Circulating levels of insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor I (IGF-I) in perimenopausal women

The study investigated possible menopause-related changes in circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels and their relationship with insulin-like growth factor I (IGF-I) plasma levels. Forty-three healthy women, aged 45–55 years, were studied (22 premenopausal and 21 postmeno-pausal, matched for age and body mass index); in all subjects plasma IGF-I and IGFBP-3 levels were measured by radioimmunoassay. No difference was found between mean IGFBP-3 plasma levels in the two groups studied (premenopausal 3.42±0.49 v postmenopausal 3.46±0.58 mg/l), while mean IGF-I levels were significantly lower in postmenopausal as compared with premenopausal women (136.7±37.86 v 175.7±51.91 ng/ml,p<0.02). Multiple regression analysis showed no significant effect of age, body mass index and years since menopause on IGFBP-3 levels; however, considering the IGF-I/IGFBP-3 ratio as a possible parameter of circulating free somatomedin C, an inverse correlation was found with years since menopause (n=43,r=–0.499,p<0.001). We conclude that lack of oestrogen induces different effects on circulating IGF-I and IGFBP-3, possibly reflecting a real decrease in IGF-I activity.     

The effect of the menopause and hormone replacement therapy on serum carboxyterminal propeptide of type I collagen

We investigated the effect of the menopause and postmenopausal hormone replacement therapy on the serum concentration of carboxyterminal propeptide of type I procollagen (PICP), which is a biochemical marker of type I collagen synthesis. A group of 124 healthy postmenopausal women, aged 45–53 years, had about 20% higher serum PICP than did a group of 40 healthy premenopausal women aged 35–52 years (114±35 µg/1 vs. 95±26 µg/l (mean ± SD);p=0.002). The 124 postmenopausal women were also participating in a double-masked longitudinal study with two placebo groups and four different hormone replacement therapy groups. The four hormone regimens resulted in similar responses in serum PICP. Compared with placebo, 1 year of treatment with any of the four hormone replacement therapies significantly decreased serum PICP to premenopausal levels. We conclude that the formation of type I collagen is increased shortly after the menopause and that hormone replacement therapy reverses this increase.     

The effects of menopause on longitudinal bone loss from the spine

Summary Two hundred and thirty women aged 45–66 years were divided into three groups according to their menopausal status and were followed to assess the changes in vertebral bone mineral density (BMD). These included 71 premenopausal, 42 perimenopausal, and 117 postmenopausal women. Menopausal status was assessed through menstrual history and plasma concentrations of 17 estradiol and luteinizing hormone. BMD was measured by dual photon absorptiometry between 2 and 5 times over an average period of 27 months, and annual rates of changes were calculated by linear regression. BMD decreased significantly (P<0.0001) in the three groups during the follow-up. Mean (±SD) annual rate of change was-0.79±1.5% for premenopausal,-2.35±1.5% for perimenopausal, and-1.24±1.5% for postmenopausal women. There was no difference in the rates of bone loss between the perimenopausal group and the postmenopausal group within 3 years after menopause (1–2 years:-2.34±2.1%; 2–3 years:-1.9±1.5%). Thereafter, rates decreased exponentially with time since menopause to fall out at the same level as the premenopausal level. These longitudinal data indicate that vertebral bone loss begins before menopause and accelerates sharply during menopause to decline exponentially with time after 3 years.     

Ultrasound Measurement of Proximal Phalanges in a Normal Polish Female Population

In this cross-sectional study 954 Polish healthy women aged 30–80 years were evaluated (mean age 50.8 ± 8.9 years). Among them were 460 premenopausal (mean age 44.4 ± 5.5 years) and 494 postmenopausal women (mean age 56.8 ± 7.2 years). Women suffering from diseases known to affect bone metabolism and/or treated with drugs that affect bone tissue were excluded. All women were volunteers from six towns in the south of Poland, who underwent bone measurements for screening purposes. Bone status was assessed using an ultrasound device (DBM Sonic 1200, Igea, Italy) that measures amplitude-dependent speed of sound (AD-SoS) in metres per second. Phalanges (II–V) of the non-dominant hand were measured and an average value was computed. In vivo short-term precision was 0.49% for intraobserver, and 0.42% for interobserver measurements. Mean AD-SoS values were: in the whole group, 1974.6 ± 90.7 m/s; in premenopausal women, 2032.1 ± 50.0 m/s; and in postmenopausal women, 1921.0 ± 87.3 m/s (p <0.0001). The mean decrease in AD-SoS value in the studied population was 6.1 m/s per year. Simple linear regression analysis showed significant, negative correlations between age and AD-SoS: in the whole group r=– 0.70 (p <0.0001); in pre- and postmenopausal women, r=– 0.29 (p <0.0001) and r=– 0.58 (p <0.0001), respectively. Years since menopause (YSM) showed a significant influence on AD-SoS: linear correlation in the whole group resulted in a value of r=– 0.59 (p <0.0001) and in the group of postmenopausal women in a value of r=– 0.57 (p <0.0001). AD-SoS decreased in the first 8 YSM by 5.1% (0.63%/year) and in the next 15 YSM by 5.44% (0.36%/year). In postmenopausal women mean AD-SoS was regressed simultaneously on age and YSM, resulting in AD-SoS = 2181.0 – 4.031 6 Age – 3.911 6 YSM. In conclusion, ultrasound measurements of proximal phalanges were found to enable detection of age- and YSM-related skeletal changes in a Polish healthy female population. Results obtained in this study showed a premenopausal decrease in the ultrasound parameter (not observed by other authors) and an AD-SoS value lower than those in French, Italian and Spanish populations. The premenopausal decline in AD-SoS, the most important observation, requires further longitudinal investigations to determine factors affecting the skeleton before menopause. Received: 2 February 1997 / Accepted: 23 December 1997     

Ultrasound velocity changes at the proximal phalanxes of the hand in pre-, peri- and postmenopausal women

We evaluated the bone tissue modifications which occur in pre-, peri- and postmenopausal women by means of an ultrasound (US) device which measures US propagation velocity in the distal metaphysis of the proximal phalanxes of the hand. Before starting the study, two operators assessed the in vivo short-term precision of the device in 12 volunteers, each measured 10 times (5 times by each operator). Then the US velocity in the dominant (DO) and non-dominant (ND) hand was measured in 228 women to evaluate whether there was a difference between US values measured at these sites. Finally, another selected group of 417 healthy pre-, peri- and postmenopausal women, aged from 40 to 65 years, was studied to evaluate the physiological climacteric changes in the US parameter measured: amplitude-dependent speed of sound (AD-SoS). In the 12 volunteers, intra- and inter-observer short-term precision (CV) was 0.4% (for both the operators) and 1.0%, respectively. DO and ND hand AD-SoS values (2074.1±63.8 m/s and 2077.1±65.5 m/s, respectively) proved to be highly correlated (r=0.96,p<0.0001) in the 228 women studied. AD-SoS distribution (417 subjects) was correlated with age, climacteric condition (premenopause with regular or irregular cycles and natural postmenopause) and body mass index (BMI). In premenopause (253 subjects) the US velocity was higher among women with regular cycles (2107.2±48.5 m/s) than among those with irregular cycles (2074.7±44.1 m/s) (p<0.0001). In postmenopause (164 subjects) an inverse correlation between AD-SoS and the time elapsed since menopause was found (r=–0.42,p<0.0001). Furthermore, age and BMI were shown to be inversely related to AD-SoS (r=–0.47,p<0.0001 andr=–0.30,p<0.0001, respectively) when evaluated in the whole study group. The results obtained confirm that US transmission at the phalanxes is sensitive to pre-, peri- and postmenopausal bone changes. Further studies are needed to evaluate its ability to predict osteoporotic fracture risk.     

A precise method for the assessment of tibial ultrasound velocity

We assessed a method for the measurement of ultrasound velocity in cortical bone of the human tibia using a probe designed to minimize the effects of surrounding soft tissues. Of four different measurement values, the maximum velocity (average of the five highest readings) gave the lowest errors of reproducibility in relation to the population variance (standardized coefficient of variation=1.8%). The maximum velocity varied according to the tibial site measured and for practical reasons the mid-tibial site was chosen for further study. The short-term intra- and inter-observer reproducibilities (coefficients of variation) were 0.35% (n=22) and 0.50% (n=27) respectively. Long-term reproducibility over 4 months in 31 subjects was 0.68%. There was no significant difference in maximum ultrasound velocity between the dominant and non-dominant tibia in 78 women (3764±209 vs 3763±199 m/s). Tibial ultrasound velocity was significantly higher in 73 premenopausal women (3999±102 m/s) than in 129 women referred for assessment of postmenopausal osteoporosis (3780±168 m/s), 26 women with steroid-induced osteoporosis (3790±188 m/s) and 4 women with hyperparathyroidism (3575±261 m/s). In premenopausal women, ultrasound velocity did not correlate significantly with age, height, weight or body mass index. In women with postmenopausal osteoporosis, ultrasound velocity decreased with age after the menopause (r=–0.47,p<0.0001) and body weight exerted a weaker protective effect. The apparent annual decrease in velocity with age in postmenopausal osteoporosis (8.5 m/s) was comparable to the error of reproducibility. We conclude that the technique for measuring tibial ultrasound velocity is highly reproducible in relation to the distribution of values in the population and is sensitive to age- and osteoporosis-induced changes in bone. Further studies are required to examine its relationship to other indices of skeletal status to determine the biological and clinical relevance of the technique.     

