Evaluation of the relationship between inflammation and bone turnover by sclerostin and Dickkopf-1 (DKK-1) levels in patients with SIRS

Hatice Betül Altınışık; Uğur Altınışık; Mehmet Aşık

doi:10.22391/fppc.1102573

Research Article

Evaluation of the relationship between inflammation and bone turnover by sclerostin and Dickkopf-1 (DKK-1) levels in patients with SIRS

Year 2022, Volume: 7 Issue: 3, 77 - 83, 31.07.2022

Hatice Betül Altınışık Uğur Altınışık Mehmet Aşık

https://doi.org/10.22391/fppc.1102573

Abstract

Introduction: In intensive care units (ICU), patients remain bedridden for a long time. In addition, severe infections are frequently seen in ICUs. Both prolonged immobilization and serious infections are associated with bone tissue loss. The Wnt pathway has recently been focused on evaluating bone tissue loss. The Wnt pathway participates in both infections and the formation of bone tissue. Wnt pathway inhibitors sclerostin and Dickkopf-1 (DKK-1) inhibit bone formation and increase osteoclastic activity. In this study, we aimed to examine bone turnover by the Wnt inhibitors sclerostin and DKK-1 and their possible associations with inflammation in SIRS patients.

Methods: We included 30 patients diagnosed with systemic inflammatory response syndrome (SIRS) in the study group and 16 in the control group. Serum sclerostin, DKK-1, white blood cell (WBC), and C-Reactive Protein (CRP) levels on the day of SIRS diagnosis (basal), the 7th, 14th, and 21stdays were evaluated in the study group, and the results were compared with the control group.

Results: When the control group was compared with the basal SIRS, there was a significant elevation in both sclerostin (p=0.003) and DKK-1 (p=0.001). Statistical analysis showed significant decreases in sclerostin levels between basal and the 7th, 14th, and 21st days (p=0.033, p=0.003, p=0.002, respectively). Similarly, significant decreases in DKK-1 levels between basal and the 7th and 21st days (p=0.015, p=0.001, respectively) and an insignificant decrease on the 14th day (p=0.191) was observed. Sclerostin was positively and significantly correlated with WBC and CRP in basal and 7th-day measurements and WBC in 7th and 14th days. DKK-1 is positively and significantly correlated with WBC in basal and 7th-daymeasurements, while DKK-1 negatively correlates with CRP in basal-7th-day measurements.

Conclusion: In this study, it was shown for the first time that the Wnt antagonists sclerostin and DKK-1 values are high in SIRS patients in ICU. Both biomarker levels decreased in parallel with the treatment. However, it could not be associated with disease severity and inflammatory marker levels. We believe that monitoring the change of Wnt antagonists will be useful in demonstrating bone turnover in patients with SIRS.

Keywords: Dickkopf-1, Intensive care unit, Sclerostin, Systemic inflammatory response syndrome, Wnt signaling pathway, Bone turnover

Keywords

Dickkopf-1, Intensive care unit, Sclerostin, Systemic inflammatory response syndrome, Wnt signaling pathway, Bone turnover

Supporting Institution

This study was supported by Çanakkale Onsekiz Mart University Scientific Research Project Unit (Project number: TSA-2015-516).

Project Number

TSA-2015-516

Thanks

The authors thank all patients who participated in this study and the Çanakkale Onsekiz Mart University Scientific Research Project Unit.

