Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of the premenopausal mean value] were enrolled in a 2-year prospective, randomized study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD measurements at the lumbar spine, total hip, and femoral neck as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin), serum bone-specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took place regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and 3.8% at the lumbar spine, total hip, and femoral neck, respectively (all P < 0.001). The biochemical markers of bone turnover were suppressed accordingly. Serum CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%, respectively, whereas serum osteocalcin and serum bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy is efficient in increasing BMD in an osteopenic postmenopausal population. Furthermore, it is well tolerated, with few adverse events and an early bleeding control, which is likely to improve compliance to the treatment over the long term.     

Reduced bone mass in daughters of women with osteoporosis

To determine whether premenopausal daughters of women with postmenopausal osteoporosis have lower bone mass than other women of the same age, we measured the bone mineral content of the lumbar spine and femoral neck and midshaft, using dual-photon absorptiometry, in 25 postmenopausal women with osteoporotic compression fractures and in 32 of their premenopausal daughters; we then compared the results with those in normal controls. As compared with normal postmenopausal women, women with osteoporosis had lower bone mineral content in the lumbar spine, femoral neck, and femoral midshaft by 33, 24, and 15 percent, respectively (P less than 0.001 for each comparison by the one-tailed t-test). As compared with normal premenopausal women, the daughters of women with osteoporosis had lower bone mineral content at these sites by 7, 5, and 3 percent, respectively (P = 0.03, 0.07, and 0.15, respectively, by the one-tailed t-test). In terms of a standardized score, we calculated that the mean (+/- SEM) relative deficits in bone mineral content in the daughters of women with osteoporosis were 58 +/- 18 percent (lumbar spine) and 34 +/- 16 percent (femoral neck) of the relative deficits in their mothers. We conclude that daughters of women with osteoporosis have reduced bone mass in the lumbar spine and perhaps in the femoral neck; this reduction in bone mass may put them at increased risk for fractures. We also conclude that postmenopausal osteoporosis may result partly from a relatively low peak bone mass rather than from excessive loss of bone.     

Relationship of osteocalcin and matrix Gla protein gene polymorphisms to serum osteocalcin levels and bone mineral density in postmenopausal Korean women

OBJECTIVE: To investigate the relationship of osteocalcin and matrix Gla protein (MGP) gene polymorphisms to serum osteocalcin levels, and bone mineral density (BMD) in postmenopausal Korean women. DESIGN: The osteocalcin gene Hind III and MGP gene cytosine-adenine polymorphisms were analyzed in 267 postmenopausal Korean women. Serum osteocalcin, bone alkaline phosphatase, C-telopeptide of type I collagen, and BMD at the lumbar spine and femoral neck were measured. RESULTS: No significant differences in BMD of the lumbar spine and femoral neck were observed across MGP genotypes, whereas a significant lower BMD at the lumbar spine (but not at the femoral neck) was observed in women with the (h) allele (lower case 'h' signifies the presence of the Hind III site) in a dose-response manner. Serum osteocalcin levels among bone turnover markers studied were significantly higher in women without the 210-bp MGP (cytosine-adenine) allele, or with the osteocalcin hh genotype. CONCLUSIONS: The osteocalcin gene Hind III polymorphism is a genetic factor that is associated with BMD of the lumbar spine in Korean women, and Gla gene polymorphisms are associated with higher osteocalcin levels.     

Levonorgestrel and 17beta-estradiol given transdermally for the prevention of postmenopausal osteoporosis

