid chromatography-tandem mass spectrometry analysis. J Chromatogr B Analyt Technol Biomed Life Sci 2012; 885-886: 1523.
  • 26
    Kassahun K, Black WC, Nicoll-Griffith D, McIntosh I, Chauret N, Day S, Rosenberg E, Koeplinger K. Pharmacokinetics and metabolism in rats, dogs, and monkeys of the cathepsin k inhibitor odanacatib: demethylation of a methylsulfonyl moiety as a major metabolic pathway. Drug Metab Dispos 2011; 39: 10791087.
  • 27
    Isabel E, Bateman KP, Chauret N, Cromlish W, Desmarais S, Duong le T, Falgueyret JP, Gauthier JY, Lamontagne S, Lau CK, Léger S, LeRiche T, Lévesque JF, Li CS, Massé F, McKay DJ, Mellon C, Nicoll-Griffith DA, Oballa RM, Percival MD, Riendeau D, Robichaud J, Rodan GA, Rodan SB, Seto C, Thérien M, Truong VL, Wesolowski G, Young RN, Zamboni R, Black WC. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett 2008; 18: 923928.
  • 28
    Garnero P. Biomarkers for osteoporosis management: utility in diagnosis, fracture risk prediction and therapy monitoring. Mol Diagn Ther 2008; 12: 157170.
  • 29
    Garnero P. Bone markers in osteoporosis. Curr Osteoporos Rep 2009; 7: 8490.