The AKR1A1 protein is a member of the aldo-keto reductase superfamily that is responsible for the conversion of D-glucuronate to L-gulonate in the ascorbic acid (vitamin C) synthesis pathway. In a pCAG-eGFP transgenic mouse line that was produced by pronuclear microinjection, the integration of the transgene resulted in a 30-kb genomic DNA deletion, including the Akr1A1 gene, and thus caused the knockout (KO) of the Akr1A1 gene and targeting of the eGFP gene. The Akr1A1 KO mice (Akr1A1eGFP/eGFP) exhibited insufficient serum ascorbic acid levels, abnormal bone development and osteoporosis. Using micro-CT analysis, the results showed that the microarchitecture of the 12-week-old Akr1A1eGFP/eGFP mouse femur was shorter in length and exhibited less cortical bone thickness, enlargement of the bone marrow cavity and a complete loss of the trabecular bone in the distal femur. The femoral head and neck of the proximal femur also showed a severe loss of bone mass. Based on the decreased levels of serum osteocalcin and osteoblast activity in the Akr1A1eGFP/eGFP mice, the osteoporosis might be caused by impaired bone formation. In addition, administration of ascorbic acid to the Akr1A1eGFP/eGFP mice significantly prevented the condition of osteoporotic femurs and increased bone formation. Therefore, through ascorbic acid administration, the Akr1A1 KO mice exhibited controllable osteoporosis and may serve as a novel model for osteoporotic research.

Primary osteoporosis (PO) is a common disease that was characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures and constitutes a pressing public health problem. But the effect of acupuncture or moxibustion treatment for PO is controversial.To provide a comprehensive systematic overview of current evidence from systematic reviews (SR)/Meta-analysis of acupuncture treatment for PO pertaining to risk of bias, quality of evidence and report quality.A total of 9 international and Chinese databases were searched for SR/meta-analysis of randomized controlled trials (RCTs). The risk of bias of SR/meta-analysis was appraised using the risk of bias in systematic reviews (ROBIS) instrument, the quality of the evidence was evaluated via Grading of Recommendations Assessment, Development and Evaluation (GRADE), and the report quality of the included studies are estimated by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA).According to ROBIS, only 2 articles were with risk of low bias; according to PRISMA, and most articles were reported incomplete, mainly in Q2, Q7, Q24, and Q27; according to GRADE, a total of 28 outcome indicators were evaluated under 4 different interventions of experimental group and control group: the evidence quality of bone mineral density (BMD) from treatment of acupuncture and moxibustion/acupuncture and moxibustion plus was high or moderate; Visual Analogue Score (VAS) of acupuncture plus moxibustion or acupuncture plus moxibustion plus other was low or very low; clinical effectiveness of acupuncture plus moxibustion or acupuncture plus moxibustion plus other was uncertain.Acupuncture and moxibustion can improve the BMD of PO patients according to high-quality evidence, and may benefit VAS, pain score, clinical efficacy based on moderate or low-quality evidence. Further research that provides higher quality evidence of SR/RCTs of acupuncture and moxibustion treatment for PO is required.

The accumulation of senescent cells is implicated in the pathology of several age-related diseases. While the clearance of senescent cells has been suggested as a therapeutic target for patients with osteoarthritis (OA), cellular senescence of bone-resident osteoblasts (OB) remains poorly explored. Since oxidative stress is a well-known inducer of cellular senescence, we here investigated the effect of antioxidant supplementation on the isolation efficiency, expansion, differentiation potential, and transcriptomic profile of OB from osteoarthritic subchondral bone. Bone chips were harvested from sclerotic and non-sclerotic regions of the subchondral bone of human OA joints. The application of 0.1 mM ascorbic acid-2-phosphate (AA) significantly increased the number of outgrowing cells and their proliferation capacity. This enhanced proliferative capacity showed a negative correlation with the amount of senescent cells and was accompanied by decreased expression of reactive oxygen species (ROS) in cultured OB. Expanded cells continued to express differentiated OB markers independently of AA supplementation and demonstrated no changes in their capacity to osteogenically differentiate. Transcriptomic analyses revealed that apoptotic, cell cycle-proliferation, and catabolic pathways were the main pathways affected in the presence of AA during OB expansion. Supplementation with AA can thus help to expand subchondral bone OB in vitro while maintaining their special cellular characteristics. The clearance of such senescent OB could be envisioned as a potential therapeutic target for the treatment of OA.

