Nanoscale mechanisms in age-related hip-fractures

Shaocheng Ma,Nick Terrill,Ulrich Hansen,Richard L Abel,Justin P Cobb,Oliver Boughton,John H Churchwell,En Lin Goh,Rajarshi Bhattacharya,Yong Wu,Tabitha Tay,Crispin C Wiles,Angelo Karunaratne

doi:10.1038/s41598-020-69783-5

Abstract

Nanoscale mineralized collagen fibrils may be important determinants of whole-bone mechanical properties and contribute to the risk of age-related fractures. In a cross-sectional study nano- and tissue-level mechanics were compared across trabecular sections from the proximal femora of three groups (n = 10 each): ageing non-fractured donors (Controls); untreated fracture patients (Fx-Untreated); bisphosphonate-treated fracture patients (Fx-BisTreated). Collagen fibril, mineral and tissue mechanics were measured using synchrotron X-Ray diffraction of bone sections under load. Mechanical data were compared across groups, and tissue-level data were regressed against nano. Compared to controls fracture patients exhibited significantly lower critical tissue strain, max strain and normalized strength, with lower peak fibril and mineral strain. Bisphosphonate-treated exhibited the lowest properties. In all three groups, peak mineral strain coincided with maximum tissue strength (i.e. ultimate stress), whilst peak fibril strain occurred afterwards (i.e. higher tissue strain). Tissue strain and strength were positively and strongly correlated with peak fibril and mineral strains. Age-related fractures were associated with lower peak fibril and mineral strain irrespective of treatment. Indicating earlier mineral disengagement and the subsequent onset of fibril sliding is one of the key mechanisms leading to fracture. Treatments for fragility should target collagen-mineral interactions to restore nano-scale strain to that of healthy bone.

Highlights

MethodsEthical approval was granted by the Imperial College Tissue Bank (R13004) and all patients consented for permission to use excess tissue from hip arthroplasty in research
There were no significant differences in age between the groups (Kruskal Wallis p = 0.135)
In complete contrast, we found a drop of 60% in the bisphosphonate-treated group while Zimmermann and colleagues[13] reported that young and bisphosphonate-treated bone had similar onset of fibril sliding and essentially that bisphosphonates had restored the nanomechanical properties of the bone

Summary

Methods

Ethical approval was granted by the Imperial College Tissue Bank (R13004) and all patients consented for permission to use excess tissue from hip arthroplasty in research. Patients’ histories of metabolic bone disease and treatment were collected from patient records. All individuals with a history of primary bone disease or underlying disorders such as cancer, which could lead to secondary bone disease were excluded from this study. A consecutive series of femoral heads were collected from 21 patients with an intracapsular fracture after written informed consent was provided at St Mary’s Hospital (London, United Kingdom) between May 2015 and September 2017. Medical records and physical assessments were examined to select 10 donors with no history of fractures, bone metabolic disease or treatments. It is important to note that it was not possible to obtain dual-energy X-ray absorptiometry (DXA), fracture risk assessment tool (FRAX) or body mass index (BMI) data for any of the donors

Results

Discussion

Conclusion