Abstract
Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It commonly occurs in older people, especially postmenopausal women. As global ageing increases, osteoporosis has become a global burden. There are a number of medications available for the treatment of osteoporosis, categorized as anabolic and anti-resorptive. Unfortunately, there is no drugs which have dual influence on bone, while all drugs have limitations and adverse events. Some serious adverse events include jaw osteonecrosis and atypical femoral fracture. Recently, a novel medication has appeared that challenges this pattern. Romosozumab is a novel drug monoclonal antibody to sclerostin encoded by the SOST gene. It has been used in Japan since 2019 and has achieved promising results in treating osteoporosis. However, it is also accompanied by some controversy. While it promotes rapid bone growth, it may cause serious adverse events such as cardiovascular diseases. There has been scepticism about the drug since its inception. Therefore, the present review comprehensively covered romosozumab from its inception to its clinical application, from animal studies to human studies, and from safety to cost. We hope to provide a better understanding of romosozumab for its clinical application.
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Background
Osteoporosis (OP) was a systemic bone disorder characterized by low bone mass, increased bone fragility, and fracture susceptibility defined in a consensus development conference in 1993 [1]. It has been a global burden for the elderly. Over 200 million people are thought to be affected by osteoporosis worldwide [2]. According to the International Osteoporosis Foundation, one in every three women over 50 years and one in every five men may have an osteoporotic fracture during their lifetimes [3]. Bone mass density (BMD) is recommended to diagnose OP. OP and osteopenia were defined as having a T score of BMD less than − 2.5 and between − 1 and − 2.5, respectively [1, 4]. Fracture Risk Algorithm (FRAX) scoring is commonly recommended to assess the risk of fractures [5, 6]. Bone turnover markers (BTMs) assess bone remodeling [7, 8]. The majority of bone osteoid is composed of type I collagen. Therefore, BTMs are associated with type I collagen activity. Type I collagen degradation (CTX‑I and NTX‑I) and synthesis (PICP and PINP) are widely used as bone resorption markers and formation markers, respectively [9]. The objectives of OP treatment are to increase bone mass and prevent fractures [10]. The drugs used to treat OP are classified as anabolic and anti-resorptive drugs [11, 12]. The anti-resorptive drugs include bisphosphonates, raloxifene, tibolone, and denosumab. The anabolic drugs include teriparatide (parathyroid (PTH) hormone analogue) and abaloparatide (human PTH hormone-related peptide analogue) [10]. Both anabolic and anti-resorptive drugs have their limitations and adverse effects [4]. Bisphosphonates, the first line treatment for OP, have an issue of drug holidays and atypical femoral fractures [13]. Raloxifene therapy increases the risk of venous thrombosis [14]. Tibolone users had twice the risk of stroke as controls [15]. Denosumab is an anti-resorptive drug, and its anti-resorptive effect rebounds rapidly after discontinuation [16]. It is generally accepted that OP treatment takes a long time. However, the use of anabolic drugs is restricted for up to 2 years due to serious adverse events [101].
Another 1-year romosozumab pre-post study was reported with 262 patients receiving romosozumab (210 mg s.c. Q4W) for 12 months. There were five new fractures reported, but no SAEs were reported. The mean percentage BMD change was 10.67% ± 0.8% (LS) and 2.04 ± 0.6% (TH), compared to the baseline at month 12. sNTX was − 3.70% (at month 1), 0.01% (at month 6), and 3.69% (at month 12) from baseline. iP1NP levels were higher at month 1 (77.34%), at month 6 (50.23%), and at month 12 (27.96%) [102].
The two pre-post studies demonstrated that romosozumab was safe and had a positive clinical effect. However, the follow-up period was short, and the sample size was small. More research is required in the future to comprehend romosozumab.
Conclusion
There is no doubt that romosozumab is a groundbreaking drug in treating OP due to its novel character of inhibiting bone resorption while promoting bone formation. Romosozumab reaffirms the immense value of biomedical applications. For OP patients with a high fracture risk, romosozumab may be more beneficial than other OP medications. In some ways, Romosozumab can replace traditional medications for osteoporosis. However, romosozumab is a new drug that will not only be available until 2019, there is still much room for research in OP. Simultaneously, can romosozumab accelerate delayed healing or ununion, treat secondary OP safely and treat bone tumors? Will other emerging technologies like nanotechnology hold significant potential to impact the field of osteoporosis treatment in the future [103]? Perhaps, there will be answers in the future.
