Sclerostin and skeletal health

Reviews in Endocrine and Metabolic Disorders

Volumn 16, Issue 2, 2015, Pages 149-156

  Sharifi, Maryam ^a   Ereifej, Lisa ^a   Lewiecki, E Michael ^a,b  

^a UNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE   (United States)

^b NEW MEXICO CLINICAL RESEARCH AND OSTEOPOROSIS CENTER   (United States)

Author keywords

Blosozumab; Osteoporosis; Romosozumab; Sclerostin; SOST; Wnt catenin pathway

Indexed keywords

BLOSOZUMAB; ROMOSOZUMAB; SCLEROSTIN; BONE MORPHOGENETIC PROTEIN; GENETIC MARKER; MONOCLONAL ANTIBODY; SOST PROTEIN, HUMAN;

BONE DENSITY; BONE DISEASE; BONE GROWTH; BONE MASS; BONE STRENGTH; DUAL ENERGY X RAY ABSORPTIOMETRY; FRACTURE HEALING; HETEROZYGOTE; HUMAN; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOLYSIS; OSTEOPOROSIS; OSTEOSCLEROSIS; PHENOTYPE; PROTEIN EXPRESSION; REVIEW; WEIGHT BEARING; WNT SIGNALING PATHWAY; ANIMAL; ANTAGONISTS AND INHIBITORS; BONE; GENETIC MARKER; GENETICS; HEALTH; HYPEROSTOSIS; IMMUNOLOGY; OSTEOCHONDRODYSPLASIAS; PHYSIOLOGY; SYNDACTYLY;

ANIMALS; ANTIBODIES, MONOCLONAL; BONE AND BONES; BONE DENSITY; BONE MORPHOGENETIC PROTEINS; GENETIC MARKERS; HEALTH; HUMANS; HYPEROSTOSIS; OSTEOCHONDRODYSPLASIAS; OSTEOPOROSIS; SYNDACTYLY;

EID: 84940577597     PISSN: 13899155     EISSN: 15732606     Source Type: Journal    
DOI: 10.1007/s11154-015-9311-6     Document Type: Review

References (61)

