• 1
    National Osteoporosis Foundation. America's bone health: the state of osteoporosis and low bone mass in our nation, 2002. Available at; accessed September 23, 2009.
  • 2
    Stoch SA, Wagner JA. Cathepsin K inhibitors: a novel target for osteoporosis therapy. Clin Pharmacol Ther. 2008;83:172176.
  • 3
    Adami S, Supronik J, Hala T, et al. 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;21 (Suppl 1): S24.
  • 4
    Papanastasiou P, Ortmann CE, Olson M, Vigneron A, Trechsel U. 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. 2006;21 (Suppl 1): S59.
  • 5
    Kumar S, Dare L, Vasko-Moser JA, et al. A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys. Bone. 2007;40:122131.
  • 6
    Gauthier JY, Chauret N, Cromlish W, et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008;18:923928.
  • 7
    Stoch S, Zajic S, Stone J, et al. 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.
  • 8
    Henriksen K, Gram J, Neutzsky-Wulff AV, et al. Characterization of acid flux in osteoclasts from patients harboring a G215R mutation in ClC-7. Biochem Biophys Res Commun. 2009;378:804809.
  • 9
    Neutzsky-Wulff AV, Karsdal MA, Henriksen K. Characterization of the bone phenotype in ClC-7-deficient mice. Calcif Tissue Int. 2008;83:425437.
  • 10
    Henriksen K, Sørensen MG, Jensen VK, Dziegiel MH, Nosjean O, Karsdal MA. Ion transporters involved in acidification of the resorption lacuna in osteoclasts. Calcif Tissue Int. 2008;83:230242.
  • 11
    Yasuda Y, Kaleta J, Brömme D. The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv Drug Deliv Rev. 2005;57:973993.
  • 12
    Vasiljeva O, Reinheckel T, Peters C, Turk D, Turk V, Turk B. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr Pharm Des. 2007;13:387403.
  • 13
    Falgueyret JP, Desmarais S, Oballa R, et al. Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity. J Med Chem. 2005;48:75357543.
  • 14
    Desmarais S, Black WC, Oballa R, et al. Effect of cathepsin K inhibitor basicity on in vivo off-target activities. Mol Pharmacol. 2008;73:147156.
  • 15
    Peroni A, Zini A, Braga V, Colato C, Adami S, Girolomoni G. Drug-induced morphea: Report of a case induced by balicatib and review of the literature. J Am Acad Dermatol. 2008;59:125129.
  • 16
    Bone HG, McClung MR, Roux C, et al. Odanacatib, a cathepsin-k inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res. 2010;25:937947.
  • 17
    Cusick T, Pennypacker B, Scott K, Duong LT, Kimmel D. Effects of odanacatib on bone mass, turnover and strength in the femoral neck of estrogen deficient adult rhesus monkeys. Presented at the 31st annual meeting of the American Society for Bone and Mineral Research, September 11-15, 2009, Denver, CO, A09002683. (
  • 18
    Pennypacker B, Shea M, Liu Q, et al. Bone density, strength, and formation in adult cathepsin K (-/-) mice. Bone. 2009;44:199207.
  • 19
    Liberman UA, Weiss SR, Bröll J, et al. 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. 1995;333:14371443.
  • 20
    Karsdal MA, Martin TJ, Bollerslev J, Christiansen C, Henriksen K. Are nonresorbing osteoclasts sources of bone anabolic activity? J Bone Miner Res. 2007;22:487494.
  • 21
    Gallagher JC, Rapuri PB, Haynatzki G, Detter JR. Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers. J Clin Endocrinol Metab. 2002;87:49144923.
  • 22
    Greenspan SL, Emkey RD, Bone HG, 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. 2002;137:875883.
  • 23
    Wasnich RD, Bagger YZ, Hosking DJ, et al. Changes in bone density and turnover after alendronate or estrogen withdrawal. Menopause. 2004;11:622630.
  • 24
    Sornay-Rendu E, Garnero P, Munoz F, Duboeuf F, Delmas PD. Effect of withdrawal of hormone replacement therapy on bone mass and bone turnover: the OFELY study. Bone. 2003;33:159166.
  • 25
    Miller PD, Bolognese MA, Lewiecki EM, 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. 2008;43:222229.
  • 26
    Black DM, Bilezikian JP, Ensrud KE, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med. 2005;353:555565.