Osteoporosis: Current and Emerging Therapies Targeted to Immunological Checkpoints

Author(s): Massimo De Martinis, Maria Maddalena Sirufo, Lia Ginaldi*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 37 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor


Osteoporosis is a skeletal pathology characterized by compromised bone strength leading to increased risk of fracture, mainly the spine and hip fractures. Osteoporosis affects more than 200 million people worldwide and because of the skeletal fractures it causes, represents a major cause of morbidity, disability and mortality in older people. Recently, the new discoveries of osteoimmunology have clarified many of the pathogenetic mechanisms of osteoporosis, helping to identify new immunological targets for its treatment opening the way for new and effective therapies with biological drugs. Currently, there are basically two monoclonal antibodies for osteoporosis therapy: denosumab and romosozumab. Here, we focus on the modern approach to the osteoporosis management and in particular, on current and developing biologic drugs targeted to new immunological checkpoints, in the landscape of osteoimmunology.

Keywords: Osteoporosis, osteoimmunology, bone remodeling, cytokines, immunological checkpoints, biological therapies.

Ensrud, K.E.; Crandall, C. J. Osteoporosis. Ann. Intern. Med., 2017, 167(3), 17-32.
[http://dx.doi.org/10.7326/AITC201708010 ] [PMID: 28761958]
Akkawi, I.; Zmerly, H. Osteoporosis: Current Concepts. Joints, 2018, 6(2), 122-127.
[http://dx.doi.org/10.1055/s-0038-1660790 ] [PMID: 30051110]
Nuti, R.; Brandi, M.L.; Checchia, G.; Di Munno, O.; Dominguez, L.; Falaschi, P.; Fiore, C.E.; Iolascon, G.; Maggi, S.; Michieli, R.; Migliaccio, S.; Minisola, S.; Rossini, M.; Sessa, G.; Tarantino, U.; Toselli, A.; Isaia, G.C. Guidelines for the management of osteoporosis and fragility fractures. Intern. Emerg. Med., 2019, 14(1), 85-102.
[http://dx.doi.org/10.1007/s11739-018-1874-2 ] [PMID: 29948835]
Hernlund, E.; Svedbom, A.; Ivergård, M.; Compston, J.; Cooper, C.; Stenmark, J.; McCloskey, E.V.; Jönsson, B.; Kanis, J.A. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch. Osteoporos., 2013, 8, 136.
[http://dx.doi.org/10.1007/s11657-013-0136-1 ] [PMID: 24113837]
De Martinis, M.; Di Benedetto, M.C.; Mengoli, L.P.; Ginaldi, L. Senile osteoporosis: is it an immune-mediated disease? Inflamm. Res., 2006, 55(10), 399-404.
[http://dx.doi.org/10.1007/s00011-006-6034-x ] [PMID: 17109066]
Bultink, I.E.M. Bone disease in connective tissue disease/systemic lupus erythematosus. Calcif. Tissue Int., 2018, 102(5), 575-591.
[http://dx.doi.org/10.1007/s00223-017-0322-z ] [PMID: 28900675]
De Martinis, M.; Ciccarelli, F.; Sirufo, M.M.; Ginaldi, L. An overview of environmental risk factors in systemic sclerosis. Expert Rev. Clin. Immunol., 2016, 12(4), 465-478.
[http://dx.doi.org/10.1586/1744666X.2016.1125782 ] [PMID: 26610037]
Panday, K.; Gona, A.; Humphrey, M.B. Medication-induced osteoporosis: screening and treatment strategies. Ther. Adv. Musculoskelet. Dis., 2014, 6(5), 185-202.
[http://dx.doi.org/10.1177/1759720X14546350 ] [PMID: 25342997]
Franceschi, C.; Garagnani, P.; Parini, P.; Giuliani, C.; Santoro, A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat. Rev. Endocrinol., 2018, 14(10), 576-590.
[http://dx.doi.org/10.1038/s41574-018-0059-4 ] [PMID: 30046148]
Okamoto, K.; Nakashima, T.; Shinohara, M.; Negishi-Koga, T.; Komatsu, N.; Terashima, A.; Sawa, S.; Nitta, T.; Takayanagi, H. Osteoimmunology: the conceptual framework unifying the immune and skeletal systems. Physiol. Rev., 2017, 97(4), 1295-1349.
