Serum Metabolomic Alteration in Rats with Osteoarthritis Treated with Palm Tocotrienol-Rich Fraction Alone or in Combination with Glucosamine Sulphate.

Osteoarthritis (OA) is a degenerative joint condition with limited disease-modifying treatments currently. Palm tocotrienol-rich fraction (TRF) has been previously shown to be effective against OA, but its mechanism of action remains elusive. This study aims to compare serum metabolomic alteration in Sprague-Dawley rats with monosodium iodoacetate (MIA)-induced OA which were treated with palm TRF, glucosamine sulphate, or a combination of both. This study was performed on thirty adult male rats, which were divided into normal control (n = 6) and OA groups (n = 24). The OA group received intra-articular injections of MIA and daily oral treatments of refined olive oil (vehicle, n = 6), palm TRF (100 mg/kg, n = 6), glucosamine sulphate (250 mg/kg, n = 6), or a combination of TRF and glucosamine (n = 6) for four weeks. Serum was collected at the study's conclusion for metabolomic analysis. The findings revealed that MIA-induced OA influences amino acid metabolism, leading to changes in metabolites associated with the biosynthesis of phenylalanine, tyrosine and tryptophan as well as alterations in the metabolism of phenylalanine, tryptophan, arginine and proline. Supplementation with glucosamine sulphate, TRF, or both effectively reversed these metabolic changes induced by OA. The amelioration of metabolic effects induced by OA is linked to the therapeutic effects of TRF and glucosamine. However, it remains unclear whether these effects are direct or indirect in nature.

A Review of the Application of Natural and Synthetic Scaffolds in Bone Regeneration.

The management of bone defects is complicated by the presence of clinical conditions, such as critical-sized defects created by high-energy trauma, tumour resection, infection, and skeletal abnormalities, whereby the bone regeneration capacity is compromised. A bone scaffold is a three-dimensional structure matrix serving as a template to be implanted into the defects to promote vascularisation, growth factor recruitment, osteogenesis, osteoconduction, and mechanical support. This review aims to summarise the types and applications of natural and synthetic scaffolds currently adopted in bone tissue engineering. The merits and caveats of natural and synthetic scaffolds will be discussed. A naturally derived bone scaffold offers a microenvironment closer to in vivo conditions after decellularisation and demineralisation, exhibiting excellent bioactivity, biocompatibility, and osteogenic properties. Meanwhile, an artificially produced bone scaffold allows for scalability and consistency with minimal risk of disease transmission. The combination of different materials to form scaffolds, along with bone cell seeding, biochemical cue incorporation, and bioactive molecule functionalisation, can provide additional or improved scaffold properties, allowing for a faster bone repair rate in bone injuries. This is the direction for future research in the field of bone growth and repair.

Comparing the performance of body mass index, waist circumference and waist-to-height ratio in predicting Malaysians with excess adiposity.

BACKGROUND: Body mass index (BMI) is a widely used surrogate tool to screen for obesity/adiposity, but it cannot differentiate between lean and fat mass. Thus, alternative tools to detect excess adiposity should be identified. AIM: This study aimed to compare the performance of BMI, waist circumference (WC) and waist-to-height ratio (WtHR) in predicting Malaysians with excess body fat defined by dual-energy X-ray absorptiometry (DXA). SUBJECTS AND METHODS: A total of 399 men and women aged ≥40 years were recruited from Klang Valley, Malaysia. The body composition of the subjects, including body fat percentage, was measured by DXA. The weight, height, WC and WHtR of the subjects were also determined. RESULTS: BMI [sensitivity = 55.7%, specificity = 86.1%, area under curve (AUC) = 0.709] and WC (sensitivity = 62.7%, specificity = 90.3%, AUC = 0.765) performed moderately in predicting excess adiposity. Their performance and sensitivity improved with lower cut-off values. The performance of WHtR (sensitivity = 96.6%, specificity = 36.1, AUC = 0.664) was optimal at the standard cut-off value and no modification was required. CONCLUSION: The performance of WC in identifying excess adiposity was greater than BMI and WHtR based on AUC values. Modification of cut-off values for BMI and WC could improve their performance and should be considered by healthcare providers in screening individuals with excess adiposity.

