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Sclerostin: from bench to bedside

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Abstract

Skeletal integrity is maintained by a meticulous balance between bone resorption and bone formation, and recent studies have revealed the essential role of canonical Wnt signaling pathways in maintaining skeletal homeostasis. The SOST gene, which encodes sclerostin, a member of Dan family glycoproteins, was originally identified as the gene responsible for two sclerosing bone dysplasias, sclerosteosis and van Buchem disease. Sclerostin is highly expressed by osteocytes, negatively regulates canonical Wnt signaling pathways by binding to low-density lipoprotein receptor-related protein (LRP) 5/6, and suppresses osteoblast differentiation and/or function. Romosozumab, a specific anti-sclerostin antibody, inhibits sclerostin-LRP5/6 interactions and indirectly activates canonical Wnt signaling pathways and bone formation. This review focuses on the mechanism of action of sclerostin and summarizes clinical studies that demonstrated the efficacy of romosozumab to increase bone mineral density and reduce osteoporotic fractures, as well as its cardiovascular safety.

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Adapted from Reference [45]

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Adapted from Reference [55]

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References

  1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, March 7-29, 2000: highlights of the conference (2001). South Med J 94:569–573

  2. Parfitt AM (1994) Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 55:273–286. https://doi.org/10.1002/jcb.240550303

    Article  CAS  PubMed  Google Scholar 

  3. Tanaka S, Nakamura K, Takahasi N, Suda T (2005) Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system (in eng). Immunol Rev 208:30–49

    Article  CAS  Google Scholar 

  4. Tanaka S (2019) Molecular understanding of pharmacological treatment of osteoporosis. EFORT Open Rev 4:158–164. https://doi.org/10.1302/2058-5241.4.180018

    Article  PubMed  PubMed Central  Google Scholar 

  5. Recker R, Lappe J, Davies KM, Heaney R (2004) Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients. J Bone Miner Res 19:1628–1633. https://doi.org/10.1359/JBMR.040710

    Article  PubMed  Google Scholar 

  6. Riggs BL, Parfitt AM (2005) Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res 20:177–184. https://doi.org/10.1359/JBMR.041114

    Article  CAS  PubMed  Google Scholar 

  7. Truswell AS (1958) Osteopetrosis with syndactyly; a morphological variant of Albers-Schonberg’s disease. J Bone Joint Surg Br 40:209–218

    PubMed  Google Scholar 

  8. Van Buchem FS, Hadders HN, Ubbens R (1955) An uncommon familial systemic disease of the skeleton: hyperostosis corticalis generalisata familiaris. Acta Radiol 44:109–120

    Article  Google Scholar 

  9. Balemans W, Van Den Ende J, Freire Paes-Alves A, Dikkers FG, Willems PJ, Vanhoenacker F, de Almeida-Melo N, Alves CF, Stratakis CA, Hill SC, Van Hul W (1999) Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21. Am J Hum Genet 64:1661–1669. https://doi.org/10.1086/302416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589. https://doi.org/10.1086/318811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Avsian-Kretchmer O, Hsueh AJW (2004) Comparative genomic analysis of the eight-membered ring cystine knot-containing bone morphogenetic protein antagonists (in English). Mol Endocrinol 18:1–12. https://doi.org/10.1210/me.2003-0227

    Article  CAS  PubMed  Google Scholar 

  12. Kusu N, Laurikkala J, Imanishi M, Usui H, Konishi M, Miyake A, Thesleff I, Itoh N (2003) Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity. J Biol Chem 278:24113–24117. https://doi.org/10.1074/jbc.M301716200

    Article  CAS  PubMed  Google Scholar 

  13. Itasaki N, Jones CM, Mercurio S, Rowe A, Domingos PM, Smith JC, Krumlauf R (2003) Wise, a context-dependent activator and inhibitor of Wnt signalling. Development 130:4295–4305. https://doi.org/10.1242/dev.00674

    Article  CAS  PubMed  Google Scholar 

  14. Collette NM, Yee CS, Murugesh D, Sebastian A, Taher L, Gale NW, Economides AN, Harland RM, Loots GG (2013) Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner. Dev Biol 383:90–105. https://doi.org/10.1016/j.ydbio.2013.08.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280:19883–19887. https://doi.org/10.1074/jbc.M413274200

    Article  CAS  PubMed  Google Scholar 

  16. Semenov M, Tamai K, He X (2005) SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 280:26770–26775. https://doi.org/10.1074/jbc.M504308200

    Article  CAS  PubMed  Google Scholar 

  17. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S et al (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523. https://doi.org/10.1016/s0092-8674(01)00571-2

    Article  CAS  PubMed  Google Scholar 

  18. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521. https://doi.org/10.1056/NEJMoa013444

