Multifactorial analysis of risk factors for reduced bone mineral density among postmenopausal women

Introduction

The study aimed to determine the risk factors for reduced bone mineral density (BMD) among postmenopausal women.

Material and methods

Two hundred and fifty-three postmenopausal women were included to the study. The study group consisted of 85 women with osteoporosis (mean age: 59.9 years) and 168 with osteopenia (mean age: 57.8 years). Patients were assigned to groups according to their BMD measured in the lumbar spine, hip and femoral neck by dual X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin and bone resorption by measuring serum C-terminal type I α-collagen chain telopeptide.

Results

Multiple regression analysis for lumbar spine showed association of age (p = 0.001), parental history of fracture (p = 0.05), use of hormone replacement therapy (p = 0.034), bisphosphonates therapy (p < 0.001), calcium and vitamin D supplements therapy (p = 0.001), oestradiol level (p = 0.007) and body mass index (p < 0.001). Multiple regression analysis for femoral neck and hip total showed association of age (p = 0.001), parental history of fracture (p = 0.049), use of bisphosphonates (p < 0.03)) use of calcium and vitamin D supplements (p = 0.039), oestradiol level (p = 0.047). All the variables together explain 40.4% of variance in BMD for the lumbar spine and 25.6% of variance in BMD for femoral neck and hip total.

Conclusions

The present study demonstrated correlations between the variables and BMD, which are known and widely described in the literature. Osteoporosis and osteopenia in Polish subjects appear to be associated with several known risk factors that are well described in the literature.     

The effect of breast-feeding duration on bone mineral density in postmenopausal Turkish women: a population-based study

Introduction

In the present study, we investigated the effects of breast-feeding time on bone mineral density (BMD) later in life.

Material and methods

The current study was based on a retrospective analysis of 586 postmenopausal women with a mean age of 60.8 years, who were screened for osteoporosis by dual energy X-ray absorptiometry (DXA).They were classified into 4 groups with respect to the duration of their breast-feeding as never (group 1), 1-24 months (group 2), 25-60 months (group 3), or > 60 months (group 4). Bone mineral density results for the femur neck and lumbar spine were classified into 3 groups according to WHO criteria as normal (T score > –1.0 SD), osteopenia (T score –1.0 to –2.5 SD), and osteoporosis (T score < –2.5 SD). Patients with osteopenia or osteoporosis (T score < –1.0 SD) were considered as having low bone mass (LBM).

Results

We found a correlation between duration of lactation and femur BMD or spine BMD in the study population (r = 0.116, p < 0.005; r = –0.151, p = 0.001, respectively). Significant differences were found between femur BMD and spine BMD of groups in one-way ANOVA analysis (p = 0.025, p = 0.005, respectively). Additionally, when compared with the other three groups, group 4 was older and had longer duration of menopause (p < 0.01). In logistic regression analysis, age and body mass index were found as independent risk factors of LBM [odds ratio: 1.084 (95% CI 1.031-1.141); odds ratio: 0.896 (95% CI 0.859-0.935)], while duration of lactation was not found as an independent predictor of LBM.

Conclusions

In this study, we have found that changes of bone metabolism during lactation had no effect on postmenopausal BMD measured by DXA. Consequently, it can be suggested that long breast-feeding duration is not a risk factor for low bone mass later in life.     

The positive association between peripheral blood cell counts and bone mineral density in postmenopausal women

Purpose

Accumulating evidence has shown a close connection between hematopoiesis and bone formation. Our aim was to evaluate the association between peripheral blood cell counts and bone mineral density (BMD) in a sample of postmenopausal women.

Materials and Methods

Three hundreds thirty eight healthy postmenopausal women who underwent BMD measurement during their health check-up were investigated. BMD was measured by dual energy X-ray asorptiometry at L1-L4 spine, femoral neck and total proximal femur. BMD was expressed as a T-score: among T-scores obtained from three different sites (L1-L4 spine, femoral neck and total proximal femur), the lowest T-score was considered to be the subject''s T-score.

Results

The prevalence of osteopenia and osteoporosis diagnosed by T-score in the study participants were 49.4% (167/338) and 5.0% (17/338), respectively. Peripheral blood white blood cell (WBC), red blood cell (RBC) and platelet counts had significant positive correlations with T-scores (p<0.001) upon simple linear regression analysis. A multiple linear regression analysis, after controlling of confounders including age, body weight, systolic blood pressure, alkaline phosphatase and creatinine, showed that WBC (β=0.127; standard error=0.043; p=0.014), RBC (β=0.192; standard error=0.139; p<0.001) and platelet (β=0.097; standard error=0.001; p=0.050) counts still had significant positive association with T-scores.