Normalisation of High Bone Remodelling due to Oestrogen Deficiency by Traditional Chinese Formulation Kang Shuai Lao Pian in Ovariectomised Rats.

Postmenopausal osteoporosis transpires due to excessive osteoclastic bone resorption and insufficient osteoblastic bone formation in the presence of oestrogen insufficiency. Kang Shuai Lao Pian (KSLP) is a red ginseng-based traditional Chinese medicine known for its anti-ageing properties. However, studies on its effect on bone loss are lacking. Thus, the current study examined the skeletal protective effects of KSLP in an ovariectomised rodent bone loss model. Three-month-old female Sprague Dawley rats (n=42) were randomised into baseline, sham and ovariectomised (OVX) groups. The OVX rats were supplemented with low- (KSLP-L; 0.15 g/kg), medium- (KSLP-M; 0.30 g/kg), high-dose KSLP (KSLP-H; 0.45 g/kg) or calcium carbonate (1% w/v). The daily supplementation of KSLP was performed via oral gavage for eight weeks. Gavage stress was stimulated in the ovariectomised control with distilled water. The rats were euthanised at the end of the study. Whole-body and femoral bone mineral content and density scans were performed at baseline and every four weeks. Blood samples were obtained for the determination of bone remodelling markers. Histomorphometry and biomechanical strength testing were performed on femurs and tibias. High bone remodelling typically due to oestrogen deficiency, indicated by the elevated bone formation and resorption markers, osteoclast surface, single-labelled surface and mineralising surface/bone surface ratio, was observed in the untreated OVX rats. Whole-body BMD adjusted to body weight and Young's modulus decreased significantly in the untreated OVX rats. High-dose KSLP supplementation counteracted these degenerative changes. In conclusion, KSLP improves bone health by normalising bone remodelling, thereby preventing bone loss and decreased bone strength caused by oestrogen deficiency. Its anti-osteoporosis effects should be validated in patients with postmenopausal osteoporosis.

Suppression of high bone remodelling by E'Jiao in ovariectomised rats.

The current prevention options for postmenopausal osteoporosis are very limited. E'Jiao is a collagen-rich traditional Chinese medicine with the potential to prevent osteoporosis but more comprehensive investigations are lacking. This study aimed to investigate the skeletal protective effects of E'Jiao in a rat model of osteoporosis caused by ovariectomy. Female Sprague Dawley rats (n = 42) were randomly assigned into baseline, sham, ovariectomised (OVX) control, OVX-treated with low-dose (0.26 g/kg), medium dose (0.53 g/kg) and high dose E'Jiao (1.06 g/kg), as well as calcium carbonate (1% w/v) groups. Daily treatment through oral gavage was initiated 7 days after OVX. The rats were euthanised after eight weeks of treatment. Bone mineral density and content were measured at baseline, 1 and 2 months after treatment. Blood was collected for the measurement of bone remodelling markers. Femur and tibial bones were collected for histomorphometry and biomechanical strength analysis. Untreated OVX rats showed high bone remodelling marked by the increased bone formation and bone resorption markers, as well as increased mineralising surface/bone surface ratio. In addition, osteoclast surface and single-labelled surface were increased while mineral apposition rate was reduced in the untreated OVX rats. These changes were antagonised by E'Jiao at all doses. However, the structural, cellular and biomechanical parameters were not affected by ovariectomy and treatment. In conclusion, E'Jiao prevented high bone remodelling during oestrogen deficiency but a long-term study will be required to establish its effects on structural and biomechanical changes due to oestrogen deficiency.

Effect of a Screening and Education Programme on Knowledge, Beliefs, and Practices Regarding Osteoporosis among Malaysians.

