Evaluation of cortical bone remodeling in canines treated with daily and weekly administrations of teriparatide by establishing AI-driven morphometric analyses and GIS-based spatial mapping
Marie Hoshi-Numahata,
Aya Takakura,
Atsuko Nakanishi-Kimura,
Haruhisa Watanabe,
Kentaro Takada,
Mai Nishiura,
Yoshiaki Sato,
Ryoko Takao-Kawabata,
Tadahiro Iimura
Affiliations
Marie Hoshi-Numahata
Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan; Department of Orthodontics, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan
Aya Takakura
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan; Corresponding authors.
Atsuko Nakanishi-Kimura
Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan; Department of Orthodontics, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan
Haruhisa Watanabe
Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan; Department of Oral Medicine and Diagnostics, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan
Kentaro Takada
Department of Natural History Sciences, Graduate School of Science, Hokkaido University, N10 W8, Sapporo 060-8010, Japan
Mai Nishiura
Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan; Department of Dentistry for Children and Disabled Persons, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan
Yoshiaki Sato
Department of Orthodontics, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan
Ryoko Takao-Kawabata
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan; Corresponding authors.
Tadahiro Iimura
Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University, N13 W7, Sapporo 060-8586, Japan; Corresponding authors.
Larger animal models with a well-developed Haversian system, as observed in humans, are ideal to analyze cortical bone remodeling in pharmacological studies of anti-osteoporosis drugs, although they have some limitations in controlling individual variability in size, weight, age, and number. This study aimed to morphometrically analyze cortical bone remodeling focusing on Haversian canals in dogs using four regimens of TPTD with daily and weekly administrations at lower and higher weekly doses (4.9 μg/kg/week and 19.8 μg/kg/week, respectively) for 9 months. A micro-computed tomography-based analysis showed no significant differences among regimen groups. By establishing artificial intelligence (AI)-driven morphometric analyses and geographical information system (GIS)-based spatial mapping of Haversian canals that does not require confocal microscopy but is possible with more commonly used wide field microscopes, we successfully observed significant morphometric distinctions among regimens applied even in dogs. Our analytical results suggested that the daily higher regimen specifically increased the number of eroded pores creating spaces between existing canals, thus stimulating cortical bone remodeling.
