Related Experiment Video
Updated: Jun 8, 2025
Scanning Skeletal Remains for Bone Mineral Density in Forensic Contexts
Published on: January 29, 2018
Blood and Bone-Derived DNA Methylation Ages Predict Mortality After Geriatric Hip Fracture: A Pilot Study
Sandip P Tarpada1, Johanna Heid2, Shixiang Sun2
1Department of Orthopaedic Surgery, R Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, Maryland.
Insights
Bone DNA methylation clocks are feasible and correlate with blood clocks in elderly hip fracture patients. Higher DNA methylation age in bone and blood is linked to increased 1-year mortality risk.
Area of Science:
- Gerontology
- Molecular Biology
- Epigenetics
Background:
- DNA methylation patterns offer insights into biological aging.
- Bone tissue epigenetics in aging and mortality remain underexplored.
- Geriatric hip fracture patients represent a vulnerable population with high mortality.
Purpose of the Study:
- To analyze bone-derived DNA methylation for the first time.
- To compare DNA methylation clocks from bone versus whole blood.
- To correlate DNA methylation age with 1-year mortality in hip fracture patients.
Main Methods:
- Prospective enrollment of hip fracture patients (≥65 years).
- Collection of preoperative whole blood and intraoperative bone samples.
- Reduced representation bisulfite sequencing (RRBS) for DNA methylation analysis.
- Computational algorithms to establish methylation age in both tissues.
- Statistical analysis of age differences and correlations.
Main Results:
- Feasibility of DNA extraction and methylation analysis from bone samples.
- Strong correlation (R=0.81, p=0.0016) between bone and blood methylation ages.
- Significantly higher DNA methylation age (ΔAge) in non-survivors (mortality cohort) compared to survivors.
- Mortality cohort showed mean ΔAgeBone of 18.33 years and ΔAgeBlood of 16.93 years.
Conclusions:
- Bone-derived DNA methylation clocks are viable and correlate with blood-derived clocks.
- Elevated DNA methylation age is independently associated with 1-year mortality post-hip fracture.
- Targeting advanced DNA methylation may reduce mortality in this population.
Background:
The purpose of this study was to (1) perform the first analysis of bone-derived DNA methylation, (2) compare DNA methylation clocks derived from bone with those derived from whole blood, and (3) establish a relationship between DNA methylation age and 1-year mortality within the geriatric hip fracture population.
Methods:
Patients ≥65 years old who presented to a Level-I trauma center with a hip fracture were prospectively enrolled from 2020 to 2021. Preoperative whole blood and intraoperative bone samples were collected. Following DNA extraction, RRBS (reduced representation bisulfite sequencing) libraries for methylation clock analysis were prepared. Sequencing data were analyzed using computational algorithms previously described by Horvath et al. to build a regression model of methylation (biological) age for each tissue type. Student t tests were used to analyze differences (Δ) in methylation age versus chronological age. Correlation between blood and bone methylation ages was expressed using the Pearson R coefficient.
Results:
Blood and bone samples were collected from 47 patients. DNA extraction, sequencing, and methylation analysis were performed on 24 specimens from 12 subjects. Mean age at presentation was 85.4 ± 8.65 years. There was no difference in DNA extraction yield between the blood and bone samples (p = 0.935). The mean follow-up duration was 12.4 ± 4.3 months. The mortality cohort (4 patients, 33%) showed a mean ΔAgeBone of 18.33 ± 6.47 years and mean ΔAgeBlood of 16.93 ± 4.02 years. In comparison, the survival cohort showed a significantly lower mean ΔAgeBone and ΔAgeBlood (7.86 ± 6.7 and 7.31 ± 7.71 years; p = 0.026 and 0.039, respectively). Bone-derived methylation age was strongly correlated with blood-derived methylation age (R = 0.81; p = 0.0016).
Conclusions:
Bone-derived DNA methylation clocks were found to be both feasible and strongly correlated with those derived from whole blood within a geriatric hip fracture population. Mortality was independently associated with the DNA methylation age, and that age was approximately 17 years greater than chronological age in the mortality cohort. The results of the present study suggest that prevention of advanced DNA methylation may play a key role in decreasing mortality following hip fracture.
Level Of Evidence:
Prognostic Level I . See Instructions for Authors for a complete description of levels of evidence.