Background: Osteoporosis is an emerging geriatric condition with high morbidity and healthcare cost in developing nations experiencing rapid population ageing. Thus, identifying strategies to prevent osteoporosis is critical in safeguarding skeletal health. This study aimed to evaluate the effects of a bone health screening and education programme on knowledge, beliefs, and practice regarding osteoporosis among Malaysians aged 40 years and above. Methods: A longitudinal study was conducted from April 2018 to August 2019. During the first phase of the study, 400 Malaysians (190 men, 210 women) aged ≥ 40 years were recruited in Klang Valley, Malaysia. Information on subjects' demography, medical history, knowledge, and beliefs regarding osteoporosis, physical activity status, and dietary and lifestyle practices were obtained. Subjects also underwent body anthropometry measurement and bone mineral density scan (hip and lumbar spine) using a dual-energy X-ray absorptiometry device. Six months after the first screening, similar investigations were carried out on the subjects. Results: During the follow-up session, 72 subjects were lost to follow up. Most of them were younger subjects with a lower awareness of healthy practices. A significant increase in knowledge, beliefs (p < 0.05), calcium supplement intake (p < 0.001), and dietary calcium intake (p = 0.036) and a reduction in coffee intake (p < 0.001) were found among subjects who attended the follow-up. In this study, the percentage of successful referrals was 41.86%. Subjects with osteoporosis were mostly prescribed alendronate plus vitamin D3 by medical doctors, and they followed the prescribed treatment accordingly. Conclusions: The bone health screening and education programmes in this study are effective in changing knowledge, beliefs, and practice regarding osteoporosis. The information is pertinent to policymakers in planning strategies to prevent osteoporosis and its associated problems among the middle-aged and elderly population in Malaysia. Nevertheless, a more comprehensive bone health education program that includes long-term monitoring and consultation is needed to halt the progression of bone loss.

Self-emulsified annatto tocotrienol improves bone histomorphometric parameters in a rat model of oestrogen deficiency through suppression of skeletal sclerostin level and RANKL/OPG ratio.

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.

A review on the molecular basis underlying the protective effects of Andrographis paniculata and andrographolide against myocardial injury.

Andrographolide is the major compound found in the medicinal plant, Andrographis paniculata (Burm.f.) Nees, which accounts for its medicinal properties. Both the plant extract and compound have been reported to exhibit potential cardiovascular activities. This review summarises related studies describing the biological activities and target mechanisms of A. paniculata and andrographolide in vivo and in vitro. The current evidence unambiguously indicated the protective effects provided by A. paniculata and andrographolide administration against myocardial injury. The intervention ameliorates the symptoms of myocardial injury by interfering with the inductive phase of a) inflammatory response mediated by nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signalling molecules; b) oxidative stress via activation of nuclear factor erythroid 2-related factor (Nrf-2) and reduction of enzymes responsible for generating reactive oxygen and nitrogen species; c) intrinsic and extrinsic mechanisms in apoptosis regulated by upstream insulin-like growth factor-1 receptor (IGF-1R) and peroxisome proliferator-activated receptor-alpha (PPAR-α); d) profibrotic growth factors thus reducing cardiac fibrosis, improving endothelial function and fibrinolytic function. In conclusion, A. paniculata and andrographolide possess therapeutic potential in the management of myocardial injury, which requires further validation in human clinical trials.

A Review on the Enhancement of Calcium Phosphate Cement with Biological Materials in Bone Defect Healing.

Calcium phosphate cement (CPC) is a promising material used in the treatment of bone defects due to its profitable features of self-setting capability, osteoconductivity, injectability, mouldability, and biocompatibility. However, the major limitations of CPC, such as the brittleness, lack of osteogenic property, and poor washout resistance, remain to be resolved. Thus, significant research effort has been committed to modify and reinforce CPC. The mixture of CPC with various biological materials, defined as the materials produced by living organisms, have been fabricated by researchers and their characteristics have been investigated in vitro and in vivo. This present review aimed to provide a comprehensive overview enabling the readers to compare the physical, mechanical, and biological properties of CPC upon the incorporation of different biological materials. By mixing the bone-related transcription factors, proteins, and/or polysaccharides with CPC, researchers have demonstrated that these combinations not only resolved the lack of mechanical strength and osteogenic effects of CPC but also further improve its own functional properties. However, exceptions were seen in CPC incorporated with certain proteins (such as elastin-like polypeptide and calcitonin gene-related peptide) as well as blood components. In conclusion, the addition of biological materials potentially improves CPC features, which vary depending on the types of materials embedded into it. The significant enhancement of CPC seen in vitro and in vivo requires further verification in human trials for its clinical application.

