Changes in blood bone markers after the first and second bouts of whole-body eccentric exercises.

The present study compared the first (EC1) and second (EC2) bouts of whole-body eccentric exercises to examine the effects of the magnitude of muscle damage on changes in blood bone markers. Fifteen sedentary young men performed nine eccentric exercises of arm, leg, and trunk muscles, and repeated them 2 weeks later. Blood samples were taken before and 2 h and 1-5 days following each bout to analyze plasma creatine kinase (CK) activity and myoglobin concentration, serum tartrate-resistant acid phosphatase (TRAP), type 1 C-terminal telopeptide (CTX-1), procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BAP), undercarboxylated-osteocalcin (ucOCN), carboxylated-osteocalcin (cOCN), and leptin concentrations. All except ucOCN changed significantly (p < 0.05) after both bouts. When comparing bouts for peak changes, P1NP (bone formation marker) and CTX-1 (bone resorption marker) increased less after EC2 (peak: 137±96% and 7±6%, respectively) than after EC1 (146 ± 80% and 30 ± 21%, respectively), whereas BAP (bone formation marker) increased more after EC2 (18 ± 16%) than after EC1 (4 ± 15%) (p < 0.05). Leptin (49 ± 58%) and cOCN (14 ± 10%) increased more (p < 0.05) after EC2 than after EC1 (-30 ± 15%, 9 ± 26%). Significant (p < 0.05) correlations were evident between peak CK activity and peak CTX-1 (r = 0.847), P1NP (r = 0.815), BAP (r = -0.707), ucOCN (r = 0.627), cCON (r = -0.759), and leptin (r = -0.740) changes after EC1, but many of these correlations disappeared after EC2. This was also found for the relationships between other muscle damage markers (myoglobin, muscle soreness, and muscle strength) and the bone markers. It was concluded that bone turnover was affected by eccentric exercise, but muscle damage was unfavorable for bone formation.

Acute responses of bone specific and related markers to maximal eccentric exercise of the knee extensors and flexors in young men.

OBJECTIVES: The present study determined time-course changes in plasma bone-specific and -related markers following a bout of maximal eccentric contractions (MaxEC) of bilateral knee extensors (KE) and flexors (KF). METHODS: Sedentary young men (n=30) performed a bout of 10 sets of 10 MaxEC (30°/s) of KE and KF with each leg, respectively. Maximal voluntary isometric contraction (MVC) torque, muscle soreness (SOR), plasma creatine kinase (CK) activity, insulin, leptin, tumor necrosis factor-α (TNF-α), undercarboxylated-osteocalcin (ucOCN), carboxy-terminal crosslinking telopeptide of type I collagen (CTX-1) and procollagen type I N-terminal propeptide (P1NP) concentrations were measured from before to 7 days after MaxEC. RESULTS: Significant changes in MVC (KE: -28%, KF: -38%), SOR and plasma CK activity (peak: 39,163 IU/L) following MaxEC were evident (P<0.05) compared to baseline. Plasma leptin (17%) concentrations decreased at 1 day after MaxEC. In bone related markers, plasma ucOCN concentrations (20%) increased at 7 days after MaxEC, and plasma CTX-1 concentrations decreased at 2, 4 and 7 days after MaxEC (6~7%; P<0.05). CONCLUSION: These results demonstrate that a lean effect of bone generation and an enhanced energy anabolism can be induced by a single bout of MaxEC.

Differences in neurocognitive performance and metabolic and inflammatory indices in male adults with obesity as a function of regular exercise.

