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The role of estrogens in osteosarcopenia: from biology to potential dual therapeutic effects

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Pages 81-87 | Received 13 Jul 2021, Accepted 25 Jul 2021, Published online: 23 Aug 2021

References

  • Inoue T, Maeda K, Nagano A, et al. Related factors and clinical outcomes of osteosarcopenia: a narrative review. Nutrients. 2021;13(2):291.
  • Kanis JA, Glüer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int. 2000;11(3):192–202.
  • Föger-Samwald U, Dovjak P, Azizi-Semrad U, et al. Osteoporosis: pathophysiology and therapeutic options. EXCLI J. 2020;19:1017–1037.
  • Akkawi I, Zmerly H. Osteoporosis: current concepts. Joints. 2018;6(2):122–127.
  • Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31.
  • Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412–423.
  • Hong AR, Kim SW. Effects of resistance exercise on bone health. Endocrinol Metab (Seoul). 2018;33(4):435–444.
  • Kirk B, Al Saedi A, Duque G. Osteosarcopenia: a case of geroscience. Aging Med (Milton). 2019;2(3):147–156.
  • Hirschfeld HP, Kinsella R, Duque G. Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int. 2017;28(10):2781–2790.
  • Skrzypczak D, Ratajczak AE, Szymczak-Tomczak A, et al. A vicious cycle of osteosarcopenia in inflammatory bowel diseases—aetiology, clinical implications and therapeutic perspectives. Nutrients. 2021;13(2):293.
  • Kaji H. Linkage between muscle and bone: common catabolic signals resulting in osteoporosis and sarcopenia. Curr Opin Clin Nutr Metab Care. 2013;16(3):272–277.
  • Sipilä S, Törmäkangas T, Sillanpää E, et al. Muscle and bone mass in middle‐aged women: role of menopausal status and physical activity. J Cachexia Sarcopenia Muscle. 2020;11(3):698–709.
  • Gruber CJ, Tschugguel W, Schneeberger C, et al. Production and actions of estrogens. N Engl J Med. 2002;346(5):340–352.
  • Shozu M, Simpson ER. Aromatase expression of human osteoblast-like cells. Mol Cell Endocrinol. 1998;139(1–2):117–129.
  • Sasano H, Uzuki M, Sawai T, et al. Aromatase in human bone tissue. J Bone Miner Res. 1997;12(9):1416–1423.
  • Matsumine H, Hirato K, Yanaihara T, et al. Aromatization by skeletal muscle. J Clin Endocrinol Metab. 1986;63(3):717–720.
  • Baird D, Fraser I. Blood production and ovarian secretion rates of estradiol-17 beta and estrone in women throughout the menstrual cycle. J Clin Endocrinol Metab. 1974;38(6):1009–1017.
  • Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001;45(3 Suppl):S116–S124.
  • Yaşar P, Ayaz G, User SD, et al. Molecular mechanism of estrogen-estrogen receptor signaling. Reprod Med Biol. 2017;16(1):4–20.
  • Albright F, Smith PH, Richardson AK. Postmenopausal osteoporosis: its clinical features. JAMA. 1941;116(22):2465–2474.
  • Riggs B, Khosla S, Melton L. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23(3):279–302.
  • Smith E, Boyd J, Frank G, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994;331(16):1056–1061.
  • Rochira V, Carani C. Aromatase deficiency in men: a clinical perspective. Nat Rev Endocrinol. 2009;5(10):559–568.
  • Bilezikian J, Morishima A, Bell J, et al. Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. N Engl J Med. 1998;339(9):599–603.
  • Carani C, Qin K, Simoni M, et al. Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med. 1997;337(2):91–95.
  • Bord S, Horner A, Beavan S, et al. Estrogen receptors alpha and beta are differentially expressed in developing human bone. J Clin Endocrinol Metab. 2001;86(5):2309–2314.
  • Hall J, McDonnell D. The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology. 1999;140(12):5566–5578.
  • Lindberg MK, Movérare S, Skrtic S, et al. Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a “ying yang” relationship between ERalpha and ERbeta in mice. Mol Endocrinol. 2003;17(2):203–208.
  • Heino TJ, Chagin AS, Sävendahl L. The novel estrogen receptor G-protein-coupled receptor 30 is expressed in human bone. J Endocrinol. 2008;197(2):R1–6.
  • Nakamura T, Imai Y, Matsumoto T, et al. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell. 2007;130(5):811–823.
  • Venken K, Callewaert F, Boonen S, et al. Sex hormones, their receptors and bone health. Osteoporos Int. 2008;19(11):1517–1525.