Aim: To evaluate the efficacy and safety of a new transdermal continuous combined hormone replacement therapy (HRT) for the prevention of postmenopausal osteoporosis. Methods: 212 osteopenic (lumbar spine and/or hip (femoral neck) bone mineral density (BMD) between −1.0 and −2.5 S.D. of the premenopausal mean value) postmenopausal women aged 45–65 years participated in a 2-year prospective study. Treatments were 45 μg 17β-estradiol combined with 30 (n = 69) or 40 μg (n = 72) levonorgestrel daily or placebo (n = 71) given as a 7-day patch. All received a daily supplement of 500 mg calcium. BMD at lumbar spine (L2–L4), hip and total body, as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin (sOC), serum bone-specific alkaline phosphatase (sBSAP), urinary calcium (uCa) and urinary CrossLaps (uCTX)) were measured regularly. Results: BMD at the lumbar spine, hip and total body increased by 8, 6 and 3% (P < 0.001), respectively, in the hormone groups versus placebo. The bone markers all decreased accordingly (sOC: 37%, sBSAP: 34% and uCTX: 65% from baseline (all P < 0.001)), except for uCa that did not change significantly. No significant dose-related effect of levonorgestrel was found. Vaginal bleeding/spotting decreased from 48 to 25% of the HRT-treated women during the study period. Skin tolerance was good in 84% of the women with no difference between the study groups. No incidences of endometrial hyperplasia, uterine or mammary cancer occurred. Conclusion: The transdermal combination of 17β-estradiol and levonorgestrel has a positive effect on BMD in an osteopenic postmenopausal population. Furthermore, a high safety profile was observed.     

Comparison of effect of treatment with etidronate and alendronate on lumbar bone mineral density in elderly women with osteoporosis

The purpose of this open-labeled prospective study was to compare the treatment effects of cyclical etidronate and alendronate on the lumbar bone mineral density (BMD), bone resorption, and back pain in elderly women with osteoporosis. Fifty postmenopausal women with osteoporosis, age ranging from 55 to 86 years (mean: 70.7 years), were randomly divided into two groups with 25 patients in each group: the cyclical etidronate group (etidronate 200 mg daily for 2 weeks every 3 months) and the alendronate group (5 mg daily). The BMD of the lumbar spine (L1-L4) measured by DXA, the urinary cross-linked N-terminal telopeptides of type I collagen (NTX) level measured by the enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Etidronate treatment sustained the lumbar BMD following a reduction in the urinary NTX level and improved back pain, while alendronate treatment reduced the urinary NTX level more significantly, resulting in an increase in the lumbar BMD, and similarly improved back pain. No serious adverse events were observed in either group. This study confirmed that alendronate treatment had a greater efficacy than etidronate treatment in increasing the lumbar BMD through the reduction of bone resorption in elderly women with osteoporosis.     

Bone mass and bone diminution of the axial and peripheral skeleton in normal and osteoporotic Austrian females.

Measurements of bone mass were performed in 133 healthy Austrian women using the quantitative computed tomography technique of the lumbar spine and single photon absorptiometry of the distal forearm. The data were compared with those of 110 Austrian females with osteoporotic spine fractures. A significant difference in mean bone density of the lumbar spine was observed between normal and osteoporotic patients in every decade, whereas forearm measurements showed statistical differences in the seventh and eighth decade but not in the sixth decade. Compared to age matched controls, bone mass of osteoporotic women showed the following diminution: sixth decade: distal forearm: -12.7%, spine: -46.8%; seventh decade: distal forearm: -19.0%, spine: -36.7%, eighth decade: distal forearm: -15.4%, spine: -33.7%. It appears that postmenopausal osteoporosis involves greater loss of bone in the spine in the first decade after menopause and slows down after this period, whereas loss of forearm bone mineral density (BMD) increases with advancing age.     

Relation of the estrogen receptor alpha gene microsatellite polymorphism to bone mineral density and the susceptibility to osteoporosis in postmenopausal Chinese women in Taiwan.

