Spine and femur densitometry at the menopause: Are both sites necessary in the assessment of the risk of osteoporosis?

Summary The aim of our study was to compare the results provided by the measurement of vertebral and femoral bone mineral density (BMD) for assessing the individual risk of osteoporosis as defined by either low BMD and/or rapid bone loss. Vertebral and femoral BMD were measured twice at a mean interval of 21 months in 85 normal, early post-menopausal women who had passed a natural menopause 6 months to 3 years previously. According to the measurement site, 36% (spine), 29% (femoral neck), 35% (Ward's triangle), and 25% (trochanter) fall in the at risk category, defined by a BMD value of 1 SD or more below the normal values for premenopausal women. Based on vertebral BMD, 39–48% of the women at risk had a normal femoral BMD. On the other hand, 24–37% of the women classified at risk based on femoral BMD maintained a low risk at the vertebral level. The annual rate of bone loss was significantly greater for the Ward's triangle (-2.7±3.8%) and femoral neck (-2.1±2.5%) than for the spine (-1.5±2.1%) and trochanter (-1.5±3.4%). There was a significant relationship between the rate of loss measured at the spine and femoral levels (r=0.34–0.58). Among the 21 women with a rapid vertebral bone loss, 48–67% had a low bone loss at the femoral level and vice versa. The ratio between mean rate of loss and the precision of the measurement sites was greater for the spine (1.6) compared with the femur (1.1–0.71). Our results indicate that vertebral and femoral BMD measurements produce discordant results in assessing the individual risk for osteoporosis.     

Menopause-related changes in bone mineral density in Japanese women: A longitudinal study on lumbar spine and proximal femur

We investigated 2-year longitudinal changes of bone mineral density (BMD) in lumbar spine and proximal femur in 64 Japanese women aged 38–67. Forty subjects were premenopausal (mean age 44.9) and 24 postmenopausal (mean age 54.6) at enrollment of the study. Six subjects experienced menopause during the 2-year study period and were defined as the perimenopausal group. Measurements of BMD were performed using dual-energy X-ray absorptiometry at L2–4, femoral neck, greater trochanter, and Ward's triangle. Paired t test revealed no significant decrease in BMD at any site in the premenopausal group. Significant annual decrease in BMD was observed in the perimenopausal group at L2–4, femoral neck, and greater trochanter. A similar tendency was observed in Ward's triangle, but did not reach statistical significance. In the postmenopausal group, significant decrease in BMD was found at the proximal femur, but not at L2–4. Significant inverse correlation between age and change rate of BMD was found at L2–4, but not at the proximal femur, in premenopausal women. In postmenopausal women, there was a significant association between body weight (BW) change and change rate in BMD at L2–4, femoral neck, or greater trochanter. This association was not found in the premenopausal group. These results suggest that effect of menopause on BMD may be different in individuals and sites of the skeleton. BW change may affect change in BMD in postmenopausal women. However, the limited variability in both BW and BMD changes among premenopausal women in this study may explain the poor association between change in BW and change in BMD in the premenopausal group. As individual differences in each group is considerably large, annual measurements of BMD may be necessary to find possible candidates for early intervention.     

Treatment of postmenopausal vertebral osteopenia with monofluorophospate: A long-term calcium-controlled study

The aim of the present study was to assess the effects of the new fluorine pro-drug monofluorophos-phate (MFP) in postmenopausal women with vertebral osteopenia and high bone turnover. We enrolled postmenopausal women (PMW, 43–59 years) who had had a natural menopause 2–5 years before the study, had vertebral bone mineral density (BMD) <13 SD from the premenopausal mean, and had at least one of the biochemical markers of bone remodeling >1 SD over the mean for premenopausal women. Patients were randomly divided into two treatment groups (group 1, 500 mg/day of oral calcium; group 2, MFP at the dose of 20 mg F-equivalents + 600 mg calcium/day) for 2 years (n=21 in each group). The lumbar vertebral (L2–4) BMD and total body bone mineral (TBBM) were measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Corporation, USA). Urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla protein (BGP) and serum alkaline phosphatase (AP) were assayed. In group 1 the markers of bone turnover and vertebral BMD did not show any significant modification, while TBBM showed a significant (p<0.05) decrease after 24 months. In group 2 a significant (p<0.05) decrease in OH-P/Cr (–23.9±2.0%), and an increase in both BGP (+19.4±2.6%) and AP(+10.3±2.6%) levels were observed after 24 months of MFP administration. In this group, both vertebral BMD (+5.01±0.9%,p<0.01) and TBBM (+4.0±0.6%,p<0.05) showed a significant increase after 24 months. Present results suggest that, in osteopenic PMW, MFP administration induces a significant increase in vertebral BMD without impairment of cortical bone, with a reduction in bone resorption and an increase in bone formation rate.     