  • Charatcharoenwitthaya N, Khosla S, Atkinson EJ, et al. Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women. J Bone Miner Res. 2007;22(5):724–729.
  • Pacifici R. Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res. 1996;11(8):1043–1051.
  • Srivastava S, Weitzmann M, Cenci S, et al. Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD. J Clin Invest. 1999;104(4):503–513.
  • Pacifici R, Vannice J, Rifas L, et al. Monocytic secretion of interleukin-1 receptor antagonist in normal and osteoporotic women: effects of menopause and estrogen/progesterone therapy. J Clin Endocrinol Metab. 1993;77(5):1135–1141.
  • Hughes D, Dai A, Tiffee J, et al. Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta. Nat Med. 1996;2(10):1132–1135.
  • Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor κB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008;29(2):155–192.
  • Eghbali-Fatourechi G, Khosla S, Sanyal A, et al. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003;111(8):1221–1230.
  • Drake MT, Khosla S. Hormonal and systemic regulation of sclerostin. Bone. 2017;96:8–17.
  • Mirza FS, Padhi ID, Raisz LG, et al. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010;95(4):1991–1997.
  • Hannon R, Blumsohn A, Naylor K, et al. Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability. J Bone Miner Res. 1998;13(7):1124–1133.
  • Weivoda MM, Ruan M, Hachfeld CM, et al. Wnt signaling inhibits osteoclast differentiation by activating canonical and noncanonical cAMP/PKA pathways. J Bone Miner Res. 2016;31(1):65–75.
  • Yang L, Smith L, Hamer M. Gender-specific risk factors for incident sarcopenia: 8-year follow-up of the English longitudinal study of ageing. J Epidemiol Community Health. 2019;73(1):86–88.
  • Forcina L, Miano C, Pelosi L, et al. An overview about the biology of skeletal muscle satellite cells. Curr Genomics. 2019;20(1):24–37.
  • Hawke TJ, Garry DJ. Myogenic satellite cells: physiology to molecular biology. J Appl Physiol (1985). 2001;91(2):534–551.
  • La Colla A, Pronsato L, Milanesi L, et al. 17β-Estradiol and testosterone in sarcopenia: role of satellite cells. Ageing Res Rev. 2015;24(Pt B):166–177.
  • Messier V, Rabasa-Lhoret R, Barbat-Artigas S, et al. Menopause and sarcopenia: a potential role for sex hormones. Maturitas. 2011;68(4):331–336.
  • Collins BC, Arpke RW, Larson AA, et al. Estrogen regulates the satellite cell compartment in females. Cell Rep. 2019;28(2):368–381.e6.
  • Morley JE, Malmstrom TK. Frailty, sarcopenia, and hormones. Endocrinol Metab Clin North Am. 2013;42(2):391–405.
  • Collins BC, Mader TL, Cabelka CA, et al. Deletion of estrogen receptor α in skeletal muscle results in impaired contractility in female mice. J Appl Physiol (1985). 2018;124(4):980–992.
  • Ribas V, Drew BG, Zhou Z, et al. Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Sci Transl Med. 2016;8(334):334ra54.
  • Collins B, Laakkonen E, Lowe D. Aging of the musculoskeletal system: How the loss of estrogen impacts muscle strength. Bone. 2019;123:137–144.
  • Smith GI, Yoshino J, Reeds DN, et al. Testosterone and progesterone, but not estradiol, stimulate muscle protein synthesis in postmenopausal women. J Clin Endocrinol Metab. 2014;99(1):256–265.
  • Smith GI, Reeds DN, Hall AM, et al. Sexually dimorphic effect of aging on skeletal muscle protein synthesis. Biol Sex Differ. 2012;3(1):11.
  • Bamman M, Hill V, Adams G, et al. Gender differences in resistance-training-induced myofiber hypertrophy among older adults. J Gerontol A Biol Sci Med Sci. 2003;58(2):108–116.
  • Hansen M, Skovgaard D, Reitelseder S, et al. Effects of estrogen replacement and lower androgen status on skeletal muscle collagen and myofibrillar protein synthesis in postmenopausal women. J Gerontol A Biol Sci Med Sci. 2012;67(10):1005–1013.
  • Bilodeau P, Coyne E, Wing S. The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation. Am J Physiol Cell Physiol. 2016;311(3):C392–403.
  • Kangas R, Pöllänen E, Rippo MR, et al. Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy-a study with monozygotic twin pairs. Mech Ageing Dev. 2014;143-144:1–8.
