Bone Health in Transgender Individuals: A Narrative Review on the Impact of Gender-Affirming Hormone Therapy
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Abstract
Bone health is a critical aspect of transgender and gender-diverse (TGD) care, as sex steroids are central for bone accrual during puberty and skeletal maintenance in adulthood. This life-course narrative review synthesizes evidence by age group, sex assigned at birth, and hormone regimen, evaluating bone mineral density (BMD), fracture risk, and monitoring practices while considering study quality and limitations. Puberty suppression with GnRH agonists in adolescents reduces lumbar spine Z-scores by 0.5–1.0 SD within two years. After gender-affirming hormone therapy (GAHT), bone indices generally recover, with lumbar spine Z-scores increasing by approximately 0.3–0.5 SD within 24–36 months; however, catch-up remains incomplete in adolescent transgender women when estradiol levels are subphysiologic. In adults, adequate GAHT preserves or increases site-specific BMD, whereas hypogonadism after gonadectomy, poor adherence, or adverse lifestyle factors may accelerate bone loss. In older adults, fracture incidence in transgender women is higher than in cisgender men (4.4 vs 2.3 per 1,000 person-years; HR 1.9, 95% CI 1.3–2.7) but comparable to that of cisgender women (HR 1.05, 95% CI 0.75–1.49). In contrast, fracture rates in transgender men are lower than or similar to those observed in cisgender men. Maintaining physiologic estradiol levels (100–200 pg/mL) in transgender women and testosterone levels (400–700 ng/dL) in transgender men is essential for bone protection. Recommended management includes risk-based dual-energy X-ray absorptiometry (DXA) monitoring, consideration of bone turnover marker (BTM) monitoring in selected individuals, vitamin D and calcium optimization, weightbearing exercise, lifestyle counseling, and fall prevention. Despite encouraging BMD outcomes, data on long-term fracture risk, skeletal microarchitecture, and diverse hormone regimens remain limited, underscoring the need for large-scale longitudinal research.
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References
United Nations Development Programme. Inclusive development and diversity in gender identity. New York: UNDP; 2020.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed., text rev. Washington (DC): American Psychiatric Association Publishing; 2022. doi: 10.1176/appi.books.9780890425787.
World Health Organization. International statistical classification of diseases and related health problems, 11th revision (ICD- 11) [Internet]. Geneva: World Health Organization; 2019 [cited 2026 Sep 15]. Available from: https://icd.who.int/
Ford K, Huggins E, Sheean P. Characterising body composition and bone health in transgender individuals receiving gender-affirming hormone therapy. J Hum Nutr Diet. 2022;35(6):1105-14. doi: 10.1111/jhn.13027.
Cheung AS, Nolan BJ, Zwickl S. Transgender health and the impact of aging and menopause. Climacteric. 2023;26(3): 256-62. doi: 10.1080/13697137.2023.2176217.
Wiepjes CM, Vlot MC, Klaver M, et al. Bone mineral density increases in trans persons after 1 year of hormonal treatment: a multicenter prospective observational study. J Bone Miner Res. 2017;32(6):1252-60. doi: 10.1002/jbmr.3102.
Bretherton I, Ghasem-Zadeh A, Leemaqz SY, et al. Bone microarchitecture in transgender adults: a cross-sectional study. J Bone Miner Res. 2022;37(4):643-8. doi: 10.1002/jbmr.4497.
van der Loos MATC, Vlot MC, Klink DT, et al. Bone mineral density in transgender adolescents treated with puberty suppression and subsequent gender-affirming hormones. JAMA Pediatr. 2023;177(12):1332-41. doi: 10.1001/jamapediatrics.2023.4588.
Tangpricha V, den Heijer M. Oestrogen and anti-androgen therapy for transgender women. Lancet Diabetes Endocrinol. 2017;5(4):291-300. doi: 10.1016/S2213-8587(16)30319-9.
Stevenson MO, Tangpricha V. Osteoporosis and bone health in transgender persons. Endocrinol Metab Clin North Am. 2019;48(2):421-7. doi: 10.1016/j.ecl.2019.02.006.
Vlot MC, Wiepjes CM, de Jongh RT, et al. Gender-affirming hormone treatment decreases bone turnover in transwomen and older transmen. J Bone Miner Res. 2019;34(10):1862-72. doi: 10.1002/jbmr.3762.
Tienforti D, Marinelli L, Vervalcke J, et al. Short-term changes in bone metabolism among transgender men starting gender-affirming hormone therapy: a systematic review and meta-analysis. Calcif Tissue Int. 2024;115(5):624-35. doi: 10.1007/s00223-024-01296-z.
Wiepjes CM, de Blok CJM, Staphorsius AS, et al. Fracture risk in trans women and trans men using long-term genderaffirming hormonal treatment: a nationwide cohort study. J Bone Miner Res. 2020;35(1):64-70. doi: 10.1002/jbmr.3862.
Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473(2):139-46. doi: 10.1016/j.abb.2008.03.018.
Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol Metab. 2012;23(11):576-81. doi: 10.1016/j.tem.2012.03.008.
Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-59. doi: 10.1210/jc.2009-2354.
Lee JY. Bone health in the transgender and gender diverse youth population. Curr Osteoporos Rep. 2023;21(4):459-71. doi: 10.1007/s11914-023-00799-2.
Nasomyont N, Meisman AR, Ecklund K, et al. Changes in bone marrow adipose tissue in transgender and gender non-conforming youth undergoing pubertal suppression: a pilot study. J Clin Densitom. 2022;25(4):485-9. doi: 10.1016/j.jocd.2022.06.006.
Chevalley T, Rizzoli R. Acquisition of peak bone mass. Best Pract Res Clin Endocrinol Metab. 2022;36(2):101616. doi: 10.1016/j.beem.2022.101616.
Akhiiarova K, Khusainova R, Minniakhmetov I, et al. Peak bone mass formation: modern view of the problem. Biomedicines. 2023;11(11):2982. doi: 10.3390/biomedicines11112982.
Schagen SEE, Wouters FM, Cohen-Kettenis PT, et al. Bone development in transgender adolescents treated with GnRH analogues and subsequent gender-affirming hormones. J Clin Endocrinol Metab. 2020;105(12):e4252-63. doi: 10.1210/clinem/dgaa604.
Olson-Kennedy J, Chan YM, Garofalo R, et al. Impact of early medical treatment for transgender youth: protocol for the longitudinal, observational Trans Youth Care Study. JMIR Res Protoc. 2019;8(7):e14434. doi: 10.2196/14434.
Royal Thai College of Obstetricians and Gynaecologists. Clinical practice guideline: transgender health care for obstetricians and gynecologists. Bangkok: Royal Thai College of Obstetricians and Gynaecologists; 2023.
Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869-903. doi: 10.1210/jc.2017-01658.
Holick MF. Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets. 2011;12(1):4-18. doi: 10.2174/138945011793591635.
Watson SL, Weeks BK, Weis LJ, et al. High-intensity resistance and impact training improves bone mineral density and physical function in postmenopausal women with osteopenia and osteoporosis: the LIFTMOR randomized controlled trial. J Bone Miner Res. 2018;33(2):211-20. doi: 10.1002/jbmr.3284.
O’Bryan SJ, Giuliano C, Woessner MN, et al. Progressive resistance training for concomitant increases in muscle strength and bone mineral density in older adults: a systematic review and meta-analysis. Sports Med. 2022;52(8):1939-60. doi: 10.1007/s40279-022-01675-2.
Ceolin C, Scala A, Dall’Agnol M, et al. Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study. J Endocrinol Invest. 2024;47(2):401-10. doi: 10.1007/s40618-023-02156-7.
Rosen HN, Hamnvik OPR, Jaisamrarn U, et al. Bone densitometry in transgender and gender non-conforming (TGNC) individuals: 2019 ISCD official position. J Clin Densitom. 2019;22(4):544-53. doi: 10.1016/j.jocd.2019.07.004.
Burrell S, Desaulniers M, Jen H, et al. CAR practice guideline on bone mineral densitometry reporting: 2024 update. Can Assoc Radiol J. 2025;76(3):417-26. doi: 10.1177/08465371241307524.
Ceolin C, Scala A, Rocca MS, et al. Influence of androgen receptor on bone health in transgender adults: insights from the COMET study. J Endocrinol Invest. 2025;48(5):1237-48. doi: 10.1007/s40618-024-02522-z.
Tornese G, Di Mase R, Munarin J, et al. Use of gonadotropin-releasing hormone agonists in transgender and gender diverse youth: a systematic review. Front Endocrinol (Lausanne). 2025;16:1555186. doi: 10.3389/fendo.2025.1555186.
Chavaengkiat S, Suwan A, Panyakhamlerd K, et al. The effects of testosterone on bone turnover markers among hormone-naive transgender men. Transgend Health. 2024;9(6):501-7. doi: 10.1089/trgh.2023.0056.
Betsi G, Goulia P, Sandhu S, et al. Puberty suppression in adolescents with gender dysphoria: an emerging issue with multiple implications. Front Endocrinol (Lausanne). 2024;15:1309904. doi: 10.3389/fendo.2024.1309904.
Shuhart CR, Cheung AM, Gill RS, et al. Executive summary of the 2023 Adult Position Development Conference of the International Society for Clinical Densitometry: DXA reporting, follow-up BMD testing and trabecular bone score application and reporting. J Clin Densitom. 2024;27(1):101435. doi: 10.1016/j.jocd.2023.101435.