Availability of data and materials
Not applicable.
Abbreviations
- PM:
-
Postmenopausal
- OP:
-
Osteoporosis
- BMD:
-
Bone marrow density
- BTMs:
-
Bone turnover markers
- LRP5/6:
-
Low-density lipoprotein-related receptors 5 and 6
- AE:
-
Adverse events
- SAE:
-
Serious adverse events
- AFF:
-
Atypical femoral fracture
- ONJ:
-
Jaw osteonecrosis
- LS:
-
Lumbar spine
- TH:
-
Total hip
- FN:
-
Femoral neck
- FRAME:
-
The Fracture Study in Postmenopausal Women with Osteoporosis
- STRUCTURE:
-
Open-Label Study to Evaluate the Effect of Treatment with Romosozumab or Teriparatide in Postmenopausal Women
- ARCH:
-
Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk
- BRIDGE:
-
Placebo-Controlled Double-Blind Study Evaluating the Efficacy and Safety of Romosozumab in treating Men with Osteoporosis
- s.c.:
-
Subcutaneously
References
Consensus Development Conference. Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993;94(6):646–50.
Reginster JY, Burlet N. Osteoporosis: a still increasing prevalence. Bone. 2006;38(2 Suppl 1):S4-9.
Sözen T, Özışık L, Başaran NÇ. An overview and management of osteoporosis. Eur J Rheumatol. 2017;4(1):46.
Compston JE, McClung MR, Leslie WD. Osteoporosis. The Lancet. 2019;393(10169):364–76.
Harvey N, Glüer C, Binkley N, McCloskey E, Brandi M-L, Cooper C, Kendler D, Lamy O, Laslop A, Camargos B. Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice. Bone. 2015;78:216–24.
Choksi P, Jepsen KJ, Clines GA. The challenges of diagnosing osteoporosis and the limitations of currently available tools. Clin Diabetes Endocrinol. 2018;4(1):1–13.
Jain S. Role of bone turnover markers in osteoporosis therapy. Endocrinol Metab Clin North Am. 2021;50(2):223–37.
Eyre DR. Bone biomarkers as tools in osteoporosis management. Spine. 1997;22(24):17S-24S.
Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012;8(7):379–89.
Reid IR, Billington EO. Drug therapy for osteoporosis in older adults. Lancet. 2022;399(10329):1080–92.
Khosla S, Hofbauer LC. Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol. 2017;5(11):898–907.
Zhou S, Huang G, Chen G. Synthesis and biological activities of drugs for the treatment of osteoporosis. Eur J Med Chem. 2020;197: 112313.
Russell RG. Bisphosphonates: the first 40 years. Bone. 2011;49(1):2–19.
D’Amelio P, Isaia GC. The use of raloxifene in osteoporosis treatment. Expert Opin Pharmacother. 2013;14(7):949–56.
Gambacciani M, Levancini M. Hormone replacement therapy and the prevention of postmenopausal osteoporosis. Menopause Review/Przegląd Menopauzalny. 2014;13(4):213–20.
Deeks ED. Denosumab: a review in postmenopausal osteoporosis. Drugs Aging. 2018;35:163–73.
Li S-S, He S-H, **e P-Y, Li W, Zhang X-X, Li T-F, Li D-F. Recent progresses in the treatment of osteoporosis. Front Pharmacol. 2021;12: 717065.
Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149(6):1192–205.
Wang Z, Liu C-H, Huang S, Chen J. Wnt Signaling in vascular eye diseases. Prog Retin Eye Res. 2019;70:110–33.
Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36(11):1461–73.
Mare A, D’Haese PC, Verhulst A. The role of sclerostin in bone and ectopic calcification. Int J Mol Sci. 2020;21(9):3199.
Miller PD, Adachi JD, Albergaria BH, Cheung AM, Chines AA, Gielen E, Langdahl BL, Miyauchi A, Oates M, Reid IR, et al. Efficacy and safety of romosozumab among postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. J Bone Miner Res. 2022;37(8):1437–45.
Lorentzon M. Treating osteoporosis to prevent fractures: current concepts and future developments. J Intern Med. 2019;285(4):381–94.
Wei FL, Gao QY, Zhu KL, Heng W, Du MR, Yang F, Gao HR, Li T, Qian JX, Zhou CP. Efficacy and safety of pharmacologic therapies for prevention of osteoporotic vertebral fractures in postmenopausal women. Heliyon. 2023;9(2): e11880.