Mushrooms are the best nonanimal food source of vitamin D2. Pulsed irradiation can enhance vitamin D2 in mushrooms quickly. We investigated the effect of supplementing high vitamin D2Pleurotus ferulae mushrooms in a mouse model of osteoporosis. Thirty-two female C57BL/6JNarl mice were divided into four groups including sham, ovariectomized (OVX), OVX+nonpulsed mushroom (NPM) and OVX+pulsed mushroom (PM). After 23 weeks of treatment, serum samples were analyzed for osteoblast and osteoclast indicators, as well as metabolites using NMR spectroscopy. To examine bone density, femurs were analyzed using micro-computed tomography. The NPM and PM treatment mice showed increased bone density in comparison with OVX mice. In addition, the PM mice showed higher osteoblast and lower osteoclast indicators in comparison with OVX mice. Serum metabolomics analysis indicated several metabolites that were different in PM mice, some of which could be correlated with bone health. Taken together, these results suggest that pulsed irradiated mushrooms are able to increase bone density in osteoporotic mice possibly through enhanced bone metabolism. Further studies in humans are needed to show their efficacy in preventing osteoporosis.

BACKGROUND:The effect of low-level laser therapy (LLLT) on bone regeneration during osseointegration and bone graft is very controversial. Despite many positive reports of in vitro and in vivo studies and more than 50 randomized clinical trials claiming a positive effect of photobiomodulation (PBM), many reports found no significant effect of lasers.

OBJECTIVE:The aim of this study was to evaluate studies correlating PBM and bone regeneration and to assesses parameters that produce positive results based on dose and output power used.

MATERIALS AND METHODS:Four electronic databases were used: PubMed, Springer, Google Scholar, and Cochrane.

RESULTS:The research yielded 230 articles. The full texts of all articles were evaluated and scored using eligibility criteria adapted from Cericato et al. After evaluation, only 19 articles met the inclusion criteria.

CONCLUSIONS:A positive effect of low-level laser energy on bone regeneration within a certain relationship between dose and output power was found. LLLT stimulates cellular metabolism, increasing protein synthesis and subsequent bone regeneration. A high dose combined with low power or a low dose combined with high power appears to produce a positive effect.

OBJECTIVE:To determine the effects of low-magnitude whole body vibration (WBV) on the structure and function of subchondral trabecular bones, cartilage degradation, bone/cartilage turnover, and osteoarthritis (OA) joint function.

METHODS:Knee osteoarthritis model was established in 96 rabbits through left anterior cruciate ligament transaction (ACLT). The rabbits were randomly divided into six groups: ACLT control group, WBV+ACLT group (five subgroups, each comprising 16 rabbits receiving 5 Hz, 10 Hz, 20 Hz, 30 Hz and 40 Hz WBV, respectively, with 2-4 mm amplitude for 40 min/d and 5 d/week over a period of 8 weeks). Joint function was tested via weight-bearing asymmetry. The microarchitecture of subchondral trabecular bones was examined using vivo micro-computed tomography (micro-CT). Cartilage samples from knee joints were taken for gross morphology and histology examinations. Serum samples were taken to detect cartilage oligomeric matrix protein (COMP), C-terminal telopeptide of typeⅠ collagen (CTX)-Ⅰ and urine CTX-Ⅱ.

RESULTS:Knee joint pain decreased with 10 Hz (P<0.05) and 20 Hz WBV treatment (P<0.05) , but increased with 40 Hz treatment (P<0.05). The micro-CT results showed that articular cartilage increased first, peaked at 20 Hz, and then decreased (P<0.05) . With increased frequency of WBV, the trabecular number, subchondral bone thickness and bone volume fraction increased, serum CTX-Ⅰ decreased, COMP and CTX-Ⅱ increased, especially at 20 Hz (P<0.05).

CONCLUSION:Lower frequency (20 Hz) WBV can improve bone microstructure, increase bone turnover, delay cartilage degeneration and improve limb function of rabbits with OA.

OBJECTIVES:The aim of this study was to review the literature about the effect of whole body vibration exercise in the BMD in patients with postmenopausal osteoporosis without medications.

METHODS:A systematic review was performed.

RESULTS:The frequency of the mechanical vibration used in the protocols has varied from 12 to 90 Hz. The time used in the protocols varied from 2 up to 22 months. Techniques with X-rays were used in nine of the twelve publications analyzed, the Dual energy X-ray absorptiometry (DEXA) in eight studies and the High resolution peripheral quantitative computed tomography (HR-pQCT) in one publication. The concentration of some biomarkers was determined, as the sclerostin, the bone alkaline phosphatase, N-telopeptide X and 25-hydroxyvitamin D. Among the twelve articles analyzed, seven of them have shown an improvement of the BMD of some bone of postmenopausal women exposed to whole body vibration exercises not associated to medications; as well as modifications in biomarkers.

