Romatoid artritli hastalarda kemik mineral yoğunluğu ile RANKL, osteoprotegerin ve katepsin-K düzeyleri arasındaki ilişki

Öz

Amaç: Bu çalışmanın amacı Romatoid Artrit\'li (RA) hastalarda Osteoprotegerin (OPG), Nükleer faktör kappa B reseptör aktivatörü ligandı (RANKL), katepsin-K düzeylerini ve ayrıca bu parametrelerin kemik mineral yoğunluğu (BMD) ile ilişkisini araştırmaktır. Gereç ve yöntem: Çalışmaya postmenopozal sağlıklı (n=30), postmenopozal osteoporozlu (n=30) ve postmenopoz RA\'lı (n=30) toplam 90 olgu alındı. Serum RANKL, OPG ve katepsin-K ELİSA yöntemiyle çalışıldı. Bulgular: Postmenopozal RA\' lı hastalarda serum RANKL ve OPG seviyeleri postmenopozal sağlıklı kontrollere kıyasla anlamlı yüksekken, serum OPG/RANKL oranı anlamlı düşük bulundu. Bununla birlikte postmenopozal RA\'lı hastalarda, postmenopozal osteoporozlu hastalara göre serum OPG ve OPG/RANKL oranı anlamlı düşük iken, serum RANKL seviyesi anlamlı yüksekti. Postmenopozal RA\'lı hastalarda lomber spine (LS) ve femur neck (FN) kemik mineral dansiteleri (BMD) ile OPG/RANKL oranı arasında pozitif korelasyon saptanırken; RANKL düzeyleri ile negatif korelasyon bulundu. Sonuç: RANKL/RANK/OPG sistemi osteoporoz ve RA patogenezinde rol alabilmektedir ve OPG/RANKL oranı kemik dansitesinin önemli bir belirleyicisi olabilir.

Anahtar Kelimeler

• Osteoporoz, romatoid artrit, RANKL, OPG, Katepsin-K

The relationship between bone mineral density and levels of RANKL, osteoprotegerin and cathepsin-K in patients with rheumatoid arthritis

Öz

Objectives: The aim of this study was to evaluate the levels of osteoprotegerin (OPG), nuclear factor kappa B receptor activator ligand (RANKL), cathepsin K in patients with rheumatoid arthritis (RA) and the relation between these parameters and bone mineral density (BMD). Materials and methods: Totally 90 cases including 30 postmenopausal and healthy women, 30 with postmenopausal osteoporosis and 30 with postmenopause RA were enrolled in the study. The serum RANKL, OPG and cathepsin K were measured by ELISA method. Results: The levels of serum RANKL and OPG in the patients with postmenopausal RA were found significantly higher compared to the postmenopausal healthy women whereas the rate of serum OPG/RANKL was found significantly lower. In addition, the rate of OPG and OPG/RANKL were significantly lower in patients with postmenopausal RA compared to the postmenopausal osteoporosis, whereas the level of serum RANKL was significantly higher. Positive correlation was detected between bone densities of lumbar spine (LS), femur neck (FN) and the rate of OPG/RANKL in patients with postmenopausal RA. Also negative correlation was detected between LS and FN bone densities and RANKL levels. Conclusions: The system of RANKL/RANK/OPG may have a role in osteoporosis and RA pathogenesis and the rate of OPG/RANKL might be a significant determiner of bone density.

Anahtar Kelimeler

• Osteoporosis, rheumatoid arthritis, RANKL, OPG, cathepsin-K

Kaynakça

1. Armas LA, Recker RR. Pathophysiology of osteoporosis: new mechanistic insights. Endocrinol Metab Clin North Am 2012;41(3):475-86.
2. Delmas PD. The role of markers of bone turnover in the as- sesment of fracture risk in postmenopausal women. Osteo- poros Int 1998;8(S1):32-6.
3. Kurban S, Mehmetoğlu İ. Osteoprotegerin RANK and RANKL. Turk J Biochem 2007;32(3);178-84.
4. Kostenuik PJ, Shalhoub V. Osteoprotegerin: A Physiological and Pharmacological Inhibitor of Bone Resorption. Curr Pharm Des 2001;7(8):613-35.
5. Boyce BF, Xing L. Biology of RANK, RANKL, and osteo- protegerin. Arthritis Res Therap 2007;9(S1):1-7.
6. McClung M. Role of RANKL inhibition in osteoporosis. Ar- thritis Res Therap 2007;9 (S1):S3.
7. Vega D, Maalouf NM, Sakhaee K. The role of receptor ac- tivator of nuclear factor-kB (RANK)/RANK ligand/os- teoprotegerin: clinical implications. J Clinical Endocrinol Metab 2007;92(12):4514-21.
8. Romas E, Sims NA, Hards DK, et al. Osteoprotegerin re- duces osteoclast numbers and prevents bone erosion in col- lageninduced arthritis. Am J Pathol 2002;161(4):1419-27.