[http://dx.doi.org/10.1152/physrev.00036.2016 ] [PMID: 28814613]
Ginaldi, L.; De Martinis, M. Osteoimmunology and beyond. Curr. Med. Chem., 2016, 23(33), 3754-3774.
[http://dx.doi.org/10.2174/0929867323666160907162546 ] [PMID: 27604089]
Harvey, N.C.W.; McCloskey, E.V.; Mitchell, P.J.; Dawson-Hughes, B.; Pierroz, D.D.; Reginster, J.Y.; Rizzoli, R.; Cooper, C.; Kanis, J.A. Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures. Osteoporos. Int., 2017, 28(5), 1507-1529.
[http://dx.doi.org/10.1007/s00198-016-3894-y ] [PMID: 28175979]
Cotts, K.G.; Cifu, A.S. Treatment of osteoporosis. JAMA, 2018, 319(10), 1040-1041.
[http://dx.doi.org/10.1001/jama.2017.21995 ] [PMID: 29536084]
Kanis, J.A.; Reginster, J.Y.; Kaufman, J.M.; Ringe, J.D.; Adachi, J.D.; Hiligsmann, M.; Rizzoli, R.; Cooper, C. A reappraisal of generic bisphosphonates in osteoporosis. Osteoporos. Int., 2012, 23(1), 213-221.
[http://dx.doi.org/10.1007/s00198-011-1796-6 ] [PMID: 21953472]
Martinkovich, S.; Shah, D.; Planey, S.L.; Arnott, J.A. Selective estrogen receptor modulators: tissue specificity and clinical utility. Clin. Interv. Aging, 2014, 9, 1437-1452.
[PMID: 25210448]
Leder, B.Z. Parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis therapy. Curr. Osteoporos. Rep., 2017, 15(2), 110-119.
[http://dx.doi.org/10.1007/s11914-017-0353-4 ] [PMID: 28303448]
Lewiecki, E.M. Denosumab in postmenopausal osteoporosis: what the clinician needs to know. Ther. Adv. Musculoskelet. Dis., 2009, 1(1), 13-26.
[http://dx.doi.org/10.1177/1759720X09343221 ] [PMID: 22870424]
Kenkre, J.S.; Bassett, J. The bone remodelling cycle. Ann. Clin. Biochem., 2018, 55(3), 308-327.
[http://dx.doi.org/10.1177/0004563218759371 ] [PMID: 29368538]
Takayanagi, H. Osteoimmunology in 2014: Two-faced immunology-from osteogenesis to bone resorption. Nat. Rev. Rheumatol., 2015, 11(2), 74-76.
[http://dx.doi.org/10.1038/nrrheum.2014.219 ] [PMID: 25561367]
Srivastava, R.K.; Dar, H.Y.; Mishra, P.K. Immunoporosis: immunology of osteoporosis-role of T cells. Front. Immunol., 2018, 9, 657.
[http://dx.doi.org/10.3389/fimmu.2018.00657 ] [PMID: 29675022]
Amjadi-Moheb, F.; Akhavan-Niaki, H. Wnt signaling pathway in osteoporosis: Epigenetic regulation, interaction with other signaling pathways, and therapeutic promises. J. Cell. Physiol., 2019.
[http://dx.doi.org/10.1002/jcp.28207 ] [PMID: 30693508]
Uehara, S.; Udagawa, N.; Kobayashi, Y. Non-canonical Wnt signals regulate cytoskeletal remodeling in osteoclasts. Cell. Mol. Life Sci., 2018, 75(20), 3683-3692.
[http://dx.doi.org/10.1007/s00018-018-2881-1 ] [PMID: 30051162]
Witcher, P.C.; Miner, S.E.; Horan, D.J.; Bullock, W.A.; Lim, K.E.; Kang, K.S.; Adaniya, A.L.; Ross, R.D.; Loots, G.G.; Robling, A.G. Sclerostin neutralization unleashes the osteoanabolic effects of Dkk1 inhibition. JCI Insight, 2018, 3(11), 98673.
[http://dx.doi.org/10.1172/jci.insight.98673 ] [PMID: 29875318]
Delgado-Calle, J.; Sato, A.Y.; Bellido, T. Role and mechanism of action of sclerostin in bone. Bone, 2017, 96, 29-37.
[http://dx.doi.org/10.1016/j.bone.2016.10.007 ] [PMID: 27742498]
Colditz, J.; Thiele, S.; Baschant, U.; Garbe, A.I.; Niehrs, C.; Hofbauer, L.C.; Rauner, M. Osteogenic Dkk1 mediates glucocorticoid-induced but not arthritis-induced bone loss. J. Bone Miner. Res., 2019, 34(7), 1314-1323.
