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Fulltext The Mechanism of Kelulut Honey in Reversing Metabolic Changes in Rats Fed with High-Carbohydrate High-Fat Diet

Hashim KN, Chin KY, Ahmad F

Molecules, 2023 Mar 20;28(6).
PMID: 36985762 DOI: 10.3390/molecules28062790

Metabolic syndrome (MetS) is composed of central obesity, hyperglycemia, dyslipidemia and hypertension that increase an individual's tendency to develop type 2 diabetes mellitus and cardiovascular diseases. Kelulut honey (KH) produced by stingless bee species has a rich phenolic profile. Recent studies have demonstrated that KH could suppress components of MetS, but its mechanisms of action are unknown. A total of 18 male Wistar rats were randomly divided into control rats (C group) (n = 6), MetS rats fed with a high carbohydrate high fat (HCHF) diet (HCHF group) (n = 6), and MetS rats fed with HCHF diet and treated with KH (HCHF + KH group) (n = 6). The HCHF + KH group received 1.0 g/kg/day KH via oral gavage from week 9 to 16 after HCHF diet initiation. Compared to the C group, the MetS group experienced a significant increase in body weight, body mass index, systolic (SBP) and diastolic blood pressure (DBP), serum triglyceride (TG) and leptin, as well as the area and perimeter of adipocyte cells at the end of the study. The MetS group also experienced a significant decrease in serum HDL levels versus the C group. KH supplementation reversed the changes in serum TG, HDL, leptin, adiponectin and corticosterone levels, SBP, DBP, as well as adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) level, area and perimeter at the end of the study. In addition, histological observations also showed that KH administration reduced fat deposition within hepatocytes, and prevented deterioration of pancreatic islet and renal glomerulus. In conclusion, KH is effective in preventing MetS by suppressing leptin, corticosterone and 11βHSD1 levels while elevating adiponectin levels.
Fulltext Palmatine as an Agent Against Metabolic Syndrome and Its Related Complications: A Review

Ekeuku SO, Pang KL, Chin KY

Drug Des Devel Ther, 2020;14:4963-4974.
PMID: 33235437 DOI: 10.2147/DDDT.S280520

Palmatine is a naturally occurring isoquinoline alkaloid with various pharmacological properties. Given its antioxidant and anti-inflammatory properties, palmatine may be able to impede the effects of metabolic syndrome (MetS) and its related diseases triggered by inflammation and oxidative stress. This review summarises the existing literature about the effects of palmatine supplementation on MetS and its complications. The evidence shows that palmatine could protect against MetS, and cardiovascular diseases, osteoporosis and osteoarthritis, which might be associated with MetS. These protective effects are mediated by the antioxidant and anti-inflammatory properties of palmatine. Although preclinical experiments have demonstrated the efficacy of palmatine against MetS and its related diseases, no human clinical trials have been performed to validate these effects. This research gap should be bridged to validate the efficacy and safety of palmatine supplementation in protecting humans against MetS and its related diseases.
Fulltext The Effects of Tocotrienol on Bone Peptides in a Rat Model of Osteoporosis Induced by Metabolic Syndrome: The Possible Communication between Bone Cells

Wong SK, Chin KY, Ima-Nirwana S

Int J Environ Res Public Health, 2019 09 09;16(18).
PMID: 31505801 DOI: 10.3390/ijerph16183313

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.
On the critical importance of meticulous data extraction for meta-analysis of genetic association study

Low TY, Chin KY, Tan SC

Arch Physiol Biochem, 2023 Dec;129(4):1007-1008.
PMID: 33689514 DOI: 10.1080/13813455.2021.1890132
Immunomodulatory Effects of Agarwood Leaf Extract on RAW264.7 Murine Macrophages

Pang KL, Chin KY, Nirwana SI

Endocr Metab Immune Disord Drug Targets, 2023;23(7):964-976.
PMID: 36597600 DOI: 10.2174/1871530323666230103153134

BACKGROUND: The immunomodulatory effects of plants have been utilised to enhance the immunity of humans against infections. However, evidence of such effects of agarwood leaves is very limited despite the long tradition of consuming the leaves as tea.
OBJECTIVE: This study aimed to investigate the immuno-modulatory effects of agarwood leaf extract (ALE) derived from Aquilaria malaccensis using RAW264.7 murine macrophages.
METHODS: In this study, RAW264.7 macrophages were incubated with ALE alone for 26 hours or ALE for 2 hours, followed by bacterial lipopolysaccharide for 24 hours. The nitrite and cytokine production (tumour necrosis factor-alpha (TNFα), interleukin (IL)-1β, IL-6, and IL-10), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) expression in the macrophages were assayed.
RESULTS: The study showed that ALE alone was immunostimulatory on the macrophages by increasing the nitrite, TNFα, and IL-6 production and COX2 expression (p<0.05 vs. untreated unstimulated cells). Pre-treatment of ALE suppressed nitrite level and iNOS expression but enhanced TNFα and IL-6 production and COX2 expression (p<0.05 vs. untreated lipopolysaccharides (LPS)-stimulated cells). ALE also increased IL-10 production regardless of LPS stimulation (p<0.05 vs. untreated cells).
CONCLUSION: ALE was able to promote the immune response of macrophages by upregulating pro-inflammatory cytokine levels and COX2 expression. It also regulated the extent of the inflammation by reducing iNOS expression and increasing IL-10 levels. Thus, ALE may have a role in enhancing the innate immune system against infection; however, its validation from in vivo studies is still pending.
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 Particulate Air Pollution and Osteoporosis: A Systematic Review