References

1. Uhthoff HK, Jaworski ZF. Bone loss in response to long-term immobilisation. J Bone Joint Surg Br. 1978;60-B(3):420-9. https://doi.org/10.1302/0301-620X.60B3.681422.
2. Sievänen H. Immobilization and bone structure in humans. Arch Biochem Biophys. 2010;503(1):146-52. https://doi.org/10.1016/j.abb.2010.07.008
3. Grimm G, Vila G, Bieglmayer C, Riedl M, Luger A, Clodi M. Changes in osteopontin and in biomarkers of bone turnover during human endotoxemia. Bone. 2010;47(2):388-91. https://doi.org/10.1016/j.bone.2010.04.602.
4. Tella SH, Gallagher JC. Biological agents in management of osteoporosis. Eur J Clin Pharmacol. 2014;70(11):1291-301. https://doi.org/10.1007/s00228-014-1735-5.
5. Ramli FF, Chin KY. A review of the potential application of osteocyte-related biomarkers, fibroblast growth factor-23, sclerostin, and Dickkopf-1 in predicting osteoporosis and fractures. Diagnostics (Basel). 2020;10(3):145. https://doi.org/10.3390/diagnostics10030145.
6. Colaianni G, Brunetti G, Faienza MF, Colucci S, Grano M. Osteoporosis and obesity: Role of Wnt pathway in human and murine models. World J Orthop. 2014;5(3):242-6. https://doi.org/10.5312/wjo.v5.i3.242.
7. Gifre L, Ruiz-Gaspà S, Monegal A, Nomdedeu B, Filella X, Guañabens N, et al. Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone. 2013;57(1):272-6. https://doi.org/10.1016/j.bone.2013.08.016.
8. Belavý DL, Baecker N, Armbrecht G, Beller G, Buehlmeier J, Frings-Meuthen P, et al. Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest. J Bone Miner Metab. 2016;34(3):354-65. https://doi.org/10.1007/s00774-015-0681-3.
9. Shahnazari M, Wronski T, Chu V, Williams A, Leeper A, Stolina M, et al. Early response of bone marrow osteoprogenitors to skeletal unloading and sclerostin antibody. Calcif Tissue Int. 2012;91(1):50-8. https://doi.org/10.1007/s00223-012-9610-9.
10. Kobayashi Y, Uehara S, Udagawa N, Takahashi N. Regulation of bone metabolism by Wnt signals. J Biochem. 2016;159(4):387-92. https://doi.org/10.1093/jb/mvv124.
11. Chapurlat RD, Confavreux CB. Novel biological markers of bone: from bone metabolism to bone physiology. Rheumatology (Oxford). 2016;55(10):1714-25. https://doi.org/10.1093/rheumatology/kev410.
12. Huelsken J, Behrens J. The Wnt signalling pathway. J Cell Sci. 2002;115(Pt 21):3977-8. https://doi.org/10.1242/jcs.00089.
13. Anastasilakis AD, Polyzos SA, Toulis KA. Role of wingless tail signaling pathway in osteoporosis: an update of current knowledge. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):383-8. https://doi.org/10.1097/MED.0b013e32834afff2.
14. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003;22(23):6267-76. https://doi.org/10.1093/emboj/cdg599.
15. Pinzone JJ, Hall BM, Thudi NK, Vonau M, Qiang YW, Rosol TJ, et al. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood. 2009;113(3):517-25. https://doi.org/10.1182/blood-2008-03-145169.
16. Altinok B, Sunguroglu A. [WNT Signaling Pathway and Cancer] (in Turkish). ASHD 2016;15(2):27-38. https://doi.org/10.1501/Ashd_0000000118
17. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228. https://doi.org/10.1007/s00134-012-2769-8.
18. Tian Y, Yao Y, Zhou J, Diao X, Chen H, Cai K, Ma X, Wang S. Dynamic APACHE II Score to Predict the Outcome of Intensive Care Unit Patients. Front Med (Lausanne). 2022;8:744907. https://doi.org/10.3389/fmed.2021.744907
19. Almansouri AY, Abdulfatah ME, Baaqil OH, Bakheet AA, Turki SA, Kotb MM, et al. Serum sclerostin levels in patients with Human Immunodeficiency Virus infection and their association with bone turnover markers and bone mineral densitometry. J Bone Metab. 2016;23(1):16-22. https://doi.org/10.11005/jbm.2016.23.1.16.
20. González-Reimers E, López-Prieto J, Pelazas-González R, Alemán-Valls MR, José de la Vega-Prieto M, Jorge-Ripper C, et al. Serum sclerostin in hepatitis C virus infected patients. J Bone Metab. 2014;21(1):69-75. https://doi.org/10.11005/jbm.2014.21.1.69.
21. Falasca K, Reale M, Di Nicola M, Ucciferri C, Zecca IA, Santilli F, et al. Circulating CD40 ligand, Dickkopf-1 and P-selectin in HIV-infected patients. HIV Med. 2019;20(10):681-90. https://doi.org/10.1111/hiv.12789.
22. Pietrzyk B, Wyskida K, Ficek J, Kolonko A, Ficek R, Więcek A, et al. Relationship between plasma levels of sclerostin, calcium-phosphate disturbances, established markers of bone turnover, and inflammation in haemodialysis patients. Int Urol Nephrol. 2019;51(3):519-26. https://doi.org/10.1007/s11255-018-2050-3.
23. Neto R, Pereira L, Magalhães J, Quelhas-Santos J, Martins S, Carvalho C, et al. Sclerostin and DKK1 circulating levels associate with low bone turnover in patients with chronic kidney disease Stages 3 and 4. Clin Kidney J. 2021;14(11):2401-8. https://doi.org/10.1093/ckj/sfab081.
24. Giordano P, Vecchio GCD, Russo G, Palmieri VV, Piacente L, Fidone C, Urbano F, Faienza MF. High Dickkopf-1 levels are associated with chronic inflammation in children with sickle cell disease. Eur J Haematol. 2022;108(4):336-41. https://doi.org/10.1111/ejh.13741.
25. Dai L, Xu D, Wan C, Liu L, Wen F. DKK1 Positively correlates with lung function in COPD patients and reduces airway inflammation. Int J Chron Obstruct Pulmon Dis. 2022;17:93-100. https://doi.org/10.2147/COPD.S341249.
26. Daoussis D, Andonopoulos AP. The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling? Semin Arthritis Rheum. 2011;41(2):170-7. https://doi.org/10.1016/j.semarthrit.2011.01.006.
27. Mazon M, Larouche V, St-Louis M, Schindler D, Carreau M. Elevated blood levels of Dickkopf-1 are associated with acute infections. Immun Inflamm Dis. 2018;6(4):428-34. https://doi.org/10.1002/iid3.232.
28. Pérez Castrillón JL, San Miguel A, Vega G, Abad L, Andres Domingo M, Gonzalez Sagredo M, et al. Levels of DKK1 in patients with acute myocardial infarction and response to atorvastatin. Int J Cardiol. 2010;145(1):164-5. https://doi.org/10.1016/j.ijcard.2009.07.025.

