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Nanomolecular changes in trabeculae due to bisphosphonate therapy


Burket et al. used a sheep model of osteoporosis to investigate the impact of bisphosphonate (BP) therapy on tissue hardness and stiffness at the trabecular and nanomolecular level.

The researchers separated 25 adult ewes aged between six and seven years into five groups; in the six to eight months of the study, one control group was fed a normal diet while the other four groups were fed to induce metabolic acidosis and, subsequently, osteoporosis. Two paired experiments looked at the effect of six months of zoledronate versus no BP treatment, and six months of raloxifene versus no BP treatment. Cancellous cores obtained from the distal femur of all of the sheep were analyzed using micro-computed tomography, compression testing and ashing, and their nanomolecular properties were investigated using nanoindentation, Raman spectroscopy and second harmonic generation microscopy.

At the nanomolecular level, sheep treated with zoledronate showed an increase in indentation modulus (+12%) and hardness (+16%) at the trabecular surface, compared to the paired control group. Raloxifene increased both properties throughout the trabeculae (+10%).

Editor’s comment: This study highlights the benefits of modeling osteoporosis in a large mammal. It also demonstrates that small tissue-level alterations in locations that are critical to determining trabecular failure could account for the degree of fracture risk reduction seen in osteoporotic women treated with BPs, which often does not correlate well with observed changes in bone mineral density.

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