Skip to main content

Advertisement

SpringerLink
Log in

A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis

  • Review
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

The study was conducted to illustrate the effect of Romosozumab in postmenopausal osteoporosis patients. Romosozumab decreased the incidence of vertebral, nonvertebral, and clinical fractures significantly. In addition, decreased incidence of falls and increased bone mineral density at lumbar spine, total hip, and femoral neck was observed. Romosozumab is a monoclonal antibody that acts against the sclerostin pathway leading to enhanced bone formation and reduced bone resorption in patients with osteoporosis. Electronic search was performed on Medline (via PubMed), The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov, till May 2020, for RCTs evaluating the effectiveness of Romosozumab in postmenopausal osteoporosis. RCTs evaluating the effect of Romosozumab on fractures and bone mineral density in postmenopausal osteoporosis patients. Meta-analysis was performed by Cochrane review manager 5 (RevMan) version 5.3. Cochrane risk of bias 2.0 tool and GRADE pro-GDT were applied for methodological quality and overall evidence quality, respectively. One hundred seventy-nine studies were screened, and 10 eligible studies were included in the analysis, with a total of 6137 patients in romosozumab group and 5732 patients in control group. Romosozumab significantly reduced the incidence of vertebral fractures [OR = 0.43 (95%CI = 0.35–0.52), High-quality evidence], nonvertebral fractures [OR = 0.78 (95%CI = 0.66–0.92), High quality], and clinical fractures [OR = 0.70 (95%CI = 0.60–0.82), High quality] at 24 months. Significant reduction in incidence risk of falls [OR = 0.87 (95%CI = 0.78–0.96), High quality] was observed with romosozumab. Bone mineral density was significantly increased in the romosozumab treated groups at lumbar spine [MD = 12.66 (95%CI = 12.66–12.67), High quality], total hip [MD = 5.69 (95%CI = 5.68 – 5.69), Moderate quality], and femoral neck [MD = 5.18 (95%CI = 5.18–5.19), Moderate quality] at 12 months. The total adverse events [RR = 0.98(95%CI = 0.96–1.01), Moderate quality] and serious adverse events [RR = 0.98(95%CI = 0.88–1.08), Moderate quality] with romosozumab were comparable to the control group. The current analysis with evidence on efficacy and safety of Romosozumab, authors opine to recommend the use of Romosozumab treatment for post-menopausal osteoporosis.

Systematic review registration: PROSPERO registration number: CRD42019112196

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on request.

Abbreviations

BPs:

Bisphosphonates

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO:

International Prospective Register of Systematic Reviews

ROMO:

Romosozumab

ROB-2:

The Risk of Bias -2 tool for randomized control trials

CI:

Confidence interval

OR:

Odd ratios

HR:

Hazard ratios

GRADE pro GDT:

Grades of Recommendations, Assessment, Development and Evaluations (GRADE) guideline development tool

OIS:

Optimal information size

vs:

Versus

References

  1. Osteoporosis prevention, diagnosis, and therapy (2001). Jama 285 785–795

  2. Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet (London, England) 377:1276–1287

    Article  CAS  Google Scholar 

  3. The International Osteoporosis Foundation (IOF) (2020) Facts & statistics. https://www.osteoporosis.foundation/facts-statistics Accessed Dec 12 2020

  4. Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136

    Article  CAS  Google Scholar 

  5. Compston JE, McClung MR, Leslie WD (2019) Osteoporosis. Lancet (London, England) 393:364–376

    Article  CAS  Google Scholar 

  6. Black DM, Rosen CJ (2016) Clinical Practice. Postmenopausal Osteoporosis. N Engl J Med 374:254–262

    Article  CAS  Google Scholar 

  7. Balemans W, Ebeling M, Patel N et al (2001) Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10:537–543

    Article  CAS  Google Scholar 

  8. Krause C, Korchynskyi O, de Rooij K et al (2010) Distinct modes of inhibition by sclerostin on bone morphogenetic protein and Wnt signaling pathways. J Biol Chem 285:41614–41626

