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Clinical effects of strontium ranelate in women with postmenopausal osteoporosis.

Postmenopausal osteoporosis has long-term physical, psychological, and social consequences with a major impact on patients' daily life. Treatment for such a chronic disease needs to be clinically effective and well tolerated, and should ultimately result in a beneficial effect on quality of life. The antifracture efficacy of strontium ranelate, 2 g/day orally, an agent that appears to have dissociation effects on resorption and formation, has been assessed in two large, randomized, double-blind, placebo-controlled clinical studies: the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial and the TReatment Of Peripheral Osteoporosis Study (TROPOS), including more than 6,700 postmenopausal women. Pending the results of TROPOS, a 3-year analysis of SOTI results shows that strontium ranelate significantly reduces new vertebral and clinical vertebral fracture incidence in postmenopausal osteoporotic women. This significant reduction in the risk of clinical and new vertebral fractures has been demonstrated as early as after 1 year of treatment (RR = 0.48, p = 0.003; and RR = 0.51, p < 0.001, respectively) and is maintained over 3 years (RR = 0.62, p < 0.001; and RR = 0.59, p < 0.001, respectively). This is accompanied by decreased back pain and body height loss in the strontium ranelate group compared with the placebo group. As strontium ranelate appears to improve clinical signs and is, furthermore, well tolerated especially in the upper gastrointestinal region, this treatment is expected to result in an improved health-related quality of life (HRQoL). Strontium ranelate thus offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal women with vertebral osteoporotic fractures.

Aged↗

Increased bone fracture prevalence in postmenopausal women suffering from pollen-allergy.

INTRODUCTION: Our aim was to investigate whether pollen-allergy can affect bone mass and fractures in postmenopausal women. METHODS: A total of 125 postmenopausal pollen-allergic women (mean age: 61.26 yr) were split into four groups: (1) treated with neither H1 histamine receptor (H1R) antagonist nor inhaled corticosteroid (n=43); (2) treated only with H1R antagonist (n=53); (3) treated with both H1R antagonist and inhaled corticosteroid (n=17); (4) treated with only inhaled corticosteroid (n=12). Treatment, in the appropriate groups, had occurred for at least 5 years, seasonally. One-hundred non-allergic postmenopausal subjects matched for age, body mass index (BMI), and age at menopause served as controls. RESULTS: Overweight and obesity (25 kg/m(2) < or =BMI) were common among the allergic women (76%). Allergic patients without treatment had a slightly lower bone density than their non-allergic counterparts. The rate (34.9%) of prevalent low-energy fractures (distal forearm, hip, and clinical vertebral fractures) in untreated allergic patients was almost triple that observed in non-allergic women (13%, chi(2) p=0.003). Bone fracture occurred more often in H1R-only treated patients (30.19%) than in controls (chi(2) p=0.01); however, clinical vertebral or hip fractures developed neither in those treated only with H1R antagonist nor in those who received both H1R antagonist and inhaled corticosteroid. Bone fractures were more frequent among patients with inhaled steroid treatment than among patients with a combined treatment of inhaled steroid and antihistamine (50 versus 29.4%). BMI predicted prevalent fractures at 1.278 (95% CI: 1.047-1.559, p=0.016) for a 1 kg/m(2) increase among untreated allergic patients. CONCLUSION: In conclusion, we found a high prevalence of low-energy fractures among pollen-allergic postmenopausal women which was associated with obesity. It is possible that the H1R antagonists compensate for both the negative effect of pollen-allergy and the adverse effect of inhaled corticosteroid treatment on bone fracture risk.

Administration, Inhalation↗

Maintenance of muscle strength may counteract weight-loss-related postmenopausal bone loss--a population-based approach.

