Abstract
New insights into mechanisms by which the skeleton is or is not maintained during the aging process have led to the development of newer therapeutics for osteoporosis. One of these newer therapeutic approaches takes advantage of an endogenous inhibitor of a major anabolic pathway of bone. The anabolic pathway known as Wnt is regulated by sclerostin. The Inhibition of sclerostin facilitates this pathway leading to an increase in bone mass. Specifically, the anti-sclerostin antibody, romosozumab, has been shown first in animal studies and then in human clinical trials to effectively allow the Wnt signaling pathway to be more completely expressed. Romosozumab reduces vertebral, hip, and nonvertebral fractures. In one trial comparing romosozumab with alendronate, romosozumab was associated with an increase in adverse cardiovascular events; this was not noted in a trial comparing romosozumab to placebo. It is not clear to what extent the cardiovascular safety signal can be attributed directly to romosozumab. The development of romosozumab gives the clinician a wider choice to tailor therapy for osteoporosis.
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References
Bandeira L, Bilezikian JP. Novel therapies for postmenopausal osteoporosis. (1558–4410 (Electronic)).
Shah AD, Shoback D, Lewiecki EM. Sclerostin inhibition: a novel therapeutic approach in the treatment of osteoporosis. (1179–1411 (Print)).
Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. (1546-170X (Electronic)).
Costa AG, Bilezikian JP. Sclerostin: therapeutic horizons based upon its actions. (1544–2241 (Electronic)).
Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. (1932–6203 (Electronic)).
Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. (1523–4681 (Electronic)).
Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. (1523–4681 (Electronic)).
Ominsky MS, Niu Q-T, Li C, Li X, Ke HZ. Tissue-level mechanisms responsible for the increase in bone formation and bone volume by sclerostin antibody. (1523–4681 (Electronic)).
Ominsky MS, Boyce RW, Li X, Ke HZ. Effects of sclerostin antibodies in animal models of osteoporosis. (1873–2763 (Electronic)).
Li X, Warmington KS, Niu Q-T, Asuncion FJ, Barrero M, Grisanti M, Dwyer D, et al. Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats. (1523–4681 (Electronic)).
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. Romosozumab treatment in postmenopausal women with osteoporosis. (1533–4406 (Electronic)).
Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. Romosozumab or Alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417–27.
Langdahl BL, Libanati C, Crittenden DB, Bolognese MA, Brown JP, Daizadeh NS, 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. (1474-547X (Electronic)).
McClung MR, Brown JP, Diez-Perez A, Resch H, Caminis J, Meisner P, 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. (1523–4681 (Electronic)).
Kendler DA-O, Bone HG, Massari F, Gielen E, Palacios S, Maddox J, et al. Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab. (1433–2965 (Electronic)).
Lewiecki EM, Blicharski T, Goemaere S, Lippuner K, Meisner PD, Miller PD, et al. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of Romosozumab in men with osteoporosis. (1945–7197 (Electronic)).
Langdahl BL, Hofbauer LC, Forfar JC. Cardiovascular safety and sclerostin inhibition - a mini-review. LID - dgab193 [pii] LID - https://doi.org/10.1210/clinem/dgab193. (1945–7197 (Electronic)).
Sing CW, Wong AY, Kiel DP, Cheung EY, Lam JK, Cheung TT, et al. Association of alendronate and risk of cardiovascular events in patients with hip fracture. (1523–4681 (Electronic)).
Cummings SR, McCulloch C. Explanations for the difference in rates of cardiovascular events in a trial of alendronate and romosozumab. (1433–2965 (Electronic)).
Fixen CA-O, Tunoa J. Romosozumab: a review of efficacy, safety, and cardiovascular risk. (1544–2241 (Electronic)).
Solomon DH, Johnston SS, Boytsov NN, McMorrow D, Lane JM, Krohn KD. Osteoporosis medication use after hip fracture in U.S. patients between 2002 and 2011. J Bone Miner Res. 2014;29:1929–37. https://doi.org/10.1002/jbmr.2202.
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Cipriani, C., Bilezikian, J.P. (2021). Sclerostin Inhibition. In: Cusano, N.E. (eds) Osteoporosis. Springer, Cham. https://doi.org/10.1007/978-3-030-83951-2_14
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DOI: https://doi.org/10.1007/978-3-030-83951-2_14
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