  • Lai S, Collins B, Colson B, et al. Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice. Am J Physiol Endocrinol Metab. 2016;310(9):E724–E733.
  • Geraci A, Calvani R, Ferri E, et al. Sarcopenia and menopause: the role of estradiol. Front Endocrinol (Lausanne). 2021;12:682012.
  • Lupsa BC, Insogna K. Bone health and osteoporosis. Endocrinol Metab Clin North Am. 2015;44(3):517–530.
  • Effects of hormone therapy on bone mineral density: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA. 1996;276(17):1389–1396.
  • de Villiers T, Stevenson J. The WHI: the effect of hormone replacement therapy on fracture prevention. Climacteric. 2012;15(3):263–266.
  • Levin VA, Jiang X, Kagan R. Estrogen therapy for osteoporosis in the modern era. Osteoporos Int. 2018;29(5):1049–1055.
  • Rozenberg S, Al-Daghri N, Aubertin-Leheudre M, et al. Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis? Osteoporos Int. 2020;31(12):2271–2286.
  • Gosset A, Pouillès JM, Trémollieres F. Menopausal hormone therapy for the management of osteoporosis. Best Pract Res Clin Endocrinol Metab. 2021 Jun;101551.
  • Hansen RD, Raja C, Baber RJ, et al. Effects of 20-mg oestradiol implant therapy on bone mineral density, fat distribution and muscle mass in postmenopausal women. Acta Diabetol. 2003;40(0):s191–S195.
  • Abdi F, Mobedi H, Bayat F, et al. The effects of transdermal estrogen delivery on bone mineral density in postmenopausal women: a meta-analysis. Iran J Pharmaceut Res. 2017;16(1):380.
  • Podfigurna A, Maciejewska-Jeske M, Nadolna M, et al. Impact of hormonal replacement therapy on bone mineral density in premature ovarian insufficiency patients. JCM. 2020;9(12):3961.
  • Nose-Ogura S, Yoshino O, Kanatani M, et al. Effect of transdermal estradiol therapy on bone mineral density of amenorrheic female athletes. Scand J Med Sci Sports. 2020;30(8):1379–1386.
  • Jäckle K, Kolb JP, Schilling AF, et al. Analysis of low-dose estrogen on callus BMD as measured by pQCT in postmenopausal women. BMC Musculoskelet Disord. 2020;21(1):693.
  • Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocrine Rev. 2000;21(2):115–137.
  • Javed AA, Mayhew AJ, Shea AK, et al. Association between hormone therapy and muscle mass in postmenopausal women: a systematic review and meta-analysis. JAMA Netw Open. 2019;2(8):e1910154.
  • Kim S-W, Kim R. The association between hormone therapy and sarcopenia in postmenopausal women: the Korea National Health and Nutrition Examination Survey, 2008–2011. Menopause. 2020;27(5):506–511.
  • Maddalozzo GF, Widrick JJ, Cardinal BJ, et al. The effects of hormone replacement therapy and resistance training on spine bone mineral density in early postmenopausal women. Bone. 2007;40(5):1244–1251.
  • Sipilä S, Cheng S, Taaffe S, et al. Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in postmenopausal women: a randomized placebo-controlled study. Clin Sci. 2001;101(2):147–157.
  • Greising S, Baltgalvis K, Lowe D, et al. Hormone therapy and skeletal muscle strength: a meta-analysis. J Gerontol Series A Biol Sci Med Sci. 2009;64A(10):1071–1081.
  • Lowe D, Baltgalvis K, Greising S. Mechanisms behind estrogen’s beneficial effect on muscle strength in females. Exerc Sport Sci Rev. 2010;38(2):61–67.
  • Cariati I, Bonanni R, Onorato F, Mastrogregori A, Rossi D, Iundusi R, Gasbarra E, Tancredi V, Tarantino U. Role of physical activity in bone-muscle crosstalk: biological aspects and clinical implications. J Funct Morphol Kinesiol. 2021 Jun 21;6(2):55.
  • Pöllänen E, Fey V, Törmäkangas T, et al. Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle. Age (Dordr). 2010;32(3):347–363.
  • Taaffe DR, Sipilä S, Cheng S, et al. The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention. Clin Physiol Funct Imaging. 2005;25(5):297–304.
  • Cheng S, Sipilä S, Taaffe DR, et al. Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in postmenopausal women. Bone. 2002;31(1):126–135.
  • Phu S, Boersma D, Duque G. Exercise and sarcopenia. J Clin Densitom. 2015;18(4):488–492.

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