Effects of Menopause on Age-Dependent Bone Loss in the Axial and Appendicular Skeletons in Healthy Japanese Women

To determine the effects of menopause on bone loss in different parts of the skeleton, bone mineral density (BMD) values were measured longitudinally in 85 healthy women. BMD values included the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) and quantitative CT (QCT) and the distal and midradius measured by DXA obtained over 5 years. BMD at the calcaneus was measured using DXA for 3 years, and the BMD values of the distal metaphyses and diaphyses of radius and tibia were measured using peripheral QCT (pQCT) for 4 years. The subjects were 19 premenopausal, 17 perimenopausal, 12 early postmenopausal and 38 late postmenopausal women with the respective average ages of 39.1 ± 7.1 (SD), 51.9 ± 2.9, 55.8 ± 1.8 and 61.9 ± 3.9 years at the start of measurement. Average years since menopause were 1.4 ± 1.8, 3.3 ± 1.3 and 12.7 ± 5.3 years, respectively. In the perimenopausal group, the annual rate of bone loss for lumbar trabecular bone measured by QCT, and for the calcaneus, and metaphyseal trabecular bone at the radius and tibia by pQCT were higher than the respective values in the premenopausal group. These values in the late postmenopausal group became significantly lower compared with those in the perimenopausal group, coming down to the level of the premenopausal group. While the annual rates of bone loss at the tibial diaphysis in the perimenopausal group were also higher than those in the premenopausal group, the values at the radial diaphysis by DXA or pQCT did not differ significantly. The reductions in the annual rates of bone loss with the passage of time after menopause were not marked in these cortical bone dominated sites. These data indicated that the annual rates of bone loss at trabecular bone dominated sites were accelerated in both axial and appendicular skeletons. Diaphyseal cortical bone, however, seemed to be less sensitive to estrogen withdrawal. Other factors, such as genetics and calcium/vitamin D metabolism, would also affect the age-dependent bone loss at the cortical bone dominated sites after menopause. Received: 30 October 1998 / Accepted: 6 April 1999     

Effects of age and menopause on bone density of entire skeleton in healthy and osteoporotic women

We studied 885 women to evaluate the effects of age and menopause on bone mineral density (BMD) in both healthy and postmenopausal osteoporotic subjects. The study cohort consisted of 161 healthy premenopausal women (age range 25–54 years), 357 healthy postmenopausal women (35–85 years) and 367 osteoporotic women (41–87 years). Total body and regional (spine, trunk, pelvis, arms, legs) BMD were measured with a dual-energy X-ray (DXA) device (Lunar DPX). Premenopausal BMD values remained essentially unchanged until the first half of the fourth decade, when they decreased. BMD values in both healthy postmenopausal and osteoporotic women were significantly lower than premenopausal values, and continued to decrease statistically after the onset of menopause. The highestZ-score (0.96±0.92) was found for total body BMD. HigherT-score values were found in osteoporotic than in normal postmenopausal women. In both healthy and osteoporotic postmenopausal women the best fits for BMD changes in total body, spine, trunk, arms and legs were obtained with the natural logarithm of years since menopause; only the pelvis BMD decreased linearly. Multiple regression analysis indicated that postmenopausal BMD changes in both normal and osteoporotic women were linked chiefly to body weight and years since the onset of menopause.     