Asadipooya K, Weinstock A. Cardiovascular outcomes of romosozumab and protective role of alendronate. Arterioscler Thromb Vasc Biol. 2019;39(7):1343–50.
Brandenburg VM, Verhulst A, Babler A, D’Haese PC, Evenepoel P, Kaesler N. Sclerostin in chronic kidney disease-mineral bone disorder think first before you block it! Nephrol Dial Transplant. 2019;34(3):408–14.
Balemans W, Van Den Ende J, Freire Paes-Alves A, Dikkers FG, Willems PJ, Vanhoenacker F, de Almeida-Melo N, Alves CF, Stratakis CA, Hill SC, et al. Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21. Am J Hum Genet. 1999;64(6):1661–9.
Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers F, Hildering P, Willems P. 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.
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.
Poole KE, Van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. 2005;19(13):1842–4.
Van Bezooijen RL, Roelen BA, Visser A, Van Der Wee-pals L, De Wilt E, Karperien M, Hamersma H, Papapoulos SE, Ten Dijke P, Löwik 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.
Semënov 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.
Cadigan KM. Wnt-β-catenin signaling. Curr Biol. 2008;18(20):R943–7.
Huang H, He X. Wnt/β-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol. 2008;20(2):119–25.
Song X, Wang S, Li L. New insights into the regulation of Axin function in canonical Wnt signaling pathway. Protein Cell. 2014;5(3):186–93.
Bienz M, Clevers H. Linking colorectal cancer to Wnt signaling. Cell. 2000;103(2):311–20.
Rim EY, Clevers H, Nusse R. The Wnt pathway: from signaling mechanisms to synthetic modulators. Annu Rev Biochem. 2022;91:571–98.
Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell. 2017;169(6):985–99.
Patel P, Woodgett JR. Glycogen synthase kinase 3: a kinase for all pathways? Curr Top Dev Biol. 2017;123:277–302.
Cheong JK, Virshup DM. Casein kinase 1: complexity in the family. Int J Biochem Cell Biol. 2011;43(4):465–9.
Stamos JL, Weis WI. The β-catenin destruction complex. Cold Spring Harb Perspect Biol. 2013;5(1): a007898.
Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destrée O, Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996;86(3):391–9.
Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann BG, Kemler R. Nuclear localization of β-catenin by interaction with transcription factor LEF-1. Mech Dev. 1996;59(1):3–10.
Daniels DL, Weis WI. β-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nat Struct Mol Biol. 2005;12(4):364–71.
Kenkre JS, Bassett J. The bone remodelling cycle. Ann Clin Biochem. 2018;55(3):308–27.
Allen MR, Burr DB. Bone modeling and remodeling. In: Basic and applied bone biology. Amsterdam: Elsevier; 2014. p. 75–90.
Lerner UH. Osteoblasts, osteoclasts, and osteocytes: unveiling their intimate-associated responses to applied orthodontic forces. In: Seminars in orthodontics. Amsterdam: Elsevier; 2012. p. 237–48.
Han Y, You X, **ng W, Zhang Z, Zou W. Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts. Bone Res. 2018;6:16.
Rutkovskiy A, Stensløkken K-O, Vaage IJ. Osteoblast differentiation at a glance. Med Sci Monit Basic Res. 2016;22:95.
Delgado-Calle J, Bellido T. New insights into the local and systemic functions of sclerostin: regulation of quiescent bone lining cells and beige adipogenesis in peripheral fat depots. J Bone Miner Res. 2017;32(5):889–91.
Kim J-M, Lin C, Stavre Z, Greenblatt MB, Shim J-H. Osteoblast-osteoclast communication and bone homeostasis. Cells. 2020;9(9):2073.
Al-Bari AA, Al Mamun A. Current advances in regulation of bone homeostasis. Faseb Bioadv. 2020;2(11):668.
Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003;22(23):6267–76.
Sutherland MK, Geoghegan JC, Yu C, Turcott E, Skonier JE, Winkler DG, Latham JA. Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formation. Bone. 2004;35(4):828–35.
Holdsworth G, Roberts SJ, Ke HZ. Novel actions of sclerostin on bone. J Mol Endocrinol. 2019;62(2):R167–85.
Ominsky MS, Boyce RW, Li X, Ke HZ. Effects of sclerostin antibodies in animal models of osteoporosis. Bone. 2017;96:63–75.
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.
