Romosozumab (sclerostin monoclonal antibody) for the treatment of osteoporosis in postmenopausal women: A review
Main Article Content
Keywords
osteoporosis, romosozumab, sclerostin, review
Abstract
Romosozumab (ROMO) (Brand name: EVENITY™), is a recently approved monoclonal antibody (U.S. FDA April 2019 and Health Canada June 2019) for the treatment of osteoporosis in postmenopausal women. ROMO works by selectively inhibiting sclerostin – a glycoprotein that inhibits osteoclasts and further promotes bone resorption. The authors reviewed three phase III clinical trials (FRAME, ARC, and STRUCTURE) that demonstrated ROMO’s ability to increase bone mineral density (BMD) at the lumbar spine and hip and reduces the risk of vertebral and clinical fractures. Additionally, clinical trials demonstrated the risk for serious cardiovascular events amongst patients that received ROMO and awaits further investigation. Although ROMO presents as a potentially exciting therapeutic with serious clinical implications, the authors recommend further analysis using real-world evidence (RWE) studies to fully elucidate the cardiovascular event risk associated with ROMO administration.
References
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2 Looker AC, Orwoll ES, Johnston CC, Lindsay RL, Wahner HW, Dunn WL et al. Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 1997; 12: 1761–8.
3 Kanis JA, Cooper C, Rizzoli R, Reginster JY. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Calcif Tissue Int 2019; 104: 235–238.
4 Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 2014; 29: 2520–2526.
5 U.S. Food and Drug Administration. FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture. 2019.https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-osteoporosis-postmenopausal-women-high-risk-fracture (accessed 23 Oct2019).
6 Health Canada. Evenity: Notice of Compliance information. 2019.https://health-products.canada.ca/noc-ac/info.do?lang=en&no=22291 (accessed 23 Oct2019).
7 Baron R, Rawadi G. Minireview: Targeting the Wnt/?-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 2007; 148: 2635–2643.
8 Poole KES, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 2005; 19: 1842–4.
9 van Bezooijen RL, Roelen BAJ, 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.
10 Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One 2011; 6: e25900.
11 Balemans W. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 2001; 10: 537–543.
12 Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, 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: 577–589.
13 Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 2002; 39: 91–97.
14 van Lierop AH, Hamdy NAT, van Egmond ME, Bakker E, Dikkers FG, Papapoulos SE. Van Buchem disease: clinical, biochemical, and densitometric features of patients and disease carriers. J Bone Miner Res 2013; 28: 848–54.
15 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.
16 Padhi D, Allison M, Kivitz AJ, Gutierrez MJ, Stouch B, Wang C et al. Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: a randomized, double-blind, placebo-controlled study. J Clin Pharmacol 2014; 54: 168–78.
17 Markham A. Romosozumab: First Global Approval. Drugs 2019; 79: 471–476.
18 Lim S, Bolster M. Profile of romosozumab and its potential in the management of osteoporosis. 2017; : 1221–1231.
19 Amgen. Romosozumab (EvenityTM): FDA prescribing information. 2019www.fda.gov/medwatch. (accessed 24 Oct2019).
20 Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 2016; 375: 1532–1543.
21 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: 1417–1427.
22 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. Lancet 2017; 390: 1585–1594.
23 Roudier M, Li X, Niu Q-T, Pacheco E, Pretorius JK, 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.
24 Kim DH, Rogers JR, Fulchino LA, Kim CA, Solomon DH, Kim SC. Bisphosphonates and risk of cardiovascular events: A meta-analysis. PLoS One 2015; 10. doi:10.1371/journal.pone.0122646.
25 Gay A, Towler DA. Wnt signaling in cardiovascular disease: Opportunities and challenges. Curr. Opin. Lipidol. 2017; 28: 387–396.
26 Sølling ASK, Harsløf T, Langdahl B. The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis. Ther. Adv. Musculoskelet. Dis. 2018; 10: 105–115.