    Article  CAS  Google Scholar 

  9. Brunkow ME, Gardner JC, Van Ness J et al (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

    Article  CAS  Google Scholar 

  10. Kanis JA, Cooper C, Rizzoli R, Reginster JY, on behalf of the Scientific Advisory Board of the European Society for C, Economic Aspects of O, the Committees of Scientific A, National Societies of the International Osteoporosis Foundation (2019) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 30:3–44

    Article  CAS  Google Scholar 

  11. Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D (2019) Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab 104:1595–1622

    Article  Google Scholar 

  12. Lim SY, Bolster MB (2017) Profile of romosozumab and its potential in the management of osteoporosis. Drug Des Dev Ther 11:1221–1231

    Article  CAS  Google Scholar 

  13. EVENITY 105 mg solution for injection in pre-filled pen Pharmacodynamic properties. https://www.medicines.org.uk/emc/product/10956#PHARMACODYNAMIC_PROPS Accessed Dec 12 2020

  14. Cosman F, Crittenden DB, Adachi JD et al (2016) Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 375:1532–1543

    Article  CAS  Google Scholar 

  15. Genant HK, Engelke K, Bolognese MA et al (2017) Effects of romosozumab compared with teriparatide on bone density and mass at the spine and hip in postmenopausal women with low bone mass. J Bone Miner Res 32:181–187

    Article  CAS  Google Scholar 

  16. 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

    Article  CAS  Google Scholar 

  17. Langdahl BL, Libanati C, Crittenden DB 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 (London, England) 390:1585–1594

    Article  CAS  Google Scholar 

  18. McClung MR, Grauer A, Boonen S et al (2014) Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 370:412–420

    Article  CAS  Google Scholar 

  19. Cosman F, Crittenden DB, Ferrari S, Khan A, Lane NE, Lippuner K, Matsumoto T, Milmont CE, Libanati C, Grauer A (2018) 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 Miner Res 33:1219–1226

    Article  CAS  Google Scholar 

  20. Shoback D, Rosen CJ, Black DM, Cheung AM, Murad MH, Eastell R (2020) Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society Guideline Update. J Clin Endocrinol Metab 105:587–594

    Article  Google Scholar 

  21. Sterne JA, Hernán MA, Reeves BC et al (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ (Clinical research ed) 355:i4919

    Google Scholar 

  22. McGuinness LA, Higgins JPT (2020) Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods 12(1):55–61

    Article  Google Scholar 

  23. Cochrane Training Cochrane Review Manager (RevMan). https://training.cochrane.org/online-learning/core-software-cochrane-reviews/revman Accessed Dec 12 2020

  24. Cochrane Training Cochrane Handbook for Systematic Reviews of Interventions. https://training.cochrane.org/cochrane-handbook-systematic-reviews-interventions Accessed Dec 12 2020

  25. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ (Clinical research ed) 327:557–560

    Article  Google Scholar 

  26. Kjaergard LL, Villumsen J, Gluud C (2001) Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 135:982–989

    Article  CAS  Google Scholar 

  27. Holger Schünemann JB, Gordon Guyatt, Andrew Oxman GRADE Handbook. https://gdt.gradepro.org/app/handbook/handbook.html#h.hnedbo8gqjqk Accessed Dec 12 2020

  28. ClinicalTrials.gov. National Library of Medicine (U.S.). (2018). A randomized phase 3 study to evaluate two formulations of romosozumab in postmenopausal women with osteoporosis. Identifier: NCT02016716. Retrieved 10 October, 2020 from https://clinicaltrials.gov/ct2/show/NCT02016716

  29. ClinicalTrials.gov. National Library of Medicine (U.S.). (2019). A safety and efficacy study to evaluate romosozumab (AMG 785) in South Korean women with osteoporosis. Identifier: NCT02791516. Retrieved 10 October, 2020 from https://clinicaltrials.gov/ct2/show/study/NCT02791516

  30. Padhi D, Allison M, Kivitz AJ, Gutierrez MJ, Stouch B, Wang C, Jang G (2014) 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 54:168–178

