Discussion
fracture, compressive buckling, osteoporosis
PERIOSTEUM, OSTEOPOROSIS
This exploratory analysis of the ACTIVE-J trial demonstrated the changes in bone geometry and biomechanical properties at the proximal femur by using conventional DXA-based HSA with daily injection of 80 μg ABL for 78 weeks. To the best of our knowledge, this is the first longitudinal study to assess the effect of ABL on bone strength indices in elderly Japanese patients with osteoporosis at high risk of fracture. Our results indicate time-dependent potential improvement in bone strength based on HSA indices (CSMI, SM, and BR) at the NN, IT, and FS.After 78 weeks of ABL treatment, the total hip and FN BMD increased from baseline when evaluated using conventional DXA [At the NN and IT, hip geometry indices of DXA-based HSA, such as CSA, improved from week 12 of ABL treatment, whereas CoTh improved from week 24 compared with PBO. At the FS, CoTh and CSA also improved after 12 weeks of ABL treatment. Moreover, improvement in CoTh and CSA was greater in the ABL vs PBO group at week 78 at all assessed regions. In contrast, the OD remained unchanged from baseline to 78 weeks of ABL treatment in all investigated regions. At the NN and IT, although the mean percent change in OD did not differ significantly, the OD value was higher in the ABL treatment group than in the PBO group. There is no clear report that suggests that the OD of the FN increases with teriparatide treatment. However, recently, it has been reported that ABL has a stronger modeling-based bone formation–promoting effect at the periosteum compared with teriparatide [Improvements in hip strength indices, such as CSMI and SM, were observed at the NN from week 12 and at the IT from week 24 of ABL treatment compared with PBO, indicating a rapid effect of ABL on bone strength. At the FS, the SM improved after 78 weeks of ABL treatment vs PBO. Improvement (decrease) in BR was observed at the IT from week 24 of ABL treatment. Moreover, improvement in CSMI at the NN and IT; SM at the NN, IT, and FS; and BR at the IT was greater in the ABL vs PBO group at week 78. As BR is predicted to explain structural strength with low bone mass, a greater decrease in BR at the IT shows greater strength against compressive buckling loads. Interestingly, similar results were seen in Japanese patients in whom denosumab improved several geometric parameters calculated using HSA for 3 years [In this exploratory analysis, male and female hip geometry data were pooled and analyzed. The ACTIVE-J trial reported that the effect of ABL on increasing lumbar spine BMD was almost the same in the analysis results when postmenopausal women and men were pooled, as well as in the analysis of postmenopausal women alone [This study has some limitations. The major limitations are the small number of patients in the ACTIVE-J trial and the lack of statistical tests to compare bone parameters at baseline and those at each time point. Second, the least significant change (LSC) was not available in the current study, and thus, discussion regarding LSC values based on the published literature was not feasible. Third, the number of patients who had CT scans available for analysis was limited. Moreover, CT imaging was performed using two different models that had two different slice thicknesses, which might have led to low resolution and higher variability and, in turn, resulted in insufficient support for the 2D-HSA data. The current HSA technique is limited by its 2D nature. Nevertheless, our results with 2D-DXA are similar to the results from the ACTIVE and ACTIVExtend trials, which used 3D-DXA analysis [In conclusion, a 78-week treatment with ABL showed improvement in HSA parameters vs PBO in Japanese patients with osteoporosis at high fracture risk. The results suggest the efficacy of daily subcutaneous injection of ABL 80 μg in improving HSA parameters associated with hip geometry and biomechanical properties.