Displaying all 11 publications

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  1. 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.

    Matched MeSH terms: Bone Resorption/drug therapy*
  2. 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.
    Matched MeSH terms: Bone Resorption/drug therapy
  3. Abukhadir SS, Mohamed N, Mohamed N
    Curr Drug Targets, 2013 Dec;14(13):1601-10.
    PMID: 24138635
    Osteoporosis is the most common bone disease in humans; it represents a major public health problem. This chronic disease is characterized by increase in bone fracture due to: reduced bone mass, deterioration of micro architectural and decreased bone strength, bone fragility; and bone mineral density 2.5 or more standard deviations below the normal mean. Secondary osteoporosis is a common cause of osteoporosis, and there are many underlying risk factors for osteoporosis. Chronic alcohol abuse is one of the modifiable risk factors in osteoporosis. There is evidence of correlation between chronic alcohol abuse and low bone mass. Alcohol is directly toxic to the bone; with increased incidence of fractures and complications. Although there is a paucity of studies regarding alcohol induced osteoporosis therapy, it can be classified into antiresorptive therapy and anabolic therapy. Bisphosphonates have been demonstrated to be clinically relevant to prevent bone damage associated with alcohol use while parathyroid hormone increased bone mineralization as well as bone formation in alcohol treated rats. Vitamin D supplementation could prevent bone toxicity in chronic drinkers. This review discussed the pathogenesis of alcohol-induced osteoporosis and the agents available for its treatment. Other potential therapies are also discussed.
    Matched MeSH terms: Bone Resorption/drug therapy
  4. Helali AM, Iti FM, Mohamed IN
    Curr Drug Targets, 2013 Dec;14(13):1591-600.
    PMID: 23957815
    Osteoporosis is a pathologic process characterized by low bone mass with skeletal fragility and an increased risk of fracture. It occurs due to an imbalance between bone resorption and formation. Although current antiresorptive therapy halts bone loss, it does not cure the condition as it also inhibits bone formation. Recent preclinical and clinical trials suggest that the inhibition of resorption by cathepsin K inhibitors increases bone formation. Cathepsin K is a papainlike cysteine protease with high potent collagenase activity and predominantly expressed in osteoclasts. While allowing demineralization, cathepsin K inhibitors suppress the degradation of type I collagen (the major organic matrix of bone) and thus enhancing bone formation. Many of these inhibitors have passed preclinical studies and are presently in clinical trials at different stages of advancement. This review explores the promising role of cathepsin K as a novel antiresorptive for the treatment of osteoporosis.
    Matched MeSH terms: Bone Resorption/drug therapy*
  5. Abdul-Majeed S, Mohamed N, Soelaiman IN
    Curr Drug Targets, 2013 Dec;14(13):1579-90.
    PMID: 23848479
    Skeletal tissue undergoes continuous remodeling which makes it unique among other body tissues. Osteoporosis is a common bone metabolic disorder affecting both men and women. Osteoporosis and its complications mainly osteoporotic fractures, have a high impact on health and economy. Current approved medications are associated with numerous side effects, which limit their use. Identification of a new and safe therapy is mandatory. Statins, also known as HMGCoA reductase inhibitors, are frequently used for the treatment of hypercholesterolemia and for the prevention of morbidity and mortality associated with cardiovascular disease. Statins improved bone health status in intact and ovariectomised rodents following high clinically intolerable oral doses. However, this beneficial effect of statins could not be significantly demonstrated in humans. The reason behind this discrepancy might be due to the safety and bioavailability of the currently used oral statins. Vitamin E, especially the tocotrienols at the dose 60 mg/kg/day provided significant antiosteoporotic effects in different animal models of osteoporosis. The use of the aforementioned dose of tocotrienols was shown to be safe in both humans and animals. Enhancement of bone formation and reduction of bone resorption were achieved more effectively by a combination of tocotrienols and statins than by either treatment when supplemented separately at clinically tolerable doses. Therefore, the adverse effects associated with high statin doses might be avoided with the coadministration of tocotrienols. Moreover, the combination therapy strategy might be useful for patients who are at high risk of osteoporosis, cardiovascular events and hypercholesterolaemia.
    Matched MeSH terms: Bone Resorption/drug therapy
  6. 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.
    Matched MeSH terms: Bone Resorption/drug therapy*
  7. Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN
    Clinics (Sao Paulo), 2013 Oct;68(10):1338-43.
    PMID: 24212841 DOI: 10.6061/clinics/2013(10)08
    OBJECTIVE: Accelerated bone loss that occurs in postmenopausal women has been linked to oxidative stress and increased free radicals. We propose the use of antioxidants to prevent and reverse postmenopausal osteoporosis. This study aimed to examine the effects of tocotrienol, a vitamin E analog, on bone loss due to estrogen deficiency. Our previous study showed that tocotrienol increased the trabecular bone volume and trabecular number in ovariectomized rats. In the current study, we investigated the effects of tocotrienol supplementation on various biochemical parameters in a postmenopausal osteoporosis rat model.

