Increased cortical porosity is associated with daily, not weekly, administration of equivalent doses of teriparatide

Introduction: The pharmacokinetic profile of parathyroid hormone (PTH) determines its effects on bone resorption and formation. When administered intermittently, anabolic effects are favored in comparison with the continuous treatment. Among the intermittent treatment regimens, lower frequency of administration may have a lower effect on bone remodeling. We therefore hypothesized that weekly administration of teriparatide will produce less increase in intracortical remodeling and porosity than reported using daily treatment. Methods: We treated 17 female New Zealand white rabbits aged 6 months for 1 month with teriparatide [human PTH(1-34)] as follows. (i) Vehicle-treated Control (n = 4); (ii) 20 μg/kg daily (n = 3); (iii) 40 μg/kg daily (n = 3); (iv) 140 μg/kg weekly (n = 3); (v) 280 μg/kg weekly (n = 4). Proximal femurs were imaged ex vivo using micro-CT (Scanco Viva CT-40) at 15 μm voxel size. Areas, pore size, and porosity were analyzed on the total, compact cortex (CC), and transitional zones in a 10 mm length region of interest (ROI) starting at the midshaft using StrAx1.0. Results: Compared to controls, the 20 μg/kg daily was associated with 3.0% higher porosity in the transitional zone (p = 0.09) while the 40 μg/kg daily was associated with a higher porosity in the cortex (8.7%; p = 0.04) and in the transitional zone (5.7%; p = 0.007). The daily regimens were also associated with a greater proportion of porosity due to pores > 15 μm2; particularly in the transitional zone where 20 and 40 μg/kg daily increased porosity 2 fold (p = 0.06) and 5 fold (p = 0.04) relative controls respectively. The 140 and 280 μg/kg weekly were not associated with an increase in porosity. There was no difference in total, compact or transitional zone cross sectional areas between the groups. Conclusion: Effects of intermittent teriparatide depend on the dose and frequency of administration. Daily dosing, particularly the higher dose, but not weekly dosing, increased cortical porosity. Work is needed to investigate the effects of the regimens on bone formation.