SIRS tanılı hastalarda enflamasyon ve kemik döngüsü arasındaki ilişkinin sklerostin ve Dickkopf-1 (DKK-1) düzeyleri ile değerlendirilmesi

Year 2022, Volume: 7 Issue: 3, 77 - 83, 31.07.2022

Hatice Betül Altınışık Uğur Altınışık Mehmet Aşık

https://doi.org/10.22391/fppc.1102573

Abstract

Giriş: Yoğun bakımlarda hastalar uzun süre yatağa bağımlı halde kalmaktadır. Ayrıca yoğun bakımlarda sıklıkla ağır enfeksiyonlar da görülmektedir. Hem uzun süreli immobilizasyon hem de ciddi infeksiyonlar kemik doku kaybı ile ilişkilidir. Son yıllarda, kemik döngüsünün değerlendirilmesinde Wnt yolağı üzerine yoğunlaşılmıştır. Wnt yolağı hem infeksiyonlarda hem de kemik dokunun formasyonunda rol alır. Wnt antagonisti olan sklerostin ve Dickkopf-1 (DKK-1), kemik yapımını azaltıcı ve osteoklastik aktiviteyi artırıcı etki yaparlar. Biz bu çalışmada, uzun süre yatağa bağımlı SIRS tanılı hastalarda, Wnt inhibitörleri olan “sklerostin ve DKK-1’in” seviyelerindeki değişimi aracılığıyla “kemik döngüsü ve bunun inflamasyonla olan ilişkisini” değerlendirmeyi amaçladık.

Yöntem: Çalışma grubuna SIRS tanısı alan 30 ve kontrol grubuna 16 hasta dahil ettik. Çalışma grubunda hastaların SIRS tanısı aldığı gün (bazal) ve takip eden 7., 14. ve 21. günlerde serum sklerostin, DKK-1, WBC ve CRP düzeylerini ölçtük, sonuçları kontrol grubu ile karşılaştırdık.