INTRODUCTION: Weight loss significantly increases postmenopausal bone loss, but the effects of muscle strength change on weight-loss-associated bone loss remain unclear. The study population, 587 peri- and postmenopausal women, was a random sample of the original Osteoporosis Risk Factor and Prevention Study (OSTPRE) study cohort (n=14,220) in Kuopio, Finland. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured with dual x-ray absorptiometry, and grip strength was measured with a pneumatic squeeze dynamometer at baseline in 1989-1991 and at the 10-year follow-up in 1999-2001. METHODS: Women were divided into three groups according to change in age-grouped grip-strength quartile in both of the measurements: "decreased" (n=133), "maintained" (n=300), and "improved" (n=154). In addition, the study sample was divided into two groups according to weight change during the follow-up: weight losers (n=156) and weight gainers (n=431). RESULTS: There were no differences in the change status of grip (muscle) strength between the weight loss and weight gain groups (p>0.500, Pearson chi-square test). Women losing weight during the follow-up and within the improved grip-strength-change group had a significantly lower bone loss rate compared with those in the maintained and decreased grip-strength-change groups (p<0.01 in comparison to the decreased group). This was in contrast to women who gained weight during the follow-up (not significant between any grip-strength-change groups). Furthermore, women who lost body weight and were in the improved grip-strength-change group had a bone loss rate comparable with that of the women who gained body weight (not significant). This was in contrast to the maintained (p<0.05 between weight losers versus gainers in LS) and decreased grip-strength-change groups (p<0.01 weight losers versus gainers in LS and FN). CONCLUSION: The present study suggests that maintaining muscle strength may counteract postmenopausal bone loss related to weight loss. Accordingly, exercise that improves muscle strength may be encouraged for postmenopausal women with weight loss intentions for other health reasons.

Absorptiometry, Photon↗

Bone mass and mineral metabolism in HIV+ postmenopausal women.

The objective of this cross-sectional study was to estimate the prevalence of and risk factors for osteoporosis in HIV+ postmenopausal women. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) and biochemical indices of mineral metabolism were measured in 31 Hispanic and African American HIV+ postmenopausal women. BMD was compared with 186 historical controls, matched for age, ethnicity and postmenopausal status. Mean BMD was significantly lower at the lumbar spine and total hip in the HIV+ group, as compared with controls. Prevalence of osteoporosis was higher in the HIV+ group than controls at the lumbar spine (42% vs 23%, p =0.03) and total hip (10% vs 1%, p =0.003). Among HIV+ women, time since menopause and weight were significant predictors of BMD, while duration or class of antiretroviral therapy (ART), AIDS diagnosis, nadir CD4, steroid use, and vitamin D deficiency were not. Prevalence of osteoporosis is substantially higher in HIV+ Hispanic and African-American postmenopausal women than in controls. Established osteoporosis risk factors were more important in predicting BMD than factors associated with HIV infection and ART. Long-term management of the growing female HIV population should include the evaluation for and management of osteoporosis.

Absorptiometry, Photon↗

The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women.

The objective was to identify single nucleotide polymorphisms (SNPs) in exons of the osteoprotegerin gene and to analyze the relationship between the SNPs and bone mineral density in postmenopausal women. We used polymerase chain reaction (PCR) and direct sequencing methods to identify SNPs and genotypes in 205 postmenopausal women. BMD at the lumbar spine (L2-4) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry (DEXA). Serum osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL) and urinary N-telopeptide of type I collagen (NTx) were also measured. In exon 1 of the OPG gene, we found the Lys3Asn SNP. In 205 postmenopausal women, the Asn-allele frequency was 26.0%, and the distribution of Lys3Asn genotypes was Lys-Lys 56.6%, Lys-Asn 34.6% and Asn-Asn 8.8%, respectively. BMD at the lumbar spine (L2-4) of the Asn-Asn genotype was significantly higher (9.5-12.6%) than Lys-Asn and Lys-Lys genotypes (P=0.012), with evidence for an allele dose effect (P=0.008). Results remained similar after adjustment for age and body mass index. The Lys3Asn polymorphism of the OPG gene alone accounted for 7.7% of the variance of the L2-4 BMD in a multiple regression model. Logistic regression analysis revealed that the OPG genotype Lys-Lys had a 2.7 times (95% CI: 0.83-9.11) greater risk for osteopenia/osteoporosis than the Asn-Asn genotype. The Lys3Asn polymorphism in the OPG gene is associated with L2-4 BMD in postmenopausal women. The Lys-allele is associated with lower BMD and an increased risk for osteoporosis.

