Reference Point Indentation of Human Trabecular Bone Treated With Bisphosphonates for Varying Durations

Reference point indentation (RPI), a novel form of micro-indentation, quantifies RPI material parameters which correlate with modulus, yield stress, strength, or toughness. Information linking bisphosphonate treatment length with the material properties of osteoporotic trabecular bone is needed to improve patient treatment. The objectives of this study were to: 1) determine if RPI can be used to successfully evaluate human trabecular bone and if so, determine an optimized test method for using RPI on trabecular bone, and 2) use this method to determine if any RPI parameters are related to the duration of bisphosphonate treatment.

Indentation using a 4 N applied force for 5 cycles was determined to be optimal and used to indent trabecular bone samples from 44 post-menopausal, osteoporotic female patients treated with bisphosphonates for varying (0.8 to 14 years) durations.

Considering patient age and calcium supplementation use as covariates, six RPI parameters were significantly (p<0.05) related to BP treatment duration. These results show that the duration of BP treatment is associated with declining RPI-parameters in human trabecular bone. Given prior findings linking these RPI parameters with established material parameters, the present findings suggest that increasing duration of BP treatment is associated with declining trabecular bone material properties.

Keywords: Reference Point Indentation; bisphosphonates; trabecular bone quality

Year	Entry
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Year

Entry

1983

Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis: implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest. October 1983;72(4):1396-1409.

2015

Katsamenis OL, Jenkins T, Thurner PJ. Toughness and damage susceptibility in human cortical bone is proportional to mechanical inhomogeneity at the osteonal-level. Bone. July 2015;76:158-168.

1999

Zysset PK, Guo XE, Hoffler CE, Moore KE, Goldstein SA. Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur. J Biomech. October 1999;32(10):1005-1012.

2011

Schilcher J, Michaëlsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. NEJM. May 5, 2011;364(18):1728-1737.

2008

Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. March 2008;42(3):456-466.