Displaying publications 1 - 20 of 71 in total

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  1. Ekeuku SO, Chin KY, Qian J, Zhang Y, Qu H, Ahmad F, et al.
    Int J Med Sci, 2023;20(13):1711-1721.
    PMID: 37928881 DOI: 10.7150/ijms.84604
    Background: Menopause is accompanied by increased oxidative stress, partly contributing to weight gain and bone marrow adiposity. Traditional Chinese medication, E'Jiao, has been demonstrated to reduce excessive bone remodelling during oestrogen deprivation, but its effects on body composition and bone marrow adiposity during menopause remain elusive. Objective: To determine the effects of E'Jiao on body composition, bone marrow adiposity and skeletal redox status in ovariectomised (OVX) rats. Methods: Seven groups of three-month-old female Sprague Dawley rats were established (n=6/group): baseline, sham, OVX control, OVX-treated with low, medium or high-dose E'Jiao (0.26, 0.53, 1.06 g/kg, p.o.) or calcium carbonate (1% in tap water, ad libitum). The supplementation was terminated after 8 weeks. Whole-body composition analysis was performed monthly using dual-energy X-ray absorptiometry. Analysis of bone-marrow adipocyte numbers and skeletal antioxidant activities were performed on the femur. Results: Increased total mass, lean mass, and bone marrow adipocyte number were observed in the OVX control versus the sham group. Low-dose E'Jiao supplementation counteracted these changes. Besides, E'Jiao at all doses increased skeletal catalase and superoxide dismutase activities but lowered glutathione levels in the OVX rats. Skeletal malondialdehyde level was not affected by ovariectomy but was lowered with E'Jiao supplementation. However, peroxisome proliferator-activated receptor gamma protein expression was not affected by ovariectomy or any treatment. Conclusion: E'Jiao, especially at the low dose, prevented body composition changes and bone marrow adiposity due to ovariectomy. These changes could be mediated by the antioxidant actions of E'Jiao. It has the potential to be used among postmenopausal women to avoid adiposity.
  2. Pang KL, Chow YY, Leong LM, Law JX, Ghafar NA, Soelaiman IN, et al.
    Life (Basel), 2021 Mar 25;11(4).
    PMID: 33805920 DOI: 10.3390/life11040272
    Osteoarthritis (OA) is the most common degenerative joint disease characterised by chondrocyte cell death. An in vitro model of chondrocyte cell death may facilitate drug discovery in OA management. In this study, the cytotoxicity and mode of cell death of SW1353 chondrocytes treated with 24 h of OA inducers, including interleukin-1β (IL-1β), hydrogen peroxide (H2O2) and monosodium iodoacetate (MIA), were investigated. The microscopic features, oxidative (isoprostane) and inflammatory markers (tumour necrosis factor-alpha; TNF-α) for control and treated cells were compared. Our results showed that 24 h of H2O2 and MIA caused oxidative stress and a concentration-dependent reduction of SW1353 cell viability without TNF-α level upregulation. H2O2 primarily induced chondrocyte apoptosis with the detection of blebbing formation, cell shrinkage and cellular debris. MIA induced S-phase arrest on chondrocytes with a reduced number of attached cells but without significant cell death. On the other hand, 24 h of IL-1β did not affect the cell morphology and viability of SW1353 cells, with a significant increase in intracellular TNF-α levels without inducing oxidative stress. In conclusion, each OA inducer exerts differential effects on SW1353 chondrocyte cell fate. IL-1β is suitable in the inflammatory study but not for chondrocyte cell death. H2O2 and MIA are suitable for inducing chondrocyte cell death and growth arrest, respectively.
  3. 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.
  4. Mohamad Asri SF, Soelaiman IN, Mohd Moklas MA, Mohd Nor NH, Mohamad Zainal NH, Mohd Ramli ES