NEW FINDINGS: What is the central question of this study? Does regular exercise have benefits with regard to the neurocognitive problems related to obesity and are regular-exercise-induced neurocognitive changes associated with changes in the levels of metabolic/inflammatory biomarkers? What is the main finding and its importance? Although obese individuals with regular exercise showed higher C-reactive protein levels as compared to the healthy-weight individuals, only the obese individuals with a sedentary lifestyle showed deviant neurocognitive performance and higher metabolic and tumour necrosis factor-α levels. The P3 amplitude was correlated with the levels of leptin in the obese individuals with regular activity, implicating that the potential mechanism of neurocognitive facilitation as a result of regular exercise could be reduced serum leptin levels. ABSTRACT: Obesity has been shown to be highly associated with deterioration in executive functions, elevated energy metabolic indices and low-grade systemic inflammation. Exercise has the capacity to reduce these negative phenomena. This work examined the effect of regular exercise on neurocognitive deficits and metabolic/inflammatory markers in obesity. Fifty-four participants were divided into three groups: healthy-weight (HW), obesity with regular exercise (ORE) and obesity with sedentary lifestyle (OSL), according to their BMI and frequency of exercise. Dual-energy X-ray absorptiometry was applied to assess the whole-body composition of the participants. The assessment included neurocognitive measures during the Posner paradigm test and fasting blood measurements. Relative to the HW group, only the OSL group showed significantly longer reaction times and smaller P3 amplitudes, even when controlling for the cardiorespiratory fitness co-variable. Although the OSL group exhibited a greater N2 amplitude than the HW group, when controlling for cardiorespiratory fitness the difference between the two groups disappeared. The OSL group showed greater levels of metabolic indices (i.e. leptin, insulin and glucose) than the HW group. The three groups had comparable interleukin (IL)-1ß and IL-6 levels. However, the ORE and OSL groups showed higher levels of C-reactive protein than the HW group. The OSL group exhibited higher tumour necrosis factor-α levels than the HW and ORE groups. P3 amplitude was negatively correlated with the levels of leptin in the ORE group. Individuals with obesity can still obtain advantages with regard to neurocognitive and metabolic/inflammatory indices through engaging in regular exercise, possibly due to reduced serum leptin levels.

Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production.

Chronic kidney disease-mineral bone disorder (CKD-MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/ß-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial ß-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.

Structural and Biomechanical Adaptations to Free-Fall Landing in Hindlimb Cortical Bone of Growing Female Rats.

The purpose of the study was to investigate the adaptation process of hindlimb cortical bone subjected to free-fall landing training. Female Wistar rats (7 weeks old) were randomly assigned to four landing (L) groups and four age-matched control (C) groups (n = 12 per group): L1, L2, L4 L8, C1, C2, C4 and C8. Animals in the L1, L2, L4 and L8 groups were respectively subjected to 1, 2, 4 and 8 weeks of free-fall-landing training (40 cm height, 30 times/day and 5 days/week) while the C1, C2, C4 and C8 groups served as age-matched control groups. The tibiae of the L8 group were higher in cortical bone mineral content (BMC) than those in the C8 group (p < 0.05). Except for the higher bone mineralization over bone surface ratio (MS/BS, %) shown in the tibiae of the L1 group (p < 0.05), dynamic histomorphometry in the tibial and femoral cortical bone showed no difference between landing groups and their age-matched control groups. In the femora, the L1 group was lower than the C1 group in cortical bone area (Ct.Ar) and cortical thickness (Ct.Th) (p < 0.05); however, the L4 group was higher than the C4 group in Ct.Ar and Ct.Th (p <0 .05). In the tibiae, the moment of inertia about the antero-posterior axis (Iap), Ct.Ar and Ct.Th was significantly higher in the L8 group than in the C8 group (p < 0.05). In biomechanical testing, fracture load (FL) of femora was lower in the L1 group than in the C1 group (p < 0.05). Conversely, yield load (YL), FL and yield load energy (YE) of femora, as well as FL of tibiae were all significantly higher in the L8 group than in the C8 group (p < 0.05). Free-fall landing training may initially compromise bone material. However, over time, the current free-fall landing training induced improvements in biomechanical properties and/or the structure of growing bones.

Neurocognitive performances of visuospatial attention and the correlations with metabolic and inflammatory biomarkers in adults with obesity.

