Peripheral Volumetric Bone Mineral Density in Pre- and Postmenopausal Chinese Women in Hong Kong

The aim of this cross-sectional study was to use a newly available precise and multislice pQCT (Densiscan 2000) for establishing reference data of volumetric bone mineral density (vBMD) of the distal radius. vBMD of the nondominant wrist was measured in 118 healthy Hong Kong Chinese women aged 41–60. Anthropometric parameters, menstrual status, and handgrip strength were also measured. Results showed that there was a significant age-related decline in trabecular BMD (tBMD), integral BMD (iBMD), and cortical BMD (cBMD), with correlation coefficients ranging from −0.401 to −0.547 (P < 0.001). The annual decline of vBMD was 2.22%, 1.79%, and 0.88% in tBMD, iBMD, and cBMD, respectively. When subjects were divided into premenopausal and postmenopausal groups, we found an age-related decline in tBMD and iBMD, but not in cBMD in both groups. The vBMD values interpreted in mg/cm³ in premenopausal women were 238.4 ± 57.2 in tBMD, 604.6 ± 82.9 in iBMD, 1415.5 ± 129.9 in cBMD, and declined significantly (all P < 0.001) to 193.7 ± 54.7 in tBMD, 500.0 ± 90.3 in iBMD, and 1306.7 ± 153.5 in cBMD in the postmenopausal women. On average, 16.7% of the subjects showed their vBMDs to be below −1 SD and only 1.7% of them lower than −2 SD. Linear regression showed that the annual decline of vBMD was faster in postmenopausal women with 2.42% in tBMD, 1.90% in iBMD, and 0.88% in cBMD compared with 1.91% in tBMD, 0.98% in iBMD, and 0.55% in cBMD in the premenopausal women. After adjustment for age, only the iBMD with dominant trabecular elements showed a significantly accelerated decrease after the onset of menopause (P= 0.008). Weak or no association was found among vBMDs with anthropometric parameters, years since menopause, or handgrip strength. In conclusion, we found a significant age-related decline of vBMDs in Hong Kong Chinese women aged 41–60 years, characterized by the early reduction of metabolically active trabecular bone after entering the fourth decade of life, with an accelerated decline after the onset of menopause. Received: 20 May 1999 / Accepted: 21 January 2000     

Factors Associated with Cortical and Trabecular Bone Loss as Quantified by Peripheral Computed Tomography (pQCT) at the Ultradistal Radius in Aging Women

Peripheral quantitative computed tomography (pQCT) allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. This cross-sectional study was designed to examine the effects of healthy aging on pQCT measurements at the ultradistal radius. In a well-defined sample of 129 community-based women, aged 70–87 years, the differences in cortical and trabecular density over the age range were equivalent to losses of −0.41% and −0.65% per year, respectively. To investigate the mechanism of this age-related decline, we assessed relationships between both parameters and height, weight, body mass index, dietary calcium intake, grip strength, and serum concentrations of insulin-like growth factor-I (IGF-I), calcidiol (25(OH)D₃), calcitriol (1,25(OH)₂D₃), parathyroid hormone (PTH), and sex hormone binding globulin (SHBG). Multiple regression was used to adjust for potential confounders. Age was not significant after controlling for other covariables. Body mass index, grip strength, serum IGF-I, 25(OH)D₃, and PTH (1–84) were found to be independent predictors of total bone density. Including (total or free) 1,25(OH)₂D₃ did not improve the model precision. These findings provide evidence that, among other factors, the activity of the growth hormone-IGF-I-axis is of importance for skeletal integrity. Grip strength, serum IGF-I, and PTH (1–84) were discovered to be significantly related to cortical but not to trabecular density, suggesting that different mechanisms may be involved in compact and cancellous bone loss. Received: 2 May 1996 / Accepted: 18 June 1996     

Volumetric Bone Density and Geometry Assessed by Peripheral Quantitative Computed Tomography in Uremic Patients on Maintenance Hemodialysis

