Abstract
Background: The expected pubertal accrual of bone mineral density (BMD) may be disrupted in trans and gender diverse (TGD) adolescents who undergo pubertal suppression with Gonadotropin Releasing Hormone agonists (GnRHa)1. The extent of this effect remains unclear and is confounded by varying methods used to assess BMD1.While BMD Z-scores in GnRHa-treated TGD adolescents may be expected to decline relative to pubertal peers, this measure provides no information on actual changes in BMD. Annualised, percent change in BMD (%BMD velocity, %BMDV) provides a standardised measure of accrual or loss, but has not been reported in this context. Aims: (1) To evaluate bone accrual or loss using %BMDV in a cohort of GnRHa-treated TGD adolescents; (2) to explore associations between baseline characteristics (BMD Z score, Vitamin D status and Tanner Stage) and %BMDV. Methods. Retrospective 10yr audit at tertiary pediatric gender service. Bone densitometry data were collected at baseline and 12-24monthly during GnRHa. Areal BMD values and Z-scores for lumbar spine (LS) and total hip (TH) were obtained. %BMDV between baseline and final scan was calculated for LS and TH. Population data for %BMDV before and during puberty were derived from the BMD in Childhood Study2. Results are reported as mean (±SD) or mean difference (MD; 95% confidence interval). Results. Data from 28 patients (20 transfemale; 8 transmale) who commenced GnRHa at 13.3 (±2.0) yrs and were observed over 23.2 (±11.5) mo were included. Mean (±SD) %aBMDV during GnRHa therapy was -0.66 (±4.54) %/yr for TH and +1.91 (±4.23) %/yr for LS, both substantially lower than %aBMDV in pre-pubertal population controls (~+3-4%/year). 53% of GnRHa-treated youth exhibited negative %aBMDV, indicating bone loss, at TH and/or LS. %aBMDV was lower in (i) Vitamin D deficient youth, with MD at TH (-6.07; -9.00, -3.13); and LS (-4.93; -9.56, -0.30) relative to Vitamin D sufficient peers and (ii) youth who were Tanner stage 4+ at baseline, with MD at TH (-4.1; -7.7, -0.44) and LS (-3.6; -7.2, 0.01) relative to Tanner stage 2-3 peers. Height-adjusted Z scores declined from baseline with GnRHa treatment in >95% of patients and were not predictive of %aBMDV. Conclusion. GnRHa-treated TGD adolescents in this cohort exhibited lower BMD accrual rates than pre-pubertal population controls. Over half of our cohort lost BMD, which is a significant concern in adolescence. Vitamin D deficiency and more advanced pubertal stage at GnRHa initiation were associated with greater bone loss during treatment. These data highlight the need to monitor and optimise bone health in GnRHa-treated TGD young people. We recommend routine annual densitometry and %BMDV evaluation regardless of baseline Z-scores as well as routine screening and treatment of vitamin D deficiency while on GnRHa.References.1.Chew D., et al., Pediatrics, 2018. 141: p.e20173742.2.Zemel B.S., et al., JCEM, 2011. 96 p.3160-9.
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