Perspectives on osteoporosis therapies

Journal of Endocrinological Investigation

Volumn 38, Issue 3, 2015, Pages 303-311

  Cairoli, E ^a,b   Zhukouskaya, V V ^a,b   Eller Vainicher, C ^a,b   Chiodini, I ^a,b  

^a FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

^b UNIVERSITY OF MILAN   (Italy)

Author keywords

Anabolics; Antiresorptives; Bone formation; Bone resorption; Osteoporosis treatment

Indexed keywords

AGENTS AFFECTING METABOLISM; ANABOLIC AGENT; CALCILYTIC AGENT; CATHEPSIN K INHIBITOR; DICKKOPF 1 PROTEIN; MONOCLONAL ANTIBODY; PROTEIN TYROSINE KINASE INHIBITOR; SCLEROSTIN; UNCLASSIFIED DRUG; WNT PROTEIN; BONE DENSITY CONSERVATION AGENT;

BONE DENSITY; DISEASE PREDISPOSITION; DRUG MECHANISM; FRAGILITY FRACTURE; HUMAN; MORBIDITY; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLAST; OSTEOCYTE; OSTEOLYSIS; OSTEOPOROSIS; REVIEW; RISK REDUCTION; SIGNAL TRANSDUCTION; BONE REMODELING; DRUG EFFECTS; OSTEOPOROSIS, POSTMENOPAUSAL;

BONE DENSITY; BONE DENSITY CONSERVATION AGENTS; BONE REMODELING; BONE RESORPTION; HUMANS; OSTEOPOROSIS; OSTEOPOROSIS, POSTMENOPAUSAL;

EID: 84924369519     PISSN: 03914097     EISSN: 17208386     Source Type: Journal    
DOI: 10.1007/s40618-014-0236-9     Document Type: Review

References (66)