Atkins GJ, Rowe PS, Lim HP, Welldon KJ, Ormsby R, Wijenayaka AR, Zelenchuk L, Evdokiou A, Findlay DM. Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism. J Bone Miner Res. 2011;26(7):1425–36.
Kovacs CS. The skeleton is a storehouse of mineral that is plundered during lactation and (Fully?) replenished afterwards. J Bone Miner Res. 2017;32(4):676–80.
Udagawa N, Koide M, Nakamura M, Nakamichi Y, Yamashita T, Uehara S, Kobayashi Y, Furuya Y, Yasuda H, Fukuda C, et al. Osteoclast differentiation by RANKL and OPG signaling pathways. J Bone Miner Metab. 2021;39(1):19–26.
Tu X, Delgado-Calle J, Condon KW, Maycas M, Zhang H, Carlesso N, Taketo MM, Burr DB, Plotkin LI, Bellido T. Osteocytes mediate the anabolic actions of canonical Wnt/β-catenin signaling in bone. Proc Natl Acad Sci USA. 2015;112(5):E478-486.
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.
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.
Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA. The laboratory rat as an animal model for osteoporosis research. Comp Med. 2008;58(5):424–30.
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 Miner Res. 2010;25(5):948–59.
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.
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.
Padhi D, Allison M, Kivitz AJ, Gutierrez MJ, Stouch B, Wang C, Jang G. 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(2):168–78.
Ishibashi H, Crittenden DB, Miyauchi A, Libanati C, Maddox J, Fan M, Chen L, Grauer A. Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: a phase 2 study. Bone. 2017;103:209–15.
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 Miner Res. 2018;33(8):1397–406.
Kendler DL, Bone HG, Massari F, Gielen E, Palacios S, Maddox J, Yan C, Yue S, Dinavahi RV, Libanati C, et al. Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab. Osteoporos Int. 2019;30(12):2437–48.
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.
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 Miner Res. 2019;34(3):419–28.
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.
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.
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.
Baek KH, Chung YS, Koh JM, Kim IJ, Kim KM, Min YK, Park KD, Dinavahi R, Maddox J, Yang W, et al. Romosozumab in postmenopausal Korean women with osteoporosis: a randomized, double-blind, placebo-controlled efficacy and safety study. Endocrinol Metab (Seoul). 2021;36(1):60–9.
Miyauchi A, Dinavahi RV, Crittenden DB, Yang W, Maddox JC, Hamaya E, Nakamura Y, Libanati C, Grauer A, Shimauchi J. Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension. Arch Osteoporos. 2019;14(1):59.
Lau EMC, Dinavahi R, Woo YC, Wu CH, Guan J, Maddox J, Tolman C, Yang W, Shin CS. Romosozumab or alendronate for fracture prevention in East Asian patients: a subanalysis of the phase III, randomized ARCH study. Osteoporos Int. 2020;31(4):677–85.
Chavassieux P, Chapurlat R, Portero-Muzy N, Roux JP, Garcia P, Brown JP, Libanati C, Boyce RW, Wang A, Grauer A. Bone-forming and antiresorptive effects of romosozumab in postmenopausal women with osteoporosis: bone histomorphometry and microcomputed tomography analysis after 2 and 12 months of treatment. J Bone Miner Res. 2019;34(9):1597–608.
Sato M, Inaba M, Yamada S, Emoto M, Ohno Y, Tsujimoto Y. Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study. J Bone Miner Metab. 2021;39(6):1082–90.
Bhandari M, Schemitsch EH, Karachalios T, Sancheti P, Poolman RW, Caminis J, Daizadeh N, Dent-Acosta RE, Egbuna O, Chines A, et al. Romosozumab in skeletally mature adults with a fresh unilateral tibial diaphyseal fracture: a randomized phase-2 study. J Bone Joint Surg Am. 2020;102(16):1416–26.
Schemitsch EH, Miclau T, Karachalios T, Nowak LL, Sancheti P, Poolman RW, Caminis J, Daizadeh N, Dent-Acosta RE, Egbuna O, et al. A randomized, placebo-controlled study of romosozumab for the treatment of hip fractures. J Bone Joint Surg Am. 2020;102(8):693–702.
Mochizuki T, Yano K, Ikari K, Okazaki K. Effects of romosozumab or denosumab treatment on the bone mineral density and disease activity for 6 months in patients with rheumatoid arthritis with severe osteoporosis: an open-label, randomized, pilot study. Osteoporos Sarcopenia. 2021;7(3):110–4.
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 Miner Res. 2018;33(7):1219–26.
Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwiński E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017;5(7):513–23.
Soreskog E, Lindberg I, Kanis JA, Akesson KE, Willems D, Lorentzon M, Strom O, Berling P, Borgstrom F. Cost-effectiveness of romosozumab for the treatment of postmenopausal women with severe osteoporosis at high risk of fracture in Sweden. Osteoporos Int. 2021;32(3):585–94.
Hagino H, Tanaka K, Silverman S, McClung M, Gandra SR, Charokopou M, Adachi K, Johnson B, Stollenwerk B. Cost effectiveness of romosozumab versus teriparatide for severe postmenopausal osteoporosis in Japan. Osteoporos Int. 2021;32(10):2011–21.
Papapoulos SE. Bone: Romosozumab—getting there but not quite yet. Nat Rev Endocrinol. 2016;12(12):691–2.
Rosen CJ. Romosozumab—promising or practice changing? N Engl J Med. 2017;377(15):1479–80.
Foulquier S, Daskalopoulos EP, Lluri G, Hermans KC, Deb A, Blankesteijn WM. WNT signaling in cardiac and vascular disease. Pharmacol Rev. 2018;70(1):68–141.
Chouinard L, Felx M, Mellal N, Varela A, Mann P, Jolette J, Samadfam R, Smith SY, Locher K, Buntich S, et al. Carcinogenicity risk assessment of romosozumab: a review of scientific weight-of-evidence and findings in a rat lifetime pharmacology study. Regul Toxicol Pharmacol. 2016;81:212–22.
Cosman: romosozumab treatment in postmenopausal osteoporosis. N Engl J Med. 2017;376(4):395–397.
Kawaguchi H. Serious adverse events with romosozumab use in Japanese patients: need for clear formulation of contraindications worldwide. J Bone Miner Res. 2020;35(5):994–5.
McClung MR, Bolognese MA, Brown JP, Reginster JY, Langdahl BL, Shi Y, Timoshanko J, Libanati C, Chines A, Oates MK. Skeletal responses to romosozumab after 12 months of denosumab. JBMR Plus. 2021;5(7): e10512.
Fuggle NR, Cooper C, Harvey NC, Al-Daghri N, Brandi ML, Bruyere O, Cano A, Dennison EM, Diez-Perez A, Kaufman JM, et al. Assessment of cardiovascular safety of anti-osteoporosis drugs. Drugs. 2020;80(15):1537–52.
Romosozumab versus alendronate and fracture risk in women with osteoporosis. N Engl J Med. 2018; 378(2):194–196.
Kim K-I, Park KU, Chun EJ, Choi SI, Cho Y-S, Youn T-J, Cho G-Y, Chae I-H, Song J, Choi D-J. A novel biomarker of coronary atherosclerosis: serum DKK1 concentration correlates with coronary artery calcification and atherosclerotic plaques. J Korean Med Sci. 2011;26(9):1178–84.
Cummings SR, McCulloch C. Explanations for the difference in rates of cardiovascular events in a trial of alendronate and romosozumab. Osteoporos Int. 2020;31(6):1019–21.
Markham A. Romosozumab: first global approval. Drugs. 2019;79(4):471–6.
Tominaga A, Wada K, Kato Y, Nishi H, Terayama Y, Okazaki K. Early clinical effects, safety, and appropriate selection of bone markers in romosozumab treatment for osteoporosis patients: a 6-month study. Osteoporos Int. 2021;32(4):653–61.
Tominaga A, Wada K, Okazaki K, Nishi H, Terayama Y, Kato Y. Early clinical effects, safety, and predictors of the effects of romosozumab treatment in osteoporosis patients: one-year study. Osteoporos Int. 2021;32(10):1999–2009.
Nasibova A. Generation of nanoparticles in biological systems and their application prospects. Adv Biol Earth Sci. 2023;8(2):140–6.
Acknowledgements
Thank for the support from Zhun Wen and Guangbin Wang.
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This work was financially supported by Natural Science Foundation of Liaoning Province (2021-MS-159).
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DW: Research literature and write original draft. LL: write partial original draft. ZW and GW: directed the overall project. This paper has been approved by all authors.
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Wu, D., Li, L., Wen, Z. et al. Romosozumab in osteoporosis: yesterday, today and tomorrow. J Transl Med 21, 668 (2023). https://doi.org/10.1186/s12967-023-04563-z
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DOI: https://doi.org/10.1186/s12967-023-04563-z