Bisphosphonates are synthetic analogues of pyrophosphate. Their main pharmacological effect is to iuhibit bone resorption by a variety of mechanisms, not all of which are clearly understood. The activity of the bisphosphonates varies depending on the compound. In clinical trials, they have been shown to stop postmenopausal bone loss and increase bone density, with a concomitant reduction in fracture rate with some agents. This article reviews the currently known mechanisms of action of the bisphosphonates and the evidence that they are useful in the treatment of osteoporosis.
This study aims to evaluate the bone mineral densities and hip axis lengths of women in the local population. 227 normal Singapore women of ages 20 to 70 years had evaluation of their bone mineral densities (BMDs) by means of dual X-ray absorptiometry (DXA). The trend of BMDs at the left femoral neck and the lumbar spine remains fairly constant with increasing age until the 45-49 years age-band, beyond which there is a consistent decline. The mean hip axis length is 10.3 cm with a standard deviation of 0.6 cm. In general, the bone mineral densities in the femoral neck and lumbar spine as measured by DXA and the hip axis length of the local population is lower than corresponding figures reported in the Western population.
The object of this study is to determine the status of an urban Malaysian woman in her menopause age group with reference to her menopausal symptoms, lipid profile, breast, pelvis and bone. One hundred and sixty four women attending the Menopause Clinic of University Hospital, Kuala Lumpur who had not previously been on hormone replacement therapy were studied. Forty nine women were perimenopausal, 74 women were in early menopause (within 5 years of menopause) and 41 women were in late menopause (after 5 years of menopause). The most common symptoms were hot flushes (56%) and generalised tiredness (49%). Eighty four percent (84%) of women had high cholesterol levels. Serum triglycerides were highest in the late menopause group. There were 2 cases of intraductal carcinoma diagnosed on routine mammography, with 8 cases of fibrocystic breast disease and 7 cases of suspicious breast lumps. Routine ultrasound (pelvic and abdominal) revealed two women with ovarian cysts, 6 women with an endometrial thickness of more than 5 mm and 8 women with uterine fibroids. Eighty five women (51.8%) had mild osteoporosis while four women had moderate osteoporosis on dual photon measurements for bone mineral density. Menopause clinics should aim at investigating a woman in her menopause as a whole. Vasomotor symptoms were common in the urban Malaysian menopausal woman. There was a high incidence of lipid abnormalities. Routine mammography, pelvic ultrasound examinations and bone mineral density tests detected significant pathology and abnormalities.
Study site: Menopause Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Vitamin E has been shown to affect bone metabolism. In this study we determined the effects of palm vitamin E and alpha-tocopherol on bone metabolism. Sprague-Dawley female rats fed with normal rat chow were divided into 4 groups and supplemented with either palm vitamin E 30 mg/kg rat weight, palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight. One group was not supplemented. Half of these rats were ovariectomised before supplementation was given for 10 months. As expected, bone mineral density of the ovariectomised rats fed on normal rat chow diet was lower compared to the intact rats. However, these changes were not seen in the supplemented group of rats. Both intact and ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight had a lower bone calcium content in both femoral and vertebral bones whilst rats fed palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight were able to maintain bone calcium content. Alkaline phosphatase activity was elevated in ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight and alpha-tocopherol 30 mg/kg rat weight compared to the intact rats. Alpha-tocopherol also reduced the activity of tartrate-resistant acid phosphatase post-ovariectomy. These findings indicate that both palm vitamin E and alpha-tocopherol maintained bone mineral density in ovariectomised rats but caused conflicting effects on bone calcium content. Further study is needed in order to determine the mechanisms involved.
