Abstract
BACKGROUND: Impaired bone health is a common morbidity in Rett syndrome (RTT). We aimed to assess lumbar bone mineral density (BMD) and trabecular bone score (TBS) in females with RTT, and to evaluate the effectiveness of bisphosphonate treatment. METHODS: This retrospective study included 40 females with RTT, aged 5-22 years, who underwent dual-energy X-ray absorptiometry (DXA) scans during 2019-2024 at a national center for RTT. Data collected included medical treatment, anthropometric measurements, and functional scores. RESULTS: The median age at the first DXA scan was 10.8 years. The mean L1-4 BMD Z-score was -2.1 ± 1.4, and the mean TBS Z-score was -0.4 ± 1.3. The L1-4 BMD Z-score correlated with height (r = 0.407, p = 0.009), weight (r = 0.551, p < 0.001), BMI (r = 0.644, p < 0.001), and TBS Z-scores (r = 0.594, p = 0.009). Poor L1-4 BMD Z-scores were associated with poor mobility scores (p = 0.05) and valproate treatment (p = 0.016). Nine patients (23%) received zoledronate, for a mean 2 years. The mean age at zoledronate initiation was 9.7 ± 2.3 years. Four completed two DXA scans (pre- and post-treatment); the mean BMD Z-score improved from -2.2 ± 0.9 to -1.4 ± 0.9 after treatment. CONCLUSIONS: Females with RTT have reduced lumbar BMD, which was associated with anthropometric factors, TBS, mobility, and valproate use. Zoledronate may be effective for some patients. IMPACT: In a retrospective study of 40 females with Rett syndrome (RTT), low bone mineral density (BMD) correlated with lower anthropometric measurements, impaired mobility, and valproic acid use. The association between BMD and trabecular bone score (TBS) in the context of RTT is a novel finding. Our preliminary data support the effectiveness and safety of zoledronate for treating osteoporosis in patients with RTT. Our findings are important in light of the increasing life expectancy of individuals with RTT, and the consequent need to prioritize bone health in this population.