Maximal Exercise Research Articles

Recalibrated FRIEND equation for peak oxygen pulse is accurate in endurance athletes: the NOODLE study

Peak oxygen pulse (O2Ppeak) is an important index of cardiorespiratory fitness (CRF). The FRIEND database is a global source of reference values for CRF. However, no reference equation is tailored for endurance athletes (EA) to predict O2Ppeak. Here, we adjusted the well-established FRIEND equation for O2Ppeak to the characteristics of the EA population. 32 (34.0%) female EA and 62 (66.0%) male well-trained EA underwent maximal cardiopulmonary exercise test on a treadmill. V̇O2max was 4.5 ± 0.5 L min−1 in males and 3.1 ± 0.4 L min−1 in females. O2Ppeak was 23.6 ± 2.8 mL beat−1 and 16.4 ± 2.0 mL beat−1 for males and females, respectively. Firstly, we externally validated the original FRIEND equation. Secondly, using multiple linear regression, we adjusted the FRIEND equation for O2Ppeak to the population of EA. The original FRIEND equation underestimated O2Ppeak for 2.9 ± 2.9 mL beat−1 (P < .001) in males and 2.2 ± 2.1 mL beat−1 (P < .001) in females. The updated equation was 1.36 + 1.07 (23.2 · 0.09 · age − 6.6 [if female]). The new equation explained 62% of the variance and significantly predicted O2Ppeak (R2 = 0.62, β = 0.78, P < .001). The error of the EA-adjusted model was 0.1 ± 2.9 mL beat−1 (P = .82) and 0.2 ± 2.1 mL beat−1 (P = .65) for males and females respectively. Recalibration of the original FRIEND equation significantly enhances its accuracy among EA. The error of the EA-adjusted model was negligible. A new recalibrated equation should be used to predict O2Ppeak in the population of EA.

Effects of coffee intake on skeletal muscle microvascular reactivity at rest and oxygen extraction during exercise: a randomized cross-over trial.

The effects of coffee ingestion on skeletal muscle microvascular function are not well understood. This study aimed to investigate the acute effects of coffee intake with varying levels of caffeine on skeletal muscle microvascular reactivity at rest and oxygen extraction during maximal incremental exercise in physically active individuals. Twenty healthy young male participants were administered coffee with low caffeine (3 mg/kg body weight; LC), high caffeine (6 mg/kg body weight; HC), and placebo (decaf) in different sessions. Skeletal muscle reactivity indexes, including tissue saturation index 10s slope (TSI10) and TSI half time recovery (TSI ½) following 5-minute ischemia were measured at rest and were measured at baseline and post-coffee consumption using near-infrared spectroscopy (NIRS). Post-coffee intake, NIRS was also used to measure microvascular oxygen extraction during exercise via maximal incremental exercise. Peak oxygen consumption and peak power output (Wpeak) were simultaneously evaluated. Post-coffee consumption, TSI10 was significantly higher in the LC condition compared to placebo (p = 0.001) and significantly higher in the HC condition compared to placebo (p < 0.001). However, no difference was detected between LC and HC conditions (p = 0.527). HC condition also showed significant less TSI ½ compared to placebo (p = 0.005). However, no difference was detected for microvascular oxygen extraction during exercise, despite the greater Wpeak found for HC condition (p < 0.001) compared to placebo. Coffee ingestion with high caffeine level (6 mg/kg body weight) significantly enhanced skeletal muscle reactivity at rest. However, the improvement of exercise performance with coffee intake is not accompanied by alterations in muscle oxygen extraction.

Heart Rate Response In Maximal Exercise Is Related With Coronary Heart Disease

Heart Rate Response In Maximal Exercise Is Related With Coronary Heart Disease

Autonomic Rebound Following Maximal Exercise In Bodybuilders And Recreationally Active Participants

Autonomic Rebound Following Maximal Exercise In Bodybuilders And Recreationally Active Participants

Cardiorespiratory Fitness And Obesity: Oxidative Stress Responses In Circulating Exosomes Following Maximal Aerobic Exercise

Cardiorespiratory Fitness And Obesity: Oxidative Stress Responses In Circulating Exosomes Following Maximal Aerobic Exercise

Affective, perceptual and physiologic responses to isokinetic contractions under blood flow restriction.

