The Relationship between Fibroblast Growth Factor-23, Insulin-Like Growth Factor-1, Bone Mineral Density, Insulin Resistance, and Hyperandrogenemia in Polycystic Ovary Syndrome

Enver Çiftel; Fatih Kılıçlı; Serpil Çiftel

doi:10.7197/cmj.1215068

Research Article

The Relationship between Fibroblast Growth Factor-23, Insulin-Like Growth Factor-1, Bone Mineral Density, Insulin Resistance, and Hyperandrogenemia in Polycystic Ovary Syndrome

Year 2022, Volume: 44 Issue: 4, 390 - 396, 31.12.2022

Enver Çiftel , Fatih Kılıçlı , Serpil Çiftel

https://doi.org/10.7197/cmj.1215068

Abstract

Aims: The aim of this study was to find out the association between the Fibroblast Growth Factor-23 (FGF-23), Insulin-Like Growth Factor-1 (IGF-1), androgens, insulin resistance (IR), and bone mineral density (BMD) in patients with PCOS (Polycyctic Ovary Syndrome) and healthy controls is presented.
Materials and Methods: The FGF-23, IGF-1, and Homeostatic Model Assessment for Insulin Resistance were evaluated in 47 patients with PCOS and 26 healthy females, and BMD was evaluated only in the PCOS group. Then these parameters were compared between groups, according to the presence of IR and hyperandrogenemia.
Results: The mean FGF-23 was 137.55± 75.42 and 414.81 ± 53.02 (pg/ml), and mean IGF-1 was 28.41 ± 99.69 and 244.26 ± 58.99 (ng/ml) in patients with PCOS and healthy controls, respectively. In PCOS group, the FGF-23 was more significantly decreased in those with IR and amenorrheic. DEXA scores were found to be similar in PCOS group in terms of hyperandrogenemia and IR.
Conclusions: Our results revealed that FGF-23 levels decreased in patients with PCOS, which was particularly significant in patients with IR. According to our findings; the low level of FGF-23 in the PCOS group with IR suggests that this marker may also be associated with the complications of PCOS, but to clarify this hypothesis, this marker needs to be investigated.

Keywords

Polycystic Ovary Syndrome, Insulin Resistance, FGF-23

Supporting Institution

Unit of the Cumhuriyet University Scientific Research Projects (CUBAP)