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.     

Effect of the menopause and hormone replacement therapy on the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen

We investigated the effect of the menopause and postmenopausal hormone replacement therapy (HRT) on the serum concentration of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), a potential new biochemical marker of bone resorption. A group of 44 healthy postmenopausal women, aged 45–54 years, had about 19% higher serum ICTP than did a group of 42 healthy premenopausal women aged 35–50 years (3.6±0.8 µg/l v 3.0±0.7 µg/l (mean ±SD);p<0.01), although there was a large overlap in the values. The 44 postmenopausal women also participated in a longitudinal clinical study, in which 20 received HRT and 24 received a placebo. Compared with the placebo group, those who received HRT had a significant (p<0.05) decrease in ICTP of about 12% at the end of 1 year of treatment, but again there was considerable overlap in the values. The menopause-and HRT-induced changes in ICTP were less than those seen in serum osteocalcin, serum total alkaline phosphatase, and fasting urinary excretion of hydroxyproline, calcium, pyridinoline and deoxypyridinoline. We conclude that the menopause increases and HRT decreases ICTP, although these changes are less pronounced than those seen in other biochemical markers of bone turnover.     

Circadian rhythm in type I collagen formation in postmenopausal women with and without osteopenia

A circadian rhythm in the serum concentration of the procollagen type I carboxyl-terminal propeptide (sPICP) has previously been demonstrated in premenopausal women. This study was performed to investigate the circadian rhythm in sPICP in healthy and osteopenic postmenopausal women. Blood samples were taken every third hour for 27 h from three groups of women: 12 early postmenopausal women (aged 55±2 years; mean±SD); 12 late postmenopausal women (aged 73±1 years); and 12 osteopenic but otherwise healthy late postmenopausal women (aged 73±1 years). A circadian rhythm in sPICP was found in all three groups, as shown by cosinor analysis (p=0.000003–0.03). The circadian rhythm in sPICP was significantly different between the osteopenic group and the age-matched healthy group (p<0.008). The amplitude of the circadian rhythm in sPICP was about twice as high in the osteopenic group, and the time of the maximum tended to be about 3 h later, as compared with the age-matched healthy group. The plasma concentration of osteocalcin, as measured by a recently developed two-site enzyme-linked immunosorbent assay, also showed a circadian rhythm in all three groups (p=0.0001–0.05), with no significant differences between groups. In conclusion, we have found a significant circadian rhythm in sPICP in both early and late postmenopausal women. In osteopenic women the nightly peak in sPICP is larger and persists later into the night as compared with non-osteopenic women.     

Tooth loss and skeletal bone density in healthy postmenopausal women

Associations between dental status and skeletal bone density were investigated in a group of 329 healthy postmenopausal women with normal bone density. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius were measured by dual-or single-photon absorptiometry. Number of teeth remaining were counted and presence of complete dentures noted by a nurse practitioner. Forty-eight women (15%) wore a complete maxillary and/or mandibular denture: 22 (7%) were completely edentulous and an additional 26 (8%) had one edentulous ridge. Among women without complete dentures (n=281), significant positive linear relationships were observed between number of teeth and BMD at the spine (p<0.05) and radius (p<0.01), controlling for years since menopause, pack-years of smoking, education and body mass index. BMD did not differ between the groups with and without dentures. However, women who acquired dentures after the age of 40 years had significantly lower mean spinal and radial BMD than women who acquired dentures at age 40 years or earlier (at the radius, 0.584±0.015 v 0.630±0.017 g/cm²,p<0.05; at the spine, 1.043±0.031 v 1.124±0.029 g/cm²,p=0.05). In linear regression analysis, significant independent correlations were found among all women (n=329) between number of teeth and age (partialr=–0.19,p<0.001), pack-years of cigarette use (partialr=–0.23,p<0.001) and years of education (partialr=+0.11,p<0.05). These associations between dental status and BMD support the hypothesis that systemic bone loss may contribute to tooth loss.     

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.     

