New treatment targets in osteoporosis

Joint Bone Spine

Volumn 77, Issue 3, 2010, Pages 222-228

  Roux, Sophie ^a  

^a UNIVERSITÉ DE SHERBROOKE   (Canada)

Author keywords

Anabolic agents; Calcilytic drugs; Catabolism inhibitors; Cathepsin K inhibitors; Osteoporosis; RANKL inhibitors; Wnt

Indexed keywords

ACE 011; ALENDRONIC ACID; ATPASE PROTON PUMP; BALICATIB; BISPHOSPHONIC ACID DERIVATIVE; C SRC PROTEIN TYROSINE KINASE INHIBITOR; CALCIMIMETIC AGENT; CATHEPSIN K; CHLORIDE CHANNEL BLOCKING AGENT; CLC 7 CHLORIDE CHANNEL INHIBITOR; DENOSUMAB; DICKKOPF 1 ANTIBODY; GLUCAGON LIKE PEPTIDE 2; L 000845704; ODANACATIB; OSTEOCLAST DIFFERENTIATION FACTOR; PLACEBO; PROTEIN ANTIBODY; PROTEIN TYROSINE KINASE INHIBITOR; PROTON PUMP; RAP 011; RECEPTOR BLOCKING AGENT; RONACALERET; SCLEROSTIN ANTIBODY; UNCLASSIFIED DRUG; VITRONECTIN RECEPTOR; WNT PROTEIN;

BEDTIME DOSAGE; BONE CELL; BONE REMODELING; CLINICAL TRIAL; CONSTIPATION; DERMATITIS; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; FRACTURE HEALING; FRAGILITY FRACTURE; HEADACHE; HEART ARRHYTHMIA; HUMAN; INFECTION; INJECTION SITE REACTION; NAUSEA; NEOPLASM; NONHUMAN; OSSIFICATION; OSTEOLYSIS; POSTMENOPAUSE OSTEOPOROSIS; PROTEIN FUNCTION; PRURITUS; RASH; SHORT SURVEY; SINGLE DRUG DOSE; SKIN DISEASE; STROKE; TREATMENT OUTCOME; URTICARIA; VERTEBRA FRACTURE; VOMITING;

ANABOLIC AGENTS; ANTIRHEUMATIC AGENTS; BONE RESORPTION; CATHEPSIN K; HUMANS; OSTEOPOROSIS, POSTMENOPAUSAL; RANK LIGAND; SIGNAL TRANSDUCTION; WNT PROTEINS;

EID: 77952544910     PISSN: 1297319X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jbspin.2010.02.004     Document Type: Short Survey

References (59)