    Int J Mol Sci, 2020 Oct 19;21(20).
    PMID: 33086468 DOI: 10.3390/ijms21207715
    Glucocorticoids are one of the causes of secondary osteoporosis. The aqueous extract of Piper sarmentosum contains flavonoids that possess antioxidant effects. In this study, we determined the effects of aqueous Piper sarmentosum leaf extract on structural, dynamic and static histomorphometric changes from osteoporotic bones of rats induced with glucocorticoids. Thirty-two Sprague-Dawley rats were divided equally into four groups-Sham control group given vehicles (intramuscular (IM) olive oil and oral normal saline); AC: Adrenalectomised (Adrx) control group given IM dexamethasone (DEX) (120 μg/kg/day) and vehicle (oral normal saline); AP: Adrx group administered IM DEX (120 μg/kg/day) and aqueous Piper sarmentosum leaf extract (125 mg/kg/day) orally; and AG: Adrx group administered IM DEX (120 μg/kg/day) and oral glycyrrhizic acid (GCA) (120 mg/kg/day). Histomorphometric measurements showed that the bone volume, trabecular thickness, trabecular number, osteoid and osteoblast surfaces, double-labelled trabecular surface, mineralizing surface and bone formation rate of rats given aqueous Piper sarmentosum leaf extract were significantly increased (p < 0.05), whereas the trabecular separation and osteoclast surface were significantly reduced (p < 0.05). This study suggests that aqueous Piper sarmentosum leaf extract was able to prevent bone loss in prolonged glucocorticoid therapy. Thus, Piper sarmentosum has the potential to be used as an alternative medicine against osteoporosis and osteoporotic fractures in patients undergoing long-term glucocorticoid therapy.
  5. Subramaniam S, Chan CY, Soelaiman IN, Mohamed N, Muhammad N, Ahmad F, et al.
    PMID: 32272697 DOI: 10.3390/ijerph17072526
    Background: The current osteoporosis screening instruments are not optimized to be used among the Malaysian population. This study aimed to develop an osteoporosis screening algorithm based on risk factors for Malaysians. Methods: Malaysians aged ≥50 years (n = 607) from Klang Valley, Malaysia were interviewed and their bone health status was assessed using a dual-energy X-ray absorptiometry device. The algorithm was constructed based on osteoporosis risk factors using multivariate logistic regression and its performance was assessed using receiver operating characteristics analysis. Results: Increased age, reduced body weight and being less physically active significantly predicted osteoporosis in men, while in women, increased age, lower body weight and low-income status significantly predicted osteoporosis. These factors were included in the final algorithm and the optimal cut-offs to identify subjects with osteoporosis was 0.00120 for men [sensitivity 73.3% (95% confidence interval (CI) = 54.1%-87.7%), specificity 67.8% (95% CI = 62.7%-85.5%), area under curve (AUC) 0.705 (95% CI = 0.608-0.803), p < 0.001] and 0.161 for women [sensitivity 75.4% (95% CI = 61.9%-73.3%), specificity 74.5% (95% CI = 68.5%-79.8%), AUC 0.749 (95% CI = 0.679-0.820), p < 0.001]. Conclusion: The new algorithm performed satisfactorily in identifying the risk of osteoporosis among the Malaysian population ≥50 years. Further validation studies are required before applying this algorithm for screening of osteoporosis in public.
  6. Subramaniam S, Chan CY, Soelaiman IN, Mohamed N, Muhammad N, Ahmad F, et al.
    Diagnostics (Basel), 2020 Mar 25;10(4).
    PMID: 32218298 DOI: 10.3390/diagnostics10040178
    BACKGROUND: Calcaneal quantitative ultrasound (QUS) is widely used in osteoporosis screening, but the cut-off values for risk stratification remain unclear. This study validates the performance of a calcaneal QUS device (CM-200) using dual-energy X-ray absorptiometry (DXA) as the reference and establishes a new set of cut-off values for CM-200 in identifying subjects with osteoporosis.

