Displaying publications 41 - 60 of 165 in total

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  1. Ng JS, Chin KY
    Int J Med Sci, 2021;18(3):604-614.
    PMID: 33437195 DOI: 10.7150/ijms.50680
    Chronic psychological stress affects many body systems, including the skeleton, through various mechanisms. This review aims to provide an overview of the factors mediating the relationship between psychological stress and bone health. These factors can be divided into physiological and behavioural changes induced by psychological stress. The physiological factors involve endocrinological changes, such as increased glucocorticoids, prolactin, leptin and parathyroid hormone levels and reduced gonadal hormones. Low-grade inflammation and hyperactivation of the sympathetic nervous system during psychological stress are also physiological changes detrimental to bone health. The behavioural changes during mental stress, such as altered dietary pattern, cigarette smoking, alcoholism and physical inactivity, also threaten the skeletal system. Psychological stress may be partly responsible for epigenetic regulation of skeletal development. It may also mediate the relationship between socioeconomic status and bone health. However, more direct evidence is required to prove these hypotheses. In conclusion, chronic psychological stress should be recognised as a risk factor of osteoporosis and stress-coping methods should be incorporated as part of the comprehensive osteoporosis-preventing strategy.
  2. Khor BH, Tiong HC, Tan SC, Wong SK, Chin KY, Karupaiah T, et al.
    PLoS One, 2021;16(7):e0255205.
    PMID: 34297765 DOI: 10.1371/journal.pone.0255205
    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.
  3. Mohamad NV, Ima-Nirwana S, Chin KY
    PMID: 33327926 DOI: 10.2174/1871530321666201216164410
    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.
  4. Mohamad NV, Ima-Nirwana S, Chin KY
    Int J Med Sci, 2021;18(16):3665-3673.
    PMID: 34790038 DOI: 10.7150/ijms.64045
    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.
  5. Wong SK, Chin KY, Ima-Nirwana S
    Drug Des Devel Ther, 2021;15:4615-4632.
    PMID: 34785890 DOI: 10.2147/DDDT.S331027
    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.
  6. Chan CY, Subramaniam S, Mohamed N, Muhammad N, Ramli FF, Ima-Nirwana S, et al.
    PMID: 34370656 DOI: 10.2174/1871530321666210809154456
    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.

  7. Pang KL, Ekeuku SO, Chin KY
    Risk Manag Healthc Policy, 2021;14:2715-2732.
    PMID: 34194253 DOI: 10.2147/RMHP.S316429
    Air pollution is associated with inflammation and oxidative stress, which predispose to several chronic diseases in human. Emerging evidence suggests that the severity and progression of osteoporosis are directly associated with inflammation induced by air pollutants like particulate matter (PM). This systematic review examined the relationship between PM and bone health or fractures. A comprehensive literature search was conducted from January until February 2021 using the PubMed, Scopus, Web of Science, Google Scholar and Cochrane Library databases. Human cross-sectional, cohort and case-control studies were considered. Of the 1500 papers identified, 14 articles were included based on the inclusion and exclusion criteria. The air pollution index investigated by most studies were PM2.5 and PM10. Current studies demonstrated inconsistent associations between PM and osteoporosis risk or fractures, which may partly due to the heterogeneity in subjects' characteristics, study design and analysis. In conclusion, there is an inconclusive relationship between osteoporosis risk and fracture and PM exposures which require further validation.
  8. Ekeuku SO, Pang KL, Chin KY
    Drug Des Devel Ther, 2021;15:259-275.
    PMID: 33519191 DOI: 10.2147/DDDT.S287280
    PURPOSE: Caffeic acid is a metabolite of hydroxycinnamate and phenylpropanoid, which are commonly synthesized by all plant species. It is present in various food sources that are known for their antioxidant properties. As an antioxidant, caffeic acid ameliorates reactive oxygen species, which have been reported to cause bone loss. Some studies have highlighted the effects of caffeic acid against bone resorption.

    METHODS: A systematic review of the literature was conducted to identify relevant studies on the effects of caffeic acid on bone. A comprehensive search was conducted from July to November 2020 using PubMed, Scopus, Cochrane Library and Web of Science databases. Cellular, animal and human studies reporting the effects of caffeic acid, as a single compound, on bone cells or bone were considered.

