Bone health and osteoporosis

Introduction

Adaptation of recommendations for osteoporosis screening to transgender populations is complicated by existing recommendations that vary widely for non-transgender people, including lack of consensus about screening for non-transgender men, and no U.S. national level recommendations on the frequency of screening.

Osteoporosis screening is currently age- and sex- based, and also individualized on the basis of risk factors. There are a number of lifestyle, genetic, endocrinologic, hematologic, rheumatoid and autoimmune diseases, as well as medications that contribute to osteoporosis. Known risk factors for osteoporosis include Caucasian or Asian race, older age, alcohol >10 drinks/week, low body mass index, smoking, chronic corticosteroid use, hypogonadism, rheumatoid arthritis, hyperparathyroidism, immobility, vitamin D deficiency and HIV infection.[1,2]

Osteoporosis risk in transgender women

In one study, researchers found that transgender women had factors which may contribute to an increased risk of osteoporosis, independent of and existing prior to hormone use, such as reduced levels of physical activity, lower muscle mass and grip strength, and lower levels of vitamin D.[3] Studies investigating BMD in transgender women receiving hormones have shown both lower, higher and no change in bone density after initiating hormones.[4-11] The differences in results may be due to the regimens used (some used unopposed androgen blockers for a period of time before initiating hormones) and length of follow-up. Known risk factors for osteoporosis include underutilization of hormones after gonadectomy or use of androgen blockers without or with insufficient estrogen. GnRH analogues also may result in short term decrease in bone mineral density (ie, GnRH analogues without concurrent estrogen, and when estrogen added, or blockers stopped bone density returns to normal).

Osteoporosis risk in transgender men

Most published studies to date have shown either no change, or an increase in bone mineral density in transgender men treated with testosterone. Risk factors for osteoporosis in this population include oophorectomy before age 45 without optimal hormone replacement.[4,6,9-13]

Current screening guidelines in non-transgender populations

There are no consistent guidelines on the optimal frequency of screening in non-transgender people. The WHO guidelines suggest every 10 years. A recent U.S. NIH funded study suggests intervals of approximately 15 years for normal bone density or mild osteopenia, 5 years for moderate osteopenia, and 1 year for advanced osteopenia. Screening intervals in transgender people can be based on these recommendations as well. All professional organizations recommend screening for all non-transgender women over age 65. Some recommend earlier screening in those with risk factors. Some older guidelines recommend screening in non-transgender men after age 70 or in those with risk factors, while others and more recent guidelines make no recommendations for men.

Recommended screening for transgender women and men

There is insufficient evidence to guide recommendations for bone density testing in transgender women or men. Transgender people (regardless of birth-assigned sex) should begin bone density screening at age 65. Screening between ages 50 and 64 should be considered for those with established risk factors for osteoporosis. Transgender people (regardless of birth assigned sex) who have undergone gonadectomy and have a history of at least 5 years without hormone replacement should also be considered for bone density testing, regardless of age (Grading: X C W).

Modality of screening

Dual-energy x-ray absorptiometry (DEXA) of the hip and lumbar spine.

Special considerations

There have been no studies to determine whether clinicians should use the natal sex or affirmed gender for assessment of osteoporosis, e.g., when using the FRAX® tool. Although some researchers use the natal sex, with the assumption that bone mass has usually peaked for transgender people who initiate hormones in early adulthood, this should be assessed on a case by case basis until there is more data available. This assumption will be further complicated by the increasing prevalence of transgender people who undergo hormonal transition at a pubertal age, or soon after puberty. Sex for comparison within risk assessment tools may be based on the age at which hormones were initiated, and length of exposure to hormones. In some cases it may be reasonable to assess risk using both the male and female calculators and using an intermediate value.

Weak evidence suggests that agonadal states contribute to an increased risk of osteoporosis, however long term studies are lacking.[14] Transgender people without gonads, and who are not using hormone replacement, should follow screening and prevention guidelines for agonadal or postmenopausal women, regardless of birth-assigned sex or gender identity (Grading: X C W).

Advice should be given to modify risk factors for osteoporosis, including tobacco cessation, Correct low vitamin D levels, maintain calcium intake in line with current guidelines for non-transgender people, weight bearing activity, and moderation of alcohol consumption.

References

1. National Osteoporosis Foundation. 2013 [cited 2016 Feb 4].
2. Watts NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, et al. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012 Jun;97(6):1802-22.
3. Van Caenegem E, Taes Y, Wierckx K, Vandewalle S, Toye K, Kaufman J-M, et al. Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy. Bone. 2013 May;54(1):92-7.
4. Wierckx K, Mueller S, Weyers S, Van Caenegem E, Roef G, Heylens G, et al. Long-term evaluation of cross-sex hormone treatment in transsexual persons. J Sex Med. 2012 Oct 1;9(10):2641-51.
5. Lapauw B, Taes Y, Simoens S, Van Caenegem E, Weyers S, Goemaere S, et al. Body composition, volumetric and areal bone parameters in male-to-female transsexual persons. Bone. 2008 Dec;43(6):1016-21.
6. Ruetsche AG, Kneubuehl R, Birkhaeuser MH, Lippuner K. Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2005 Jul;16(7):791-8.
7. Reutrakul S, Ongphiphadhanakul B, Piaseu N, Krittiyawong S, Chanprasertyothin S, Bunnag P, et al. The effects of oestrogen exposure on bone mass in male to female transsexuals. Clin Endocrinol (Oxf). 1998 Dec 1;49(6):811-4.
8. van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf). 1997 Sep;47(3):337-42.
9. Meriggiola MC, Armillotta F, Costantino A, Altieri P, Saad F, Kalhorn T, et al. Effects of testosterone undecanoate administered alone or in combination with letrozole or dutasteride in female to male transsexuals. J Sex Med. 2008 Oct 1;5(10):2442-53.
10. Mueller A, Haeberle L, Zollver H, Claassen T, Kronawitter D, Oppelt PG, et al. Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals. J Sex Med. 2010 Sep 1;7(9):3190-8.
11. Schlatterer K, Auer DP, Yassouridis A, von Werder K, Stalla GK. Transsexualism and osteoporosis. Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc. 1998;106(4):365-8.
12. Van Caenegem E, Wierckx K, Taes Y, Dedecker D, Van de Peer F, Toye K, et al. Bone mass, bone geometry, and body composition in female-to-male transsexual persons after long-term cross-sex hormonal therapy. J Clin Endocrinol Metab. 2012 Jul;97(7):2503-11.
13. Turner A, Chen TC, Barber TW, Malabanan AO, Holick MF, Tangpricha V. Testosterone increases bone mineral density in female-to-male transsexuals: a case series of 15 subjects. Clin Endocrinol (Oxf). 2004 Nov;61(5):560-6.
14. Garcia C, Lyon L, Conell C, Littell RD, Powell CB. Osteoporosis risk and management in BRCA1 and BRCA2 carriers who undergo risk-reducing salpingo-oophorectomy. Gynecol Oncol. 2015 Sep;138(3):723-6.