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  1. Mohamad NV, Ima-Nirwana S, Chin KY
    Biomed Pharmacother, 2021 May;137:111368.
    PMID: 33582449 DOI: 10.1016/j.biopha.2021.111368
    Tocotrienol has been shown to prevent bone loss in animal models of postmenopausal osteoporosis, but the low oral bioavailability might limit its use. A self-emulsifying drug delivery system (SEDDS) could increase the bioavailability of tocotrienol. However, evidence of this system in improving the skeletal effects of tocotrienol is scanty. This study aims to evaluate the therapeutic efficacy of annatto tocotrienol with SEDDS in a rat model of postmenopausal bone loss. Ten-month-old female Sprague Dawley rats were randomized into six groups. The baseline group was euthanatized at the onset of the study. Four other groups underwent ovariectomy to induce estrogen deficiency. The sham underwent similar surgery procedure, but their ovaries were retained. Eight weeks after surgery, the ovariectomized rats received one of the four different regimens orally daily: (a) SEDDS, (b) annatto tocotrienol [60 mg/kg body weight (b.w.)] without SEDDS, (c) annatto-tocotrienol (60 mg/kg b.w.) with SEDDS, (d) raloxifene (1 mg/kg b.w.). After eight weeks of treatment, blood was collected for the measurement of delta-tocotrienol level and oxidative stress markers. The rats were euthanized and their bones were harvested for the evaluation of the bone microstructure, calcium content and strength. Circulating delta-tocotrienol level was significantly higher in rats receiving annatto tocotrienol with SEDDS compared to the group receiving unformulated annatto-tocotrienol (p 
    Matched MeSH terms: Osteoporosis, Postmenopausal/prevention & control*
  2. Toh LS, Lai PSM, Low BY, Wong KT, Anderson C
    Int J Clin Pharm, 2020 Feb;42(1):11-17.
    PMID: 32221825 DOI: 10.1007/s11096-019-00960-x
    Background Population screening for osteoporosis using bone mineral density scan is not feasible in Malaysia as this test is costly. Hence, there is a need to develop a more efficient method to screen for osteoporosis.Objectives To determine the feasibility of an interprofessional collaborative osteoporosis screening programme (IPC-OSP). Methods Postmenopausal women aged ≥ 50 years, who had not been diagnosed with osteoporosis were recruited from a primary care clinic from June to August 2014. Patients were assessed for their osteoporosis risk and were counselled on prevention methods. Patients at risk were referred to the doctor with a recommendation for a bone mineral density (BMD) scan. Results Fifty out of 55 patients were recruited (response rate = 90.9%). A total 26/50 (52.0%) went for a bone mineral density scan, none were osteoporotic, 17/50 (34%) were osteopenic, 2/50 (4.0%), were started on osteoporosis medications and 14/50 (28%) modified their lifestyle to improve bone health or started on calcium supplements. Osteoporosis knowledge significantly increased from baseline to month two (46.3 ± 21.4 vs. 79.1 ± 14.3, p 
    Matched MeSH terms: Osteoporosis, Postmenopausal/epidemiology*
  3. 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: Osteoporosis, Postmenopausal/diagnosis; Osteoporosis, Postmenopausal/drug therapy; Osteoporosis, Postmenopausal/metabolism*
  4. Mohammadi F, Amirzadeh Iranagh J, Motalebi SA, Hamid TA
    Women Health, 2019 02;59(2):145-154.
    PMID: 29400628 DOI: 10.1080/03630242.2018.1434592
    This study examined the relationship between reproductive characteristics and bone mineral density (BMD) in postmenopausal women who had been referred to the menopause clinics of the National Population and Family Development Board and of the Hospital Kuala Lumpur from July 2011 to January 2012. The participants of this study were 201 postmenopausal Malaysian women aged 45-71 years. Some socio-demographic, lifestyle, and reproductive factors were recorded. Calcaneal BMD was measured by quantitative ultra-sonography. Correlations of reproductive factors with BMD were assessed by Pearson's correlation test and multiple regression analysis. Age at menopause was not significantly correlated with BMD, while the years after menopause, age at the first menstrual period, number of pregnancies, and total lactation periods were inversely correlated with it. Among reproductive factors, only the association between lactation duration and BMD remained significant after adjusting for age, body mass index, activity, and calcium intake. The results indicated that except for prolonged total time of lactation, other reproductive factors were not significantly associated with BMD in postmenopausal women.
    Matched MeSH terms: Osteoporosis, Postmenopausal/epidemiology*
  5. Lim SY, Zalilah MS, Chin YS, Ramachandran V, Chan YM
    Nutrients, 2018 Jul 17;10(7).
    PMID: 30018240 DOI: 10.3390/nu10070915
    The interaction of dietary and genetic factors may affect the development of bone deterioration. This study investigated whether the effects of dietary acid load (DAL) on bone loss in postmenopausal Chinese women were moderated by the insulin-like growth factor-1 (IGF-1) single nucleotide polymorphism, a known gene that plays a role in the regulation of bone formation and bone remodeling. A total of 217 healthy participants were recruited from the National Council of Senior Citizens Organizations Malaysia. Serum collagen type 1 cross-linked C-telopeptide was used as a surrogate bone marker to assess bone resorption and Agena® MassARRAY genotyping analysis was used to identify the signaling of IGF-1 rs35767. The dietary acid load was measured by potential renal acid load score while physical activity was ascertained using the Global Physical Activity Questionnaire. Hierarchical regression was applied to test the main and interaction effects of DAL and IGF-1 genotypes in bone resorption. The result supported the diet-dependent acid-base balance theory that higher DAL was positively associated with bone resorption (β = 0.152, p = 0.031, F(6,207) = 2.11, sig-F = 0.036, R² = 0.079). However, the results indicated that there was no significant correlation between IGF-1 and bone resorption, or any significant interaction between DAL and IGF-1. In conclusion, there was no moderating effect of IGF-1 on the relationship between DAL and bone resorption.
    Matched MeSH terms: Osteoporosis, Postmenopausal/ethnology; Osteoporosis, Postmenopausal/etiology*; Osteoporosis, Postmenopausal/genetics; Osteoporosis, Postmenopausal/epidemiology
  6. Nik Mohd Hatta NNK, Lokman M, Said N M, Daud A, Ibrahim M, Sharifudin MA, et al.
    Enferm Clin, 2018 Feb;28 Suppl 1:232-235.
    PMID: 29650194 DOI: 10.1016/S1130-8621(18)30074-3
    OBJECTIVE: The study aims to identify the risk of obtaining a fracture among post-menopausal women with osteopenia and osteoporosis.

    METHOD: This work was a cross-sectional study involving a purposive sample of 87 post-menopausal women who attended the orthopedic and menopause clinics of Hospital Tengku Ampuan Afzan, Kuantan. The data were entered into the WHO fracture risk assessment tool (FRAX®) to predict major fracture and risk for hip fracture in 10 years' time.

    RESULTS: The mean age of the respondents was 61.6 years (SD=7.9). Among the respondents, 50.6% had osteopenia and nearly half (48.3%) had osteoporosis. The mean number of menopausal years of the respondents was 11.9 (SD=8.5), ranging between 1 and 44 years. The FRAX findings indicated 9.7% major osteoporotic fracture probability and 3.5% hip fracture probability, which were denoted as high risk. A Pearson correlation coefficient was computed to assess the relationship between menopausal years and the FRAX major osteoporotic fracture probability. A significant positive correlation was found between the two, but the correlation was weak (r=0.581, n=87, p < 0.001).

    CONCLUSIONS: The present findings indicate that menopausal years have a positive correlation with the risk of obtaining a fracture.

    Study site: orthopedic and menopause clinics of Hospital Tengku Ampuan Afzan, Kuantan.
    Matched MeSH terms: Osteoporosis, Postmenopausal*
  7. Bokhari RA, Lau SF, Mohamed S
    Menopause, 2018 02;25(2):202-210.
    PMID: 28926512 DOI: 10.1097/GME.0000000000000980
    OBJECTIVE: Orthosiphon stamineus (OS) or Misai Kucing (Java tea) is a popular herbal supplement from Southeast Asia for various metabolic, age-related diseases. This study investigated the potential use of OS leaf extracts to ameliorate osteoporosis in ovariectomized rats.

    METHODS: Fifty-six female Sprague-Dawley rats were randomly allocated into eight groups (n = 7): SHAM (healthy sham control); OVX (ovarietomized) nontreated rats (negative control); OVX + Remifemin (100 mg/kg body weight), and 2% green tea extract (positive controls); OVX + OS 50% ethanolic and aqueous extracts, both at either 150 or 300 mg/kg. After 16 weeks, the rats' bones and blood were evaluated for osteoporosis indicators (protein and mRNA expressions), micro-computed tomography for bone histomorphometry, and three-point bending test for tibia mechanical strength.

    RESULTS: The extracts dose-dependently and significantly (P 

    Matched MeSH terms: Osteoporosis, Postmenopausal/metabolism; Osteoporosis, Postmenopausal/pathology; Osteoporosis, Postmenopausal/prevention & control*
  8. Parvaneh M, Karimi G, Jamaluddin R, Ng MH, Zuriati I, Muhammad SI
    Clin Interv Aging, 2018;13:1555-1564.
    PMID: 30214175 DOI: 10.2147/CIA.S169223
    Purpose: Osteoporosis is one of the major health concerns among the elderly population, especially in postmenopausal women. Many menopausal women over 50 years of age lose their bone density and suffer bone fractures. In addition, many mortality and morbidity cases among the elderly are related to hip fracture. This study aims to investigate the effect of Lactobacillus helveticus (L. helveticus) on bone health status among ovariectomized (OVX) bone loss-induced rats.

    Methods: The rats were either OVX or sham OVX (sham), then were randomly assigned into three groups, G1: sham, G2: OVX and G3: OVX+L. helveticus (1 mL of 108-109 colony forming units). The supplementation was force-fed to the rats once a day for 16 weeks while control groups were force-fed with demineralized water.

    Results: L. helveticus upregulated the expression of Runx2 and Bmp2, increased serum osteocalcin, bone volume/total volume and trabecular thickness, and decreased serum C-terminal telopeptide and total porosity percentage. It also altered bone microstructure, as a result increasing bone mineral density and bone strength.

    Conclusion: Our results indicate that L. helveticus attenuates bone remodeling and consequently improves bone health in OVX rats by increasing bone formation along with bone resorption reduction. This study suggests a potential therapeutic effect of L. helveticus (ATCC 27558) on postmenopausal osteoporosis.

    Matched MeSH terms: Osteoporosis, Postmenopausal/prevention & control*
  9. Venugopal Y, Hatta SFWM, Musa N, Rahman SA, Ratnasingam J, Paramasivam SS, et al.
    Asia Pac J Clin Nutr, 2017 May;26(3):412-420.
    PMID: 28429905 DOI: 10.6133/apjcn.042016.10
    BACKGROUND AND OBJECTIVES: Vitamin D3 (cholecalciferol) dose required to maintain sufficiency in non- Caucasian women with postmenopausal osteoporosis (PMO) inthe tropics has not been well studied. Some guidelines mandate 800-1000 IU vitamin D/day but the Endocrine Society (US) advocates 1500-2000 IU/day to maintain 25-hydroxyvitamin-D (25(OH)D) concentration at >75 nmol/L. We aimed to establish oral cholecalciferol dose required to maintain 25(OH)D concentration at >75 nmol/L in PMO Chinese Malaysian women, postulating lower dose requirements amongst light-skinned subjects in the tropics.

    METHODS AND STUDY DESIGN: 90 Chinese Malaysian PMO women in Kuala Lumpur, Malaysia (2°30'N) with baseline serum 25(OH)D levels >=50 nmol/L were recruited. Prior vitamin D supplements were discontinued and subjects randomized to oral cholecalciferol 25,000 IU/4-weekly (Group-A) or 50,000 IU/4-weekly (Group- B) for 16 weeks, administered under direct observation. Serum 25(OH)D, PTH, serum/urinary calcium were measured at baseline, 8 and 16 weeks.

    RESULTS: Baseline characteristics, including osteoporosis severity, sun exposure (~3 hours/week), and serum 25(OH)D did not differ between treatment arms. After 16 weeks, 91% of women sufficient at baseline, remained sufficient on 25,000 IU/4-weekly compared with 97% on 50,000 IU/4-weekly with mean serum 25(OH)D 108.1±20.4 and 114.7±18.4 SD nmol/L respectively (p=0.273). At trial's end, 39% and 80% of insufficient women at baseline attained sufficiency in Group A and Group B (p=0.057). Neither dose was associated with hyperparathyroidism or toxicity.

    CONCLUSIONS: Despite pretrial vitamin D supplementation and adequate sun exposure, 25.6% Chinese Malaysian PMO women were vitamin D insufficient indicating sunshine alone cannot ensure sufficiency in the tropics. Both ~900 IU/day and ~1800 IU/day cholecalciferol can safely maintain vitamin D sufficiency in >90% of Chinese Malaysian PMO women. Higher doses are required with baseline concentration <75 nmol/L.
    Matched MeSH terms: Osteoporosis, Postmenopausal/drug therapy*
  10. Wen HJ, Huang TH, Li TL, Chong PN, Ang BS
    Osteoporos Int, 2017 02;28(2):539-547.
    PMID: 27613719 DOI: 10.1007/s00198-016-3759-4
    Measurement of bone turnover markers is an alternative way to determine the effects of exercise on bone health. A 10-week group-based step aerobics exercise significantly improved functional fitness in postmenopausal women with low bone mass, and showed a positive trend in reducing resorption activity via bone turnover markers.

    INTRODUCTION: The major goal of this study was to determine the effects of short-term group-based step aerobics (GBSA) exercise on the bone metabolism, bone mineral density (BMD), and functional fitness of postmenopausal women (PMW) with low bone mass.

    METHODS: Forty-eight PMW (aged 58.2 ± 3.5 years) with low bone mass (lumbar spine BMD T-score of -2.00 ± 0.67) were recruited and randomly assigned to an exercise group (EG) or to a control group (CG). Participants from the EG attended a progressive 10-week GBSA exercise at an intensity of 75-85 % of heart rate reserve, 90 min per session, and three sessions per week. Serum bone metabolic markers (C-terminal telopeptide of type 1 collagen [CTX] and osteocalcin), BMD, and functional fitness components were measured before and after the training program. Mixed-models repeated measures method was used to compare differences between the groups (α = 0.05).

    RESULTS: After the 10-week intervention period, there was no significant exercise program by time interaction for CTX; however, the percent change for CTX was significantly different between the groups (EG = -13.1 ± 24.4 % vs. CG = 11.0 ± 51.5 %, P 

    Matched MeSH terms: Osteoporosis, Postmenopausal/blood; Osteoporosis, Postmenopausal/physiopathology; Osteoporosis, Postmenopausal/rehabilitation
  11. 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.

    Matched MeSH terms: Osteoporosis, Postmenopausal/metabolism; Osteoporosis, Postmenopausal/prevention & control*
  12. Benjamin B, Benjamin MA, Swe M, Sugathan S
    Osteoporos Sarcopenia, 2016 Jun;2(2):77-81.
    PMID: 30775470 DOI: 10.1016/j.afos.2016.03.003
    Objectives: Osteoporosis is a rapidly rising cause of concern for elderly patients. Various classes of drugs are available in the market. Bisphosphonates are considered as a first-line therapy for the prevention and treatment. Denosumab is an antiresorptive agent which is a RANK ligand inhibitor. There is a scarcity of comparison between these two classes of drugs. The aim of this study is to compare efficacy of Bisphosphonates and Denosumab in various parameters.

    Methods: Literature search was done for randomized controlled trials (RCTs) comparing bisphosphonates with denosumab. RCTs with a treatment period of at least one year with a baseline bone mineral density (BMD) and bone turnover markers (BTM) and follow up values at one year were included in the study. All included studies were also analysed for complications. The study has also been registered in PROSPERO International prospective register of systematic reviews.

    Results: A total of five RCTs were identified providing data on 3751 participants. In all five studies, the BMD changes at both hip and spine were statistically significant in favour of denosumab. Result was similar in three studies that studied BMD changes at the wrist. Denosumab also produced significant reduction in BTM as early as one month, but at one year there was no difference compared to the bisphosphonates. There was no statistically significant differences in the complication rates.

    Conclusions: Though both bisphosphonates and denosumab were effective with similar side effects, the latter was statistically superior in increasing the BMD and reducing the BTM.
    Matched MeSH terms: Osteoporosis, Postmenopausal*
  13. Zain NM, Seriramulu VP, Chelliah KK
    Asian Pac J Cancer Prev, 2016;17(7):3229-34.
    PMID: 27509955
    BACKGROUND: Bone mineral density (BMD) is a lifetime marker of estrogen in a woman's body and has been associated with increased breast cancer risk. Nonetheless the actual association is still debatable. Furthermore, estrogen is very crucial in maintaining human bone density and gradually decreases over age. A systematic search was conducted to assess any association of BMD with breast cancer risk factors among premenopausal and postmenopausal women.

    MATERIALS AND METHODS: Review identification was performed through databases searching on MEDLINE, CINAHL and SCOPUS and 19 qualified studies were elected. The keywords used were "bone mineral density", "breast cancer", and "breast density".

    RESULTS: A total of 19 articles showed variation with the majority of the studies focused on postmenopausal and a few focused on premenopausal women. Overall there was no concensus on effects.

    CONCLUSIONS: An enormous effort is being undertaken by researchers to prove that BMD might be one of the significant risk factors for breast cancer.
    Matched MeSH terms: Osteoporosis, Postmenopausal/complications*
  14. Mohd Effendy N, Abdullah S, Yunoh MF, Shuid AN
    BMC Complement Altern Med, 2015 Mar 12;15:58.
    PMID: 25887391 DOI: 10.1186/s12906-015-0567-x
    BACKGROUND: Post-menopausal osteoporosis has long been treated and prevented by estrogen replacement therapy (ERT). Despite its effectiveness, ERT is associated with serious adverse effects. Labisia pumila var. alata (LP) is a herb with potential as an alternative agent to ERT due to its phytoestrogenic, antioxidative and anti-inflammatory effects on bone. This study aimed to determine the effects of LP supplementation on bone biomechanical strength of postmenopausal osteoporosis rat model.

    METHODS: Ninety-six female Sprague-Dawley rats aged 4 to 5 months old were randomly divided into six groups; six rats in the baseline group (BL) and eighteen rats in each group of; Sham- operated (Sham), ovariectomised control (OVXC) and ovariectomised with daily oral gavages of Premarin at 64.5 μg/kg (ERT), LP at 20 mg/kg (LP20) and LP at 100 mg/kg (LP100) respectively. These groups were subdivided into three, six and nine weeks of treatment periods. Rats in BL group were euthanized before the start of the study, while other rats were euthanized after completion of their treatments. Femora were dissected out for biomechanical strength analysis using Instron Universal Model 5848 Micro Tester.

    RESULTS: OVXC group showed deterioration in the bone biomechanical strength with time. Both ERT and LP supplemented rats showed improvements in bone strength parameters such as maximum load, displacement, stiffness, stress, and Young Modulus. The most improved bone strength was seen in rats given LP at the dose of 100 mg/kg for nine weeks.

    CONCLUSION: LP supplementation at 100 mg/kg was more effective than ERT in reversing ovariectomy-induced bone biomechanical changes.
    Matched MeSH terms: Osteoporosis, Postmenopausal/drug therapy*; Osteoporosis, Postmenopausal/etiology; Osteoporosis, Postmenopausal/pathology
  15. Toh LS, Lai PS, Wu DB, Wong KT, Low BY, Anderson C
    PLoS One, 2015;10(5):e0124553.
    PMID: 25938494 DOI: 10.1371/journal.pone.0124553
    Objectives: To develop and validate Osteoporosis Prevention and Awareness Tool (OPAAT) in Malaysia.
    Methods: The OPAAT was modified from the Malaysian Osteoporosis Knowledge Tool and developed from an exploratory study on patients. Face and content validity was established by an expert panel. The OPAAT consists of 30 items, categorized into three domains. A higher score indicates higher knowledge level. English speaking non-osteoporotic postmenopausal women 50 years of age and pharmacists were included in the study.
    Results: A total of 203 patients and 31 pharmacists were recruited. Factor analysis extracted three domains. Flesch reading ease was 59.2. The mean±SD accuracy rate was 0.60±0.22 (range: 0.26-0.94). The Cronbach’s α for each domain ranged from 0.286-0.748. All items were highly correlated (Spearman’s rho: 0.761-0.990, p<0.05), with no significant change in the overall test-retest scores, indicating that OPAAT has achieved stable reliability. Pharmacists had higher knowledge score than patients (80.9±8.7vs63.6±17.4, p<0.001), indicating
    that the OPAAT was able to discriminate between the knowledge levels of pharmacists and patients.
    Conclusion: The OPAAT was found to be a valid and reliable instrument for assessing patient’s knowledge about osteoporosis and its prevention in Malaysia. The OPAAT can be used to identify individuals in need of osteoporosis educational intervention.
    Study site:: Primary care clinic, tertiary hospital, Malaysia
    Matched MeSH terms: Osteoporosis, Postmenopausal/prevention & control*
  16. Wu DB, Hussain S, Mak V, Lee KK
    Value Health, 2014 Nov;17(7):A382.
    PMID: 27200852 DOI: 10.1016/j.jval.2014.08.2625
    OBJECTIVES. Osteoporotic fractures are common in older adults and are often associated with high morbidity and mortality. As the incidence increases with age, it is natural that osteoporotic fractures have become a major health problem worldwide. Increasing number of patients with osteoporotic fracture will have a serious economic impact on the patient themselves and the society. The objective of this study is to study the cost-effectiveness of strontium ranelate compared to alendronate for patients with post-menopausal osteoporotic fractures in Malaysia.
    METHODS. A Markov model was developed to project clinical and economic benefits of strontium in a hypothetical cohort of patients (N=1,000) over a 5-year time horizon. This study was conducted from a payer perspective. Model parameters including transition probabilities and costs of treating fracture at various sites were Malaysia-specific. Drug costs were obtained from a public teaching hospital in Kuala Lumpur. Utilities were derived from previous literatures and efficacy data were derived from two pivotal trials, i. e. SOTI and TROPOS trials. Outcomes were presented as cost per quality-adjusted life year (QALY) gained. A discount rate of 3% was applied. Both 1-way and multivariate probabilistic sensitivity analyses were undertaken to evaluate robustness of results.
    RESULTS. Compared to alendronate, strontium could prevent 328 wrist, 192 hip, 7 vertebra and 115 multiple fractures respectively over 5 years, which was translated into 27.9 QALYs gained. Using strontium can lead to cost reduction of MYR1,416,595 (USD442,685), MYR478,257 (USD149,455), MYR22,784 (USD7,120) and MYR61,883 (USD113,088) due to reduced episodes of fractures at wrist/hip/vertebra/multiple sites respectively. The total reduction of direct medical costs of MYR2,279,519 (USD712,349) was larger than the extra drug cost, hence making strontium a cost-saving therapy.
    CONCLUSIONS. It was shown that strontium appeared to be more cost-effective compared to alendronate and hence should be recommended in the public sector in Malaysia.
    Matched MeSH terms: Osteoporosis, Postmenopausal*
  17. Ibrahim N', Khamis MF, Mod Yunoh MF, Abdullah S, Mohamed N, Shuid AN
    PLoS One, 2014;9(12):e115595.
    PMID: 25526611 DOI: 10.1371/journal.pone.0115595
    Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.
    Matched MeSH terms: Osteoporosis, Postmenopausal/complications*
  18. Shuid AN, Ibrahim N', Mohd Amin MC, Mohamed IN
    Curr Drug Targets, 2013 Dec;14(13):1558-64.
    PMID: 24200294
    Anti-osteoporotic drugs are available for treatment of osteoporosis and for preventing osteoporosis complications especially fractures. Most of the current anti-osteoporotic drugs are administered orally or parenterally to target the osteoporosis-affected bones. However, bone is a peripheral organ with limited blood supply. Therefore, the drugs delivered are exposed to various physicochemical and biological factors which affect the bioavailability of the drugs. In preclinical research, the dose of a potential anti-osteoporotic agent used in animal model may be too high for human application when administered via the conventional route of administration. The current anti-osteoporotic drugs need to be administered at higher doses to account for pharmacological interactions. However, this will expose the patients to adverse effects such as the cancer risks of postmenopausal women who took estrogen replacement therapy. There is also problem with patient compliance as anti-osteoporotic drugs may have to be taken for prolonged duration. The current deliveries of drugs need to be improved to overcome these problems. This review discussed several potential drug delivery systems which are able to contain the anti-osteoporosis drugs and release them slowly to the targeted bone. Among them are various carriers, polymers and microsponges, which may not only increase drug efficacy but also reduce adverse effects. The delivery systems allow the drugs to be administered locally at the targeted bone for longer duration, therefore reducing drug frequency and improving patient's compliance. It is hoped that these delivery systems may be applicable for the treatment of osteoporosis in the future to keep tab of the rising osteoporotic fracture incidence.
    Matched MeSH terms: Osteoporosis, Postmenopausal/complications*; Osteoporosis, Postmenopausal/drug therapy*
  19. 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: Osteoporosis, Postmenopausal/diagnosis; Osteoporosis, Postmenopausal/drug therapy*
  20. Ibrahim N', Mohamed N, Shuid AN
    Curr Drug Targets, 2013 Dec;14(13):1524-32.
    PMID: 23876090
    Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.
    Matched MeSH terms: Osteoporosis, Postmenopausal/complications*; Osteoporosis, Postmenopausal/drug therapy
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