Conclusion

The study results showed a positive relationship between blood cell counts and bone mineral density in postmenopausal women, supporting the idea of a close connection between hematopoiesis and bone formation. The study results also suggest that blood cell counts could be a putative marker for estimating BMD in postmenopausal women.     

Relationship between BMD, dental panoramic radiographic findings and biochemical markers of bone turnover in diagnosis of osteoporosis

OBJECTIVE: Mandibular indices, measured on panoramic radiographs, may be useful screening implements for low skeletal bone mass density (BMD). Recent studies suggest that radiographic examination of mandible may constitute an effective process for the early diagnosis of osteoporosis. Biochemical markers of bone turnover may be of value for prediction of individual bone loss and they may help in predicting risk of fracture in elderly women. In contrast to the vast information available on dental radiographic findings and BMD only scarce data exist on the relationship between panoramic mandibular indices and biochemical markers. The aim of this study was to examine the diagnostic performance of dental panoramic radiography and biochemical markers of bone turnover in relation to BMD at the spine in a group of postmenopausal women. SUBJECTS AND METHODS: An assessment of the number of lost teeth, mandibular cortical width (MCW) at the mental region and morphologic classification of mandibular inferior cortex (MIC grade) was performed on dental panoramic radiographs in a group of 141 postmenopausal women 38-81 years of age. BMD at the lumbar spine was measured by dual energy X-ray absorptiometry. BMD values were categorized as normal (T-score greater than 1.0), and as indicative of osteopenia (T-score -1.0 to -2.5) or osteoporosis (T-score less than -2.5) according to the World Health Organization classification. Serum bone alkaline phosphatase (BAP) was measured with an enzyme immunoassay. Cross-linked N-telopeptides of type I collagen (NTx) corrected for creatinine secretion, was measured with a competitive-inhibition enzyme-linked immunosorbent assay ELISA. RESULTS: In our study, a decrease in MCW by 1mm increases the likelihood of osteopenia or osteoporosis to 47% (p-value<0.05), having taken into consideration the effect of the years elapsed since menopause. The increase of alkaline phosphatase (ALP) per unit increase the likelihood of osteopenia or osteoporosis to 14% (p-value<0.05), having checked the effect of the years since menopause. A decrease in MCW by 1mm increases the likelihood of moderately or severely eroded cortex to 97% (p-value<0.001). The increase in ALP per 1 unit increases the likelihood of moderate or severe erosion per 10% (p-value<0.05), taking into account the years since menopause. CONCLUSIONS: Our results suggest that dentists have sufficient clinical and radiographic information that enables them to play a significant role in early diagnosis of osteoporosis in postmenopausal women. Panoramic radiographs and biochemical markers of bone turnover may be of value for prediction of individual bone loss and they may help in predicting risk of fracture in elderly women.     

Relationship between blood pressure levels and bone mineral density in postmenopausal Turkish women

Introduction

We investigated the association between bone mineral density (BMD) detected by dual-energy X-ray absorptiometric (DXA) method and blood pressure (BP) in a large sample of postmenopausal women.

Material and methods

The current study was based on a retrospective analysis of 586 postmenopausal women with a mean age of 60.8 ±8.8 years, who were screened for osteopenia or osteoporosis by DXA. Patients with hypertension (HT, n= 306) were compared with normotensive (NT, n = 290) individuals. Bone mineral density results for the femur neck and spine were classified into 3 groups according to World Health Organization criteria: normal (T score > –1.0 SD), osteopenia (T score –1.0 to –2.5 SD) and osteoporosis (T score < –2.5 SD). Patients with osteopenia or osteoporosis (T score < –1.0 SD) were grouped as having low bone mass (LBM).

Results

There were no significant differences in femur T score, femur BMD, femur Z score, spinal T score, spinal BMD and spinal Z score between hypertensive and normotensive groups. The group of patients with low bone mass calculated from femur T scores had higher age, systolic BP, duration of hypertension and duration of menopause, but lower BMI. Similarly, patients with low spine BMD had higher age and duration of menopause, but lower BMI. Linear regression analysis showed a significant correlation between systolic BP and femur BMD and T score values. Furthermore, logistic regression analysis revealed that hypertension is an independent predictor of spinal osteopenia and osteoporosis.

Conclusions

The presence of hypertension is an independent predictor of spinal low bone density in Turkish women after menopause.     

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.     

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.     

The Value of Calcaneal Bone Mass Measurement Using a Dual X-Ray Laser Calscan Device in Risk Screening for Osteoporosis

OBJECTIVE

To evaluate how bone mineral density in the calcaneus measured by a dual energy X-ray laser (DXL) correlates with bone mineral density in the spine and hip in Turkish women over 40 years of age and to determine whether calcaneal dual energy X-ray laser variables are associated with clinical risk factors to the same extent as axial bone mineral density measurements obtained using dual energy x-ray absorbtiometry (DXA).