[http://dx.doi.org/10.1002/jbmr.3702 ] [PMID: 30779862]
Ciccarelli, F.; De Martinis, M.; Ginaldi, L. Glucocorticoids in patients with rheumatic diseases: friends or enemies of bone? Curr. Med. Chem., 2015, 22(5), 596-603.
[http://dx.doi.org/10.2174/0929867321666141106125051 ] [PMID: 25386817]
Zhang, J.; Fu, Q.; Ren, Z.; Wang, Y.; Wang, C.; Shen, T.; Wang, G.; Wu, L. Changes of serum cytokines-related Th1/Th2/Th17 concentration in patients with postmenopausal osteoporosis. Gynecol. Endocrinol., 2015, 31(3), 183-190.
[http://dx.doi.org/10.3109/09513590.2014.975683 ] [PMID: 25384921]
Suzuki, T.; Nakamura, Y.; Kato, H. Effects of denosumab on bone metabolism and bone mineral density with anti-TNF inhibitors, tocilizumab, or abatacept in osteoporosis with rheumatoid arthritis. Ther. Clin. Risk Manag., 2018, 14, 453-459.
[http://dx.doi.org/10.2147/TCRM.S156350 ] [PMID: 29535527]
Saribal, D.; Hocaoglu-Emre, F.S.; Erdogan, S.; Bahtiyar, N.; Caglar Okur, S.; Mert, M. Inflammatory cytokines IL-6 and TNF-α in patients with hip fracture. Osteoporos. Int., 2019, 30(5), 1025-1031.
[http://dx.doi.org/10.1007/s00198-019-04874-2 ] [PMID: 30701344]
Ginaldi, L.; De Martinis, M.; Ciccarelli, F.; Saitta, S.; Imbesi, S.; Mannucci, C.; Gangemi, S. Increased levels of interleukin 31 (IL-31) in osteoporosis. BMC Immunol., 2015, 16, 60.
[http://dx.doi.org/10.1186/s12865-015-0125-9 ] [PMID: 26449657]
Holgado, A.; Braun, H.; Van Nuffel, E.; Detry, S.; Schuijs, M.J.; Deswarte, K.; Vergote, K.; Haegman, M.; Baudelet, G.; Haustraete, J.; Hammad, H.; Lambrecht, B.N.; Savvides, S.N.; Afonina, I.S.; Beyaert, R. IL-33trap is a novel IL-33-neutralizing biologic that inhibits allergic airway inflammation. J. Allergy Clin. Immunol., 2019, 144(1), 204-215.
[http://dx.doi.org/10.1016/j.jaci.2019.02.028 ] [PMID: 30876911]
Ginaldi, L.; De Martinis, M.; Saitta, S.; Sirufo, M.M.; Mannucci, C.; Casciaro, M.; Ciccarelli, F.; Gangemi, S. Interleukin-33 serum levels in postmenopausal women with osteoporosis. Sci. Rep., 2019, 9(1), 3786.
[http://dx.doi.org/10.1038/s41598-019-40212-6 ] [PMID: 30846811]
De Martinis, M.; Sirufo, M.M.; Ginaldi, L. Allergy and aging: an old/new emerging health issue. Aging Dis., 2017, 8(2), 162-175.
[http://dx.doi.org/10.14336/AD.2016.0831 ] [PMID: 28400983]
Dar, H.Y.; Azam, Z.; Anupam, R.; Mondal, R.K.; Srivastava, R.K. Osteoimmunology: the Nexus between bone and immune system. Front. Biosci., 2018, 23, 464-492.
[http://dx.doi.org/10.2741/4600 ] [PMID: 28930556]
van Dam, P.A.; Verhoeven, Y.; Trinh, X.B.; Wouters, A.; Lardon, F.; Prenen, H.; Smits, E.; Baldewijns, M.; Lammens, M. RANK/RANKL signaling inhibition may improve the effectiveness of checkpoint blockade in cancer treatment. Crit. Rev. Oncol. Hematol., 2019, 133, 85-91.
[http://dx.doi.org/10.1016/j.critrevonc.2018.10.011 ] [PMID: 30661662]
Massimini, M.; Palmieri, C.; De Maria, R.; Romanucci, M.; Malatesta, D.; De Martinis, M.; Maniscalco, L.; Ciccarelli, A.; Ginaldi, L.; Buracco, P.; Bongiovanni, L.; Della Salda, L. 17-AAG and apoptosis, autophagy, and mitophagy in canine osteosarcoma cell lines. Vet. Pathol., 2017, 54(3), 405-412.
