Displaying publications 1 - 20 of 43 in total

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  1. Harun NH, Froemming GRA, Mohd Ismail A, Nawawi H, Mokhtar SS, Abd Muid S
    Int J Mol Sci, 2022 Nov 23;23(23).
    PMID: 36498945 DOI: 10.3390/ijms232314616
    Low mineralization activity by human osteoblast cells (HOBs) indicates abnormal bone remodeling that potentially leads to osteoporosis. Oxidation, the most prominent form of high-density lipoprotein (HDL) modification, is suggested to affect bone mineralization through the inflammatory pathway. Adiponectin, which possesses anti-inflammatory activity, is postulated to have the ability to suppress the detrimental effects of oxidized HDL (oxHDL). This study aimed to investigate the effects of HDL before and after oxidation on markers of mineralization and inflammation. The protective effects of adiponectin on demineralization and inflammation induced by oxHDL were also investigated. OxHDL at 100 µg/mL protein had the highest inhibitory effect on mineralization, followed by lower calcium incorporation. OxHDL also had significantly lower expression of a mineralization marker (COL1A2) and higher expression of inflammatory markers (IL-6, TNF-α, and RELA proto-oncogene, NF-κβ (p65)) compared to the unstimulated control group. These findings suggest that oxHDL reduces the mineralization activity of HOBs by increasing the expression of inflammatory markers. Interestingly, co-incubation of adiponectin and oxHDL in HOBs resulted in higher expression of mineralization markers (ALPL, COL1A2, BGLAP, and RUNX2) and significantly reduced all targeted inflammatory markers compared to the oxHDL groups. On the contrary, HDL increased the expression of mineralization markers (COL1A2 and STAT-3) and exhibited lower expression of inflammatory cytokines (IL-6 and TNF-α), proving the protective effect of HDL beyond the reverse cholesterol transport activity.
    Matched MeSH terms: Bone Remodeling
  2. Abdulhameed EA, Al-Rawi NH, Omar M, Khalifa N, Samsudin ABR
    PeerJ, 2022;10:e12951.
    PMID: 35261818 DOI: 10.7717/peerj.12951
    BACKGROUND: Titanium dioxide dental implants have a controversial effect on reactive oxygen species (ROS) production. ROS is necessary for cellular signal transmission and proper metabolism, but also has the ability to cause cell death as well as DNA, RNA, and proteins damage by excessive oxidative stress. This study aimed to systematically review the effect of titanium dioxide dental implant-induced oxidative stress and its role on the osteogenesis-angiogenesis coupling in bone remodeling.

    METHODS: This systematic review was performed conforming to preferred reporting items for systematic review and meta-analysis (PRISMA) model. Four different databases (PubMed, Science Direct, Scopus and Medline databases) as well as manual searching were adopted. Relevant studies from January 2000 till September 2021 were retrieved. Critical Appraisal Skills Programme (CASP) was used to assess the quality of the selected studies.

    RESULTS: Out of 755 articles, only 14 which met the eligibility criteria were included. Six studies found that titanium dioxide nanotube (TNT) reduced oxidative stress and promoted osteoblastic activity through its effect on Wnt, mitogen-activated protein kinase (MAPK) and forkhead box protein O1 (FoxO1) signaling pathways. On the other hand, three studies confirmed that titanium dioxide nanoparticles (TiO2NPs) induce oxidative stress, reduce ostegenesis and impair antioxidant defense system as a significant negative correlation was found between decreased SIR3 protein level and increased superoxide (O2 •-). Moreover, five studies proved that titanium implant alloy enhances the generation of ROS and induces cytotoxicity of osteoblast cells via its effect on NOX pathway.

    CONCLUSION: TiO2NPs stimulate a wide array of oxidative stress related pathways. Scientific evidence are in favor to support the use of TiO2 nanotube-coated titanium implants to reduce oxidative stress and promote osteogenesis in bone remodeling. To validate the cellular and molecular cross talk in bone remodeling of the present review, well-controlled clinical trials with a large sample size are required.

