Mustafa ISİK, Ahmet TUTOGLU, Irfan KOCA, Yusuf Ziya IGCİ, Mehri IGCİ, Bulent GOGEBAKAN, Ahmet BOYACİ, Esra GEYİK

The effect of antiresorptive treatment on osteopontin values in osteoporosis

Amaç: Yüksek osteopontin (OPN) seviyelerinin kemik rezorpsiyonu ile ilişkili olduğu bildirilmiştir.Osteoporozda (OP) anabolik etki amacıyla uygulanan parathormonun, OPN düzeylerinde düşmeye nedenolduğu tespit edilmiştir. Bu çalışmanın amacı OP tedavisi için antirezorptif tedavi alan hastalarda OPNdüzeylerinin değerlendirilmesidir. Materyal ve metot: Çalışmamıza, 45-70 yaş arası, en az bir yıldır menopoza girmiş, OP tanısı alan 90 kadınhasta ve 80 sağlıklı kadın gönüllü dahil edildi. OP hastaları antirezorptif kullanan (60 hasta;15 bifosfonat, 15kalsitonin, 15 raloksifen, 15 strontium ranelate kullanan hasta) ve kullanmayanlar (30 hasta) olmak üzere ikigruba ayrıldı. Hastalara KMY ölçümü, DEXA (Dual Enerji X-Ray Absorbsiyometri) yöntemi ile yapıldı.Plazma OPN konsantrasyonu enzyme-link immunosorbent assay (ELISA) methodu kullanılarak hesaplandı.Bulgular: Antirezorptif kullanan OP grubunda OPN düzeyleri, antirezorptif almayan OP grubuna ve OPolmayan sağlıklı kontrol grubuna göre istatistiksel olarak anlamlı düzeyde daha düşüktü (sırasıyla p0.05).Sonuç: Sonuçlarımızın, antirezorptif tedavinin OPN seviyelerinde düşmeye neden olduğunu göstermesi,bize OPN'nin, antirezorptif tedavinin takibinde bir biomarker olarak kullanılabileceğini düşündürdü.

Osteoporozda antirezorptif tedavinin osteopontin değerleri üzerine etkisi

Background: An association between increased OPN levels and lowered bone mineral density (BMD) withincreased bone turnover markers was established. The aim of this study is to evaluate the levels of OPN in OPpatients who receive antiresorptive treatment (ART).Methods: Ninety female OP patients in the post-menopausal period for at least a year in the age range of 45 -70 years and 80 healthy female volunteers were included in the study. OP patients were divided into 2subgroups as ART-receiving (60 patients; bisphosphonate (15), calcitonin (15), raloxifene (15), strontiumranelate (15) and ART non-receiving (30 patients). Bone mineral density was analyzed using the dual energyX-ray absorptiometry method. The plasma OPN concentration was calculated using the enzyme-linkimmunosorbent assay method.Result s : OPN levels were significantly lower in antiresorptive-receiving OP patients compared to OPpatients who did not receive ART and compared to the control group (p0.05).Conclusions: Lowered OPN levels in ART-receiving OP patients suggest that OPN could be used as abiomarker in ART follow-up in OP.