[http://dx.doi.org/10.1177/0300985816681409 ] [PMID: 28438108]
Infante, M.; Fabi, A.; Cognetti, F.; Gorini, S.; Caprio, M.; Fabbri, A. RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives. J. Exp. Clin. Cancer Res., 2019, 38(1), 12.
[http://dx.doi.org/10.1186/s13046-018-1001-2 ] [PMID: 30621730]
Shupp, A.B.; Kolb, A.D.; Mukhopadhyay, D.; Bussard, K.M. Cancer metastases to bone: concepts, mechanisms, and interactions with bone osteoblasts. Cancers (Basel), 2018, 10, 3390.
Vishal, M.; Swetha, R.; Thejaswini, G.; Arumugam, B.; Selvamurugan, N. Role of Runx2 in breast cancer-mediated bone metastasis. Int. J. Biol. Macromol., 2017, 99, 608-614.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.03.021 ] [PMID: 28268169]
Sigl, V.; Jones, L.P.; Penninger, J.M. RANKL/RANK: from bone loss to the prevention of breast cancer. Open Biol., 2016, 6(11), 160230.
[http://dx.doi.org/10.1098/rsob.160230 ] [PMID: 27881737]
Baron, R.; Ferrari, S.; Russell, R.G. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone, 2011, 48(4), 677-692.
[http://dx.doi.org/10.1016/j.bone.2010.11.020 ] [PMID: 21145999]
Bone, H.G.; Wagman, R.B.; Brandi, M.L.; Brown, J.P.; Chapurlat, R.; Cummings, S.R.; Czerwiński, E.; Fahrleitner-Pammer, A.; Kendler, D.L.; Lippuner, K.; Reginster, J.Y.; Roux, C.; Malouf, J.; Bradley, M.N.; Daizadeh, N.S.; Wang, A.; Dakin, P.; Pannacciulli, N.; Dempster, D.W.; Papapoulos, S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol., 2017, 5(7), 513-523.
[http://dx.doi.org/10.1016/S2213-8587(17)30138-9 ] [PMID: 28546097]
Cummings, S.R.; San Martin, J.; McClung, M.R.; Siris, E.S.; Eastell, R.; Reid, I.R.; Delmas, P.; Zoog, H.B.; Austin, M.; Wang, A.; Kutilek, S.; Adami, S.; Zanchetta, J.; Libanati, C.; Siddhanti, S.; Christiansen, C. FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med., 2009, 361(8), 756-765.
[http://dx.doi.org/10.1056/NEJMoa0809493 ] [PMID: 19671655]
Lorentzon, M. Treating osteoporosis to prevent fractures: current concepts and future developments. J. Intern. Med., 2019, 285(4), 381-394.
[http://dx.doi.org/10.1111/joim.12873 ] [PMID: 30657216]
Zanchetta, M.B.; Boailchuk, J.; Massari, F.; Silveira, F.; Bogado, C.; Zanchetta, J.R. Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study. Osteoporos. Int., 2018, 29(1), 41-47.
[http://dx.doi.org/10.1007/s00198-017-4242-6 ] [PMID: 28975362]
Leder, B.Z.; Tsai, J.N.; Neer, R.M.; Uihlein, A.V.; Wallace, P.M.; Burnett-Bowie, S.A. Response to therapy with teriparatide, denosumab, or both in postmenopausal women in the DATA (denosumab and teriparatide administration) study randomized controlled trial. J. Clin. Densitom., 2016, 19(3), 346-351.
[http://dx.doi.org/10.1016/j.jocd.2016.01.004 ] [PMID: 26900146]
Leder, B.Z.; Tsai, J.N.; Jiang, L.A.; Lee, H. Importance of prompt antiresorptive therapy in postmenopausal women discontinuing teriparatide or denosumab: The Denosumab and Teriparatide Follow-up study (DATA-Follow-up). Bone, 2017, 98, 54-58.
[http://dx.doi.org/10.1016/j.bone.2017.03.006 ] [PMID: 28286299]
Leder, B.Z. Optimizing sequential and combined anabolic and antiresorptive osteoporosis therapy. JBMR Plus, 2018, 2(2), 62-68.