    Matched MeSH terms: Bone Remodeling
  3. Arzmi MH, John A, Rismayuddin NAR, Kenali NM, Darnis DS
    Data Brief, 2021 Apr;35:106769.
    PMID: 33537383 DOI: 10.1016/j.dib.2021.106769
    Deer antler velvet (DAV) has been traditionally used in Chinese medicine, including treatment on toothache [1]. Due to its rapid and regenerative capacity, deer antlers were proposed to be the good model for bone remodelling in mammals [2]. The data presented in this work is on the liquid chromatography and mass spectrometry (LC-MS) profile and bioactive potential of Malayan deer antler velvet (DAV) on different Candida species that has clinical importance. Aqueous extraction of DAV samples was subjected to Liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) profiling. Reverse phase (RP) separation was used due to the process extraction using water as a solvent to separate polar compound. The data was interpreted using Profile Analysis 2.1V. The DAV samples were also tested for the effect on the biofilm formation of seven Candida species in a 96 well plate [3]. The biofilms were developed for 72 h in aerobic environment. Following that, the biofilms biomass was determined using crystal violet assay.
    Matched MeSH terms: Bone Remodeling
  4. Wu CH, Chang YF, Chen CH, Lewiecki EM, Wüster C, Reid I, et al.
    J Clin Densitom, 2021;24(1):3-13.
    PMID: 31010789 DOI: 10.1016/j.jocd.2019.03.004
    Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.
    Matched MeSH terms: Bone Remodeling
  5. Mohamad NV, Ima-Nirwana S, Chin KY
    Aging Male, 2020 Dec;23(5):327-334.
    PMID: 29495911 DOI: 10.1080/13685538.2018.1446075
    This study aimed to compare the skeletal effect between GnRH agonist therapy and orchidectomy in male rats assessed using serum turnover markers and bone histomorphometry. Three-month-old male Sprague-Dawley rats (n = 46) were divided into three experimental arms, baseline, buserelin, and orchidectomy. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline or buserelin acetate at 25 µg/kg or 75 µg/kg. In the orchidectomy arm, the rats were either sham-operated or orchidectomized. The rats were euthanized after the three-month treatment. Blood was collected for the evaluation of bone turnover markers. Femurs were harvested for bone histomorphometry examination. A significant increase in serum C-telopeptide of type 1 collagen was observed in the orchidectomized group compared with the sham group (p bone volume, number and significantly increased trabecular separation in rats compared with their respective controls (p bone microarchitecture and increased bone resorption similar to orchidectomy after three months.
    Matched MeSH terms: Bone Remodeling
  6. Ramli FF, Chin KY
    Diagnostics (Basel), 2020 Mar 06;10(3).
    PMID: 32155909 DOI: 10.3390/diagnostics10030145
    Bone turnover markers (BTMs) derived from the secretory activities of osteoblasts and the matrix-degrading activities of osteoclasts are useful in monitoring the progression of osteoporosis and the efficacy of anti-osteoporotic treatment. However, the usefulness of BTMs in predicting osteoporosis remains elusive. Osteocytes play a central role in regulating bone formation and resorption. The proteins secreted by osteocytes, such as fibroblast growth factor-23 (FGF23), sclerostin (SOST), and dickkopf-1 (DKK1), could be candidates for osteoporosis screening and fracture prediction. This review summarizes the current evidence on the potential of osteocyte-related proteins as biomarkers for osteoporosis and fracture prediction. The literature reports that SOST may be a potential marker for osteoporosis screening but not for fracture prediction. FGF23 is a potential marker for increased fracture risk, but more studies are needed to confirm its usefulness. The role of DKK1 as a marker to predict osteoporosis and fracture risk cannot be confirmed due to a lack of consistent evidence. In conclusion, circulating osteocyte markers are potential osteoporosis biomarkers, but more studies are warranted to validate their clinical use.
    Matched MeSH terms: Bone Remodeling
  7. Pang KL, Low NY, Chin KY
    Drug Des Devel Ther, 2020;14:4029-4051.
    PMID: 33061307 DOI: 10.2147/DDDT.S270829
    Denosumab is a receptor activator of nuclear factor kappa-Β ligand inhibitor, which suppresses the bone resorption process to preserve bone mass. It is usually recommended to postmenopausal women and men with high fracture risk. With the recent publication of the results from FREEDOM study and its extension, the long-term effect of denosumab in preventing fragility fractures has been put forward. This review aims at summarising the evidence of denosumab in reducing fracture risk and its safety derived from clinical studies. Most of the evidence are derived from FREEDOM trials up to 10 years of exposure. Denosumab is reported to prevent vertebral and non-vertebral fractures. It is also proven effective in Japanese women, patients with chronic kidney diseases and breast cancer patients receiving antineoplastic therapy. Denosumab discontinuation leads to high remodeling, loss of bone mineral density and increased fracture risk. These negative effects might be preventable by bisphosphonate treatment. The safety profile of denosumab is consistent with increased years of exposure. In conclusion, denosumab is a safe and effective option for reducing fracture risk among patients with osteoporosis.
    Matched MeSH terms: Bone Remodeling/drug effects
  8. Mohamad NV, Ima-Nirwana S, Chin KY
    PMID: 32496996 DOI: 10.2174/1871530320666200604160614
    Osteoporosis is one of the major health issues associated with menopause-related estrogen deficiency. Various reports suggest that the hormonal changes related to menopausal transition may lead to the derangement of redox homeostasis and ultimately oxidative stress. Estrogen deficiency and oxidative stress may enhance the expression of genes involved in inflammation. All these factors may contribute, in synergy, to the development of postmenopausal osteoporosis. Previous studies suggest that estrogen may act as an antioxidant to protect the bone against oxidative stress, and as an antiinflammatory agent in suppressing pro-inflammatory and pro-osteoclastic cytokines. Thus, the focus of the current review is to examine the relationship between estrogen deficiency, oxidative stress and inflammation, and the impacts of these phenomena on skeletal health in postmenopausal women.
    Matched MeSH terms: Bone Remodeling/physiology*
  9. Loh HH, Yee A, Loh HS
    Minerva Endocrinol., 2019 Dec;44(4):387-396.
    PMID: 30482008 DOI: 10.23736/S0391-1977.18.02867-5
    INTRODUCTION: Recent studies showed a possible association between hyperaldosteronism and secondary hyperparathyroidism leading to reduced bone health, however results are conflicting.

