Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (-0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.

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Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels leads to increased oxidative stress in bone remodeling. Tocotrienol, a member of vitamin E that exhibits antioxidant activities, has shown potential as an agent for the treatment of osteoporosis. Most studies on the osteoprotective effects of tocotrienols had used the oral form of tocotrienols, despite their low bioavailability due the lack of transfer proteins and high metabolism in the liver. Several bone studies have utilized tocotrienol combined with a nanocarrier to produce a controlled release of tocotrienol particles into the system. However, the potential of delivering tocotrienol-nanocarrier combination through the intraosseous route has never been explored. In this study, tocotrienol was combined with a nanocarrier, poly lactic-co-glycolic acid (PLGA), and injected intraosseously into the bones of ovariectomized rats to produce targeted and controlled delivery of tocotrienol into the bone microenvironment. This new form of tocotrienol delivery was compared with the conventional oral delivery in terms of their effects on bone parameters. Forty Sprague-Dawley rats were divided into five groups. The first group was sham operated, while other groups were ovariectomized (OVX). Following 2 months, the right tibiae of all the rats were drilled at the metaphysis region to provide access for intraosseous injection. The estrogen group (OVX + ESTO) and tocotrienol group (OVX + TTO) were given daily oral gavages of Premarin (64.5 mg/kg) and annatto-tocotrienol (60 mg/kg), respectively. The locally administered tocotrienol group (OVX + TTL) was given a single intraosseous injection of tocotrienol-PLGA combination. After 8 weeks of treatment, both OVX + TTO and OVX + TTL groups have significantly lower bone markers and higher bone mineral content than the OVX group. In terms of bone microarchitecture, both groups demonstrated significantly higher trabecular separation and connectivity density than the OVX group (p < 0.05). Both groups also showed improvement in bone strength by the significantly higher stress, strain, stiffness, and Young’s modulus parameters. In conclusion, daily oral tocotrienol and one-time intraosseous injection of tocotrienol-PLGA combination were equally effective in offering protection against ovariectomy-induced bone changes.

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Vitamin E incorporation into highly cross-linked polyethylene (HXLPE) has been introduced to improve wear resistance, and vitamin E incorporated HXLPE (VEPE) has been used in total hip arthroplasty.The aim of this meta-analysis was to investigate the wear properties of VEPE in clinical practice by synthesizing the data provided in randomized clinical trials.The effects on implant stability, functional outcomes and revision rate of VEPE were also compared with those of HXPLE or ultra-high molecular weight polyethylene (UHMWPE).Literature searches were conducted on 1 January 2020 using MEDLINE, EMBASE, Cochrane and ClinicalTrials.gov databases. Randomized controlled trials (RCTs) comparing the aforementioned parameters between VEPE and standard HXPLE/UHMWPE liners were included.Methodological quality and the bias of the included studies were analysed. Meta-analyses were performed using the Review Manager software.Nine RCTs met the eligibility criteria and were included. At early and mid-term follow-up, the vertical penetration and the total penetration of the femoral head were both significantly reduced in the VEPE group. The steady state wear rate of the VEPE group was also remarkably lower.However, at two-year follow-up, significantly increased cup migration was observed in the VEPE group. Moreover, the mid-term clinical outcomes of the VEPE group were worse, while the total revision rates between the two groups were not significantly different.The limited number of included studies may compromise our conclusion regarding clinical outcomes of the VEPE bearing surface. More RCTs with longer follow-up periods are needed to further investigate the effects of VEPE in total hip arthroplasty.