BACKGROUND AND PURPOSE:Decreased bone mineral density (BMD) is a common condition in postmenopausal women that can be managed with impact activities. Among the activities studied are the whole-body vibration (WBV) and muscle-strengthening exercises. The purpose of this study was to compare the effects of WBV versus Pilates exercise on BMD in postmenopausal women.

METHODS:In this study, 51 postmenopausal women were randomized into 3 groups: vibration (n = 17), Pilates (n = 17), and control (n = 17). Outcomes were the areal bone mineral density (aBMD) (lumbar spine, femoral neck, total hip, trochanter, intertrochanter, and ward's area) assessed by dual-energy x-ray absorptiometry at baseline and follow-up. The interventions were performed 3 times a week for 6 months, totaling 78 sessions. The analysis was performed with intention-to-treat and covariance analyses adjusted for baseline outcomes.

RESULTS:After 6 months, 96.1% of the participants completed the follow-up. The analyses demonstrated significant mean between-group differences in favor of the interventions: vibration versus control, for the aBMD of the lumbar spine (0.014 g/cm; 95% confidence interval [CI], 0.006-0.022; P= .018, d = 1.21) and trochanter (0.018 g/cm; 95% CI, 0.006-0.030; P = .012, d = 1.03); and Pilates versus control, for the aBMD of the lumbar spine (0.016 g/cm; 95% CI, 0.007-0.025; P = .008, d = 1.15) and trochanter (0.020 g/cm; 95% CI, 0.010-0.031; P = .005, d = 1.28).

CONCLUSION:In postmenopausal women, 3 weekly sessions of WBV or Pilates administered for 6 months provided an equal effect on BMD.

BACKGROUND AND PURPOSE:Decreased bone mineral density (BMD) is a common condition in postmenopausal women that can be managed with impact activities. Among the activities studied are the whole-body vibration (WBV) and muscle-strengthening exercises. The purpose of this study was to compare the effects of WBV versus Pilates exercise on BMD in postmenopausal women.

METHODS:In this study, 51 postmenopausal women were randomized into 3 groups: vibration (n = 17), Pilates (n = 17), and control (n = 17). Outcomes were the areal bone mineral density (aBMD) (lumbar spine, femoral neck, total hip, trochanter, intertrochanter, and ward's area) assessed by dual-energy x-ray absorptiometry at baseline and follow-up. The interventions were performed 3 times a week for 6 months, totaling 78 sessions. The analysis was performed with intention-to-treat and covariance analyses adjusted for baseline outcomes.

RESULTS:After 6 months, 96.1% of the participants completed the follow-up. The analyses demonstrated significant mean between-group differences in favor of the interventions: vibration versus control, for the aBMD of the lumbar spine (0.014 g/cm; 95% confidence interval [CI], 0.006-0.022; P= .018, d = 1.21) and trochanter (0.018 g/cm; 95% CI, 0.006-0.030; P = .012, d = 1.03); and Pilates versus control, for the aBMD of the lumbar spine (0.016 g/cm; 95% CI, 0.007-0.025; P = .008, d = 1.15) and trochanter (0.020 g/cm; 95% CI, 0.010-0.031; P = .005, d = 1.28).

CONCLUSION:In postmenopausal women, 3 weekly sessions of WBV or Pilates administered for 6 months provided an equal effect on BMD.

Background:In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This review summarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To further understand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventions that can be used in future exercise-related studies.

Methods:PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treating various diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity [Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters: one that limited publication dates to"in 10 years"and one that sorted the results as"best match". Then we grouped the commonly used exercise methods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseases and organ functions in 8 different systems.

Results:A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exercise interventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascular system (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and the system related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntary wheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, most of them demonstrated positive effects on various systemic diseases and organ functions. Most diseases were remitted with exercise regardless of the exercise method used, although some diseases showed the best remission effects when a specific method was used.

Conclusion:Our review strongly suggests that exercise intervention is a cornerstone in disease prevention and treatment in mice. Because exercise interventions in humans typically focus on chronic diseases, national fitness, and body weight loss, and typically have low intervention compliance rates, it is important to use mice models to investigate the molecular mechanisms underlying the health benefits from exercise interventions in humans.

