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Fulltext Performance of Osteoporosis Self-Assessment Tool (OST) in predicting osteoporosis - a review

Subramaniam S, Ima-Nirwana S, Chin KY

Int J Environ Res Public Health, 2018 07 09;15(7).
PMID: 29987247 DOI: 10.3390/ijerph15071445

Bone health screening plays a vital role in the early diagnosis and treatment of osteoporosis to prevent fragility fractures among the elderly and high-risk individuals. Dual-energy X-ray absorptiometry (DXA), which detects bone mineral density, is the gold standard in diagnosing osteoporosis but is not suitable for screening. Therefore, many screening tools have been developed to identify individuals at risk for osteoporosis and prioritize them for DXA scanning. The Osteoporosis Self-assessment Tool (OST) is among the first tools established to predict osteoporosis in postmenopausal women. It can identify the population at risk for osteoporosis, but its performance varies according to ethnicity, gender, and age. Thus, these factors should be considered to ensure the optimal use of OST worldwide. Overall, OST is a simple and economical screening tool to predict osteoporosis and it can help to optimize the use of DXA.
Fulltext Effects of astaxanthin on the protection of muscle health (Review)

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.
Fulltext Annatto tocotrienol improves indices of bone static histomorphometry in osteoporosis due to testosterone deficiency in rats

Chin KY, Abdul-Majeed S, Fozi NF, Ima-Nirwana S

Nutrients, 2014 Nov;6(11):4974-83.
PMID: 25389899 DOI: 10.3390/nu6114974

This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05). The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent.
Total testosterone and sex hormone-binding globulin are significantly associated with metabolic syndrome in middle-aged and elderly men

Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Ngah WZ

Exp. Clin. Endocrinol. Diabetes, 2013 Jul;121(7):407-12.
PMID: 23765753 DOI: 10.1055/s-0033-1345164

Testosterone and sex hormone-binding globulin (SHBG) have been shown to be associated with metabolic syndrome (MS) in men. This study aimed at validating these relationships in a group of middle-aged and elderly men and assessing their strength of association to MS. A cross-sectional study of 332 Malaysian men aged 40 years and above was conducted. The blood of subject was collected under fasting condition for determination of testosterone, SHBG, glucose and lipid levels. Their medical history, smoking and alcohol consumption status, waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. All testosterone and SHBG levels were significantly reduced in MS subjects compared to non-MS subjects (p<0.05). Testosterone and SHBG were correlated significantly with most of the MS indicators without adjustments. In multiple regression analysis, the triglyceride level was the only MS indicator that was significantly, inversely and independently associated with all testosterone measurements and SHBG (p<0.05). Waist circumference was significantly and negatively associated with SHBG level (p<0.05) though not independent of BMI. Total testosterone and SHBG were significantly and inversely associated with the presence of MS. Testosterone and SHBG are potential intervention targets for the prevention of MS in men.
Fulltext The Anti-Inflammatory, Phytoestrogenic, and Antioxidative Role of Labisia pumila in Prevention of Postmenopausal Osteoporosis

Nadia ME, Nazrun AS, Norazlina M, Isa NM, Norliza M, Ima Nirwana S

Adv Pharmacol Sci, 2012;2012:706905.
PMID: 22611381 DOI: 10.1155/2012/706905

Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-α. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis.
Low dose of tocotrienols protects osteoblasts against oxidative stress

Nizar AM, Nazrun AS, Norazlina M, Norliza M, Ima Nirwana S

Clin Ter, 2011;162(6):533-8.
PMID: 22262323

Vitamin E is an antioxidant that may protect bone against oxidative stress-induced osteoporosis. This in vitro study was conducted to determine the protective effects of a-tocopherol and γ-tocotrienol on osteoblasts, the bone forming cells, against oxidative stress.
Fulltext Effects of vitamin E on receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in rats treated with nicotine