    Article  CAS  PubMed  Google Scholar 

  19. Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M et al (2002) A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet 70:11–19. https://doi.org/10.1086/338450

    Article  CAS  PubMed  Google Scholar 

  20. Brance ML, Brun LR, Coccaro NM, Aravena A, Duan S, Mumm S, Whyte MP (2020) High bone mass from mutation of low-density lipoprotein receptor-related protein 6 (LRP6). Bone 141:115550. https://doi.org/10.1016/j.bone.2020.115550

    Article  CAS  PubMed  Google Scholar 

  21. Whyte MP, McAlister WH, Zhang F, Bijanki VN, Nenninger A, Gottesman GS, Lin EL, Huskey M, Duan S, Dahir K, Mumm S (2019) New explanation for autosomal dominant high bone mass: mutation of low-density lipoprotein receptor-related protein 6. Bone 127:228–243. https://doi.org/10.1016/j.bone.2019.05.003

    Article  CAS  PubMed  Google Scholar 

  22. Leupin O, Piters E, Halleux C, Hu S, Kramer I et al (2011) Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem 286:19489–19500. https://doi.org/10.1074/jbc.M110.190330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA (2003) Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22:6267–6276. https://doi.org/10.1093/emboj/cdg599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li X, Ominsky MS, Niu QT, Sun N, Daugherty B et al (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23:860–869. https://doi.org/10.1359/jbmr.080216

    Article  PubMed  Google Scholar 

  25. Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R (2006) Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res 21:1738–1749. https://doi.org/10.1359/jbmr.060810

    Article  CAS  PubMed  Google Scholar 

  26. Semenov MV, He X (2006) LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem 281:38276–38284. https://doi.org/10.1074/jbc.M609509200

    Article  CAS  PubMed  Google Scholar 

  27. Cui Y, Niziolek PJ, MacDonald BT, Zylstra CR, Alenina N et al (2011) Lrp5 functions in bone to regulate bone mass. Nat Med 17:684–691. https://doi.org/10.1038/nm.2388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Holdsworth G, Roberts SJ, Ke HZ (2019) Novel actions of sclerostin on bone. J Mol Endocrinol 62:R167–R185. https://doi.org/10.1530/JME-18-0176

    Article  CAS  PubMed  Google Scholar 

  29. Yee CS, Manilay JO, Chang JC, Hum NR, Murugesh DK, Bajwa J, Mendez ME, Economides AE, Horan DJ, Robling AG, Loots GG (2018) Conditional deletion of Sost in MSC-derived lineages identifies specific cell-type contributions to bone mass and B-cell development. J Bone Miner Res 33:1748–1759. https://doi.org/10.1002/jbmr.3467

    Article  CAS  PubMed  Google Scholar 

  30. van Lierop AH, Witteveen JE, Hamdy NA, Papapoulos SE (2010) Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls. Eur J Endocrinol 163:833–837. https://doi.org/10.1530/EJE-10-0699

    Article  CAS  PubMed  Google Scholar 

  31. Kramer I, Loots GG, Studer A, Keller H, Kneissel M (2010) Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res 25:178–189. https://doi.org/10.1359/jbmr.090730

    Article  CAS  PubMed  Google Scholar 

  32. Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283:5866–5875. https://doi.org/10.1074/jbc.M705092200

    Article  CAS  PubMed  Google Scholar 

  33. Tu X, Rhee Y, Condon KW, Bivi N, Allen MR, Dwyer D, Stolina M, Turner CH, Robling AG, Plotkin LI, Bellido T (2012) Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone 50:209–217. https://doi.org/10.1016/j.bone.2011.10.025

    Article  CAS  PubMed  Google Scholar 

  34. Ardawi MS, Al-Kadi HA, Rouzi AA, Qari MH (2011) Determinants of serum sclerostin in healthy pre- and postmenopausal women. J Bone Miner Res 26:2812–2822. https://doi.org/10.1002/jbmr.479

    Article  CAS  PubMed  Google Scholar 

  35. Kanbay M, Siriopol D, Saglam M, Kurt YG, Gok M, Cetinkaya H, Karaman M, Unal HU, Oguz Y, Sari S, Eyileten T, Goldsmith D, Vural A, Veisa G, Covic A, Yilmaz MI (2014) Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients. J Clin Endocrinol Metab 99:E1854–E1861. https://doi.org/10.1210/jc.2014-2042

    Article  CAS  PubMed  Google Scholar 

  36. Li X, Ominsky MS, Warmington KS, Morony S, Gong J et al (2009) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24:578–588. https://doi.org/10.1359/jbmr.081206