NEW FINDINGS: What is the central question of this study? Obesity is linked to cognitive deficits, elevated energy metabolic indices and low-grade systemic inflammation. Do the relationships between neurocognitive performance and the biochemical markers (e.g. energy metabolic indices and inflammatory cytokines) occur independently of factors known to be associated with neurocognitive dysfunction (i.e. cardiorespiratory fitness) in young adults? What is the main finding and its importance? Young obese adults showed poorer neuropsychological performances, aberrant neural activity and higher C-reactive protein and energy metabolic indices. The higher leptin and C-reactive protein concentrations showed a significant negative association with lower P3 amplitudes. However, leptin was the sole predictive factor, implicating hyperleptinaemia in the altered neurocognitive function observed in obesity. The present study was designed to explore the neurophysiological mechanism of visuospatial attention deficits in obese adults and to examine the relationships between neurocognitive (neuropsychological and neurophysiological) performances and the biochemical markers. Thirty obese adults and 30 healthy-weight control subjects, categorized by body mass index and percentage fat as measured with dual-energy X-ray absorptiometry, provided a fasting blood sample and performed a visuospatial attention protocol with concomitant electrophysiological recording. The obese group showed slower reaction times and smaller P3 amplitudes when performing the cognitive task. Even when controlling for the covariable of cardiorespiratory fitness, the results remained. In addition, the serum concentrations of insulin, glucose, leptin and C-reactive protein were significantly higher in the obese group relative to the control group, but not those of interleukin-6, interleukin-1ß and tumour necrosis factor-α. Partial correlations adjusting for cardiorespiratory fitness showed that leptin and C-reactive protein concentrations in the obese group were negatively associated with poorer neurophysiological (i.e. P3 amplitude) performance. However, the regression analysis showed that leptin was the sole predictor of P3 amplitude in the obese group. These findings indicate that the individuals with obesity exhibited neurocognitive deficits when performing the visuospatial attention task, and serum leptin concentrations could be one of the influential factors.

Bone morphogenetic proteins signal via SMAD and mitogen-activated protein (MAP) kinase pathways at distinct times during osteoclastogenesis.

To investigate the role of bone morphogenetic protein (BMP) signaling in osteoclastogenesis in vivo, we eliminated BMPRII in osteoclasts by creating a BMPRII(fl/fl);lysM-Cre mouse strain. Conditional knock-out (cKO) mice are osteopetrotic when compared with WT controls due to a decrease in osteoclast activity. Bone marrow macrophages (BMMs) isolated from cKO mice are severely inhibited in their capacity to differentiate into mature osteoclasts in the presence of M-CSF and receptor activator of NF-κB (RANK) ligand. We also show that BMP noncanonical (MAPK) and canonical (SMAD) pathways are utilized at different stages of osteoclast differentiation. BMP2 induces p38 phosphorylation in pre-fusion osteoclasts and increases SMAD phosphorylation around osteoclast precursor fusion. Phosphorylation of MAPKs was decreased in differentiated BMMs from cKO animals. Treating BMMs with the SMAD inhibitor dorsomorphin confirms the requirement for the canonical pathway around the time of fusion. These results demonstrate the requirement for BMP signaling in osteoclasts for proper bone homeostasis and also explore the complex signaling mechanisms employed by BMP signaling during osteoclast differentiation.

A methionine-restricted diet and endurance exercise decrease bone mass and extrinsic strength but increase intrinsic strength in growing male rats.