This study aims to determine the relationship between calcium intake and lifestyle factors with bone health status among 56 postmenopausal women in the Evergreen Senior Citizens Club, Petaling Jaya. Purposive sampling technique was used for sample selection. Bone mineral density (BMD) of the femur proximal and lumbar L2-L4 was measured based on the Dual Energy X-ray Absorptionmetry (DEXA) technique at KVOTC Clinic, Subang Jaya. The interview sessions were conducted using a questionnaire followed by anthropometric measurements. The results revealed that the average age of the respondents was 64.0 years old. The average weight and height of the respondents were 53.68 kg and 1.55 meters, respectively. Overall, the average body mass index (BMI) of the respondents was quite satisfactory (22.4 kg/m²) with only 17.9% of them categorized as overweight (>25 kg/m²). The average total calcium intake was 807.31 mg and about 76.2% was contributed by food intake. About 83.9% of the respondents met the recommended calcium intake according to the Malaysian RDA. The average BMD of the lumbar, neck, wards and trochanter was 9.983 ± 0.178 g/cm², 0.745 ± 0.126 g/cm², 0.604 ± 0.150 g/cm² and 0.674 ± 0.127 g/cm², respectively. About 32.1% of the respondents were categorized as osteoporotic at the femoral wards, while 10.7% respectively was at the lumbar L2-L4 and femoral neck. Half of the respondents had osteopenia at the femoral neck (53.6%) and wards (50.0%) and at the lumbar L2-L4 (53.6%). Pearson correlation test showed significant negative correlations between age and BMD in the neck (r = -0.419, p
The aim of this study was to determine the effects of palm oil-derived vitamin E on glucocorticoid-induced osteoporosis. Three-month old male Wistar rats were adrenalectomised to remove circulating glucocorticoids. The animals were then administered with Dexamethasone 120 µg/kg body weight/day. Treatment with palm vitamin E 60 mg/kg body weight/day was given simultaneously. The results showed that palm vitamin E prevented the loss in regional and whole body bone mineral density seen in the Dexamethasone treated animals. Palm vitamin E improved femoral length and calcium content in the Dexamethasone treated animals. The results confirmed that palm oil-derived vitamin E was effective in preventing glucocorticoid-induced osteoporosis.
In this study the effects of vitamin E deficiency and supplementation on bone calcification were determined using 4-month-old female Sprague-Dawley rats. The rats weighed between 180 and 200 g. The study was divided in three parts. In experiment I the rats were given normal rat chow (RC, control group), a vitamin E deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2 the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60 mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In experiment 3 the rats were fed RC and given the same supplements as in experiment 2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and 118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P < 0.05) and L5 vertebra (28.3 +/- 4.0 mg and 39.5 +/- 6.2 mg compared with 51.4 +/- 5.8 mg; P < 0.05). Supplementing the VED group with PVE60 improved bone calcification in the left femur (133.6 +/- 5.0 mg compared with 91.6 +/- 13.3 mg; P < 0.05) and L5 vertebra (41.3 +/- 3.3 mg compared with 28.3 +/- 4.0 mg; P < 0.05) while supplementation with PVE30 improved bone calcium content in the L5 vertebra (35.6 +/- 3.1 mg compared with 28.3 +/- 4.0 mg; P < 0.05). However, supplementation with ATF did not change the lumbar and femoral bone calcium content compared to the VED group. Supplementing the RC group with PVE30, PVE60 or ATF did not cause any significant changes in bone calcium content. In conclusion, vitamin E deficiency impaired bone calcification. Supplementation with the higher dose of palm vitamin E improved bone calcium content, but supplementation with pure ATF alone did not. This effect may be attributed to the tocotrienol content of palm vitamin E. Therefore, tocotrienols play an important role in bone calcification.
In healthy Caucasian postmenopausal women, raloxifene increases bone mineral density (BMD), decreases biochemical markers of bone turnover, and lowers low-density lipoprotein (LDL) cholesterol, without effects on high-density lipoprotein (HDL) cholesterol and triglycerides. This randomized, double-blind study examines the effects of raloxifene 60 mg/d (n = 483) or placebo (n = 485) in healthy postmenopausal Asian women (mean age 57 yr) from Australia, Hong Kong, India, Indonesia, Malaysia, Pakistan, Philippines, Singapore, Taiwan, and Thailand. Serum osteocalcin, serum N-telopeptide, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were assessed at baseline and 6 months. Lumbar spine BMD was measured at baseline and 1 yr in 309 women from 4 countries. Clinical adverse events were recorded at each interim visit. At 6 months, raloxifene 60 mg/d significantly decreased osteocalcin, N-telopeptide, total cholesterol, and LDL cholesterol by medians of 15.9%, 14.6%, 5.3%, and 7.7%, respectively, from placebo. Changes in HDL cholesterol and triglycerides were similar between raloxifene and placebo. Raloxifene 60 mg/d increased mean lumbar spine BMD (1.9%) from placebo at 1 yr (P = 0.0003). The incidences of hot flashes (placebo 3.5%, raloxifene 5.6%, P = 0.12), and leg cramps (placebo 2.7%, raloxifene 4.3%, P = 0.16) were not different between groups. No case of venous thromboembolism was reported. The effects of raloxifene 60 mg/d on bone turnover, BMD, and serum lipids in healthy postmenopausal Asian women were similar to that previously reported in Caucasian women.