Norazlina M, Maizatul-Neza J, Azarina A, Nazrun AS, Norliza M, Ima-Nirwana S

Med J Malaysia, 2010 Mar;65(1):14-7.
PMID: 21265240 MyJurnal

Vitamin E is found to reverse the effects of nicotine on bone and this study aimed to determine its mechanism. Male Sprague Dawley rats were divided into four groups and treated for 3 months: Group 1 was the control group (RC). Groups 2 (N), 3 (N+TT) and 4 (N+ATF) received nicotine 7 mg/kg throughout the treatment period. In addition, groups 3 and 4 received tocotrienol 60 mg/kg and alpha-tocopherol 60 mg/kg respectively during months 2 and 3. Parameters measured were serum osteoprotegerin (OPG), serum receptor activator of nuclear factor kappa B ligand (RANKL), femoral and lumbar bone calcium content and body weight. Nicotine did not affect OPG or RANKL levels but reduced bone calcium content suggesting the calcium loss is not due to increase osteoclastogenesis. OPG was increased in N+ATF while RANKL was slightly increased in N+TT. Both vitamin E supplements restored bone calcium loss induced by nicotine. Nicotine impaired weight gain in all treatment groups starting week 4 however, N+TT group was comparable to RC from week 6 onwards. Bone protective effects of ATF, but not TT, may be partly due to inhibition of osteoclastogenesis.
Beneficial effects of tocotrienol and tocopherol on bone histomorphometric parameters in sprague-dawley male rats after nicotine cessation

Hermizi H, Faizah O, Ima-Nirwana S, Ahmad Nazrun S, Norazlina M

Calcif. Tissue Int., 2009 Jan;84(1):65-74.
PMID: 19020790 DOI: 10.1007/s00223-008-9190-x

This study was conducted to determine the effectiveness of three forms of vitamin E supplements following nicotine treatment on bone histomorphometric parameters in an adult male rat model. Rats were divided into seven groups: baseline (B, killed without treatment), control (C, normal saline for 4 months), nicotine (N, nicotine for 2 months), nicotine cessation (NC), tocotrienol-enhanced fraction (TEF), gamma-tocotrienol (GTT), and alpha-tocopherol (ATF). Treatments for the NC, TEF, GTT, and ATF groups were performed in two phases. For the first 2 months they were given nicotine (7 mg/kg), and for the following 2 months nicotine administration was stopped and treatments with respective vitamin E preparations (60 mg/kg) were commenced except for the NC group, which was allowed to recover without treatment. Rats in the N and NC groups had lower trabecular bone volume, mineral appositional rate (MAR), and bone formation rate (BFR/BS) and higher single labeled surface and osteoclast surface compared to the C group. Vitamin E treatment reversed these nicotine effects. Both the TEF and GTT groups, but not the ATF group, had a significantly higher trabecular thickness but lower eroded surface (ES/BS) than the C group. The tocotrienol-treated groups had lower ES/BS than the ATF group. The GTT group showed a significantly higher MAR and BFR/BS than the TEF and ATF groups. In conclusion, nicotine induced significant bone loss, while vitamin E supplements not only reversed the effects but also stimulated bone formation significantly above baseline values. Tocotrienol was shown to be slightly superior compared to tocopherol. Thus, vitamin E, especially GTT, may have therapeutic potential to repair bone damage caused by chronic smoking.
Fulltext Lessons from the Bone Chapter of the Malaysian Aging Men Study

Chin KY, Wan Ngah WZ, Ima-Nirwana S

Int J Environ Res Public Health, 2016 05 25;13(6).
PMID: 27231930 DOI: 10.3390/ijerph13060531

Male osteoporosis in Malaysia is a largely neglected problem. Therefore, a bone health study in men using quantitative ultrasonometry was launched as part of the Malaysian Aging Men Study in 2009-2012. This review aimed to summarize the findings of the aforementioned bone health study. The study examined the bone health of Chinese and Malaysian men aged 20 years and above living in Kuala Lumpur using a quantitative ultrasound device. Participants answered a questionnaire on their demographic details and physical activity status. Body anthropometry of the participants was measured and their blood collected for biochemical analysis. Results showed that a significant proportion of the Malaysian Chinese and Malay men had suboptimal bone health indicated by calcaneal speed of sound and vitamin D status. Age-related decline of the calcaneal speed of sound in these men was gradual and biphasic without ethnic difference. Body anthropometry such as height, weight, body mass index, and body fat percentage contributed to the variation of the calcaneal speed of sound in Malaysian men. Age-related changes in testosterone, insulin-like growth factor 1, and thyroid stimulating hormone also influenced the calcaneal speed of sound in these men. This study serves as a reminder that male osteoporosis in Malaysia should be an issue of concern. It is also a basis for a more comprehensive study on bone health in men in the future.
Vitamin D is significantly associated with total testosterone and sex hormone-binding globulin in Malaysian men