    METHODS: The bone health status of Malaysians aged ≥40 years was assessed using CM-200 and DXA. Sensitivity, specificity, area under the curve (AUC) and the optimal cut-off values for risk stratification of CM-200 were determined using receiver operating characteristic (ROC) curves and Youden's index (J). Results: From the data of 786 subjects, CM-200 (QUS T-score 0.05). Modified cut-off values for the QUS T-score improved the performance of CM-200 in identifying subjects with osteopenia (sensitivity 67.7% (95% CI: 62.8-72.3%); specificity 72.8% (95% CI: 68.1-77.2%); J = 0.405; AUC 0.702 (95% CI: 0.666-0.739); p < 0.001) and osteoporosis (sensitivity 79.4% (95% CI: 70.0-86.9%); specificity 61.8% (95% CI: 58.1-65.5%); J = 0.412; AUC 0.706 (95% CI: 0.654-0.758); p < 0.001). Conclusion: The modified cut-off values significantly improved the performance of CM-200 in identifying individuals with osteoporosis. Since these values are device-specific, optimization is necessary for accurate detection of individuals at risk for osteoporosis using QUS.

  7. Wan Hasan WN, Chin KY, Abd Ghafar N, Soelaiman IN
    Drug Des Devel Ther, 2020;14:969-976.
    PMID: 32184566 DOI: 10.2147/DDDT.S224941
    Purpose: Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis and promote differentiation of pre-osteoblastic cells. However, the mechanism of action of AnTT in achieving these effects is unclear. This study aims to investigate the mechanism of action of AnTT on MC3T3-E1 pre-osteoblasts via the mevalonate pathway.

    Methods: Murine pre-osteoblastic cells, MC3T3-E1, were cultured with the density of 1 × 104 cells/mL and treated with 4 concentrations of AnTT (0.001-1 µg/mL). Expression of HMG-CoA reductase (HMGR) gene was carried out using qPCR after treatment with AnTT for 21 days. RhoA activation and bone morphogenetic protein-2 (BMP-2) were measured using immunoassay after 9 and 15 days of AnTT treatment. Lovastatin was used as the positive control. Mineralized nodules were detected using Von Kossa staining after 21 days of AnTT treatment.

    Results: The results showed that HMGR was up-regulated in the lovastatin group on day 9 and 21 compared to the control. Lovastatin also inhibited RhoA activation (day 9 and 15) and increased BMP-2 protein (day 15). On the other hand, AnTT at 0.001 μg/mL (day 3) and 0.1 μg/mL (day 21) significantly down-regulated HMGR gene expression compared to the control. On day 21, HMGR gene expression was significantly reduced in all groups compared to day 15. AnTT at 0.1 μg/mL significantly decreased RhoA activation on day 9 compared to the control. AnTT at 1 μg/mL significantly increased BMP-2 protein on day 15 compared to the control (P<0.05). Mineralized calcium nodules were more abundant in AnTT treated groups compared to the control on day 21.

    Conclusion: AnTT suppresses the mevalonate pathway by downregulating HMGR gene expression and inhibiting RhoA activation, leading to increased BMP-2 protein in MC3T3-E1 cells. This explains the stimulating effects of AnTT on osteoblast mineralization.

  8. Chin KY, Thong BKS, Kamalulloh RF, Mohamad NV, Wong SK, Mohd Arlamsyah A, et al.
    Drug Des Devel Ther, 2020;14:2561-2572.
    PMID: 32753839 DOI: 10.2147/DDDT.S260565
    Purpose: Prolonged use of proton pump inhibitors may cause bone loss, and limited therapeutic agents are available to prevent this skeletal side effect. The combination of annatto tocotrienol, a bone anabolic agent, with calcium presents a novel strategy to prevent bone loss caused by proton pump inhibitors. This study aims to compare the effects of calcium alone and in combination with annatto tocotrienol or vitamin D3 (Caltrate Plus) in preventing bone loss caused by pantoprazole.

    Methods: Three-month-old Sprague Dawley male rats (n=30) were randomised into five groups (n=6/group). Bone loss was induced by pantoprazole (3 mg/kg p.o.) in four groups, and they were treated concurrently with either calcium carbonate (77 mg p.o.), calcium carbonate (77 mg p.o.) plus annatto tocotrienol (60 mg/kg p.o.) or Caltrate Plus (31 mg p.o.) for 60 days. The rats were euthanised at the end of the experiment, and their femurs were harvested for X-ray micro-computed tomography, bone cellular histomorphometry and bone mechanical strength analysis.