Blood flow restriction (BFR) has been shown to enhance the effectiveness of low load resistance exercise, but less research has examined its utility in conjunction with maximal isokinetic contractions, which may depend on the restrictive pressure and speed of contraction. Individuals reported to the laboratory for three visits to complete three sets of 20 maximal elbow flexion exercises at 60°/s and 300°/s under 0%, 40% and 80% of their arterial occlusion pressure. Muscle thickness was measured before and after exercise, and ratings of discomfort, perceived activation, and exercise-induced feelings were obtained at the completion of each exercise. Fatigue was assessed as the decline in average peak torque across the three sets. A total of 27 individuals (11 females, 16 males) completed the study. There was a significant interaction for torque at both 60°/s and 300°/s (P<0.001), with each increasing pressure resulting in greater fatigue. Muscle swelling was present across all conditions but was lowest in the 40% BFR condition applied during the 300°/s speed. At both 60°/s and 300°/s speeds, the 80% BFR pressure was associated with lower enjoyment, greater discomfort, and greater perceived activation (all P<0.05). The combined effects of BFR to maximal isokinetic contractions increased fatigue with less of an impact on muscle swelling. These results indicate that BFR may enhance the effectiveness of long-term isokinetic training, but it is also important to consider the addition of BFR was associated with lower levels of enjoyment and greater discomfort which may decrease adherence.

Reliability Of A Cognitive Test Battery Pre And Post Maximal Cycling Exercise

Reliability Of A Cognitive Test Battery Pre And Post Maximal Cycling Exercise

The association between aerobic capacity and spinal curvature and mobility in young soccer players

BackgroundThere is a lot of research in terms of injuries and performance in football and nowadays aerobic capacity, spinal posture and mobility have been taken into consideration separately in terms of performance. Considering from a biomechanical perspective, we thought spinal curvature and mobility may affect aerobic performance and investigated the relationship between them. Research questionDo young soccer players' segmental spinal curvature and mobility affect their aerobic capacity and maximal exercise performance? MethodsThirty-four young league players (mean age 16.56 ±1.11 years) were evaluated pre-season. Spinal assessments in the sagittal plane with a non-invasive, computer-assisted electromechanical device and aerobic capacity assessment with a cardiopulmonary exercise-testing device were applied. The relationship between spinal postural variables with aerobic capacity was done by Pearson correlation analysis, and simple linear regression analysis was used to estimate the effect of spinal curvature and mobility on aerobic performance. ResultsVarious parameters of aerobic performance were related to spinal curvature and mobility. Maximal oxygen uptake (VO2max) and maximal heart rate (HRmax) were negatively correlated with thoracic angle (r=-0.343, p=0.047 and r=-0.344, p=0.046; respectively). Thoracic angle was also associated with tidal volume (VT) and VO2/HR (r=-0.347, p=0.044 and r=-0.348, p=0.044; respectively). Higher thoracic mobility caused to reach the anaerobic threshold (VAT) earlier (r=-0.368, p=0.032), at a lower speed (r=-0.367, p=0.033). In other segments, lumbar mobility was negatively correlated with VT at VAT (r=-0.346; p=0.045), while spinal inclination with HR at VAT (r=-0.387, p=0.024). SignificanceAlthough it is within physiological ranges, increased spinal curvature and mobility are associated with a decrease in aerobic capacity in young soccer players. Spinal curvature and mobility especially in the thoracic region may affect the aerobic performance of a soccer player. The trainers should consider spinal alignment for not only the technical and tactical but also the general performance of the soccer player.

Changes In Motivation States For Physical Activity With Maximal Exercise Vary By Aerobic Fitness Level

Changes In Motivation States For Physical Activity With Maximal Exercise Vary By Aerobic Fitness Level

Prediction of central Augmentation Index in healthy adults.

Central Augmentation Index (AIx) is a surrogate marker of large artery stiffness that may provide valuable insight to cardiovascular health. The aim of this study was to evaluate the relationship between AIx and components of physical fitness. One hundred eighty-five healthy men and women (aged 20-79 years) underwent non-invasive assessment of arterial wave reflection to determine AIx, which was corrected to a heart rate of 75 beats per minute (AI×75). Body composition was evaluated using dual energy X-ray absorptiometry (DXA) and aerobic capacity (VO<inf>2max</inf>) was derived from expired gas analysis during a symptom limited exercise test on a treadmill. A multiple linear regression revealed age and VO<inf>2max</inf> as significant predictors of AI×75 [AI×75=32.055 + (0.252×age) - (0.722×VO<inf>2max</inf>)]. Upon removal of VO<inf>2max</inf> from regression analysis, resting heart rate (RHR) and % body fat (BF%) were revealed to be significant predictors of AI×75: AI×75=-61.316 + (0.481×age) + (0.565×BF%) + (0.56×RHR). Our findings demonstrate that central Augmentation Index can be reliably predicted in healthy adults who undergo a maximal exercise or body composition assessment. These prediction equations may be applied in non-medical settings to assist in creating comprehensive health and fitness profiles for healthy clientele.