Chin KY, Ima-Nirwana S, Wan Ngah WZ

Aging Male, 2015;18(3):175-9.
PMID: 26004987 DOI: 10.3109/13685538.2015.1034686

OBJECTIVE: Cross-sectional studies in the Caucasian population have shown a significant relationship between vitamin D and testosterone levels, but data in the Asian population are limited. This study aimed to determine the association between vitamin D and testosterone levels in Malaysian men.
METHODS: Chinese and Malay men (n = 382) aged 20 years or above residing in the Klang Valley, Malaysia were recruited. Their fasting blood was collected for serum testosterone, sex hormone-binding globulin (SHBG) and 25-hydroxyvitamin D (25(OH)D) assays. Relationship between 25(OH)D and testosterone levels was analyzed using multiple regression analysis. Testosterone and SHBG levels among subjects with different vitamin D status were compared using univariate analysis. Confounders such as age, ethnicity and body mass index (BMI) were adjusted.
RESULTS: 25(OH)D was significantly and positively associated with total testosterone and SHBG levels before and after adjustment for age and ethnicity (p 0.05).
CONCLUSION: 25(OH)D is significantly associated with total testosterone and SHBG in Malaysian men but this association is BMI-dependent.
Tocotrienols are needed for normal bone calcification in growing female rats

Norazlina M, Ima-Nirwana S, Abul Gapor MT, Abdul Kadir Khalid B

Asia Pac J Clin Nutr, 2002;11(3):194-9.
PMID: 12230232

In this study the effects of vitamin E deficiency and supplementation on bone calcification were determined using 4-month-old female Sprague-Dawley rats. The rats weighed between 180 and 200 g. The study was divided in three parts. In experiment I the rats were given normal rat chow (RC, control group), a vitamin E deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2 the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60 mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In experiment 3 the rats were fed RC and given the same supplements as in experiment 2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and 118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P < 0.05) and L5 vertebra (28.3 +/- 4.0 mg and 39.5 +/- 6.2 mg compared with 51.4 +/- 5.8 mg; P < 0.05). Supplementing the VED group with PVE60 improved bone calcification in the left femur (133.6 +/- 5.0 mg compared with 91.6 +/- 13.3 mg; P < 0.05) and L5 vertebra (41.3 +/- 3.3 mg compared with 28.3 +/- 4.0 mg; P < 0.05) while supplementation with PVE30 improved bone calcium content in the L5 vertebra (35.6 +/- 3.1 mg compared with 28.3 +/- 4.0 mg; P < 0.05). However, supplementation with ATF did not change the lumbar and femoral bone calcium content compared to the VED group. Supplementing the RC group with PVE30, PVE60 or ATF did not cause any significant changes in bone calcium content. In conclusion, vitamin E deficiency impaired bone calcification. Supplementation with the higher dose of palm vitamin E improved bone calcium content, but supplementation with pure ATF alone did not. This effect may be attributed to the tocotrienol content of palm vitamin E. Therefore, tocotrienols play an important role in bone calcification.
Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone

Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S

Clin Exp Pharmacol Physiol, 2005 Sep;32(9):761-70.
PMID: 16173934

1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.
Fulltext Vitamin A and Bone Health: A Review on Current Evidence

Yee MMF, Chin KY, Ima-Nirwana S, Wong SK

Molecules, 2021 Mar 21;26(6).
PMID: 33801011 DOI: 10.3390/molecules26061757

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 β-cryptoxanthin) may also protect bone. In vitro evidence showed that carotene and β-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.
Fulltext The effects of repeatedly heated frying oil and high cholesterol diet on the bone in ovariectomised rats

Nazrun AS, Chew CM, Norazlina M, Kamsiah J, Ima Nirwana S

Malays J Nutr, 2007 Mar;13(1):89-99.
PMID: 22692192 MyJurnal

The use of repeatedly heated frying oils and intake of high cholesterol diet have been linked to bone damage. The aim of this study is to determine the combined effects of taking repeatedly heated frying oils (palm or soy oil) and high cholesterol diet on the dynamic histomorphometric parameters of bone. Ovariectomised rats were used as animal model of post-menopausal osteoporosis. After six months of treatment, Double-labeled Surface (dLS/BS), Mineralising surface (MS/BS) and Bone Formation Rate (BFR/BS) of ovariectomised rats (OvxC) were significantly reduced compared to the normal control group. Additions of fresh or once-heated palm or soy oil into high cholesterol diet seem to have improved the dynamic parameters towards the normal control values. However, when these oils were repeatedly heated, the protective effects were lost and the dynamic parameters except MS/BS dropped back towards the ovariectomised-control values.
Fulltext A Review on the Enhancement of Calcium Phosphate Cement with Biological Materials in Bone Defect Healing