1. Teitelbaum S.L. Osteoclasts: what do they do and how do they do it?. Am J Pathol 170 (2007) 427-435
2. Blair H.C., Teitelbaum S.L., Ghiselli R., et al. Osteoclastic bone resorption by a polarized vacuolar proton pump. Science 245 (1989) 855-857
3. Mattsson J.P., Skyman C., Palokangas H., et al. Characterization and cellular distribution of the osteoclast ruffled membrane vacuolar H+-ATPase B-subunit using isoform-specific antibodies. J Bone Miner Res 12 (1997) 753-760
4. Baron R. Molecular mechanisms of bone resorption: therapeutic implications. Rev Rhum Engl Ed 63 (1996) 633-638
5. Shinohara M., and Takayanagi H. Novel osteoclast signaling mechanisms. Curr Osteoporos Rep 5 (2007) 67-72
6. Hofbauer L.C., Khosla S., Dunstan C.R., et al. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 15 (2000) 2-12
7. Krishnan V., Bryant H.U., and Macdougald O.A. Regulation of bone mass by Wnt signaling. J Clin Invest 116 (2006) 1202-1209
8. Clowes J.A., Riggs B.L., and Khosla S. The role of the immune system in the pathophysiology of osteoporosis. Immunol Rev 208 (2005) 207-227
9. Pacifici R. Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 11 (1996) 1043-1051
10. Eghbali-Fatourechi G., Khosla S., Sanyal A., et al. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 111 (2003) 1221-1230
11. Hofbauer L.C., Khosla S., Dunstan C.R., et al. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140 (1999) 4367-4370
12. Shevde N.K., Bendixen A.C., Dienger K.M., et al. Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc Natl Acad Sci U S A 97 (2000) 7829-7834
13. Riggs B.L., Khosla S., and Melton III L.J. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 23 (2002) 279-302
14. Bekker P.J., Holloway D.L., Rasmussen A.S., et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19 (2004) 1059-1066
15. Bone H.G., Bolognese M.A., Yuen C.K., et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 93 (2008) 2149-2157
16. Cummings S.R., San Martin J., McClung M.R., et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361 (2009) 756-765
17. Lewiecki E.M., Miller P.D., McClung M.R., et al. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res 22 (2007) 1832-1841
18. McClung M.R., Lewiecki E.M., Cohen S.B., et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354 (2006) 821-831
19. Miller P.D., Bolognese M.A., Lewiecki E.M., 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 (2008) 222-229
20. Brown J.P., Prince R.L., Deal C., et al. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 24 (2009) 153-161
21. Kendler D.L., Roux C., Benhamou C.L., et al. Effects of Denosumab on Bone Mineral Density and Bone Turnover in Postmenopausal Women Transitioning from Alendronate Therapy. J Bone Miner Res (2009) doi: 10.1359/jbmr.090716
22. Stoch S.A., and Wagner J.A. Cathepsin K inhibitors: a novel target for osteoporosis therapy. Clin Pharmacol Ther 83 (2008) 172-176
23. Nishi Y., Atley L., Eyre D.E., et al. Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation. J Bone Miner Res 14 (1999) 1902-1908
24. Fratzl-Zelman N., Valenta A., Roschger P., et al. Decreased bone turnover and deterioration of bone structure in two cases of pycnodysostosis. J Clin Endocrinol Metab 89 (2004) 1538-1547
25. 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 95 (1998) 13453-13458
26. Gauthier J.Y., Chauret N., Cromlish W., et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett 18 (2008) 923-928
27. Bone H.G., McClung M.R., 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 (2009) doi: 10.1359/jbmr.091035
28. Frisch S.M., and Screaton R.A. Anoikis mechanisms. Curr Opin Cell Biol 13 (2001) 555-562
29. Zhao H., Ross F.P., and Teitelbaum S.L. Unoccupied alpha(v)beta3 integrin regulates osteoclast apoptosis by transmitting a positive death signal. Mol Endocrinol 19 (2005) 771-780
30. Engleman V.W., Nickols G.A., Ross F.P., et al. A peptidomimetic antagonist of the alpha(v)beta3 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo. J Clin Invest 99 (1997) 2284-2292
31. Teitelbaum S.L., Abu-Amer Y., and Ross F.P. Molecular mechanisms of bone resorption. J Cell Biochem 59 (1995) 1-10
32. McHugh K.P., Kitazawa S., Teitelbaum S.L., et al. Cloning and characterization of the murine beta(3) integrin gene promoter: identification of an interleukin-4 responsive element and regulation by STAT-6. J Cell Biochem 81 (2001) 320-332