Circulating Biomarkers Related to Osteocyte and Calcium Homeostasis Between Postmenopausal Women with and without Osteoporosis.

BACKGROUND: The currently available bone turnover markers are mostly derived from osteoblasts or osteoclasts. Protein markers derived from osteocytes, the most abundant bone cells that can regulate bone turnover activities by other cells, are less explored. OBJECTIVE: This study aimed to compare the circulating markers of osteocytes and calcium homeostasis between Malaysian postmenopausal women with and without osteoporosis. METHODS: Postmenopausal women with (n=20) or without osteoporosis (n=20) as determined by dual- energy X-ray absorptiometry were randomly drawn from a bone health cohort. Their fasting blood was collected and assayed by a multiplex immunoassay panel. RESULTS: The results showed that osteoprotegerin and sclerostin levels were significantly lower among postmenopausal women with osteoporosis than the normal control. No significant differences in other markers were observed between the two groups. Sclerostin level correlated positively with spine Bone Mineral Density (BMD), while 25-hydroxyvitamin D correlated negatively with hip BMD in the control group. No significant correlation was observed between other markers with spine or hip BMD. CONCLUSION: These data provide an insight into the possible roles of osteocyte markers, especially osteoprotegerin and sclerostin, in classifying subjects with osteoporosis. However, the lack of association between these markers and BMD indicates that osteoporosis is a complex and multifactorial condition.

Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.

Studies investigating the effects of tocotrienols on inflammation and oxidative stress have yielded inconsistent results. This systematic review and meta-analysis aimed to evaluate the effects of tocotrienols supplementation on inflammatory and oxidative stress biomarkers. We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception until 13 July 2020 to identify randomized controlled trials supplementing tocotrienols and reporting circulating inflammatory or oxidative stress outcomes. Weighted mean difference (WMD) and corresponding 95% confidence interval (CI) were determined by pooling eligible studies. Nineteen studies were included for qualitative analysis, and 13 studies were included for the meta-analyses. A significant reduction in C-reactive protein levels (WMD: -0.52 mg/L, 95% CI: -0.73, -0.32, p < 0.001) following tocotrienols supplementation was observed, but this finding was attributed to a single study using δ-tocotrienols, not mixed tocotrienols. There were no effects on interleukin-6 (WMD: 0.03 pg/mL, 95% CI: -1.51, 1.58, p = 0.966), tumor necrosis factor-alpha (WMD: -0.28 pg/mL, 95% CI: -1.24, 0.68, p = 0.571), and malondialdehyde (WMD: -0.42 µmol/L, 95% CI: -1.05, 0.21, p = 0.189). A subgroup analysis suggested that tocotrienols at 400 mg/day might reduce malondialdehyde levels (WMD: -0.90 µmol/L, 95% CI: -1.20, -0.59, p < 0.001). Future well-designed studies are warranted to confirm the effects of tocotrienols on inflammatory and oxidative stress biomarkers, particularly on different types and dosages of supplementation. PROSPERO registration number: CRD42020198241.

Skeletal microenvironment system utilising bovine bone scaffold co-cultured with human osteoblasts and osteoclast-like cells.