    Article  CAS  PubMed  Google Scholar 

  37. Li X, Ominsky MS, Warmington KS, Niu QT, Asuncion FJ, Barrero M, Dwyer D, Grisanti M, Stolina M, Kostenuik PJ, Simonet WS, Paszty C, Ke HZ (2011) Increased bone formation and bone mass induced by sclerostin antibody is not affected by pretreatment or cotreatment with alendronate in osteopenic, ovariectomized rats. Endocrinology 152:3312–3322. https://doi.org/10.1210/en.2011-0252

    Article  CAS  PubMed  Google Scholar 

  38. Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B et al (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25:948–959. https://doi.org/10.1002/jbmr.14

    Article  CAS  PubMed  Google Scholar 

  39. Li X, Niu QT, Warmington KS, Asuncion FJ, Dwyer D, Grisanti M, Han CY, Stolina M, Eschenberg MJ, Kostenuik PJ, Simonet WS, Ominsky MS, Ke HZ (2014) Progressive increases in bone mass and bone strength in an ovariectomized rat model of osteoporosis after 26 weeks of treatment with a sclerostin antibody. Endocrinology 155:4785–4797. https://doi.org/10.1210/en.2013-1905

    Article  CAS  PubMed  Google Scholar 

  40. Ominsky MS, Niu QT, Li C, Li X, Ke HZ (2014) Tissue-level mechanisms responsible for the increase in bone formation and bone volume by sclerostin antibody. J Bone Miner Res 29:1424–1430. https://doi.org/10.1002/jbmr.2152

    Article  CAS  PubMed  Google Scholar 

  41. Ominsky MS, Brown DL, Van G, Cordover D, Pacheco E, Frazier E, Cherepow L, Higgins-Garn M, Aguirre JI, Wronski TJ, Stolina M, Zhou L, Pyrah I, Boyce RW (2015) Differential temporal effects of sclerostin antibody and parathyroid hormone on cancellous and cortical bone and quantitative differences in effects on the osteoblast lineage in young intact rats. Bone 81:380–391. https://doi.org/10.1016/j.bone.2015.08.007

    Article  CAS  PubMed  Google Scholar 

  42. Agholme F, Li X, Isaksson H, Ke HZ, Aspenberg P (2010) Sclerostin antibody treatment enhances metaphyseal bone healing in rats. J Bone Miner Res 25:2412–2418. https://doi.org/10.1002/jbmr.135

    Article  CAS  PubMed  Google Scholar 

  43. Ominsky MS, Li C, Li X, Tan HL, Lee E, Barrero M, Asuncion FJ, Dwyer D, Han CY, Vlasseros F, Samadfam R, Jolette J, Smith SY, Stolina M, Lacey DL, Simonet WS, Paszty C, Li G, Ke HZ (2011) Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones. J Bone Miner Res 26:1012–1021. https://doi.org/10.1002/jbmr.307

    Article  CAS  PubMed  Google Scholar 

  44. 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 26:19–26. https://doi.org/10.1002/jbmr.173

    Article  CAS  PubMed  Google Scholar 

  45. Appelman-Dijkstra NM, Papapoulos SE (2016) Sclerostin inhibition in the management of osteoporosis. Calcif Tissue Int 98:370–380. https://doi.org/10.1007/s00223-016-0126-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 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 370:412–420. https://doi.org/10.1056/NEJMoa1305224

    Article  CAS  PubMed  Google Scholar 

  47. Ishibashi H, Crittenden DB, Miyauchi A, Libanati C, Maddox J, Fan M, Chen L, Grauer A (2017) Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: a phase 2 study. Bone 103:209–215. https://doi.org/10.1016/j.bone.2017.07.005

    Article  CAS  PubMed  Google Scholar 

  48. McClung MR, Brown JP, Diez-Perez A, Resch H, Caminis J, Meisner P, Bolognese MA, Goemaere S, Bone HG, Zanchetta JR, Maddox J, Bray S, Grauer A (2018) Effects of 24 months of treatment with romosozumab followed by 12 months of denosumab or placebo in postmenopausal women with low bone mineral density: a randomized, double-blind, phase 2, parallel group study. J Bone Miner Res 33:1397–1406. https://doi.org/10.1002/jbmr.3452

    Article  CAS  PubMed  Google Scholar 

  49. Kendler DL, Bone HG, Massari F, Gielen E, Palacios S, Maddox J, Yan C, Yue S, Dinavahi RV, Libanati C, Grauer A (2019) Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab. Osteoporos Int 30:2437–2448. https://doi.org/10.1007/s00198-019-05146-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Cosman F, Nieves JW, Dempster DW (2017) Treatment sequence matters: anabolic and antiresorptive therapy for osteoporosis. J Bone Miner Res 32:198–202. https://doi.org/10.1002/jbmr.3051