Absorptiometry, Photon↗

Association of red blood cell 5-methyltetrahydrofolate folate with bone mineral density in postmenopausal Iranian women.

Recent studies have suggested that hyperhomocysteinemia and low plasma folate are associated with fracture and also bone mineral density (BMD) and that they may contribute to the pathogenicity of osteoporosis in postmenopausal women. However, as plasma total homocysteine (tHcy) and plasma folate can be regarded as short-term markers when compared to a long-term variable such as BMD, in this study we tested the hypothesis that low red blood cell 5-methyltetrahydrofolate (RBC 5-MTHFR) as a long-term marker of the folate status may be a better predictor of BMD than plasma 5-MTHF, and its deficiency may contribute to the pathogenicity of osteoporosis in postmenopausal Iranian women. The BMD at the femoral neck and lumbar spine (measured by dual-energy X-ray absorptiometry, DXA) together with anthropometric and biochemical components of the homocysteine re-methylation pathway including plasma tHcy, 5-MTHF and vitamin B12, RBC 5-MTHF and creatinine were determined in 366 postmenopausal women. RBC 5-MTHF was more highly correlated with BMD at the lumbar spine (r=0.21, P=0.001) and femoral neck (r=0.19, P=0.004) than was plasma 5-MTHF (lumbar spine; r=0.14, P=0.03 and femoral neck; r=0.17, P=0.006). Stepwise multiple linear regression analyses revealed that RBC 5-MTHF was one of the predictors of BMD explaining 4.3 and 4.0% variance of BMD at the lumbar spine and femoral neck, respectively, whereas plasma 5-MTHF was excluded in the model and not determined to be a predictor of BMD at both the lumbar spine and femoral neck when adjusted for age, BMI, years since menopause and RBC 5-MTHF. This study suggests that RBC 5-MTHF is a better predictor of BMD than plasma 5-MTHFR when compared to a long-term marker such as BMD, and its deficiency is associated with low BMD that may contribute to the pathogenicity of osteoporosis in postmenopausal women.

Absorptiometry, Photon↗

Use of dental panoramic radiographs in identifying younger postmenopausal women with osteoporosis.

INTRODUCTION: Eroded or thin inferior cortex of the mandible detected on dental panoramic radiographs may be useful for identifying postmenopausal women with low bone mineral density (BMD) or osteoporosis. The purpose of this study was to evaluate whether these panoramic measurements are useful for identifying low BMD or osteoporosis in postmenopausal women younger than 65 years. METHODS: We compared the diagnostic performances of panoramic measurements with those of the osteoporosis self-assessment tool (OST) for identifying women with low BMD (T-score of -2.0 or less at either the lumbar spine or the femoral neck) and osteoporosis (T score of -2.5 or less) in 158 healthy Japanese postmenopausal women aged 46 years to 64 years. Mandibular cortical shape (erosion) and width were evaluated on dental panoramic radiographs. Receiver operating characteristic curve analysis was used to determine the optimal cutoff thresholds for cortical width and OST index. RESULTS: The sensitivity and specificity, respectively, for identifying women with low BMD were 82.3% and 55.2% for OST index, 79.0% and 50.0% for cortical width, and 72.6% and 74.0% for cortical shape. The sensitivity and specificity, respectively, for identifying women with osteoporosis were 86.7% and 46.9% for OST index, 90.0% and 45.3% for cortical width, and 86.7% and 65.6% for cortical shape. Likelihood ratio for identifying women with low BMD was 13.90 for thin cortical width (<3.0 mm) and 10.84 for severely eroded cortex. That for identifying women with osteoporosis was 6.40 for thin cortical width and 7.11 for severely eroded cortex. CONCLUSIONS: Dentists may be able to refer postmenopausal women younger than 65 years for bone densitometry on the basis of incidental findings on dental panoramic radiographs.