OBJECTIVE: Osteoporosis is a common disorder with a strong genetic component. Our aim was to investigate the correlation of the estrogen receptor alpha gene microsatellite polymorphism (TA dinucleotide repeat polymorphism 5' upstream of exon 1) with bone mineral density and their relationship to osteoporosis. METHODS: We determined the estrogen receptor alpha gene microsatellite polymorphism using polymerase chain reaction-based microsatellite analysis in postmenopausal Chinese women in Taiwan. Bone mineral density of the lumbar spine and proximal femur were measured using dual-energy X-ray absorptiometry. RESULTS: The ERalpha genotype was classified into '12' through '27' according to the number of TA dinucleotide repeats they contained, as a 'signpost'. After adjustment for potential confounding factors including age, height, and weight, subjects with genotype 18+ (n=4) had lower bone mineral density values and a 54.5 times greater risk for osteoporosis when compared with subjects with genotype 18- (n=170) at the lumbar spine. This should be interpreted with caution because of the small number of subjects with the unfavorable genotype 18+. According to mean number of TA dinucleotide repeats, women with a high number of repeats (TA > or =20) (n=38) had the lowest bone mineral density and a 6.1 times greater risk for osteoporosis than women with a low number of repeats (TA < or =15) (n=61) at the femoral neck, after adjustment for potential confounding factors such as age, height, and weight. CONCLUSION: The present study suggests that the estrogen receptor alpha gene microsatellite polymorphism may be a candidate genetic marker for risk of osteoporosis in postmenopausal Chinese women in Taiwan.     

Bone Mineral Density and Prevalence of Osteoporosis in Postmenopausal Korean Women with Low-Energy Distal Radius Fractures

The aim of this study was to evaluate the bone mineral density and the prevalence of osteoporosis in postmenopausal Korean women with low-energy distal radius fractures and compared with those of aged-matched normal Korean women. Two hundred and six patients with distal radius fractures between March 2006 and March 2010 were included in this study. Patients were divided into three groups by age; group 1 (50-59 years), group 2 (60-69 years), and group 3 (70-79 years). Controls were age-matched normal Korean women. The bone mineral density values at all measured sites, except for the spine, were significantly lower in group 1 than those of control. While the bone mineral density values in group 2 and 3 were lower than those of controls, these differences were not statistically significant. All groups had significantly higher prevalence of osteoporosis at the Ward’s triangle; however, at the spine, femoral neck and trochanteric area it was not significantly different from those of age-matched controls. Although the prevalence of osteoporosis of the postmenopausal women with low-energy distal radius fractures may not be higher than that of the control, osteoporosis should be evaluated especially in younger postmenopausal patients to prevent other osteoporotic hip and/or spine fractures.     

Changes in bone markers after once-weekly low-dose alendronate in postmenopausal women with moderate bone loss

BACKGROUND: High bone turnover, with bone resorption exceeding bone formation, is a major mechanism of postmenopausal osteoporosis. Therefore, inhibition of bone resorption is a rational approach for the prevention of bone loss. The objective of the current study was to determine the short-term efficacy of once-weekly low-dose alendronate in the prevention of bone loss, via bone turnover markers, in early postmenopausal Korean women with moderate bone loss. METHODS: This study involved a 12-week, randomized, double-blind clinical trial that compared the effects of placebo with alendronate 20mg once weekly. All subjects received supplemental calcium 600 mg and vitamin D 400IU daily. We recruited 63 postmenopausal women (ranging from 50 to 65 years of age) with the lowest lumbar spine bone mineral density (BMD) at least 2.0 S.D. below the mean value for young healthy adults. BMD was measured at baseline and serum alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide of type I collagen (CTX), and osteoprotegerin (OPG) were measured at baseline and 12 weeks after treatment. RESULTS: We randomly assigned 63 women to either placebo or alencronate 20 mg once a week for 3 months. Forty-nine women continued and completed all 3 months. After 3 months, bone resorption markers were significantly decreased in the alendronate group than in the placebo group: CTX -47.2% vs. 15% (p<0.01), ALP 1.6% vs. 25.9% (p=0.01), osteocalcin -29.2% vs. -13.6 (p=0.06). Women who received alendronate showed similar results to those who received placebo with regard to adverse events. CONCLUSION: Once-weekly low-dose alendronate may be a cost-effective and safe method of suppressing bone turnover in early postmenopausal women with moderate bone loss.     

