#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Follicle-stimulating hormone and its effects on bone and cartilage


Authors: K. Brábníková Marešová
Authors‘ workplace: Revmatologický ústav Praha
Published in: Čes. Revmatol., 30, 2022, No. 4, p. 166-170.
Category: Review Article

Overview

The prevalence of osteoporosis and osteoarthritis increases during menopause and is associated with changes in serum levels of estrogen and follicle-stimulating hormone (FSH). The progression of osteoporosis and osteoarthritis in postmenopausal women is effectively prevented by estrogen treatment, possible side effects of which, however, discourage the wider use of hormone replacement therapy for the prevention of osteoporosis and osteoarthritis. Follicle-stimulating hormone can influence bone remodeling and cartilage metabolism independently of estrogens. This is how FSH was applied in the regulation of bone remodeling in women with FSH receptor polymorphism (FSHR). A receptor for FSH has been demonstrated in osteoclasts. Blocking FSHR can suppress bone resorption and increase vertebral bone mass in ovariectomized mice. In articular cartilage, FSH binds to a specific receptor and suppresses the synthesis of extracellular matrix proteins. This effect can be blocked. The use of experimental and clinical knowledge on FSH can represent another direction in the prevention of postmenopausal osteoporosis and osteoarthritis.

Keywords:

cartilage – bone – menopause – FSH – receptor for FSH


Sources

1. Hernlund E, Svedbom A, Ivergård M, Compston C, Cooper C, Stenmark J, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 2013; 8(1): 136.

2. Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol 2006; 20(1): 3–25.

3. Barrett-Connor E, Wehren LE, Siris ES, Miller P, Ya-Ting Chen YT, Abbott TA 3rd, et al. Recency and duration of postmenopausal hormone therapy: effects on bone mineral density and fracture risk in the National Osteoporosis Risk Assessment (NORA) study. Menopause 2003; 10(5): 412–419.

4. Barnabei VM, Cochrane BB, Aragaki AK, Nygaard I, Williams RS, McGovern PG, et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women’s Health Initiative. Obstet Gynecol 2005; 105(5 Pt 1): 1063–1073.

5. Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomised trials. BMC Musculoskelet Disord 2001; 2: 7.

6. Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA 2001; 285(22): 2891–2897.

7. Freemantle N, Cooper C, Diez-Perez A, Gitlin M, Radcliffe H, Shepherd S, et al. Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis. Osteoporos Int 2013; 24(1): 209–217.

8. Randell KM, Honkanen RJ, Kröger H, Saarikoski S. Does hormone- replacement therapy prevent fractures in early postmenopausal women? J Bone Miner Res 2002; 17(3): 528–533.

9. Sniekers YH, Weinans H, Bierma-Zeinstra SM, van Leeuwen JP, van Osch GJ. Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment – a systematic approach. Osteoarthritis Cartilage 2008; 16(5): 533–541.

10. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 2013; 310(13): 1353–1368.

11. Santen RJ, Allred DC, Ardoin SP, Archer DF, Boyd N, Braunstein GD, et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010; 95(7 Suppl 1): s1–s66.

12. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019; 394(10204): 1159–1168.

13. Mehta J, Kling JM, Manson JE. Risks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts. Front Endocrinol (Lausanne) 2021; 12: 564781.

14. Bjørnerem A, Straume B, Midtby M, Fønnebø V, Sundsfjord J, Svartberg J, et al. Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromsø Study. J Clin Endocrinol Metab 2004; 89(12): 6039–6047.

15. Siris ES, Harris ST, Eastell R, Zanchetta JR, Goemaere S, Diez- Perez A, et al. Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study. J Bone Miner Res 2005; 20(9): 1514–1524.

16. Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW, et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat 2001; 65(2): 125–134.

17. Silverman SL, Christiansen C , Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res 2008; 23(12): 1923–1934.

18. Jochems C, Lagerquist M, Håkansson C, Ohlsson C, Carlsten H. Long-term anti-arthritic and anti-osteoporotic effects of raloxifene in established experimental postmenopausal polyarthritis. Clin Exp Immunol 2008; 152(3): 593–597.

19. Sun L, Peng Y, Sharrow AC, Iqbal J, Zhang Z, Papachristou DJ, et al. FSH directly regulates bone mass. Cell 2006; 125(2): 247–260.

20. Zhu LL, Tourkova IL, Yuen T, Robinson LJ, Bian Z, Zaidi M, et al. Blocking FSH action attenuates osteoclastogenesis. Biochem Biophys Res Commun 2012; 422(1): 54–58.

21. Iqbal J, Sun L, Kumar TR, Blair HC, Zaidi M. Follicle-stimulating hormone stimulates TNF production from immune cells to enhance osteoblast and osteoclast formation. Proc Natl Acad Sci USA 2006; 103(40): 14925–14930.

