Adolescence is the critical window in which most of the bone mass of a lifetime is accumulated. That is why any treatment that interferes with this process raises legitimate doubts. A new meta-analysis published in JAMA Pediatrics (a journal of the JAMA family, one of the most influential in the world in pediatrics) has brought together the best available evidence to answer a specific question: what happens to the bones of adolescents with gender dysphoria who receive puberty blockers and, afterwards, hormone therapy?
What the researchers did
The team, coordinated from the University of L’Aquila (Italy) and Ghent University (Belgium), analyzed ten longitudinal studies with a total of 751 adolescents (427 assigned female at birth and 324 assigned male at birth). Combining the data with meta-analysis techniques, they followed the evolution of bone density at three time points: at baseline, after puberty suppression and after hormone therapy.
What they found during puberty suppression
During treatment with gonadotropin-releasing hormone (GnRH) agonists, that is, puberty blockers, absolute bone density remained stable. However, the z-score of the lumbar spine —which compares the values with those of the reference population of the same sex assigned at birth and the same age— decreased significantly: almost one point in people assigned female and just under three quarters of a point in those assigned male.
That drop is expected: by slowing down the sex hormones, the rate of bone accumulation is also slowed. The authors also note that puberty suppression reduces lean mass and increases fat, which can weaken the so-called “muscle-bone unit”, a key driver of skeletal development.
What happened when hormone therapy was started
The good news came in the second phase. After starting hormone therapy (with a median duration of 36 months), absolute bone density increased in both groups: by 0.09 g/cm² in people assigned female and by 0.13 g/cm² in those assigned male. The z-score partially recovered, although it still remained somewhat below the baseline value at the end of follow-up.
The important thing, the authors stress, is that those remaining differences were not statistically significant at most of the skeletal sites analyzed. In other words, a “modest and uncertain” delay in recovery was observed, not a demonstrated permanent deficit.
What favors a better outcome
The meta-analysis identified several factors associated with better bone health: a higher body mass index, a shorter duration of blockers and longer exposure to hormone therapy. The lumbar spine was the area most sensitive to hormonal changes, while in the hip and femoral neck the recovery was more modest and variable.
Recommendations for clinical practice
The researchers insist that bone health should be monitored throughout the entire treatment, and not only in one phase. Among their advice: start hormone therapy promptly, ensure an adequate intake of calcium and vitamin D (vitamin D insufficiency was common in the studies), encourage weight-bearing exercise and carry out follow-up with densitometry (DXA).
What it means for science
The work has limitations that the authors themselves acknowledge: relatively short follow-ups, the absence of a parallel cisgender comparison group and little information on fractures or bone turnover markers. Even so, it provides one of the most complete evidence syntheses to date on a central topic in the medical debate. The conclusion, qualified but clear, is that puberty suppression temporarily slows bone accumulation, but hormone therapy allows a recovery that should be closely monitored.
Source: Bone Accrual During Puberty Suppression and Gender-Affirming Therapy in Transgender Adolescents: A Systematic Review and Meta-analysis. Tienforti D, et al. JAMA Pediatrics 2026. DOI: 10.1001/jamapediatrics.2026.2470.