    MATERIALS AND METHODS: A total of 32 female Wistar rats were randomly divided into four groups. The baseline group was sacrificed at the start of the study, and another group was sham operated. The remaining rats were ovariectomized and either given olive oil as a vehicle or treated with tocotrienol at a dose of 60 mg/kg body weight. After four weeks of treatment, blood was withdrawn for the measurement of interleukin-1 (IL1) and interleukin-6 (IL6) (bone resorbing cytokines), serum osteocalcin (a bone formation marker) and pyridinoline (a bone resorption marker).

    RESULTS: Tocotrienol supplementation in ovariectomized rats significantly reduced the levels of osteocalcin, IL1 and IL6. However, it did not alter the serum pyridinoline level.

    CONCLUSION: Tocotrienol prevented osteoporotic bone loss by reducing the high bone turnover rate associated with estrogen deficiency. Therefore, tocotrienol has the potential to be used as an anti-osteoporotic agent in postmenopausal women.

    Matched MeSH terms: Bone Resorption/drug therapy
  8. Sakthiswary R, Das S
    Curr Drug Targets, 2013 Dec;14(13):1552-7.
    PMID: 23848441
    Osteoporosis is a common complication observed in rheumatoid arthritis (RA). Accelerated bone loss is always a matter of concern. The pathogenesis of RA may be important for better understanding of the bone loss. The mechanism involved in the bone loss in RA is not well understood although cytokines such as interleukin 1 and tumour necrosis factor α (TNF α) have been strongly implicated. TNF α antagonists have revolutionised the treatment of RA in the recent years. Beyond the control of disease activity in RA, accumulating evidence suggests that this form of therapy may provide beneficial effects to the bone metabolism and remodeling. An extensive search of the literature was performed in the Medline, Scopus and EBSCO databases to evaluate the documented research on the effects of TNF α antagonists in RA on bone mineral density and bone turnover markers. The available data based on our systematic review, depict a significant association between TNF α antagonists treatment and suppression of bone resorption.
    Matched MeSH terms: Bone Resorption/drug therapy*
  9. Parvaneh K, Ebrahimi M, Sabran MR, Karimi G, Hwei AN, Abdul-Majeed S, et al.
    Biomed Res Int, 2015;2015:897639.
    PMID: 26366421 DOI: 10.1155/2015/897639
    Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects of Bifidobacterium longum (B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL of B. longum 10(8)-10(9) colony forming units (CFU)/mL). B. longum was given once daily for 16 weeks, starting from 2 weeks after the surgery. The B. longum supplementation increased (p < 0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p < 0.05) the expression of Sparc and Bmp-2 genes. B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation.
    Matched MeSH terms: Bone Resorption/drug therapy
  10. Shalan NA, Mustapha NM, Mohamed S
    Nutrition, 2017 Jan;33:42-51.
    PMID: 27908549 DOI: 10.1016/j.nut.2016.08.006
    OBJECTIVE: Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats.

    METHODS: Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh).

    RESULTS: The water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density.

    CONCLUSIONS: The catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women.

    Matched MeSH terms: Bone Resorption/drug therapy
  11. Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S
    Bone, 2018 11;116:8-21.
    PMID: 29990585 DOI: 10.1016/j.bone.2018.07.003
    Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienol has been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.
    Matched MeSH terms: Bone Resorption/drug therapy*
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