Dietary methionine restriction (MR) has been suggested to be comparable to endurance exercise with respect to its beneficial effects on health. To further investigate the effects of MR and endurance exercise on growing bone, 7-wk-old male Sprague-Dawley rats were fed different l-methionine (Met)-containing diets with or without endurance exercise intervention (Ex; 0.86% Met, 0.52% Met, 0.17% Met, 0.86% Met-Ex, 0.52% Met-Ex, and 0.17% Met-Ex groups). After an 8-wk intervention period, exercise-trained rats had a 9.2% lower body weight (BW) than did sedentary rats (P < 0.05). Additionally, 0.17% Met-fed rats had 32% lower BW when compared with rats fed the other 2 diets (P < 0.05). Serum osteocalcin was lower in the 0.17% Met-Ex group compared with the other 2 exercise groups and the 0.17% Met group (P < 0.05). Serum concentrations of C-terminal telopeptide of type 1 collagen were lower in exercise-trained and 0.17% Met-fed rats than in sedentary rats and rats fed the other 2 diets (P < 0.05 for both). Rats fed the 0.17% Met diet had lower trabecular bone volume, bone mineralization activities, and bone mineral content (BMC; e.g., total, cortical, and spongy BMC) and bone mineral density (BMD; e.g., total and spongy BMD) indices compared with rats fed the other 2 diets (P < 0.05). Exercise-trained rats also had lower bone mineralization activity, trabecular osteoclast density, total BMC, cortical BMC, and total BMD compared with sedentary rats (P < 0.05). In total BMD, only the 0.17% Met-Ex group had values lower than the other 2 exercise groups and the 0.17% Met group (P < 0.05). Compared with rats fed the other 2 diets and sedentary rats, the femora of 0.17% Met-fed and exercise-trained rats, respectively, had smaller size and/or lower extrinsic strength but enhanced intrinsic biomechanical properties (P < 0.05). The results indicate that MR and endurance exercise caused lower whole bone mass, size, and/or strength but might enhance intrinsic bone strength.

Short-term free-fall landing causes reduced bone size and bending energy in femora of growing rats.

The purpose of this study was to determine the effects of a mechanical loading course (short-term free-fall landing) on femoral geometry and biomechanical properties in growing rats. Thirty-two female Wistar rats (7-week-old) were randomly assigned to three groups: L30 (n = 11), L10 (n = 11) and CON (n = 10) groups. Animals in the L10 and L30 groups were subjected to a 5-day free-fall landing program in which animals were dropped from a height of 40cm 10 and 30 times per day, respectively. Landing ground reaction force (GRF) was measured on the 1(st) and 5(th) days of landing training. All animals were subjected to two fluorescent labeling injections on the days before and after the 5-day landing training. Three days after the last labeling injection, animals were sacrificed under deep anesthesia. Methods of dynamic histomorphometry, tissue geometry and tissue biomechanical measurements were used to investigate the response in femora. A significant decrease in peak GRF in the hind-limb was shown from day 1 to day 5. No significant difference was shown among groups in dynamic histomorphometry. Biomechanical property analyses showed significantly lower maximal energy and post-yield energy in the L10 and L30 groups as compared to the CON group (p < 0.05). Moreover, geometric measurements revealed that cross-sectional cortical areas and thicknesses were significantly lower in landing groups than in the CON group. Short-term (5-day) free-fall landing training resulted in minor compromised long bone tissue, as shown by reduced bending energy and cortical bone area but not in other mechanical properties or tissue measurements (e.g. weights and length) of growing female rats. Further studies would be valuable to investigate whether this compromised bone material represents the existence of a latency period in the adaptation of bone material to external mechanical loading. Key pointsShort-term free-fall landing causes compromised bone material as shown by reduced post-yield energy in long bones of rodents.The results of the current study suggest the existence of unsettled bone material after a short-term mechanical loading regime.The connection of the present animal study to the stress fractures occurring in young athletes needs to be clarified.

Acute effects of plyometric jumping and intermittent running on serum bone markers in young males.

The purpose of this study was to investigate whether different modes of single-bout exercise would cause different responses in short-term bone metabolism. 24 untrained male college students (19.1 ± 0.1 years old) were recruited and randomly assigned to three groups: (1) a single-bout plyometric exercise group (the PL group, n = 8), (2) a 200-meter × 10 intermittent running group (the IR group, n = 8) and (3) a sedentary control group, which followed the same time schedule of experimentation without performing any exercise (the CON group, n = 8). Serial blood samples were collected before (baseline) and 5 min, 15 min, 1 h, 3 h, 6 h, 24 h, 48 h, and 72 h after exercise trials. Within 15 min of exercise, the PL and IR groups showed significantly higher serum phosphorus than did the control group (P < 0.05). Osteocalcin levels were significantly higher in the PL group at 5 min and 1 h after exercise (P < 0.05), while serum tartrate-resistant acid phosphatase (TRAP) showed no differences among groups. Exercises with different mechanical impact levels responded differently in serum bone formation markers as shown by osteocalcin. Because the increase in osteocalcin in the PL group was revealed shortly after the exercise bout, the changes might due to an exercise-induced mechanical impact rather than bone cellular activities.

