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  1. Fulltext Calcaneal quantitative ultrasound as a determinant of bone health status: what properties of bone does it reflect?
    Chin KY, Ima-Nirwana S
    Int J Med Sci, 2013;10(12):1778-83.
    PMID: 24273451 DOI: 10.7150/ijms.6765
    Quantitative ultrasound (QUS) has emerged as a convenient and popular screening tool for osteoporosis. This review aimed to provide basic information on the principle of QUS measurement and discuss the properties of bone reflected by QUS indices. QUS employed high frequency sound waves generated by the device to determine bone health status in humans. In vitro studies showed that QUS indices were significantly associated with bone mineral density (BMD), bone microarchitecture and mechanical parameters. In humans, QUS indices were found to be associated with BMD as well. In addition, QUS could discriminate subjects with and without fracture history and predict risk for future fracture. In conclusion, QUS is able to reflect bone quality and should be used in the screening of osteoporosis, especially in developing countries where dual-X-ray absorptiometry devices are less accessible to the general population.
    Matched MeSH terms: Osteoporosis/pathology
  2. Ficus deltoidea Prevented Bone Loss in Preclinical Osteoporosis/Osteoarthritis Model by Suppressing Inflammation
    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 
    Matched MeSH terms: Osteoporosis/pathology*
  3. Tocotrienols for bone health: a translational approach
    Shen CL, Klein A, Chin KY, Mo H, Tsai P, Yang RS, et al.
    Ann N Y Acad Sci, 2017 Aug;1401(1):150-165.
    PMID: 28891093 DOI: 10.1111/nyas.13449
    Osteoporosis, a degenerative bone disease, is characterized by low bone mass and microstructural deterioration of bone tissue resulting in aggravated bone fragility and susceptibility to fractures. The trend of extended life expectancy is accompanied by a rise in the prevalence of osteoporosis and concomitant complications in the elderly population. Epidemiological evidence has shown an association between vitamin E consumption and the prevention of age-related bone loss in elderly women and men. Animal studies show that ingestion of vitamin E, especially tocotrienols, may benefit bone health in terms of maintaining higher bone mineral density and improving bone microstructure and quality. The beneficial effects of tocotrienols on bone health appear to be mediated via antioxidant/anti-inflammatory pathways and/or 3-hydroxy-3-methylglutaryl coenzyme A mechanisms. We discuss (1) an overview of the prevalence and etiology of osteoporosis, (2) types of vitamin E (tocopherols versus tocotrienols), (3) findings of tocotrienols and bone health from published in vitro and animal studies, (4) possible mechanisms involved in bone protection, and (5) challenges and future direction for research.
    Matched MeSH terms: Osteoporosis/pathology
  4. Osteoporosis is associated with metabolic syndrome induced by high-carbohydrate high-fat diet in a rat model
    Wong SK, Chin KY, Suhaimi FH, Ahmad F, Jamil NA, Ima-Nirwana S
    Biomed Pharmacother, 2018 Feb;98:191-200.
    PMID: 29257979 DOI: 10.1016/j.biopha.2017.12.042
    This study aimed to investigate the bone quality in rats induced with metabolic syndrome (MetS) using high-carbohydrate high-fat (HCHF) diet. Male Wistar rats (n = 14) were randomized into two groups. The normal group was given standard rat chow. The MetS group was given HCHF diet. Diet regimen was assigned for a period of 20 weeks. Metabolic syndrome parameters were measured monthly until MetS was established. Left tibiae were scanned using micro-computed tomography at week 0, 8, 12, 16, and 20 to analyze the trabecular and cortical bone structure. At the end of the study, rats were euthanized and their bones were harvested for analysis. Metabolic syndrome was established at week 12 in the HCHF rats. Significant deterioration of trabecular bone was observed at week 20 in the HCHF group (p  0.05). Femur length and width in the HCHF group were significantly shorter than the normal group (p 
    Matched MeSH terms: Osteoporosis/pathology
  5. The use of delta-tocotrienol and lovastatin for anti-osteoporotic therapy
    Abdul-Majeed S, Mohamed N, Soelaiman IN
    Life Sci, 2015 Mar 15;125:42-8.
    PMID: 25534439 DOI: 10.1016/j.lfs.2014.12.012
    Statins are competitive inhibitors of HMGCoA reductase and are commonly used as antihypercholesterolemic agents. Experimental studies clearly demonstrate the beneficial effects of statins on bone. Tocotrienols have also been shown to have anti-osteoporotic effects on the skeletal system. This study was conducted to observe the effect of a combination of delta-tocotrienol and lovastatin on structural bone histomorphometry and bone biomechanical strength in a postmenopausal rat model at clinically tolerable doses, and to compare it with the effect of delta-tocotrienol or lovastatin.
    Matched MeSH terms: Osteoporosis/pathology
  6. Can soy prevent male osteoporosis? A review of the current evidence
    Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2013 Dec;14(14):1632-41.
    PMID: 24354587