    Article  CAS  PubMed  Google Scholar 

  51. Langdahl BL, Libanati C, Crittenden DB, Bolognese MA, Brown JP et al (2017) Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet 390:1585–1594. https://doi.org/10.1016/S0140-6736(17)31613-6

    Article  CAS  PubMed  Google Scholar 

  52. Dempster DW, Zhou H, Recker RR, Brown JP, Recknor CP, Lewiecki EM, Miller PD, Rao SD, Kendler DL, Lindsay R, Krege JH, Alam J, Taylor KA, Melby TE, Ruff VA (2018) Remodeling- and modeling-based bone formation with teriparatide versus denosumab: a longitudinal analysis from baseline to 3 months in the AVA study. J Bone Miner Res 33:298–306. https://doi.org/10.1002/jbmr.3309

    Article  CAS  PubMed  Google Scholar 

  53. Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A (2016) Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 375:1532–1543. https://doi.org/10.1056/NEJMoa1607948

    Article  CAS  PubMed  Google Scholar 

  54. Cosman F, Crittenden DB, Ferrari S, Lewiecki EM, Jaller-Raad J, Zerbini C, Milmont CE, Meisner PD, Libanati C, Grauer A (2018) Romosozumab FRAME study: a post hoc analysis of the role of regional background fracture risk on nonvertebral fracture outcome. J Bone Miner Res 33:1407–1416. https://doi.org/10.1002/jbmr.3439

    Article  CAS  PubMed  Google Scholar 

  55. Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, Gielen E, Milmont CE, Libanati C, Grauer A (2019) One year of romosozumab followed by two years of denosumab maintains fracture risk reductions: results of the FRAME extension study. J Bone Miner Res 34:419–428. https://doi.org/10.1002/jbmr.3622

    Article  CAS  PubMed  Google Scholar 

  56. Lewiecki EM, Blicharski T, Goemaere S, Lippuner K, Meisner PD, Miller PD, Miyauchi A, Maddox J, Chen L, Horlait S (2018) A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab 103:3183–3193. https://doi.org/10.1210/jc.2017-02163

    Article  PubMed  Google Scholar 

  57. Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A (2017) Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 377:1417–1427. https://doi.org/10.1056/NEJMoa1708322

    Article  CAS  PubMed  Google Scholar 

  58. Asadipooya K, Weinstock A (2019) Cardiovascular outcomes of romosozumab and protective role of alendronate. Arterioscler Thromb Vasc Biol 39:1343–1350. https://doi.org/10.1161/ATVBAHA.119.312371

    Article  CAS  PubMed  Google Scholar 

  59. Sing CW, Wong AY, Kiel DP, Cheung EY, Lam JK, Cheung TT, Chan EW, Kung AW, Wong IC, Cheung CL (2018) Association of alendronate and risk of cardiovascular events in patients with hip fracture. J Bone Miner Res 33:1422–1434. https://doi.org/10.1002/jbmr.3448

    Article  CAS  PubMed  Google Scholar 

  60. Takashima N, Arima H, Kita Y, Fujii T, Miyamatsu N, Komori M, Sugimoto Y, Nagata S, Miura K, Nozaki K (2017) Incidence, management and short-term outcome of stroke in a general population of 1.4 million Japanese- Shiga stroke registry. Circ J 81:1636–1646. https://doi.org/10.1253/circj.CJ-17-0177

    Article  PubMed  Google Scholar 

  61. Rumana N, Kita Y, Turin TC, Murakami Y, Sugihara H, Morita Y, Tomioka N, Okayama A, Nakamura Y, Abbott RD, Ueshima H (2008) Trend of increase in the incidence of acute myocardial infarction in a Japanese population: Takashima AMI Registry, 1990–2001. Am J Epidemiol 167:1358–1364. https://doi.org/10.1093/aje/kwn064

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Sakae Tanaka

  2. Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan

    Toshio Matsumoto

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Correspondence to Sakae Tanaka.

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Sakae Tanaka received consulting fees, speaking fees, and/or honoraria from Asahi Kasei Pharma Co., Daiichi-Sankyo Co., Ltd., Teijin Pharma, Ltd., and Amgen Inc., and research grants from Asahi Kasei Pharma Co., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd., Eli Lilly Japan K.K., and Teijin Pharma Ltd. Toshio Matsumoto received consulting fees, and/or speaker honoraria from Chugai Pharmaceutical Co., Daiichi-Sankyo Co., Ltd., Teijin Pharma, Ltd., Astellas Pharma Inc. and Amgen Inc.

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Tanaka, S., Matsumoto, T. Sclerostin: from bench to bedside. J Bone Miner Metab 39, 332–340 (2021). https://doi.org/10.1007/s00774-020-01176-0

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