    Results: Pantoprazole caused significant deterioration of trabecular bone microstructures but did not affect other skeletal indices. Calcium supplementation with or without annatto tocotrienol prevented the deterioration of trabecular microstructures at the femur but did not improve other skeletal indices. Annatto tocotrienol did not enhance the skeletal actions of calcium, whereas Caltrate Plus did not affect the bone health indices in these rats.

    Conclusion: Calcium supplementation per se can prevent the deterioration of bone trabecular microstructures in rats receiving long-term treatment of pantoprazole.

  9. Subramaniam S, Chan CY, Soelaiman IN, Mohamed N, Muhammad N, Ahmad F, et al.
    Arch Osteoporos, 2019 11 28;14(1):117.
    PMID: 31781876 DOI: 10.1007/s11657-019-0666-2
    The concordance between osteoporosis self-assessment tool for Asians (OSTA) and dual-energy X-ray absorptiometry (DXA) was fair in the study. Modification of OSTA cutoff values improved its sensitivity to identify subjects at risk for suboptimal bone health (osteopenia/osteoporosis) and osteoporosis.

    PURPOSE: Osteoporosis self-assessment tool for Asians (OSTA) is a convenient screening algorithm used widely to identify patients at risk of osteoporosis. Currently, the number of studies validating OSTA in Malaysian population is limited. This study aimed to validate the performance of OSTA in identifying subjects with osteoporosis determined with DXA.

    METHODS: This cross-sectional study recruited 786 Malaysians in Klang Valley, Malaysia. Their bone health status was assessed by DXA and OSTA. The association and agreement between OSTA and bone mineral density assessment by DXA were determined by Pearson's correlation and Cohen's kappa, respectively. Receiver operating characteristics (ROC) curves were used to determine the sensitivity, specificity, and area under the curve (AUC) for OSTA.

    RESULTS: OSTA and DXA showed a fair association in the study (r = 0.382, κ = 0.159, p 

  10. Giaze TR, Shuid AN, Soelaiman IN, Muhammad N, Jamal JA, Fauzi MB, et al.
    J Tradit Complement Med, 2019 Oct;9(4):393-400.
    PMID: 31453136 DOI: 10.1016/j.jtcme.2019.01.002
    Background: Marantodes pumilum var. alata (MPva), popularly known as Kacip Fatimah, is widely used to maintain female reproductive health, facilitate post-partum recovery and manage symptoms of menopause and osteoporosis in South-East Asia. This study aims to further evaluate the osteoprotective potential of MPva in view of reports of its bone-protective properties in postmenopausal condition.

    Methods: Thirty female Sprague-Dawley rats were sorted into 5 groups (n = 6) namely: MPv (leaf treatment); MPr (root treatment); ERT (estrogen treatment); OVXC (untreated ovariectomized control) and Sham (untreated sham-operated control). All rats (except the Sham) were ovariectomized to induce a state of estrogen deficiency that simulates menopause. Two weeks after ovariectomy, the rats were treated for 8 weeks with oral gavages of estrogen and plant extracts. The ERT group received 64.5 μg/kg/day dose of estrogen while MPv and MPr groups received 20 mg/kg/day dose of leaf and root extracts, respectively. At the end of treatment, left femora were excised from euthanized rats and investigated for changes in bone micro-architecture, mineral density, and biomechanical properties.