Comparison of effects of alendronate and raloxifene on lumbar bone mineral density, bone turnover, and lipid metabolism in elderly women with osteoporosis

PURPOSE: To compare the effects of alendronate and raloxifene on lumbar bone mineral density (BMD), bone turnover, and lipid metabolism in elderly women with osteoporosis. SUBJECTS AND METHODS: One hundred twenty-two postmenopausal women with osteoporosis (mean age: 69.4 years) were randomly divided into 2 groups of 61 patients: the alendronate group and the raloxifene group. BMD of the lumbar spine, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP), total cholesterol (TC), high and low density lipoprotein cholesterols (LDL-C and HDL-C, respectively), and triglycerides (TG) were measured during the 12-month-treatment period. RESULTS: The trial in 50 patients in the alendronate group and 52 patients in the raloxifene group could be completed. Both alendronate and raloxifene increased lumbar BMD (+8.0% and +2.4% at 12 months, respectively), followed by reductions of urinary NTX level and serum ALP level; however, the effects of alendronate were more pronounced than those of raloxifene. Only raloxifene reduced the serum levels of TC and LDL-C (-3.9% and -7.7% at 12 months, respectively), without any significant effect on the serum HDL-C and TG levels. CONCLUSION: The present study confirmed the efficacy of alendronate greater than raloxifene in increasing lumbar BMD through its effect on marked reduction of the bone turnover more than by raloxifene, and some beneficial effects of raloxifene on lipid metabolism in elderly women with osteoporosis.     

Soy isoflavones for osteoporosis: an evidence-based approach

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.     

Peripheral quantitative computed tomography (pQCT) is useful for monitoring bone mineral density of the patients who receive hormone replacement therapy

OBJECTIVE: A forearm fracture (Colles' fracture) is often the first sign of osteoporosis and should alert the patient and physician to the possibility of underlying skeletal fragility. Therefore, the establishment of a more accurate and reliable method for the measurement of bone mineral density (BMD) at the distal radius would be beneficial for the patients who suffer from osteoporosis. The objective of the present study was to evaluate the usefulness of peripheral quantitative computed tomography (pQCT) to assess the change of BMD at the distal radius in early postmenopausal women who receive hormone replacement therapy (HRT). METHODS: Twenty healthy early postmenopausal women who were diagnosed as osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin, deoxypyridinoline) every 6 months. RESULTS: The placebo group showed a significant decrease from the baseline in the trabecular BMD of the radius at 12 months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and placebo groups were statistically different at 12 months (p<0.05). On the other hand, in the cortical BMD of the radius, no significant differences were seen between the changes of bone densities in the HRT and control groups after 1 year of treatment. pQCT could detect a significant loss of BMD of the radius in early postmenopausal women after 1 year and HRT prevented its loss. CONCLUSION: Our preliminary clinical trial showed that pQCT might be useful for the early detection of bone loss in early postmenopausal women and for the monitoring BMD of the patients who receive HRT.     

Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: a two-year study

OBJECTIVE: To determine the relationships among bone mineral density changes, bone marker changes, and plasma estrogens in postmenopausal women receiving estrogen replacement therapy. DESIGN: A total of 406 postmenopausal women received 1,000 mg calcium and continuous esterified estrogens (0.3 mg, 0.625 mg, or 1.25 mg) or placebo daily for up to 24 months. Bone mineral density and bone marker measurements were determined at 6-month intervals; plasma estrogens were measured in a subset after 12, 18, and 24 months. RESULTS: Esterified estrogens produced significant increases in bone mineral density (lumbar spine, hip) compared with baseline and placebo at 6, 12, 18, and 24 months. Bone markers decreased from baseline with all esterified estrogen doses relative to placebo. Bone marker changes at 6 months correlated negatively with bone mineral density changes at 24 months (correlation coefficient range = -0.122 to -0.439). The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin. Mean plasma estrogen levels increased with esterified estrogen dose, and bone mineral density changes correlated positively with plasma estrogen levels. Positive bone mineral density changes were noted in treatment groups with plasma estradiol levels at and above 25 pg/mL. CONCLUSIONS: Esterified estrogens, at doses from 0.3 mg to 1.25 mg/day, unopposed by progestin, increase bone mineral density of the spine and hip in postmenopausal women. These bone mineral density changes correlated significantly with bone marker changes at 6 months and with plasma estrogens at 12, 18, or 24 months. Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy.     

