Bone Density Appears to Rebound in Transgender Youth After Puberty Blockers Are Done

Key Takeaways - Pubertal suppression has been flagged as a time of skeletal vulnerability among transgender and gender-diverse adolescents. - A meta-analysis linked puberty blocker use to temporary lumbar spine z-score drops, which partially recovered after gender-affirming hormone therapy. - Absolute bone mineral density was stable during puberty suppression and modestly increased with gender-affirming hormone therapy. Bone growth among transgender and gender-diverse adolescents slowed compared with peers during pubertal suppression, but partially recovered after starting gender-affirming hormone therapy, a systematic review and meta-analysis showed. Across 10 longitudinal studies involving 751 adolescents, absolute bone mineral density (BMD) remained stable during gonadotropin-releasing hormone agonist (GnRHa) therapy over mean durations up to 38.4 months. However, lumbar spine BMD z-scores dropped significantly compared with sex-assigned-at-birth normative references: - Assigned female at birth (AFAB) z-score change: -0.97 (95% CI -1.09 to -0.85) - Assigned male at birth (AMAB) z-score change: -0.73 (95% CI -0.93 to -0.53) Partial z-score recovery followed gender-affirming hormone therapy during a median treatment duration of 36 months but remained numerically below baseline for AFAB (-0.51, 95% CI -0.69 to -0.34) and AMAB (-0.52, 95% CI -0.82 to -0.21), reported Daniele Tienforti, MD, of the University of L'Aquila in Italy, and colleagues. "At follow-up, z-scores remained numerically lower than baseline but were generally not statistically different across most skeletal sites, suggesting at most a modest and uncertain shortfall in catch-up rather than a demonstrated persistent deficit," the authors wrote in JAMA Pediatrics. After gender-affirming hormone therapy (GAHT), absolute BMD increased modestly in AFAB (mean difference 0.09 g/cm2) and AMAB youth (mean difference 0.13 g/cm2), "indicating ongoing bone accrual during GAHT despite residual numerical differences in z-scores," the authors noted. "Our results suggest that puberty suppression temporarily slows bone accrual, but this is followed by a clear recovery after gender-affirming hormone therapy is initiated," Tienforti told MedPage Today. Mechanistically, the authors explained that skeletal vulnerability during pubertal suppression "may be compounded by GnRHa-induced reductions in lean mass and increases in fat mass, impairing the muscle-bone unit, a key driver of skeletal development." Lower baseline BMD has also been observed in some transgender and gender-diverse adolescents, particularly those AMAB, "potentially increasing vulnerability to treatment-related bone changes," they added. While the initial slowdown in bone accrual was expected based on prior research, Tienforti said that he found the consistency of the recovery pattern particularly interesting. "Across different cohorts and healthcare settings, we observed the same overall trajectory: bone mineral density increased and bone accrual resumed after the introduction of sex steroids," he said. "At the same time, our findings highlight an important gap in the current evidence. Although bone mineral density improves, z-scores often remain below baseline during the available follow-up." Because adolescence is the primary window for acquiring lifelong bone mass, Tienforti emphasized that monitoring of bone health should be part of routine gender-affirming care throughout treatment. "Rather than focusing on a single phase of treatment, I think it's important to view skeletal development as a dynamic process that deserves ongoing attention throughout care," he noted. Tienforti advised clinicians to focus on modifiable lifestyle factors -- such as adequate calcium and vitamin D intake, regular weight-bearing exercise, and structured DXA surveillance -- while tailoring treatment timing and duration to each patient. For the meta-analysis, the researchers searched major academic databases through September 2025. The final pooled cohort comprised 427 AFAB and 324 AMAB adolescents. Anatomical site-specific analyses revealed that the lumbar spine was the most responsive site to hormonal changes. Trajectories at the total hip and femoral neck were more modest and heterogeneous, though they generally followed the same pattern of temporary z-score declines during GnRHa followed by partial rebound on gender-affirming hormone therapy. Meta-regressions indicated that higher body mass index, shorter GnRHa duration, longer gender-affirming hormone therapy exposure, and older age at GnRHa initiation were associated with more favorable bone density outcomes. Baseline vitamin D insufficiency was common across cohorts. Given its critical role in bone metabolism and accrual, the authors advised routine supplementation of approximately 600 IU/day of cholecalciferol alongside balanced nutrition and physical activity. The team acknowledged several limitations, including relatively short follow-up periods across cohorts, lack of parallel cisgender comparator groups, inconsistent adjustment for key confounders, and sparse reporting of bone turnover markers or fracture rates. "Since peak bone mass is reached in early adulthood, we still need longer-term studies to understand whether bone mineral density continues to recover into adulthood," Tienforti said.