Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats

Abstract

To investigate whether the administration frequency of parathyroid hormone (PTH) is associated with the development of cortical porosity, this study established 15 dosage regimens of teriparatide [human PTH(1–34), TPTD] with four distinct concentrations and four distinct administration frequencies of TPTD to 16-week-old ovariectomized rats. Our analyses demonstrated that the bone mineral density, mechanical properties, and bone turnover were associated with the total amount of TPTD administered. Our observations further revealed that the cortical porosity was markedly developed as a result of an increased administration frequency with a lower concentration of total TPTD administration in our setting, although the highest concentration also induced cortical porosity. Deconvolution fluorescence tiling imaging on calcein-labeled undecalcified bone sections also demonstrated the development of cortical porosity to be closely associated with the bone site where periosteal bone formation took place. This site-specific cortical porosity involved intracortical bone resorption and an increased number and proximity of osteocytic lacunae, occasionally causing fused lacunae. Taken together, these findings suggested the involvement of local distinctions in the rate of bone growth that may be related to the site-specific mechanical properties in the development of cortical porosity induced by frequent and/or high doses of TPTD.

Bone microarchitecture: Different hormone regimens affect bone porosity

The effect on bone porosity of a drug that promotes bone growth depends on the dosing and treatment frequency. A team in Japan led by Tadahiro Iimura from Ehime University and Ryoko Takao-Kawabata from Asahi Kasei Pharma Corporation injected female rats that had had their ovaries removed to mimic the effects of menopause with 15 different regimens of a synthetic form of the human parathyroid hormone. The regimens comprised four different concentrations of the drug and four distinct administration frequencies. The researchers found that more frequent treatment schedules and higher hormone doses created more porous, fragile vertebrae that were prone to fractures. These changes in bone microarchitecture were more pronounced in the front part of the vertebrae than in the back. The findings could help inform clinical dosing regimens for post-menopausal women receiving synthetic parathyroid hormone.

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