    Results: Bone volume fraction, degree of anisotropy and structure-model-index of bone were significantly improved (p 

  11. Aminuddin A, Salamt N, Ahmad Fuad AF, Chin KY, Ugusman A, Soelaiman IN, et al.
    Medicina (Kaunas), 2019 Sep 08;55(9).
    PMID: 31500378 DOI: 10.3390/medicina55090575
    Background and objectives: Obesity is associated with poor vascular function and may lead to future cardiovascular disease (CVD). Obesity is also related to increased inflammation and a low testosterone level. This study was conducted to determine the relationship between inflammation, testosterone level, and vascular function among subjects with an increased body mass index (BMI) and to determine whether both low testosterone and high inflammation have synergistic effects towards vascular dysfunction. Materials and Methods: A total of 303 men aged 40-80 years were recruited from Klang Valley, Malaysia. Their height, weight, blood pressure (BP), lipid, blood glucose level, total testosterone (TT), free testosterone (FT), and C-reactive protein (CRP) were measured. The carotid femoral pulse wave velocity (PWVCF) and augmentation index (AI) were also recorded as markers of vascular function. Results: The mean age of all the subjects was 54.46 ± 9.77 years. Subjects were divided into a low/normal body mass index (BMI) group (BMI < 25 kg/m2; NG, n = 154) and high BMI group (BMI ≥ 25 kg/m2; OG, n = 149). The mean BMI for NG was 22.20 ± 1.94 kg/m2 while for OG was 28.87 ± 3.24 kg/m2 (p < 0.01). The level of TT (OG = 21.13 ± 6.44 versus NG = 16.18 ± 6.16 nmol/L, p < 0.01) and FT (OG = 0.34 ± 0.12 versus NG = 0.39 ± 0.11 nmol/L, p < 0.01) were reduced while the level of CRP [OG = 1.05 (2.80) versus NG = 0.50 (1.50) mmol/L, p = 0.01] was increased in OG compared to NG. PWVCF (OG = 8.55 ± 1.34 versus NG = 8.52 ± 1.42 m/s, p = 0.02) and AI (OG = 16.91% ± 6.00% versus 15.88% ± 5.58%, p < 0.01) were significantly increased in OG after adjustment for other CVD risk factors. The subjects that had both a low FT and an increased CRP had higher AI when compared to those with a high CRP and high FT (p < 0.01). Conclusions: The increased BMI was associated with vascular dysfunction, mediated by a low testosterone level and increased inflammation. Furthermore, having both conditions concurrently lead to higher vascular dysfunction. Weight loss, testosterone supplementation, and the anti-inflammatory agent may be beneficial for men to prevent vascular dysfunction.
  12. Mohamad NV, Soelaiman IN, Chin KY
    Biomed Pharmacother, 2018 Jul;103:453-462.
    PMID: 29674281 DOI: 10.1016/j.biopha.2018.04.083
    INTRODUCTION: Osteoporosis is a debilitating skeletal side effect of androgen deprivation therapy based on gonadotropin-releasing hormone (GnRH) agonist in men. Tocotrienol from Bixa orellana (annatto) has been demonstrated to offer protection against osteoporosis by exerting anabolic effects on bone. Thus, it may prevent osteoporosis among GnRH agonist users.

    OBJECTIVE: This study aimed to determine the effectiveness of annatto-tocotrienol on the bone turnover markers and bone histomorphometry in a model of male osteoporosis induced by buserelin (a GnRH agonist).

    METHODS: Forty-six three-months-old male Sprague-Dawley rats (three months old; 300-350 g) were randomly divided into six groups. The baseline control group (n = 6) was sacrificed at the onset of the study. The normal control group (n = 8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n = 8) received corn oil orally daily and subcutaneous buserelin injection 75 μg/kg/day daily. The calcium control (n = 8) received 1% calcium in drinking water and subcutaneous buserelin injection 75 μg/kg/day. The remaining rats were treated with two different treatments, i.e., (1) oral annatto tocotrienol at 60 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8); (2) oral annatto tocotrienol at 100 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8). The rats were injected with calcein twice before being sacrificed to label the bones. The rats were euthanized, and their blood and right femur were harvested at the end of the treatment for bone turnover markers and bone histomorphometry examination.