    RESULTS: The literature search found 226 articles on this topic, but only 24 articles met the inclusion criteria and were included in this review. The results showed that caffeic acid supplementation reduced osteoclastogenesis and bone resorption, possibly through its antioxidant potential and increased expression of osteoblast markers. However, some studies showed that caffeic acid did not affect bone resorption in ovariectomized rats and might impair bone mechanical properties in normal rats.

    CONCLUSION: Caffeic acid potentially regulates the bone remodelling process by inhibiting osteoclastogenesis and bone resorption, as well as osteoblast apoptosis. Thus, it has medicinal values against bone diseases.

  9. Mohd Ramli ES, Sukalingam K, Kamaruzzaman MA, Soelaiman IN, Pang KL, Chin KY
    Diabetes Metab Syndr Obes, 2021;14:241-256.
    PMID: 33500644 DOI: 10.2147/DMSO.S291828
    Metabolic syndrome (MetS) refers to the simultaneous presence of hypertension, hyperglycemia, dyslipidemia and/or visceral obesity, which predisposes a person to cardiovascular diseases and diabetes. Evidence suggesting the presence of direct and indirect associations between MetS and osteoporosis is growing. Many studies have reported the beneficial effects of polyphenols in alleviating MetS in in vivo and in vitro models through their antioxidant and anti-inflammation actions. This review aims to summarize the effects of honey (based on unifloral and multi-floral nectar sources) on bone metabolism and each component of MetS. A literature search was performed using the PubMed and Scopus databases using specific search strings. Original studies related to components of MetS and bone, and the effects of honey on components of MetS and bone were included. Honey polyphenols could act synergistically in alleviating MetS by preventing oxidative damage and inflammation. Honey intake is shown to reduce blood glucose levels and prevent excessive weight gain. It also improves lipid metabolism by reducing total cholesterol, triglycerides and low-density lipoprotein, as well as increasing high-density lipoprotein. Honey can prevent bone loss by reducing the adverse effects of MetS on bone homeostasis, apart from its direct action on the skeletal system. In conclusion, honey supplementation could be integrated into the management of MetS and MetS-induced bone loss as a preventive and adjunct therapeutic agent.
  10. Mohamad NV, Ima-Nirwana S, Chin KY
    Aging Male, 2020 Dec;23(5):327-334.
    PMID: 29495911 DOI: 10.1080/13685538.2018.1446075
    This study aimed to compare the skeletal effect between GnRH agonist therapy and orchidectomy in male rats assessed using serum turnover markers and bone histomorphometry. Three-month-old male Sprague-Dawley rats (n = 46) were divided into three experimental arms, baseline, buserelin, and orchidectomy. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline or buserelin acetate at 25 µg/kg or 75 µg/kg. In the orchidectomy arm, the rats were either sham-operated or orchidectomized. The rats were euthanized after the three-month treatment. Blood was collected for the evaluation of bone turnover markers. Femurs were harvested for bone histomorphometry examination. A significant increase in serum C-telopeptide of type 1 collagen was observed in the orchidectomized group compared with the sham group (p 
  11. Wong SK, Ima-Nirwana S, Chin KY
    Bosn J Basic Med Sci, 2020 Nov 02;20(4):423-429.
    PMID: 32156247 DOI: 10.17305/bjbms.2020.4664
    Telomeres are repetitive DNA sequences located at the end of chromosomes that serve as a protective barrier against chromosomal deterioration during cell division. Approximately 50-200 base pairs of nucleotides are lost per cell division, and new repetitive nucleotides are added by the enzyme telomerase, allowing telomere maintenance. Telomere shortening has been proposed as an indicator for biological aging, but its relationship with age-related osteoporosis is ambiguous. We summarize the current evidence on the relationship between telomere length and bone health in experimental and epidemiological studies, which serve as a scientific reference for the development of novel diagnostic markers of osteoporosis or novel therapeutics targeting telomere and telomerase of bone cells to treat osteoporosis.
  12. Wong SK, Ima-Nirwana S, Chin KY
    Exp Ther Med, 2020 Oct;20(4):2941-2952.
    PMID: 32855659 DOI: 10.3892/etm.2020.9075
    Sarcopenia refers to the involuntary and generalized deterioration of skeletal muscle mass and strength, which may lead to falls, frailty, physical disability, loss of independence, morbidity and mortality. The majority of molecular and cellular changes involved in the degeneration of muscle tissues are mediated by oxidative stress. Therefore, astaxanthin may act as a potential adjunct therapy for sarcopenia owing to its antioxidant activity. The present review examines the effects of astaxanthin on the promotion of skeletal muscle performance and prevention of muscle atrophy and the potential mechanisms underlying these effects. The available evidence till date was retrieved from PubMed and Medline electronic databases. The present review reported the beneficial effects of astaxanthin in preventing muscle degeneration in various animal models of sarcopenia. In humans, the effects of astaxanthin in combination with other antioxidants on muscle health are mixed, wherein positive and negligible effects were reported. Mechanistic studies revealed that astaxanthin promotes muscle health by reducing oxidative stress, myoblast apoptosis and proteolytic pathways while promoting mitochondria regeneration and formation of blood vessels. Thus, astaxanthin is a potential therapeutic agent for sarcopenia but its effects in humans require further validation.
  13. Shahudin NN, Sameeha MJ, Mat Ludin AF, Manaf ZA, Chin KY, Jamil NA
    Nutrients, 2020 Sep 30;12(10).
    PMID: 33007799 DOI: 10.3390/nu12102994
    The prevalence of vitamin D insufficiency is significant even in tropical countries such as Malaysia. Sun exposure is the primary source of vitamin D for most people due to limited intakes of food containing vitamin D and supplements. This study explored the perception of barriers towards sun exposure and strategies to overcome these barriers among vitamin D insufficient women workers in Kuala Lumpur, Malaysia. Twenty-five female indoor workers with serum 25-hydroxyvitamin D < 50 nmol/L participated in seven focus group discussions (FGDs). Barriers towards sun exposure were lack of accurate knowledge of vitamin D, health concern towards sun exposure, time constraints, desire to have fair and beautiful skin, sedentary lifestyle, indoor workplace, weather, lack of social support, living arrangement, safety concerns, and religious or cultural practices. The improvement strategies were classified into lifestyle changes and workplace opportunity for sun exposure. Public education on safe sun exposure to produce an optimal level of vitamin D is necessary. Future studies should evaluate the effectiveness of sunlight exposure program at workplace for the high-risk vitamin D deficiency group.
  14. Chan CY, Subramaniam S, Mohamed N, Ima-Nirwana S, Muhammad N, Fairus A, et al.
    Arch Osteoporos, 2020 09 12;15(1):142.
    PMID: 32918631 DOI: 10.1007/s11657-020-00821-5
    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.

