title: Up-regulation of site-specific remodeling without accumulation of microcracking and loss of osteocytes.
abstract: Functional adaptation of bone normally protects the skeleton from fracture during daily activity. Accumulation of microcracking and loss of osteocytes have been implicated in the regulation and initiation of targeted (reparative) remodeling of bone and, in certain situations, the development of fatigue or stress fracture. We performed a histologic study of the dorsal cortex of the mid-diaphysis of the third metacarpal (Mc-III) bone of Thoroughbred racehorses after bones were bulk-stained in basic fuchsin and transverse calcified sections were prepared. The Thoroughbred racehorse is an extreme athlete whose Mc-III bone experiences particularly high cyclic strains during training and racing. A group of non-athletic horses was also included in the experiment. The following variables were quantified: activation frequency (Ac.f); bone formation rate (BFR); resorption space density (Rs.N/T.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar; Ot.N/B.Ar); and bone volume fraction (B.Ar/T.Ar). Ac.f and BFR were estimated using a mathematical algorithm. Using confocal microscopy, bones were examined for fine microcracks, diffuse matrix injury, and disruption of the osteocyte syncytium. Low values for Cr.Dn (#/mm2) were found in both groups (0.022+/-0.008 and 0.013+/-0.006 for racing Thoroughbreds and non-athletic horses, respectively). There was no significant relationship between Cr.Dn and Ot.N/T.Ar; Ot.N/B.Ar, B.Ar/T.Ar, and Ot.N/T.Ar; Ot.N/B.Ar, and remodeling (Ac.f, Rs.N/T.Ar) and Ot.N/T.Ar; Ot.N/B.Ar. Intense remodeling of the Mc-III dorsal cortex was found in the racing Thoroughbreds (Ac.f 12.8+/-7.4 #/mm2/year; BFR 31.5+/-15.6%; Rs.N/T.Ar 0.19+/-0.09 #/mm2) and was significantly increased compared with non-athletic horses. Overall, remodeling was weakly correlated with Cr.Dn (r2=0.15, P<0.05). Subtle matrix injury, not detectable by bright-field microscopy, was particularly evident adjacent to resorption spaces in Thoroughbred bone. In non-athletic horses, disruption of the dendritic cell processes of osteocytes associated with cement lines and interstitial fragments was more evident. Taken together, these findings suggest that site-specific (targeted) induction of remodeling during functional adaptation of bone in a high-strain skeletal site is not dependent on accumulation of microcracking or loss of osteocytes. We hypothesize that athleticism can directly influence bone turnover in this extreme athlete through pathways that do not involve classical linear microcracks.
authors.affiliation: Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Da Costa Gómez
authors.forename: J G
authors.initials: JG
authors.lastname: Barrett
authors.forename: S J
authors.initials: SJ
authors.lastname: Sample
authors.forename: C L
authors.initials: CL
authors.lastname: Radtke
authors.forename: V L
authors.initials: VL
authors.lastname: Kalscheur
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: M D
authors.initials: MD
authors.lastname: Markel
authors.forename: E M
authors.initials: EM
authors.lastname: Santschi
authors.forename: M C
authors.initials: MC
authors.lastname: Scollay
authors.forename: P
authors.initials: P
authors.lastname: Muir
mesh_terms: D000367:Age Factors; D000818:Animals; D001857:Bone Matrix / Q000473:pathology; D016723:Bone Remodeling; D002452:Cell Count; D006253:Haversian System / Q000473:pathology; D006736:Horses; D008663:Metacarpus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018613:Microscopy, Confocal; D010011:Osteocytes / Q000473:pathology*; D010805:Physical Conditioning, Animal; D015854:Up-Regulation