9. Gravallese EM, Manning C, Tsay A, et al. Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum 2000;43(2):250-8.
10. Baud’huin M, Lamoureuxa F, Duplomba L, et al. RANKL, RANK, osteoprotegerin: key partners of osteoimmünology and vascular diseases. Cell Mol Life Sci 2007;64(18):2334- 50.
11. Hou WS, Li Z, Gordon RE, et al. Cathepsin K is a critical protease in synovial fibroblast-mediated collagen degrada- tion. Am J Pathol 2001;159(6):2167-77.
12. Goto T, Yamaza T, Tanaka T. Cathepsins in the osteoclast. J Electron Microsc. 2003;52(6):551-8.
13. Rieman DJ, McClung HA, Dodds RA, et al. Biosynthesis and processing of cathepsin K in cultured human osteo- clasts. Bone 2001;28(3):282-9.
14. Arnett FC, Edworthy SM, Bloch DA, et al. The Ameri- can Rheumaıtism Association 1987 criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31(3):315-24.
15. Wong BR, Rho J, Arron J, et al. TRANCE is a novel li- gand of the tumor necrosis factor receptor family that ac- tivates c-Jun N-terminal kinase in T cells. J Biol Chem 1997;272(40):25190-4.
16. Haynes DR, Crotti TN, Capone M, et al. Osteoprote- gerin and receptor activator of nuclear factor kappaB li- gand (RANKL) regulate osteoclast formation by cells in the human rheumatoid arthritic joint. Rheumatology 2001;40(6):623-30.
17. Nosaka K, Miyamoto T, Sakai T, et al. Mechanism of hy- percalcemia in adult T-cell leukemia: overexpression of re- ceptor activator of nuclear factor jB ligand on adult T-cell leukemia cells. Blood 2002;99(2):634-40.
18. Haugeberg G, Uhlig T, Falch JA, et al. Bone mineral den- sity and frequency of osteoporosis in female patient with rheumatoid arthritis: result from 394 patients in the Olso county rheumatoid arthritis register. Arthritis Rheum 2000;43(3):522-30.
19. Urbanek R, Tlustochowicz W, Patola J, et al. Incidence of osteoporosis in patients with rheumatoid arthritis. Przegl Lek 2000;57(2):103-7.
20. Oelzner P, Franke S, Lehmann G, et al. Soluble recep- tor activator of NFkappa B-ligand and osteoprotegerin in rheumatoid arthritis relationship with bone mineral den- sity, disease activity and bone turnover. Clin Rheumatol 2007;26(12):2127-35.
21. Xu S, Wang Y, Lu J and Xu J. Osteoprotegerin and RANKL in the pathogenesis of rheumatoid arthritis-induced osteo- porosis. Rheumatol Int 2011,DOI 10.1007/s00296-011- 2175-5.
22. Lodder MC, De Jong Z, Kostense PJ, et al. Bone mineral density in patients with rheumatoid arthritis: relation be- tween disease severity and low bone mineral density. Ann Rheum Dis 2004;63(12):1576-80.
23. Cohen SB, Dore RK, Lane NE, et al. The Denosumab Rheu- matoid arthritis Study Group Denosumab treatment effects on structural damage, bone mineral density, and bone turn- over in rheumatoid arthritis: a twelvemonth, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 2008;58(5):1299-309.
24. Skoumal M, Kolarz G, Woloszczuk W, et al. Serum cathep- sin K levels of patients with destructive rheumatoid arthri- tis: correlation with radiological destruction. Arthritis Res Ther 2005;7(1):65-70.