33. Murphy M.G., Cerchio K., Stoch S.A., et al. Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 90 (2005) 2022-2028
34. Henriksen D.B., Alexandersen P., Hartmann B., et al. Disassociation of bone resorption and formation by GLP-2: a 14-day study in healthy postmenopausal women. Bone 40 (2007) 723-729
35. Henriksen D., Alexandersen P., Hartmann B., et al. GLP-2 significantly increases hip BMD in postmenopausal women: A 120-day study [abstract]. J Bone Miner Res 22 Suppl. 1 (2007) S 37
36. Soriano P., Montgomery C., Geske R., et al. Targeted disruption of the c-src protooncogene leads to osteopetrosis in mice. Cell 64 (1991) 693-702
37. Recchia I., Rucci N., Funari A., et al. Reduction of c-Src activity by substituted 5,7-diphenyl-pyrrolo[2,3-d]-pyrimidines induces osteoclast apoptosis in vivo and in vitro. Involvement of ERK1/2 pathway. Bone 34 (2004) 65-79
38. Boyce B.F., Xing L., Yao Z., et al. Future anti-catabolic therapeutic targets in bone disease. Ann N Y Acad Sci 1068 (2006) 447-457
39. Vaananen H.K., Karhukorpi E.K., Sundquist K., et al. Evidence for the presence of a proton pump of the vacuolar H(+)-ATPase type in the ruffled borders of osteoclasts. J Cell Biol 111 (1990) 1305-1311
40. Frattini A., Orchard P.J., Sobacchi C., et al. Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat Genet 25 (2000) 343-346
41. Kornak U., Ostertag A., Branger S., et al. Polymorphisms in the CLCN7 gene modulate bone density in postmenopausal women and in patients with autosomal dominant osteopetrosis type II. J Clin Endocrinol Metab 91 (2006) 995-1000
42. Schaller S., Henriksen K., Sveigaard C., et al. The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation. J Bone Miner Res 19 (2004) 1144-1153
43. Brown E.M. The calcium-sensing receptor: physiology, pathophysiology and CaR-based therapeutics. Subcell Biochem 45 (2007) 139-167
44. Hodsman A.B., Bauer D.C., Dempster D.W., et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 26 (2005) 688-703
45. Fitzpatrick L.A., Brennan E., Kumar S., et al. Ronacaleret, a novel calcium-sensing receptor antagonist, demonstrates potential as an oral bone forming therapy in healthy postmenopausal women [abstract]. J Bone Miner Res 23 Suppl. 1 (2008) S50
46. Li X., Zhang Y., Kang H., et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280 (2005) 19883-19887
47. Winkler D.G., Sutherland M.K., Geoghegan J.C., et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22 (2003) 6267-6276
48. Li X., Ominsky M.S., Niu Q.T., et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23 (2008) 860-869
49. Li X., Ominsky M.S., Warmington K.S., et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24 (2009) 578-588
50. Padhi D., Stouch B., Jang G., et al. Anti-sclerostin antibody increases markers of bone formation in healthy postmenopausal women [abstract]. J Bone Miner Res 22 Suppl. 1 (2007) S37
51. Semenov M.V., Zhang X., and He X. DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation. J Biol Chem 283 (2008) 21427-21432
52. MacDonald B.T., Joiner D.M., Oyserman S.M., et al. Bone mass is inversely proportional to Dkk1 levels in mice. Bone 41 (2007) 331-339
53. Glantschnig H., Hampton R., Wei N., et al. Fully human anti-DKK1 antibodies increase bone formation and resolve osteopenia in mouse models of estrogen-deficiency induced bone loss [abstract]. J Bone Miner Res 23 Suppl. 1 (2008) S60
54. Fukuda T., Kohda M., Kanomata K., et al. Constitutively Activated ALK2 and Increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. J Biol Chem 284 (2009) 7149-7156
55. Pearsall R.S., Canalis E., Cornwall-Brady M., et al. A soluble activin type IIA receptor induces bone formation and improves skeletal integrity. Proc Natl Acad Sci U S A 105 (2008) 7082-7087
56. Ruckle J., Jacobs M., Kramer W., et al. Single-dose, randomized, double-blind, placebo controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 24 (2009) 744-752
57. Fajardo RJ, Manoharan RK, Pearsall RS, et al. Treatment with a soluble receptor for activin improves bone mass and structure in the axial and appendicular skeleton of female cynomolgus macaques (Macaca fascicularis). Bone 2010;46:64-71.
58. Takayanagi H., Ogasawara K., Hida S., et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 408 (2000) 600-605
59. Wei S., Wang M.W., Teitelbaum S.L., et al. Interleukin-4 reversibly inhibits osteoclastogenesis via inhibition of NF-kappa B and mitogen-activated protein kinase signaling. J Biol Chem 277 (2002) 6622-6630