1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285(6):785-795
2. Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359(9319):1761-1767
3. Ishtiaq S, Fogelman I, Hampson G (2014) Treatment of post-menopausal osteoporosis: beyond bisphosphonates. J Endocrinol Invest. doi: 10.1007/s40618-014-0152-z
4. Leung P, Pickarski M, Zhuo Y, Masarachia PJ, Duong LT (2011) The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone resorption and vesicular trafficking. Bone 49(4):623-635. doi: 10.1016/j.bone.2011.06.014
5. Vääräniemi J, Halleen JM, Kaarlonen K, Ylipahkala H, Alatalo SL, Andersson G, Kaija H, Vihko P, Väänänen HK (2004) Intracellular machinery for matrix degradation in bone-resorbing osteoclasts. J Bone Miner Res 19(9):1432-1440
6. Zerbini CA, McClung MR (2013) Odanacatib in postmenopausal women with low bone mineral density: a review of current clinical evidence. Ther Adv Musculoskelet Dis 5(4):199-209. doi: 10.1177/1759720X13490860
7. Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, Hustad CM, DaSilva C, Santora AC, Ince BA (2010) Odanacatib, a cathepsin-K inhibitor forosteoporosis: a 2-year study in postmenopausal women with low bone density. J Bone Miner Res 25(5):937-947. doi: 10.1359/jbmr.091035
8. Gauthier JY, Chauret N, Cromlish W, Desmarais S, le Duong T, Falgueyret JP, Kimmel DB, Lamontagne S, Léger S, LeRiche T, Li CS, Massé F, McKay DJ, Nicoll-Griffith DA, Oballa RM, Palmer JT, Percival MD, Riendeau D, Robichaud J, Rodan GA, Rodan SB, Seto C, Thérien M, Truong VL, Venuti MC, Wesolowski G, Young RN, Zamboni R, Black WC (2008) The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett 18(3):923-928. doi: 10.1016/j.bmcl.2007.12.047
9. Masarachia PJ, Pennypacker BL, Pickarski M, Scott KR, Wesolowski GA, Smith SY, Samadfam R, Goetzmann JE, Scott BB, Kimmel DB, le Duong T (2012) Odanacatib reduces bone turnover and increases bone mass in the lumbar spine of skeletally mature ovariectomized rhesus monkeys. J Bone Miner Res 27(3):509-523. doi: 10.1002/jbmr.1475
10. Cusick T, Chen CM, Pennypacker BL, Pickarski M, Kimmel DB, Scott BB, le Duong T (2012) 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 27(3):524-537. doi: 10.1002/jbmr.1477
11. 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 (2009) 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 86(2):175-182. doi: 10.1038/clpt.2009.60
12. Eisman JA, Bone HG, Hosking DJ, McClung MR, Reid IR, Rizzoli R, Resch H, Verbruggen N, Hustad CM, DaSilva C, Petrovic R, Santora AC, Ince BA, Lombardi A (2011) Odanacatib in the treatment of postmenopausal women with low bone mineral density: 3-year continued therapy and resolution of effect. J Bone Miner Res 26(2):242-251. doi: 10.1002/jbmr.212
13. Langdahl B, Binkley N, Bone H, Gilchrist N, Resch H, Rodriguez Portales J, Denker A, Lombardi A, Le Bailly De TC, Dasilva C, Rosenberg E, Leung A (2012) Odanacatib in the treatment of postmenopausal women with low bone mineral density: 5 years of continued therapy in a phase 2 study. J Bone Miner Res 27(11):2251-2258. doi: 10.1002/jbmr.1695
14. Brixen K, Chapurlat R, Cheung AM, Keaveny TM, Fuerst T, Engelke K, Recker R, Dardzinski B, Verbruggen N, Ather S, Rosenberg E, de Papp AE (2013) Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab 98(2):571-580. doi: 10.1210/jc.2012-2972
15. Engelke K, Fuerst T, Dardzinski B, Kornak J, Ather S, Genant HK, de Papp A (2014) Odanacatib treatment affects trabecular and cortical bone in the femur of postmenopausal women - results of a 2-year placebo-controlled trial. J Bone Miner Res. doi: 10.1002/jbmr.2292
16. Feng S, Luo Z, Liu D (2014) Efficacy and safety of odanacatib treatment for patients with osteoporosis: a meta-analysis. J Bone Miner Metab. doi: 10.1007/s00774-014-0609-3
17. Gajic-Veljanoski O, Tomlinson G, Srighanthan J, Adachi JD, Josse R, Brown JP, Cheung AM (2014) Effect of odanacatib on BMD and fractures: estimates from Bayesian Univariate and bivariate meta-analyses. J Clin Endocrinol Metab 99(9):3070-3079. doi: 10.1210/jc.2014-1162
