title: Frequency of Teriparatide Administration Affects the Histological Pattern of Bone Formation in Young Adult Male Mice.
abstract: Evidence supports that daily and once-weekly administration of teriparatide, human (h)PTH(1-34), enhance bone mass in osteoporotic patients. However, it is uncertain whether different frequencies of hPTH(1-34) administration would induce bone formation similarly in terms of quantity and quality. To investigate that issue, mice were subjected to different frequencies of PTH administration, and their bones were histologically examined. Frequencies of administration were 1 time/2 days, 1 time a day, and 2 and 4 times a day. Mice were allocated to either to control or to 3 different dosing regimens: 80 μg/kg of hPTH(1-34) per injection (80 μg/kg per dose), 80 μg/kg of hPTH(1-34) per day (80 μg/kg · d), or 20 μg/kg of hPTH(1-34) per day (20 μg/kg · d). With the regimens of 80 μg/kg per dose and 80 μg/kg · d, high-frequency hPTH(1-34) administration increased metaphyseal trabecular number. However, 4 doses per day induced the formation of thin trabeculae, whereas the daily PTH regimen resulted in thicker trabeculae. A similar pattern was observed with the lower daily hPTH(1-34) dose (20 μg/kg · d): more frequent PTH administration led to the formation of thin trabeculae, showing a thick preosteoblastic cell layer, several osteoclasts, and scalloped cement lines that indicated accelerated bone remodeling. On the other hand, low-frequency PTH administration induced new bone with mature osteoblasts lying on mildly convex surfaces representative of arrest lines, which suggests minimodeling-based bone formation. Thus, high-frequency PTH administration seems to increase bone mass rapidly by forming thin trabeculae through accelerated bone remodeling. Alternatively, low-frequency PTH administration leads to the formation of thicker trabeculae through bone remodeling and minimodeling.
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Tomomaya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Muneteru
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hongo
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Tsuboi
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Haraguchi
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahata
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Luiz de Freitas
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Takakura
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takao-Kawabata
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Isogai
authors.affiliation: Department of Developmental Biology of Hard Tissue (T.Y., T.H., H.H., K.T., M.H., N.A.), Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586 Japan; Department of Applied Prosthodontics (M.S.), Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588 Japan; Department of Orthopedic Surgery Graduate School of Medicine (T.S., M.O., M.T.), Hokkaido University, Sapporo, 951-8514 Japan; Division of Biochemistry (K.O.), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514 Japan; Department of Dentistry (P.H.L.d.F.), Federal University of Sergipe at Lagarto, Campus Legarto, 49400-000 Brazil; and Asahi Kasei Pharma Co. Ltd (A.T., R.T.-K., Y.I.), Tokyo, 101-8101 Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D019379:Teriparatide / Q000008:administration & dosage*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide