Low Bone Mineral Density in Early Pubertal Transgender/Gender Diverse Youth: Findings From the Trans Youth Care Study

Findings From the Trans Youth Care Study

Disclosures

J Endo Soc. 2020;4(9) 

In This Article

Discussion

We identified a high prevalence of low BMD (Z-score < -2) in early-pubertal TGD youth before starting GnRHa therapy, with higher rates in DMAB than in DFAB. Our findings extend prior studies in late-pubertal transgender youth,[9] by demonstrating that low BMD is already present by early puberty and thus this disparity could arise before puberty. Earlier identification of low BMD in prepubertal TGD youth could therefore expand the time for potential interventions to mitigate this pretreatment discordance in BMD and, in turn, the expected further decrease in BMD Z-scores with GnRHa.[9,10,14,15] Our linear regression results support this concept because age at puberty blocker placement was negatively associated with BMD Z-scores at the hip sites, suggesting that underlying factors contributing to low BMD may potentially have more time to exert negative effects. This negative association can also be explained, in part, by the differential timing of puberty in DMAB versus DFAB individuals, as DMAB youth had both lower BMD Z-scores and later ages at pubertal onset. Additionally, because eligibility was based on early-pubertal status, older individuals in the study cohort started puberty at the later end of the usual age range, so it is expected that they would have lower BMD compared with reference ranges based on youth who largely had more typical timing of puberty and thus had significant exposure to sex steroids by that age. Contribution of Tanner stage at time of blocker initiation to BMD Z-scores was not statistically significant at any anatomical sites, but the mostly positive β-coefficients in our regression models suggest that later Tanner stage at time of puberty blocker placement had a positive effect on BMD Z-scores, reflecting the positive effect of pubertal hormones on bone mineralization.

We additionally noted that there were statistically significant differences in BMD Z-scores at the hip sites between DMAB and DFAB groups. Although the International Society for Clinical Densitometry notes that the hip is not a preferred site for pediatric DXA measurements,[29] the hip is primarily cortical bone, whereas the lumbar spine is primarily trabecular bone. The hip mineralizes earlier than the spine,[30] such that we may be able to observe differences at the hip before they are apparent in other regions. The hip is also a weight-bearing site, and the lower BMD Z-scores in the DMAB youth make sense given the findings of lower PAQ-C scores in the DMAB youth. Finally, the International Society for Clinical Densitometry does suggest potential utility in proximal femur DXA measurements for assessing children with reduced weight-bearing of the lower extremities who would benefit from serial DXA measurements into adulthood.[29]

With respect to determinants of skeletal health, PAQ-C scores were low overall and significantly lower in DMAB than DFAB youth, providing a potential explanation for the lower pretreatment BMD Z-scores in the DMAB group. However, regression models showed that PAQ-C scores could not completely account for these differences, suggesting that other factors may also contribute to this difference. Further reinforcing the postulation that lower physical activity contributes to the low BMD Z-scores are the statistically significantly lower PAQ-C scores in the group with low BMD when compared with the group with normal BMD. Prior studies according to recorded sex (gender identity was not ascertained) have reported that boys have higher PAQ-C scores than girls;[21,22] thus, TGD youth in our study tended to have physical activity levels that correspond to gender identity.

In contrast to physical activity, no significant differences were found in serum 25-hydroxyvitamin D, dietary calcium intake, and BMI Z-scores between DFAB and DMAB groups, or between low-BMD and normal-BMD groups. However, daily calcium intake was globally suboptimal in our early-pubertal TGD youth cohort. The majority of the literature supports adequate calcium intake in improving BMD,[28] with greater gains seen in those who begin supplementation at earlier stages of puberty[31] and who have lower baseline daily calcium intake.[32] However, there are still gains seen in those who are later in puberty and have higher baseline daily calcium intakes.[33] These results suggest that potential interventions for improving BMD could include standard recommendations for optimizing dietary calcium and vitamin D intake as well as increasing weight-bearing exercise, which could be initiated in the prepubertal to early-pubertal time period.[34–36] Additionally, BMI Z-scores were a significant positive predictor of BMD Z-scores at the TBLH site, reinforcing that careful assessment of physical activity and dietary history to screen for eating disorders should be done,[37] particularly if low BMD is found.

Strengths of our study include assessments of dietary calcium intake, physical activity, and vitamin D status, which have not been reported previously in transgender youth. A limitation of this study is related to the observational and multisite nature of the Trans Youth Care study, such that BMD measurements were not standardized across all sites. Despite this limitation, we obtained comparable results across the different imaging modalities, lending robustness to our findings. As of yet, fracture data have not been reported in transgender adolescents and, thus, BMD Z-scores are the only current proxy for estimating future fracture risk.

It has been shown that significant bone mineralization occurs after linear growth is complete.[30] Because timing of puberty influences peak bone mineral content, such that later pubertal onset leads to lower adult bone mineral content,[38–40] longitudinal follow-up of this cohort with continued skeletal imaging will be critical for understanding the trajectory of bone mineral accrual as these youth are treated with GnRHa and progress to treatment with gender-affirming sex steroids. Findings from this pretreatment analysis will be followed up by longitudinal assessments over time and will further inform our current treatment and monitoring protocols.

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