Bone Density↗

Skeletal benefits of two years of alendronate treatment are similar for early postmenopausal Asian and Caucasian women.

Alendronate has been shown to increase bone density among early postmenopausal women. Osteoporosis is common among both Asian and Caucasian women, but most clinical trials have consisted primarily of Caucasian women, and it does not appear that the effectiveness of antiresorptive agents such as alendronate has been compared between the two races. In this study we compared the response of bone density and biochemical markers to alendronate among 136 Asian and 126 Caucasian women who participated in the Early Postmenopausal Interventional Cohort (EPIC) at the Hawaii center. Approximately 40 women of each race were randomly assigned to placebo or to 2.5 mg/day or 5 mg/day alendronate. Bone mineral density (BMD) was measured at the spine, total hip and total body at baseline, 12 months and 24 months; biochemical markers of bone turnover were measured at 6-month intervals. Responses were greater for the 5 mg dose than 2.5 mg, and were similar in the two races. For example, mean (SE) changes in spine BMD at 24 months for Caucasians and Asians, respectively, were -1.9% (0.5%) and -1.9% (0.4%) for the placebo group, 2.0% (0.5%) and 3.4% (0.5%) at 2.5 mg/day and 4.2% (0. 5%) for both races at 5 mg/day. Corresponding changes in urinary N-telopeptide collagen crosslinks were -33.6% (5.6%) and -27.8% (5. 8%) for placebo, -51.4% (4.0%) and -62.1 (4.3%) at 2.5 mg/day and -70.8% (2.4%) and -73.5% (3.1%) at 5 mg/day. We conclude that (1) the rate of bone loss in untreated Asian and Caucasian postmenopausal women is similar, with the possible exception of the hip; (2) 5 mg alendronate daily provides greater skeletal benefits than 2.5 mg/day in both Asian and Caucasian early postmenopausal women; and (3) the response at 5 mg/day is similar in the two races.

Alendronate↗

Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group.

Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age +/- SD: 60.2 +/- 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: -2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCL (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p < 0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p < 0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p < 0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p < 0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density.

Aged↗

Unbalanced diet to lower serum cholesterol level is a risk factor for postmenopausal osteoporosis and distal forearm fracture.

The purpose of this study was to assess whether dietary changes aimed at reducing serum cholesterol can increase the risk of osteoporosis (OP) and fracture. The study group consisted of 311 postmenopausal women with high serum cholesterol levels and following a diet low in dairy products (calcium intake estimated at less than 300 mg/day) for 27.3 +/- 29.1 months. This sample was compared with a case-control group of 622 healthy postmenopausal women paired for age and age at menopause and with a calcium intake estimated at more than 1 g/day. Bone mineral density was measured at the lumbar spine by dual-energy X-ray absorptiometry. Prevalence of OP was significantly higher in women with a low dairy calcium intake (42.1% vs 22.3%; p < 0.0001), as was the number of Colles' fractures occurring after menopause (4.5% vs 1.6%; p = 0.008). Multiple logistic regression analyses demonstrated that a diet low in dairy calcium was a risk factor for OP (OR = 2.52, 95% CI 1.84-3.45) and Colles' fracture (OR = 2.72, 95% CI 1.18-6.26). In the low dairy calcium group, diet duration significantly influenced the risk of OP (OR = 1.13, 95% CI 1.01-1.25 for 1 year of diet). No differences in further risk factors for coronary heart disease were found between the groups, but the proportion of women physically active was lower in the women with high serum cholesterol levels. A diet that severely limits calcium intake from dairy products in an attempt to correct raised serum cholesterol levels is a risk factor for postmenopausal OP and Colles' fracture. Dietary intervention methods to lower serum cholesterol in postmenopausal women should maintain an adequate calcium intake by providing calcium from low-fat dairy products or calcium supplements.