Bulgular: Kontrol grubu ile kıyaslandığında, çalışma grubundaki (SIRS) hastaların bazal ölçümlerinde hem sklerostin (p=0,003) hem DKK-1 değerlerinde istatistiksel olarak anlamlı yükseklik vardı (p=0,001). Çalışma grubunda; sklerostin değerlerinde, bazal ile karşılaştırıldığında 7., 14. ve 21. günlerde anlamlı ve progresif bir azalma olduğu gösterildi (sırasıyla p=0,033, p=0,003, p=0,002). Yine çalışma grubundaki DKK-1 seviyelerinde, bazal değer ile kıyaslandığında 7. ve 21. günlerde anlamlı (sırasıyla p=0,015, p=0,001), 14. günde anlamsız azalma görüldü (p=0,191). Korelasyon analizinde; çalışma grubunda sklerostin ile WBC arasında bazal - 7. gün, 7.-14. gün, sklerostin ile CRP arasında bazal - 7. gün pozitif korelasyon tespit edildi. DKK-1 ile WBC arasında bazal - 7. gün pozitif korelasyon vardı. Diğer taraftan DKK-1 ile CRP arasında bazal - 7. gün negatif korelasyon vardı.

Sonuç: Bu çalışmada, yoğun bakımdaki SIRS olgularında Wnt antagonistleri olan sklerostin ve DKK-1 değerlerinin yüksek olduğu ilk kez gösterildi. Her iki biomarker seviyeleri tedaviye paralel olarak azaldı. Bununla birlikte inflamatuar marker düzeylerindeki değişim ile ilişki bulunmadı. Wnt antagonistlerinin düzeylerindeki değişimin takip edilmesinin, SIRS tanılı hastaların kemik döngüsünün gösterilmesinde faydalı olacağı kanaatindeyiz.

Anahtar kelimeler: Dickkopf-1, Yoğun bakım ünitesi, Sklerostin, Sistemik inflamatuar yanıt sendromu, Wnt sinyal yolağı, Kemik döngüsü

Keywords

Dickkopf-1, Yoğun bakım ünitesi, Sklerostin, Sistemik inflamatuar yanıt sendromu, Wnt sinyal yolağı, Kemik döngüsü