MATERIALS AND METHODS

A total of 2,884 Turkish women, aged 40–90 years, living in Ankara were randomly selected. Calcaneal bone mineral density was evaluated using a dual energy X-ray laser Calscan device. Subjects exhibiting a calcaneal dual energy X-ray laser T- score ≤-2.5 received a referral for DXA of the spine and hip. Besides dual energy X-ray laser measurements, all subjects were questioned about their medical history and the most relevant risk factors for osteoporosis.

RESULTS

Using a T-score threshold of −2.5, which is recommended by the World Health Organization (WHO), dual energy X-ray laser calcaneal measurements showed that 13% of the subjects had osteoporosis, while another 56% had osteopenia. The mean calcaneal dual energy X-ray laser T-score of postmenopausal subjects who were smokers with a positive history of fracture, hormone replacement therapy (HRT), covered dressing style, lower educational level, no regular exercise habits, and low tea consumption was significantly lower than that obtained for the other group (p<0.05). A significant correlation was observed between the calcaneal dual energy X-ray laser T-score and age (r=−0.465, p=0.001), body mass index (BMI) (r=0.223, p=0.001), number of live births (r=−0.229, p=0.001), breast feeding time (r=−0.064, p=0.001), and age at menarche (r=−0.050, p=0.008). The correlations between calcaneal DXL and DXA T-scores (r=0.340, p=0.001) and calcaneal DXL and DXA Z-scores (r=0.360, p=0.001) at the spine, and calcaneal DXL and DXA T- scores (r=0.28, p=0.001) and calcaneal DXL and DXA Z-scores (r=0.33, p=0.001) at the femoral neck were statistically significant.

CONCLUSION

Bone mineral density measurements in the calcaneus using a dual energy X-ray laser are valuable for screening Turkish women over 40 years of age for the risk of osteoporosis.     

Association between osteoporosis and hepatitis B cirrhosis: a case-control study

Background and aimsHepatitis B virus (HBV)-related cirrhosis is associated with decreased bone mineral density (BMD); however, the mechanism is yet unknown. To assess the incidence of osteoporosis in patients with HBV-associated cirrhosis and relevant mechanisms.MethodsA total of 80 hospitalized patients with HBV-associated cirrhosis and 80 healthy controls were enrolled. The levels of serum osteocalcin, total procollagen type 1 amino-terminal propeptide, β-C-terminal telopeptide of type I collagen (β-CTX), and 25-hydroxy vitamin D3 (25(OH)D3) was evaluated in the cirrhosis group.ResultsThe BMDs of the lumbar spine (P<0.001) and hip joints (P=0.015) in the cirrhosis group were significantly lower than those in the controls. The incidence of osteoporosis in the cirrhosis group was significantly higher than that in the control group (P<0.001). Compared to the patients of the Child-Pugh grade A and B, the BMD of lumbar spine and 25(OH)D3 was significantly decreased in patients of grade C, while β-CTX was elevated. Patients in the cirrhosis group faced a higher risk of osteoporosis as compared to the controls(P<0.001).ConclusionsEnhanced bone resorption accounted for increased risk of osteoporosis in severe cirrhosis. Thus, HBV-associated cirrhosis was a risk factor for osteoporosis.     

Association of the MTHFR C677T polymorphism and bone mineral density in postmenopausal women: a meta-analysis

Osteoporosis is a condition characterized by low bone mineral density (BMD) and micro-architectural changes in the bone tissue. The risk of osteoporosis is partly determined by genetic factors. The role of C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in postmenopausal osteoporosis. However, the relationship between MTHFR polymorphism and BMD is still controversial. We carried out a meta-analysis of 5,833 subjects to evaluate the association of MTHFR and BMD in postmenopausal women. Databases of MEDLINE, Web of Science, Scopus and CNKI were retrieved for all publications relating to MTHFR polymorphism and BMD in postmenopausal women. Five eligible studies were selected for meta-analysis. All these articles studied the association of MTHFR polymorphism and BMD of the femoral neck and lumbar spine in postmenopausal women. Our analysis suggested that postmenopausal women with the TT genotype had lower femoral neck BMD than the women with the CC/CT genotype, and the weighted mean difference (WMD) was -0.01 g/cm² [95% confidence interval (CI): (-0.01, -0.01), P < 0.01]. However, BMD of the lumbar spine of postmenopausal women with the TT genotype was not significantly different from that of women with the CC/CT genotype. In the random effects model, the WMD between the TT and TC/CC genotype was -0.01 g/cm² [95% CI: (-0.04, 0.01), P = 0.32]. The C677T polymorphism of the MTHFR gene is associated with BMD of the femoral neck in postmenopausal women. Women with the TT genotype of the MTHFR gene have lower BMD, suggesting that the TT genotype may be a risk factor for postmenopausal osteoporosis.     

