Öz
Amaç
Bu çalışmanın amacı, gerçek yaşam koşullarında romosozumab tedavisinin bir yıllık sürede kemik mineral yoğunluğu (KMY) ve T-skorları üzerindeki etkilerini Türk şiddetli osteoporoz kohortunda değerlendirmektir.
Gereç ve Yöntem
Bu tek merkezli retrospektif kesitsel çalışmada, Ekim 2023-Mart 2025 tarihleri arasında takip edilen 124 ardışık hasta tarandı, dışlama kriterlerini karşılayan 29 hasta çalışma dışı bırakıldı. Kalan 95 hasta, 12 ay boyunca aylık 210 mg romosozumab tedavisi almıştı. Lomber omurga (L1-L4 ve L2-L4), femur boynu ve total kalça bölgelerinde KMY ölçümleri dual enerjili X-ışını absorbsiyometri yöntemiyle başlangıçta, 6. ayda ve 12. ayda yapılmıştı. Grup içi değişimler Wilcoxon işaretli sıralar testi, bağımsız gruplar arası karşılaştırmalar Mann-Whitney U testi ile değerlendirildi.
Bulgular
Katılımcıların %89,5’i kadındı ve medyan yaş 73 yıldı. Başlangıçta L1-L4 bölgesinde medyan KMY 0,671 g/cm² (T-skoru -3,50) iken, 12. ayda 0,762 g/cm²’ye yükseldi (+%13,6; p<0,001). L2-L4 bölgesinde KMY 0,750 g/cm²’ye (+%14,9; p<0,001), femur boynunda 0,548 g/cm²’ye (+%4,9; p<0,001) ve total kalçada 0,668 g/cm²’ye (+%3,7; p<0,001) yükseldi. T-skoru artışları sırasıyla +0,47, +0,52, +0,11 ve +0,08 standart sapma birimi oldu. Artışlar cinsiyete veya önceki tedavi durumuna göre farklılık göstermedi (tüm p>0,05). Bir hastada çarpıntı nedeniyle tedavi sonlandırılmıştı; dokuz hastada (%9,5) nazofarenjit, enjeksiyon bölgesi reaksiyonu ve bel ağrısı gibi hafif advers olaylar bildirilmişti.
Sonuç
Gerçek yaşam verilerine dayalı bu 95 hastalık kohortta romosozumab, omurga ve kalça KMY’sinde hızlı ve klinik olarak anlamlı artışlar sağlamış, bu kazanımlar 12 ay boyunca korunmuş ve cinsiyet ya da önceki farmakoterapiden bağımsız olmuştur. Olumlu güvenlilik profili, şiddetli osteoporozu olan hastalarda romosozumab kullanımını desteklemektedir.
Anahtar Kelimeler:
Osteoporoz, romosozumab, kemik mineral yoğunluğu, retrospektif çalışmalar
Kaynaklar
1
Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013;24:23-57.
2
Sözen T, Özışık L, Başaran N. An overview and management of osteoporosis. Eur J Rheumatol. 2017;4:46-56.
3
Harvey N, Dennison E, Cooper C. Osteoporosis: impact on health and economics. Nat Rev Rheumatol. 2010;6:99-105.
4
Black DM, Rosen CJ. Clinical practice. Postmenopausal osteoporosis. N Engl J Med. 2016;374:254-62. Erratum in: N Engl J Med. ;374:1797.
5
Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. 2017;12:43.
6
Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological management of osteoporosis in postmenopausal women: an endocrine society* clinical practice guideline. J Clin Endocrinol Metab. 2019;104:1595-622.
7
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. J Bone Miner Res. 2018;33:1397-406.
8
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;377:1417-27.
9
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;375:1532-43.
10
Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Wong S, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med. 2018;379:2407-16.
11
Cooper C, Reginster JY, Cortet B, Diaz-Curiel M, Lorenc RS, Kanis JA, et al. Long-term treatment of osteoporosis in postmenopausal women: a review from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the International Osteoporosis Foundation (IOF). Curr Med Res Opin. 2012;28:475-91.
12
McCloskey EV, Harvey NC, Johansson H, Lorentzon M, Liu E, Vandenput L, et al. Fracture risk assessment by the FRAX model. Climacteric. 2022;25:22-8.
13
Kirazlı Y, Atamaz Çalış F, El Ö, Gökçe Kutsal Y, Peker Ö, Sindel D, et al. Updated approach for the management of osteoporosis in Turkey: a consensus report. Arch Osteoporos. 2020;15:137.
14
Prather C, Adams E, Zentgraf W. Romosozumab: a first-in-class sclerostin inhibitor for osteoporosis. Am J Health Syst Pharm. 2020;77:1949-56.
15
Baek KH, Chung YS, Koh JM, Kim IJ, Kim KM, Min YK, et al. Romosozumab in postmenopausal Korean women with osteoporosis: a randomized, double-blind, placebo-controlled efficacy and safety study. Endocrinol Metab (Seoul). 2021;36:60-9.