We studied the effect of boron supplement on experimental osteopenia caused by strenuous exercise in 93- d-old female Wistar rats. A control group of 15 rats was not manipulated. The exercise group of 30 rats was divided into 2 groups of 15 rats each, one that was fed a diet supplemented with 50 mg/kg of boron in the form of Na(2)B(4)O(7), and other that, did not receive a boron supplement. The length and weight were determined in the femur and fifth lumbar vertebra and the bone mineral content and density were assessed through densitometry, and trabecular bone volume, trabecular number, trabecular thickness, and trabecular separation with histomorphometry. The femur length and weight, and vertebra weight, and femur and vertebra bone mineral content and density were significantly lower and the trabecular separation was higher in the exercise group than in the others (p<0.005 in all). The femur weight, bone mineral content and density, trabecular bone volume and trabecular thickness, were significantly higher in the exercise plus boron group (p<0.005 to 0.0001). It was concluded that boron preserves bone mass in rats that have been exposed to intense exercise.

To summarize the existing evidence and evaluate the efficacy of acupuncture as a clinical treatment for osteoporosis. Six English and four Chinese databases were searched from their inception to April 2017. Randomized controlled trials were included, in which warm acupuncture, needling or electroacupuncture were compared with sole Western medicine with osteoporosis. All the data were assessed and extracted by two authors independently. The bias risk assessment recommended by the Cochrane Collaboration's tool was used to assess the quality of the selected studies. This meta-analysis was conducted by using RevMan 5.3. Pooled analyses were calculated by standardized mean difference (SMD) and 95% confidence interval (CI). Heterogeneity was assessed by Itest. Thirty-five studies involving 3014 patients were located. Meta-analysis showed that warm acupuncture could increase the bone mineral density of lumar (SMD [Formula: see text] 0.93, 95% CI [Formula: see text] 0.65, 1.21, [Formula: see text][Formula: see text]0.00001) and femur (MD[Formula: see text][Formula: see text][Formula: see text]0.11, 95% CI[Formula: see text][Formula: see text][Formula: see text]0.05, 0.16, P[Formula: see text][Formula: see text][Formula: see text]0.0002), the level of serum calcium (MD[Formula: see text][Formula: see text][Formula: see text]0.18, 95% CI[Formula: see text][Formula: see text][Formula: see text]0.13, 0.24, [Formula: see text][Formula: see text]0.00001) and estradiol (SMD[Formula: see text][Formula: see text][Formula: see text]0.65, 95% CI[Formula: see text][Formula: see text][Formula: see text]0.32, 0.98, P[Formula: see text][Formula: see text][Formula: see text]0.0001), relieve pain (MD[Formula: see text][Formula: see text][Formula: see text]-1.64, 95% CI[Formula: see text][Formula: see text][Formula: see text]-2.69, -0.59, P[Formula: see text][Formula: see text][Formula: see text]0.002), decrease the level of serum alkaline phosphatase (MD[Formula: see text][Formula: see text][Formula: see text]-7.8, 95% CI[Formula: see text][Formula: see text][Formula: see text]-14.17, -0.84, P [Formula: see text] 0.03) compared with sole Western medicine. Electroacupuncture could relieve pain (MD[Formula: see text][Formula: see text] -1.32, 95% CI[Formula: see text][Formula: see text][Formula: see text]-2.15, -0.48, P[Formula: see text][Formula: see text][Formula: see text]0.002), increase the level of serum calcium (MD[Formula: see text][Formula: see text][Formula: see text]-0.12, 95% CI [Formula: see text] -0.16,-0.09, [Formula: see text][Formula: see text]0.00001) and decrease the level of serum alkaline phosphatase (MD [Formula: see text] -3.63, 95% CI [Formula: see text] -6.60, -0.66, P [Formula: see text] 0.02) compared with sole Western medicine. Needling could relieve pain (MD [Formula: see text] -2.27, 95% CI [Formula: see text] -3.11, -1.43, [Formula: see text][Formula: see text]0.00001) compared with sole Western medicine. This present systematic review indicated that acupuncture could be an effective therapy for treating osteoporosis. Warm acupuncture seemed to more effective than electroacupuncture and needling for osteoporosis in comparison to sole Western medicine.