Adult↗

Multisite quantitative ultrasound: Colles' fracture discrimination in postmenopausal women.

Distal forearm fractures are the most common perimenopausal fracture and are generally associated with osteoporosis. The aim of this study was to evaluate the capability of speed of sound (SOS) measurements in cortical bone at the phalanx, radius, tibia and metatarsal to discriminate Colles' fracture cases from controls in postmenopausal women and to compare this with bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA). Sixty-three postmenopausal Colles' fracture cases and 191 postmenopausal controls had SOS measurements of the radius, tibia, phalanx and metatarsal using a semi-reflection ultrasound technique and BMD measurements of the lumbar spine and proximal femur using DXA. The age-adjusted odds ratios (ORs) for fracture for the SOS measurement sites were 1.50 [95% CI 1.07-2.10] for the radius, 1.23 [0.86-1.76] for the tibia, 1.85 [1.06-3.23] for the phalanx and 1.74 [1.12-2.71] for the metatarsal site. For the BMD measurements the ORs were 1.95 [1.34-2.85] for the lumbar spine, 2.21 [1.43-3.40] for the femoral neck and 2.62 [1.69-4.08] for the total hip. The benefits of combining sites either by taking their average Z-score or by using the manufacturer's ORI algorithm were evaluated. The two methods yielded similar results and the ORs for the combination of the radius and phalanx were 2.00 [1.21-3.33], for the radius and metatarsal 1.67 [1.05-2.67], for the phalanx and metatarsal 1.86 [1.11-3.08] and for the radius, phalanx and metatarsal 1.81 [1.07-3.06]. Combinations of DXA sites gave 2.22 [1.44-3.41] for the lumbar spine and femoral neck and 2.41 [1.57-3.70] for the lumbar spine and total hip. In conclusion, semi-reflection ultrasound measurements at the radius, phalanx or metatarsal demonstrated an ability to discriminate fracture cases from controls in postmenopausal Colles' fracture patients, although the odds ratios were lower than with spine and femur BMD.

Absorptiometry, Photon↗

Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age.

Although several observational studies have demonstrated an association between vitamin K status and bone mineral density (BMD) in postmenopausal women, no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far. In the trial presented here we have investigated the potential complementary effect of vitamin K1 (1 mg/day) and a mineral + vitamin D supplement (8 microg/day) on postmenopausal bone loss. The design of our study was a randomized, double-blind, placebo-controlled intervention study; 181 healthy postmenopausal women between 50 and 60 years old were recruited, 155 of whom completed the study. During the 3-year treatment period, participants received a daily supplement containing either placebo, or calcium, magnesium, zinc, and vitamin D (MD group), or the same formulation with additional vitamin K1 (MDK group). The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years, as measured by DXA. The group receiving the supplement containing additional vitamin K1 showed reduced bone loss of the femoral neck: after 3 years the difference between the MDK and the placebo group was 1.7% (95% Cl: 0.35-3.44) and that between the MDK and MD group was 1.3% (95% Cl: 0.10-3.41). No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine. If co-administered with minerals and vitamin D, vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck.

Absorptiometry, Photon↗

Susceptibility for postmenopausal osteoporosis: interaction between genetic, hormonal and lifestyle factors.

