Roger Zebaze1, Ryoko Takao-Kawabata2, Yu Peng3, Ali Ghasem Zadeh4, Kyoko Hirano2, Hiroshi Yamane2, Aya Takakura2, Yukihiro Isogai2, Toshinori Ishizuya2, Ego Seeman5. 1. Dept Endocrinology and Medicine, Austin Health, University of Melbourne, Melbourne, Australia; StraxCorp PTY LTD, Melbourne, Australia. Electronic address: zebaze@unimelb.edu.au. 2. Laboratory for Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Tokyo, Japan. 3. StraxCorp PTY LTD, Melbourne, Australia. 4. Dept Endocrinology and Medicine, Austin Health, University of Melbourne, Melbourne, Australia. 5. Dept Endocrinology and Medicine, Austin Health, University of Melbourne, Melbourne, Australia; StraxCorp PTY LTD, Melbourne, Australia; Institute for Health and Ageing, Australian Catholic University, Australia.
Abstract
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 6months for 1month with teriparatide [human PTH(1-34)] as follows. (i) Vehicle-treated Control (n=4); (ii) 20μg/kg daily (n=3); (iii) 40μg/kg daily (n=3); (iv) 140μg/kg weekly (n=3); (v) 280μg/kg weekly (n=4). Proximal femurs were imaged ex vivo using micro-CT (Scanco Viva CT-40) at 15μmvoxel size. Areas, pore size, and porosity were analyzed on the total, compact cortex (CC), and transitional zones in a 10mm length region of interest (ROI) starting at the midshaft using StrAx1.0. RESULTS: Compared to controls, the 20μg/kg daily was associated with 3.0% higher porosity in the transitional zone (p=0.09) while the 40μg/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 >15μm2; particularly in the transitional zone where 20 and 40μg/kg daily increased porosity 2 fold (p=0.06) and 5 fold (p=0.04) relative controls respectively. The 140 and 280μg/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.
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 6months for 1month with teriparatide [humanPTH(1-34)] as follows. (i) Vehicle-treated Control (n=4); (ii) 20μg/kg daily (n=3); (iii) 40μg/kg daily (n=3); (iv) 140μg/kg weekly (n=3); (v) 280μg/kg weekly (n=4). Proximal femurs were imaged ex vivo using micro-CT (Scanco Viva CT-40) at 15μmvoxel size. Areas, pore size, and porosity were analyzed on the total, compact cortex (CC), and transitional zones in a 10mm length region of interest (ROI) starting at the midshaft using StrAx1.0. RESULTS: Compared to controls, the 20μg/kg daily was associated with 3.0% higher porosity in the transitional zone (p=0.09) while the 40μg/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 >15μm2; particularly in the transitional zone where 20 and 40μg/kg daily increased porosity 2 fold (p=0.06) and 5 fold (p=0.04) relative controls respectively. The 140 and 280μg/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.
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