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Perspectives on osteoporosis therapies

Journal of Endocrinological Investigation volume 38, pages 303–311 (2015)Cite this article

Abstract

Osteoporosis is a skeletal disease which predisposes to fragility fractures with high morbidity and economic impact, and, therefore, the goal of any osteoporosis treatment is to reduce the fracture risk. In the various forms of osteoporosis an imbalance between bone resorption and apposition is present, that generally leads to a reduction of bone mineral density and bone quality, and finally to the increased fracture risk. Nowadays, several drugs are available with a demonstrated anti-fracturative effect obtained by inhibiting bone resorption or stimulating bone formation. However, their use is not free from limitations and side effects. Importantly, to date, the available antiresorptive drugs have also an inhibiting, though to a lesser extent, effect on bone apposition and, similarly, the anabolic drugs lead to an increase also of bone resorption. Advances in our knowledge about bone biology, with molecular insights into mechanisms underlying osteoblast, osteoclast, and osteocyte activity, have led to the recognition of new potential targets and consequently to the formulation of new therapeutic agents to treat osteoporosis. New potential developments among the antiresorptive drugs include cathepsin K inhibitors and among the osteoanabolic drugs those activating the Wnt signaling pathway, such as the monoclonal antibodies against sclerostin. The novelty of these compounds is that their mechanism of action gives the exciting possibility to uncouple bone resorption and bone formation, and data available so far appear to be promising. Finally, several new therapeutic targets are under investigation in preclinical studies which could open further approaches to treat osteoporosis in the future.

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References

  1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285(6):785–795

    Article  Google Scholar 

  2. Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359(9319):1761–1767

    Article  PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    PubMed Central  Google Scholar 

  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

    Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Google Scholar 

  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

    Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Google Scholar 

  56. Iwamoto J (2014) Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients 6(5):1971–1980. doi:10.3390/nu6051971

    Article  PubMed Central  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

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E. Cairoli, V. V. Zhukouskaya, C. Eller-Vainicher and I. Chiodini declare they have no conflict of interest.

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  1. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Padiglione Granelli, Via F. Sforza 35, 20122, Milan, Italy

    E. Cairoli, V. V. Zhukouskaya, C. Eller-Vainicher & I. Chiodini

  2. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    E. Cairoli, V. V. Zhukouskaya, C. Eller-Vainicher & I. Chiodini

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Cairoli, E., Zhukouskaya, V.V., Eller-Vainicher, C. et al. Perspectives on osteoporosis therapies. J Endocrinol Invest 38, 303–311 (2015). https://doi.org/10.1007/s40618-014-0236-9

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Keywords

  • Osteoporosis treatment
  • Bone resorption
  • Bone formation
  • Antiresorptives
  • Anabolics