Osteoporozda Antirezorptif Tedavinin Osteopontin Değerleri Üzerine Etkisi
Amaç: Yüksek osteopontin (OPN) seviyelerinin kemik rezorpsiyonu ile ilişkili olduğu bildirilmiştir.
Osteoporozda (OP) anabolik etki amacıyla uygulanan parathormonun, OPN düzeylerinde düşmeye neden
olduğu tespit edilmiştir. Bu çalışmanın amacı OP tedavisi için antirezorptif tedavi alan hastalarda OPN düzeylerinin değerlendirilmesidir.
Materyal ve metot: Çalışmamıza, 45-70 yaş arası, en az bir yıldır menopoza girmiş, OP tanısı alan 90 kadın
hasta ve 80 sağlıklı kadın gönüllü dahil edildi. OPhastaları antirezorptif kullanan (60 hasta;15 bifosfonat, 15
kalsitonin, 15 raloksifen, 15 strontium ranelate kullanan hasta) ve kullanmayanlar (30 hasta) olmak üzere iki
gruba 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 OP
olmayan sağlıklı kontrol grubuna göre istatistiksel olarak anlamlı düzeyde daha düşüktü (sırasıyla p<0.001
ve p=0.008). OP olmayan sağlıklı kontrollerle ilaç kullanmayan OP grubunun OPN değerleri arasında
istatistiksel olarak anlamlı bir fark yoktu (p>0.05).
Sonuç: Sonuçlarımızın, antirezorptif tedavinin OPN seviyelerinde düşmeye neden olduğunu göstermesi,
bize OPN'nin, antirezorptif tedavinin takibinde bir biomarker olarak kullanılabileceğini düşündürdü.
The effect of antiresorptive treatment on osteopontin values in osteoporosis
Background: An association between increased OPN levels and lowered bone mineral density (BMD) with
increased bone turnover markers was established. The aim of this study is to evaluate the levels of OPN in OP
patients who receive antiresorptive treatment (ART).
Methods: Ninety female OPpatients 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 2
subgroups as ART-receiving (60 patients; bisphosphonate (15), calcitonin (15), raloxifene (15), strontium
ranelate (15) and ART non-receiving (30 patients). Bone mineral density was analyzed using the dual energy
X-ray absorptiometry method. The plasma OPN concentration was calculated using the enzyme-link
immunosorbent assay method.
Results: OPN levels were significantly lower in antiresorptive-receiving OP patients compared to OP
patients who did not receive ART and compared to the control group (p<0.001 and p=0.008 respectively).
There was no meaningful difference in terms of the OPN values between the controls and OP patients who
did not receive ART(p>0.05).
Conclusions: Lowered OPN levels in ART-receiving OP patients suggest that OPN could be used as a
biomarker in ARTfollow-up in OP.
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- 1) Sipos W, Pietschmann P, Rauner M,
Ke rs c h a n -Sc h i n d l K, Pa ts c h J.
Pathophysiology of osteoporosis.Wien
Med Wochenschr 2009;159 (2):230-4.
2) Vilela P, Nunes T. Osteoporosis.
Neuroradiology 2011;53:185-9.
3) S a n d h u S K , H amp s o n G . T h e
pathogenesis, diagnosis, investigation and
management of osteoporosis. J Clin Pathol
2011;64(3):1042-50.
4) Epstein S. Update of current therapeutic
o p t i o n s f o r t h e t r e a t m e n t o f
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, placebocontrolled, 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
r e m o d e l i n g . J C e l l B i o c h e m
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
o s t e o p o n t i n . J B i o l C h e m
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
E L I S A s y st e m . B M C C a n c e r
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
a n d m e c h a n is m s o f a c t i o n o f
bisphosphona t e s. Bioge rontology
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):281–9.
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):1–10.
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):2097–104.
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):842–8.
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
d e f i c i e n c y . C a l c i f T i s s u e I n t
2003;73(1):86–92.
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
m a r r o w c e l l s . J E n d o c r i n o l
2007;193(2):235–243.
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):136–144.
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-menopaus a l women. BMC
Musculoskeletal Disorders 2011;12(4):209.
31) Bock O, Felsenberg D. Bisphosphonates in the
management of postmenopausal osteoporosisoptimizing efficacy in clinical practice. Clin
Interv Aging 2008;3(2):279-97.
32) Arlot ME, Jiang Y, Genant HK, Zhao J, BurtPichat 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.