Lumbar bone mineral density in very long-term renal transplant recipients: Impact of circulating sex hormones

The influence of circulating sex hormones and gender on the bone mineral density (BMD) in long-term renal transplant recipients needs further investigation. We performed a retrospective analysis of lumbar BMD between 6 years and 20 years after renal transplantation. In 67 patients (47±12 years, 38 male) with a minimum interval of 72 months after transplantation, lumbar BMD measurements (dual energy X-ray absorptiometry) were performed (=complete cohort). Thirty-one patients (=longitudinal cohort) underwent at least three serial BMD measurements (mean follow-up 39±18 months, start at 86±22 months). All patients received prednisolone. In the complete cohort, BMD was significantly reduced in comparison to young healthy (mean T -score –1.33±1.40) and age-matched controls (mean Z -score –0.91±1.45) at 88±31 months ( p <0.05). Osteopenia or osteoporosis were present in two-thirds of patients. In the longitudinal cohort, a mean annual lumbar BMD loss of –0.6±1.9% was detectable equivalent to a –0.03±0.15 reduction of Z -scores per year (regression analysis). Impact of hormonal status: In the complete cohort, postmenopausal status was associated with significantly lower BMD levels compared to men ( p =0.0441). Women and men within the lowest tertile of sex hormone levels (LH, FSH, DHEAS, testosterone, progesterone, estradiol) did not exhibit significant differences in terms of lumbar BMD compared to those in the highest tertile. The mean annual bone loss was statistically indistinguishable between men and women. There was no significant correlation of sex hormone levels and BMD in men and premenopausal women. In postmenopausal women, however, low estradiol and high LH levels correlated with the extent of annual BMD loss ( p <0.05). Our data confirm significantly reduced lumbar T -scores in the very late period after renal transplantation. The lumbar BMD decreased by –0.6±1.9% per year. In postmenopausal long-term renal transplant recipients, low estradiol levels were associated with accelerated bone loss.The data were presented in part at the 37th annual meeting of the American Society of Nephrology, ASN 2004 (Renal Week 2004)     

Rates of Change in Spinal Bone Density Among Japanese Women

To determine the rates of change in bone mineral density (BMD) at the spine in healthy Japanese women, longitudinal measurements of spinal BMD using dual X-ray absorptiometry were collected from 984 women over 17 years of age (mean age 51.6) at eight medical research centers. They were followed up for 20.9 months on average without any treatment influencing bone and calcium metabolism. Measurements of BMD obtained by two different scanners were converted into standardized BMD (sBMD) values. The multiple linear regression model predicts that spinal sBMD increases up to about 23 years of age: the estimated average rates of increases were 0.13%/year for women aged 20 years. After the age of 23, the sBMD began decreasing: the rates of loss increased by 0.045%/year for each year increase in age among premenopausal women. In perimenopausal women, the rate of loss was 2.1%/year. In postnatural menopausal women, the rates of loss decreased exponentially with increasing years since menopause. The rates of loss increased by 0.04%/year for 1 kg decrease in body weight or by 0.1%/year for 1 kg/m² decrease in body mass index. No significant differences in changes in sBMD were found between scanners and between centers after multiple adjustment. We conclude that the rates of change in spinal sBMD are associated with age in premenopausal women, and with years since menopause and weight or BMI in postmenopausal women. Caution is needed, however, when using data from different densitometers to evaluate rates in bone loss in multicenter trials. Received: 13 March 1997 / Accepted: 27 January 1998     

Baseline BMD and Bone Loss at Distal Radius Measured by Peripheral Quantitative Computed Tomography in Peri- and Postmenopausal Hong Kong Chinese Women

The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal (n = 26) and postmenopausal (n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM (r ranges from −0.283 to −0.502; p<0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss ≥3%), normal bone losers (with annual tBMD loss ≥ 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence. Received: 12 November 2001 / Accepted: 18 July 2002     

Influence of menopause on mandibular bone quantity and quality in Japanese women receiving dental implants

Summary

The purpose of this study was to evaluate the effect of menopause on bone mineral density and bone width of the mandible. Results indicate that menopause affects the bone quality and quantity of the partially edentulous molar region of the mandible, which should be considered in dental implant treatment for postmenopausal women.