[http://dx.doi.org/10.1002/jbm4.10041 ] [PMID: 30283892]
Fusco, V.; Santini, D.; Armento, G.; Tonini, G.; Campisi, G. Osteonecrosis of jaw beyond antiresorptive (bone targeted) agents: new horizons in oncology. Expert Opin. Drug Saf., 2016, 15(7), 925-935.
[http://dx.doi.org/10.1080/14740338.2016.1177021 ] [PMID: 27074901]
Suh, Y.S.; Jang, B.W.; Nho, J.H.; Won, S.H.; Lee, W.S. Atypical incomplete femoral neck fracture in patients taking long-term bisphosphonate: Case report, a report of 2 cases. Medicine (Baltimore), 2019, 98(9), e14701.
[http://dx.doi.org/10.1097/MD.0000000000014701 ] [PMID: 30817607]
Lou, S.; Lv, H.; Yin, P.; Li, Z.; Tang, P.; Wang, Y. Combination therapy with parathyroid hormone analogs and antiresorptive agents for osteoporosis: a systematic review and meta-analysis of randomized controlled trials. Osteoporos. Int., 2019, 30(1), 59-70.
[http://dx.doi.org/10.1007/s00198-018-4790-4 ] [PMID: 30539271]
Bhattacharyya, S.; Pal, S.; Chattopadhyay, N. Targeted inhibition of sclerostin for post-menopausal osteoporosis therapy: A critical assessment of the mechanism of action. Eur. J. Pharmacol., 2018, 826, 39-47.
[http://dx.doi.org/10.1016/j.ejphar.2018.02.028 ] [PMID: 29476877]
Chang, B.; Quan, Q.; Li, Y.; Qiu, H.; Peng, J.; Gu, Y. Treatment of osteoporosis, with a focus on 2 monoclonal antibodies. Med. Sci. Monit., 2018, 24, 8758-8766.
[http://dx.doi.org/10.12659/MSM.912309 ] [PMID: 30508820]
Clarke, B.L. Anti-sclerostin antibodies: utility in treatment of osteoporosis. Maturitas, 2014, 78(3), 199-204.
[http://dx.doi.org/10.1016/j.maturitas.2014.04.016 ] [PMID: 24842796]
van Lierop, A.H.; Hamdy, N.A.; Hamersma, H.; van Bezooijen, R.L.; Power, J.; Loveridge, N.; Papapoulos, S.E. Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover. J. Bone Miner. Res., 2011, 26(12), 2804-2811.
[http://dx.doi.org/10.1002/jbmr.474 ] [PMID: 21786318]
Robling, A.G.; Drake, M.T.; Papapoulos, S.E. Sclerostin: From bedside to bench, and back to bedside. Bone, 2017, 96, 1-2.
[http://dx.doi.org/10.1016/j.bone.2017.01.019 ] [PMID: 28115280]
Lewiecki, E.M.; Dinavahi, R.V.; Lazaretti-Castro, M.; Ebeling, P.R.; Adachi, J.D.; Miyauchi, A.; Gielen, E.; Milmont, C.E.; Libanati, C.; Grauer, A. One year of romosozumab followed by two years of denosumab maintains fracture risk reductions: results of the FRAME extension study. J. Bone Miner. Res., 2019, 34(3), 419-428.
[http://dx.doi.org/10.1002/jbmr.3622 ] [PMID: 30508316]
Cosman, F.; Crittenden, D.B.; Adachi, J.D.; Binkley, N.; Czerwinski, E.; Ferrari, S.; Hofbauer, L.C.; Lau, E.; Lewiecki, E.M.; Miyauchi, A.; Zerbini, C.A.; Milmont, C.E.; Chen, L.; Maddox, J.; Meisner, P.D.; Libanati, C.; Grauer, A. Romosozumab treatment in postmenopausal women with osteoporosis. N. Engl. J. Med., 2016, 375(16), 1532-1543.
[http://dx.doi.org/10.1056/NEJMoa1607948 ] [PMID: 27641143]
Cosman, F.; Crittenden, D.B.; Ferrari, S.; Khan, A.; Lane, N.E.; Lippuner, K.; Matsumoto, T.; Milmont, C.E.; Libanati, C.; Grauer, A. FRAME study: the foundation effect of building bone with 1 year of romosozumab leads to continued lower fracture risk after transition to denosumab. J. Bone Miner. Res., 2018, 33(7), 1219-1226.