Project Number

TSA-2015-516

References

1. Uhthoff HK, Jaworski ZF. Bone loss in response to long-term immobilisation. J Bone Joint Surg Br. 1978;60-B(3):420-9. https://doi.org/10.1302/0301-620X.60B3.681422.
2. Sievänen H. Immobilization and bone structure in humans. Arch Biochem Biophys. 2010;503(1):146-52. https://doi.org/10.1016/j.abb.2010.07.008
3. Grimm G, Vila G, Bieglmayer C, Riedl M, Luger A, Clodi M. Changes in osteopontin and in biomarkers of bone turnover during human endotoxemia. Bone. 2010;47(2):388-91. https://doi.org/10.1016/j.bone.2010.04.602.
4. Tella SH, Gallagher JC. Biological agents in management of osteoporosis. Eur J Clin Pharmacol. 2014;70(11):1291-301. https://doi.org/10.1007/s00228-014-1735-5.
5. Ramli FF, Chin KY. A review of the potential application of osteocyte-related biomarkers, fibroblast growth factor-23, sclerostin, and Dickkopf-1 in predicting osteoporosis and fractures. Diagnostics (Basel). 2020;10(3):145. https://doi.org/10.3390/diagnostics10030145.
6. Colaianni G, Brunetti G, Faienza MF, Colucci S, Grano M. Osteoporosis and obesity: Role of Wnt pathway in human and murine models. World J Orthop. 2014;5(3):242-6. https://doi.org/10.5312/wjo.v5.i3.242.
7. Gifre L, Ruiz-Gaspà S, Monegal A, Nomdedeu B, Filella X, Guañabens N, et al. Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone. 2013;57(1):272-6. https://doi.org/10.1016/j.bone.2013.08.016.
8. Belavý DL, Baecker N, Armbrecht G, Beller G, Buehlmeier J, Frings-Meuthen P, et al. Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest. J Bone Miner Metab. 2016;34(3):354-65. https://doi.org/10.1007/s00774-015-0681-3.
9. Shahnazari M, Wronski T, Chu V, Williams A, Leeper A, Stolina M, et al. Early response of bone marrow osteoprogenitors to skeletal unloading and sclerostin antibody. Calcif Tissue Int. 2012;91(1):50-8. https://doi.org/10.1007/s00223-012-9610-9.
10. Kobayashi Y, Uehara S, Udagawa N, Takahashi N. Regulation of bone metabolism by Wnt signals. J Biochem. 2016;159(4):387-92. https://doi.org/10.1093/jb/mvv124.
11. Chapurlat RD, Confavreux CB. Novel biological markers of bone: from bone metabolism to bone physiology. Rheumatology (Oxford). 2016;55(10):1714-25. https://doi.org/10.1093/rheumatology/kev410.
12. Huelsken J, Behrens J. The Wnt signalling pathway. J Cell Sci. 2002;115(Pt 21):3977-8. https://doi.org/10.1242/jcs.00089.
13. Anastasilakis AD, Polyzos SA, Toulis KA. Role of wingless tail signaling pathway in osteoporosis: an update of current knowledge. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):383-8. https://doi.org/10.1097/MED.0b013e32834afff2.
14. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003;22(23):6267-76. https://doi.org/10.1093/emboj/cdg599.
15. Pinzone JJ, Hall BM, Thudi NK, Vonau M, Qiang YW, Rosol TJ, et al. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood. 2009;113(3):517-25. https://doi.org/10.1182/blood-2008-03-145169.
16. Altinok B, Sunguroglu A. [WNT Signaling Pathway and Cancer] (in Turkish). ASHD 2016;15(2):27-38. https://doi.org/10.1501/Ashd_0000000118
17. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228. https://doi.org/10.1007/s00134-012-2769-8.
18. Tian Y, Yao Y, Zhou J, Diao X, Chen H, Cai K, Ma X, Wang S. Dynamic APACHE II Score to Predict the Outcome of Intensive Care Unit Patients. Front Med (Lausanne). 2022;8:744907. https://doi.org/10.3389/fmed.2021.744907
19. Almansouri AY, Abdulfatah ME, Baaqil OH, Bakheet AA, Turki SA, Kotb MM, et al. Serum sclerostin levels in patients with Human Immunodeficiency Virus infection and their association with bone turnover markers and bone mineral densitometry. J Bone Metab. 2016;23(1):16-22. https://doi.org/10.11005/jbm.2016.23.1.16.
20. González-Reimers E, López-Prieto J, Pelazas-González R, Alemán-Valls MR, José de la Vega-Prieto M, Jorge-Ripper C, et al. Serum sclerostin in hepatitis C virus infected patients. J Bone Metab. 2014;21(1):69-75. https://doi.org/10.11005/jbm.2014.21.1.69.
21. Falasca K, Reale M, Di Nicola M, Ucciferri C, Zecca IA, Santilli F, et al. Circulating CD40 ligand, Dickkopf-1 and P-selectin in HIV-infected patients. HIV Med. 2019;20(10):681-90. https://doi.org/10.1111/hiv.12789.
22. Pietrzyk B, Wyskida K, Ficek J, Kolonko A, Ficek R, Więcek A, et al. Relationship between plasma levels of sclerostin, calcium-phosphate disturbances, established markers of bone turnover, and inflammation in haemodialysis patients. Int Urol Nephrol. 2019;51(3):519-26. https://doi.org/10.1007/s11255-018-2050-3.
23. Neto R, Pereira L, Magalhães J, Quelhas-Santos J, Martins S, Carvalho C, et al. Sclerostin and DKK1 circulating levels associate with low bone turnover in patients with chronic kidney disease Stages 3 and 4. Clin Kidney J. 2021;14(11):2401-8. https://doi.org/10.1093/ckj/sfab081.
24. Giordano P, Vecchio GCD, Russo G, Palmieri VV, Piacente L, Fidone C, Urbano F, Faienza MF. High Dickkopf-1 levels are associated with chronic inflammation in children with sickle cell disease. Eur J Haematol. 2022;108(4):336-41. https://doi.org/10.1111/ejh.13741.
25. Dai L, Xu D, Wan C, Liu L, Wen F. DKK1 Positively correlates with lung function in COPD patients and reduces airway inflammation. Int J Chron Obstruct Pulmon Dis. 2022;17:93-100. https://doi.org/10.2147/COPD.S341249.
26. Daoussis D, Andonopoulos AP. The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling? Semin Arthritis Rheum. 2011;41(2):170-7. https://doi.org/10.1016/j.semarthrit.2011.01.006.
27. Mazon M, Larouche V, St-Louis M, Schindler D, Carreau M. Elevated blood levels of Dickkopf-1 are associated with acute infections. Immun Inflamm Dis. 2018;6(4):428-34. https://doi.org/10.1002/iid3.232.
28. Pérez Castrillón JL, San Miguel A, Vega G, Abad L, Andres Domingo M, Gonzalez Sagredo M, et al. Levels of DKK1 in patients with acute myocardial infarction and response to atorvastatin. Int J Cardiol. 2010;145(1):164-5. https://doi.org/10.1016/j.ijcard.2009.07.025.