Dietary studies often report low calcium intake amongst post-menopausal Malaysian women and calcium deficiency has been implicated as part of the etiology of age-related bone loss leading to osteoporosis. Therefore, the objective of this study was to examine the effectiveness of high calcium skimmed milk (Anlene Gold, New Zealand Milk, Wellington, New Zealand) to reduce bone loss in Chinese postmenopausal women. Two hundred subjects aged 55-65 years and who were more than 5 years postmenopausal were randomized to a milk group and control group. The milk group consumed 50 g of high calcium skimmed milk powder daily, which contained 1200 mg calcium (taken as two glasses of milk a day). The control group continued with their usual diet. Using repeated measures ANCOVA, the milk supplement was found to significantly reduce the percentage of bone loss at the total body compared to the control group at 24 months (control -1.04%, milk -0.13%; P<0.001). At the lumbar spine, the percentage of bone loss in the control group was significantly higher (-0.90%) when compared to the milk (-0.13%) supplemented group at 24 months (P<0.05). Similarly, milk supplementation reduced the percentage of bone loss at the femoral neck (control -1.21%, milk 0.51%) (P<0.01) and total hip (control -2.17%, milk -0.50%) (P<0.01). The supplemented group did not experience any significant weight gain over the 24 months. The serum 25-hydroxy vitamin D level improved significantly (P<0.01) from 69.1 +/- 16.1 nmol/l at baseline to 86.4 +/- 22.0 nmol/l at 24 months in the milk group. In conclusion, ingestion of high calcium skimmed milk was effective in reducing the rate of bone loss at clinically important lumbar spine and hip sites in postmenopausal Chinese women in Malaysia. Supplementing with milk had additional benefits of improving the serum 25-hydroxy vitamin D status of the subjects.
Ethnic differences in bone density and hip geometry are known to exist, even within the same population. A recent study in Singapore showed that there were significant racial differences in hip fracture rates, with Chinese having the highest incidence of hip fractures. The aim of this study was to compare the bone mineral density (BMD) and hip axis length in Chinese, Malay, and Indian women. A total of 1575 women aged 20-59 yr were recruited, of which 77.6% (1222) were Chinese, 7.7% (122) Malays, and 14.7% (231) Indians. There was no significant difference in peak BMD of both lumbar spine and femoral neck among the three ethnic groups. However, in the older age group (50-59 yr), both Chinese and Malay women had significantly lower femoral neck BMD compared to Indian women. There was no significant loss in BMD of the lumbar spine between the second and fifth decades in all the three races. Between the second and fifth decade, Chinese and Malay women had significant bone loss in the femoral neck of 6.6% and 8.2%, respectively, whereas Indian women did not show any significant bone loss. Chinese women had significantly longer hip axis length compared to either Malay or Indian women (9.87 +/- 0.52 cm vs 9.67 +/- 0.49 cm; p < 0.005; and 9.69 +/- 0.55 cm, p < 0.05, respectively). The initial findings suggest racial differences in bone density and hip geometry exist in the local community. Future research should include prospective, longitudinal studies to determine the age-related bone loss in these three racial groups. It is also important to investigate the differences of spine and hip fracture rates and their relationship with bone density and hip axis length.
Long-term glucocorticoid treatment is associated with severe side effects, such as obesity and osteoporosis. A palm oil-derived vitamin E mixture had been shown previously to be protective against osteoporosis in rats given 120 microg/kg dexamethasone daily for 12 weeks. In this study we determined the effects of two isomers of vitamin E (i.e., palm oil-derived gamma-tocotrienol and the commercially available alpha-tocopherol, 60 mg/kg of body weight/day) on body composition and bone calcium content in adrenalectomized rats replaced with two doses of dexamethasone, 120 microg/kg and 240 microg/kg daily. Treatment period was 8 weeks. gamma-Tocotrienol (60 mg/kg of body weight/day) was found to reduce body fat mass and increase the fourth lumbar vertebra bone calcium content in these rats, while alpha-tocopherol (60 mg/kg of body weight/day) was ineffective. Therefore, in conclusion, palm oil-derived gamma-tocotrienol has the potential to be utilized as a prophylactic agent in prevention of the side effects of long-term glucocorticoid use.
