Skip to main content
SpringerLink
Log in

Sclerostin Inhibition in the Treatment of Osteoporosis

  • Chapter
  • First Online:
Osteoporosis

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

The discovery of a few mutations that cause rare human diseases with altered skeletal mass has identified components of the WNT signaling pathway as candidates for therapeutic intervention aimed at increasing bone mass and strength for the treatment of osteoporosis. In particular, the high bone mass syndrome, sclerosteosis, and van Buchem syndromes were linked to inhibition of sclerostin expression and/or activity. Sclerostin is a WNT antagonist secreted by osteocytes, and its deletion in animal studies or its inhibition in animals and in several human clinical trials has proven to be a very efficient osteoanabolic approach. One year of monthly administration of antibodies to sclerostin rapidly decreases bone resorption and increases bone formation and bone density at all sites, decreasing markedly fracture risk in treated patients. The effect of sclerostin inhibition is however self-regulated and thereby limited in time, although this does not prevent sclerostin antibodies treatment from being the most rapid and efficient way available today to increase bone mineral density and reduce fracture risk in osteoporotic patients. Few safety issues have been identified except that cardiovascular adverse events have been reported in one clinical trial, preventing the use of these antibodies in patients at increased cardiovascular risk.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Baron R, Ferrari S, Russell RG. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone. 2011;48(4):677–92.

    Article  CAS  PubMed  Google Scholar 

  2. Baron R, Hesse E. Update on bone anabolics in osteoporosis treatment: rationale, current status, and perspectives. J Clin Endocrinol Metab. 2012;97(2):311–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB. Effects of a one-month treatment with PTH(1-34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res. 2007;22(4):495–502.

    Article  CAS  PubMed  Google Scholar 

  4. Silva BC, Bilezikian JP. Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr Opin Pharmacol. 2015;22:41–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001;107(4):513–23.

    Article  CAS  PubMed  Google Scholar 

  6. Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002;70(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  7. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002;346(20):1513–21.

    Article  CAS  PubMed  Google Scholar 

  8. van Bezooijen RL, Roelen BA, Visser A, van der Wee-Pals L, de Wilt E, Karperien M, Hamersma H, Papapoulos SE, ten Dijke P, Lowik CW. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199(6):805–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Loots GG, Kneissel M, Keller H, Baptist M, Chang J, Collette NM, Ovcharenko D, Plajzer-Frick I, Rubin EM. Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res. 2005;15(7):928–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002;39(2):91–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68(3):577–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Boudin E, Yorgan T, Fijalkowski I, Sonntag S, Steenackers E, Hendrickx G, Peeters S, De Mare A, Vervaet B, Verhulst A, et al. The Lrp4R1170Q homozygous Knock-in mouse recapitulates the bone phenotype of Sclerosteosis in humans. J Bone Miner Res. 2017;32(8):1739–49.

    Article  CAS  PubMed  Google Scholar 

  13. Chang MK, Kramer I, Huber T, Kinzel B, Guth-Gundel S, Leupin O, Kneissel M. Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels. Proc Natl Acad Sci U S A. 2014;111(48):E5187–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fijalkowski I, Geets E, Steenackers E, Van Hoof V, Ramos FJ, Mortier G, Fortuna AM, Van Hul W, Boudin E. A novel domain-specific mutation in a sclerosteosis patient suggests a role of LRP4 as an anchor for sclerostin in human bone. J Bone Miner Res. 2016;31(4):874–81.

    Article  CAS  PubMed  Google Scholar 

  15. Leupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F, Bouwmeester T, Schirle M, Bueno-Lozano M, Fuentes FJ, et al. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011;286(22):19489–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R. Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res. 2006;21(11):1738–49.

    Article  CAS  PubMed  Google Scholar 

  17. Morvan F, Boulukos K, Clement-Lacroix P, Roman Roman S, Suc-Royer I, Vayssiere B, Ammann P, Martin P, Pinho S, Pognonec P, et al. Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res. 2006;21(6):934–45.