The effects of systemic chemical sympathectomy on local bone loss induced by sciatic neurectomy.

BACKGROUND: It has been suggested that the sympathetic nervous system (SNS) is involved in bone metabolism and that blockade of the SNS could reduce bone loss and stimulate bone formation. However, the question of whether suppression of SNS tone could compensate for mechanical unloading-induced bone loss must be further clarified. The purpose of this study was to investigate whether systemically inhibiting sympathetic nervous system (SNS) tone could prevent bone loss from mechanical-inactivity-induced osteopenia. METHODS: Female Wistar rats (12 weeks old) were randomly assigned to three groups: the SN group (n = 10), or single leg sciatic neurectomy group; the SNP group (n = 12), or single leg sciatic neurectomy + propranolol treatment (0.5 g/L in dietary water) group; and the CON group (n = 10), or single leg sham-operated group. Animals were fed with distilled water or propranolol in water, in accordance with their group design, for 30 days. Histomorphometry, geometry, tissue weight, and serum markers were assessed. RESULTS: Propranolol-treated animals drank significantly less water, but did not differ in daily chow consumption or body weight gain. In histomorphometric analysis, the spongy bone volume ratio in proximal tibiae was significantly lower in the two sciatic neurectomy groups, but there was no difference between the SN and SNP groups. Architecture analysis showed that the SN group had significantly thinner trabeculae and fewer trabeculae than the CON group (p < 0.05), but there was no difference between the SNP and CON groups. There were no significant differences for tissue weight, geometric measurement, or serum markers assay. CONCLUSION: It was observed that blockade of the SNS prevented neurectomy-induced bone resorption, as demonstrated by various histomorphometric data, although the difference between SN and SNP did not reach significance. In further work it would be valuable to study possible gender, age, and dose-dependent efficacy of propranolol on bone metabolism.

Changes in plasma C1q, apelin and adropin concentrations in older adults after descending and ascending stair walking intervention.

This study compared changes in plasma complement component 1q (C1q), apelin and adropin concentrations in older obese women after descending (DSW) and ascending stair walking (ASW) training (n = 15/group) performed twice a week for 12 weeks, with gradual increases in exercise time from 5 to 60 min. Fasting blood samples were collected 3 days before the first and 4 days after the last training session. The improvements in the maximal voluntary isometric contraction (MVIC) strength of the knee extensors, functional physical fitness [e.g., 30-s chair stand (CS) performance], resting systolic blood pressure (SBP), insulin sensitivity [e.g., oral glucose tolerance test (OGTT)] and blood lipid profiles [e.g., total cholesterol (TC)] were greater (p < 0.05) in the DSW than ASW group. Plasma C1q decreased (- 51 ± 30%), and apelin (23 ± 15%) and adropin (127 ± 106%) increased (p ≤ .0.05) only after DSW. Significant (p ≤ 0.01) partial correlations were found between the pre- to post-DSW changes in C1q, apelin or adropin and changes in outcome measures [e.g., C1q and MVIC (r = - 0.837), apelin and SBP (r = - 0.854), and andropin and OGTT (r = - 0.729)]. These results showed that greater decreases in plasma C1q and greater increases in apelin and adropin concentrations were associated with greater improvements in outcome measures after DSW than after ASW.

Swimming training increases the post-yield energy of bone in young male rats.

