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

Author:

Johnson Gabriel1,Griffin Lanny V1,Qiu Shijing234,Rao Sudhaker D234ORCID

Affiliation:

1. Department of Biomedical Engineering, California Polytechnic State University (Cal Poly) , San Luis Obispo, CA, 93407-0365 , United States

2. Bone & Mineral Research Laboratory, Henry Ford Health/Wayne State University Integrative Biosciences (IBio) Research Facility , Detroit, MI, 48202 , United States

3. Division of Endocrinology , Diabetes, and Bone & Mineral Disorders, , Detroit, MI, 48202 , United States

4. Henry Ford Health , Diabetes, and Bone & Mineral Disorders, , Detroit, MI, 48202 , United States

Abstract

Abstract Atypical femur fractures (AFFs) 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 experience 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 suggestive of 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.

Funder

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institutes of Health

Publisher

Oxford University Press (OUP)

Reference23 articles.

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