Muscle and bone changes are out of step in children with progeria
Abnormal forearm bone shapes appeared in 70% of children with progeria but not healthy controls; lonafarnib did not normalize muscle–bone patterns after 24 months.
24 months, non-randomized trial, controlled
Limit: Failure to undergo normal puberty could explain some muscle and bone divergence from controls
Edited by Boris Djordjevic · AgingResearch.News
Children aged 2–18 with classic Hutchinson-Gilford Progeria Syndrome, a rare genetic premature-aging disease, underwent forearm scans in three open-label clinical trials. Researchers compared baseline scans from 71 participants (37 females and 34 males) with 45 healthy controls aged 3–16 (22 females and 23 males). They also compared scans before lonafarnib and after 24 months of treatment.
Bone shape abnormalities were present before changes in muscle area. Muscle area relative to body size resembled controls at younger ages but diverged with age. The authors concluded that muscle and bone changes did not follow their usual relationship. Lonafarnib did not normalize this pattern, although 25% of those with follow-up scans had partial normalization of bone shape. During follow-up, two participants (3%) fractured a forearm bone after significant trauma.
Why it matters
The authors suggested that early treatment, while muscle area was still normal for body size, may offer an opportunity to avoid later abnormalities in this premature-aging disease.
Caveats
Comparisons with healthy controls were cross-sectional, while treatment follow-up lacked an untreated comparison group; not all participants had 24-month scans. The findings concern classic progeria, not typical aging.
From the paper
- Participants
Seventy-two children and adolescents with the classic form of HGPS (LMNA p.G608G c.1824 C>T) from 32 countries, aged 2–18 years were enrolled in one or more of three successive single center open label clinical trials (NCT00425607, NCT00879034, NCT00916747) at Boston Children’s Hospital (BCH), each having pQCT data for review …
- Sex
There was at least one bone measurement for 71 (37 females and 34 males) participants with HGPS and 45 healthy controls without HGPS (22 females and 23 males) included in the cross-sectional analyses.
- Duration
For the participants with classic HGPS, pQCT at baseline trial visit while untreated, and at 24 months of treatment with lonafarnib, were included in the study.
- Muscle area
Fat and muscle differences were readily apparent, with extremely low fat and muscle area in HGPS versus controls (both p<0.001).
Results, Participants with HGPS have reduced forearm fat and skeletal muscle
- Radial area
Compared to controls, radial area was drastically lower in individuals with HGPS (26.8 mm² v. 100.9 mm², p<0.001).
Results, Participants with HGPS have abnormal radial architecture and radial area
Quoted word for word from the full text on PubMed Central.
The paper
Broad Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development
Journal of Bone and Mineral Research, Dec 4, 2025, Open access, accepted manuscript