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.     

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.     

Bone mineral density in mild and advanced ankylosing spondylitis

To compare the bone mineral density (BMD) and determine the frequency of osteoporosis in mild and advanced ankylosing spondylitis (AS) cases. Seventy three patients with AS were enrolled in this study. The BMD was analyzed at the lumbar spine and hip by dual energy X-ray absorptiometry. The patients were diagnosed as being "normal, osteopenia, or osteoporosis" according to the WHO classification. Using the BASRI-lumbar and BASRI-hip scores, the patients were grouped in mild and advanced AS categories. The mean BMD in the lumbar spine and hip of patients with mild and advanced AS was similar (p > 0.05). While 61.6% of the patients were found to have osteopenia or osteoporosis in the lumbar spine, 46.6% had osteopenia or osteoporosis in the total hip. Of the patients with advanced AS 54.3% had osteopenia or osteoporosis in the lumbar spine, 75% in the total hip. Of the patients with mild AS patients had 68.4% osteopenia or osteoporosis in the lumbar spine, and 42.3% in the total hip. The osteopenia or osteoporosis frequency of the mild and advanced cases of AS in the lumbar spine was similar (p > 0.05). In the advanced AS patients, osteopenia or osteoporosis frequency was significantly higher in the total hip than in the mild AS patients (p < 0.05). In conclusion, there was evidence of osteoporosis in both the advanced AS and mild AS patients. The reason why the anteroposterior lumbar DXA results in the advanced AS patients were similar to the mild ones may be due to the existence of syndesmophytes and ligament calcification. In these cases, it is more convenient to use a hip DXA for assessing the extent of osteoporosis.     

Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized,Double-Blind,Placebo-Controlled Trial with Open-Label Extension

PurposeThe efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study.ResultsBaseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals.ConclusionDenosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.     

Creatinine clearance at menopause is not related to bone mass in later life

Objective: To investigate whether creatinine clearance (Ccr) at menopause is related to bone mass later in life. Methods: Ccr was measured within 5 years after natural menopause in two groups af normal women. Bone mineral content (BMC) of the distal forearm, lumbar spine, and proximal femur were measured by photon absorptiometry and dual energy X-ray absorptiometry in these women 6 years (n = 47) and 14 years later (n = 98). Results: Ccr corrected for body surface area just after the menopause did not correlate with BMC, 6.5 years and 14.5 years later. Conclusion: Low Ccr within the normal range at menopause is not an independent risk factor for osteopenia in later life.     

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.     

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.     

Sex steroids concentrations in relation to bone mineral density in men with coronary atherosclerosis

BACKGROUND: Although suspected, relationships between sex steroids and bone mineral density (BMD) are not fully defined in male population. According to recent data there may also exist an association between low BMD and atherosclerosis. OBJECTIVE: Our aim was to investigate relationships between serum sex steroids and BMD, and between BMD and atherosclerosis in men with coronary artery disease (CAD). SUBJECTS AND METHODS: We recruited for the study 55 men aged 40-60 years with angiographically confirmed CAD and 30 healthy, age-matched controls. In each of the examined subjects serum levels of total testosterone (T), estradiol (E(2)), estrone and DHEA-S, as well as femoral neck, lumbar spine and total skeleton BMD were measured. RESULTS: We found that the prevalence of osteopenia/osteoporosis recognized on spine and/or femoral BMD (T-score below -1.0) did not differ between men with CAD and healthy controls (respectively 47% versus 47%; p=0.8 in chi(2) Yates test). The mean BMD value at different regions did not differ between both groups either. Hormonal status of men with CAD and normal BMD was similar to men with CAD and osteopenia/osteoporosis except for the level of testosterone. After adjustment for age and BMI, men with lower BMD had lower testosterone and lower T/E(2) ratio than men with normal BMD (geometric means for testosterone were respectively: 16.1+/-8.3 versus 16.2+/-4.2; p<0.05 in ANCOVA with BMI and age as covariates; for T/E(2) ratio it was: 202.1+/-94.7 versus 222.8+/-83.9; p=0.05). However, we did not find any correlation between sex hormones concentrations and bone mineral density. There was a relationship between the advance of atherosclerosis (ranged by number of stenotic arteries) and BMD: men with the most advanced form of the disease (three-vessels) had the lowest femoral neck BMD. The groups did not differ in lumbar spine BMD. CONCLUSIONS: Our data suggest that in middle-aged men with CAD: (1) lower serum testosterone and lower T/E(2) ratio are associated with lower BMD; (2) advance of coronary atherosclerosis is inversely related to femoral neck BMD, however this relationship is weak and requires further investigation.