The purpose of this study is to investigate the effects of non-weight-bearing exercise on growing bone. Male Wistar rats (7 week-old) were assigned to one baseline control group, one control group and two swimming training groups, which were trained with 2 and 4% body-weight mass added, respectively. After an 8-week training period, three groups showed significant development compared to the baseline control group. Among the three 15-week-old groups, swimming-trained rats were lower in body weight (BW), densitometry and size-related measurements. In femoral biomechanical testing, swimming training groups were significantly lower in yield moment and ultimate moment, which may be due to a significantly lower long bone cross-sectional moment of inertia. However, the two swimming groups were higher in post-yield energy absorption and displacement. Further, in estimated tissue-level biomaterial properties, no differences were shown in yield stress, strain or toughness among the three groups. Using BW as a covariate, results of ANCOVA showed no differences in size-related parameters among the three groups, and some parameters were even higher in the two swimming groups. Regarding Pearson's correlation, size-related parameters correlated well to BW and whole bone strength but not to tissue post-yield behaviors. In conclusion, when compared to age-matched control group, swimming rats showed lower bone strength and lower yield energy absolutely at the structural level, but similar yield stress and yield toughness at the tissue level. Moreover, swimming training benefited growing bone in post-yield behaviors. Further studies should investigate the parameters that contribute to this exercise-induced post-yield behavior.

The effects of a 226-km ironman triathlon race on bone turnover in amateur male triathletes.

BACKGROUND: The purpose of this study was to investigate the effects of an Ironman-distance triathlon on bone metabolism. METHODS: Nine recreational male triathletes (39.7±8.2 years old) were voluntarily recruited before a 226-km Ironman triathlon race. Baseline blood samples were collected >1 hour before race. Serial post-race blood sampling time points included immediately (0hr), 1 hour (1hr), 1 day (d), 3 d, and 5 d after the Ironman race. RESULTS: Serum muscle damage markers, serum myoglobin, creatine kinase (CK) and lactate dehydrogenase (LDH) revealed significant post-race peak values immediately, 1hr and 1d after the race, respectively. Except for the marginally higher serum CK and myoglobin at 5d (P=0.01~0.05), all post-race serum levels of muscle damage markers were significantly higher than baseline levels (P<0.01). Serum phosphorus values were significantly higher immediately (0hr) after the Ironman race. Serum osteocalcin, an index specific to bone formation, showed a significant decrease at time points 0hr and 1hr, but a significant increase 1 day after (P<0.01) and a marginal increase 3 and 5 days after (P=0.01~0.05) the race. No difference was shown in type I collagen C-telopeptide (CTX-1), a bone resorption marker. Pearson's correlation between serum osteocalcin and CTX-1 was done at each time point, and significant correlation was shown on the 5th d after the race (r=0.591, P<0.05). CONCLUSIONS: An Ironman-distance contest induces a bone-formative-favoring turnover during the post-race period for amateur male triathletes.

Ultrasound stimulates MMP-13 expression through p38 and JNK pathway in osteoblasts.

It has been shown that ultrasound (US) stimulation accelerates fracture healing, bone maturation, and remodeling in the animal models and in clinical studies. One of the major factor involves in remodeling process is matrix metalloproteinases (MMPs) such as MMP-13 that has been shown to degrade the native interstitial collagens in several tissues. Here we found that US stimulation increased the secretion of MMP-13 in cultured rat osteoblasts, as shown by zymographic analysis. US stimulation also increased the mRNA level of MMP-13, c-Fos, and c-Jun. Cycloheximide (an inhibitor of protein translocation) and actinomycin D (an inhibitor of gene transcription) did not inhibit the MMP-13, c-Fos, and c-Jun mRNA expression, suggesting that such expression does not require de novo protein synthesis and not change their stabilities. p38 inhibitor, SB203580 or JNK inhibitor, SP600125 but not ERK inhibitor, PD98059 attenuated the US-induced MMP-13, c-Fos, and c-Jun expression; these results were further substantiated by transfecting with the dominant negative mutants of p38 or JNK. The binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter and the enhancement of AP-1 luciferase activity was enhanced by US stimulation. Taken together, our results provide evidence that US stimulation increases MMP-13 expression through p38 and JNK signaling pathway to regulate bone remodeling.

Onion decreases the ovariectomy-induced osteopenia in young adult rats.

