KEMİĞİN PAGET HASTALIĞININ KLİNİK SEYRİNİN RETROSPEKTİF OLARAK DEĞERLENDİRİLMESİ

Abstract

Amaç: Kemiğin Paget hastalığı (KPH), fokal, kronik, metabolik bir kemik hastalığıdır ve kemik deformitesi, kırıklar ve kalp yetmezliği gibi komplikasyonlara neden olur. Bu çalışma, KPH hastalarının klinik özelliklerini ve hastaların antiresorptif tedavilere yanıtlarını değerlendirmeyi amaçladı. Gereç ve Yöntemler: Bu çalışmada İstanbul Tıp Fakültesi’nde KPH tanısı ile takip edilen ve antirezorptif tedavi uygulanan hastaların tıbbi kayıtları retrospektif olarak değerlendirildi. Bulgular: KPH olan toplam 26 hasta (12 kadın/14 erkek) değerlendirildi. Ortalama tanı yaşı 62.9±13.5 idi. Semptomların başlangıcından tanıya kadar geçen medyan süre 17.5 aydı (1-480 arası). Belirtilerden ağrı 16 hastada, şişlik 3 hastada, kızarıklık 2 hastada, kırık 1 hastada, nefrolitiazis 1 hastada, işitme kaybı 1 hastada mevcuttu. Laboratuvar incelemesinde ortalama alkalen fosfataz (ALP) 512±557 U/L, kemiğe özgü ALP 81.2±51.4 µg/L ve ALP üst limitin 4.12±4 katı idi. Hastalığın tutulum yerleri %58 pelvis, %46 vertebra, %35 kafatası, %23 femur, %11.5 tibia, %3.8 humerus şeklinde idi. Toplam 26 hastanın 21’i tek başına zoledronik asit ile tedavi edilmişti. Dört hastada nüks meydana geldi ve tedaviden nükse kadar geçen ortalama süre 72.25±28.7 aydı. Sonuç: Zoledronik asit çok güçlü bir antirezorptif ilaçtır ve tek doz tedavi ile bile hastalığın uzun süreli remisyonunu sağlar.

Keywords

• Kemiğin Paget hastalığı
• zoledronik asit
• alkalen fosfataz

RETROSPECTIVE EVALUATION OF THE CLINICAL COURSE OF PAGET’S DISEASE OF BONE

Abstract

Objective: Paget’s disease of bone (PDB) is a focal, chronic, metabolic disorder of bones and causes complications such as bone deformity, fractures, and heart failure. This study aimed to evaluate the clinical characteristics of patients with PDB and patients’ responses to antiresorptive treatments. Material and Methods: In the study, we retrospectively evaluated the medical records of patients who were followed up with PDB at the Istanbul Faculty of Medicine and treated with antiresorptive therapy. Results: A total of 26 patients (12 females/14 males) with PDB were evaluated. The mean age at diagnosis was 62.9±13.5 years. The median time from the onset of symptoms to diagnosis was 17.5 months (range 1-480). The symptoms were as follows: pain in 16, swelling in 3, rubor in 2, bone fracture in 1, nephrolithiasis in 1, and hearing loss in 1 patient. Laboratory tests revealed the following results (mean±SD); Alkaline phosphatase (ALP) 512±557 U/L, bone-specific ALP 81.2±51.4 µg/L, and the mean ALP was 4.12±4 times of upper limit of the normal range. The distribution of the disease was as follows: pelvis in 58%, vertebra in 46%, skull in 35%, femur in 23%, tibia in 11.5%, humerus in 3.8% of the patients. Of 26 patients, 21 were treated with zoledronic acid alone. Relapse occurred in four patients; the mean duration from therapy to relapse was 72.25±28.7 months. Conclusion: Zoledronic acid is a very potent antiresorptive drug and provides long-term remission of the disease even with a single dose of therapy.

