title: Quantitative regional associations between remodeling, modeling, and osteocyte apoptosis and density in rabbit tibial midshafts.
abstract: Evidence suggests that osteocyte apoptosis is involved in the adaptive response of bone, although the specific role of osteocytes in the signaling mechanism is unknown. Here, we examined and correlated regional variability in indices of remodeling, modeling, osteocyte apoptosis, and osteocyte density in rabbit tibia midshafts. Histomorphometric analysis indicated that remodeling parameters (BMU activation frequency, osteon density, forming osteon density, and resorption cavity density) were lower in the cranial region compared to other quadrants. In addition, pericortical subregions displayed less remodeling relative to intracortical and endocortical ones. Modeling indices also demonstrated regional variability in that periosteal surfaces exhibited a greater extent of bone forming surface than endosteal ones across all anatomic quadrants. In contrast, endosteal surfaces demonstrated significantly greater surface mineral apposition rates compared to periosteal surfaces in caudal, medial, and lateral but not cranial quadrants. Using TUNEL analysis to detect osteocytes undergoing apoptosis, the density of apoptotic osteocytes was found to be lower in cranial quadrants relative to medial ones. In addition, the densities of osteocyte lacunae, empty lacunae, and total osteocytes were higher in lateral fields relative to caudal quadrants. There was a strong, statistically significant linear correlation between the remodeling indices and apoptotic osteocyte density, supporting the theory that osteocytes undergoing apoptosis produce signals that attract or direct bone remodeling. In contrast, the modeling parameters did not exhibit a correlation with apoptotic osteocytes, although there was a strong correlation between the modeling indices and the density of empty osteocyte lacunae, corroborating previous studies that have found that osteocytes inhibit bone formation. It was found that osteocyte density and osteocyte lacunar density did not significantly correlate with modeling or remodeling parameters, suggesting that cell viability should be examined in studies correlating bone turnover parameters with the functional role of osteocytes in bone adaptation.
authors.affiliation: Lawrence J Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis Medical Center, Sacramento, CA 95817, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Hedgecock
authors.forename: Tamer
authors.initials: T
authors.lastname: Hadi
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Chen
authors.forename: Shane B
authors.initials: SB
authors.lastname: Curtiss
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Martin
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hazelwood
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology; D010011:Osteocytes / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D011817:Rabbits; D013977:Tibia / Q000166:cytology / Q000502:physiology*