There are 28 citations in total.

Details

Primary Language	English
Subjects	Clinical Sciences
Journal Section	Original Research
Authors	Hatice Betül Altınışık 0000-0001-9273-0876 Uğur Altınışık 0000-0002-0856-9125 Mehmet Aşık 0000-0002-0716-0221
Project Number	TSA-2015-516
Publication Date	July 31, 2022
Submission Date	April 13, 2022
Acceptance Date	July 27, 2022
Published in Issue	Year 2022Volume: 7 Issue: 3

Cite

APA	Altınışık, H. B., Altınışık, U., & Aşık, M. (2022). Evaluation of the relationship between inflammation and bone turnover by sclerostin and Dickkopf-1 (DKK-1) levels in patients with SIRS. Family Practice and Palliative Care, 7(3), 77-83. https://doi.org/10.22391/fppc.1102573
AMA	Altınışık HB, Altınışık U, Aşık M. Evaluation of the relationship between inflammation and bone turnover by sclerostin and Dickkopf-1 (DKK-1) levels in patients with SIRS. Fam Pract Palliat Care. July 2022;7(3):77-83. doi:10.22391/fppc.1102573
Chicago	Altınışık, Hatice Betül, Uğur Altınışık, and Mehmet Aşık. “Evaluation of the Relationship Between Inflammation and Bone Turnover by Sclerostin and Dickkopf-1 (DKK-1) Levels in Patients With SIRS”. Family Practice and Palliative Care 7, no. 3 (July 2022): 77-83. https://doi.org/10.22391/fppc.1102573.
EndNote	Altınışık HB, Altınışık U, Aşık M (July 1, 2022) Evaluation of the relationship between inflammation and bone turnover by sclerostin and Dickkopf-1 (DKK-1) levels in patients with SIRS. Family Practice and Palliative Care 7 3 77–83.
IEEE	H. B. Altınışık, U. Altınışık, and M. Aşık, “Evaluation of the relationship between inflammation and bone turnover by sclerostin and Dickkopf-1 (DKK-1) levels in patients with SIRS”, Fam Pract Palliat Care, vol. 7, no. 3, pp. 77–83, 2022, doi: 10.22391/fppc.1102573.
ISNAD	Altınışık, Hatice Betül et al. “Evaluation of the Relationship Between Inflammation and Bone Turnover by Sclerostin and Dickkopf-1 (DKK-1) Levels in Patients With SIRS”. Family Practice and Palliative Care 7/3 (July 2022), 77-83. https://doi.org/10.22391/fppc.1102573.
JAMA	Altınışık HB, Altınışık U, Aşık M. Evaluation of the relationship between inflammation and bone turnover by sclerostin and Dickkopf-1 (DKK-1) levels in patients with SIRS. Fam Pract Palliat Care. 2022;7:77–83.
MLA	Altınışık, Hatice Betül et al. “Evaluation of the Relationship Between Inflammation and Bone Turnover by Sclerostin and Dickkopf-1 (DKK-1) Levels in Patients With SIRS”. Family Practice and Palliative Care, vol. 7, no. 3, 2022, pp. 77-83, doi:10.22391/fppc.1102573.
Vancouver	Altınışık HB, Altınışık U, Aşık M. Evaluation of the relationship between inflammation and bone turnover by sclerostin and Dickkopf-1 (DKK-1) levels in patients with SIRS. Fam Pract Palliat Care. 2022;7(3):77-83.