18. Eastell R, Nagase S, Ohyama M, Small M, Sawyer J, Boonen S, Spector T, Kuwayama T, Deacon S (2011) Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the ocean study. J Bone Miner Res 26(6):1303-1312. doi: 10.1002/jbmr.341
19. Eastell R, Nagase S, Small M, Boonen S, Spector T, Ohyama M, Kuwayama T, Deacon S (2014) Effect of ONO-5334 on bone mineral density and biochemical markers of bone turnover in postmenopausal osteoporosis: 2-year results from the ocean study. J Bone Miner Res 29(2):458-466. doi: 10.1002/jbmr.2047
20. Engelke K, Nagase S, Fuerst T, Small M, Kuwayama T, Deacon S, Eastell R, Genant HK (2014) The effect of the cathepsin K inhibitor ONO-5334 on trabecular and cortical bone in postmenopausal osteoporosis: the ocean study. J Bone Miner Res 29(3):629-638. doi: 10.1002/jbmr.2080
21. Nagase S, Ohyama M, Hashimoto Y, Small M, Sharpe J, Manako J, Kuwayama T, Deacon S (2014) Bone turnover markers and pharmacokinetics of a new sustained-release formulation of the cathepsin K inhibitor, ONO-5334, in healthy post-menopausal women. J Bone Miner Metab. doi: 10.1007/s00774-013-0558-2
22. Tanaka M, Hashimoto Y, Sekiya N, Honda N, Deacon S, Yamamoto M (2014) Effects of novel cathepsin K inhibitor ONO-5334 on bone resorption markers: a study of four sustained release formulations with different pharmacokinetic patterns. J Bone Miner Metab 32(4):447-454. doi: 10.1007/s00774-013-0517-y
23. Soriano P, Montgomery C, Geske R, Bradley A (1991) Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64(4):693-702
24. Marzia M, Sims NA, Voit S, Migliaccio S, Taranta A, Bernardini S, Faraggiana T, Yoneda T, Mundy GR, Boyce BF, Baron R, Teti A (2000) Decreased c-Src expression enhances osteoblast differentiation and bone formation. J Cell Biol 151(2):311-320
25. de Vries TJ, Mullender MG, van Duin MA, Semeins CM, James N, Green TP, Everts V, Klein-Nulend J (2009) The Src inhibitor AZD0530 reversibly inhibits the formation and activity of human osteoclasts. Mol Cancer Res 7(4):476-488. doi: 10.1158/1541-7786.MCR-08-0219
26. Hannon RA, Clack G, Rimmer M, Swaisland A, Lockton JA, Finkelman RD, Eastell R (2010) Effects of the Src kinase inhibitor saracatinib (AZD0530) on bone turnover in healthy men: a randomized, double-blind, placebo-controlled, multiple-ascending-dose phase I trial. J Bone Miner Res 25(3):463-471. doi: 10.1359/jbmr.090830
27. Fitzpatrick LA, Dabrowski CE, Cicconetti G, Gordon DN, Papapoulos S, Bone HG 3rd, Bilezikian JP (2011) The effects of ronacaleret, a calcium-sensing receptor antagonist, on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mineral density. J Clin Endocrinol Metab 96(8):2441-2449. doi: 10.1210/jc.2010-2855
28. Halse J, Greenspan S, Cosman F, Ellis G, Santora A, Leung A, Heyden N, Samanta S, Doleckyj S, Rosenberg E, Denker AE (2014) A phase 2, randomized, placebo-controlled, dose-ranging study of the calcium-sensing receptor antagonist MK-5442 in the treatment of postmenopausal women with osteoporosis. J Clin Endocrinol Metab 99(11):E2207-E2215. doi: 10.1210/jc.2013-4009
29. Rochefort GY (2014) The osteocyte as a therapeutic target in the treatment of osteoporosis. Ther Adv Musculoskelet Dis 6(3):79-91. doi: 10.1177/1759720X14523500
30. Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26(1):19-26. doi: 10.1002/jbmr.173
31. McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, Katz L, Maddox J, Yang YC, Libanati C, Bone HG (2014) Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 370(5):412-420. doi: 10.1056/NEJMoa1305224
32. McColm J, Hu L, Womack T, Tang CC, Chiang AY (2014) Single- and multiple-dose randomized studies of blosozumab, a monoclonal antibody against sclerostin, in healthy postmenopausal women. J Bone Miner Res 29(4):935-943. doi: 10.1002/jbmr.2092
33. Recker R, Benson C, Matsumoto T, Bolognese M, Robins D, Alam J, Chiang AY, Hu L, Krege JH, Sowa H, Mitlak B, Myers S (2014) A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J Bone Miner Res. doi: 10.1002/jbmr.2351
