Structural alterations during fracture healing lead to void spaces developing in surrounding bone microarchitecture

Abstract Distal radius fractures are among the most common fracture sites, with a high incidence across all age groups. High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled assessment of bone microarchitecture in vivo at the distal radius, providing new insights into the healing process. However, we have observed structural bone loss that is not captured by standard analysis. This study uses void space analysis to quantify development of localized structural bone loss during fracture healing. Twenty-six participants (21 female, 5 male, aged 18-79 years) with conservatively-treated distal radius fractures were scanned using HR-pQCT at 6 study visits post-fracture (weeks 1, 3, 5, 12, 26, and 52). Total BMD (Tt.BMD), bone volume fraction (BV/TV), and void space volume fraction (VS/TV) were measured. Grip strength relative to the non-fractured wrist and Patient Rated Wrist Evaluation (PRWE) were measured at all study visits after cast removal. The cumulative expansion of VS/TV across sequential study visits was quantified to differentiate voids that developed during healing from pre-existing void space. A five-fold increase in median VS/TV was observed during the follow-up period, from 1.0% (0.6-9.0%) to 5.5% (2.5-12.4%). Tt.BMD and BV/TV did not significantly change in this same time interval. Relative grip strength after cast removal was significantly inversely correlated with final VS/TV (⍴ = -0.63, p=.02) and cumulative expansion of new void space during healing (R = -0.67, p<.01), whereas no significant associations were found with age or PRWE. This study suggests that there are adverse changes in bone microarchitecture during fracture healing, despite the preservation of overall Tt.BMD and BV/TV in the same region. Reduced grip strength is correlated with more severe void space formation, but the mechanistic relationship requires further exploration. The formation of void spaces may have long-term implications on bone strength and could provide insight into risk of re-fracture.