    RESULTS: Both serum osteocalcin and C-telopeptide of type 1 collagen were not significantly different between treated groups and buserelin control (P > 0.05). The buserelin control group had a significantly lower bone volume and higher eroded surface compared with the normal control group (P 

  13. Jolly JJ, Chin KY, Alias E, Chua KH, Soelaiman IN
    PMID: 29751644 DOI: 10.3390/ijerph15050963
    Osteoporosis is a serious health problem affecting more than 200 million elderly people worldwide. The early symptoms of this disease are hardly detectable. It causes progressive bone loss, which ultimately renders the patients susceptible to fractures. Osteoporosis must be prevented because the associated fragility fractures result in high morbidity, mortality, and healthcare costs. Many plants used in herbal medicine contain bioactive compounds possessing skeletal protective effects. This paper explores the anti-osteoporotic properties of selected herbal plants, including their actions on osteoblasts (bone forming cells), osteoclasts (bone resorbing cells), and bone remodelling. Some of the herbal plant families included in this review are Berberidaceae, Fabaceae, Arecaceae, Labiatae, Simaroubaceaea, and Myrsinaceae. Their active constituents, mechanisms of action, and pharmaceutical applications were discussed. The literature shows that very few herbal plants have undergone human clinical trials to evaluate their pharmacological effects on bone to date. Therefore, more intensive research should be performed on these plants to validate their anti-osteoporotic properties so that they can complement the currently available conventional drugs in the battle against osteoporosis.
  14. Hasan WNW, Chin KY, Jolly JJ, Ghafar NA, Soelaiman IN
    PMID: 29683099 DOI: 10.2174/1871530318666180423122409
    BACKGROUND: Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling.

    OBJECTIVE: This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential.

    DISCUSSION: Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans.

    CONCLUSION: Mevalonate pathway can be exploited to develop effective antiosteoporosis agents.

  15. Mohamed N, Muhammad N, Shuid AN, Soelaiman IN
    Curr Drug Targets, 2018;19(12):1424-1430.
    PMID: 28950810 DOI: 10.2174/1389450118666170925154428
    Nicotine is one of the most abused substances worldwide and can cause several harmful effects on health. One of the harmful effects, which is often ignored, is osteoporosis. Smoking has been shown to cause a decrease in bone mineral density in humans. Animal studies have proven that nicotine exerts negative effects on bone. The number of people who smoke increases each day. Those who smoke start at a very young age and they usually smoke for years. This will increase the risk of developing osteoporosis. As the prevalence of osteoporosis increases, the risk of fractures also increases. The major concerns are disability following fractures, mortality due to complications after fractures and the increasing cost of management and therapy. This paper will review the effects of nicotine on bone and the potential natural products which can be used as treatment for nicotine-induced osteoporosis.
  16. Mohamad NV, Che Zulkepli MAA, May Theseira K, Zulkifli N, Shahrom NQ, Ridzuan NAM, et al.
    Int J Med Sci, 2018;15(4):300-308.
    PMID: 29511366 DOI: 10.7150/ijms.22732
    Introduction: Orchidectomy is currently the preferred method to induce bone loss in preclinical male osteoporosis model. Gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer treatment can induce testosterone deficiency but its effects on bone in preclinical male osteoporosis model are less studied. Objective: This study aimed to evaluate the skeletal effect of buserelin (a GnRH agonist) in male rats and compare it with orchidectomy. Methods: Forty-six three-month-old male Sprague-Dawley rats were divided into three experimental arms. The baseline arm (n=6) was sacrificed at the onset of the study. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline (n=8), buserelin acetate at 25 µg/kg (n=8) or 75 µg/kg (n=8). In the orchidectomy arm, the rats were either sham-operated (n=8) or orchidectomized (n=8). All groups underwent in-vivo X-ray micro-computed tomography scanning at the left proximal tibia every month. Blood was collected at the beginning and the end of the study for testosterone level evaluation. The rats were euthanized after the three-month treatment. The femurs were harvested for biomechanical strength and bone calcium determination. Results: The results showed that buserelin at both doses caused a significant decline in testosterone level and deterioration in bone microstructure (p<0.05), but did not affect bone calcium content (p>0.05). Buserelin at 25 µg/kg decreased displacement and strain of the femur significantly (p<0.05). Similar changes were observed in the orchidectomized group compared to the sham-operated group but without any significant changes in biomechanical strength (p>0.05). Conclusion: Buserelin can induce testosterone deficiency and the associated deterioration of bone microarchitecture similar to orchidectomy in three months. However, it may require a longer time to show significant effects on bone strength and mineral content.
  17. Mohamad NV, Soelaiman IN, Chin KY
    Endocr Metab Immune Disord Drug Targets, 2017 Nov 16;17(4):276-284.
    PMID: 28925899 DOI: 10.2174/1871530317666170919112757
    BACKGROUND AND OBJECTIVE: Prostate cancer is the most prevalent non-cutaneous cancer in men, which causes significant mortality among the patients. Since prostate cancer cells are stimulated by androgen, effective androgen ablation in men is one of the essential strategies in the management of prostate cancer.