The effect of tibolone on bone mineral density in postmenopausal women with osteopenia or osteoporosis--8 years follow-up

OBJECTIVES: This longitudinal observational study evaluated the effect of 8 years of uninterrupted treatment of tibolone on bone mineral density (BMD) in postmenopausal women with significant osteopenia or osteoporosis. MATERIAL AND METHODS: Subjects were 66 postmenopausal women (29 with moderate or severe osteopenia and 37 with osteoporosis) who took tibolone (2.5 mg nocte) uninterruptedly for over 8 years and who attended for annual BMD assessments. Their mean age was 66.7 (0.86) years (range 50-86 years). BMD measurements at the lumbar spine and proximal femur were performed annually by dual-energy X-ray absorptiometry (DEXA). RESULTS: During the 8 years of treatment with tibolone there was a significant increase in BMD at the spine (P < 0.001) and at the hip (P < 0.001). Women who did not have previous oestrogen therapy had significantly greater response to tibolone than those who had previous treatment with conventional hormone replacement therapy (HRT). CONCLUSION: This long-term observational study provides evidence of the effectiveness of tibolone in postmenopausal women with moderate/severe osteopenia and osteoporosis in terms of a significant increase in BMD.     

Relationship between self-reported periodontal status and skeletal bone mineral density in Japanese postmenopausal women

OBJECTIVE: Several investigators have linked periodontal disease progression and low skeletal bone mineral density in postmenopausal women. However, little is known about whether self-reported periodontal status is the reflection of skeletal bone mineral density. We investigated whether self-reported poor periodontal status is associated with low skeletal bone mineral density in postmenopausal women. DESIGN: Relationships among self-reported periodontal status, number of teeth remaining, and bone mineral density of the lumbar spine and the femoral neck were evaluated in 253 Japanese postmenopausal women (mean +/- SD, 56.6 +/- 7.7) recruited from the patients who visited our clinic for bone mineral assessment between 1997 and 2003. Self-reported periodontal symptoms included gingival swelling, gingival bleeding, purulent discharge, and tooth mobility at the time of bone mineral assessment. RESULTS: Analysis of covariance adjusted for age, height, weight, years since menopause, duration of estrogen use, and regular oral care revealed that subjects without periodontal symptoms had significantly higher BMD of the lumbar spine than did those with periodontal symptoms (mean +/- SEM, 0.962 +/- 0.014 vs 0.921 +/- 0.013; P = 0.038); however, there were no significant differences in the number of remaining teeth and bone mineral density of the femoral neck between them. The odds of low spine bone mineral density in subjects with periodontal symptoms was 2.01 (95% CI = 1.15 to 3.50). CONCLUSION: Our results suggest that self-reported poor periodontal status may be associated with low bone mineral density of the lumbar spine in postmenopausal women.     

Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer.

BACKGROUND AND METHODS. Tamoxifen, a synthetic antiestrogen, increases disease-free and overall survival when used as adjuvant therapy for primary breast cancer. Because it is given for long periods, it is important to know whether tamoxifen affects the skeleton, particularly since it is used extensively in postmenopausal women who are at risk for osteoporosis. Using photon absorptiometry, we studied the effects of tamoxifen on the bone mineral density of the lumbar spine and radius and on biochemical measures of bone metabolism in 140 postmenopausal women with axillary-node-negative breast cancer, in a two-year randomized, double-blind, placebo-controlled trial. RESULTS. In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 0.61 percent per year, whereas in those given placebo it decreased by 1.00 percent per year (P less than 0.001). Radial bone mineral density decreased to the same extent in both groups. In a subgroup randomly selected from each group, serum osteocalcin and alkaline phosphatase concentrations decreased significantly in women given tamoxifen (P less than 0.001 for each variable), whereas serum parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not change significantly in either group. CONCLUSIONS. In postmenopausal women, treatment with tamoxifen is associated with preservation of the bone mineral density of the lumbar spine. Whether this favorable effect on bone mineral density is accompanied by a decrease in the risk of fractures remains to be determined.     

