title: Damaging fatigue loading stimulates increases in periosteal vascularity at sites of bone formation in the rat ulna.
abstract: Bone formation in a variety of contexts depends on angiogenesis; however, there are few reports of the vascular response to osteogenic skeletal loading. We used the rat forelimb compression model to characterize vascular changes after fatigue loading. The right forelimbs of 72 adult rats were loaded cyclically in vivo to one of four displacement levels, to produce four discrete levels of ulnar damage. Rats were killed 3-14 days after loading, and their vasculature was perfused with silicone rubber. Transverse histological sections were cut along the ulnar diaphysis. We quantified vessel number, average vessel area, total vessel area, and bone area. On day 3, we observed a dramatic periosteal expansion near the ulnar midshaft, with significant increases in periosteal vascularity; total vessel area was increased 250-450% (P < 0.001). Vascularity remained elevated on days 7 and 14. Vessel number and average vessel area were not correlated (P = 0.09) and contributed independently to total vascular increases. Bone area was not increased on day 3 but on days 7 and 14 was increased significantly in all displacement groups (P < 0.01) due to periosteal woven bone formation. Vascular and bone changes depended on longitudinal location (P < 0.001), with peak increases 2 mm distal to the midshaft. Vascular and bone changes also depended on displacement level (P < 0.005), with greater increases at higher levels of fatigue displacement. We conclude that skeletal fatigue loading induces a rapid increase in periosteal vascularity, followed by an increase in bone area. The angiogenic-osteogenic response is spatially coordinated and scaled to the level of the mechanical stimulus.
authors.affiliation: Orthopedic Research Laboratory, Department of Orthopedic Surgery, Washington University, 1 Barnes-Jewish Hospital Plaza, Suite 11300 WP, St. Louis, MO 63110, USA.
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Wohl
authors.forename: Deborah V
authors.initials: DV
authors.lastname: Novack
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lynch
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001846:Bone Development; D001842:Bone and Bones / Q000473:pathology; D019245:Compressive Strength; D008297:Male; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D051381:Rats; D011916:Rats, Inbred F344; D013314:Stress, Mechanical; D014457:Ulna / Q000098:blood supply / Q000473:pathology*; D014458:Ulna Fractures; D016474:Weight-Bearing