27 Frieden TR. Evidence for Health Decision Making — Beyond Randomized, Controlled Trials. N Engl J Med 2017; 377: 465–475.
28 Camm AJ, Fox KAA. Strengths and weaknesses of ‘real-world’ studies involving non-vitamin K antagonist oral anticoagulants. Open Hear 2018; 5: e000788.
2 Looker AC, Orwoll ES, Johnston CC, Lindsay RL, Wahner HW, Dunn WL et al. Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 1997; 12: 1761–8.
3 Kanis JA, Cooper C, Rizzoli R, Reginster JY. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Calcif Tissue Int 2019; 104: 235–238.
4 Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 2014; 29: 2520–2526.
5 U.S. Food and Drug Administration. FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture. 2019.https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-osteoporosis-postmenopausal-women-high-risk-fracture (accessed 23 Oct2019).
6 Health Canada. Evenity: Notice of Compliance information. 2019.https://health-products.canada.ca/noc-ac/info.do?lang=en&no=22291 (accessed 23 Oct2019).
7 Baron R, Rawadi G. Minireview: Targeting the Wnt/?-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 2007; 148: 2635–2643.
8 Poole KES, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 2005; 19: 1842–4.
9 van Bezooijen RL, Roelen BAJ, 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.
10 Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One 2011; 6: e25900.
11 Balemans W. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 2001; 10: 537–543.
12 Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, 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: 577–589.
13 Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 2002; 39: 91–97.
14 van Lierop AH, Hamdy NAT, van Egmond ME, Bakker E, Dikkers FG, Papapoulos SE. Van Buchem disease: clinical, biochemical, and densitometric features of patients and disease carriers. J Bone Miner Res 2013; 28: 848–54.
15 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.
16 Padhi D, Allison M, Kivitz AJ, Gutierrez MJ, Stouch B, Wang C et al. Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: a randomized, double-blind, placebo-controlled study. J Clin Pharmacol 2014; 54: 168–78.
17 Markham A. Romosozumab: First Global Approval. Drugs 2019; 79: 471–476.
18 Lim S, Bolster M. Profile of romosozumab and its potential in the management of osteoporosis. 2017; : 1221–1231.
19 Amgen. Romosozumab (EvenityTM): FDA prescribing information. 2019www.fda.gov/medwatch. (accessed 24 Oct2019).
20 Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 2016; 375: 1532–1543.
21 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: 1417–1427.
22 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. Lancet 2017; 390: 1585–1594.
23 Roudier M, Li X, Niu Q-T, Pacheco E, Pretorius JK, 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.
24 Kim DH, Rogers JR, Fulchino LA, Kim CA, Solomon DH, Kim SC. Bisphosphonates and risk of cardiovascular events: A meta-analysis. PLoS One 2015; 10. doi:10.1371/journal.pone.0122646.
25 Gay A, Towler DA. Wnt signaling in cardiovascular disease: Opportunities and challenges. Curr. Opin. Lipidol. 2017; 28: 387–396.
26 Sølling ASK, Harsløf T, Langdahl B. The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis. Ther. Adv. Musculoskelet. Dis. 2018; 10: 105–115.
27 Frieden TR. Evidence for Health Decision Making — Beyond Randomized, Controlled Trials. N Engl J Med 2017; 377: 465–475.
28 Camm AJ, Fox KAA. Strengths and weaknesses of ‘real-world’ studies involving non-vitamin K antagonist oral anticoagulants. Open Hear 2018; 5: e000788.
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Published
Jan 6, 2020
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How to Cite
Shakeri, A., & Adanty, C. (2020). Romosozumab (sclerostin monoclonal antibody) for the treatment of osteoporosis in postmenopausal women: A review. Journal of Population Therapeutics and Clinical Pharmacology, 27(1), e25-e31. https://doi.org/10.15586/jptcp.v27i1.655
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