The Physiological and Performance Effects of Actovegin during Maximal Cardiopulmonary Exercise Testing: A Randomized, Double-Blind, Placebo-Controlled Trial.

Evidence regarding the performance-related effects of Actovegin is limited, despite legislated restrictions being in place for this supplement within sport settings. Our study examined the effects of Actovegin on physiological responses and performance during maximal cardiopulmonary exercise in collegiate athletes. A randomized, double-blind, placebo-controlled experimental design was adopted. Moderately trained collegiate athletes from various sports were randomly allocated to placebo (n = 8) or Actovegin (n = 8) groups. All athletes consumed three capsules across each day for seven days of loading. Athletes underwent two separate cardiopulmonary exercise tests one week apart. Separate 2 × 2 mixed ANOVAs and effect sizes (ηp2) were used to assess for between- and within-group differences. A significant time * group effect (p = 0.036, ηp2 = 0.278) was observed in systolic blood pressure. Significant main effects were only observed for time in several variables, with increases in peak oxygen uptake (VO2) (p < 0.001, ηp2 = 0.893), peak minute ventilation (p = 0.004, ηp2 = 0.456), ventilatory equivalents for carbon dioxide (p = 0.002, ηp2 = 0.517), oxygen pulse (p = 0.006, ηp2 = 0.434), VO2 at first ventilatory threshold (p = 0.002, ηp2 = 0.520), velocity at second ventilatory threshold (p < 0.001, ηp2 = 0.997), VO2 at second ventilatory threshold (p < 0.001, ηp2 = 0.628), and peak velocity (p = 0.010, ηp2 = 0.386), and a decrease in respiratory exchange ratio (p < 0.001, ηp2 = 0.695). Our findings suggest that although physiological and performance alterations were evident with Actovegin supplementation during cardiopulmonary exercise, no further benefits beyond those obtained with a placebo were attained.

The Five Times Sit to Stand Test as a Tool to Assess Disability and Physical Capacity after Hospitalization for COVID-19

Background: Assessment of exercise tolerance should be an integral part of the follow- up of COVID-19 survivors. Objective: We aimed in this study to investigate the correlation between the 5 Times Sit to Stand Test (5STST) and the 6-Minute Walk Test (6MWT) and to determine their place in assessing exercise tolerance and disability in COVID-19 survivors. Methods: This was a cross-sectional study that included 201 survivors of COVID-19. All patients underwent a detailed medical questionnaire, assessment of disability by the Lawton scale, and sub- -maximal exercise tolerance by 6MWT and 5STST. Our study population was divided into two groups based on the Length of Hospital Stay (LHS) (&lt;10 or ≥10 days). Results: Compared with the group with a LHS &lt; 10 days, the group with prolonged LHS (≥10 days) had a significantly greater mean value of 5STST. In contrast, the mean values of 6-minute Walk Distance (6MWD) and Minimal Oxygen Saturation (MOS) were significantly lower. A significant correlation of 5STST with Lawton score (r = -0.373; p &lt; 0.0001) and 6MWD (r = -0.563; p &lt; 0.0001) was also found. Conclusion: Our results showed that the 5STST was correlated with the 6MWD and Lawton score. Hence, it could be proposed to assess physical capacity and disability, especially in patients who had a prolonged LHS for COVID-19.