1. Nusse R, Varmus H. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982;31:99–109.
2. Lewiecki EM. Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases. Ther Adv Musculoskelet Dis. 2014;6(2):48–57.
3. Kim J, Liu X, Wang J, Chen X, Zhang H, Kim S, et al. Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskelet Dis. 2013;5:13–31.
4. Ke H, Richards W, Li X, Ominsky M. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012;33:747–83.
5. Lewiecki E. New targets for intervention in the treatment of postmenopausal osteoporosis. Nat Rev Rheumatol. 2011;7:631–8.
6. Goldring M. Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Ther Adv Musculoskelet Dis. 2012;4:269–85.
7. Krause C, Korchynskyi O, de Rooij K, et al. Distinct modes of inhibition by sclerostin on bone morphogenetic protein and Wnt signaling pathways. J Biol Chem. 2010;285(53):41614–26.
8. Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005;280(20):19883–7.
9. Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005;280(29):26770–5.
10. Van Bezooijen RL, Svensson JP, Eefting D, et al. Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation. J Bone Miner Res. 2007;22(1):19–28.
11. Van Buchem FS, Hadders HN, Ubbens R. An uncommon familial systemic disease of the skeleton: hyperostosis corticalis generalisata familiaris. Acta Radiol. 1955;44(2):109–20.
12. Truswell AS. Osteopetrosis with syndactyly; a morphological variant of albers-schonberg’s disease. J Bone Joint Surg (Br). 1958;40-B(2):209–18.
13. Costa AG, Bilezikian JP & Lewiecki EM. Update on romosozumab:a humanized monoclonal antibody to sclerostin. Expert Opin. Biol. Ther. 2014[Early Online].
14. van Bezooijen R, Roelen B, Visser A, Van der Wee-Pals L, de Wilt E, Karperien M, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199:805–14.
15. Kansara M, Tsang M, Kodjabachian L, Sims NA, Trivett MK, Ehrich M, et al. Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice. J Clin Invest. 2009;119(4):837–51.
16. Kanis J. Assessment of osteoporosis at the primary health-care level. Technical report. World Health Organization Collaborating Centre for Metabolic Bone Diseases. 2007; Sheffield: University of Sheffield.
17. Delmas PD, van de Langerijt L, Watts NB, Eastell R, Genant H, Grauer A, et al. Underdiagnosis of vertebral fractures is a worldwide problem: the IMPACT study. J Bone Miner Res Off J Am Soc Bone Miner Res. 2005;20(4):557–63.
18. Foley KA, Foster SA, Meadows ES, Baser O, Long SR. Assessment of the clinical management of fragility fractures and implications for the new HEDIS osteoporosis measure. Med Care. 2007;45(9):902–6.
19. Roudier M, Li X, Niu Q, Pacheco E, Pretorius J, Graham K, et al. Sclerostin is expressed in articular cartilage but loss or inhibition does not affect cartilage remodeling during aging or following mechanical injury. Arthritis Rheum. 2013;65:721–31.
20. Brunkow M, Gardner J, Van N, Paeper B, Kovacevich B, Proll S, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68:577–89.
21. Veverka V, Henry A, Slocombe P, Ventom A, Mulloy B, Muskett F, et al. Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt mediated bone formation. J Biol Chem. 2009;284:10890–900.
22. Balemans W, Ebeling M, Patel N, Van H, Olson P, Dioszegi M, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001;10:537–43.
23. Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PVN, Komm BS, et al. Canonical Wnt signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem. 2005;280(39):33132–40.
24. Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem. 2006;281(32):22429–33.
25. Bodine PVN, Komm BS. Wnt signaling and osteoblastogenesis. Rev Endocr Metab Disord. 2006;7(1–2):33–9.
26. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005;280:19883–7.
27. Baron R, Rawadi G. Targeting the Wnt/ beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007;148:2635–43.
28. Li X, Ominsky M, Niu Q, Sun N, Daugherty B, D’Agostin D, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008;23:860–9.
29. Beighton P, Davidson J, Durr L, Hamersma H. Sclerosteosis – an autosomal recessive disorder. Clin Genet. 1977;11:1–7.
30. Hamersma H, Gardner J, Beighton P. The natural history of sclerosteosis. Clin Genet. 2003;63:192–7.
31. Gardner J, van Bezooijen R, Mervis B, Hamdy N, Lowik C, Hamersma H, et al. Bone mineral density in sclerosteosis; affected individuals and gene carriers. J Clin Endocrinol Metab. 2005;90:6392–5.
32. Van Lierop A, Hamdy N, Hamersma H, van Bezooijen R, Power J, Loveridge N, et al. Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover. J Bone Miner Res. 2011;26:2804–11.