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Menopause is the leading cause of osteoporosis for elderly women due to imbalanced bone remodelling in the absence of oestrogen. The ability of tocotrienol in reversing established bone loss due to oestrogen deficiency remains unclear despite the plenitude of evidence showcasing its preventive effects. This study aimed to investigate the effects of self-emulsified annatto tocotrienol (SEAT) on bone histomorphometry and remodelling in ovariectomised rats. Female Sprague Dawley rats (n=36) were randomly assigned into baseline, sham, ovariectomised (OVX) control, OVX-treated with annatto tocotrienol (AT) (60 mg/kg), SEAT (60 mg/kg) and raloxifene (1 mg/kg). Daily treatment given through oral gavage was started two months after castration. The rats were euthanised after eight weeks of treatment. Blood was collected for bone biomarkers. Femur and lumbar bones were collected for histomorphometry and remodelling markers. The results showed that AT and SEAT improved osteoblast numbers and trabecular mineralisation rate (p<0.05 vs untreated OVX). AT also decreased skeletal sclerostin expression in OVX rats (p<0.05 vs untreated OVX). Similar effects were observed in the raloxifene-treated group. Only SEAT significantly increased bone formation rate and reduced RANKL/OPG ratio (p<0.05 vs untreated OVX). However, no changes in osteoclast-related parameters were observed among the groups (p>0.05). In conclusion, SEAT exerts potential skeletal anabolic properties by increasing bone formation, suppressing sclerostin expression and reducing RANKL/OPG ratio in rats with oestrogen deficiency.

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Several treatment protocols for medication-related osteonecrosis of the jaw (MRONJ) have been published. Despite the efficacy of surgical therapy of approximately 90% as primary therapy, the role of other agents, such as drug administration, should not be underestimated. Based on previous experience with osteoradionecrosis, the association of pentoxifylline and tocopherol has shown encouraging results in MRONJ patients. Despite the need for long-term use of the combination, compliance has been good. However, studies in breast cancer patients revealed that pentoxifylline can require dose reduction or discontinuation due to nausea and epigastric pain. Cilostazol has been used as a substitute for pentoxifylline in peripheral artery disease. Herein we report a case in which cilostazol replaced pentoxifylline at a dose of 100mg, 2 times/day with tocopherol 500UI, 2 times/day, in a 77-year-old female patient that could not tolerate pentoxifylline for the management of MRONJ. After an uneventful 22 months of follow-up, a cone-beam computed tomography revealed complete bone formation and no signs of recurrence. Cilostazol may be a useful and safe alternative to pentoxifylline as part of MRONJ management protocols.

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Objective: To investigate the association between vitamin E and handgrip strength (HGS) with multiple factors.

Methods: A total of 1,814 participants were included (822 men and 981 women) from the Korean subjects of the 7th Korea National Health and Nutrition Examination Survey in 2018. Data were analyzed using multiple logistic regression to determine the correlation between vitamin E and HGS with potential confounding factors.

Results: In the multiple logistic regression model, only the young age group (19-40 years) of men showed a positive relationship between vitamin E and HGS. However, in older age groups (41-80 years) of men and all age groups of women, there was no statistically significant result. After adjusting for confounding factors, young men showed higher vitamin E levels and higher HGS. Conversely, women and older age groups did not show significant results after adjusting for confounding factors.

Conclusion: In this study, the serum vitamin E level had a positive effect on HGS in young men (<40 years). Further research is needed on this topic regarding vitamin E intake and other objective measures.

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Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at p < 5 × 10^-8 in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm² increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome.

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Dietary habits are of considerable interest as a modifiable factor for the maintenance of muscle health, especially sarcopenia. The present study aimed to investigate the association between dietary intake and sarcopenia prevalence in community-dwelling Japanese subjects. This cross-sectional study was conducted using data from the fifth survey of the Research on Osteoarthritis/Osteoporosis against Disability (ROAD) study, and 1345 participants (437 men and 908 women) aged ≥60 years were included in the analysis. Sarcopenia was determined by the definition of the Asian Working Group for Sarcopenia established in 2014, and dietary intake was assessed with the brief-type self-administered diet history questionnaire. Overall, 77 subjects (5.7%) were identified as having sarcopenia, 5.0% of men and 6.1% of women. Multiple logistic regression analysis showed that the odds ratios of sarcopenia for the dietary intake of vitamin E (α-tocopherol, 0.14 (CI 0.04-0.49), β-tocopherol (0.24, CI 0.07-0.78), γ-tocopherol (0.28, CI 0.09-0.87), and fats (fat 0.27, CI 0.08-0.96; monounsaturated fatty acids, 0.22, CI 0.07-0.72, polyunsaturated fatty acids, 0.28, CI 0.09-0.89) at the highest quantile were significantly lower compared with those at the lowest quantile. Therefore, higher dietary intakes of vitamin E and fats would be associated with a lower prevalence of sarcopenia.

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