A three-dimensional ex vivo bone cell culture system mimicking the skeletal system is useful for bone tissue engineering and as drug discovery platforms. The present study aimed to establish a three-dimensional skeletal culture system using native bovine bone scaffolds and human bone cells. Bovine bone scaffolds were cultured with human foetal osteoblasts 1.19 and human peripheral blood mononuclear cells for 21 days under standard culture conditions. The following groups were established: Decalcified unseeded bone scaffold (DUBS) as baseline control, decalcified seeded bone scaffold (DSBS) to mimic osteoporosis condition and undecalcified seeded bone scaffold to mimic normal condition. The scaffold's porosity and cell attachment on the scaffolds were determined using scanning electron microscopy. Histological evaluation was used to examine changes in trabecular bone structure. Dual-energy X-ray absorptiometry analysis was performed to determine the bone mineral density (BMD) and bone mineral content (BMC) of the scaffolds. A compression test was performed to examine the total biomechanical strength of the scaffolds. The trabecular thickness and number increased, while the trabecular separationwas reduced slightly in DSBS than in DUBS (P>0.05). The BMD and BMC increased significantly (P<0.05), while the compressive strength only increased slightly in DSBS than in DUBS (P>0.05). In conclusion, the ex vivo skeletal microenvironment comprising native bovine bone scaffolds seeded with bone cells is structurally, functionally and mechanically comparable with natural bone. This system may be used as a platform to understand bone physiology and screen for potential drug candidates.

Vitamin A and Bone Health: A Review on Current Evidence.

Vitamin A is a fat-soluble micronutrient essential for growth, immunity, and good vision. The preformed retinol is commonly found in food of animal origin whereas provitamin A is derived from food of plant origin. This review summarises the current evidence from animal, human and cell-culture studies on the effects of vitamin A towards bone health. Animal studies showed that the negative effects of retinol on the skeleton were observed at higher concentrations, especially on the cortical bone. In humans, the direct relationship between vitamin A and poor bone health was more pronounced in individuals with obesity or vitamin D deficiency. Mechanistically, vitamin A differentially influenced the stages of osteogenesis by enhancing early osteoblastic differentiation and inhibiting bone mineralisation via retinoic acid receptor (RAR) signalling and modulation of osteocyte/osteoblast-related bone peptides. However, adequate vitamin A intake through food or supplements was shown to maintain healthy bones. Meanwhile, provitamin A (carotene and ß-cryptoxanthin) may also protect bone. In vitro evidence showed that carotene and ß-cryptoxanthin may serve as precursors for retinoids, specifically all-trans-retinoic acid, which serve as ligand for RARs to promote osteogenesis and suppressed nuclear factor-kappa B activation to inhibit the differentiation and maturation of osteoclasts. In conclusion, we suggest that both vitamin A and provitamin A may be potential bone-protecting agents, and more studies are warranted to support this hypothesis.

Effect of vitamin E on periodontitis: Evidence and proposed mechanisms of action.

BACKGROUND: Periodontitis is a noncommunicable inflammatory disease of the soft tissue and bone surrounding the teeth in the jaw, which affects susceptible individuals with poor oral hygiene. A growing interest has been seen in the use of dietary supplements and natural products for the treatment and prevention of periodontitis. Vitamin E consists of two major groups, namely tocopherols and tocotrienols, which are botanical lipophilic compounds with excellent anti-inflammatory and antioxidant properties. HIGHLIGHT: This review aimed to summarize the preclinical and clinical findings on the effects of vitamin E on periodontitis. The current literature suggests that vitamin E could improve the periodontal status by correcting redox status imbalance, reducing inflammatory responses, and promoting wound healing, thus highlighting the potential of vitamin E in the management of periodontitis. CONCLUSION: Direct evidence for the use of vitamin E supplementation or treatment of periodontitis in humans is still limited. More well-designed and controlled studies are required to ascertain its effectiveness.

Osteoporosis knowledge and practice among Malaysian university students.

OBJECTIVE: This study aimed to investigate osteoporosis knowledge and bone health practices among students of a Malaysian public university. METHODS: A cross-sectional study was conducted amongst university students from a Malaysian's public university. A total of 228 students responded to a self-administered questionnaire consisting of items evaluating knowledge and practices of osteoporosis. RESULTS: The students showed a moderate level of osteoporosis awareness with a score of 63.3%. Male subjects had higher awareness scores of osteoporosis complications compared to female subjects (p= 0.010). Malay (p= 0.002) and Chinese (p= 0.005) had higher levels of osteoporosis awareness compared to Indian students. Coffee and alcohol intakes were significantly different between the sexes (p= 0.013) and the ethnic groups (p= 0.029). Most of the subjects in our study were minimally active (43.9%). CONCLUSIONS: The students had a reasonable levels of knowledge about osteoporosis, but their health activities to avoid osteoporosis were insufficient. This illustrates the need for educational programmes to improve students' knowledge and awareness for successful osteoporosis prevention.