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.
Fulltext Effects of Caffeic Acid and Its Derivatives on Bone: A Systematic Review

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.
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.
Bioaccumulation and depuration of anthracene in Penaeus monodon (Fibricius) through food ingestion

Ong PT, Yong JC, Chin KY, Hii YS

Chemosphere, 2011 Jul;84(5):578-84.
PMID: 21529890 DOI: 10.1016/j.chemosphere.2011.03.059

Understanding on the bioaccumulation and depuration of PAHs (polycyclic aromatic hydrocarbons) in Penaeus monodon is important in seafood safety because it is one of the most popular seafood consumed worldwide. In this study, we used anthracene as the precursor compound for PAHs accumulation and depuration in the shrimp. Commercial feed pellets spiked with anthracene were fed to P. monodon. At 20 mg kg(-1) anthracene, P. monodon accumulated 0.1% of the anthracene from the feed. P. monodon deputed the PAH two times faster than its accumulation. The shrimp reduced its feed consumption when anthracene content in the feed exceeded 20 mg kg(-1). At 100 mg kg(-1) anthracene, P. monodon started to have necrosis tissues on the posterior end of their thorax. The bioaccumulation factor (BAF), uptake rate constant (k(1)) and depuration rate constant (k(2)) of anthracene in P. monodon were 1.15×10(-3), 6.80×10(-4) d(-1) and 6.28×10(-1) d(-1), respectively. The depuration rate constant is about thousand times higher than the uptake rate constant and this indicated that this crustacean is efficient in depurating hydrocarbons from their tissue.
Fulltext Significant association between parathyroid hormone and uric acid level in men

Chin KY, Nirwana SI, Ngah WZ

Clin Interv Aging, 2015;10:1377-80.
PMID: 26346636 DOI: 10.2147/CIA.S90233

Previous reports of patients undergoing parathyroidectomy and of patients receiving teriparatide as antiosteoporotic treatment have suggested a plausible relationship between parathyroid hormone (PTH) and uric acid. However, similar data at population level were lacking. The current study aimed to determine the relationship between PTH and uric acid in a group of apparently healthy Malaysian men.
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.
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 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 Factors Associated with Bone Health in Malaysian Middle-Aged and Elderly Women Assessed via Quantitative Ultrasound

Chin KY, Low NY, Dewiputri WI, Ima-Nirwanaa S

Int J Environ Res Public Health, 2017 07 06;14(7).
PMID: 28684685 DOI: 10.3390/ijerph14070736

Risk factors for osteoporosis may vary according to different populations. We aimed to investigate the relationship between risk factors of osteoporosis and bone health indices determined via calcaneal quantitative ultrasound (QUS) in a group of Malaysian women aged 50 years or above. A cross-sectional study was performed on 344 Malaysian women recruited from a tertiary medical centre in Kuala Lumpur, Malaysia. They answered a self-administered questionnaire on their social-demographic details, medical history, lifestyle, and physical activity status. Their height was measured using a stadiometer, and their body composition estimated using a bioelectrical impedance device. Their bone health status was determined using a water-based calcaneal QUS device that generated three indices, namely speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI). A T-score was computed from SI values using a reference database from a mainland Chinese population. Women with three or more lifetime pregnancies, who were underweight and not drinking coffee had a significantly lower BUA. Stepwise multiple linear regression showed that SOS was predicted by age alone, BUA and SI by years since menopause, body mass index (BMI), and number of lifetime pregnancies, and T-score by years since menopause and percentage of body fat. As a conclusion, suboptimal bone health in middle-aged and elderly Malaysian women as indicated by QUS is associated with old age, being underweight, having a high body fat percentage, and a high number of lifetime pregnancies. Women having several risk factors should be monitored more closely to protect their bones against accelerated bone loss.
Fulltext A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health

Chin KY, Pang KL, Mark-Lee WF

Int J Med Sci, 2018;15(10):1043-1050.
PMID: 30013446 DOI: 10.7150/ijms.25634

Bisphenol A (BPA) is an endocrine disruptor which can bind to the oestrogen receptor. It also possesses oestrogenic, antiandrogenic, inflammatory and oxidative properties. Since bone responds to changes in sex hormones, inflammatory and oxidative status, BPA exposure could influence bone health in humans. This review aimed to summarize the current evidence on the relationship between BPA and bone health derived from cellular, animal and human studies. Exposure to BPA (0.5-12.5 µM) decreased the proliferation of osteoblast and osteoclast precursor cells and induce their apoptosis. Bisphenol AF (10 nM) enhanced transforming growth factor beta signalling but bisphenol S (10 nM) inhibited Wnt signalling involved in osteoblast differentiation in vitro. In animals, BPA and its derivatives demonstrated distinct effects in different models. In prenatal/postnatal exposure, BPA increased femoral bone mineral content in male rats (at 25 ug/kg/day) but decreased femoral mechanical strength in female mice (at 10 µg/kg/day). In oestrogen deficiency models, BPA improved bone mineral density and microstructures in aromatase knockout mice (at very high dose, 0.1% or 1.0% w/w diet) but decreased trabecular density in ovariectomized rats (at 37 or 370 ug/kg/day). In contrast, bisphenol A diglycidyl ether (30 mg/kg/day i.p.) improved bone health in normal male and female rodents and decreased trabecular separation in ovariectomized rodents. Two cross-sectional studies have been performed to examine the relationship between BPA level and bone mineral density in humans but they yielded negligible association. As a conclusion, BPA and its derivatives could influence bone health and a possible gender effect was observed in animal studies. However, its effects in humans await verification from more comprehensive longitudinal studies in the future.

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