    Article  CAS  PubMed  Google Scholar 

  18. Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet. 2008;371(9623):1505–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE, Oei L, Albagha OM, Amin N, Kemp JP, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44(5):491–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Garcia-Ibarbia C, Perez-Nunez MI, Olmos JM, Valero C, Perez-Aguilar MD, Hernandez JL, Zarrabeitia MT, Gonzalez-Macias J, Riancho JA. Missense polymorphisms of the WNT16 gene are associated with bone mass, hip geometry and fractures. Osteoporos Int. 2013;24(9):2449–54.

    Article  CAS  PubMed  Google Scholar 

  21. Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36(11):1461–73.

    Article  CAS  PubMed  Google Scholar 

  22. Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19(2):179–92.

    Article  CAS  PubMed  Google Scholar 

  23. Brommage R. Genetic approaches to identifying novel osteoporosis drug targets. J Cell Biochem. 2015;116(10):2139–45.

    Article  CAS  PubMed  Google Scholar 

  24. Kakugawa S, Langton PF, Zebisch M, Howell S, Chang TH, Liu Y, Feizi T, Bineva G, O’Reilly N, Snijders AP, et al. Notum deacylates Wnt proteins to suppress signalling activity. Nature. 2015;519(7542):187–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Torres VI, Godoy JA, Inestrosa NC. Modulating Wnt signaling at the root: porcupine and Wnt acylation. Pharmacol Ther. 2019;198:34.

    Article  CAS  PubMed  Google Scholar 

  26. Glass DA 2nd, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005;8(5):751–64.

    Article  CAS  PubMed  Google Scholar 

  27. Kramer I, Halleux C, Keller H, Pegurri M, Gooi JH, Weber PB, Feng JQ, Bonewald LF, Kneissel M. Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol. 2010;30(12):3071–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC, Bouxsein ML, Deng L, Clemens TL, Williams BO. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem. 2005;280(22):21162–8.

    Article  CAS  PubMed  Google Scholar 

  29. Wei W, Zeve D, Suh JM, Wang X, Du Y, Zerwekh JE, Dechow PC, Graff JM, Wan Y. Biphasic and dosage-dependent regulation of osteoclastogenesis by beta-catenin. Mol Cell Biol. 2011;31(23):4706–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kiper POS, Saito H, Gori F, Unger S, Hesse E, Yamana K, Kiviranta R, Solban N, Liu J, Brommage R, et al. Cortical-bone fragility–insights from sFRP4 deficiency in Pyle’s disease. N Engl J Med. 2016;374(26):2553–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Marcus R. GFaB. Wnt signaling in skeletal homeostasis and diseases. Osteoporosis. 4th ed. Academic Press Elsevier; 2013. p. 411–428.

    Google Scholar 

  32. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005;280(20):19883–7.

    Article  CAS  PubMed  Google Scholar 

  33. ten Dijke P, Krause C, de Gorter DJ, Lowik CW, van Bezooijen RL. Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am. 2008;90(Suppl 1):31–5.

    Article  PubMed  Google Scholar 

  34. Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011;26(2):229–38.

    Article  CAS  PubMed  Google Scholar 

  35. Prideaux M, Findlay DM, Atkins GJ. Osteocytes: the master cells in bone remodelling. Curr Opin Pharmacol. 2016;28:24–30.

    Article  CAS  PubMed  Google Scholar 

  36. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, Manolagas SC, Jilka RL. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005;146(11):4577–83.

    Article  CAS  PubMed  Google Scholar 

  37. Drake MT, Khosla S. Hormonal and systemic regulation of sclerostin. Bone. 2017;96:8–17.

    Article  CAS  PubMed  Google Scholar 

  38. Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone. 2005;37(2):148–58.

    Article  CAS  PubMed  Google Scholar 

  39. Wijenayaka AR, Yang D, Prideaux M, Ito N, Kogawa M, Anderson PH, Morris HA, Solomon LB, Loots GG, Findlay DM, et al. 1alpha,25-dihydroxyvitamin D3 stimulates human SOST gene expression and sclerostin secretion. Mol Cell Endocrinol. 2015;413:157–67.

