title: Partial gravity unloading inhibits bone healing responses in a large animal model.
abstract: The reduction in mechanical loading associated with space travel results in dramatic decreases in the bone mineral density (BMD) and mechanical strength of skeletal tissue resulting in increased fracture risk during spaceflight missions. Previous rodent studies have highlighted distinct bone healing differences in animals in gravitational environments versus those during spaceflight. While these data have demonstrated that microgravity has deleterious effects on fracture healing, the direct translation of these results to human skeletal repair remains problematic due to substantial differences between rodent and human bone. Thus, the objective of this study was to investigate the effects of partial gravitational unloading on long-bone fracture healing in a previously-developed large animal Haversian bone model. In vivo measurements demonstrated significantly higher orthopedic plate strains (i.e. load burden) in the Partial Unloading (PU) Group as compared to the Full Loading (FL) Group following the 28-day healing period due to inhibited healing in the reduced loading environment. DEXA BMD in the metatarsus of the PU Group decreased 17.6% (p<0.01) at the time of the ostectomy surgery. Four-point bending stiffness of the PU Group was 4.4 times lower than that of the FL Group (p<0.01), while µCT and histomorphometry demonstrated reduced periosteal callus area (p<0.05), mineralizing surface (p<0.05), mineral apposition rate (p<0.001), bone formation rate (p<0.001), and periosteal/endosteal osteoblast numbers (p<0.001/p<0.01, respectively) as well as increased periosteal osteoclast number (p<0.05). These data provide strong evidence that the mechanical environment dramatically affects the fracture healing cascade, and likely has a negative impact on Haversian system healing during spaceflight.
authors.affiliation: Orthopaedic Research Laboratory, Department of Mechanical Engineering and School of Biomedical Engineering, Colorado State University, 1374 Campus Delivery, Fort Collins, CO, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Gadomski
authors.affiliation: Orthopaedic Research Laboratory, Department of Mechanical Engineering and School of Biomedical Engineering, Colorado State University, 1374 Campus Delivery, Fort Collins, CO, USA.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: McGilvray
authors.affiliation: Surgical Research Laboratory, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Jeremiah T
authors.initials: JT
authors.lastname: Easley
authors.affiliation: Surgical Research Laboratory, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Ross H
authors.initials: RH
authors.lastname: Palmer
authors.affiliation: Phillip Speigel Orthopaedic Research Laboratory, Foundation for Orthopedic Research and Education, Tampa, FL, USA.
authors.forename: Brandon G
authors.initials: BG
authors.lastname: Santoni
authors.affiliation: Orthopaedic Research Laboratory, Department of Mechanical Engineering and School of Biomedical Engineering, Colorado State University, 1374 Campus Delivery, Fort Collins, CO, USA. Electronic address: puttlitz@engr.colostate.edu.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Puttlitz
mesh_terms: D000818:Animals; D001860:Bone Plates; D002146:Bony Callus / Q000000981:diagnostic imaging / Q000503:physiopathology; D005260:Female; D017102:Fracture Healing / Q000502:physiology*; D008682:Metatarsal Bones / Q000000981:diagnostic imaging / Q000503:physiopathology*; D023421:Models, Animal; D010012:Osteogenesis; D012756:Sheep; D013026:Space Flight; D014893:Weightlessness; D055114:X-Ray Microtomography
keywords: Bone; Fracture healing; Sheep; Spaceflight; Unloading