Localized bone deterioration predicts declining failure load and increased fracture risk.

UNLABELLED: Localized bone loss, known as void spaces, has not been previously assessed longitudinally. This study investigated age- and sex-related changes in void spaces over time and explored their relationship with fracture risk and bone strength. We found that void space increases with age, progresses more rapidly in females, and is associated with both fracture risk and bone strength.

INTRODUCTION

Localized regions of trabecular deterioration, termed void spaces, are weak spots in bone that compromise strength. Prior studies have used cross-sectional data to explore temporal changes, but this is limited by secular effects. This study aimed to assess age- and sex-related changes in void spaces using longitudinal data and to explore their relationship with fracture risk and bone strength.

METHODS

We analyzed 603 participants (63.2% female) from a longitudinal population study. HR-pQCT scans of the distal radius and tibia were acquired using the fixed offset positioning at two visits 3-10 years apart. Scans were registered, and void space was quantified as the ratio of void space to total volume (VS/TV [%]). Linear mixed-effects models evaluated the influence of age, sex, and site on void space progression. Associations with fracture risk and bone strength were assessed using linear regression.

RESULTS

The average age was 53.7 ± 15.3 years, with a mean follow-up of 6.8 ± 1.8 years. Void space increased by 0.02% per year of age (p< 0.001), with males showing 1.04% lower VS/TV at baseline and slower progression (p< 0.001). A 1% increase in VS/TV was correlated with a 0.5% increase in fracture risk (p< 0.01) and a reduction in failure load of 31.6 N at the radius (p = 0.073) and 111.3 N at the tibia (p = 0.006).

CONCLUSION

Void spaces increased with age, progressed slower in males, and were strongly associated with reduced bone strength, especially at the tibia. While the impact on fracture risk was modest, void space may serve as an early marker of skeletal deterioration, supporting the potential role in osteoporosis monitoring.