    The Asian population whose soy intake is higher compared to Western populations shows a significantly lower incidence of osteoporotic fracture. Several meta-analyses have revealed that supplementation of soy isoflavones improve bone health status in women. This review examined the current evidence as to whether soy could exhibit similar bone protective effects on the male population. In vivo studies revealed that supplementation of soy protein or soy isoflavones improved bone health in both normal and osteoporotic male rodents. Cell culture studies showed that soy isoflavones influenced osteogenesis and osteoclastogenesis through mechanisms such as estrogen receptor binding activity, antiinflammatory activity and anti-parathyroid hormone activity. Soy isoflavones also affected calcium channel signaling and might exhibit direct effects on the osteoblastogenesis modulator, core binding factor 1. However, limited clinical trials involving soy intervention in males generally showed insignificant results. This could be attributed to the short duration of intervention, characteristics of the subjects or method of bone health assessment. More well-planned clinical trials are required to establish possible bone protective effects of soy in men.
    Matched MeSH terms: Osteoporosis/pathology
  7. Bone metabolism and histomorphometric changes in murine models treated with sclerostin antibody: a systematic review
    Das S, Sakthiswary R
    Curr Drug Targets, 2013 Dec;14(14):1667-74.
    PMID: 24354585
    Preventing osteoporotic fractures in millions of individuals may significantly reduce the associated morbidity and health-care expenditures incurred. As such, the search for newer anti-osteoporotic agents has been ongoing for years. Genetic studies have proven that the secreted protein sclerostin is one of the main culprits, which negatively regulates the bone formation. Recently, sclerostin-neutralizing monoclonal antibodies (Scl-Ab) in rodent studies have shown positive effects on bone homeostasis. An extensive search of the literature was performed in the BIOSIS, Cinahl, EMBASE, Pub- Med, Web of Science and Cochrane Library databases to evaluate the published murine studies on the effects of Scl-Ab on the bone metabolism and histomorphometric parameters. Our systematic review depicts a significant association between Scl-Ab administration and improvement in bone formation, bone density, bone volume and trabecular thickness.
    Matched MeSH terms: Osteoporosis/pathology
  8. Pathogenesis of alcohol-induced osteoporosis and its treatment: a review
    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: Osteoporosis/pathology
  9. Milk thistle: a future potential anti-osteoporotic and fracture healing agent
    Mohd Fozi NF, Mazlan M, Shuid AN, Isa Naina M
    Curr Drug Targets, 2013 Dec;14(14):1659-66.
    PMID: 24093748
    Osteoporosis is a progressive disease of the skeleton characterised by bone fragility due to a reduction in bone mass and possibly to alteration in bone architecture that lead to a propensity to fracture with minimum trauma. Most osteoporotic fractures occur at locations rich in trabecular or cancellous bone and usually related to post menopausal women. Recently, silymarin received attention due to its alternative beneficial effect on bone formation. It is a mixture of flavonoids with powerful antioxidant properties. This review focuses on the use of milk thistle or silymarin for the treatment of osteoporosis that may be related to fracture bone. Silymarin shows potent antioxidant herb that may modulate multiple genes in favour of helping to build bone and prevent bone loss. In the mouse fracture healing model, silymarin supplementation improved tibial healing with elevated BMD and serum levels of ALP and osteocalcin. Silymarin also demonstrated clear estrogenic antiosteoporotic effects in bone structure. Silymarin appears to play a crucial role to prevent bone loss and might regulate osteogenesis and may be beneficial for fracture healing. If silymarin is considered for the use of post menopausal women, it may be used for the treatment of osteoporosis. It would be of great benefit to postmenopausal women to develop an oestrogen antagonist that is as potent and efficacious as oestrogen in preventing bone loss without the major side effect associated with HRT.
    Matched MeSH terms: Osteoporosis/pathology
  10. Piper sarmentosum: a new hope for the treatment of osteoporosis
    Mohd Ramli ES, Suhaimi F, Ahmad F, Shuid AN, Mohamad N, Ima-Nirwana S
    Curr Drug Targets, 2013 Dec;14(14):1675-82.
    PMID: 24107234
    Osteoporosis is a major global health problem. Osteoporosis is characterized by the loss of bone mass and strength which leads to an increased risk of fracture. Glucocorticoid treatment is the leading cause of secondary osteoporosis. Glucocorticoid action in bone depends upon the expression of 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). The oestrogen deficient state causes osteoporosis due to enhancement of osteoclastogenesis by oxidative stress which leads to increased bone resorption. Piper sarmentosum (Daun Kaduk) is commonly used in the local cuisine of South East Asia. It is also traditionally used to treat many diseases such as inflammation, dermatitis and joint pain. Studies have revealed antioxidant properties through its flavonoids compound naringenin which acts as a superoxide scavenger that may help in the endogenous antioxidant defence system to protect bone against osteoporosis. Recent studies found that Ps extract has the ability to inhibit the expression and activity of 11β-HSD1 in adipose tissue and bone which restored bone structure and strength. It also accelerates fracture healing in the oestrogen deficient state through its antioxidant properties. The cost of conventional treatment is high and together with the adverse effects it leads to noncompliance. Treatment modalities with herbal medicine, less side effects and is cheaper need to be explored.This review focused on the therapeutic effect of Ps extract on fracture healing in ovariectomized rats and its protective effects against glucocorticoid induced osteoporotic rats.
    Matched MeSH terms: Osteoporosis/pathology
  11. Effects of tocotrienol from Bixa orellana (annatto) on bone histomorphometry in a male osteoporosis model induced by buserelin
    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 

