title: Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography.
abstract: In this study we established an image analysis scheme for the investigation of cortical and trabecular bone development during skeletal growth and tested this concept on in vivo μCT images of rats. To evaluate its efficacy, we applied the technique to young (1-month-old) and adult (3-month-old) rat tibiae with vehicle (Veh) or intermittent parathyroid hormone (PTH) treatment. By overlaying 2 sequential scans based on their distinct trabecular microarchitecture, we calculated the linear growth rate of young rats to be 0.31 mm/day at the proximal tibia. Due to rapid growth (3.7 mm in 12 days), the scanned bone region at day 12 had no overlap with the bone tissue scanned at day 0. Instead, the imaged bone region at day 12 represented newly generated bone tissue from the growth plate. The new bone of the PTH-treated rats had significantly greater trabecular bone volume fraction, number, and thickness than those of the Veh-treated rats, indicating PTH's anabolic effect on bone modeling. In contrast, the effect of PTH on adult rat trabecular bone was found to be caused by PTH's anabolic effect on bone remodeling. The cortical bone at the proximal tibia of young rats also thickened more in the PTH group (23%) than the Veh group (14%). This was primarily driven by endosteal bone formation and coalescence of trabecular bone into the cortex. This process can be visualized by aligning the local bone structural changes using image registration. As a result, the cortex after PTH treatment was 31% less porous, and had a 22% greater polar moment of inertia compared to the Veh group. Lastly, we monitored the longitudinal bone growth in adult rats by measuring the distance of bone flow away from the proximal tibial growth plate from 3 months to 19 months of age and discovered a total of 3.5mm growth in 16 months. It was demonstrated that this image analysis scheme can efficiently evaluate bone growth, bone modeling, and bone remodeling, and is ready to be translated into a clinical imaging platform.
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: alaltman@mail.med.upenn.edu.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Altman
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: weits@mail.med.upenn.edu.
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Tseng
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: chantald@seas.upenn.edu.
authors.forename: Chantal M J
authors.initials: CMJ
authors.lastname: de Bakker
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: abhic@mail.med.upenn.edu.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Chandra
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province, People's Republic of China; Department of Orthopaedic Surgery, Wuhan General Hospital of Guangzhou Military Command, Hubei Province, People's Republic of China. Electronic address: shenghuilan@gmail.com.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Lan
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: bhuh@seas.upenn.edu.
authors.forename: Beom Kang
authors.initials: BK
authors.lastname: Huh
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: shiming@sas.upenn.edu.
authors.forename: Shiming
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States; Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States. Electronic address: leonard5@stanford.edu.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: qinling@mail.med.upenn.edu.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: xiaoweil@mail.med.upenn.edu.
authors.forename: X Sherry
authors.initials: XS
authors.lastname: Liu
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000502:physiology*; D005260:Female; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000000981:diagnostic imaging; D055114:X-Ray Microtomography
chemical_list: D010281:Parathyroid Hormone
keywords: Bone modeling; Bone remodeling; Endochondral bone development; In vivo μCT; Parathyroid hormone; Trabecular coalescence