Elevated arterial stiffness in postmenopausal women with osteoporosis

OBJECTIVES: Osteoporosis and increased pulse wave velocity (PWV) are cardiovascular risk factors. We investigated the relationship between PWV and bone mass in the lumbar spine in postmenopausal women. METHODS: We studied the PWV in 95 women; 38 postmenopausal women with normal spinal bone mineral density (BMD), 32 osteopenic postmenopausal women, and 25 osteoporotic postmenopausal women. The brachial-ankle PWV (baPWV) was measured using an automated device. The BMD of the lumbar spine (L2-L4) was measured using dual-energy X-ray absorptiometry. RESULTS: After adjusting for age and years since menopause, women with osteoporosis had a significantly higher baPWV than those with normal BMD (1500 +/- 220 cm/s versus 1340 +/- 215 cm/s; P < 0.05), but no significant differences in baPWV were seen between the osteoporotic and osteopenic groups or between the osteopenic and normal BMD groups. In univariate regression analysis, the baPWV was significantly negatively correlated with BMD (r = -0.450, P < 0.01), and significantly positively correlated with age (r = 0.601, P < 0.01), years since menopause (r = 0.577, P < 0.01), systolic blood pressure (r = 0.295, P < 0.01), and diastolic blood pressure (r = 0.264, P < 0.05), but was not with other variables. In multivariate regression analysis, the baPWV was significantly correlated with BMD (P < 0.05), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis may have elevated arterial stiffness, suggesting that osteoporotic postmenopausal women may have a higher risk of cardiovascular disease.     

Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years

OBJECTIVE: Raloxifene hydrochloride (60 mg/day) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene treatment for 3 years increases bone mineral density (BMD) and, unlike tamoxifen (a triphenylethylene selective estrogen receptor modulator), does not stimulate the endometrium in healthy postmenopausal women. The effect of longer duration of treatment with raloxifene is not known. Therefore, the main objectives of these analyses are (1) to compare the effect of 5 years of treatment with raloxifene (60 mg/day) with placebo in terms of the likelihood of developing osteoporosis and (2) to evaluate the effect of 5 years of raloxifene treatment on the endometrium and incidence of vaginal bleeding. DESIGN: The current analyses include integrated data from two identically designed, prospective, double-blinded trials including postmenopausal women (mean age, 55 years) randomly assigned to either placebo (n = 143) or raloxifene (60 mg/day; n = 185). Osteoporosis and osteopenia were diagnosed according to World Health Organization criteria, using the manufacturer's database for the lumbar spine and the National Health and Nutrition Examination Survey's 1998 reference base for the hip. Endometrial thickness was determined using transvaginal ultrasonography. Clinical diagnoses of endometrial hyperplasia or endometrial cancer were confirmed by blinded review of histopathology reports. RESULTS: Compared with the case of placebo, raloxifene treatment for 5 years reduced bone turnover markers (osteocalcin: -10.9%, P < 0.001; bone-specific alkaline phosphatase: -7.2%, P = 0.042; urinary C-telopeptide: -11.1%, P = 0.034) and was associated with increased BMD in the lumbar spine (2.8%; P < 0.001) and total hip BMD (2.6%; P < 0.001). Women taking raloxifene were less likely to develop osteoporosis (relative risk [RR] for raloxifene v placebo: 0.13; 95% CI: 0.00, 0.37; P = 0.001) or osteopenia (RR: 0.23; 95% CI: 0.00, 0.81; P = 0.038) at the lumbar spine and were more likely to convert to normal BMD status at the lumbar spine (RR: 4.01; 95% CI: 1.34, 11.23; P = 0.043) and total hip (RR: 3.92; 95% CI: 1.12,14.27; P = 0.011) at 5 years, compared with the case of placebo. Raloxifene also significantly reduced total cholesterol (-5.5%; P < 0.001) and low-density lipoprotein cholesterol (-8.7%; P < 0.001), compared with the case of placebo. No significant changes in high-density lipoprotein cholesterol (P = 0.257) or triglycerides (P = 0.620) were detected. Incidence of hot flashes was higher among women taking raloxifene compared with those taking placebo [raloxifene, 47 (28.8%); placebo, 21 (16.8%); P = 0.017]. Women taking placebo or raloxifene reported a similar incidence of vaginal bleeding (P = 0.999) or of mean endometrial thickness of more than 5 mm at baseline and at each visit, up to the 5-year endpoint (P >/= 0.349). No diagnoses of endometrial hyperplasia or endometrial cancer were made in either treatment group. CONCLUSIONS: Five years of raloxifene treatment in healthy postmenopausal women preserves BMD, significantly reduces the likelihood of development of osteoporosis, and was not associated with an increased rate of vaginal bleeding, endometrial hyperplasia, or endometrial carcinoma, compared with the case of placebo.     

