Up-regulation of site-specific remodeling without accumulation of microcracking and loss of osteocytes
Introduction
New insights in biology often come from studies of animals that exhibit extremes of performance. The Thoroughbred horse is a large cursorial mammal that runs at speeds exceeding 15 m/s; during such performance, surface strains in excess of −5000 μɛ are applied to the mid-diaphysis of the third metacarpal (Mc-III) bone [1]. The Mc-III bone is a common site for fatigue fracture [2], [3]; training and racing induce an extensive, principally periosteal, modeling response in the Mc-III bone [4]. Functional adaptation in the Thoroughbred must protect the skeleton from fracture and also minimize bone mass to enable continued athletic performance.
Previous studies [5], [6] have shown that development of linear fatigue microcracks leads to a loss of osteocytes in bone adjacent to the microcracks (<100 μm) and that this loss of osteocytes is co-localized with the subsequent formation of resorption spaces. These observations have led to the suggestion that the osteocyte is the effector cell responsible for sensing load and regulating functional bone adaptation through apoptosis [7], [8], [9], although the proportion of remodeling that is targeted to the repair of matrix failure because of fatigue, as opposed to stochastic (random) remodeling, is unclear [10]. Although active remodeling is found in the Mc-III mid-diaphysis of racing Thoroughbreds, this is associated with only small numbers of linear microcracks [11], even though particularly high cyclic strains are experienced by the bone tissue [1]. It has been hypothesized that a minimal syncytial network of >600 osteocytes/mm2 is needed for effective detection and repair of fatigue damage through necrosis or apoptosis of osteocytes [5], [6], [12]. More recently, it has also been suggested that osteocytes within bone may be capable of responding to mechanical loading by inducing remodeling without the associated development of osteocyte apoptosis adjacent to linear microcracks [13].
The purpose of the present study was to quantify remodeling and microcracking in a group of athletic horses trained for extreme performance and in a separate group of non-athletic horses. We also assessed whether remodeling within the Mc-III mid-diaphysis was associated with fewer osteocytes and whether remodeling was targeted to bone regions that had experienced canalicular disruption or matrix injury. Based on current understanding of targeted remodeling [5], [6], [7], [8], [10], [12], we hypothesized that remodeling in the equine Mc-III mid-diaphysis would be significantly associated with the presence of fatigue microcracks and loss of osteocytes.
Section snippets
Horses
Left and right Mc-III bones were collected from 12 Thoroughbred racehorses that had sustained a serious orthopedic injury while racing that was severe enough to result in euthanasia. Paired bones were collected to control for any confounding effects from skeletal injury and counter-clockwise racing. Age and racing history were obtained. A single Mc-III bone, randomly selected from the left or right limb, was also collected from 11 horses of various breeds that had not been trained for flat
Influence of horse activity on microcracking
In the racing Thoroughbred group, mean age was 3.2 ± 1.0 years (range 1.8 to 4.8 years) and in the non-athletic group, mean age was 9.8 ± 5.4 years (range 2.5 to 18.0 years). The non-athletic horses were significantly older than the racing Thoroughbred group (P < 0.001). Little microcracking was found in the dorsal cortex of the Mc-III bone, although microcracking was increased in the racing Thoroughbred group (P < 0.05, Table 1). There was no significant relationship between microcracking and
Discussion
The mechanisms that are responsible for the development of insufficiency-type fatigue (stress) fractures in the elderly, individuals with osteoporosis, and classical fatigue fractures in younger active human beings are not understood at the microscopic level. Targeted remodeling, as a component of bone adaptation, is an important bone repair mechanism thought to prevent the accumulation of fatigue microcracks, which can result from the cyclic loading that occurs during daily activity [10].
Acknowledgments
This work was partially supported by grants from the AO VET Center, Switzerland, and a Surgeon-in-Training research grant from the American College of Veterinary Surgeons awarded to Támara M. Da Costa Gómez.
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2012, Journal of Equine Veterinary ScienceCitation Excerpt :When the intensity of exercise is decreased, such as when training is suspended, this inhibition of bone remodeling ceases and remodeling may proceed unimpeded [1,3]. Even so, focal or site-specific areas of intense bone remodeling, represented by resorption cavities, are commonly found in locations such as the parasagittal groove and the mid-dorsal cortex of McIII—sites where stress fractures most often occur in racing Thoroughbreds [1,3,4]. Whether remodeling of the damaged bone, which includes bone resorption, is accelerated once training ceases or it simply resumes at a normal rate remains to be determined.