It has been suggested that fruit and vegetable consumption are associated with good bone health. Onion, in particular, has been verified in its efficacy in bone resorption activity. In this study, we further investigated the effects of an onion-containing diet on ovariectomy-induced bone loss using methods of serum marker assay, histomorphometric analysis and biomechanical tests. Sixty-four female Wistar rats (14-week-old) with sham operations or ovariectomy were assigned to 6 groups: CON, sham-operated control group; OVX, ovariectomized group; ALN, ovariectomized rats treated with alendronate (1 mg/kg/day, p.o.); and 3% ON, 7% ON and 14% ON, ovariectomized rats fed with diets containing 3%, 7% and 14% (wt/wt) onion powder, respectively. Animals were sacrificed after a six-week treatment course. In the serum marker assay, alendronate and all three onion-enriched diets significantly decreased serum calcium level (p<0.05). Both 14% ON group and the ALN group even showed similarly lower level of serum osteocalcin (p<0.05), suggesting a down-regulation of bone turnover. The histomorphometric analysis showed that ovariectomy markedly decrease bone trabeculae. The ALN and 14% ON rats were 80% and 46% higher, respectively, in BV/TV than the OVX rats (p<0.05), and the rats fed with onion-enriched food showed a lesser ovariectomy-induced bone loss in a dose-dependent manner. Additionally, both ALN and 14% ON groups had significantly more trabecular number, less separated trabeculae, and fewer osteoclasts (p<0.05), but the protective efficacy from the 14% onion-enriched diet was slightly inferior to that of alendronate. Ovariectomy also significantly decreased tissue weight and biomechanical strength in the OVX group (p<0.05). The ALN and 14% ON groups equivalently showed a lesser decrease in tissue weight, though the difference was not significant. On the other hand, both the ALN and 14% ON groups represented similar biomaterial properties of femurs, and both reduced the ovariectomy-induced decrease in bending load and bending energy (p<0.05). The present study further verified that an onion-enriched diet could counteract ovariectomy-induced bone loss and deterioration of biomechanical properties.

Low-intensity pulsed ultrasound-promoted bone healing is not entirely cyclooxgenase 2 dependent.

OBJECTIVE: The purpose of this study was to investigate whether low-intensity pulsed ultrasound (LIPUS) promotes bone healing through the cyclooxgenase 2 (COX-2) pathway. METHODS: Each male Sprague Dawley rat (n = 48 total) in the study underwent bilateral drilled hole injury in the proximal tibiae. Then the animals were randomly assigned to 2 groups: a COX-2 inhibitor (COX-2in) group, treated with the selective COX-2 inhibitor rofecoxib (3 mg/kg/d), and a control (CON) group, treated with distilled water. Low-intensity pulsed ultrasound was applied to the injured site of a single limb of each rat for 20 min/d at a consistent intensity (30 mW/cm(2)) and frequency (1.5 MHz). Subsets of animals from both groups were killed after 3, 7, or 14 days of single-limb LIPUS treatment. Tissue sections were subjected to alcian blue staining, and the healing status was quantified according to a scoring system. RESULTS: After 3 and 7 days, the CON group's LIPUS-treated limbs had significantly higher healing scores than its nontreated limbs and the COX-2in group's LIPUS-treated limbs (P < .05). Interestingly, after the 14-day treatment, the COX-2in group's LIPUS-treated limbs had significantly higher healing scores than its nontreated limbs (P < .05) but showed no difference when compared with the CON group. CONCLUSIONS: Low-intensity pulsed ultrasound did show accelerative efficacy on bone healing. Selective inhibition of COX-2 could delay but not entirely block the benefits of LIPUS on bone healing. Low-intensity ultrasound treatment could promote bone healing through other, non-COX-2-dependent, pathways.

Exercise training ameliorates glucosamine-induced insulin resistance in ovariectomized rats.