22. Cannon JG, Cortez-Cooper M, Meaders E, Stallings J, Haddow S, Kraj B, et al. Follicle-stimulating hormone, interleukin-1, and bone density in adult women. Am J Physiol Regul Integr Comp Physiol 2010; 298(3): R790–798.

23. Sun L, Zhang Z, Zhu LL, Peng Y, Liu X, Li J, et al. Further evidence for direct pro-resorptive actions of FSH. Biochem Biophys Res Commun 2010; 394(1): 6–11.

24. Wang J, Zhang W, Yu CH, Zhang X, Zhang H, Guan Q, et al. Follicle-stimulating hormone increases the risk of postmenopausal osteoporosis by stimulating osteoclast differentiation. PLoS One 2015; 10(8): e0134986.

25. Zhu LL, Blair H, Cao J, Yuen T, Latif R, Guo L, et al. Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis. Proc Natl Acad Sci USA 2012; 109(36): 14574–14579.

26. Cheung E, Tsang S, Bow C, Soong C, Yeung S, Loong C, et al. Bone loss during menopausal transition among southern Chinese women. Maturitas 2011; 69(1): 50–56.

27. García-Martín A, Reyes-García R, García-Castro JM, Rozas- Moreno P, Escobar-Jiménez F, Muñoz-Torres M. Role of serum FSH measurement on bone resorption in postmenopausal women. Endocrine 2012; 41(2): 302–308.

28. Sowers MR, Zheng H, Greendale GA, Neer RM, Cauley JA, Ellis J, et al. Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity. J Clin Endocrinol Metab 2013; 98(7): 2854–2863.

29. Randolph, JF, Jr ., Sowers M, Bondarenko IV, Harlow SD, Luborsky JL, Little RJ. Change in estradiol and follicle-stimulating hormone across the early menopausal transition: effects of ethnicity and age. J Clin Endocrinol Metab 2004; 89(4): 1555–1561.

30. Devleta B, Adem B, Senada S. Hypergonadotropic amenorrhea and bone density: new approach to an old problém. J Bone Miner Metab 2004; 22(4): 360–364.

31. Rendina D, Gianfrancesco F, De Filippo G, Merlotti D, Esposito T, Mingione A, et al. FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women. Eur J Endocrinol 2010; 163(1): 165–172.

32. Liu Y, Zhang M, Kong D, Wang Y, Li J, Liu W, et al. High follicle-stimulating hormone levels accelerate cartilage damage of knee osteoarthritis in postmenopausal women through the PI3K/AKT/ NF-κB pathway. FEBS Open Bio 2020; 10(10): 2235–2245.

33. Zhang X, Qiao P, Guo Q, Liang Z, Pan J, Wu F, et al. High Folliclestimulating hormone level associated with risk of rheumatoid arthritis and disease activity. Front Endocrinol (Lausanne) 2022; 13: 862849.

34. Kong D , Guan Q, Li G, Xin W, Qi X, Guo Y, et al. Expression of FSHR in chondrocytes and the effect of FSH on chondrocytes. Biochem Biophys Res Commun 2018; 495(1): 587–593.

35. Zhang M, Wang Y, Huan Z, Liu Y, Zhang W, Kong D, et al. FSH modulated cartilage ECM metabolism by targeting the PKA/ CREB/SOX9 pathway. J Bone Miner Metab 2021; 39(5): 769–779.

36. Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, et al. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 1994; 79(6): 1111–1120.

37. Ng NJ, Wheatley S, Muscat GE, Conway-Campbell J, Bowles J, Wright E, et al. SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev Biol 1997; 183(1): 108–121.

38. Sekiya I, Tsuji K, Koopman P, Watanabe H, Yamada Y, Shinomiya K, et al. SOX9 enhances aggrecan gene promoter/enhancer activity and is up-regulated by retinoic acid in a cartilage-derived cell line, TC6. J Biol Chem 2000; 275(15): 10738–10744.

39. Xiong J, Kang SS, Wang Z, Liu X, Kuo TCH, Korkmaz F, et al. FSH blockade improves cognition in mice with Alzheimer’s disease. Nature 2022; 603(7901): 470–476.

40. Xu Y, Yan H, Zhang X, Zhuo J, Han Y, Zhang H, et al. Roles of altered macrophages and cytokines: implications for pathological mechanisms of postmenopausal osteoporosis, rheumatoid Arthritis, and Alzheimer’s disease. Front Endocrinol (Lausanne) 2022; 13: 876269.

Labels
Dermatology & STDs Paediatric rheumatology Rheumatology
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#