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.
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.
Matched MeSH terms: Bone Density/drug effects; Bone Density Conservation Agents/pharmacology; Bone Density Conservation Agents/therapeutic use*
The primary objective of this study was to determine the relationship between dietary calcium intake and bone mineral density (BMD) in premenopausal women with systemic lupus erythematosus (SLE) on corticosteroids (CS). The secondary aim was to identify other risk factors for osteoporosis in these patients. A cross-sectional sample of patients attending the SLE Clinic at a teaching hospital was recruited. BMD was measured using dual-energy X-ray absorptiometry. Daily dietary calcium intake was assessed using a structured validated food frequency questionnaire, in which patients were asked to estimate their food intake based on their recent 2-month dietary habits. Sixty subjects were recruited with a mean age of 33.70+/-8.46 years. The median duration of CS use was 5.5 years (range 0.08-24). The median cumulative dose of steroids was 17.21 g (range 0.16-91.37). The median daily dietary calcium intake was 483 mg (range 78-2101). There was no significant correlation between calcium intake and BMD, even after correcting for CS use. There were also no correlations between BMD and the duration of SLE, cumulative CS use, duration of CS use, smoking, alcohol intake, and SLE disease activity index score. Twenty-eight (46.7%) patients had normal BMD, 28 (46.7%) had osteopenia, and four (6.6%) had osteoporosis. Duration of SLE significantly correlated with cumulative CS dosage. In conclusion, 6.7% of these Asian premenopausal SLE women had osteoporosis and only 46.7% had normal BMD. Daily dietary calcium intake did not correlate with BMD.
Study site: SLE clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
We report part of the findings of a study conducted to determine the correlation between bone mineral content (BMC) and biochemical bone markers in very low birth weight (VLBW) infants.
The incidence of osteoporosis is increasing worldwide. It has great impact on the life of the elderly population. The most significant medical consequence of osteoporosis is fragility fracture which without proper treatment will cause severe medical and psychosocial complications. The overall cost in managing osteoporosis and its related fractures is escalating. Using bone densitometry to measure bone mineral density is useful in the diagnosis of osteoporosis but it is costly and not feasible in the community. Drugs such as estrogen replacement, raloxifene and calcitonin are effective in prevention and treatment of osteoporosis but they are also expensive. Identifying modifiable risk factors such as smoking, lack of exercise, low dietary calcium and vitamin D intake and healthy life style remain strategy in the primary prevention of osteoporosis in the community.
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: Bone Density/drug effects*; Bone Density Conservation Agents/administration & dosage; Bone Density Conservation Agents/pharmacology*
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.
Matched MeSH terms: Bone Density; Bone Density Conservation Agents/therapeutic use*
Palm oil is shown to have antioxidant, anticancer and cholesterol lowering effects. It is resistant to oxidation when heated compared to other frying oils such as soy oil. When a frying oil is heated repeatedly, it forms toxic degradation products, such as aldehydes which when consumed, may be absorbed into the systemic circulation. We have studied the effects of taking soy or palm oil that were mixed with rat chow on the bone histomorphometric parameters of ovariectomised rats. Female Sprague-Dawley rats were divided into eight groups: (1) normal control group; (2) ovariectomised-control group; (3) ovariectomised and fresh soy oil; (4) ovariectomised and soy oil heated once; (5) ovariectomised and soy oil heated five times; (6) ovariectomised and fresh palm oil; (7) ovariectomised and palm oil heated once; (8) ovariectomised and palm oil heated five times. These oils were mixed with rat chow at weight ratio of 15:100 and were given to the rats daily for six months. Ovariectomy had caused negative effects on the bone histomorphometric parameters. Ingestion of both fresh and once-heated oils, were able to offer protections against the negative effects of ovariectomy, but these protections were lost when the oils were heated five times. Soy oil that was heated five times actually worsens the histomorphometric parameters of ovariectomised rats. Therefore, it may be better for postmenopausal who are at risk of osteoporosis to use palm oil as frying oil especially if they practice recycling of frying oils.