Project Number

T574 numbered project

References

1. Ganie MA, Vasudevan V, Wani IA, Baba MS, Arif T, Rashid A. Epidemiology, pathogenesis, genetics & management of polycystic ovary syndrome in India. Indian J. Med Res. 2019; 150(4): 333–344.
2. Ibanez L, Oberfield SE, Witchel SF,Auchus RJ, Chang RJ, Codner E, Dabadghao P, Darendeliler F, Elbarbary N, Gambineri A, Rudaz CG, Hoeger KM, Bermejo AL, Ong K, Pena AS, Reinehr T, Santoro N, Sempere MT, Tao R, Yildiz BO, Alkhayyat H, Deeb A, Joel D, Horikawa R, Zegher F, Lee P. An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence. Horm. Res. Paediatr. 2017; 88(6): 371–395
3. Li Y, Chen C, Ma Y, Xiao J, Luo G, Li Y, Wu D. Multi-system reproductive metabolic disorder: Significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS). Life Sci. 2019;228:167–175.
4. Zeng X, Xie Y-J, Liu Y-T, Long S-L, Mo Z-C. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin. Chim. Acta. 2020; 502: 214–221.
5. Zhang C, Hu J, Wang W, Sun Y, Sun K. HMGB1-induced aberrant autophagy contributes to insulin resistance in granulosa cells in PCOS. FASEB J. 2020; 34(7): 9563–9574.
6. Toosy S, Sodi R, Pappachan JM. Lean polycystic ovary syndrome (PCOS): an evidence-based practical approach. J Diabetes Metab Disord. 2018; 17(2):277–285.
7. Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD. Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX. J Biol Chem. 2003; 278 (39): 37419-26.
8. Miyamoto K, Ito M, Kuwahata M, Kato S, Segawa H. Inhibition of intestinal sodium-dependent inorganic phosphate transport by fibroblast growth factor 23. Ther Apher Dial. 2005; 9(4):331-5.
9. Danziger J. The bone-renal axis in early chronic kidney disease: an emerging paradigm. Nephrol Dial Transplant. 2008; 23(9):2733-37.
10. Lu Y, Feng JQ. FGF23 in skeletal modeling and remodeling. Curr Osteoporos Rep. 2011; 9(2):103-8.
11. Martínez-García MA, Moncayo S, Insenser M, Álvarez-Blasco F, Luque-Ramírez, M, Escobar-Morreale H. F. Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex. Nutrients. 2019; 11(11): 2566.
12. Murer H, Hernando N, Forster I, Biber J. Proximal tubular phosphate reabsorption: Molecular mechanisms. Physiological Reviews. 2000; 80(4): 1373–1409.
13. Abuduli M, Ohminami H, Otani T, Kubo H, Ueda H, Kawai Y, Masuda M, Yamanaka-Okumura H, Sakaue H, Yamamoto H, Yamamoto H, Takeda E, Taketani Y. Effects of dietary phosphate on glucose and lipid metabolism. Am. J. Physiol. Endocrinol. Metab. 2016; 310(7): E526-38.
14. Akter S, Eguchi M, Kochi T, Kabe I, Nanri A, Mizoue T. Association of Serum Calcium and Phosphate Concentrations with Glucose Metabolism Markers: The Furukawa Nutrition and Health Study. Nutrients. 2020; 12(8): 2344.
15. Wojcik M, Dolezal-Oltarzewska K, Janus D, Drozdz D, Sztefko K, Starzyk JB. FGF23 contributes to insulin sensitivity in obese adolescents — preliminary results. Clinical Endocrinology. 2012; 77(4): 537–40.
16. Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol. 2020; 16(11) :654–667.
17. Sahin SB, Ayaz T, Cure MC, Sezgin H, Ural UM, Balik G, Sahin FK. Fibroblast growth factor 21 and its relation to metabolic parameters in women with polycystic ovary syndrome. ScandJ Clin Lab Invest. 2014; 74(6): 465–469
18. Yüksel O, Dökmetaş HS, Topcu S, Erselcan T, Sencan M. Relationship between bone mineral density and insulin resistance in polycystic ovary syndrome. J Bone Miner Metab. 2001; 19(4):257-62
19. Mørch NF, Aziz M, Svendsen PF. Bone mass density in lean and overweight women with polycystic ovary syndrome. ScandJ Clin Lab Invest. 2022; 82(3): 210–217
20. Yang HY, Lee HS, Huang WT, Chen MJ, Chen SC, Hsu YH. Increased risk of fractures in patients with polycystic ovary syndrome: a nationwide population-based retrospective cohort study. J Bone Miner Metab. 2018; 36(6), 741–748.
21. Zhang R, LuY, YeL, Yuan B, YuS, Qin C, Xie Y, Gao T, Drezner MK, Bonewald LF, Feng JQ. Unique roles of phosphorus in endochondral bone formation and osteocyte maturation. J Bone miner Res. 2011; 26(5): 1047-56.
22. Wang H, Yoshiko Y, Yamamoto R, Minamizaki T, Kozai K, Tanne K, Aubin JE, Maeda N. Overexpression of fibroblast growth factor 23 suppresses osteoblast differention and matrix mineralization in vitro. J. Bone Miner Res.2008; 23(6):939·48.
23. Kawata T, Imanishi Y, Kobayashi K, Miki T, Arnold A, Inaba M, Nishizawa Y. Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. J Am Soc Nephrol. 2007; 18(10): 2683-8.
24. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O’Brien CA, Manolagas SC, Jilka RL. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005; 146(11):4577-83.
25. Goobel S, Lienau J, Rammoser U, Seefried L, Wintgens KF, Seufert J, Duda G, Jakob F, Ebert R. FGF23 is a putative marker for bone healing and regeneration. J Orthop Res.2009; 27(9) :1141-46.
26. Westerberg PA, Tivesten Å, Karlsson MK, Mellström D, Orwoll E, Ohlsson C, Larsson TE, Linde T, Ljunggren Ö. Fibroblast growth factor 23, mineral metabolism and mortality among elderly men (Swedish MrOs) BMC Nephrol. 2013; 14:85.
27. Celik E, Guzel S, Abalı R, Guzelant AY, Guzel EC, Kucukyalcin V. The relationship between fibroblast growth factor 23 and osteoporosis in postmenapousal women. Minerva Med.2013; 104(5):497-504.
28. Ix JH, Chonchol M, Laughlin GA, Shlipak MG, Whooley MA. Relation of sex and estrogen therapy to serum fibroblast growth factor 23, serum phosphorus, and urine phosphorus: the Heart and Soul Study. Am J Kidney Dis. 2011; 58(5):737-45.
29. Ogunmoroti O, Osibogun O, Zhao D, Mehta RC, Ouyang P, Lutsey PL, Robinson-Cohen C, Michos E D. Associations between endogenous sex hormones and FGF-23 among women and men in the Multi-Ethnic Study of Atherosclerosis. PloS one. 2022; 17(5): e0268759.