  15. Wong SK, Chin KY, Ima-Nirwana S
    Int J Mol Sci, 2020 Sep 03;21(17).
    PMID: 32899435 DOI: 10.3390/ijms21176448
    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.
  16. Wong SK, Chin KY, Ahmad F, Ima-Nirwana S
    J Food Biochem, 2020 Aug 03.
    PMID: 32744348 DOI: 10.1111/jfbc.13371
    This study aimed to evaluate the oxidative stress status, antioxidants capacity, and presence of nonalcoholic fatty liver disease (NAFLD) in an animal model of MetS induced by high-carbohydrate high-fat (HCHF) diet. Male Wistar rats were randomized into two groups, assigned for two different types of diet (standard rat pellet or HCHF diet) for 20 weeks. Liver was excised, weighed, and subjected to lipid peroxidation, nitric oxide (NO·) production, antioxidants activity, and histological assessment. The HCHF rats had higher lipid peroxidation and NO· level but lower enzymatic and nonenzymatic antioxidant levels than the normal animals. Histological evaluation revealed higher lobular inflammation, hepatocellular ballooning, NAFLD activity score, and lipid accumulation in the liver of HCHF group. In conclusion, the HCHF diet causes an increase in oxidative stress, depletion of antioxidants capacity, NAFLD, and liver injury. The induction of oxidative stress may be partially responsible for the development of NAFLD in MetS. PRACTICAL APPLICATIONS: The prevalence of MetS is estimated to increase rapidly with the escalating levels of obesity, diabetes, hypertension, and dyslipidemia. A suitable animal model of MetS that best mimicked the human disease state with known underlying mechanisms responsible for the pathogenesis of MetS is indispensable to search for potential adjunct therapies and drug targets. Thus, our current study elucidated the involvement of oxidative stress in linking MetS and NAFLD which might resemble the pathogenesis of MetS among Southeast Asian population.
  17. Wong SK, Chin KY, Ima-Nirwana S
    Phytomedicine, 2020 Jul 15;73:152892.
    PMID: 30902523 DOI: 10.1016/j.phymed.2019.152892
    BACKGROUND: Musculoskeletal disorders are a group of disorders that affect the joints, bones, and muscles, causing long-term disability. Berberine, an isoquinoline alkaloid, has been previously established to exhibit beneficial properties in preventing various diseases, including musculoskeletal disorders.

