OSTEOGENEZİS İMPERFEKTALI ÇOCUKLARDA PAMİDRONAT TEDAVİSİNİN BOY, KEMİK MİNERAL YOĞUNLUĞU, KIRIK SIKLIĞI VE KABA MOTOR BECERİLERE ETKİSİ

Year 2023, , 313 - 320, 31.08.2023

Yağmur Ünsal

https://doi.org/10.24938/kutfd.1331912

Abstract

Amaç: Osteogenezis imprefekta (Oİ), kemik mikromimari bozukluğu nedeniyle osteopeni ve tekrarlayan kemik kırıklarının görüldüğü genetik, sistemik bağ doku hastalığıdır. Oİ’nin tedavisinde bisfosfonat grubu (pamidronat, zoledronik asit (ZA)) antirezorptif ilaçlar kullanılır. Bu çalışmada klinik olarak Oİ tanısı alan 16 olguda pamidronat tedavisinin boy, kemik mineral içeriği (KMİ) ve kemik mineral yoğunluğu (KMY), vertebra kırıkları, vertebra dışı kırıklar ve kaba motor alandaki becerilere etkisinin incelenmesi amaçlanmıştır.

Gereç ve Yöntemler: Şubat 2022-Temmuz 2023 arasında Şanlıurfa Eğitim ve Araştırma Hastanesi çocuk endokrinoloji polikliniğinde izlenen ve Oİ tanısı alan 16 olgu (K/E=5/11) retrospektif olarak incelendi. Tıbbi geçmiş, antropometrik ölçümler, laboratuvar, radyolojik ve genetik incelemeler kaydedildi, olgular Sillence sınıflamasına göre gruplandırıldı.

Bulgular: Olguların 14’ü tip III Oİ, 2’si tip I Oİ’ydi. Tip III Oİ ile izlenen olgular daha erken (0.4±0.5 yaş) tanı almıştı; 7.4±2.2 yıl izlenen olgular son kontrolde 7.9±1.8 yaşındaydı. Tip III olgular in-utero kırık (5/14), yaşamın ilk altı ayında tekrarlayan kırık (9/14), kardeşinde Oİ öyküsü (3/14) ile getirilmişti. 13’ü pamidronat, 3’ü zoledronik asit kullanan olguların tedaviyle boy SDS’sinde (önce: -4.2±0.5/son kontrol: -3.9±0.6) ve vücut kitle indeksi SDS’inde anlamlı değişim olmadı (p=0.09, p=0.08).

Pamidronat tedavisi alan tip III Oİ’li olgularda KMİ ve KMD yaşa göre düşük olsa da yaşla birlikte KMİ ve KMY kazanımı gerçekleşti. Kemik mineral içeriği en fazla 5 yaşında kazanıldı. Vertebra dışı kırık sayısı tedavinin birinci yılında anlamlı derecede azaldı (sırasıyla 6.8±1.3 kırık/yıl, 2.4±1.2 kırık/yıl) (p=0.001); azalma son kontrolde de devam etti.

Sonuç: Pamidronat tedavisi alan Oİ’li olgular kendi büyüme eğrilerinde büyümeye devam eder; belirgin boy persentili kazanımı olmasa da yaşa ve cinsiyete uygun büyüme hızı sağlanır; boy persentili kaybı engellenir. Tip III Oİ’li olgularda pamidronat tedavisi KMİ ve KMY’de belirgin artışı, vertebra dışı kırıklarda belirgin azalmayı, kaba motor alanda yeti kazanımını sağlayarak bağımsız hareket edebilmeyi sağlar.

Keywords

Osteogenezis imperfekta, pamidronat, tedavi yanıtı, kemik mineral yoğunluğu, vertebra dışı kırıklar, kaba motor beceriler

Supporting Institution

Çalışmaya ilişkin hiçbir kurum ya da kişiden finansal destek alınmamıştır.

Project Number

Çalışmaya ilişkin hiçbir kurum ya da kişiden finansal destek alınmamıştır.

Thanks

Çalışmaya katılmayı kabul eden hasta ve ailelerine teşekkür ederiz.

Impact of Pamidronate on Height, Bone Mineral Density, Fracture Rate and Gross Motor Function Among Children with Osteogenesis Imperfecta

Abstract

Objective: Osteogenesis imperfecta (OI) is a genetic, systemic connective tissue disease characterized by osteopenia and recurrent bone fractures. Bisphosphonates (pamidronate and zoledronic acid (ZA)) are antiresorptives used in OI. The aim of this study is to evaluate the impact of pamidronate on height, bone mineral content (BMC), bone mineral density (BMD), vertebral and non-vertebral fractures as well as gross motor functions among children with OI.

Material and Methods: 16 patients (F/M=5/11) with OI followed in Şanlıurfa Training and Research Hospital between February 2022-July 2023 were retrospectively evaluated . Medical history, anthropometric measures, laboratory, radiologic and genetic results were recorded, and patients were grouped according to Sillence classification.

Results: 14 were type III OI while 2 were type I OI. Type III OI was diagnosed earlier (0.4±0.5 years). After 7.4±2.2 years of follow-up, patients were 7.9±1.8 years old on the last last examination. Patients with type III OI were diagnosed due to inutero fractures (5/14), recurrent fractures in the first six months (9/14) or a sibling diagnosed with OI (3/14). 13 used pamidronate while 3 used ZA. Height SDS (before: -4.2±0.5/last examination: -3.9±0.6) and body mass index remained unchanged (p=0.09, p=0.08).When type III OI was investigated, although BMC and BMD were low for age and gender, a gain in total BMC and BD was obtained with age. The highest gain was achieved in fifth year. Non-vertebral fractures decreased dramatically in the first year of treatment (6.8±1.3 fracture/year vs 2.4±1.2 fracture/year) (p=0.001); this reduction was sustained until last examination.

