Differences in tissue-Level Properties as Assessed by Nano-Scratching in Patients With and Without Atypical Femur Fractures on Long-Term Bisphosphonate Therapy: A Proof-of-Concept Pilot Study

Atypical femur fractures (AFF) are a well-established complication of long-term bisphosphonate (BP) therapy, but their pathogenesis is not fully understood. Although many patients on long-term BP therapy have severe suppression of bone turnover (SSBT), not all such patients AFF even though SSBT is a major contributor to AFF. Accordingly, we evaluated tissue level properties using nano-scratch testing of trans-iliac bone biopsy specimens in 12 women (6 with and 6 without AFF matched for age and race). Nano-scratch data were analyzed using a mixed model ANOVA with volume normalized scratch energy as a function of AFF (Yes or No), region (periosteal or endosteal), and a first-order interaction between region and AFF. Tukey Post-hoc analyses of the differences of least squared means of scratch energy were performed and reported as significant if P<.05. The volume normalized scratch energy was 10.6% higher in AFF than in non-AFF patients (P=.003) and 17.9 % higher in the periosteal than in the endosteal region (P=.004). The differences in normalized scratch energy are consistent with a higher hardness of the bone tissue after long-term BP therapy. The results of this study are consistent with other studies in the literature and demonstrate the efficacy of using Nano-Scratch technique to evaluate bone tissue that exhibits SSBT and AFF. Further studies using nano-scratch may help quantify and elucidate underlying mechanisms for the pathogenesis of AFF.