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1) Sipos W, Pietschmann P, Rauner M, Kerschan-Schindl K, Patsch J. Pathophysiology of osteoporosis.Wien Med Wochenschr 2009;159 (2):230-4.
2) Vilela P, Nunes T. Osteoporosis. Neuroradiology 2011;53:185-9.
3) Sandhu SK, Hampson G. The pathogenesis, diagnosis, investigation and management of osteoporosis. J Clin Pathol 2011;64(3):1042-50.
4) Epstein S. Update of current therapeutic options for the treatment of postmenopausal osteoporosis. Clin Ther 2006;28(5):151-73.
5) Guyatt GH, Cranney A, Griffith L, Walter S, Krolicki N, Favus M, Rosen C. Summary of meta-analyses of therapies for postmenopausal osteoporosis and the relationship between bone density and fractures. Endocrine Rev 2002;23(4):570- 78.
6) Pols HA, Felsenberg D, Hanley DA, Stepan J, et al. Multinational, placebo- controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT Study. Foxamax International Trial Study Group. Osteoporos Int 1999;9(5):461-8.
7) Denhardt DT, Noda M. Osteopontin expression and function: role in bone remodeling. J Cell Biochem 1998;72(2):92-102.
8) Ihara H, Denhardt DT, Furuya K, et al. Parathyroid hormone-induced bone resorption does not occur in the absence of osteopontin. J Biol Chem 2001;276(3):13065-71.
9) Gögebakan B, Igci YZ, Arslan A, Igci M, Erturhan S, Oztuzcu S, et al. Association between the T-593A and C6982T polymorphisms of the osteopontin gene and risk of developing nephrolithiasis. Arch Med Res 2010;41(6):442-8.
10) Ohmori R. Plasma osteopontin levels are associated with the presence and extend of coronary artery disease. Atherosclerosis 2003;170(4):333-37.
11) Vordermark D, Said HM, Katzer A, et al. Plasma osteopontin levels in patients with head and neck cancer and cervix cancer are critically dependent on the choice of ELISA system. BMC Cancer 2006;6(2):207.
12) Chang IC, Chiang TI, Yeh KT, et al. Increased serum osteopontin is a risk factor for osteoporosis in menopausal women. Osteoporos Int 2010;21(4):1401-9.
13) Daniela F, Cosmina B, Adriana A, Siao-pin S, Alexandra C, Laura M. The Value of Osteopontin in the Assessment of Bone Mineral Density Status in Postmenopausal Women. J Investig Med 2013;61(4):15-21.
14) Chiang TI, Chang IC, Lee HS, et al. Osteopontin regulates anabolic effect in human menopausal osteoporosis with intermittent parathyroid hormone treatment. Osteoporos Int 2011;22(2):577-85.
15) Schneider DL, Morton DJ. Timing of postmenopausal estrogen for optimal bone mineral density. In The Management of The Menopause (ed): J Studd. Parthenon Publishing, New York, p.135,1998.
16) Hopkins RB, Goeree R, Pullenayegum E, Adachi JD, Papaioannou A, Xie F, et al. The relative efficacy of nine osteoporosis medications for reducing the rate of fractures in post-menopausal women. BMC Musculoskeletal Disorders 2011;12(4):209.
17) Dominquez LJ, Di Bella G, Belvedere M, Barbagallo M. Physiology of the aging bone and mechanisms of action of bisphosphonates. Biogerontology 2011;12(4):397-408.
18) Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, et al. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 2002;112(1):2819.
19) Sarkar S, Mitlak BH, Wong M, Stock JL, Black DM, Harper KD. Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 2002;17(4):110.
20) Watts NB, Geusens P, Barton IP, Felsenberg D. Relationship between changes in BMD and nonvertebral fracture incidence associated with risedronate: reduction in risk of nonvertebral fracture is not related to change in BMD. J Bone Miner Res 2005;20(2):2097104.
21) Chapurlat RD, Palermo L, Ramsay P, Cummings SR. Risk of fracture among women who lose bone density during treatment with alendronate. The Fracture Intervention Trial. Osteoporos Int 2005;16(3):8428.
22) Compston J. Monitoring osteoporosis treatment. Best Pract Res Clin Rheumatol 2009;23(6):781-8.
23) Miller PD. Monitoring osteoporosis therapies. Curr Osteoporos Rep 2007;5:38- 43.
24) Yoshitake H, Rittling SR, Denhardt DT, et al. Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption. Proc Natl Acad Sci U S A. 1999;96(2):8156-60.
25) Franze´n A, Hultenby K, Reinholt FP, et al. Altered osteoclast development and function in osteopontin deficient mice. J Orthop Res. 2008;26(2):721-8.
26) Shapses SA, Cifuentes M, Spevak L, Chowdhury H, Brittingham J, Boskey AL, Denhardt DT. Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency. Calcif Tissue Int 2003;73(1):8692.
27) Ishijima M, Tsuji K, Rittling SR, Yamashita T, Kurosawa H, Denhardt DT, Nifuji A, Ezura Y, Noda M Osteopontin is required for mechanical stress-dependent signals to bone marrow cells. J Endocrinol 2007;193(2):235243.
28) Kavukcuoglu NB, Denhardt DT, Guzelsu N, Mann AB. Osteopontin deficiency and aging on nanomechanics of Mouse bone. J Biomed Mater Res 2007;83(1):136144.
29) Duvall CL, Taylor WR, Weiss D, et al. Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice. J Bone Miner Res. 2007;22(1):286-97.
30) Hopkins RB, Goeree R, Pullenayegum E, Adachi JD, Papaioannou A, Xie F, et al. The relative efficacy of nine osteoporosis medications for reducing the rate of fractures in post-menopausal women. BMC Musculoskeletal Disorders 2011;12(4):209.
31) Bock O, Felsenberg D. Bisphosphonates in the management of postmenopausal osteoporosis- optimizing efficacy in clinical practice. Clin Interv Aging 2008;3(2):279-97.
32) Arlot ME, Jiang Y, Genant HK, Zhao J, Burt- Pichat B, Roux JP et al. Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res 2008;223(1):215-22.
33) Rittling SR, Matsumoto HN, McKee MD, et al. Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. J Bone Miner Res 1998;13(2):1101-11.
34) Vasikaran S, Eastell R, Bruyere O, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 2011;22(3):391- 420.