Impact of Non Steroidal Anti-Inflammatory Drug Administration Pre- or Post-Resistance Training on Bone

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been shown to suppress bone formation when administered before, but not if administered after, an acute bout of mechanical load. The effects of giving NSAIDs pre- and post-resistance training over multiple training sessions are not yet well defined. Therefore, the aim of this study was to elucidate the effects of NSAIDs when administered pre and post simulated resistance training (SRT) in a small animal model. We hypothesize that gains in bone mass and increased bone size will be diminished in adult rats given ibuprofen before each training session, but will be enhanced if ibuprofen is given after each exercise bout. Methods: Fifteen 5-month-old virgin female Sprague-Dawley rats completed 9 SRT sessions at 75% peak isometric strength for 4 sets of 5 repetitions; each contraction included 1 sec isometric + 1 sec eccentric contraction. Animals were blocked assigned by body weight to one of three groups: (1) ibuprofen (30mg/kg) before exercise, placebo after (I:P)(n=4), (2) placebo before exercise, ibuprofen after (P:I)(n=5) and (3) placebo before exercise, placebo after (P:P)(n=6). In vivo pQCT scans measured changes in total volumetric bone mineral density (vBMD), cancellous vBMD, and total area at the proximal tibia, and cortical vBMD, cortical bone mineral content (BMC) and total area at midshaft tibia from days -7 and 21. Body weights were measured at days 4, 14 and 21. Results: There were no significant changes in body weight over the course of the study (P:P -2.6%, I:P -2.3% & P:I -3.8%, day 21 vs day 4). Furthermore, there was no significant difference across time in midshaft cortical vBMD, but the P:I group did exhibit a significantly different response in cortical vBMD when normalized to body weight (+5.1%) (p\u3c .05) compared to I:P (-1.4%) and P:P (-0.3%). There were no differences among groups for change in cancellous vBMD, total vBMD and total area at the proximal region, as well as cortical BMC and total area at midshaft tibia. Conclusion: These data are preliminary but suggest that ibuprofen given after exercise may produce additional gains in cortical bone following resistance training; we have no evidence thus far that ibuprofen taken before exercise has any effect. Supported by Huffines Institute of Sports Medicine and Human Performance, Texas A&M University

Short-Term Reduction in Energy Availability Does Not Impair Exercise-Induced Gains in Bone Formation Rate

Reduced energy availability (EA, defined as total energy intake minus exercise energy expenditure) can induce significant bone loss in humans and in rodents, but this effect may vary with exercise status. Purpose: This study focused on the effects of graded reductions in EA achieved with and without exercise on mid-shaft tibia cortical bone. We hypothesized that markers of bone formation would be reduced with 4 weeks of decreased EA, but these reductions would be mitigated in exercising animals. Methods: After 8 weeks of acclimation to AIN-93M purified diet, 5 mo-old virgin female Sprague-Dawley rats (n=72) were randomized in to sedentary (SED) and exercise (EX) groups, each of which was divided into 3 energy status groups: -12% EA/g body mass (-12EA) and -25% EA/g body mass (-25EA) vs. ad lib-fed controls. EX rats were restricted on diet intake slightly less than SED to account for the energy cost (+10%/day) of treadmill running (80-90 min/d, 4 d/wk, ~60% VO2max); custom versions of AIN-93M were used to assure restriction of only kcal (other nutrients at 100%). Calcein injections 9 and 2 days prior to euthanasia labeled mineralizing surfaces for histomorphometric analyses 2 mm proximal to the tibio-fibular junction for mineralizing surface (%MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR) on periosteal and endocortical surfaces. Results: After 4 weeks, only -25EA SED lost body mass (-11%); virtually all of this was fat mass. Periosteal BFR was 2 to 4 fold higher in EX rats vs. SED animals within each energy status group. The impact of EX on endocortical BFR was even greater (~5-fold increase) for all groups except in the -25 EA cohorts (-25 EA EX BFR ~ equal to -25EA SED BFR). Increases in BFR with EX were achieved by increases in both %MS/BS and MAR on both cortical surfaces. Conclusions: These data suggest that short-term graded reductions in EA do not inhibit BFR in SED animals nor the robust stimulation of BFR by moderately vigorous exercise training. The one exception observed was a suppression of the EX induced gain in endocortical BFR with the more stringent level of reduced EA. Whether this lack of effect of EA on BFR gains with EX persists with more chronic reductions in EA has yet to be determined. Funded by the Department of Defense #WSIXWH-06-1-047

Treadmill Running and Tower Climbing Resistance Exercise Mitigate Disuse Bone Loss in Mice Equally Well

Ground-Based Model for Lunar Disuse Bone Loss During spaceflight, astronauts are susceptible to decrements in bone mineral density. This suscetibility leaves astronauts at an increased risk of fracture and compromises their likelihood of repeat missions. Our ground-based Lunar model simulates disuse bone loss. Through our novel exercise regimens, we were able to mitigate losses seen by group members not exercised

Impact of Omega-3 Polyunsaturated Fatty Acids on Bone Adaptations to Simulated Resistance Training

Young and ovariectomized animals eating diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit enhanced bone formation and decrease bone loss, respectively. Eicosapentaenoic acid, an n-3 PUFA found in fish oil, competes with arachidonic acid, an n-6 PUFA, for the cyclooxygenase enzyme, modulating prostaglandin E2, a mediator of bone mechanotransduction. Whether this diet affects bone gains during exercise is not well defined. We hypothesized rats consuming a high n-3 PUFA diet would gain more bone mass with increased bone formation compared to the rats consuming a high n-6 PUFA diet in response to exercise. Virgin Sprague-Dawley rats (5-mo-old, n=18) were assigned to one of two groups: diet rich in corn oil with a n-6:n-3 dietary ratio of 23:1 (O6) or a diet rich in fish oil with an n-6:n-3 dietary ratio of 2:1 (O3). After acclimation, rats completed 9 sessions on alternate days of stimulated muscle contractions at 75% peak isometric strength. Structural and densitometric properties of proximal tibia were measured using in vivo peripheral quantitative CT. Bone formation rate was quantified on the periosteal the surface by standard bone histomorphometry after intraperitoneal injections of calcein. There was a significant main effect due to diet on total volumetric bone mineral density. The diet rich in n-3 PUFAs also allowed for increases in cancellous volumetric bone mineral density at the proximal tibia independent from exercise, as high as 28%. However, proximal tibia metaphysis bone size and shape was not modified due to changes in diet. The training protocol resulted in a robust increase in bone formation, mass, and area at the midshaft tibia. Mineral apposition rate and bone formation rate were significantly greater in the O3 group compared to the O6 group with exercise at the midshaft tibia, ~36% and ~38% respectively. However, the greater bone formation seen in the O3 groups did not translate over to significantly greater bone mass and size as noted by the pQCT results at the same bone site, because there were no detectable differences between groups. In summary, our data demonstrate that a diet high in n-3 PUFAs independently increases bone density at the proximal tibia. In addition, there was enhanced BFR due to a diet high in n-3 PUFAs with exercise, but those increases did not translate over to increased cortical bone mass or size. These data provide evidence that fish oil consumption with and without simulated resistance training exercise can be beneficial to bone outcomes