16
Lewiecki EM, Binkley N, Morgan SL, Shuhart CR, Camargos BM, Carey JJ, et al. Best practices for dual-energy X-ray absorptiometry measurement and reporting: international society for clinical densitometry guidance. J Clin Densitom. 2016;19:127-40.
17
Albano D, Agnollitto PM, Petrini M, Biacca A, Ulivieri FM, Sconfienza LM, et al. Operator-related errors and pitfalls in dual energy X-ray absorptiometry: how to recognize and avoid them. Acad Radiol. 2021;28:1272-86.
18
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. 2020;32:653-61.
19
Vestergaard Kvist A, Faruque J, Vallejo-Yagüe E, Weiler S, Winter EM, Burden AM. Cardiovascular safety profile of romosozumab: a pharmacovigilance analysis of the US food and drug administration adverse event reporting system (FAERS). J Clin Med. 2021;10:1660.
20
Gooden CK. Minor adverse events. In: Gooden CK, Lowrie L, Jackson BF, editors. The Pediatric Procedural Sedation Handbook. New York: Oxford; 2018.
21
Horikawa N, editor. Handling of adverse events and serious adverse events before and after treatment period in Clinical Trials. 2019.
22
Fonck S, Deserno T. Modeling an IT support for handling serious adverse events in clinical trials. Stud Health Technol Inform. 2017;245:1262.
23
Ishibashi H, Crittenden DB, Miyauchi A, Libanati C, Maddox J, Fan M, et al. Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: a phase 2 study. Bone. 2017;103:209-15.
24
Dilshani M, Jayasekara L, Liyanage G, Lekamwasam S. Effects of romosozumab on bone mineral density and fractures in postmenopausal women: a meta-analysis. Journal of the Ceylon College of Physicians. 2024;55:29-35.
25
Kobayakawa T, Suzuki T, Nakano M, Saito M, Miyazaki A, Takahashi J, et al. Real-world effects and adverse events of romosozumab in Japanese osteoporotic patients: a prospective cohort study. Bone Rep. 2021;14:101068.
26
Singh S, Dutta S, Khasbage S, Kumar T, Sachin J, Sharma J, et al. A systematic review and meta-analysis of efficacy and safety of romosozumab in postmenopausal osteoporosis. Osteoporos Int. 2022;33:1-12.
27
Anno S, Iida T, Yamada Y, Okano T, Sugioka Y, Inui K, et al. Pos1146 romosozumab increase bone mineral density at lumbar and femoral irrespective of preosteoporosis treatment, history of fragility fracture and combination of vitamin D. Annals of the Rheumatic Diseases. 2022;81:901.
28
Kanayama Y, Hattori K. AB1221 cliniclal efficacy of sequential treatment after romosozumab in patients with rheumatoid arthritis comparison with primary osteoporosis for 24 months. Annals of the Rheumatic Diseases. 2023;82:1837-8.
29
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;39:1082-90.
30
Mochizuki T, Yano K, Ikari K, Hiroshima R, Okazaki K. Comparison of romosozumab versus denosumab treatment on bone mineral density after 1 year in rheumatoid arthritis patients with severe osteoporosis: a randomized clinical pilot study. Mod Rheumatol. 2023;33:490-5.
31
Cosman F, Crittenden DB, Ferrari S, Lewiecki EM, Jaller-Raad J, Zerbini C, et al. Romosozumab FRAME study: a post hoc analysis of the role of regional background fracture risk on nonvertebral fracture outcome. J Bone Miner Res. 2018;33:1407-16.
32
Ebina K, Hirao M, Tsuboi H, Nagayama Y, Kashii M, Kaneshiro S, et al. Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis. Bone. 2020:115574.
33
Ravji P, Mcrorie M, Berg K, Ralston S, Hauser B. Pos0390 prior antiresorptive treatment reduces lumbar spine bmd response to romosozumab in caucasian postmenopausal women with severe osteoporosis. Annals of the Rheumatic Diseases. 2023;82(Suppl 1):450.
34
Ebina K, Tsuboi H, Nagayama Y, Kashii M, Kaneshiro S, Miyama A, et al. Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis. Joint Bone Spine. 2021;88:105219.
35
Mariscal G, Nuñez JH, Bhatia S, Barrios C, Domenech-Fernández P. Safety of romosozumab in osteoporotic men and postmenopausal women: a meta-analysis and systematic review. Monoclon Antib Immunodiagn Immunother. 2020;39:29-36.
36
Chen Z, Li M, Li S, Li Y, Wu J, Qiu K, et al. A pharmacovigilance analysis of FDA adverse event reporting system events for romosozumab. Expert Opin Drug Saf. 2023;22:339-42.
37
Bovijn J, Krebs K, Chen CY, Boxall R, Censin JC, Ferreira T, et al. Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics. Sci Transl Med. 2020;12:eaay6570.
38
Soen S, Wang A, Hamaya E, Chien HC, Lin TC. Drug utilization pattern of romosozumab and other osteoporosis treatments in Japan, 2019-2021. J Bone Miner Metab. 2024;42:653-67.