Dietary patterns and cardiorespiratory fitness in midlife and subsequent all-cause dementia: findings from the Cooper Center Longitudinal Study

BackgroundIdentifying lifestyle factors that independently or jointly lower dementia risk is a public health priority given the limited treatment options available to patients. In this cohort study, we examined the associations between Mediterranean or Dietary Approaches to Stop Hypertension (DASH) diet adherence and cardiorespiratory fitness (CRF) with later-life dementia, and assessed whether the associations between dietary pattern and dementia are modified by CRF.MethodsData are from 9,095 adults seeking preventive care at the Cooper Clinic (1987–1999) who completed a 3-day dietary record and a maximal exercise test. Alzheimer’s disease and related disorders or senile dementia (i.e., all-cause dementia) was identified from Medicare administrative claims (1999–2019). Illness-death models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between Mediterranean or DASH diet adherence (primary exposure), CRF (secondary exposure), and all-cause dementia, adjusted for demographic and clinical factors. An interaction term was included between diet score and CRF to assess effect modification by CRF.ResultsThe mean age at baseline was 50.6 (standard deviation [SD]: 8.4) years, and a majority of the study sample were men (77.5%) and White (96.4%). 1449 cases of all-cause dementia were identified over a mean follow-up of 9.2 (SD: 5.8) years. Neither Mediterranean nor DASH diet adherence was associated with dementia risk in fully adjusted models (HR per SD of Mediterranean diet score: 1.00, 95% CI: 0.94, 1.05; HR per SD of DASH diet score: 1.02, 95% CI: 0.96, 1.08). However, participants with higher CRF had a decreased hazard of dementia (HR, per metabolic equivalent of task [MET] increase, Mediterranean model: 0.95, 95% CI: 0.92, 0.98; HR, per MET increase, DASH model: 0.96, 95% CI: 0.92, 0.97). No effect modification by CRF was observed in the association between diet and dementia.ConclusionsIn this sample of apparently healthy middle-aged adults seeking preventive care, higher CRF at midlife was associated with a lower risk of all-cause dementia, though adherence to a Mediterranean or DASH diet was not, and CRF did not modify the diet-dementia association. CRF should be emphasized in multimodal interventions for dementia prevention and investigated among diverse samples.

Association Between Cardiorespiratory Fitness and Trend of Age-Related Rise in Arterial Stiffness in Individuals With and Without Hypertension or Diabetes

Abstract BACKGROUND This study aimed to investigate whether higher cardiorespiratory fitness (CRF) can modify the trend of age-related rise in arterial stiffness in individuals with and without hypertension (HTN) or diabetes. METHODS The study included 4,935 participants who underwent maximal cardiopulmonary exercise testing with respiratory gas analysis in a health screening program. CRF was directly measured using peak oxygen uptake during the cardiopulmonary exercise test, while arterial stiffness was evaluated using brachial–ankle pulse wave velocity (baPWV). RESULTS Participants with high CRF levels had significantly lower baPWV compared with those with low CRF levels, regardless of HTN or diabetes status (P &amp;lt; 0.05). The trend of baPWV increased with age, but the rate of age-related increase in baPWV was lower in individuals with moderate-to-high CRF levels compared with those with low CRF levels, regardless of HTN or diabetes status. Joint association analysis indicated that the trend of age-related increase in baPWV was the lowest in fit individuals without HTN or diabetes compared with unfit individuals with HTN or diabetes (P &amp;lt; 0.01). However, the trend of age-related increase in baPWV was not attenuated in fit with HTN or diabetes compared with unfit with HTN or diabetes. CONCLUSIONS These findings suggest that higher CRF levels may mitigate the trend of age-related rise in arterial stiffness in individuals with and without HTN or diabetes. However, this attenuating trend appears more pronounced in individuals without HTN or diabetes.

Diastolic Stress Echocardiography in Patients With Hypertrophy Cardiomyopathy: Association With Exercise Capacity