Therapeutic potential of annatto tocotrienol with self-emulsifying drug delivery system in a rat model of postmenopausal bone loss.

Tocotrienol has been shown to prevent bone loss in animal models of postmenopausal osteoporosis, but the low oral bioavailability might limit its use. A self-emulsifying drug delivery system (SEDDS) could increase the bioavailability of tocotrienol. However, evidence of this system in improving the skeletal effects of tocotrienol is scanty. This study aims to evaluate the therapeutic efficacy of annatto tocotrienol with SEDDS in a rat model of postmenopausal bone loss. Ten-month-old female Sprague Dawley rats were randomized into six groups. The baseline group was euthanatized at the onset of the study. Four other groups underwent ovariectomy to induce estrogen deficiency. The sham underwent similar surgery procedure, but their ovaries were retained. Eight weeks after surgery, the ovariectomized rats received one of the four different regimens orally daily: (a) SEDDS, (b) annatto tocotrienol [60 mg/kg body weight (b.w.)] without SEDDS, (c) annatto-tocotrienol (60 mg/kg b.w.) with SEDDS, (d) raloxifene (1 mg/kg b.w.). After eight weeks of treatment, blood was collected for the measurement of delta-tocotrienol level and oxidative stress markers. The rats were euthanized and their bones were harvested for the evaluation of the bone microstructure, calcium content and strength. Circulating delta-tocotrienol level was significantly higher in rats receiving annatto tocotrienol with SEDDS compared to the group receiving unformulated annatto-tocotrienol (p < 0.05). Treatment with unformulated or SEDDS-formulated annatto tocotrienol improved cortical bone thickness, preserved bone calcium content, increased bone biomechanical strength and increased antioxidant enzyme activities compared with the ovariectomized group (p < 0.05). Only SEDDS-formulated annatto tocotrienol improved trabecular microstructure, bone stiffness and lowered malondialdehyde level (p < 0.05 vs the ovariectomized group). The improvement caused by annatto tocotrienol was comparable to raloxifene. In conclusion, SEDDS improves the bioavailability and skeletal therapeutic effects of annatto tocotrienol in a rat model of postmenopausal bone loss. This formulation should be tested in a human clinical trial to validate its efficacy.

The Skeletal Effects of Gonadotropin-Releasing Hormone Antagonists: A Concise Review.

Prolonged treatment with Gonadotropin-Releasing Hormone (GnRH) agonists is known to induce bone loss among prostate cancer patients. However, evidence on the skeletal effects of GnRH antagonists is relatively less well-known. This review aims to examine the effects of GnRH antagonists on bone health. GnRH antagonists are an effective treatment for hormone-dependent conditions, such as advanced prostate cancer and endometriosis. They induce a competitive and reversible GnRH-receptor blockage, thereby suppressing the release of gonadotropins and sex hormones. The sex hormone ablation results in undesirable side effects, including accelerated bone loss. In animal studies, treatment with GnRH antagonists is reported to cause deterioration of bone microstructure. Human clinical trials revealed significant bone loss at the spine, hip and femur in patients treated with GnRH antagonists. Thus, osteoporosis and the resultant fragility fractures pose a significant impact on health and quality of life of GnRH antagonist users. Thus, early preventive measures of bone loss are critical in preventing fractures and its associated morbidity in these patients.

Positive association between metabolic syndrome and bone mineral density among Malaysians.