Introduction

The recovery of oral function with dental implant is clinically effective and highly predictable. Bone quantity and quality at the implant installation site affect its prognosis; however, the effects of menopause on jaw bone have not been well documented. The purpose of this study was to evaluate the effect of menopause on bone mineral density (BMD) and bone width of the mandible.

Methods

The subjects were 72 female patients with a partially edentulous molar region of the mandible: 30 premenopausal and 42 postmenopausal women aged 30 to 70?years. Trabecular BMD was measured with quantitative computed tomography. Trabecular region width (TW) and cortical width (CW) were measured with CT. The BMD, TW, and CW of the two groups were compared.

Results

The trabecular BMD of postmenopausal women was lower than that of the premenopausal women. The TW of postmenopausal women was greater than that of premenopausal women, whereas the CW of postmenopausal women was significantly smaller than that of premenopausal women. In all these women, BMD correlated negatively with TW and positively with CW. In the premenopausal women, BMD negatively correlated with TW, but it did not correlate with CW. In the postmenopausal women, there was no correlation between BMD and bone width.

Conclusion

These results indicate that menopause affects the bone quality and quantity of the partially edentulous molar region of the mandible, which should be considered in dental implant treatment for postmenopausal women.     

Bone mineral density and risk factors for osteoporosis—A population-based study of 1600 perimenopausal women

Population-based epidemiological studies on osteoporosis are few. Our study evaluated the effects of menopause and certain putative behavioral risk factors on bone mineral density (BMD). Spinal and femoral neck BMD were measured with dual X-ray absorptiometry (DXA) from 1600 perimenopausal women aged 48–59 years (mean 53.2 years) with no diseases or medications known to affect bone metabolism. These women were a selected sample of the Kuopio Osteoporosis Risk Factor and Prevention Study population (n=14,220). There was a wide variation of BMD among perimenopausal women. Menopause had a major effect on BMD. Postmenopausal women had significantly lower BMD in both spine (-6.2%) and femoral neck (-3.9%) as compared with premenopausal women. Multiple regression analysis showed that weight, menopausal status, age, and grip strength were significant independent predictors of both spinal and femoral BMD. Additionally, physical activity was found to be a significant predictor of femoral BMD, and alcohol consumption was a significant predictor of spinal BMD. However, current anthropometric and lifestyle factors explained only 18.7–25.4% of the variability of BMD. Therefore, the estimation of the risk factor status at menopause is not an adequate substitute for bone densitometry. However, our results may in part help clinicians to identify the risk groups at which to direct bone density measurements.     

The effect of menopause on biochemical markers and ultrasound densitometry in healthy females

Urinary pyridinoline (pyr) and deoxypyridinoline (dpyr) are new markers for bone resorption, and serum osteocalcin reportedly indicates osteoblastic activity. Recently, a new ultrasound bone densitometer instrument has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index. The effects of menopause on biochemical markers and ultrasound densitometry were investigated in 40 healthy females, 36–39 years, with regular menstruation, and in 117 healthy perimenopausal females, 47–57 years, who were divided into a premenopausal group and a postmenopausal group. Significantly elevated values of pyr, dpyr, and serum osteocalcin were found for the postmenopausal group as a whole compared with the premenopausal group. We examined postmenopausal groups 48–57 years of age stratified into 2-year intervals (within 2 years of the menopause, 2–4 years postmenopause and 4–6 years postmenopause). Elevated values of urinary pyr, dpyr, and serum osteocalcin were evident even in the first 2 years postmenopause compared with the premenopausal group, and these higher values were exhibited until 6 years after menopause. We found a significant decrease in SOS, BUA, and stiffness index of the postmenopausal group as a whole, compared with those of the premenopausal group. SOS, BUA, and stiffness index of the group within 2 years of menopause significantly decreased compared with those of the premenopausal group. The Z-scores of the increase in biochemical markers and the decrease in stiffness index in the postmenopausal group were approximately 0.7–1.3 compared with the premenopausal group. The results suggest that these biochemical markers and ultrasound densitometry are potentially sensitive parameters of postmenopausal bone change.     