    EVIDENCE ACQUISITION: We conducted a meta-analysis to evaluate the relationship between primary aldosteronism (PA) with bone biochemical markers and to assess bone mineral density in patients with primary aldosteronism.

    EVIDENCE SYNTHESIS: A total of 939 subjects were examined (37.5% with PA). Patients with PA had significantly higher serum parathyroid hormone, lower serum calcium, higher urine calcium excretion and higher serum alkaline phosphatase compared to patients without PA, with no significant difference in serum vitamin D between both groups. Bone mineral density of lumbar spine, femoral neck and total neck of femur were similar between two groups. With PA treatment, there was a significant increment in serum calcium and reduction in serum parathyroid hormone.

    CONCLUSIONS: PA is associated with hypercalciuria with subsequent secondary hyperparathyroidism. This potentially affects bone health. We recommend this to be part of complication screening among patients with PA.

    Matched MeSH terms: Bone Remodeling
  10. Le MHT, Noor Hayaty AK, Zaini ZM, Dom SM, Ibrahim N, Radzi ZB
    Korean J Orthod, 2019 Jul;49(4):235-245.
    PMID: 31367578 DOI: 10.4041/kjod.2019.49.4.235
    Objective: This study examined bone microstructure restoration after rapid maxillary expansion (RME) with and without corticotomy over multiple retention periods.

    Methods: Eighteen male Dorper sheep were randomly distributed into three groups (n = 6 each group): group 1, RME with corticotomy on the buccal and palatal sides; group 2, conventional RME treatment; and group 3, no treatment. Post-RME, trabecular bone microstructure and new bone formation were evaluated by using microcomputed tomography (microCT) and histomorphometry after a 4- or 12-week retention period. Intergroup differences in bone quality and bone remodeling were analyzed by using two-way analysis of variance with Bonferroni post-hoc test.

    Results: The bone volume fraction (bone volume [BV]/total volume [TV]) values relative to the control in groups 1 and 2 were 54.40% to 69.88% after the 4-week retention period and returned to approximately 80% after the 12-week retention period. The pooled BV/TV values of the banded teeth in groups 1 and 2 were significantly lower than those of the control after the 4-week retention period (p < 0.05). However, after the 12-week retention period, the pooled BV/TV values in group 2 were significantly lower than those in groups 1 and 3 (p < 0.05). Histomorphological analysis showed that the new bone formation area in group 1 was approximately two to three times of those in group 2 and control.