[http://dx.doi.org/10.1002/jbmr.3427 ] [PMID: 29573473]
Langdahl, B.L.; Libanati, C.; Crittenden, D.B.; Bolognese, M.A.; Brown, J.P.; Daizadeh, N.S.; Dokoupilova, E.; Engelke, K.; Finkelstein, J.S.; Genant, H.K.; Goemaere, S.; Hyldstrup, L.; Jodar-Gimeno, E.; Keaveny, T.M.; Kendler, D.; Lakatos, P.; Maddox, J.; Malouf, J.; Massari, F.E.; Molina, J.F.; Ulla, M.R.; Grauer, A. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet, 2017, 390(10102), 1585-1594.
[http://dx.doi.org/10.1016/S0140-6736(17)31613-6 ] [PMID: 28755782]
Saag, K.G.; Petersen, J.; Brandi, M.L.; Karaplis, A.C.; Lorentzon, M.; Thomas, T.; Maddox, J.; Fan, M.; Meisner, P.D.; Grauer, A. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N. Engl. J. Med., 2017, 377(15), 1417-1427.
[http://dx.doi.org/10.1056/NEJMoa1708322 ] [PMID: 28892457]
Genant, H.K.; Engelke, K.; Bolognese, M.A.; Mautalen, C.; Brown, J.P.; Recknor, C.; Goemaere, S.; Fuerst, T.; Yang, Y.C.; Grauer, A.; Libanati, C. Effects of romosozumab compared with teriparatide on bone density and mass at the spine and hip in postmenopausal women with low bone mass. J. Bone Miner. Res., 2017, 32(1), 181-187.
[http://dx.doi.org/10.1002/jbmr.2932 ] [PMID: 27487526]
Wu, M.; Chen, G.; Li, Y.P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res., 2016, 4, 16009.
[http://dx.doi.org/10.1038/boneres.2016.9 ] [PMID: 27563484]
Xian, L.; Wu, X.; Pang, L.; Lou, M.; Rosen, C.J.; Qiu, T.; Crane, J.; Frassica, F.; Zhang, L.; Rodriguez, J.P.; Jia, X.; Yakar, S.; Shouhong, X.; Efstratiadis, A.; Wan, M.; Cao, X. IGF-1 released from bone matrix stimulates osteoblastic differentiation of MSCs by activation of mTOR during bone remodeling. Nat. Med., 2012, 18(7), 1095-1101.
[http://dx.doi.org/10.1038/nm.2793 ] [PMID: 22729283]
Irelli, A.; Sirufo, M.M.; Scipioni, T.; De Pietro, F.; Pancotti, A.; Ginaldi, L.; De Martinis, M. mTOR links tumor immunity and bone metabolism: what are the clinical implications? Int. J. Mol. Sci., 2019, 20(23), 5841.
[http://dx.doi.org/10.3390/ijms20235841 ] [PMID: 31766386]
de Queiroz Fernandes, J.; de Lima, V.N.; Bonardi, J.P.; Filho, O.M.; Queiroz, S.B.F. Bone regeneration with recombinant human bone morphogenetic protein 2: a systematic review. J. Maxillofac. Oral Surg., 2018, 17(1), 13-18.
[http://dx.doi.org/10.1007/s12663-016-0988-1 ] [PMID: 29382988]
Oryan, A.; Kamali, A.; Moshiri, A. Potential mechanisms and applications of statins on osteogenesis: Current modalities, conflicts and future directions. J. Control. Release, 2015, 215, 12-24.
[http://dx.doi.org/10.1016/j.jconrel.2015.07.022 ] [PMID: 26226345]
Ruaro, B.; Casabella, A.; Paolino, S.; Pizzorni, C.; Ghio, M.; Seriolo, C.; Molfetta, L.; Odetti, P.; Smith, V.; Cutolo, M. Dickkopf-1 (Dkk-1) serum levels in systemic sclerosis and rheumatoid arthritis patients: correlation with the Trabecular Bone Score (TBS). Clin. Rheumatol., 2018, 37(11), 3057-3062.
[http://dx.doi.org/10.1007/s10067-018-4322-9 ] [PMID: 30291470]
Wu, M.; Chen, M.; Ma, Y.; Yang, J.; Han, R.; Yuan, Y.; Hu, X.; Wang, M.; Zhang, X.; Xu, S.; Liu, R.; Jiang, G.; Xu, J.; Shuai, Z.; Zou, Y.; Pan, G.; Pan, F. Dickkopf-1 in ankylosing spondylitis: Review and meta-analysis. Clin. Chim. Acta, 2018, 481, 177-183.