33. Wergedal J, Veskovic K, Hellan M, Nyght C, Balemans W, Libanati C, et al. Patients with Van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal. J Clin Endocrinol Metab. 2003;88:5778–83.
34. Robling A, Niziolek P, Baldridge L, Condon K, Allen M, Alam I, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/ sclerostin. J Biol Chem. 2008;283:5866–75.
35. Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/betacatenin signaling. J Bone Miner Res. 2009;24:1651–61.
36. Kramer I, Loots G, Studer A, Keller H, Kneissel M. Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res. 2010;25:178–89.
37. Lories R, Luyten F. The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol. 2011;7:43–9.
38. Luyten F, Tylzanowski P, Lories R. Wnt signaling and osteoarthritis. Bone. 2009;44:522–7.
39. Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C, et al. Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res. 2009;24:12–21.
40. Zhu M, Chen M, Zuscik M, Wu Q, Wang Y, Rosier R, et al. Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum. 2008;58:2053–64.
41. Chan B, Fuller E, Russell A, Smith S, Smith M, Jackson M, et al. Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis. Osteoarthr Cartil. 2011;19:874–85.
42. Babcook J, Leslie K, Olsen O, Salmon R, Schrader J. A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities. Proc Natl Acad Sci U S A. 1993;93(15):7843–8.
43. Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res Off J Am Soc Bone Miner Res. 2010;25(5):948–59.
44. Agholme F, Li X, Isaksson H, Ke HZ, Aspenberg P. Sclerostin antibody treatment enhances metaphyseal bone healing in rats. J Bone Miner Res Off J Am Soc Bone Miner Res. 2010;25(11):2412–8.
45. Li X, Warmington KS, Niu QT, Asuncion FJ, Barrero M, Grisanti 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.
46. Ominsky M, Samadfan R, Jolette J, Vlasseros F, Smith S, Kostenuik P, et al. Sclerostin monoclonal antibody stimulates bone formation and improves the strength and density of the fracture callus and lumbar spine in a primate fibular osteotomy model. J Bone Miner Res. 2009;24 Suppl 1:S89–90.
47. 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;26:19–26.
48. Wang W, Wang E, Balthasar J. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84:548–58.
49. McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370(5):412–20.
50. McClung MR, Chines A, Brown JP, Diez-Perez A, Resch H, Caminis J,Bolognese Ma, Goemaere S, Bone HG, Zanchetta JR, Maddox J, Rosen O, Bray S, Grauer A. Effects of 2 years of treatment with romosozumab followed by 1 year of denosumab or placebo in postmenopausal women with low bone mineral density. Presented in ASBMR Sep 2014.
51. Whitmarsh T, Treece G, Gee A, Bolognese M, Brown JP, Goemaere S, Grauer A, Hanley D, Mautalen C, Recknor C, Yang Y, Libanati C, Poole K. Romosozumab and teriparatide effects on vertebral cortical mass, thickness, and density in postmenopausal women with low bone mineral density (BMD). Presented in ASBMR Sep 2014.
52. Treece G, Gee A, Mayhew P, Poole K. High resolution cortical bone thickness measurement from clinical CT data. Med Image Anal. 2010;14(3):276–90.
53. McColm J, Womack T, Hu L, Tang C, Chiang A. Blosozumab, a humanized monoclonal antibody against sclerostin, demonstrated anabolic effects on bone in postmenopausal women. J Bone Miner Res. 2012;27 Suppl 1:S9.
54. Benson, C., Robins, D., Recker, R., Alam, J., Chiang, A., Mitlak, B. et al. Effect of blosozumab on bone mineral density: results of a phase 2 study of postmenopausal women with low bone mineral density. Bone Abstracts. 2013; 1: OC5.3.
55. Benson C, Chiang A, Hu L, Jahangir A, Mitlak B, Recker R, Robins D, Sowa H, Sipos A. Effect of blosozumab on bone mineral density: 52-week follow-up of a phase 2 study of postmenopausal women with low bone mineral density. Presented in ASBMR Sep 2014.
56. Cornell CN. Internal fracture fixation in patients with osteoporosis. J Am Acad Orthop Surg. 2003;11(2):109–19.
57. Goldhahn J, Féron J-M, Kanis J, Papapoulos S, Reginster J-Y, Rizzoli R, et al. Implications for fracture healing of current and new osteoporosis treatments: an ESCEO consensus paper. Calcif Tissue Int. 2012;90(5):343–53.
58. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65.
59. Neogi T, Zhang Y. Epidemiology of osteoarthritis. Rheum Dis Clin N Am. 2013;39(1):1–19.
60. Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M. Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol. 2004;32(4):426–38.
61. Cipriani C, Capriani C, Irani D, Bilezikian JP. Safety of osteoanabolic therapy: a decade of experience. J Bone Miner Res Off J Am Soc Bone Miner Res. 2012;27(12):2419–28.