Relationships Between the Changes of Serum Levels of OPG and RANKL with Age, Menopause, Bone Biochemical Markers and Bone Mineral Density in Chinese Women Aged 20-75

The correlations between the serum levels of OPG, RANKL with age, menopause, bone markers, and bone mineral densities (BMDs) at the lumbar spine and proximal femur were studied in 504 pre- and postmenopausal Chinese women aged 20–75 years. We found that age was positively and negatively correlated with serum concentrations of OPG (r = 0.442, P < 0.001) and RANKL (r = –0.263, P < 0.001), respectively. Compared with premenopausal women, postmenopausal women showed higher serum OPG levels (107.6 ± 3.0 vs 72.0 ± 1.8 pg/ml, P < 0.001), lower serum RANKL concentrations (4.7 ± 0.4 vs. 5.8 ± 0.3 pg/ml, P < 0.001) and RANKL/OPG ratios (0.045 ± 0. 004 vs. 0.099 ± 0.008, P < 0.001). Neither serum levels of OPG nor RANKL or RANKL/OPG ratio correlated with BMDs after adjustment of age and menopause. They also showed no differences among normal, osteopenic and osteoporotic postmenopausal women. Serum levels of OPG were positively correlated with urinary excretion of NTx (r = 0.1453, P = 0.006). Serum levels of RANKL (r = –0.1928, P < 0.001) and RANKL/OPG ratio (r = –0.1303, P = 0.013) were inversely correlated with serum concentrations of OC. In multiple regression analysis, up to 20% variance (R² = 0.106–0.224) of the OPG-RANKL system in peripheral circulation can be explained by age, menopause and bone markers.These results suggest that although serum OPG and RANKL concentrations were unrelated with BMDs, the age– and menopause– dependent changes of serum OPG and RANKL might be a protective mechanism against the accelerated bone loss in postmenopausal women.     

Influence of weight and weight change on bone loss in perimenopausal and early postmenopausal Scottish women

Weight is recognized as an important factor in determining an individuals risk of osteoporosis. However, little is known about whether weight or weight change influences bone loss around the time of the menopause, and the relationship with energy intake and physical activity level remains largely undefined. Healthy premenopausal women (1,064 selected from a random population of 5,119 women aged 45–54 years at baseline) each had bone mineral density (BMD), weight and height measurements, and completed a food frequency and physical activity questionnaire. Of the original participants, 907 women (85.2%) returned 6.3 ± 0.6 years later for repeat BMD measurements, and 896 women completed the questionnaires. Bone loss at the hip (FN) and spine (LS) occurred before the menopause. Weight change rather than weight was associated with FN BMD loss (r=0.102, p=0.002), but weight at follow-up was associated with LS BMD change (r=0.105, p=0.002). Although an increase in physical activity level (PAL) appeared to be beneficial for FN BMD in women who were heavy weight gainers, PAL was associated with increased LS BMD loss in women who lost weight. For current HRT users, neither weight nor weight change was associated with change in BMD. Postmenopausal women not taking HRT should be made aware that low body weight or losing weight during this particularly vulnerable period may worsen bone loss.     

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.     

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.     

Measurements of broadband ultrasonic attenuation in the calcaneus in premenopausal and postmenopausal women

We report a study of broadband ultrasonic attenuation (BUA) in the calcaneus in 248 women. Measurements were performed with a Walker-Sonix UBA-575 ultrasonic bone analyser. The populations studied were 15 healthy young volunteers (group 1, mean age 26 years), 200 healthy pre- and postmenopausal women (group 2, mean age 53 years) and 33 osteoporotic women with vertebral crush fractures (group 3, mean age 66 years). Subjects in group 1 each had 10 repeated measurements of their right heel. Duplicate BUA measurements in the right heel were performed in 96 subjects and bilateral scans in a further 87 women in group 2. The remaining 17 subjects in group 2 and those in group 3 had a single scan of the right heel. All women in groups 2 and 3 had dual X-ray absorptiometry (DXA) scans of the lumbar spine and femoral neck.The precision study on the women in group 1 gave a root mean square (RMS) coefficient of variation (CV) of 4.2%. Individual CV results showed statistically significant differences (range 1.3%–7.6%). Duplicate scans in subjects in group 2 gave a RMS CV of 4.6% while the bilateral measurements showed no significant difference between the two heels. Linear regression analysis gave the following relationship between BUA and age: BUA=87.1–0.76 (Age –40) dB/MHz (r=–0.31,p<0.001, SEE=14.0 dB/MHz). Multivariate regression analysis showed that, in addition to age, years since the menopause was also a significant factor in predicting BUA. In the first 5 years following the menopause BUA decreased by 2.5%/year, while in the next 5 years the decrease fell to 0.5%/year. The BUA measurements in the osteoporotic subjects in group 3 gave a mean T-score of –2.1 compared with 66 premenopausal normal women and a mean Z-score of –1.0 compared with 27 age-matched elderly normal women in group 2. In comparison the lumbar spine DXA measurements for the same women gave a mean T-score of –3.2 and a mean Z-score of –1.8. DXA therefore gave substantially better discrimination between osteoporotic and normal subjects than the BUA measurements.     