[http://dx.doi.org/10.1016/j.cca.2018.03.010 ] [PMID: 29544750]
Jin, Y.; Xu, L.; Wu, X.; Feng, J.; Shu, M.; Gu, H.; Gao, G.; Zhang, J.; Dong, B.; Chen, X. Synergistic efficacy of the demethylation agent decitabine in combination with the protease inhibitor bortezomib for treating multiple myeloma through the Wnt/βcatenin pathway. Oncol. Res., 2019, 27(6), 729-737.
[http://dx.doi.org/10.3727/096504018X15443011011637 ] [PMID: 30837032]
Wang, M.; Park, S.; Nam, Y.; Nielsen, J.; Low, S.A.; Srinivasarao, M.; Low, P.S. Bone-fracture-targeted dasatinib-oligoaspartic acid conjugate potently accelerates fracture repair. Bioconjug. Chem., 2018, 29(11), 3800-3809.
[http://dx.doi.org/10.1021/acs.bioconjchem.8b00660 ] [PMID: 30380292]
Gaur, T.; Wixted, J.J.; Hussain, S.; O’Connell, S.L.; Morgan, E.F.; Ayers, D.C.; Komm, B.S.; Bodine, P.V.; Stein, G.S.; Lian, J.B. Secreted frizzled related protein 1 is a target to improve fracture healing. J. Cell. Physiol., 2009, 220(1), 174-181.
[http://dx.doi.org/10.1002/jcp.21747 ] [PMID: 19301255]
Schweiger, J.U.; Schweiger, U.; Hüppe, M.; Kahl, K.G.; Greggersen, W.; Jauch-Chara, K.; Fassbinder, E. The use of antidepressive agents and bone mineral density in women: a meta-analysis. Int. J. Environ. Res. Public Health, 2018, 15(7), 15.
[http://dx.doi.org/10.3390/ijerph15071373 ] [PMID: 29966324]
Yadav, V.K.; Balaji, S.; Suresh, P.S.; Liu, X.S.; Lu, X.; Li, Z.; Guo, X.E.; Mann, J.J.; Balapure, A.K.; Gershon, M.D.; Medhamurthy, R.; Vidal, M.; Karsenty, G.; Ducy, P. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat. Med., 2010, 16(3), 308-312.
[http://dx.doi.org/10.1038/nm.2098 ] [PMID: 20139991]
Bone, H.G.; Dempster, D.W.; Eisman, J.A.; Greenspan, S.L.; McClung, M.R.; Nakamura, T.; Papapoulos, S.; Shih, W.J.; Rybak-Feiglin, A.; Santora, A.C.; Verbruggen, N.; Leung, A.T.; Lombardi, A. Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the long-term odanacatib fracture trial. Osteoporos. Int., 2015, 26(2), 699-712.
[http://dx.doi.org/10.1007/s00198-014-2944-6 ] [PMID: 25432773]
Antebi, B.; Pelled, G.; Gazit, D. Stem cell therapy for osteoporosis. Curr. Osteoporos. Rep., 2014, 12(1), 41-47.
[http://dx.doi.org/10.1007/s11914-013-0184-x ] [PMID: 24407712]
Kim, G.; Park, Y.S.; Lee, Y.; Jin, Y.M.; Choi, D.H.; Ryu, K.H.; Park, Y.J.; Park, K.D.; Jo, I. Tonsil-derived mesenchymal stem cell embedded in situ crosslinkable gelatin hydrogel therapy recovers postmenopausal osteoporosis through bone regeneration. Plos One, 2018, 13(7), e0200111.
[http://dx.doi.org/10.1371/journal.pone.0200111 ] [PMID: 29975738]
Yang, Y.; Fang, S. Small non-coding RNAs-based bone regulation and targeting therapeutic strategies. Mol. Cell. Endocrinol., 2017, 456, 16-35.
[http://dx.doi.org/10.1016/j.mce.2016.11.018 ] [PMID: 27888003]
Feng, Q.; Zheng, S.; Zheng, J. The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis. Biosci. Rep., 2018, 38(3), BSR20180453.