Although previous studies have established the importance of genetic, hormonal and lifestyle factors separately, the integral role of these factors on bone mass in postmenopausal women is still controversial. We examined the association of the collagen 1-alpha-1 gene (COLIA1) and vitamin D receptor gene (VDR) polymorphisms, s-IGF-I, s-25OHD and lifestyle factors with bone mineral density (BMD) in postmenopausal women. We determined anthropometric parameters, lifestyle factors, serum levels of IGF-I and 25OHD, the COLIA1 Sp1 (Mscl) and VDR (Bsml, Taql) polymorphisms by PCR and BMD by dual X-ray absorptiometry in 141 ambulatory postmenopausal Spanish women. There were significant linear correlations between S-25OHD and BMD and between s-IGF-I and BMD. BMD was statistically higher in active subjects. Of the three different polymorphisms, only the COLIA1 Sp1 polymorphism was significantly associated with BMD. In the logistic regression model, the COLIA1 Sp1 polymorphism, S-25OHD, s-IGF-I and physical activity variables were independently associated with osteoporosis. Our study shows that COLIA1 Sp1 polymorphism, S-25OHD and s-IGF-I serum levels and physical activity are independently associated with BMD in postmenopausal Spanish women.

Anthropometry↗

Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women.

Osteoporosis is one of the most common skeletal disorders affecting postmenopausal women. The purpose of this study was to investigate whether a 24-week program of aerobic high-impact loading exercise was beneficial for enhancing physical fitness and bone mineral density (BMD) in osteopenic postmenopausal women. Forty-three postmenopausal women aged 48-65 years participated in this study. The BMD of the spine (L2-L4) and right femoral neck of each woman was below 1 SD of the mean of premenopausal women, as examined by dual X-ray absorptiometry. The assignment of subjects into exercise or control group was not randomized but based on each subject's anticipated compliance to the 6-month long exercise program. Twenty-two subjects joined the exercise group and attended the training programs and 21 served as the control group. Exercise programs included treadmill walking at an intensity above 70% of maximal oxygen consumption (VO2max) for 30 minutes, followed by 10 minutes of stepping exercise using a 20-cm-high bench. The program was conducted three times per week for 24 weeks. Physical fitness measurements included testing of flexibility, muscular strength and endurance, body composition, and cardiopulmonary fitness. The results showed that the quadriceps strength, muscular endurance, and VO2max in the exercise group had significant improvements, whereas no improvement was found in any of the physical fitness parameters in the control group. The BMD of the L2-L4 and the femoral neck in the exercise group increased 2.0% (P > 0.05) and 6.8% (P < 0.05) and those in the control group decreased 2.3% (P < 0.05) and 1.5% (P > 0.05), respectively. In conclusion, aerobics combined with high-impact exercise at a moderate intensity was effective in offsetting the decline in BMD in osteopenic postmenopausal women.

Absorptiometry, Photon↗

Systematic review of randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women.

Studies of the effect of exercise programs on bone mass appear inconsistent. Our objective was to systematically review and meta-analyze randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women. A computerized MEDLINE search was conducted for the years 1966-1997. Thirty-five randomized trials were identified. Meta-analytic methods were used to statistically pool results of studies of the effect of impact (e.g., aerobics) and non-impact (e.g., weight training) exercise on the lumbar spine and femoral neck. The most studied bone site was the lumbar spine in postmenopausal women (15 studies), where both impact [1.6% bone loss prevented, 95% confidence intervals (CI): 1.0%-2.2%] and non-impact (1.0%, 95% CI: 0.4%-1.6%) exercise programs had a positive effect. Results for the lumbar spine in premenopausal women (eight studies) were similar: 1.5% (95% CI: 0.6%-2.4%) less bone loss (or net gain) after impact exercise and 1.2% (95% CI: 0.7%-1.7%) after non-impact exercise. Impact exercise programs appeared to have a positive effect at the femoral neck in postmenopausal women (five studies), 1.0% (95% CI: 0.4%-1.6%) bone loss prevented, and possibly in premenopausal women, 0.9% (95% CI: -0.2%-2.0%) bone loss prevented. There were too few trials to draw conclusions from meta-analyses of the effect of non-impact exercise on the neck of femur. This systematic review of randomized trials shows that both impact and non-impact exercise have a positive effect at the lumbar spine in pre- and postmenopausal women. Impact exercise probably has a positive effect at the femoral neck. More studies are required to determine the optimal intensity and type of exercise.