Keywords

• Paget’s disease of bone
• zoledronic acid
• alkaline phosphatase

References

1. 1- Meunier PJ, Coindre JM, Edouard CM, Arlot ME. Bone histomorphometry in Paget’s disease. Quantitative and dynamic analysis of pagetic and nonpagetic bone tissue. Arthritis Rheum 1980;23(10):1095-103. google scholar
2. 2- Altman RD, Bloch DA, Hochberg MC, Murphy WA. Prevalence of pelvic Paget’s disease of bone in the United States. J Bone Miner Res 2000;15(3):461-5. google scholar
3. 3- Husseini JS, Oganesyan R, Staffa SJ, Huang E, Habibollahi S, Hemke R, et al. Prevalence of Paget’s disease of bone: review of consecutive abdominopelvic CT scans and literature. Acta Radiol 2023;64(3):1086-92. google scholar
4. 4- Cook MJ, Pye SR, Lunt M, Dixon WG, Ashcroft DM, O’Neill TW. Incidence of Paget’s disease of bone in the UK: evidence of a continuing decline. Rheumatology (Oxford) 2021;60(12):5668-76. google scholar
5. 5- Mays S. Archaeological skeletons support a northwest European origin for Paget’s disease of bone. J Bone Miner Res 2010;25(8):1839-41. google scholar
6. 6- Guanabens N, Garrido J, Gobbo M, Piga AM, del Pino J, Torrijos A, et al. Prevalence of Paget’s disease of bone in Spain. Bone 2008;43(6):1006-9. google scholar
7. 7- Reddy SV, Singer FR, Roodman GD. Bone marrow mononuclear cells from patients with Paget’s disease contain measles virus nucleocapsid messenger ribonucleic acid that has mutations in a specific region of the sequence. J Clin Endocrinol Metab 1995;80(7):2108-11. google scholar
8. 8- Hocking LJ, Herbert CA, Nicholls RK, Williams F, Bennett ST, Cundy T, et al. Genomewide search in familial Paget disease of bone shows evidence of genetic heterogeneity with candidate loci on chromosomes 2q36, 10p13, and 5q35. Am J Hum Genet 2001;69(5):1055-61. google scholar

9. 9- Cronin O, Subedi D, Forsyth L, Goodman K, Lewis SC, Keerie C, et al. Characteristics of early Paget’s disease in SQSTM1 mutation carriers: Baseline analysis of the ZiPP study cohort. J Bone Miner Res 2020;35(7):1246-52. google scholar
10. 10- Singer FR, Bone HG 3rd, Hosking DJ, Lyles KW, Murad MH, Reid IR et al. Endocrine Society. Paget’s disease of bone: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014;99(12):4408-22. google scholar
11. 11- Ralston SH, Corral-Gudino L, Cooper C, Francis RM, Fraser WD, Gennari L, et al. Diagnosis and Management of Paget’s Disease of Bone in Adults: A Clinical Guideline. J Bone Miner Res 2019;34(4):579-604. google scholar
12. 12- Reid IR, Lyles K, Su G, Brown JP, Walsh JP, del Pino-Montes J, el al. A single infusion of zoledronic acid produces sustained remissions in Paget disease: Data to 6.5 years. J Bone Miner Res 2011;26(9):2261-70. google scholar
13. 13- Tan A, Ralston SH. Clinical presentation of Paget’s disease: evaluation of a contemporary cohort and systematic review. Calcif Tissue Int 2014;95(5):385-92. google scholar
14. 14- Guyer PB. Paget’s disease of bone: the anatomical distribution. Metab Bone Dis Relat Res 1981;3(4-5):239-41. google scholar
15. 15- Hocking LJ, Lucas GJ, Daroszewska A, Mangion J, Olavesen M, Cundy T, et al. Domain specific mutations in Sequestosome 1 (SQSTM1) cause familial and sporadic Paget’s disease. Hum Mol Genet 2002;11(22):2735-9. google scholar
16. 16- Moscat J, Diaz-Meco MT. p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 2009;137(6):1001-4. google scholar
17. 17- Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med 2005;353(9):898-908. google scholar