    Conclusions: Corticotomy significantly enhanced the restoration of bone quality after the retention periods for banded teeth. This benefit might result from the increased new bone formation after corticotomy.

    Matched MeSH terms: Bone Remodeling
  11. Kamaruzzaman MA, Chin KY, Mohd Ramli ES
    PMID: 31641368 DOI: 10.1155/2019/8543618
    Bone remodelling is a complex and tightly regulated process. Disruption of bone remodelling skewing towards resorption will cause osteoporosis and increase the risk of fragility fracture. Honey is a natural product containing various bioactive ingredients with health benefits, especially polyphenols. Therefore, honey may be a novel dietary supplement to prevent osteoporosis. This review aims to summarize the current evidence on the effects of honey on bone health. The evidence reported so far indicates a skeletal-beneficial effect of honey in animal models of osteoporosis. However, the number of studies on humans is limited. Honey can protect the bone via its antioxidant and anti-inflammatory properties, primarily through its polyphenol content that acts upon several signalling pathways, leading to bone anabolic and antiresorptive effects. In conclusion, honey is a potential functional food for bone health, but the dose and the bioactive contents of honey need to be verified prior to its application in humans.
    Matched MeSH terms: Bone Remodeling
  12. Kruger MC, Chan YM, Lau LT, Lau CC, Chin YS, Kuhn-Sherlock B, et al.
    Eur J Nutr, 2018 Dec;57(8):2785-2794.
    PMID: 28975432 DOI: 10.1007/s00394-017-1544-6
    PURPOSE: In Malaysia, hip fracture incidence is higher in Chinese women than other ethnic groups. This study compared the effects of a high-calcium vitamin D fortified milk with added FOS-inulin versus regular milk over 1 year on aspects of bone health in Chinese postmenopausal women in Malaysia.

    METHODS: One-hundred and twenty-one women (mean age 59 (± 4) years) were randomized into two groups: control (n = 60; regular milk, 428 mg calcium per day) or intervention (n = 61; fortified milk at 1200 mg calcium, 96 mg magnesium, 2.4 mg zinc, 15 μg vitamin D and 4 g FOS-inulin per day). At baseline, weeks 12, 24, 36 and 52, parathyroid hormone (PTH), C-Telopeptide of Type I Collagen (CTx-1), Procollagen I Intact N-Terminal propeptide (PINP) and vitamin D levels were assessed. Bone density (BMD) was measured at baseline and week 52 using a GE Lunar iDXA.

    RESULTS: Body mass index, lumbar spine and femoral neck BMD did not differ between groups at baseline. Over 52 weeks, mean plasma 25 (OH) D3 levels increased to 74.8 nmol/L (intervention group) or remained at 63.1 nmol/L (control group) (p bone turnover markers and tended to increase femoral neck BMD.