[http://dx.doi.org/10.1042/BSR20180453 ] [PMID: 29848766]
Liang, C.; Guo, B.; Wu, H.; Shao, N.; Li, D.; Liu, J.; Dang, L.; Wang, C.; Li, H.; Li, S.; Lau, W.K.; Cao, Y.; Yang, Z.; Lu, C.; He, X.; Au, D.W.; Pan, X.; Zhang, B.T.; Lu, C.; Zhang, H.; Yue, K.; Qian, A.; Shang, P.; Xu, J.; Xiao, L.; Bian, Z.; Tan, W.; Liang, Z.; He, F.; Zhang, L.; Lu, A.; Zhang, G. Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. Nat. Med., 2015, 21(3), 288-294.
[http://dx.doi.org/10.1038/nm.3791 ] [PMID: 25665179]
Zhao, R.; Xie, P.; Zhang, K.; Tang, Z.; Chen, X.; Zhu, X.; Fan, Y.; Yang, X.; Zhang, X. Selective effect of epigenetic regulation of osteoblastic cell function by HANPs has significant implication on defining design parameters for a potential therapeutic use of nanomaterials. Acta Biomater., 2017, 59, 338-350.
[http://dx.doi.org/10.1016/j.actbio.2017.07.009 ] [PMID: 28698163]
Tucker, W.O.; Kinghorn, A.B.; Fraser, L.A.; Cheung, Y.W.; Tanner, J.A. Selection and characterization of a DNA aptamer specifically targeting human HECT ubiquitin ligase WWP1. Int. J. Mol. Sci., 2018, 19(3), 19.
[http://dx.doi.org/10.3390/ijms19030763 ] [PMID: 29518962]
Lee, M.S.; Su, C.M.; Yeh, J.C.; Wu, P.R.; Tsai, T.Y.; Lou, S.L. Synthesis of composite magnetic nanoparticles Fe3O4 with alendronate for osteoporosis treatment. Int. J. Nanomedicine, 2016, 11, 4583-4594.
[http://dx.doi.org/10.2147/IJN.S112415 ] [PMID: 27695319]
Abdelkarem, H.M.; Fadda, L.H.; El-Sayed, E.M.; Radwan, O.K. Potential role of L-arginine and vitamin E against bone loss induced by nano-zinc oxide in rats. J. Diet. Suppl., 2018, 15(3), 300-310.
[http://dx.doi.org/10.1080/19390211.2017.1343889 ] [PMID: 28759296]
Moon, N.; Effiong, L.; Song, L.; Gardner, T.R. Soung, DY Tart Cherry prevents bone loss through inhibition of RANKL in TNF-overexpressing mice. Nutrients, 2019, 11, 63.
Chai, L.J.; Zhang, Y.; Zhang, P.Y.; Bi, Y.N.; Yuan, X.M.; Li, Y.H.; Wang, Y.Y.; Song, L.; Sun, L.K.; Zhou, K. The antiosteoporosis effects of Zhuanggu Guanjie Pill in vitro and in vivo. BioMed Research. Int., 2018, 5, 1-11.
[http://dx.doi.org/10.1155/2018/9075318 ]
Cho, Y.; Lee, S.; Kim, J.; Kang, J.W.; Baek, Y.H.; Seo, B.K.; Lee, J.D. The efficacy and safety of herbal medicine BHH10 in postmenopausal women with osteoporosis: study protocol for a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial. Trials, 2018, 19(1), 482.
[http://dx.doi.org/10.1186/s13063-018-2854-6 ] [PMID: 30201024]
Tabatabaei-Malazy, O.; Salari, P.; Khashayar, P.; Larijani, B. New horizons in treatment of osteoporosis. Daru, 2017, 25(1), 2.
[http://dx.doi.org/10.1186/s40199-017-0167-z ] [PMID: 28173850]
Ciccarelli, F.; De Martinis, M.; Sirufo, M.M.; Ginaldi, L. Psoriasis induced by anti-Tumor Necrosis Factor-alpha agents: a comprehensive review of the literature. Acta Dermatovenerol. Croat., 2016, 24(3), 169-174.
[PMID: 27663916]
Moseley, K.F.; Naidoo, J.; Bingham, C.O.; Carducci, M.A.; Forde, P.M.; Gibney, G.T.; Lipson, E.J.; Shah, A.A.; Sharfman, W.H.; Cappelli, L.C. Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series. J. Immunother. Cancer, 2018, 6(1), 104.
[http://dx.doi.org/10.1186/s40425-018-0417-8 ] [PMID: 30305172 ]

open access plus

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 06 November, 2020
Page: [6356 - 6372]
Pages: 17
DOI: 10.2174/0929867326666190730113123

Article Metrics

PDF: 74