Age-related differences in total and regional bone mass: A cross-sectional study with DXA in 429 normal women

Total body bone mineral content (TBBMC), total body bone mineral density (TBBMD) and regional bone mineral content (BMC) and density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA) in 429 normal women aged 15–83 years, of whom 242 were premenopausal and 187 postmenopausal. The population was divided into 5-year age groups. In the premenopausal women no changes in TBBMC, TBBMD or regional BMC and BMD were observed with age, and TBBMC and TBBMD values correlated well with body weight (p<0.001). Postmenopausal women showed an overall reduction in bone mass (p<0.001), more marked at the axial level than peripherally (1.6% vs. 0.8%/year). The values of TBBMC and TBBMD correlated well with chronological age, time since the onset of menopause and body weight (p<0.001). In these women age did not correlate with body weight, which suggests that postmenopausal bone mass loss depends more on chronological age and time since the onset of menopause than on other variables. The stability observed in bone mass values from ages 15–19 to menopause highlights the importance of stimulating the acquisition of an appropriate peak bone mass in women before adolescence begins.     

The relationship between endogenous estrogen,sex hormone-binding globulin,and bone loss in female residents of a rural Japanese community: the Taiji Study

 The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants—50 women in each of four age decades—were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal (n= 38), perimenopausal (n= 14), postmenopausal group 1 (5 years or less since menopause; n= 18), and postmenopausal group 2 (6 years or more since menopause; n= 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up (P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up (P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck (P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle (P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter (P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone. Received: November 29, 2001 / Accepted: February 28, 2002     

Relation of early menarche to high bone mineral density

The study of background factors in individuals with high bone mineral density (BMD) may provide useful information in the prevention of osteoporosis. We investigated the relationship of reproductive factors to BMD. In 519 female volunteers (327 postmenopausal and 192 premenopausal women) ranging in age from 21 to 74 (mean 52.3 ±11.8) years, spinal BMD values were obtained using both quantitative computed tomography and dual x-ray absorptiometry. The z score was calculated from the mean BMD in each 5-year age group, and high BMD and low BMD was defined as BMD with z score >+1.5 and <-1.5, respectively. Normal BMD was defined as BMD within the range-1.0 <z score <+1.0. Long reproductive period, early menarche, and late menopause were associated with high BMD. Among these, the reproductive period showed the strongest association with BMD. In postmenopausal women, early menopause had a significant relationship with low BMD, and early menarche also had some relation to high BMD. In premenopausal women, there was a significant relationship between early menarche and high BMD. The age at menarche may have a strong association with peak bone mass, as suggested by the positive correlation of early menarche with high BMD observed in this study. It is considered important to prevent risk factors that disturb the beginning of menstruation in adolescent girls.     

Velocity of ultrasound at the patella: Influence of age,menopause and estrogen replacement therapy

Determination of apparent velocity of ultrasound (AVU) in bone has been proposed as a valuable tool for discriminating between normal and osteoporotic women. We have studied the influence of age, menopause and estrogen replacement therapy (ERT) on AVU at the patella in a large sample of pre- and postmenopausal women. Three hundred and eighteen woman aged 40–60 year participated in the study (112 women were premenopausal, 21 were perimenopausal and 185 were postmenopausal of whom 110 had received ERT for a minimum of 1 year). AVU was determined as the mean of four measurements at each patella using a Signet instrument (Osteo-Technology, Framingham, MA). An age-dependent decline in AVU was observed only after menopause (r=–0.33,p=0.0055); in premenopausal women there was a slight but not significant decrease in AVU with age (r=–0.12,p>0.05). AVU was significantly lower in postmenopausal women compared with premenopausal women (1882±84 m/s vs 1961±73 m/s,p<0.05). ERT prevented the menopause-related fall in AVU. There was a significant positive correlation between the duration of ERT and AVU measurements. Our findings demonstrate a pronounced influence of estrogens on AVU at the patella, supporting the concept of a protective role of ERT in bone stability. AVU measurements therefore merit further investigation as an inexpensive method for predicting fracture risk that does not expose the subject to radiation.     