    Matched MeSH terms: Bone Remodeling*
  13. Che Ahmad Tantowi NA, Lau SF, Mohamed S
    Calcif. Tissue Int., 2018 10;103(4):388-399.
    PMID: 29808374 DOI: 10.1007/s00223-018-0433-1
    Osteoporosis (OP) and osteoarthritis (OA) are debilitating musculoskeletal diseases of the elderly. Ficus deltoidea (FD) or mistletoe fig, a medicinal plant, was pre-clinically evaluated against OP- and OA-related bone alterations, in postmenopausal OA rat model. Thirty twelfth-week-old female rats were divided into groups (n = 6). Four groups were bilateral ovariectomized (OVX) and OA-induced by intra-articular monosodium iodoacetate (MIA) injection into the right knee joints. The Sham control and OVX-OA non-treated groups were given deionized water. The three other OVX-OA groups were orally administered daily with FD extract (200, 400 mg/kg) or diclofenac (5 mg/kg) for 4 weeks. The rats' bones and blood were evaluated for protein and mRNA expressions of osteoporosis and inflammatory indicators, and micro-CT computed tomography for bone microstructure. The non-treated OVX-OA rats developed severe OP bone loss and bone microstructural damage in the subchondral and metaphyseal regions, supported by reduced serum bone formation markers (osteocalcin, osteoprotegerin) and increased bone resorption markers (RANKL and CTX-I). The FD extract significantly (p bone microstructural and biomarker changes by dose-dependently down-regulating pro-inflammatory NF-κβ, TNF-α, and IL-6 mRNA expressions. The FD extract demonstrated good anti-osteoporotic properties in this OP/OA preclinical model by stimulating bone formation and suppressing bone resorption via anti-inflammatory pathways. This is among the few reports relating the subchondral bone plate and trabecular thickening with the metaphyseal trabecular osteopenic bone loss under osteoporotic-osteoarthritis conditions, providing some insights on the debated inverse relationship between osteoporosis and osteoarthritis.
    Matched MeSH terms: Bone Remodeling/drug effects
  14. Alias MA, Buenzli PR
    Biomech Model Mechanobiol, 2018 Oct;17(5):1357-1371.
    PMID: 29846824 DOI: 10.1007/s10237-018-1031-x
    The geometric control of bone tissue growth plays a significant role in bone remodelling, age-related bone loss, and tissue engineering. However, how exactly geometry influences the behaviour of bone-forming cells remains elusive. Geometry modulates cell populations collectively through the evolving space available to the cells, but it may also modulate the individual behaviours of cells. To factor out the collective influence of geometry and gain access to the geometric regulation of individual cell behaviours, we develop a mathematical model of the infilling of cortical bone pores and use it with available experimental data on cortical infilling rates. Testing different possible modes of geometric controls of individual cell behaviours consistent with the experimental data, we find that efficient smoothing of irregular pores only occurs when cell secretory rate is controlled by porosity rather than curvature. This porosity control suggests the convergence of a large scale of intercellular signalling to single bone-forming cells, consistent with that provided by the osteocyte network in response to mechanical stimulus. After validating the mathematical model with the histological record of a real cortical pore infilling, we explore the infilling of a population of randomly generated initial pore shapes. We find that amongst all the geometric regulations considered, the collective influence of curvature on cell crowding is a dominant factor for how fast cortical bone pores infill, and we suggest that the irregularity of cement lines thereby explains some of the variability in double labelling data as well as the overall speed of osteon infilling.
    Matched MeSH terms: Bone Remodeling
  15. 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 bone volume, trabecular thickness and osteoblast number, as well as a significantly lower single-labelled surface compared with the buserelin control (P bone loss by increasing the mineralising surface and osteoblasts number. Thus, it has a potential role in preventing bone loss in men using GnRH agonist.

    Matched MeSH terms: Bone Remodeling/drug effects*; Bone Remodeling/physiology
  16. Jayusman PA, Mohamed IN, Shuid AN
    Int J Endocrinol Metab, 2018 Jul;16(3):e64038.
    PMID: 30197659 DOI: 10.5812/ijem.64038
    Background: Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone.

    Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats.

    Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis.

    Results: Bilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group. However, no significant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups.

    Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

    Matched MeSH terms: Bone Remodeling
  17. Jayusman PA, Mohamed IN, Alias E, Mohamed N, Shuid AN
    Nutrients, 2018 Jun 21;10(7).
    PMID: 29933617 DOI: 10.3390/nu10070799
    Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats. Ninety-six male Sprague⁻Dawley rats were randomly assigned to baseline, sham-operated (Sham), orchidectomised or chemically castrated groups. Chemical castration was achieved via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomised and degarelix-castrated rats were then divided into negative control groups (ORX, DGX), testosterone-treated groups (intramuscular injection at 7 mg/kg weekly) (ORX + TES, DGX + TES), and EL-supplemented groups receiving daily oral gavages at doses of 25 mg/kg (ORX + EL25, DGX + EL25), 50 mg/kg (ORX + EL50, DGX + EL50), and 100 mg/kg (ORX + EL100, DGX + EL100). Following 10 weeks of treatment, the rats were euthanized and their blood and femora were collected. Bone biochemical markers, serum testosterone, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa β-ligand (RANKL) levels and histomorphometric indices were evaluated. Quassinoid-rich EL supplementation was found to reduce degenerative changes of trabecular structure by improving bone volume, trabecular number, and separation. A reduction in the percentage of osteoclast and increase in percentage of osteoblast on bone surface were also seen with EL supplementation. Dynamic histomorphometric analysis showed that the single-labeled surface was significantly decreased while the double-labeled surface was significantly increased with EL supplementations. There was a marginal but significant increase in serum testosterone levels in the ORX + EL25, DGX + EL50, and DGX + EL100 groups compared to their negative control groups. Quassinoid-rich EL extract was effective in reducing skeletal deteriorations in the androgen-deficient osteoporosis rat model.
    Matched MeSH terms: Bone Remodeling/drug effects*
  18. Loh HH, Kamaruddin NA, Zakaria R, Sukor N
    Minerva Endocrinol., 2018 Jun;43(2):117-125.
    PMID: 28001017 DOI: 10.23736/S0391-1977.16.02553-0
    BACKGROUND: Recent studies showed association between hyperaldosteronism and low bone density among patients with primary aldosteronism (PA) due to secondary hyperparathyroidism. Our objective is to assess bone turnover markers (BTM) and bone mineral density (BMD) of PA patients compared to essential hypertension.