Diastolic dysfunction plays a major role in precipitating congestive heart failure (CHF) in hypertrophic cardiomyopathy (HCM) patients. In many such patients, symptoms are unmasked only during exercise, as left ventricular (LV) filling pressure is normal at rest but increase with exercise. We sought to establish if abnormal post-exercise diastolic parameters are associated with reduced exercise capacity in patients with HCM. We examined 590 asymptomatic/minimally symptomatic HCM patients (54±14 years, 57% men, body mass index 30±6 kg/m2, 84% on betablockers) with HCM by two-dimensional and Doppler echocardiography at rest and following maximal treadmill exercise echocardiography (TSE). A complete echocardiogram (including LV ejection fraction, LV thickness, LV outflow tract [LVOT] gradient, degree of mitral regurgitation [MR]) was recorded. Diastolic parameters (septal and lateral [e’] velocities of the mitral annulus, peak early [E] and late [A] mitral inflow velocity, E/A ratio, E/e’, right ventricular systolic pressure [RVSP] and left atrial volume index [LAVI]) were recorded at rest and post-TSE. Exercise functional capacity was recorded and divided into <85% or >85% of age-gender predicted metabolic equivalents (AGP-METs). Following maximal exercise, 32% patients had at least moderate MR, mean LVOT gradient was 61±59 mmHg, E/A ratio was 1.2± 1.0, average E/e’ ratio 12.9±1.0 and peak RVSP was 36±15 mm Hg. Only 42% patients achieved >85% of AGP-METs; mean Mets were 7±3. On multivariable logistic regression analysis, higher body mass index (odds ratio [OR] 1.05), betablocker use (OR 2.58), higher LAVI (OR 1.02), higher peak-stress LVOTG (OR 1.06), peak-stress E/e’ (OR 1.04) and higher RVSP (OR 1.03) were independently associated with <85% AGP-METs achieved (all p<0.05). In conclusion, in asymptomatic/minimally symptomatic patients with HCM undergoing TSE, there is a significant and independent association between abnormal diastolic response to exercise and reduced exercise capacity in HCM. Incorporating diastolic parameters during stress echocardiography could provide incremental diagnostic utility in deciphering the exact etiology of dyspnea in such patients.

Validity of Wrist-Worn Activity Tracker Heart Rate Detection in Fontan Patients During Exercise.

Physical activity and a healthy lifestyle play an essential role in optimizing long-term health in patients with Fontan physiology. Wrist-worn activity trackers may be useful in medically directed exercise programs for patients with Fontan physiology. The objective of this study was to measure the validity of Garmin and Fitbit activity tracker heart rate detection in patients with Fontan circulation when compared to electrocardiogram (ECG) during cardiopulmonary exercise testing (CPET). 47 Fontan patients undergoing CPET for clinical indications were included and wore activity trackers during CPET. Heart rate via the activity tracker was collected at baseline, maximal exercise, and recovery. Patient heart rates, peak VO2, and peak respiratory exchange ratio (RER) were collected using standard CPET protocols and equipment. Heart rate at each time point was compared between the activity trackers and CPET ECG. Median age of participants was 17.1 years, 15.1 years since Fontan completion. Mean percent of predicted peak VO2 was 56.8%, z-score -3.2 with 61.7% of participants completing a maximal CPET (RER ≥ 1.09). Baseline oxygen saturation mean was 92.9%, 90.0% at maximal exercise. Activity trackers demonstrated mean absolute percentage error < 10% at most time points, comparable with other studies. Demographics, Fontan-associated comorbidities, and echocardiogram findings did not impact the accuracy. Consumer-oriented wrist-worn activity trackers show promising accuracy for heart rate monitoring in medically directed exercise programs for adolescents and young adults with Fontan physiology. Further validation across different exercise modalities is needed.

The Gut Microbiota characterization of a World-Class Mountain Trail runner during a complete competition season: a case report.

In the present case study, the gut microbiota (GM) profile of a male Elite Mountain Runner (34 years, 171cm, 59 kg, VO2max: 92 mL·min-1 ·kg-1) was analyzed over 5 months competitive period (6 samples). The GM diversity increased through the season coinciding higher levels to the peak performance and shorter and longer race (42 vs. 172 km) produced different phenotypic GM changes. Shorter race promoted the elevation of protective bacteria related to positive benefits (higher production of short-chain fatty acids (SCFAs), lactate resynthesis, mucin degraders). In contrast, longer race promoted an elevation of opportunistic pathogenic bacteria while reducing protective commensal bacteria. The present findings indicate that a higher resilience of the GM after competitions may support rapid recovery from maximal exercise. The GM analyses pre- and post-competition could represent a rapid indicator for the (patho)physiological impact of exercise and provide information on gut health and recovery time needed.

Effect of the ACTN3 R577X Polymorphism on Serum Creatine Kinase and Interleukin-6 Levels after Maximal Eccentric Exercise.