    Article  CAS  PubMed  Google Scholar 

  40. Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283(9):5866–75.

    Article  CAS  PubMed  Google Scholar 

  41. Uda Y, Azab E, Sun N, Shi C, Pajevic PD. Osteocyte mechanobiology. Curr Osteoporos Rep. 2017;15(4):318–25.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, Bonewald LF, Kodama T, Wutz A, Wagner EF, et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17(10):1231–4.

    Article  CAS  PubMed  Google Scholar 

  43. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011;17(10):1235–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shalhoub V, Tipton B, Haldankar R, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009;24(4):578–88.

    Article  CAS  PubMed  Google Scholar 

  45. Tian X, Jee WS, Li X, Paszty C, Ke HZ. Sclerostin antibody increases bone mass by stimulating bone formation and inhibiting bone resorption in a hindlimb-immobilization rat model. Bone. 2011;48(2):197–201.

    Article  CAS  PubMed  Google Scholar 

  46. Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Lowik CW, Reeve J. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. 2005;19(13):1842–4.

    Article  CAS  PubMed  Google Scholar 

  47. Gardner JC, van Bezooijen RL, Mervis B, Hamdy NA, Lowik CW, Hamersma H, Beighton P, Papapoulos SE. Bone mineral density in sclerosteosis; affected individuals and gene carriers. J Clin Endocrinol Metab. 2005;90(12):6392–5.

    Article  CAS  PubMed  Google Scholar 

  48. Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008;23(6):860–9.

    Article  PubMed  Google Scholar 

  49. Li X, Warmington KS, Niu QT, Asuncion FJ, Barrero M, Grisanti M, Dwyer D, Stouch B, Thway TM, Stolina M, et al. Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats. J Bone Miner Res. 2010;25(12):2647–56.

    Article  PubMed  CAS  Google Scholar 

  50. Jacobsen CM. Application of anti-Sclerostin therapy in non-osteoporosis disease models. Bone. 2017;96:18–23.

    Article  CAS  PubMed  Google Scholar 

  51. Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Min Res. 2010;25(5):948–59.

    Article  CAS  Google Scholar 

  52. Ominsky MS, Niu QT, Li C, Li X, Ke HZ. Tissue-level mechanisms responsible for the increase in bone formation and bone volume by sclerostin antibody. J Bone Min Res. 2014;29(6):1424–30.

    Article  CAS  Google Scholar 

  53. Ominsky MS, Boyd SK, Varela A, Jolette J, Felx M, Doyle N, Mellal N, Smith SY, Locher K, Buntich S, et al. Romosozumab improves bone mass and strength while maintaining bone quality in ovariectomized cynomolgus monkeys. J Bone Min Res. 2017;32(4):788–801.

    Article  CAS  Google Scholar 

  54. Kim SW, Lu Y, Williams EA, Lai F, Lee JY, Enishi T, Balani DH, Ominsky MS, Ke HZ, Kronenberg HM, et al. Sclerostin antibody administration converts bone lining cells into active osteoblasts. J Bone Min Res. 2017;32(5):892–901.

    Article  CAS  Google Scholar 

  55. Taylor S, Ominsky MS, Hu R, Pacheco E, He YD, Brown DL, Aguirre JI, Wronski TJ, Buntich S, Afshari CA, et al. Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats. Bone. 2016;84:148–59.

    Article  CAS  PubMed  Google Scholar 

  56. Ominsky MS, Brown DL, Van G, Cordover D, Pacheco E, Frazier E, Cherepow L, Higgins-Garn M, Aguirre JI, Wronski TJ, et al. 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. 2015;81:380–91.

    Article  CAS  PubMed  Google Scholar 

  57. Balani DH, Ono N, Kronenberg HM. Parathyroid hormone regulates fates of murine osteoblast precursors in vivo. J Clin Invest. 2017;127(9):3327–38.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Jang MG, Lee JY, Yang JY, Park H, Kim JH, Kim JE, Shin CS, Kim SY, Kim SW. Intermittent PTH treatment can delay the transformation of mature osteoblasts into lining cells on the periosteal surfaces. J Bone Miner Metab. 2016;34(5):532–9.

