Bone Density, Puberty Blockers & Gender-Affirming Hormones

🦴 Does puberty suppression affect bone development?

This new systematic review and meta-analysis pulled together the available longitudinal research on bone development to find out when puberty is suppressed — and what happens after gender-affirming hormones are started?

📚 The paper

Tienforti D, Marinelli L, Terrana G, et al. Bone Accrual During Puberty Suppression and Gender-Affirming Therapy in Transgender Adolescents: A Systematic Review and Meta-Analysis. JAMA Pediatrics. Published online August 3, 2026.

The researchers wanted to answer a pretty important question:

What happens to bone mineral density in young people accessing gender affirming medical treatments

🔬 First, a little bone science...

Adolescence is a really important time for building bone.

Think of your skeleton as having a “bone-building season” during puberty. A lot of the bone mass you build during these years contributes to your skeletal health later in life.

Puberty blockers (GnRHa) temporarily suppress sex hormones. Because sex hormones contribute to bone development, researchers have been interested in whether delaying puberty affects this process.

News in this study? Bone development doesn't simply stop, but there is a measurable change in the way bone density develops during puberty suppression and hormones

👥 Who was studied?

The researchers combined 10 longitudinal studies involving 751 TGD adolescents:

• 427 participants registered as female at birth (AFAB)

• 324 participants registered as male at birth (AMAB)
• 🇳🇱 🇧🇪 🇨🇦 🇬🇧 🇺🇸  Studies from several countries
• 📊 3 prospective studies + 7 retrospective studies

The researchers looked at three important parts of the skeleton:

🦴 Lumbar spine
🦴 Total hip
🦴 Femoral neck

They used DXA scans to measure bone mineraldensity (BMD).

The researchers then looked at bone measurements at three stages:

T0 → Before puberty suppression

⬇️

T1 → After puberty suppression

⬇️

T2 → After gender-affirming hormones

📉 What happened during puberty suppression?

This was the clearest finding in the study.

Bone-density z-scores went down

At the lumbar spine, the average change during puberty suppression was:

AFAB: −0.97
AMAB: −0.73

These were statistically significant changes

Similar decreases were seen at the hip

But here's the important Geek Out detail... a z-score isn't the same thing as your actual amount of bone.

It tells us how someone's bone measurement compares with a reference population of the same age and sex.

In this research, the z-scores were calculated using sex-assigned-at-birth reference standards, because there aren't currently validated reference databases specifically for Trans adolescents

So a lower z-score doesn't automatically mean:

“This person's bones are becoming weak.”

It means their bone density is lower relative to the reference population used for comparison.

And that distinction becomes especially important when interpreting what happens after hormone therapy

🔄 Then came gender-affirming hormones...

Here's where the story gets interesting.

After Hormones began:

📈 Actual bone mineral density increased.

At the lumbar spine, BMD increased by approximately:

+0.09 g/cm² in AFAB adolescents

+0.13 g/cm² in AMAB adolescents

And bone-density z-scores started to recover.

So the pattern looked roughly like this:

PUBERTYSUPPRESSION

🦴Bone-density z-score
⬇️ decreases

↓

GAHT

🦴 Bone mineral density
⬆️ increases

🦴 z-score
⬆️ partially recovers

But...

‍

🧐 Had bone density completely “caught up”?

Not clearly.

At the end of the follow-up period, z-scores were still numerically lower than baseline.

At the lumbar spine, the difference from baseline was approximately:

AFAB: −0.51

AMAB: −0.52

However, when the researchers looked specifically at participants who had complete measurements at all three timepoints,

🧐 The differences between baseline and follow-up were not statistically significant.

The researchers describe this as a “modest and uncertain shortfall in catch-up”, rather than evidence of a demonstrated permanent bone deficit.

🧠 So... do puberty blockers make your bones weaker?

The evidence doesn't suggest that participants developed clinically significant low bone density.

The researchers found that residual differences at the hip and femoral neck were generally modest.

Importantly, no study consistently reported a clinically relevant proportion of participants with a z-score ≤ −2.0 after GAHT — the threshold commonly used to identify low bone density

And the authors conclude that current evidence does not support a high prevalence of clinically significant skeletal impairment in this population.

That's quite different from saying:

“There is no effect on bone.”

There is an effect on bone-density measurements during puberty suppression.

The question is what happens over the longer term — and that's where the evidence becomes less certain.

⏰ Timing seems to matter

The researchers also looked at factors that might influence bone outcomes.

They found associations suggesting:

⏳ Longer time on puberty blockers

was associated with less favourable z-score trajectories, particularly among AFAB adolescents.

💉 Longer exposure to GAHT

was associated with better lumbar-spine z-score outcomes in AMAB adolescents.

⚖️ Higher BMI

was associated with more favourable bone-density changes.

The researchers specifically describe these analyses as exploratory and hypothesis-generating because there were relatively few cohorts and there may be other differences between participants that weren't fully accounted for.

☀️ Vitamin D & lifestyle matter too

There was another interesting finding hiding in the data:

Vitamin D insufficiency was common across the studies.

But none of the 10 studies consistently accounted for vitamin D status or physical activity when analysing bone outcomes.

Only two studies adjusted for both BMI and pubertal stage.

That means bone health isn't just about hormones.

Nutrition, vitamin D, body composition and physical activity all potentially contribute to skeletal development.

The authors therefore recommend paying attention to these modifiable factors during treatment.

‍

⚠️ GeekOut: What are the limitations?

1️⃣ We don't yet have decades of follow-up

Most of the studies followed participants for relatively short periods.

So we cannot yet answer the really long-term question:

Does this affect fracture risk or peak bone mass decades later?

No included study reported fracture outcomes.

2️⃣ There weren't cisgender control groups

None of the studies included a parallel cisgender comparison group.

That makes it harder to know exactly how the observed changes compare with normal variation in bone development.

3️⃣ Not everyone had complete longitudinal data

So the most useful “before → blockers → GAHT” analysis represents a smaller subset of the overall group.

4️⃣ The z-score comparison is imperfect

This one is particularly important.

The researchers had to compare participants against sex-assigned-at-birth reference standards because there aren't validated Trans-specific normative databases.

But someone receiving GAHT has a hormonal environment that is different from the population represented by those reference standards.

The authors say this may over estimate some residual differences, particularly at follow-up.

5️⃣ The studies weren't all identical

Different studies used different DXA machines, had different follow-up periods and didn't all adjust for the same potential confounders.

That makes combining them more complicated, however, sensitivity analyses suggested that no single study drove the overall findings

🧩 Putting it all together

The best way to visualise the evidence is:

Before treatment

🦴 Bone development is occurring

↓

Puberty suppression

🦴Bone-density z-scores decrease

↓

GAHT begins

🦴 Actual BMD continues to increase
🦴 z-scores begin to recover

↓

Follow-up

🦴 z-scores may remain somewhat below baseline
🦴 but the evidence does not demonstrate a persistent clinically significant deficit

And we still need longer-term research to know what happens to peak bone mass and fracture risk.

‍

💡 GEEKOUT TAKEAWAY

🦴 Puberty suppression is associated with reduced bone-density z-scores comparative to 'no intervention' in same birth registered sex group

🔄 GAHT is associated with increasing BMD and partial recovery of z-scores.

🧐 Whether there is a meaningful long-term shortfall in peak bone mass remains uncertain

📚 Current evidence does not show clinically significant skeletal impairment.

‍