34. Evenepoel P, D'Haese P, Brandenburg V (2014) Romosozumab in postmenopausal women with osteopenia. N Engl J Med 370(17):1664. doi: 10.1056/NEJMc1402396#SA1
35. van Lierop AH, Hamdy NA, Hamersma H, van Bezooijen RL, Power J, Loveridge N, Papapoulos SE (2011) Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover. J Bone Miner Res 26(12):2804-2811. doi: 10.1002/jbmr.474
36. van Lierop AH, Hamdy NA, van Egmond ME, Bakker E, Dikkers FG, Papapoulos SE (2013) Van Buchem disease: clinical, biochemical, and densitometric features of patients and disease carriers. J Bone Miner Res 28(4):848-854. doi: 10.1002/jbmr.1794
37. Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Van Hul W (2011) Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10(5):537-543
38. Loots GG, Kneissel M, Keller H, Baptist M, Chang J, Collette NM, Ovcharenko D, Plajzer-Frick I, Rubin EM (2005) Genomic deletion of a long-range bone enhancer mis-regulates sclerostin in Van Buchem disease. Genome Res 15(7):928-935
39. Gardner JC, van Bezooijen RL, Mervis B, Hamdy NA, Löwik CW, Hamersma H, Beighton P, Papapoulos SE (2005) Bone mineral density in sclerosteosis; affected individuals and gene carriers. J Clin Endocrinol Metab 90(12):6392-6395
40. Morvan F, Boulukos K, Clément-Lacroix P, Roman SR, Suc-Royer I, Vayssière B, Ammann P, Martin P, Pinho S, Pognonec P, Mollat P, Niehrs C, Baron R, Rawadi G (2006) Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 21(6):934-945
41. Li J, Sarosi I, Cattley RC, Pretorius J, Asuncion F, Grisanti M, Morony S, Adamu S, Geng Z, Qiu W, Kostenuik P, Lacey DL, Simonet WS, Bolon B, Qian X, Shalhoub V, Ominsky MS, Zhu KH, Li X, Richards WG (2006) Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 39(4):754-766
42. Li X, Grisanti M, Fan W, Asuncion FJ, Tan HL, Dwyer D, Han CY, Yu L, Lee J, Lee E, Barrero M, Kurimoto P, Niu QT, Geng Z, Winters A, Horan T, Steavenson S, Jacobsen F, Chen Q, Haldankar R, Lavallee J, Tipton B, Daris M, Sheng J, Lu HS, Daris K, Deshpande R, Valente EG, Salimi-Moosavi H, Kostenuik PJ, Li J, Liu M, Li C, Lacey DL, Simonet WS, Ke HZ, Babij P, Stolina M, Ominsky MS, Richards WG (2011) Dickkopf-1 regulates bone formation in young growing rodents and upon traumatic injury. J Bone Miner Res 26(11):2610-2621. doi: 10.1002/jbmr.472
43. Glantschnig H, Scott K, Hampton R, Wei N, McCracken P, Nantermet P, Zhao JZ, Vitelli S, Huang L, Haytko P, Lu P, Fisher JE, Sandhu P, Cook J, Williams D, Strohl W, Flores O, Kimmel D, Wang F, An Z (2011) A rate-limiting role for Dickkopf-1 in bone formation and the remediation of bone loss in mouse and primate models of postmenopausal osteoporosis by an experimental therapeutic antibody. J Pharmacol Exp Ther 338(2):568-578. doi: 10.1124/jpet.111.181404
44. Iyer SP, Beck JT, Stewart AK, Shah J, Kelly KR, Isaacs R, Bilic S, Sen S, Munshi NC (2014) A phase IB multicentre dose-determination study of BHQ880 incombination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events. Br J Haematol. doi: 10.1111/bjh.13056
45. Joshua J, Schwaerzer GK, Kalyanaraman H, Cory E, Sah RS, Li M, Vaida F, Boss GR, Pilz RB (2014) Soluble guanylate cyclase as a novel treatment target forosteoporosis. Endocrinology. doi: 10.1210/en.2014-1343
46. Iyer S, Han L, Bartell SM, Kim HN, Gubrij I, de Cabo R, O'Brien CA, Manolagas SC, Almeida M (2014) Sirtuin1 (Sirt1) promotes cortical bone formation by preventing β-catenin sequestration by FoxO transcription factors in osteoblast progenitors. J Biol Chem 289(35):24069-24078. doi: 10.1074/jbc.M114.561803
47. Zhao H, Li X, Li N, Liu T, Liu J, Li Z, Xiao H, Li J (2014) Long-term resveratrol treatment prevents ovariectomy-induced osteopenia in rats without hyperplastic effects on the uterus. Br J Nutr 111(5):836-846. doi: 10.1017/S0007114513003115
48. Ornstrup MJ, Harsløf T, Kjær TN, Langdahl BL, Pedersen SB (2014) Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial. J Clin Endocrinol Metab. doi: 10.1210/jc.2014-2799
49. Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P (2010) Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med 16:308-312
50. Fu HJ, Zhou YR, Bao BH, Jia MX, Zhao Y, Zhang L, Li JX, He HL, Zhou XM (2014) Tryptophan hydroxylase 1 (Tph-1)-targeted bone anabolic agents for osteoporosis. J Med Chem 57(11):4692-4709. doi: 10.1021/jm5002293
51. Muscogiuri G, Cignarelli A, Giorgino F, Prodram F, Santi D, Tirabassi G, Balercia G, Modica R, Faggiano A, Colao A (2014) GLP-1: benefits beyond pancreas. J Endocrinol Invest. doi: 10.1007/s40618-014-0137-y
52. Ceccarelli E, Guarino EG, Merlotti D, Patti A, Gennari L, Nuti R, Dotta F (2013) Beyond glycemic control in diabetes mellitus: effects of incretin-based therapies on bone metabolism. Front Endocrinol 4(73):1-12. doi: 10.3389/fendo.2013.00073
53. Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, Holst JJ, Christiansen C (2009) Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD. Bone 45(5):833-842. doi: 10.1016/j.bone.2009.07.008
54. de Castro LF, Lozano D, Portal-Núñez S, Maycas M, De la Fuente M, Caeiro JR, Esbrit P (2012) Comparison of the skeletal effects induced by daily administration of PTHrP (1-36) and PTHrP (107-139) to ovariectomized mice. J Cell Physiol 227(4):1752-1760. doi: 10.1002/jcp.22902
55. Leder BZ, O'Dea LS, Zanchetta JR, Kumar P, Banks K, McKay K, Lyttle CR, Hattersley G (2014) Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. doi: 10.1210/jc.2014-3718
56. 2 therapy for postmenopausal osteoporosis. Nutrients 6(5):1971-1980. doi: 10.3390/nu6051971
57. Kim KM, Lim SK (2014) Role of miRNAs in bone and their potential as therapeutic targets. Curr Opin Pharmacol 16:133-141. doi: 10.1016/j.coph.2014.05.001
58. Zuo B, Zhu JF, Li J, Wang CD, Zhao XY, Cai GQ, Li Z, Peng J, Wang P, Shen C, Huang Y, Xu J, Zhang XL, Chen XD (2014) MicroRNA-103a functions as a mechno-sensitive microRNA to inhibit bone formation through targeting Runx2. J Bone Miner Res. doi: 10.1002/jbmr.2352
59. Ruckle J, Jacobs M, Kramer W, Pearsall AE, Kumar R, Underwood KW, Seehra J, Yang Y, Condon CH, Sherman ML (2009) Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 24(4):744-752. doi: 10.1359/jbmr.081208
60. Lotinun S, Pearsall RS, Horne WC, Baron R (2012) Activin receptor signaling: a potential therapeutic target for osteoporosis. Curr Mol Pharmacol 5(2):195-204
61. Gambardella A, Nagaraju CK, O'Shea PJ, Mohanty ST, Kottam L, Pilling J, Sullivan M, Djerbi M, Koopmann W, Croucher PI, Bellantuono I (2011) Glycogen synthase kinase-3α/β inhibition promotes in vivo amplification of endogenous mesenchymal progenitors with osteogenic and adipogenic potential and their differentiation to the osteogenic lineage. J Bone Miner Res 26(4):811-821. doi: 10.1002/jbmr.266
62. Marsell R, Sisask G, Nilsson Y, Sundgren-Andersson AK, Andersson U, Larsson S, Nilsson O, Ljunggren O, Jonsson KB (2012) GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone 50(3):619-627. doi: 10.1016/j.bone.2011.11.007
63. Park JS, Bae SJ, Choi SW, Son YH, Park SB, Rhee SD, Kim HY, Jung WH, Kang SK, Ahn JH, Kim SH, Kim KY (2014) A novel 11β-HSD1 inhibitor improves diabesity and osteoblast differentiation. J Mol Endocrinol 52(2):191-202. doi: 10.1530/JME-13-0177
64. Wu L, Qi H, Zhong Y, Lv S, Yu J, Liu J, Wang L, Bi J, Kong X, Di W, Zha J, Liu F, Ding G (2013) 11β-Hydroxysteroid dehydrogenase type 1 selective inhibitor BVT.2733protects osteoblasts against endogenous glucocorticoid induced dysfunction. Endocr J 60(9):1047-1058
65. Duque G, Li W, Vidal C, Bermeo S, Rivas D, Henderson J (2013) Pharmacologicalinhibition of PPARγ increases osteoblastogenesis and bone mass in male C57BL/6mice. J Bone Miner Res 28(3):639-648. doi: 10.1002/jbmr.1782
66. Hayashi M, Nakashima T, Taniguchi M, Kodama T, Kumanogoh A, Takayanagi H (2012) Osteoprotection by semaphorin 3A. Nature 485(7396):69-74. doi: 10.1038/nature11000