Inhibition of cathepsin K for treatment of osteoporosis

Current Osteoporosis Reports

Volumn 10, Issue 1, 2012, Pages 73-79

  Boonen, Steven ^a   Rosenberg, Elizabeth ^b   Claessens, Frank ^a   Vanderschueren, Dirk ^a   Papapoulos, Socrates ^c  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b MERCK RESEARCH LABORATORIES   (United States)

^c LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Cathepsin K inhibition; Osteoporosis

Indexed keywords

ALENDRONIC ACID; BALICATIB; BISPHOSPHONIC ACID DERIVATIVE; CATHEPSIN K; CATHEPSIN K INHIBITOR; CYSTEINE PROTEINASE INHIBITOR; DENOSUMAB; MIV 711; ODANACATIB; ONO 5334; PLACEBO; RELACATIB; UNCLASSIFIED DRUG; ALKALINE PHOSPHATASE; BIPHENYL DERIVATIVE; ONO-5334; THIAZOLIDINE DERIVATIVE;

ARTICLE; BONE DENSITY; BONE REMODELING; CATHEPSIN K GENE; CHROMOSOME 1Q; DOSE RESPONSE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FRACTURE; GENE; GENE DELETION; GENE MUTATION; GENE OVEREXPRESSION; HUMAN; LOW DRUG DOSE; MORPHEA; NONHUMAN; OSSIFICATION; OSTEOLYSIS; OSTEOPOROSIS; PATHOGENESIS; PROTEIN CLEAVAGE; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN SYNTHESIS INHIBITION; UNSPECIFIED SIDE EFFECT; ANIMAL; BLOOD; DRUG ANTAGONISM; DRUG EFFECT; PATHOPHYSIOLOGY; PHYSIOLOGY; POSTMENOPAUSE OSTEOPOROSIS; REVIEW;

ALKALINE PHOSPHATASE; ANIMALS; BIPHENYL COMPOUNDS; BONE DENSITY; BONE REMODELING; BONE RESORPTION; CATHEPSIN K; HUMANS; OSTEOPOROSIS; OSTEOPOROSIS, POSTMENOPAUSAL; THIAZOLIDINES;

EID: 84862250915     PISSN: 15441873     EISSN: 15442241     Source Type: Journal    
DOI: 10.1007/s11914-011-0085-9     Document Type: Article

References (54)

1. Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet. 2011;377:1276-87.
2. Sambrook P, Cooper C. Osteoporosis. Lancet. 2006;367:2010-8. (Pubitemid 43867702)
3. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359:1761-7.
4. Fast Facts. nof.org/node/40. Accessed 7 June 2011.
5. Teitelbaum SL. Bone resorption by osteoclasts. Science. 2000;289:1504-8.
6. Vaananen HK, Laitala-Leinonen T. Osteoclast lineage and function. Arch Biochem Biophys. 2008;473:132-8.
7. Lecaille F, Bromme D, Lalmanach G. Biochemical properties and regulation of cathepsin K activity. Biochimie. 2008;90:208-26. (Pubitemid 351200459)
8. Karsdal MA, Martin TJ, Bollerslev J, et al. Are nonresorbing osteoclasts sources of bone anabolic activity? J Bone Miner Res. 2007;22:487-94. (Pubitemid 47457424)
9. Henriksen K, Neutzsky-Wulff AV, Bonewald LF, Karsdal MA. Local communication on and within bone controls bone remodeling. Bone. 2009;44:1026-33.
10. Matsuo K, Irie N. Osteoclast-osteoblast communication. Arch Biochem Biophys. 2008;473:201-9.
11. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473:139-46.
12. Fuller K, Lawrence KM, Ross JL, et al. Cathepsin K inhibitors prevent matrix-derived growth factor degradation by human osteoclasts. Bone. 2008;42:200-11. (Pubitemid 350302017)
13. Tang Y, Wu X, Lei W, et al. TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med. 2009;15:757-65.
14. Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell. 2008;133:38-52. (Pubitemid 351442996)
15. Zhao C, Irie N, Takada Y, et al. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab. 2006;4:111-21. (Pubitemid 44138718)
16. Segovia-Silvestre T, Neutzsky-Wulff AV, Sorensen MG, et al. Advances in osteoclast biology resulting from the study of osteopetrotic mutations. Hum Genet. 2009;124:561-77.
17. Drake FH, Dodds RA, James IE, et al. Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts. J Biol Chem. 1996;271:12511-6. (Pubitemid 26160923)
18. Bromme D, Okamoto K, Wang BB, Biroc S. Human cathepsin O2, a matrix protein-degrading cysteine protease expressed in osteoclasts. Functional expression of human cathepsin O2 in Spodoptera frugiperda and characterization of the enzyme. J Biol Chem. 1996;271:2126-32.
19. Garnero P, Borel O, Byrjalsen I, et al. The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J Biol Chem. 1998;273:32347-52. (Pubitemid 29177183)
20. Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science. 1996;273:1236-8.
21. Schilling AF, Mulhausen C, Lehmann W, et al. High bone mineral density in pycnodysostotic patients with a novel mutation in the propeptide of cathepsin K. Osteoporos Int. 2007;18:659-69. (Pubitemid 46525550)
22. Ho N, Punturieri A, Wilkin D, et al. Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein. J Bone Miner Res. 1999;14:1649-53. (Pubitemid 29455812)
23. Saftig P, Hunziker E, Wehmeyer O, et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A. 1998;95:13453-8. (Pubitemid 28522993)
24. Gowen M, Lazner F, Dodds R, et al. Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res. 1999;14:1654-63. (Pubitemid 29455813)
25. Li CY, Jepsen KJ, Majeska RJ, et al. Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass. J Bone Miner Res. 2006;21:865-75. (Pubitemid 43787993)
26. Pennypacker B, Shea M, Liu Q, et al. Bone density, strength, and formation in adult cathepsin K (-/-) mice. Bone. 2009;44:199-207.
27. Kiviranta R, Morko J, Uusitalo H, et al. Accelerated turnover of metaphyseal trabecular bone in mice overexpressing cathepsin K. J Bone Miner Res. 2001;16:1444-52. (Pubitemid 32675196)
28. 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;57:973-93. (Pubitemid 40703885)
29. Stoch SA, Wagner JA. Cathepsin K inhibitors: a novel target for osteoporosis therapy. Clin Pharmacol Ther. 2008;83:172-6.
30. Yamashita DS, Marquis RW, Xie R, et al. Structure activity relationships of 5-, 6-, and 7-methyl-substituted azepan-3-one cathepsin K inhibitors. J Med Chem. 2006;49:1597-612. (Pubitemid 43376505)
31. 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;18:923-8. (Pubitemid 351179363)
32. Adami S, Supronik J, Hala T, et al. Effect of 1 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 S1):S24. Abstract 1085.
33. Peroni A, Zini A, Braga V, et al. Drug-induced morphea: report of a case induced by balicatib and review of the literature. J Am Acad Dermatol. 2008;59:125-9.
34. Runger TM, Adami S, Benhamou CL, et al. Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib. J Am Acad Dermatol. 2011. doi:10.1016/j.jaad2010.11.033
35. Pennypacker BL, Duong lT, Cusick TE, et al. Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J Bone Miner Res. 2011;26:252-62.
36. Stroup GB, Kumar S, Jerome CP. Treatment with a potent cathepsin K inhibitor preserves cortical and trabecular bone mass in ovariectomized monkeys. Calcif Tissue Int. 2009;85:344-55.
37. Masarachia PJ, Pennypacker B, Pickarski M, et al. Odanacatib reduces bone turnover and increases bone mass in lumbar spine of skeletally mature ovariectomized rhesus monkeys. J Bone Miner Res. 2011, in press. Uses non-human primates to explore the mechanism of action of cathepsin K inhibitors for osteoporosis.
38. Yamada H, Mori H, Kunishige A, et al. Efficacy of ONO-5334, a cathepsin K inhibitor, on bone turnover markers and bone mineral density in ovariectomized cynomolgus monkeys. Presented at European Calicified Tissue International, Glasgow, Scottland; 2010.
39. Yamada H, Ochi Y, Kunishige A, et al. Efficacy of ONO-5334, a cathepsin K inhibitor, on bone mass and strength in ovariectomized cynomolgus monkeys. Bone. 2011;48:S221.
40. Ochi Y, Yamada H, Kunishige ANS, et al. Efficacy of ONO-5334, a cathepsin K inhibitor, on bone turnover and cortical geometry in ovariectomized cynolmolgus monkeys. Bone. 2011;48:S72.
41. Mayhew PM, Thomas CD, Clement JG, et al. Relation between age, femoral neck cortical stability, and hip fracture risk. Lancet. 2005;366:129-35. (Pubitemid 40991213)
42. Jerome C, Missbach M, Gamse R. Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys. Osteoporos Int. 2011.
43. Cusick T, Chen CM, Pennypacker BL, et al. Odanacatib treatment increases Hi bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in ovariectomized adult rhesus monkey. J Bone Miner Res. 2011, in press. Uses non-human primates to explore the mechanism of action of cathepsin K inhibitors for osteoporosis.
44. 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;25:937-47. Reports clinical results of drugs in development that use the novel mechanism of action of inhibition of cathepsin K.
45. Eisman JA, Bone HG, Hosking DJ, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res. 2011;26:242-51. Reports clinical results of drugs in development that use the novel mechanism of action of inhibition of cathepsin K.
46. Binkley N, Bone H, Gilcrist N, et al. Treatment with the cathepsin K inhibitor odanacatib in postmenopausal women with low BMD: 5 year results of a phase 2 trial. Presented at the American Society of Bone and Mineral Research, San Diego, CA; 2011.
47. Bone H, Dempster D, Eisman J, et al. Phase 3 fracture trial of odanacatib for osteoporosis - study design. Presented at the Endocrine Society meeting, San Diego, CA; 2010.
48. Eastell R, Nagase S, Ohyama M, et al. Safety and efficacy of the Cathepsin K inhibitor, ONO-5334, in postmenopausal osteoporosis - the OCEAN study. J Bone Miner Res. 2011;26:1303-12. Reports clinical results of drugs in development that use the novel mechanism of action of inhibition of cathepsin K.
49. Eastell R, Nagase S, Small M, et al. Effect of the cathepsin K inhibitor ONO-5334 on biochemical markers of bone turnover in the treatment of postmennopausal osteopenia or osteoporosis: 2- year results from the OCEAN atudy. J Bone Miner Res. 2011.
50. Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999;282:1344-52. (Pubitemid 29483192)
51. Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006;296:2927-38. (Pubitemid 46021497)
52. 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;87:4914-23. (Pubitemid 35316325)
53. 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;43:222-9.
54. Stakkestad JA, Lakatos P, Lorenc R, et al. Monthly oral ibandronate is effective and well tolerated after 3 years: the MOBILE long-term extension. Clin Rheumatol. 2008;27:955-60.