Animals↗

Prediction of bone loss rate in healthy postmenopausal women.

Prevention of fractures is the only way to drastically reduce osteoporosis-related health expenditures. In order to optimize the cost/benefit ratio of a strategy of prevention, it is essential to identify, as early as possible, women who will develop fractures later in their life. Therefore, and since postmenopausal bone loss is an asymptomatic process, screening procedures should detect, at the time of the menopause, women whose postmenopausal bone loss is higher than the mean, and will, a couple of years later, exhibit a low mineral content and a subsequent high risk for fractures. For 3 years we have followed a cohort of 92 healthy women who had undergone menopause less than 36 months previously. By a multivariate discriminant analysis based on the differences in lumbar bone density, assessed by dual photon absorptiometry, and in a few routine biochemical parameters (serum phosphorus, estrone, androstenedione, and urine calcium) observed during the first 6 months of the study, we have been able to correctly predict the rate of spinal bone loss, observed at the end of the 3 years, in 76% of the subjects. All of the women who presented a bone loss higher than 10% over the 3 years were correctly isolated by our discriminant functions after 6 months of follow-up. We conclude that a measurement of lumbar bone mineral density coupled with a few routine biochemical determinations, repeated twice at a 6-month interval in healthy postmenopausal women, can isolate 100% of postmenopausal "fast bone losers" with an overall specificity of 76%.

Absorptiometry, Photon↗

Etidronate and hormone replacement therapy (HRT) for postmenopausal women with osteoporosis despite HRT.

Hormone replacement therapy (HRT) is effective treatment for postmenopausal bone loss and osteoporosis. However, postmenopausal women with low bone mass fail to respond after a few years of HRT and some postmenopausal women show no bone response to HRT. In these cases, additive therapy is necessary. Bisphosphonates are highly effective in postmenopausal osteoporosis. We investigated the effects of adding etidronate, a bisphosphonate, to HRT. The addition of etidronate to HRT improved bone density (4.40+/-1.12% increase per year) in patients showing no increase or even a decrease after at least 1 year of HRT (5.39+/-2.40% decrease per year).

Absorptiometry, Photon↗

Assessment of reliability endometrial brush cytology in detection etiology of late postmenopausal bleedings.

We evaluated the possibility of discovering bleeding causes in late postmenopausal period with cytological examination of material received by endometrial brush in comparison with Pap test and fractionated curettage. Sixty-two women in late postmenopausal period with cervical canal bleeding, treated in gynecological department of clinical hospital in Osijek, were cytological and histological processed. Final diagnosis in 29 from 62 (46.8%) women with late postmenopausal bleeding was cancer. 25 (40.3%) women had endometrial adenocarcinoma and 4 (6.5%) of them had squamous endocervical carcinoma. Two women had endometrial precancerous (3.2%). With Pap test accurate diagnosis was set up in 13 from 25 (52.0%) women with endometrial adenocarcinoma and in all of them with squamous endocervical carcinoma. With endometrial brush accurate diagnosis was set up in 14 from 25 (56.0%) women with endometrial adenocarcinoma and in 3 from 4 (75.0%) women with squamous endocervical carcinoma. With fractional curettage the diagnosis of endometrial adenocarcinoma was accurately correct in 21 from 25 (84.0%) women and in all of them with squamous endocervical carcinoma. Cytological examination of material derived with endometrial brush, alike vaginal cytology, is not enough reliable method in our conditions for discovering bleeding causes in late postmenopausal period. Diagnostic exactness of procedure could be increased by histopathological examination of material from endometrial brush procedure and with ultrasound evaluation of endometrium thickness.

Adenocarcinoma↗