Heel ultrasound in women after long-term ERT compared with bone densities in the forearm,spine and hip

To compare heel ultrasound values with bone densitites at different measurement sites as determined by single photon absorptiometry (SPA) and dual-energy X-ray absorptiometry (DXA) in long-term users of estrogen replacement therapy (ERT), we analyzed data from 30 users of estradiol implants (mean duration of treatment 16 years) and 32 non-users, comprising 28 complete age-matched pairs. The precision errors in vivo of ultrasound measurements were 0.18%, 1.3% and 1.5% for speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index, respectively. In the controls, ultrasound parameters correlated well with values from SPA and DXA measurements (r=0.51–0.63,p<0.004). In long-term users of ERT, however, measurements with ultrasound did not correlate with DXA in the spine and hip (r=0.01–0.31, NS) but correlated well with SPA in the forearm (r=0.47–0.66,p<0.009). Implant users, compared with non-users, had small and just significantly different values when measured by ultrasound (at most 12%,p=0.03–0.04) but significantly higher bone mineral densities (18%–25%,p=0.0001–0.01) in the forearm, spine and hip when measured by SPA or DXA. Data indicated that a substantial proportion of long-term users of estrogen may be non-responders concerning the effect of estrogen on bone qualities expressed in heel ultrasound values. In a multivariate regression analysis the effect of increasing age and increasing treatment duration were both negative for the ultrasound parameters. This is in contrast to our previous finding for bone density parameters in which the negative effect of increasing age was more than compensated by the positive effect of increasing treatment duration. Heel ultrasound correlated poorly with DXA measurement of axial bone density in long-term estrogen users. It has been stated that ultrasound measurements of bone status represent architecture and structure independently of bone mass. If so, then longterm ERT seems, in a substantial proportion of women, to preserve the bone mass and density better than the structure of the bone. Thus, the present study demonstrates a situation where ultrasound determinations can not simply be extrapolated to reflect the mineral density of the central skeleton.     

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.     

Body segment lengths and arm span in healthy men and women and patients with vertebral fractures

We studied 112 healthy men and 261 healthy women aged 18–92 years, and 34 men and 73 postmenopausal women with vertebral fractures aged 45–90 years to determine (i) whether patients with vertebral fractures have shorter stature before fracture, and (ii) whether the difference between arm span and standing or sitting height can be used to identify patients with fractures. Arm span was measured by using a calibrated extended ruler. Standing height, sitting height and leg length were measured by using a Holtain stadiometer. The results were expressed in absolute term and standard deviation (SD) or Z-scores (mean±SEM). Advancing age was associated with decreased sitting height (r=–0.37 to –0.41, both P<0.01) and a trend towards decreased arm span (r=–0.12 to –0.17, P=0.06 and 0.07) in healthy men and women; leg length was independent of age in both sexes (r=–0.09 to –0.12, NS). In patients with vertebral fractures, sitting height was reduced in women (Z=–0.83±0.14 SD, P<0.01) and men (Z=–1.37±0.21 SD, P<0.01) but only the women had reduced leg length (Z=–0.46±0.15 SD, P<0.01) and arm span (Z=–0.76±0.15 SD, P<0.01). Univariate and multivariate analyses suggest that the predictive ability of the difference between arm span and standing or sitting height to identify patients with vertebral fractures is limited. We concluded that women, not men, with vertebral fractures may come from a population with short stature. The difference between arm span and standing or sitting height cannot be used to predict vertebral fracture risk.     

Potential value of urinary oestrogen assays in the identification of fast bone losers after the menopause

We determined the rate of change of bone mineral content (BMC) in the distal forearm of 89 healthy postmenopausal women by single-photon absorptiometry. The BMC measurements were taken at 6- or 12-monthly intervals for up to 4 years. Urinary oestrogen excretion and anthropometry were assessed at the time of the first BMC measurement. Urinary oestradiol glucuronide (E₂G) excretion was related to the rate of change of proximal BMC in women 1–7 years past the menopause (r=0.52,p<0.01). Body mass index was less highly correlated with the rate of change of BMC in these women (r=0.41,p<0.05). We conclude that urinary E₂G excretion could contribute to a screening procedure for the assessment in women soon after the menopause of the risk of osteoporotic fracture in later life.