Aging changes in vertebral morphometry

We analyzed the vertebral morphometry of healthy premenopausal women and their changes with age and menopause in order to better define the reference population for the clinical and epidemiological evaluation of vertebral fractures. Vertebral morphometry has been performed on lateral thoracic and lumbar spine films from 50 premenopausal and 76 postmenopausal normal women, age range 39–74 years. Vertebral heights and the anterior height/posterior height ratio are significantly lower in postmenopausal compared with premenopausal women. Vertebral anterior height decreases about 1.5 mm/year, whereas middle and posterior height decreases about 1.3 and 1.2/mm year, respectively. A statistically significant reduction of vertebral heights by around 1 mm/vertebra was observed in postmenopausal (n=16) compared with premenopausal women (n=20) of the same age (P<0.05). The results demonstrate that vertebral heights are lower with advancing age and menopause and that the vertebral heights difference in elderly people is not only the consequence of a cohort effect. The results also contribute to better defining the reference population to be chosen for evaluatin vertebral deformation.     

The effect of previous oral contraceptive use on bone mineral density in perimenopausal women

The bone mineral density (BMD) of the lumbar vertebrae L2–4 and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) in 3222 perimenopausal women — a random stratified sample of the population-based Kuopio Osteoporosis Study (OSTPRE). The mean age of the women was 53.4 years (range 47.9–59.6 years). Twenty-nine percent of the women were past users of oral contraceptives (OC) containing 50 µg or less of ethinyl estradiol and 7.4% (n=250) of the women reported OC use for more than 6 years. There was a slight but statistically significant difference between OC users (n=939) and non-users (n=2283) in lumbar BMD (1.134±0.155 g/cm² v 1.123±0.161 g/cm²,p=0.014). A statistically significant difference was recorded also after adjustment for years since menopause, duration of hormonal replacement therapy (HRT) and present weight (p=0.044). When the analysis was performed among women who had never used oestrogen replacement therapy (n=1427) and among premenopausal women (n=387), no differences in BMD were found between OC users and non-users. Similarly, femoral neck BMD did not differ between the groups. This population-based study demonstrated a slightly higher lumbar BMD among past OC users. However, OC users and non-users differed from each other in many behavioral characteristics. Thus, the differences in BMD may be accounted for more by other factors than by past OC use itself. The low-dosage estrogen OCs used today would not be expected to have any positive bone effects among future perimenopausal women.     

Age-related changes in os calcis ultrasonic indices: A 2-year prospective study

We performed repeated ultrasound measurements approximately 2 years apart (average 23 months ±3 months) on the os calcis of 113 healthy postmeno-pausal women recruited from two large prospective cohort studies named OFELY and EPIDOS. Group A (from OFELY) consisted of 88 women aged 52–72 (63±5) years, randomly selected from a large insurance company, and group B (from EPIDOS) consisted of 25 women aged 75–88 (80±4) years, randomly selected from the voting lists. We obtained broadband ultrasonic attenuation (BUA) and speed of sound (SOS) measurements, as well as the Stiffness index, with a Lunar Achilles ultrasound machine. We performed dual energy X-ray absorptiometry (DXA) measurements of femoral neck bone mineral density (neck BMD) with a Hologic QDR 2000 for group A and with a Lunar DPX Plus for group B. The decrease that we observed over 2 years was on average ±1 SD: –1.01±4.6 dB/MHz (p=0.02) for BUA (which is approximately equal to the long-term precision error in vitro), –11.3±9.2 m/s (p=0.0001) for SOS (approximately 5 times the precision error), –3.8±4.2 %YA (p=0.0001) for Stiffness (2.5 times the precision error) and –0.01±0.03 g/cm2 (p=0.0001) for neck BMD (approximately equal to the precision error). In terms of percentage change this represents: –1.0%±4.3% for BUA, –0.8%±0.6% for SOS and –1.85%±4.4% for neck BMD. At the individual level, most SOS and Stiffness values were consistent with a decrease, whereas BUA and neck BMD values were spread out above and below the zero line of no change. The decreases in SOS and Stiffness were significantly larger in the early postmenopause (20 years since menopause [YSM]) than in the late postmenopause (>20 YSM). We observed a similar trend for BUA and BMD but this did not reach statistical significance. We found a weak but significant correlation between changes in ultrasound variables and changes in neck BMD. However, the 2-year changes observed in SOS were not significantly correlated with changes in BUA. This study suggests that the heel ultrasound measurements of SOS and Stiffness are valuable indices of postmenopausal bone loss, and could be used for follow-up in therapeutic trials.     

