The bone architecture is enhanced with combined PTH and alendronate treatment compared to monotherapy while maintaining the state of surface mineralization in the OVX rat

This study examined the effect of PTH and alendronate alone and in combination on the bone architecture, mineralization, and estimated mechanics in the OVX rat. Female Wistar rats aged 7-9 months were assigned to one of five groups: (1) sham + vehicle, (2) OVX + vehicle, (3) OVX + PTH, (4) OVX + alendronate, and (5) OVX + PTH and alendronate. Surgery was performed at baseline (week 0), and biweekly treatment (15 μg/kg of alendronate and/or daily (5 days/week) 40 μg/kg hPTH(1-34)) was administered from week 6 to week 14. Micro-CT scans of the right proximal tibial metaphysis were made in vivo at weeks 0, 6, 8, 10, 12 and 14 and measurements of bone microarchitecture and estimated mechanical parameters (finite element analysis) were made from the images. Synchrotron radiation micro-CT scans of the proximal tibia and fourth lumbar vertebrae were conducted ex vivo at the study endpoint to determine the degree and spatial distribution of the bone mineralization. Alendronate preserved the microarchitecture after OVX, and increased cortical (9%, p < 0.05) and trabecular thickness (5%, p < 0.05). PTH mono- and combined therapy induced increases in cortical (25-35%, p < 0.05) and trabecular thicknesses (46-48%, p < 0.05), resulting in a full restoration of bone volume in the PTH group, and an increase beyond baseline in the combined group. Improvements in estimated mechanical outcomes were observed in all treatment groups by the end of the study, with the combined group experiencing the greatest increase in predicted stiffness (63%, p < 0.05). Alendronate treatment increased the peak mineral content above the other treatment groups at the trabecular (tibia: 6% above PTH, 6% above combined, L4: 4% above PTH, 4% above combined) and endocortical (tibia: 4% above PTH, 3% above combined, L4: 1% above PTH, 2% above combined) surfaces, while no differences in mineralization between the PTH and combined groups were observed. Combined treatment resulted in more pronounced improvements of the bone architecture than PTH monotherapy, while maintaining the state of mineralization observed with PTH treatment.

Research highlights► PTH promotes bone formation and ALN reduces bone resorption in ovariectomized rats. ► Combining these treatments enhances recovery of bone architecture over monotherapy. ► Combination treatment results in same state of mineralization as PTH monotherapy. ► Architectural improvements result from thickening of existing trabecular elements.