    Article  CAS  PubMed  Google Scholar 

  59. Drake MT, Clarke BL, Oursler MJ, Khosla S. Cathepsin K inhibitors for osteoporosis: biology, potential clinical utility, and lessons learned. Endocr Rev. 2017;38(4):325–50.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;26(1):19–26.

    Article  CAS  PubMed  Google Scholar 

  61. McColm J, Hu L, Womack T, Tang CC, Chiang AY. Single- and multiple-dose randomized studies of blosozumab, a monoclonal antibody against sclerostin, in healthy postmenopausal women. J Bone Min Res. 2014;29(4):935–43.

    Article  CAS  Google Scholar 

  62. McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370(5):412–20.

    Article  CAS  PubMed  Google Scholar 

  63. Recker RR, Benson CT, Matsumoto T, Bolognese MA, Robins DA, Alam J, Chiang AY, Hu L, Krege JH, Sowa H, et al. A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J Bone Min Res. 2015;30(2):216–24.

    Article  CAS  Google Scholar 

  64. Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532–43.

    Article  CAS  PubMed  Google Scholar 

  65. Cosman F, Crittenden DB, Ferrari S, Khan A, Lane NE, Lippuner K, Matsumoto T, Milmont CE, 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 Min Res. 2018;33(7):1219–26.

    Article  CAS  Google Scholar 

  66. Cosman F, Crittenden DB, Ferrari S, Lewiecki EM, Jaller-Raad J, Zerbini C, Milmont CE, Meisner PD, Libanati C, Grauer A. Romosozumab FRAME study: a post hoc analysis of the role of regional background fracture risk on nonvertebral fracture outcome. J Bone Min Res. 2018;33(8):1407–16.

    Article  CAS  Google Scholar 

  67. Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, Gielen E, Milmont CE, 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 Min Res. 2019;34(3):419–28.

    Article  CAS  Google Scholar 

  68. Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417–27.

    Article  CAS  PubMed  Google Scholar 

  69. Gay A, Towler DA. Wnt signaling in cardiovascular disease: opportunities and challenges. Curr Opin Lipidol. 2017;28(5):387–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lewiecki EM, Blicharski T, Goemaere S, Lippuner K, Meisner PD, Miller PD, Miyauchi A, Maddox J, Chen L, Horlait S. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab. 2018;103(9):3183–93.

    Article  PubMed  Google Scholar 

  71. McClung MR, Brown JP, Diez-Perez A, Resch H, Caminis J, Meisner P, Bolognese MA, Goemaere S, Bone HG, Zanchetta JR, et al. 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 Min Res. 2018;33(8):1397–406.

    Article  CAS  Google Scholar 

  72. Langdahl BL, Libanati C, Crittenden DB, Bolognese MA, Brown JP, Daizadeh NS, Dokoupilova E, Engelke K, Finkelstein JS, Genant HK, et al. 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):1585–94.

    Article  CAS  PubMed  Google Scholar 

  73. Moustafa A, Sugiyama T, Prasad J, et al. Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered. Osteoporos Int. 2012;23(4):1225–34.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Harvard School of Medicine, Boston, MA, USA

    Roland Baron

  2. Department of Oral Medicine, Infection and Immunity, Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA, USA

    Francesca Gori

  3. Endocrine Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Benjamin Z. Leder

Authors
  1. Roland Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Gori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Benjamin Z. Leder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roland Baron .

Editor information

Editors and Affiliations

  1. Massachusetts General Hospital, Boston, MA, USA

    Benjamin Z. Leder

  2. Massachusetts General Hospital, Boston, MA, USA

    Marc N. Wein

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Baron, R., Gori, F., Leder, B.Z. (2020). Sclerostin Inhibition in the Treatment of Osteoporosis. In: Leder, B., Wein, M. (eds) Osteoporosis. Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-319-69287-6_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-69287-6_19

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-319-69286-9

  • Online ISBN: 978-3-319-69287-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation