OBJECTIVE: The number of hip fractures is expected to double in the next 20 years, with current estimates that Asia will account for 37% of these cases. As bone mineral density (BMD) may be used as a measure of fracture risk, we sought to compare the effects of teriparatide with salmon calcitonin treatment on changes in BMD, biochemical bone markers, and safety in postmenopausal Asian women with osteoporosis.
METHODOLOGY: A total of 104 patients (n = 47 teriparatide [20 g/day subcutaneously] and n = 57 calcitonin [100 IU/day subcutaneously]) were enrolled in Hong Kong, Singapore, Philippines, Malaysia, and Thailand. Calcium (> or = 500 mg/day) and vitamin D (200-400 IU/day) supplements were taken throughout the 6-month controlled, randomized study.
RESULTS: Teriparatide was associated with a 5.03 +/- 4.77% increase in lumbar spine BMD (p < 0.0001, mean +/- SD change from baseline), whereas changes in lumbar spine BMD for patients on calcitonin were not statistically significant (mean change of 0.36 +/- 4.12%, p = 0.16). Comparison of the two groups indicated that teriparatide treatment improved lumbar spine BMD statistically significantly more than calcitonin (p < 0.0001). No statistically significant changes were observed for total hip or femoral neck BMD. Serum bone-specific alkaline phosphatase (BSAP) increased by 55.9% (median change from baseline, p < 0.0001) in the teriparatide group, and remained stable with calcitonin (5.0% change, p = 0.24); osteocalcin increased by 156.15% (median change from baseline, p < 0.0001) with teriparatide, and decreased with calcitonin (-15.25%, p = 0.03). Similar rates of adverse events were observed, with nausea and dizziness the most commonly reported for both groups (teriparatide versus calcitonin, 13.0% versus 23.2% p = 0.21, 10.9% versus 21.4% p = 0.19, respectively). There were no clinically relevant changes observed in laboratory parameters.
CONCLUSIONS: Both treatments were similarly tolerated, however teriparatide was associated with greater increases in lumbar spine BMD and bone formation markers, demonstrating the unique mechanism of action and safety of this treatment for osteoporosis in these Asian women.
A previous study on a randomized controlled trial in 173 postmenopausal Chinese women in Kuala Lumpur showed that milk supplementation was effective to reduce bone loss at the total body, lumbar spine, femoral neck and total hip compared to the control group on a usual diet (Chee et al. 2003).
Matched MeSH terms: Osteoporosis, Postmenopausal/drug therapy*; Osteoporosis, Postmenopausal/prevention & control
A systematic review was conducted to evaluate evidence concerning the effect of non-drug interventions by healthcare professionals on community-dwelling postmenopausal osteoporotic women. Evidence available indicates that such interventions are effective in improving the quality of life, medication compliance, and calcium intake, but effect on other outcomes is less conclusive.
INTRODUCTION: The purpose of this study is to conduct a systematic review to evaluate evidence concerning the effect of non-drug interventions by healthcare professionals on community-dwelling postmenopausal osteoporotic women.
METHODS: Randomized controlled trials (RCTs) published in English between year 1990 and 2009 were identified. Types of patient outcome used as assessment included quality of life (QOL), bone mineral density (BMD), medication compliance and persistence, knowledge level, and lifestyle modification.
RESULTS: Twenty four RCTs met the inclusion criteria. Seven studies assessed interventions by physiotherapists, six by physicians, seven by nurses, three by multi-disciplinary teams and one by dietitians. Variability in the types and intensity of interventions made comparison between each study difficult. Collectively, these studies provided some evidence to show that interventions by healthcare professionals improved the QOL medication compliance and calcium intake of patients but its effects on BMD, medication persistence, knowledge, and other lifestyle modifications were less conclusive.
CONCLUSIONS: From this review, it was found that some outcome measures of such non-drug interventions still required further studies. Future studies should use validated instruments to assess the outcomes, with focus on common definitions of interventions and outcome measures, more intensive one-to-one interventions, appropriate control groups, adequate randomization procedures, and also provide information on effect size.
BACKGROUND: Osteoporosis treatment guidelines recommend calcium and vitamin D supplementation for both prevention as well as treatment, however, compliance with these guidelines is often unsatisfactory. This study investigated the opinion of Asian physicians and Asian patients regarding vitamin D and calcium and patients' use of both.
METHODS: Physicians selected from Malaysia, Taiwan, Philippines, Korea and Singapore were asked to grade the significance of vitamin D and calcium in the treatment of osteoporosis and their patients' use of these supplements. In addition, physicians recruited seven eligible osteoporotic women to answer a questionnaire to determine their use of vitamin D and calcium, and their attitudes and beliefs regarding these supplements.
RESULTS: In total, 237 physicians and 1463 osteoporosis patients completed the questionnaire. The results revealed that 22% of physicians in Malaysia, 12% in Taiwan, 72% in the Philippines, 50% in Korea and 24% in Singapore rated the importance of vitamin D supplementation as being extremely important. For calcium, 27% of physicians in Malaysia, 30% in Taiwan, 80% in the Philippines, 50% in Korea and 38% in Singapore rated the importance as being extremely important. Forty-three percent of patients in Malaysia, 38% in Taiwan, 73% in the Philippines, 35% in Korea and 39% in Singapore rated the importance of vitamin D as being extremely important. For calcium, 69% of patients in Malaysia, 58% in Taiwan, 90% in the Philippines, 70% in Korea and 55% in Singapore rated the importance as being extremely important. In addition, results of the patient questionnaire revealed that only a very small number regularly took both supplements. In addition, the results indicated that, with the exception of patients from the Philippines, the majority of patients had no or infrequent discussion with their physician about vitamin D and calcium.
CONCLUSIONS: There is generally suboptimal appreciation by both physicians and patients of the importance of vitamin D and calcium for maintenance of bone health as reflected in the low number of patients who reported regularly taking these supplements. Recognition of this problem should translate to appropriate action to improve education for both physicians and patients, with a goal to increase use of these supplements among Asian patients with osteoporosis.
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.
The aim of this study was to identify risk factors associated with osteoporosis in urban midlife Malaysian women and to assess the effectiveness of lifestyle intervention in bone loss prevention with hormone replacement therapy (HRT) as a positive control. A total of 514 disease-free, uterus-intact, non-HRT-using women aged 45 years and older were recruited into the study. After initial bone mineral density (BMD) assessments, they were randomized into three groups: GI (control), G2 (lifestyle intervention), and G3 (lifestyle intervention with HRT). The study group was composed of 67.5% Chinese, 27.8% Malay, and 4.2% Indians with a mean age of 51.07+/-5.28 years. Two-fifths were postmenopausal, and the prevalence of osteoporosis was 24.1%, seen predominantly at the hip. Postmenopausal women had significantly lower mean BMD and a higher incidence of osteoporosis compared with the premenopausal women, 42.1% vs. 11.1% (p<0.0005). A lower incidence of osteoporosis was found in women who took calcium supplementation regularly as opposed to those who do not, 18.7% vs. 29.3% (p=0.036). Age and a greater postmenopausal duration showed a significant negative association with BMD, whereas higher family income, weight, body mass index, and waist and hip circumference were positively correlated. After 18-20 months, the effect of intervention was assessed based on BMD values of 279 women at baseline and after intervention. Lifestyle intervention alone was effective in premenopausal women, preventing over 90% of spinal bone loss compared with the controls, who lost 11.6% (0.046 g/cm2) bone mass with similar losses of hip bone, 2.0% (0.026 g/cm2) vs. 1.5% (0.020 g/cm2). Premenopausal women on HRT also showed a substantial decrease in spine and hip BMD, 18.6% (0.081 g/cm2) and 9.0% (0.122 g/cm2), respectively. The lifestyle intervention program retarded postmenopausal bone loss by 21% and 37% compared with controls, who lost 9.6% (0.141 g/cm2) and 6.0% (0.138 g/cm2) bone mass at the spine and hip. In comparison, lifestyle intervention with HRT increased postmenopausal BMD by 12.7% (0.216 g/cm2) at the spine and 1.9% (0.042 g/cm2) at the hip. The changes in hip BMD were influenced by current age, ethnicity, and income, while intervention had the strongest effect on spine BMD changes. In conclusion, lifestyle intervention prevented spinal bone loss in premenopausal women and retarded postmenopausal spine and hip bone loss compared with controls. The benefits of physical activity on spine and hip BMD highlight its potential as a safe and cost-effective alternative to HRT, which is not advocated because of its potential adverse effects.
A cross-sectional study was conducted to determine bone health status and nutrient intakes among post-menopausal women residing in low cost houses in Cheras, Kuala Lumpur.
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.
Postmenopausal estrogen deficiency often causes bone density loss and osteoporosis. This study evaluated the effects of an oral administration of oil palm leaf extract (OPL) on bone calcium content and structure, bone density, ash weights, and serum total alkaline phosphatase (T-ALP) of estrogen-deficient ovariectomized (OVX) rats.
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.
We evaluated adherence with raloxifene therapy compared with daily bisphosphonate in Asian postmenopausal women at increased risk of osteoporotic fractures. In this 12-month observational study conducted in Asia (Hong Kong, Malaysia, Pakistan, Philippines, Singapore, Taiwan), 984 postmenopausal women (aged 55 years or older) were treated with raloxifene 60 mg/day (n = 707; 72%) or daily bisphosphonate (alendronate 10 mg/day; n = 206; 21%, or risedronate 5 mg/day; n = 71; 7%) during their normal course of care. Patients were assessed at baseline, 6, and 12 months. Baseline characteristics (including age, race, education, menopausal status, and baseline fractures) were comparable between the raloxifene and bisphosphonate groups. More women on raloxifene completed the study compared with those on bisphosphonate (50.2% versus 37.5%; P < 0.001). Patients also took raloxifene for a longer period than bisphosphonate (median, 356 versus 348 days; P = 0.011). Compared with those taking bisphosphonate, significantly fewer patients taking raloxifene discontinued the study because of stopping treatment (5.7% versus 10.1%, P = 0.017) or changing treatment (2.8% versus 9.7%, P < 0.001). Inconvenient dosing was reported as a primary reason for discontinuation due to stopping or changing treatment in 19 (6.9%) bisphosphonate patients compared with 0 raloxifene patients. The percentage of patients who had consumed 80% or more of their study medication was similar for raloxifene patients (48-56 weeks; 95.2%) and bisphosphonate patients (48-56 weeks; 93.3%). More raloxifene patients responded that they were satisfied with their medication than bisphosphonate patients at 48-56 weeks (P = 0.002). We concluded that Asian postmenopausal women at increased risk of osteoporotic fractures showed a greater propensity to remain on raloxifene compared with bisphosphonate. The women on raloxifene exhibited lower discontinuation rates and higher treatment satisfaction.
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.
Osteoporosis is a metabolic disease affecting both men and women especially in postmenopausal women. Curcumin possesses many medicinal properties. In this study, thirty two female Sprague-Dawley rats were used to determine the potential effect of curcumin in prevention of bone loss following ovariectomy. The animals were divided into Sham group, ovariectomised control, ovariectomised treated with curcumin 110 mg/kg and ovariectomised treated with Premarin 100 μg/kg. The treatments were given via daily oral gavages for 60 days. The structural parameters such as bone volume, trabecular number, trabecular thickness and trabecular separation were found to be deteriorated in ovariectomised rats compared to Sham group. Moreover, the reduced osteoblast count, the increased osteoclast count and increased eroded surface were found in ovariectomised groups. Treatment with curcumin was able to reverse all these ovariectomy-induced deteriorations. Curcumin treatment was as effective as Premarin in most parameters except the bone volume and eroded surface, which were better than Premarin. The high dose of curcumin treatment was not only able to reduce the osteoclast number but also increase the osteoblast count. Therefore, the potential effect of curcumin can be applied as an alternative to oestrogen for prevention of postmenopausal osteoporosis.
BACKGROUND: Osteoporotic fracture is a major health burden. Early diagnosis and management would improve the quality of life and reduce costs to the society.
OBJECTIVE: We aimed to identify risk factors associated with osteoporosis followed by development and validation of a screening tool in the hope of providing an appropriate regime to detect low bone density (BMD) in Malaysia.
METHODOLOGY: Between November 1999 and November 2002, 514 healthy women aged ≥ 45 with intact uterus, non-HRT users were recruited. Following BMD testing, a screening tool was developed. For validation, 72 women were recruited from June 2003 to December 2003.
RESULTS: Age and a longer duration postmenopause were negatively linked to BMD. Higher family income, BMI, waist and hip circumference were positively correlated. A score of ≥ 4, the screening tool had a sensitivity of 73.2%, a specificity of 61.6% for identifying women with low BMD (T score ≤ -2) plus a sensitivity of 80.2% in selecting women with osteoporosis. The tool enabled a 45.9% reduction in unnecessary DEXA testing. Validation of the screening tool showed a negative predictive value of 97.8%, sensitivity and specificity of 87.5% and 70.3%, respectively.
CONCLUSION: The Malaysian Osteoporosis Screening Tool (MOST) is relatively simple. Its usage may reduce unnecessary DEXA test.
OBJECTIVES: To develop and validate the Osteoporosis Patient Satisfaction Questionnaire (OPSQ) and to assess the opinion of postmenopausal osteoporotic women towards pharmaceutical care.
METHODS: A 16-item instrument was designed. Each response consists of a five-point Likert-like scale with higher scores indicating greater satisfaction. The face and content validity was established via consultation with an endocrinologist and three pharmacists as well as feedback from participants in a preliminary study. Postmenopausal osteoporotic women taking bisphosphonates were recruited and randomly allocated to the intervention (n=90) and control groups (n=90). Pharmaceutical care was provided at month 2 to the intervention group while the control group received standard pharmacy services. The OPSQ was administered at month 6 (end of the intervention period), to assess patients' satisfaction. Factor analysis was performed using varimax rotation. Internal reliability was established using Cronbach's alpha. Construct validity was performed by using the Mann-Whitney U test.
RESULTS: The internal reliability of the OPSQ produced a Cronbach's alpha of 0.86. Factor analysis identified one component in the OPSQ, which measured patient satisfaction. The intervention group showed significantly better overall OPSQ score than the control group (91.89+/-7.22% versus 84.32+/-7.48%, p<0.001). This indicates that the OPSQ was able to differentiate between participants who received pharmaceutical care from those who did not.
CONCLUSIONS: The 16-item OPSQ developed in this study has high internal reliability and is a valid instrument for assessing osteoporotic women's satisfaction with pharmaceutical care service in Malaysia.
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.
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.
The aim of our study was to see the efficacy of petroleum ether extract of Cissus quadrangularis (CQ) on development of osteopenia in ovariectomy induced Wistar rats.
Oxidative stress has been associated with postmenopausal osteoporosis which pre-disposes to risk of fracture. Palm tocotrienol is a potent antioxidant and has the poten-tial to be used for treatment of post-menopausal osteoporosis. The aim of the study is to determine if palm tocotrienol supplementation could alleviate oxidative stress in ovariectomised rat model and improve its bone strength. The rats were di- vided into four groups: (i) sham-operated group (SHAM) (ii) ovariectomised-control group (OVX) (iii) ovariectomised and given 60mg/kg α-tocopherol by oral gavage (OVX + ATF) (iv) ovariectomised and given 60mg/kg palm tocotrienols by oral gavage (OVX + PTT). After eight weeks of treatment, blood samples were taken to measure oxida-tive status (MDA, SOD and GPX) while the femurs were biomechanically tested for strength and resistance to fracture. Ovariectomy was shown to induce oxidative stress as shown by the raised MDA levels and reduced GPX activity. Palm tocotrienols seemed to offer protection against the ovariectomy-induced oxidative stress as shown by the suppression of MDA levels and raised GPX and SOD activities in the OVX+PTT group. In comparison, α-tocopherol was only able to raise the SOD but not as high as palm tocotrienols. The biomechanical tests have shown that ovariectomy has not af-fected the bone strength significantly after eight weeks. Palm tocotrienols supplemen-tation for eight weeks was effective in preventing oxidative stress in a post-meno-pausal rat.
Studies have shown that comprehensive interventions by pharmacists can improve adherence and persistence to osteoporosis therapy, but the association between adherence and bone turnover markers (BTMs) has never been studied. Therefore, the aim of this study was to evaluate the effects of pharmaceutical care on medication adherence (and its effects on BTMs), as well as persistence of postmenopausal osteoporotic women to prescribed bisphosphonates.