This study explored the interaction among ACTN3 R577X polymorphism, muscle damage, and post-exercise inflammatory response by assessing changes over time in serum creatine kinase and interleukin-6 levels. Ninety-five active Japanese participants (50 men and 45 women: 22.2 ± 2.3 years) who did not perform daily upper limb strength exercises were enrolled. Participants executed five sets of six maximal eccentric elbow flexion exercises. The exercise duration was 9 min, including rest between sets (90 s). Maximum voluntary isometric contraction, range of motion, muscle soreness, and serum creatine kinase and interleukin-6 levels were assessed pre and post and 1, 2, 3, and 5 d after exercise. Genotype groups were classified as RR + RX and XX based on the absence of ACTN3 expression. A significant time and group interaction (p = 0.045) on creatine kinase levels was observed between the groups, indicating that the absence of ACTN3 significantly affects creatine kinase changes. Conversely, no significant interaction on change in interleukin-6, maximum voluntary isometric contraction, range of motion, and muscle soreness was observed between groups. The results highlight an interaction on creatine kinase activity post-exercise by ACTN3 R577X polymorphism, with elevated activity in the XX genotype.

Effect of aortic valve replacement on myocardial perfusion and exercise capacity in patients with severe aortic stenosis

Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6–12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63 m/s, aortic valve area index 0.45 ± 0.13cm2/m2). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO2). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p < 0.001), with a corresponding 15% increase in myocardial perfusion reserve (MPR) (2.04 ± 0.57 to 2.34 ± 0.68; p = 0.004). Increasing severity of AS, presence of late gadolinium enhancement, lower baseline stress MBF and MPR were associated with a greater improvement in MPR post-AVR. On multivariable analysis low baseline MPR was independently associated with increased MPR post-AVR. There was no significant change in peak VO2 post-AVR, but a significant increase in exercise duration. Change in MPR was associated with change in peak VO2 post AVR (r = 0.346, p = 0.045). Those with the most impaired stress MBF and MPR at baseline demonstrate the greatest improvements in these parameters following AVR and the magnitude of change in MPR correlated with improvement in peak VO2, the gold standard measure of aerobic exercise capacity.

PSV-4 Clodronate re-release in response to controlled exercise and bone stressors in juvenile horses

Abstract Concerns over the extra-label use of bisphosphonates in skeletally immature horses has extended to include its likely re-release from bone into circulation in response to stressors. Therefore, the objective of this study was to be first to quantify the re-release of clodronate in response to controlled stressors. Yearling Quarter horses (n = 32) were stratified by age, body weight (BW), sex, and initial bone optical density into four treatment groups for a 168-d trial. Treatments consisted of control (CON; n = 8), single-dose (1X; d 84; n = 8), 2-dose (2X; d 0 and 84; n = 8), and four-dose groups (4X; d 0, 42, 84, and 126; n = 8). All horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW clodronate disodium (OSPHOSÒ) or saline (placebo) on d 0, 42, 84, and 126. Horses were housed in individual stalls (3.6 m × 7.2 m). Diets were formulated to meet nutrient requirements including concentrate offered every 12-h and ad libitum coastal bermudagrass (Cynodon dactylon) hay and water. Horses were exercised 5 d/wk with a progressive workload, and maximum exercise intensity was reached on d 120, verified via heart rate and blood lactate. On d 120, blood samples were collected prior to the start of the exercise bout (pre), and 0-, 0.5-, 1-, 3-, 12-, and 24-h post exercise. Both tuber coxae of each horse were biopsied on d 168 with blood samples collected prior to (pre), and 0, 12, 24, 48, 72, 168, and 336 h post biopsy. Clodronate was quantified in plasma from exercise and biopsy samples using liquid chromatography tandem mass spectrometry. Exercise and biopsy serum were analyzed for cortisol, a marker of stress, while biopsy serum was analyzed for substance P, a pain marker. Data were analyzed using SAS PROC MIXED. Exercise did not result in clodronate re-release as there was no treatment x time interaction or time effect (P ≥ 0.44), but clodronate was dose-dependently greater in treated groups throughout the exercise collection period (P &amp;lt; 0.01). A treatment x time interaction (P ≤ 0.01) was observed for clodronate concentrations surrounding bone biopsy in which concentrations decreased at 168 h post biopsy before increasing at 336 h in 4X horses. Substance P increased over time (P &amp;lt; 0.01) following biopsy, regardless of treatment. Despite decreasing over time (P ≤ 0.01), there were similarly no treatment differences (P ≥ 0.46) nor treatment ´ time interactions (P ≥ 0.78) for cortisol following either exercise or bone insult. In conclusion, submaximal exercise did not result in re-release of clodronate; however, direct bone insult disrupted clodronate concentrations in horses receiving 4 administrations of bisphosphonate despite no treatment impact on stress or pain indicators.