    DISCUSSION: Several treatment options are available for different stages of prostate cancer. Hormone therapy known as androgen deprivation therapy (ADT) is the first line treatment used to treat advanced prostate cancer. Chemical castration by gonadotropin-releasing hormone agonists suppresses lutenizing hormone production, which in turn inhibits the production of testosterone and dihydrotestosterone. This will prevent the growth of prostate cancer cells. However, ADT causes deleterious effects on bone health because the androgens are essential in preserving optimal bone health in men.

    CONCLUSION: Various observational studies showed that long-term ADT for advanced or metastatic prostate cancer was associated with decreased bone mineral density, as well as altered body composition that might affect bone health. Considering the potential impact of osteoporotic fracture, interventions to mitigate these skeletal adverse effects should be considered by physicians when initiating ADT on their patients.

  18. Chin KY, Low NY, Kamaruddin AAA, Dewiputri WI, Soelaiman IN
    Ther Clin Risk Manag, 2017;13:1333-1341.
    PMID: 29070951 DOI: 10.2147/TCRM.S145519
    BACKGROUND: Calcaneal quantitative ultrasound (QUS) is a useful tool in osteoporosis screening. However, QUS device may not be available at all primary health care settings. Osteoporosis self-assessment tool for Asians (OSTA) is a simple algorithm for osteoporosis screening that does not require any sophisticated instruments. This study explored the possibility of replacing QUS with OSTA by determining their agreement in identifying individuals at risk of osteoporosis.

    METHODS: A cross-sectional study was conducted to recruit Malaysian men and women aged ≥50 years. Their bone health status was measured using a calcaneal QUS device and OSTA. The association between OSTA and QUS was determined using Spearman's correlation and their agreement was assessed using Cohen Kappa and receiver-operating curve.

    RESULTS: All QUS indices correlated significantly with OSTA (p<0.05). The agreement between QUS and OSTA was minimal but statistically significant (p<0.05). The performance of OSTA in identifying subjects at risk of osteoporosis according to QUS was poor-to-fair in women (p<0.05), but not statistically significant for men (p>0.05). Changing the cut-off values improved the performance of OSTA in women but not in men.

    CONCLUSION: The agreement between QUS and OSTA is minimal in categorizing individuals at risk of osteoporosis. Therefore, they cannot be used interchangeably in osteoporosis screening.
  19. Shen CL, Mo H, Yang S, Wang S, Felton CK, Tomison MD, et al.
    BMJ Open, 2016 12 23;6(12):e012572.
    PMID: 28011809 DOI: 10.1136/bmjopen-2016-012572
    INTRODUCTION: Osteoporosis is a major health concern in postmenopausal women, and oxidative stress contributes to the development of bone loss. Cellular studies and ovariectomised rat model mimicking bone loss in postmenopausal women show the bone-protective effect of tocotrienols (TTs) with antioxidant capability. We aim to access the safety and efficacy of TT consumption for bone health in postmenopausal women.

    METHODS AND ANALYSIS: In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2'-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. 'Intent-to-treat' principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ2 analysis and regression will be used for comparisons.

    ETHICS AND DISSEMINATION: This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or nutrition and international conferences.

    TRIAL REGISTRATION NUMBER: NCT02058420; results.

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