Role of chronic health disorders in perimenopausal fractures

Only a few studies have examined the risk of individual chronic health disorders on perimenopausal (i.e., around menopause) fractures in a single study. We evaluated the effect of chronic illnesses on fracture rate in a prospective cohort study of 3,078 women. These women were a stratified sample from the population base of 14,220 women aged 47–56 years and residing in the province of Kuopio in eastern Finland in 1989. Data on physician-diagnosed chronic diseases were collected by a baseline questionnaire in 1989. For certain diseases, questionnaire information of self-reported chronic disorders were compared with drug reimbursement data provided by the Social Insurance Institution of Finland. Axial bone mineral density (BMD) measurements from the femoral neck and lumbar spine were performed in 1989–91. Two hundred sixty-five (265) women experienced at least one fracture during the follow-up period of 3.6 years (SD±0.78). The first fracture during the follow-up period was taken to be the end-point event. The risk of follow-up fracture for an individual health disorder was estimated with the Coxs proportional hazards model. Several chronic health disorders increased the fracture risk in perimenopausal women. However, hypertension was a statistically significant ( p=0.018) risk factor for fracture (adjusted hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1–1.9), especially in overweight and obese (body mass index 28) women (HR, 2.0; 95% CI, 1.4–3.0). In addition, coronary heart disease (adjusted HR, 1.76; 95% CI, 1.13–2.76), hyperthyroidism (adjusted HR, 1.7; 95% CI, 1.0–2.9), epilepsy (adjusted HR, 2.0; 95% CI, 1.1–3.6), alcoholism (adjusted HR, 3.5; 95% CI, 1.3–9.5) and chronic hepatic disease (adjusted HR, 5.2; 95% CI, 1.7–16.4) predicted fracture. BMD was either normal or even elevated in disease groups. However, women with a fracture during the follow-up usually had decreased bone density, although the difference was statistically significant only in women with hypertension and hyperthyroidism. We conclude that hypertension, coronary heart disease, alcoholism, epilepsy and hyperthyroidism can markedly increase the risk of fracture in perimenopausal women and should be taken into account when assessing the risk of future fracture in an individual patient. Furthermore, in contrast to previous data, obesity alone does not increase the risk of perimenopausal fracture, but in association with hypertension the risk seems to be markedly elevated.     

Variability of vertebral and femoral postmenopausal bone loss: A longitudinal study

The rate of postmenopausal bone loss varies considerably between individuals and it has been suggested that about 1 in 3 women loses significant amount of bone mineral in the forearm. The rate of vertebral and femoral bone loss was determined by dual-energy X-ray absorptiometry throughout two consecutive 22-month periods, in 93 healthy women who had passed a natural menopause 6–60 months earlier. In all cases the bone changes were normally distributed, ranging from –6.9% to +2.8% per year in the spine and from –7% to +4.8% per year in the femur. No significant relationship was found between the two fractional rates of bone loss. When the women were stratified into three groups according to their individual rate of bone loss, we found that only 20%–47% retained their first classification during the second period of follow-up. In particular, less than 10% of the women showed a rapid rate of bone loss throughout the study. We conclude that spontaneous vertebral and femoral bone loss exhibit a great variability within the first postmenopausal years and that only a small minority of women sustain a fast rate of bone loss over several years. These results raise the question as to whether the evaluation of individual rates of bone loss at menopause might be useful in the identification of women at higher risk of osteoporosis.