Objectives: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that elevates the individual risk of cardiovascular diseases. These abnormalities are also known to alter bone remodelling. Therefore, MetS may be associated with osteoporosis. This study aims to determine the association between MetS and its components and bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) among Malaysians. Methods: 400 Malaysians aged ≥ 40 years (52.5% women) residing in Klang Valley, Malaysia, were recruited. Subjects' demographic and lifestyle details were collected using a questionnaire, and blood pressure and body anthropometry were measured. Subjects' lumbar spine and total hip BMD were measured by DXA. Their fasting blood was collected for blood glucose level and lipid profile analysis. Regression analysis was used to analyze the relationship between MetS or its components and BMD. Results: Subjects with MetS had higher BMD compared to subjects without MetS in models unadjusted for BMI (spine p=0.008; hip p<0.001). This difference was attenuated with BMI adjustment (spine p=0.625; hip p=0.478). Waist circumference was associated positively with BMD in models unadjusted for BMI (spine p=0.012; hip p<0.001), but the association became negative with BMI adjustment (spine p=0.044; hip p=0.021). Systolic blood pressure was associated positively with total hip BMD (p=0.019) but BMI adjustment attenuated the relationship (p=0.080). Triglyceride level was associated with osteoporosis in a fully adjusted model (p=0.001). Overall, MetS was associated with osteoporosis (p=0.019) but lifestyle (p=0.188) and BMI adjustment attenuated the relationship (p=0.904). Conclusion: MetS is positively associated with BMD, and this relationship is predominantly mediated by BMI. Although MetS is not a significant risk factor for osteoporosis, the inverse relationship between waist circumference, a marker of central obesity, and BMD highlights the need to prevent adiposity to improve metabolic and skeletal health.

Prevalence and factors of T-score discordance between hip and spine among middle-aged and elderly Malaysians.

T-score discordance between hip and spine is a common problem in the diagnosis of osteoporosis based on dual-energy X-ray absorptiometry. Not much information on the prevalence and risk factors of this problem is available in Malaysia. Our study found that factors like age, height, physical activity and menopausal status should be taken into account in the diagnosis of osteoporosis. INTRODUCTION AND OBJECTIVE: T-score discordance between hip and spine is a common problem in bone mineral density assessment. A difference ≥ 1 standard deviation (SD) (regardless of diagnostic class) is considered minor, and a difference more than one diagnostic class is considered major discordance. This study aimed to determine the prevalence and factors of hip and spine T-score discordance in a population aged ≥ 40 years in Klang Valley, Malaysia. SUBJECTS AND METHODS: In this cross-sectional study, subjects answered a demographic questionnaire and underwent body composition and bone health assessment using dual-energy X-ray absorptiometry. Chi-square and binary logistic regression analysis were used to assess the prevalence of T-score discordance among the subjects. RESULTS: A total of 786 Malaysians (382 men, 404 women) subjects were recruited. The prevalence of minor and major discordance was 30.3% and 2.3%, respectively. Overall, factors related to T-score discordance were advanced age, decreased height, and being physically active. Sub-analysis showed that decreased height and being physically active predicted T-score discordance in men, being menopausal and Indian (vs Chinese) were predictors in women. CONCLUSIONS: T-score discordance between hip and spine is common among Malaysian middle-aged and elderly population. Diagnosis of osteopenia/osteoporosis should be based on the T-score of more than one skeletal site as per the current recommendations.

Quercetin as an Agent for Protecting the Bone: A Review of the Current Evidence.

Quercetin is a flavonoid abundantly found in fruits and vegetables. It possesses a wide spectrum of biological activities, thus suggesting a role in disease prevention and health promotion. The present review aimed to uncover the bone-sparing effects of quercetin and its mechanism of action. Animal studies have found that the action of quercetin on bone is largely protective, with a small number of studies reporting negative outcomes. Quercetin was shown to inhibit RANKL-mediated osteoclastogenesis, osteoblast apoptosis, oxidative stress and inflammatory response while promoting osteogenesis, angiogenesis, antioxidant expression, adipocyte apoptosis and osteoclast apoptosis. The possible underlying mechanisms involved are regulation of Wnt, NF-κB, Nrf2, SMAD-dependent, and intrinsic and extrinsic apoptotic pathways. On the other hand, quercetin was shown to exert complex and competing actions on the MAPK signalling pathway to orchestrate bone metabolism, resulting in both stimulatory and inhibitory effects on bone in parallel. The overall interaction is believed to result in a positive effect on bone. Considering the important contributions of quercetin in regulating bone homeostasis, it may be considered an economical and promising agent for improving bone health. The documented preclinical findings await further validation from human clinical trials.