OBJECTIVE: Glucosamine (GlcN), which has been reported to induce insulin resistance (IR), is a popular nutritional supplement used to treat osteoarthritis in menopausal women. We previously demonstrated that GlcN treatment caused IR in ovariectomized rats by reducing the expression of glucose transport protein subtype 4 (GLUT-4) in skeletal muscle. In the present study, we hypothesized that endurance exercise training can reverse GlcN-induced IR. METHODS: Fifty female rats were randomly divided into five groups with 10 rats in each group: (1) sham-operated group; (2) sham-operated group with GlcN treatment for 14 days; (3) ovariectomy (OVX) group; (4) OVX with GlcN treatment; and (5) OVX with GlcN treatment followed by exercise training (running program) for 8 weeks. RESULTS: Fasting plasma glucose increased in the OVX + GlcN group, and fasting plasma insulin and the homeostasis model assessment-insulin resistance (HOMA-IR) were significantly higher only in this group. After the rats received exercise training for 8 weeks, no increase in the fasting plasma glucose, insulin, or HOMA-IR was observed. In an intraperitoneal glucose tolerance test, the plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index were significantly elevated only in the OVX with GlcN treatment group. However, the plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index decreased after exercise training for 8 weeks, implying that GlcN-induced IR in OVX rats could be reversed through exercise. A histological analysis revealed that exercise training can reduce islet hypertrophy and maintain GLUT-4 in skeletal muscle. CONCLUSIONS: Exercise training can alleviate IR in OVX rats treated with GlcN. Islet hyperplasia was subsequently prevented. Preserving GLUT-4 expression may be one of the mechanisms by which exercise prevents IR.

Dietary restrictions, bone density, and bone quality.

Caloric restriction (CR), protein restriction (PR), and specific amino acid restriction (e.g., methionine restriction (MR)) are different dietary interventions that have been confirmed with regard to their comprehensive benefits to metabolism and health. Based on bone densitometric measurements, weight loss induced by dietary restriction is known to be accompanied by reduced areal bone mineral density, bone mass, and/or bone size, and it is considered harmful to bone health. However, because of technological advancements in bone densitometric instruments (e.g., high-resolution X-ray tomography), dietary restrictions have been found to cause a reduction in bone mass/size rather than volumetric bone mineral density. Furthermore, when considering bone quality, bone health consists of diverse indices that cannot be fully represented by densitometric measurements alone. Indeed, there is evidence that moderate dietary restrictions do not impair intrinsic bone material properties, despite the reduction in whole-bone strength because of a smaller bone size. In the present review, we integrate research evidence from traditional densitometric measurements, metabolic status assays (e.g., energy metabolism, oxidative stresses, and inflammatory responses), and biomaterial analyses to provide revised conclusions regarding the effects of CR, PR, and MR on the skeleton.

Methionine restriction alters bone morphology and affects osteoblast differentiation.

Methionine restriction (MR) extends the lifespan of a wide variety of species, including rodents, drosophila, nematodes, and yeasts. MR has also been demonstrated to affect the overall growth of mice and rats. The objective of this study was to evaluate the effect of MR on bone structure in young and aged male and female C57BL/6J mice. This study indicated that MR affected the growth rates of males and young females, but not aged females. MR reduced volumetric bone mass density (vBMD) and bone mineral content (BMC), while bone microarchitecture parameters were decreased in males and young females, but not in aged females compared to control-fed (CF) mice. However, when adjusted for bodyweight, the effect of MR in reducing vBMD, BMC and microarchitecture measurements was either attenuated or reversed suggesting that the smaller bones in MR mice is appropriate for its body size. In addition, CF and MR mice had similar intrinsic strength properties as measured by nanoindentation. Plasma biomarkers suggested that the low bone mass in MR mice could be due to increased collagen degradation, which may be influenced by leptin, IGF-1, adiponectin and FGF21 hormone levels. Mouse preosteoblast cell line cultured under low sulfur amino acid growth media attenuated gene expression levels of Col1al, Runx2, Bglap, Alpl and Spp1 suggesting delayed collagen formation and bone differentiation. Collectively, our studies revealed that MR altered bone morphology which could be mediated by delays in osteoblast differentiation.