Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo

In vivo, indomethacin blockade of bone formation has been used to illustrate the role of prostaglandins. Indomethacin blocks the constitutive (COX-1) and inducible (COX-2) forms of cyclo-oxygenase, and is therefore nonspecific in its action. To test the hypothesis that COX-2 mediates the bone formation response to loading, rats were treated with vehicle, NS-398 (a specific COX-2 inhibitor) or indomethacin at 0.02, 0.2, or 2.0 mg/kg p.o. 3 h before loading the right tibia in four-point bending. Bending or sham loads of 65 N were applied for one bout of 300 cycles and bone formation assessed 5-8 days after loading. Mechanically induced bone formation at the endocortical surface was calculated by subtracting formation indices of the left leg (control) from those of the right (loaded), and woven bone surface and area were measured at the periosteal surface. Endocortical bone formation was significantly increased by bending but not sham loading (p < 0.05). The increase in the endocortical bone formation rate and mineralizing surface caused by bending was only partially inhibited by indomethacin, even at the highest dose, whereas NS-398 completely blocked bone formation at all doses (p < 0.05). The mineral apposition rate was depressed in a dose-response fashion by NS-398 (p < 0.05), but not by indomethacin. Woven bone formation at the periosteal surface was not prevented by treatment with indomethacin nor NS-398, suggesting that its formation is not dependent on prostaglandin production. These data suggest that induction of COX-2 is important for lamellar bone formation elicited by mechanical strain

Histomorphometric changes in the wing bones of the fruit bat, Pteropus poliocephalus, (Megachiroptera: Pteropidae) in relation to increased bone strain

Fluorochrome labelling of bone formation was used to examine the effect of exercise (flight) on the wing skeleton of fruit bats, Pteropus poliocephalus, over a 194 day period. The bats in this study had been born and raised in captivity and it was hypothesised that the large increases in bone strain that accompanied active flight would result in bone formation at the periosteal bone surface, leading to increased mechanical stiffness and strength. This hypothesis was not supported by the results. Bone formation rates, percentage mineralising surface and mineral apposition rates at the mid-shaft periosteal surface of the radius, metacarpal III and metacarpal V were small. The proximal phalanx of digit V did not display any bone formation at this surface. Bone appositional activity was not significantly different between baseline, control (non-flight) and treatment (flight) groups at any time-point of the experiment. Apposition, although limited, occurred primarily at the endocortical surface in all bones of all animals. No correlation was found between activity and bone formation. Active intracortical remodelling (a total of four secondary osteons) was only seen in three individuals.There was evidence of earlier remodelling activity in most bones, although there was no evidence of any secondary remodelling in the proximal phalanx

Repetitive loading, in vivo, of the tibia and femora of rats: Effects of a single bout of treadmill running

The presence of microdamage in the tibiae and femora of rats following repetitive loading in vivo was investigated by subjecting 48 male rats, aged 12 weeks, to treadmill running (26.8 m.min-1 on 10% grade) for 0.56 hours (5,000 cycles, E1), 1.13 hours, (10,000 cycles, E2), 2.27 hours (20,000 cycles, E3), and 3.4 hours (30,000 cycles, E4) with Group C as control. Following exercise, tibiae and femora were excised and the right limbs were tested in torsion at 180°.sec-1. Transverse sections were cut from the proximal, mid- and distal diaphysis of left tibiae and femora, bulk stained in basic fuchsin, cut to 50 μm thick, and examined for the presence of microdamage. Following these periods of loading, tibiae and femora showed no evidence of microdamage initiation, as evidenced by light microscopy, or corresponding alterations in mechanical properties. It was concluded that the magnitude of loading produced by single bouts of intensive exercise, which encompassed up to 30,000 loading cycles, was insufficient to initiate fatigue microdamage in tibiae or femora of rats

Effects of exercise on bone morphology: Vascular channels studied in the rat tibia

14 male rats were divided into exercise and control groups to examine the effect of a 1-month exercise program on the vascular morphology of the tibial diaphysis. Following the exercise program the number of haversian canals per mm increased in the middle third of the cortex, but not in the outer or inner zone. No change was observed in the number of non-haversian canals. the size of the nonhaversian canals increased following the training program, which was not evident in the haversian canals

Effects of exercise on bone growth mechanical and physical properties studied in the rat

Thirty-four pubescent male rats were divided into exercise and control groups to examine the effects of a 1-month intensive exercise programme on the mechanical, physical (group 1) and histological properties (group 2) of the tibia and femur. At the completion of training, rats were sacrificed and the right hind-limbs dissected and stored at -60°C prior to torsional-testing at a speed of 180/s. Left tibiae and femora were measured for length and weight' Values for the width of the epiphyseal plate were also obtained from animals in group 2. Following the exercise programme the tibiae showed significant reductions in energy absorbed to failure, bone length and width of the proximal epiphyseal plate. No change was observed for the mechanical properties of the femora, but significant reductions occurred in bone length and weight

Scaling segmental moments of inertia for individual subjects

The purpose of this investigation was to validate methods of scaling human segmental moments of inertia for the transverse principal axis. Firstly, two methods of scaling Chandler et al.'s (Pamphlets DOT HS-801 430 and AMRL TR-74-137, Wright Patterson Air Force Base, OH, 1975) mean subject data to estimate the segmental moments of inertia were used. Chandler et al.'s data were scaled using body mass and segment length (formula 1) or body mass and standing height (formula 2). These data were then compared with a procedure of using the cadaver whose anthropometric measurements most closely match those of the subject. The difference between the criterion data (Chandler's subject data) and scaled values were plotted on scatter diagrams with confidence limits of p < 0.05 at d.f. = 17. For procedure 1, 43% of the scaled values were plotted within the confidence limits using formula (2) (mass and standing height), compared with 26% for formula (1) (mass and segment length). Formula (1) markedly underestimated the tallest and heaviest subjects. In procedure 2, only 16% and 21% of the scaled values, using formula (1) and (2), respectively, fell within the confidence limits. Results suggested that scaling formulae approximate the moment of inertia of body segments with only limited accuracy. However, if scaling was to be adopted then mean moment of inertia data from an appropriate data set, using the formula that incorporates subject mass and standing height, gave results closest to the criterion value

Increased bone formation in rat tibiae after a single short period of dynamic loading in vivo

Based on our quantum concept for mechanically adaptive bone formation, we hypothesized that a single bout of loading would increase bone formation at the endosteal surface in rat tibiae, with a maximal response 4-8 days after loading and a stimulus-response relationship for load magnitude. Bending loads were applied to right tibiae of rats at 31, 43, 53, or 65 N for a single bout of 36 or 360 cycles; bone formation was assessed 1-4, 5-8, or 9-12 days after loading. A single loading episode increased lamellar bone formation rate (BFR) in all groups (