Study Design Systematic review and meta-analysis. Background It remains unclear whether exercise combining different types of physical activities (combined exercise interventions) would effectively preserve postmenopausal women's bone mineral density (BMD) at different sites. Objectives To examine the impact of combined exercise interventions on lumbar spine, femoral neck, total hip and total body BMD in postmenopausal women. Methods An electronic database search was conducted in PubMed, EMBASE, SPORTDiscus, and Web of Science up to Jan1, 2016. Randomized controlled trials (RCTs) that conducted combined exercise interventions and reported BMD values in postmenopausal women were included. Two authors independently extracted the data from individual studies. The primary endpoint was the change in BMD values from baseline to follow-up. The effect sizes were estimated by the standardized mean difference (SMD) methods using fixed-effects models. Results Eleven RCTs including 1061 postmenopausal women met the inclusion criteria. The levels of between-study heterogeneity were relatively low (I(2)<50%). Exercise integrating different physical activities significantly increased lumbar spine (SMD=0.170, 95%=0.027-0.313, p=0.019), femoral neck (SMD=0.177, 95%CI=0.030-0.324, p=0.018), total hip (SMD=0.198, 95%CI=0.037-0.3590, p=0.016) and total body (SMD=0.257, 95%CI=0.053-0.461, p=0.014) BMD. Combined exercise interventions generated a beneficial effect on femoral neck BMD (SMD=0.219, 95%CI=0.034-0.404, p=0.020) in groups with participants' age<60 years, and significantly improved lumbar spine BMD (SMD=0.349, 95%CI=0.064-0.634, p=0.016) in groups with women's age≥60 years. Conclusion Our findings suggest that combined exercise interventions appear to be effective in preserving postmenopausal women's BMD at lumbar spine, femoral neck, total hip and total body. Level of Evidence Therapy, level 1a. J Orthop Sports Phys Ther, Epub 3 Mar 2017. doi:10.2519/jospt.2017.6969.

[Purpose] This study was designed to investigate the effects of lactose-free milk intake and whole-body vibration exercises on bone density in elderly female nursing home residents who had difficulty exercising outdoors and had not consumed milk. [Subjects and Methods] Twenty seven elderly women aged 70 or older from 3 nursing homes located in Incheon, Korea participated in the study. The experimental group (n=13) carried out whole-body vibration exercises and drank lactose-free milk, while the control group (n=14) continued to live their ordinary nursing home lives. Weight, BMI, T-scores, and Z-scores were compared between the experimental and control groups after 12 weeks. [Results] The comparison of changes in weight and BMI in the control group before and after the 12-week experiment found no statistically significant differences. However, bone mineral density was significantly different, with the T-score significantly decreasing from -2.99 to -3.48 and the Z-score decreasing from -1.87 to -2.58. The other comparisons of physical changes in the control group before and after the 12-week experiment found no statistical significance. [Conclusion] The results indicate that regular consumption of lactose-free milk and performing whole-body vibration exercises can delay the progression of bone density loss in older adults in nursing homes; adequate exercise and calcium intake could eventually help prevent fractures.

Resistance training (RT) has been known to be effective in maintaining and improving bone strength, which is based on bone mineral density (BMD) and bone quality. However, it is not clear whether RT is effective in improving bone strength in patients with type-2 diabetes mellitus (T2DM), who have a high risk of fracture. Therefore, we tested the effects of a 6-week RT regimen using percutaneous electrical stimulation in T2DM model rats, male Otsuka Long-Evans Tokushima Fatty (OLETF), and its control, Long-Evans Tokushima Otsuka (LETO). After 6 weeks of RT, tibial BMD in RT legs was significantly higher than that in control (CON) legs in both groups. In diaphyseal cortical bone, bone area/tissue area, and cortical thickness was significantly increased in RT legs compared with CON legs in both groups. Cortical porosity was highly observedin OLETF compared with LETO, but RT improved cortical porosity in both groups. Interestingly, trabecular number, trabecular thickness and trabecular space as well as BMD and bone volume/tissue volume in proximal tibial metaphyseal trabecular bone were significantly improved in RT legs compared withCON legs in both groups. In contrast, connectivity density and structural model index were not affected by RT. These results indicate that the 6-week RT regimen effectively increased BMD and improved bone quality in T2DM model rats as well as control rats. Therefore, RT may have the potential to improve bone strength and reduce fracture risk, even in patients with T2DM.

OBJECTIVE:Assess the effectiveness of selected yoga postures in raising bone mineral density (BMD).

METHODS:Ten-year study of 741 Internet-recruited volunteers comparing preyoga BMD changes with postyoga BMD changes.

OUTCOME MEASURES:Dual-energy x-ray absorptiometric scans. Optional radiographs of hips and spine and bone quality study (7 Tesla).

RESULTS:Bone mineral density improved in spine, hips, and femur of the 227 moderately and fully compliant patients. Monthly gain in BMD was significant in spine (0.0029 g/cm(2), P = .005) and femur (0.00022 g/cm(2), P = .053), but in 1 cohort, although mean gain in hip BMD was 50%, large individual differences raised the confidence interval and the gain was not significant for total hip (0.000357 g/cm(2)). No yoga-related serious injuries were imaged or reported. Bone quality appeared qualitatively improved in yoga practitioners.

CONCLUSION:Yoga appears to raise BMD in the spine and the femur safely.