Bisphosphonate treatment changes regional distribution of trabecular microstructure in human lumbar vertebrae

In osteoporosis patients, antiresorptive treatments such as alendronate reduce the resorption of trabecular bone and thus minimize vertebral fracture risk. However, fracture risk reduction efficacy of antiresorptive drugs varies between skeletal sites and is highest for vertebral bone. In human vertebrae, cancellous bone is distributed heterogeneously between regions. This microstructural heterogeneity is changing with patient age and is likely to play a major role in vertebral failure mechanisms and fracture susceptibility. Whether antiresorptive treatment affects the heterogeneity of vertebral microstructure in osteoporosis has not been unraveled.

Our aim was to assess whether antiresorptive treatment would have a region-dependent influence on vertebral trabecular bone. Therefore, we used high-resolution peripheral quantitative computed tomography (HR-pQCT), microcomputed tomography (microCT) and uniaxial compression testing to determine the structure and mechanical properties of trabecular bone cores from anterior and posterior regions of 22 lumbar vertebrae from elderly osteoporotic women. We analyzed age-matched ex vivo bone samples from bisphosphonate-treated female osteoporosis patients (age: 82 ± 7y, bisphosphonate treatment period: 4 ± 2 years) along treatment-naïve female controls (82 ± 7y).

MicroCT analysis showed a significantly lower bone volume fraction (p = 0.006) and lower trabecular number (p = 0.003) for the anterior bone cores compared to posterior bone cores in the treatment-naïve group. The bisphosphonate-treated group had a more homogeneous bone volume distribution and did not show significant regional differences in bone volume, it however also displayed significantly different trabecular numbers (p = 0.016). In bone cores of the bisphosphonate-treated group, trabeculae were thicker in comparison to treatment-naïve controls (p = 0.011). Differences in bone volume further resulted in different maximum forces during compression testing between the samples. In addition, the percental difference between BV/TV_μCT in anterior and posterior bone cores was lower in bisphosphonate-treated vertebrae when vertebrae with directly adjacent fractures (n = 3) were excluded.

In conclusion, regional trabecular bone microstructure in lumbar vertebrae of bisphosphonate-treated women was more homogeneous compared to treatment-naïve controls. Bisphosphonate treatment, which specifically targets resorption surfaces common in anterior vertebral bone, might have resulted in a region-specific preservation of vertebral microstructure and loading capacity. This could have positive implications for the reduction of wedge fracture risk and add to the explanation of the higher efficacy of fracture risk reduction in vertebrae in comparison to other fracture regions.