    METHODS: This was an open-label, prospective, case-controlled study, conducted over 12 months. Fifty-two consecutive patients referred for secondary hypertension were screened. Eighteen patients with confirmed PA (diagnosis based on the Endocrine Society clinical guideline) and seventeen matched controls with essential hypertension were recruited. BTM (CTX and P1NP), BMD, intact parathyroid hormone (iPTH), and bone profile were assessed at baseline and three months following treatment among the PA patients. Calcium intake was assessed using a validated questionnaire. Primary outcomes were the changes of bone markers and BMD following treatment of PA, and their relation to other parameters.

    RESULTS: PA patients had significantly lower serum calcium and higher iPTH despite comparable vitamin D levels with control group. Both BTM were significantly higher among the PA group. BMD of lumbar spine, neck of femur and distal radius did not differ between groups. Three months following treatment, there were significant: 1) reduction in BTM; 2) improvement in the lumbar spine BMD; 3) reduction in iPTH level; and 4) increment of serum 25-OH vitamin D level.

    CONCLUSIONS: Our findings support that bone loss and potential fracture risk among PA patients are likely a result of aldosterone-mediated secondary hyperparathyroidism. Patients with early PA may already exhibit increased bone turnover despite no significant changes in BMD.

    Matched MeSH terms: Bone Remodeling*
  19. Alazzawi MMJ, Husein A, Alam MK, Hassan R, Shaari R, Azlina A, et al.
    Prog Orthod, 2018 Apr 16;19(1):10.
    PMID: 29658096 DOI: 10.1186/s40510-018-0208-2
    BACKGROUND: Quality bone regeneration, which leads to the improvement of bone remodeling, is essential for orthodontic treatment. In order to improve bone regeneration and increase the amount of tooth movement, different techniques have been implemented. The object of this study is to compare the effects of low-level laser therapy (LLLT), low-intensity pulsed ultrasound (LIPUS), and their combination on bone remodeling during orthodontic tooth movement.

    METHODS: Eighty (80) male, 6-week-old Sprague Dawley rats were grouped in to four groups, the first group was irradiated with (940 nm) diode laser, second group with LIPUS, and third group with combination of both LLLT and LIPUS. A forth group used was a control group in an incomplete block split-mouth design. The LLLT and LIPUS were used to treat the area around the moving tooth once a day on days 0-7, then the experiment was ended in each experimental endpoint (1, 3, 7, 14, and 21 days). For amount of tooth movement, models were imaged and analyzed. Histological examination was performed after staining with (hematoxylin and eosin) and (alizarin red and Alcian Blue) stain. One step reverse transcription-polymerase chain reaction RT-PCR was also performed to elucidate the gene expression of RANK, RANKL, OPG, and RUNX-2.

    RESULTS: The amount of tooth movement, the histological bone remodeling, and the RT-PCR were significantly greater in the treatment groups than that in the control group. Among the treatment groups, the combination group was the highest and the LIPUS group was the lowest.

    CONCLUSION: These findings suggest that LLLT and LIPUS can enhance the velocity of tooth movement and improve the quality of bone remodeling during orthodontic tooth movement.

    Matched MeSH terms: Bone Remodeling*
  20. 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.

    Matched MeSH terms: Bone Remodeling/drug effects*
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