Conclusion: Although significant height gain and catch-up growth were not observed in OI who are on pamidronate, growth rate consistent with peers was achieved and height percentile loss was prevented. Pamidronate ensures a significant increase in BMC, BMD and gross motor function and reduction of non-vertebral fractures enabling independent mobilization.

Keywords

Osteogenesis imperfecta, pamidronate, treatment response, bone mineral density, non-vertebral fractures, gross motor function

Project Number

Çalışmaya ilişkin hiçbir kurum ya da kişiden finansal destek alınmamıştır.

References

• Marom R, Rabenhorst BM, Morello R. Osteogenesis imperfecta: An update on clinical features and therapies. Eur J Endocrinol. 2020;183(4):R95-R106.
• Forlino A, Marini JC. Osteogenesis imperfecta. Lancet. 2016;387(10028):1657-71.
• Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S et al. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: Regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 2007;28(3):209-21.
• Essawi O, Symoens S, Fannana M, Darwish M, Farraj M, Willaert A et al. Genetic analysis of osteogenesis imperfecta in the Palestinian population: Molecular screening of 49 affected families. Mol Genet Genomic Med. 2018;6(1):15-26.
• Liu Y, Asan, Ma D, Lv F, Xu X, Wang J et al. Gene mutation spectrum and genotype-phenotype correlation in a cohort of Chinese osteogenesis imperfecta patients revealed by targeted next generation sequencing [published correction appears in Osteoporos Int. 2018 Jan;29(1):261]. Osteoporos Int. 2017;28(10):2985-95.
• Rauch F, Lalic L, Roughley P, Glorieux FH. Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. Eur J Hum Genet. 2010;18(6):642-7.
• Ralston SH, Gaston MS. Management of osteogenesis Imperfecta. Front Endocrinol (Lausanne). 2020;10:924.
• Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2014;(7):CD005088.
• Palomo T, Fassier F, Ouellet J, Sato A, Montpetit K, Glorieux FH et al. Intravenous bisphosphonate therapy of young children with osteogenesis ımperfecta: Skeletal findings during follow up throughout the growing years. J Bone Miner Res. 2015;30(12):2150-7.
• Plotkin H, Rauch F, Bishop NJ, Montpetit K, Ruck-Gibis J, Travers R et al. Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab. 2000;85(5):1846-50.
• Cintas HL, Siegel KL, Furst GP, Gerber LH. Brief assessment of motor function: Reliability and concurrent validity of the gross motor scale. Am J Phys Med Rehabil. 2003;82(1):33-41.
• İstatistiklerle Aile, 2022. Erişim: 17 Temmuz 2023. https://data.tuik.gov.tr/Bulten/Index?p=Istatistiklerle-Aile-2022-49683#:~:text=Akraba%20evlili%C4 %9Fi%20oran%C4%B1%202022%20y%C4%B1l%C4%B1nda,%253%2C9%20oldu%C4%9Fu%20g%C3%B6r%C3%BCld%C3%BC.
• T Tüysüz B, Elkanova L, Uludağ Alkaya D, Güleç Ç, Toksoy G et al. Osteogenesis imperfecta in 140 Turkish families: Molecular spectrum and, comparison of long-term clinical outcome of those with COL1A1/A2 and biallelic variants. Bone. 2022;155:116293.
• Zeitlin L, Rauch F, Plotkin H, Glorieux FH. Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adoles- cents with osteogenesis imperfecta types I, III, and IV, Pediatrics. 2003;111(5 Pt 1):1030-6.
• DiMeglio LA, Peacock M. Two‐year clinical trial of oral alendronate versus intravenous pamidronate in children with osteogenesis imperfecta. J Bone Miner Res. 2006;21(1):132-40.
• Letocha AD, Cintas HL, Troendle JF, Reynolds JC, Cann CE, Chernoff EJ et al. Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement. J Bone Miner Res. 2005;20(6):977-86.
• Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2014;7:CD005088.
• Marini JC. Should children with osteogenesis imperfecta be treated with bisphosphonates? Nat Clin Pract Endocrinol Metab. 2006;2(1):14-15.
• Phillipi CA, Remmington T, Steiner RD. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2008;8(4):CD005088.
• Montpetit K, Dahan-Oliel N, Ruck-Gibis J, Fassier F, Rauch F, Glorieux F. Activities and participation in young adults with osteogenesis imperfecta. J Pediatr Rehabil Med. 2011;4:13-22.
• Constantino CS, Krzak JJ, Fial AV, Kruger KM, Rammer JR, Radmanovic K et al. Effect of bisphosphonates on function and mobility among children with osteogenesis ımperfecta: A systematic review. JBMR Plus. 2019;3(10):e10216.
• Li LJ, Zheng WB, Zhao DC, Yu W, Wang O, Jiang Y et al. Effects of zoledronic acid on vertebral shape of children and adolescents with osteogenesis imperfecta. Bone. 2019;127:164-171.
• Mahmoud I, Bouden S, Sahli M, Rouached L, Ben Tekaya A, Tekaya R et al. Efficacy and safety of intravenous Zolidronic acid in the treatment of pediatric osteogenesis imperfecta: A systematic review. J Pediatr Orthop B. 2023;10.1097/BPB.0000000000001104.