Wong SK, Wong YH, Chin KY, Ima-Nirwana S

Polymers (Basel), 2021 Sep 12;13(18).
PMID: 34577976 DOI: 10.3390/polym13183075

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.
Fulltext Effects of age, sex, and ethnicity on bone health status of the elderly in Kuala Lumpur, Malaysia

Chin KY, Kamaruddin AA, Low NY, Ima-Nirwana S

Clin Interv Aging, 2016;11:767-73.
PMID: 27358558 DOI: 10.2147/CIA.S108772

Osteoporosis is a significant health problem in the developing countries and its prevalence data are important for the estimation of health care burden and policy making. This study aimed to determine the age-related changes in bone health and the prevalence of osteoporosis in males and females aged 50 years or above living in Kuala Lumpur, Malaysia.
Fulltext A review of knowledge, belief and practice regarding osteoporosis among adolescents and young adults

Chan CY, Mohamed N, Ima-Nirwana S, Chin KY

Int J Environ Res Public Health, 2018 08 12;15(8).
PMID: 30103534 DOI: 10.3390/ijerph15081727

Osteoporosis is a major public health problem affecting millions of people worldwide. Increasing knowledge, correcting health belief and promoting osteoprotective practices are effective measures for building and maintaining strong bone throughout ones' life-span. This review aims to summarize the contemporary evidence on the knowledge, beliefs and practice of adolescents and young adults on bone health. We performed literature searches using the PubMed and Scopus databases to identify original studies from 2008 to May 2018 using the search terms "(knowledge OR beliefs OR attitude OR practice OR behaviours OR physical activity OR exercise OR diet OR nutrition) AND (young OR youth OR adolescents OR children OR young adults OR students OR teenager) AND (osteoporosis OR bone health)". Of the 3206 articles found, 34 met the inclusion criteria. Studies showed that most adolescents and young adults had poor knowledge and expressed disinterest in osteoporosis. They believed that other diseases were more serious than osteoporosis, contributing to low perceived susceptibility and seriousness towards this disease. Popular media emerged as a platform to obtain information regarding osteoporosis. The lack of knowledge and misconceptions about osteoporosis led to poor osteoprotective practices. As a conclusion, the current evidence revealed a lack of awareness about osteoporosis among adolescents and young adults. Educational interventions may be useful to improve the awareness of osteoporosis among this population.
Fulltext Effects of vitamin E supplementation on bone metabolism in nicotine-treated rats

Norazlina M, Lee PL, Lukman HI, Nazrun AS, Ima-Nirwana S

Singapore Med J, 2007 Mar;48(3):195-9.
PMID: 17342286

Nicotine has been shown to exert negative effects on bone. This study determined whether vitamin E supplementation is able to repair the nicotine-induced adverse effects in bone.
Fulltext Proton Pump Inhibitors and Fracture Risk: A Review of Current Evidence and Mechanisms Involved

Thong BKS, Ima-Nirwana S, Chin KY

Int J Environ Res Public Health, 2019 May 05;16(9).
PMID: 31060319 DOI: 10.3390/ijerph16091571

The number of patients with gastroesophageal problems taking proton pump inhibitors (PPIs) is increasing. Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. This review aimed to investigate the longitudinal studies published in the last five years on the relationship between PPIs and fracture risk. The mechanism underlying this relationship was also explored. Overall, PPIs were positively associated with elevated fracture risk in multiple studies (n = 14), although some studies reported no significant relationship (n = 4). Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, mineral absorption, and muscle strength, contributing to increased fracture risk among PPI users. As a conclusion, there is a potential relationship between PPIs and fracture risks. Therefore, patients on long-term PPI treatment should pay attention to bone health status and consider prophylaxis to decrease fracture risk.
Biochemical and histopathological assessment of liver in a rat model of metabolic syndrome induced by high-carbohydrate high-fat diet

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.

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