    Article  CAS  Google Scholar 

  31. Saag KG, Petersen J, Grauer A (2018) Romosozumab versus Alendronate and Fracture risk in women with osteoporosis. N Engl J Med 378:195–196

    PubMed  Google Scholar 

  32. 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

    Article  Google Scholar 

  33. 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

    Article  CAS  Google Scholar 

  34. McClung MR, Brown JP, Diez-Perez A et al (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

    Article  CAS  Google Scholar 

  35. Schemitsch EH, Miclau T, Karachalios T et al (2020) A randomized, placebo-controlled study of romosozumab for the treatment of hip fractures. J Bone Joint Surg Am 102:693–702

    Article  Google Scholar 

  36. Liu Y, Cao Y, Zhang S, Zhang W, Zhang B, Tang Q, Li Z, Wu J (2018) Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials. Climacteric 21:189–195

    Article  CAS  Google Scholar 

  37. Hernandez AV, Pérez-López FR, Piscoya A, Pasupuleti V, Roman YM, Thota P, Herrera A (2019) Comparative efficacy of bone anabolic therapies in women with postmenopausal osteoporosis: a systematic review and network meta-analysis of randomized controlled trials. Maturitas 129:12–22

    Article  CAS  Google Scholar 

  38. 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

    Article  CAS  Google Scholar 

  39. Möckel L, Bartneck M, Möckel C (2020) Risk of falls in postmenopausal women treated with romosozumab: preliminary indices from a meta-analysis of randomized, controlled trials. Osteoporosis Sarcopenia 6:20–26

    Article  Google Scholar 

  40. Kaveh S, Hosseinifard H, Ghadimi N, Vojdanian M, Aryankhesal A (2020) Efficacy and safety of Romosozumab in treatment for low bone mineral density: a systematic review and meta-analysis. Clin Rheumatol 39:3261–3276

    Article  Google Scholar 

  41. Chen W, Yang H, Jiang XJAoJ, (2020) Effects of romosozumab on low bone mineral density or osteoporosis in postmenopausal women: a systematic review. Ann Joint 5:18–18

    Article  Google Scholar 

  42. Mariscal G, Nuñez JH, Bhatia S, Barrios C, Domenech-Fernández P (2020) Safety of romosozumab in osteoporotic men and postmenopausal women: a meta-analysis and systematic review. Monoclonal antibodies in immunodiagnosis and immunotherapy 39:29–36

    Article  CAS  Google Scholar 

  43. EVENITY™ (romosozumab-aqqg) (2019) Prescribing information: Romosozumab. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761062s000lbl.pdf Accessed Dec 12 2020

Download references

Acknowledgements

We acknowledge GRADE Pro team [McMaster University and Evidence Prime Inc. available from: https://gradepro.org/] for letting us use the software for the synthesis and overall assessment and grading of systematic review.

Author information

Authors and Affiliations

  1. Department of Pharmacology, All India Institute of Medical Sciences, Rajasthan, 342005, Jodhpur, India

    S. Singh, S. Dutta, T. Kumar, J. Sachin, J. Sharma & S B Varthya

  2. Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, India

    S. Khasbage

Authors
  1. S. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Dutta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Khasbage
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Sachin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S B Varthya
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study design and planning of systematic review—All of the authors

Literature search—SD, SS

Figures—SS, SD, SK

Tables—JS, SK, SS

Data collection and analysis—SS, SBV

ROB—SD, SS, Query resolved by all authors

GRADE Analysis—SS Query resolved by all authors

Data interpretation—SS, SD, SK

Writing—SS, SD, TK

Corrections and Final approval of Manuscript—All of the authors

The corresponding author attests that all listed authors meet authorship criteria as per ICJME and that the manuscript is an honest, accurate, and transparent account of the study being reported.

Corresponding author

Correspondence to S. Dutta.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflicts of interest

None.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, S., Dutta, S., Khasbage, S. et al. A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis. Osteoporos Int 33, 1–12 (2022). https://doi.org/10.1007/s00198-021-06095-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-021-06095-y

Keywords

Search

Navigation