    Matched MeSH terms: Osteoporosis/pathology
  12. Eurycoma longifolia as a potential alternative to testosterone for the treatment of osteoporosis: Exploring time-mannered proliferative, differentiative and morphogenic modulation in osteoblasts
    Thu HE, Mohamed IN, Hussain Z, Shuid AN
    J Ethnopharmacol, 2017 Jan 04;195:143-158.
    PMID: 27818256 DOI: 10.1016/j.jep.2016.10.085
    ETHNOPHARMACOLOGICAL RELEVANCE: Eurycoma longifolia (EL) has been well-studied traditionally as a chief ingredient of many polyherbal formulations for the management of male osteoporosis. It has also been well-recognised to protect against bone calcium loss in orchidectomised rats.

    AIM OF THE STUDY: To evaluate the effects of EL on the time-mannered sequential proliferative, differentiative, and morphogenic modulation in osteoblasts compared with testosterone.

    MATERIALS AND METHODS: Cell proliferation was analysed using MTS assay and phase contrast microscopy. Osteogenic differentiation of MC3T3-E1 cells was assessed through a series of characteristic assays which include crystal violet staining, alkaline phosphatase (ALP) activity and Van Gieson staining. Taken together, the bone mineralization of extra cellular matrix (ECM) was estimated using alizarin red s (ARS) staining, von kossa staining, scanning electron microscopic (SEM) and energy dispersive x-ray (EDX) analysis.

    RESULTS: The cell proliferation data clearly revealed the efficiency of EL particularly at a dose of 25µg/mL, in improving the growth of MC3T3-E1 cells compared with the untreated cells. Data also showed the prominence of EL in significantly promoting ALP activity throughout the entire duration of treatment compared with the testosterone-treated cells. The osteogenic differentiation potential of EL was further explored by analysing mineralization data which revealed that the calcified nodule formation (calcium deposition) and phosphate deposition was more pronounced in cells treated with 25µg/mL concentration of EL at various time points compared with the untreated and testosterone treated cells. The scanning electron microscopic (SEM) analysis also revealed highest globular masses of mineral deposits (identified as white colour crystals) in the ECM of cultured cells treated with 25µg/mL concentration of EL.

    CONCLUSION: Compared to testosterone, greater potential of EL in promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells provides an in vitro basis for the prevention of male osteoporosis. Thus, we anticipate that EL can be considered as an alternative approach to testosterone replacement therapy (TRT) for the treatment of male osteoporosis.

    Matched MeSH terms: Osteoporosis/pathology
  13. Fulltext Obstructive sleep apnoea syndrome (OSAS) as a risk factor for secondary osteoporosis in children
    Sies NS, Zaini AA, de Bruyne JA, Jalaludin MY, Nathan AM, Han NY, et al.
    Sci Rep, 2021 02 04;11(1):3193.
    PMID: 33542317 DOI: 10.1038/s41598-021-82605-6
    Repetitive hypoxia seen in obstructive sleep apnoea syndrome (OSAS) may affect bone metabolism increasing the risk for secondary osteoporosis. This study investigates the association between OSAS in children and secondary osteoporosis. This cross-sectional study included 150 children aged 10-17 years: 86 with OSAS and 64 with no OSAS. OSAS was confirmed by polysomnography. Quantitative ultrasound (QUS) of calcaneum measuring speed of sound (SoS) and broadband ultrasound attenuation (BUA) were collected. Other parameters collected including bone profile, vitamin D levels, physical activity scoring and dietary calcium intake. Majority were male and Malay ethnicity. OSAS children were mostly obese (84%) and 57% had moderate to severe OSAS. Most had lower physical activities scores. Mean (SD) phosphate and Alkaline phosphatase were lower in OSA children compared to controls: PO4, p = 0.039 and ALP, p 
    Matched MeSH terms: Osteoporosis/pathology*
  14. Regulatory actions of 3',5'-cyclic adenosine monophosphate on osteoclast function: possible roles of Epac-mediated signaling
    Jeevaratnam K, Salvage SC, Li M, Huang CL
    Ann N Y Acad Sci, 2018 Dec;1433(1):18-28.
    PMID: 29846007 DOI: 10.1111/nyas.13861
    Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.
    Matched MeSH terms: Osteoporosis/pathology
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