    PURPOSE: This review article aims to recapitulate the therapeutic potential of berberine and its mechanism of action in treating musculoskeletal disorders.

    METHODS: A wide range of literature illustrating the effects of berberine in ameliorating musculoskeletal disorders was retrieved from online electronic databases (PubMed and Medline) and reviewed.

    RESULTS: Berberine may potentially retard the progression of osteoporosis, osteoarthritis and rheumatoid arthritis. Limited studies reported the effects of berberine in suppressing the proliferation of osteosarcoma cells. These beneficial properties of berberine are mediated in part through its ability to target multiple signaling pathways, including PKA, p38 MAPK, Wnt/β-catenin, AMPK, RANK/RANKL/OPG, PI3K/Akt, NFAT, NF-κB, Hedgehog, and oxidative stress signaling. In addition, berberine exhibited anti-apoptotic, anti-inflammatory, and immunosuppressive properties.

    CONCLUSION: The current evidence indicates that berberine may be effective in preventing musculoskeletal disorders. However, findings from in vitro and in vivo investigations await further validation from human clinical trial.

  18. Abd Aziz NH, Yazid NA, Abd Rahman R, Abd Rashid N, Wong SK, Mohamad NV, et al.
    PMID: 32397276 DOI: 10.3390/ijerph17093291
    Information on the role of 25-hydroxyvitamin D (25(OH)D) in preventing adverse pregnancy/neonatal outcomes is limited in Malaysia. This study aims to determine the relationship between the level of maternal 25(OH)D in the first trimester of pregnant women and their pregnancy/neonatal outcomes. A total of 60 pregnant women in the first trimester were recruited and followed until the end of their pregnancy. The occurrence of any antenatal, delivery, and neonatal complications was recorded. Their blood was collected in the first trimester for total serum 25(OH)D determination using enzyme-linked immunosorbent assay. Overall, 10% of the women had vitamin D deficiency, while 57% had vitamin D insufficiency in their first trimester. No statistically significant difference in 25(OH)D level/status was observed between women with or without antenatal and delivery complications (p > 0.05). No difference in maternal serum 25(OH)D level and vitamin D status was observed between neonates with or without complications (p > 0.05). In conclusion, there is a high prevalence of vitamin D insufficiency among Malaysian pregnant women, but it is not associated with adverse maternal and neonatal outcomes. More comprehensive studies should be planned to verify this relationship.
  19. Chin KY
    Nutrients, 2020 Apr 25;12(5).
    PMID: 32344816 DOI: 10.3390/nu12051208
    Vitamin K is a cofactor of γ-glutamyl carboxylase, which plays an important role in the activation of γ-carboxyglutamate (gla)-containing proteins that negatively regulate calcification. Thus, vitamin K status might be associated with osteoarthritis (OA), in which cartilage calcification plays a role in the pathogenesis of the disease. This review collates the evidence on the relationship between vitamin K status (circulating or dietary intake level of vitamin K, or circulating uncarboxylated gla proteins) and OA from human observational studies and clinical trial, to examine its potential as an agent in preventing OA. The current literature generally agrees that a sufficient level of vitamin K is associated with a lower risk of OA and pathological joint features. However, evidence from clinical trials is limited. Mechanistic study shows that vitamin K activates matrix gla proteins that inhibit bone morphogenetic protein-mediated cartilage calcification. Gla-rich proteins also inhibit inflammatory cascade in monocytic cell lines, but this function might be independent of vitamin K-carboxylation. Although the current data are insufficient to establish the optimal dose of vitamin K to prevent OA, ensuring sufficient dietary intake seems to protect the elderly from OA.
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