Bone mineral density in postmenopausal women treated with a vaginal ring delivering systemic doses of estradiol acetate

OBJECTIVE: To evaluate the effect on bone mineral density of vaginal rings delivering estradiol acetate at two systemic doses versus a locally active vaginal ring in healthy postmenopausal women. DESIGN: A total of 174 postmenopausal women (younger than age 65 years) were randomly assigned to a 0.05 mg/day vaginal ring, 0.1 mg/day vaginal ring, or 0.0075 mg/day vaginal ring (active comparator), and treated for 96 weeks. Of these, 170 took a study drug; 85 taking the study drug had data at 96 weeks, and 132 women were included in the intent-to-treat analysis. Non-hysterectomized women received 1 mg of norethisterone taken on the last 12 days of each 28-day monthly cycle. The primary endpoint was change in lumbar spine bone mineral density (L2-L4); change in total hip bone mineral density was a secondary endpoint. RESULTS: At 96 weeks, mean lumbar spine bone mineral density increased 2.7% and 3.3% from baseline, respectively, in the 0.05-mg and 0.1-mg groups (P < 0.001 for both) compared with an 0.3% increase in the 0.0075-mg group (P = 0.56). Mean total hip bone mineral density increased 1.7% and 1.8% from baseline, respectively, in both the 0.05-mg and 0.1-mg groups (P < 0.001) and decreased 1.2% in the 0.0075-mg group (P = 0.001). All vaginal ring doses were well tolerated. CONCLUSIONS: Vaginal rings delivering systemic doses of estradiol increase bone mineral density of the lumbar spine and total hip in healthy postmenopausal women. Safety and acceptability were similar to existing estradiol therapies.     

Bone mass and biochemical parameters in metabolic bone diseases

We studied the relationship between the bone mass and biochemical parameters in 175 normal premenopausal, 72 normal postmenopausal and osteoporotic postmenopausal women, between 20 and 88 years old, and in 40 patients with hyperthyroidism, and 23 patients with primary hyperparathyroidism, between 13 and 64 years old. The bone mineral density (BMD) of the spine (L2-L4) and proximal femur (femoral neck) was measured by dual-energy X-ray absorptiometry using a QDR-1000, Hologic. The bone mineral content (BMC) of the radius was measured by single photon absorptiometry (SPA) using a model 2780, Norland. Serum PTH, BGP and calcitonin (CT) were determined by radioimmunoassay. The BMD of the spine (L2-L4), and the proximal femur in postmenopausal women were negatively correlated with age. The mean BMD in patients with postmenopausal osteoporosis was significantly lower than that in normal postmenopausal women. In postmenopausal women, age was positively correlated with BGP, PTH, CT and negatively correlated with P. In patients with osteoporosis, the BMD of the spine was negatively correlated with serum BGP. The BMC of radius in patients with hyperthyroidism decreased significantly compared with that in the controls, and was negatively correlated with F-T3. The BMC of the radius in patients with primary hyperparathyroidism was significantly lower than that in the controls, and was negatively correlated with serum BGP and serum calcium. The measurements of biochemical parameters such as serum BGP, ALP and PTH may be useful in the assessment of metabolic bone diseases.