The aim of this study was to establish, by means of peripheral quantitative computed tomography (pQCT) at the distal radius, the existence of cortical and/or trabecular osteopenia, and to assess the integrity of bone geometry in uremic patients undergoing maintenance hemodialysis. Our results show a clearcut selective reduction in volumetric cortical density, more evident in women (p=–0.0001) than men (p= 0.030), which appears to be independent of age and menopausal status. Trabecular density was not significantly changed in either sex. Cortical density of the patients correlated inversely with age (p = 0.003), duration of dialysis (p= 0.002) and parathyroid hormone (PTH) levels (p= 0.03). Trabecular density correlated only with age. Normally, cortical density is age-dependent and its reduction is accompanied by compensatory geometry changes. Compared with control subjects, in our female patients both cortical area and cortical thickness were reduced (p= 0.02 and 0.008), while cross-sectional area did not change (p= 0.67). Conversely, in the males only cross-sectional area was reduced (p= 0.02). In conclusion, in uremic patients we observed a selective cortical osteopenia, more evident in the female sex, and a sex-specific pattern of geometry impairment, with resultant apparent increased bone fragility in the uremic women. We suggest that the prolonged PTH excess could be responsible, directly and/or interacting with estrogen deficiency. Received: 5 May 1997 / Accepted: 12 February 1998     

Longitudinal Alveolar Bone Loss in Postmenopausal Osteoporotic/Osteopenic Women

The purpose of this 2-year longitudinal clinical study was to investigate alveolar (oral) bone height and density changes in osteoporotic/osteopenic women compared with women with normal lumbar spine bone mineral density (BMD). Thirty-eight postmenopausal women completed this study; 21 women had normal BMD of the lumbar spine, while 17 women had osteoporosis or osteopenia of the lumbar spine at baseline. All subjects had a history of periodontitis and participated in 3- to 4-month periodontal maintenance programs. No subjects were current smokers. All patients were within 5 years of menopause at the start of the study. Four vertical bitewing radiographs of posterior sextants were taken at baseline and 2-year visits. Radiographs were examined using computer-assisted densitometric image analysis (CADIA) for changes in bone density at the crestal and subcrestal regions of interproximal bone. Changes in alveolar bone height were also measured. Radiographic data were analyzed by the t-test for two independent samples. Osteoporotic/osteopenic women exhibited a higher frequency of alveolar bone height loss (p<0.05) and crestal (p<0.025) and subcrestal (p<0.03) density loss relative to women with normal BMD. Estrogen deficiency was associated with increased frequency of alveolar bone crestal density loss in the osteoporotic/osteopenic women and in the overall study population (p<0.05). These data suggest that osteoporosis/osteopenia and estrogen deficiency are risk factors for alveolar bone density loss in postmenopausal women with a history of periodontitis. Received: 9 April 1998 / Accepted: 18 August 1998     

Effects of Lifetime Volleyball Exercise on Bone Mineral Densities in Lumbar Spine, Calcaneus and Tibia for Pre-, Peri- and Postmenopausal Women

To clarify the effects of habitual volleyball exercise on bone in women during the menopausal periods, we measured bone mineral densities (BMDs) of the lumbar spine, calcaneus and tibia every 12 months for 2 years and estimated factors related to the baseline values and annual loss rates. Forty Japanese female volleyball players 42–62 years of age, who had belonged to the district non-professional club for more than 10 years on average, were recruited. Twenty women had regular menstruation at the start, but 7 underwent menopause during the study. Fifty-nine healthy women who did not participate in habitual exercise, but were otherwise comparable with the players, were recruited as the controls. The lumbar and calcaneus BMDs were measured by dual-energy X-ray absorptiometry (DXA), and both the volumetric BMDs and cross-sectional geometry at the diaphysis of the tibia were measured by peripheral quantitative computed tomography. The baseline BMDs of all measured sites and the values of the cortical area and moment of inertia of the tibia in the players were significantly higher than the values in the control women. In the peri- and postmenopausal players, the baseline values of the lumbar and calcaneus BMDs related to total years of participating in regular exercises during adulthood including volleyball (TYE), body mass index (BMI) and years since menopause (YSM). Tibia cortical area and moment of inertia values related to TYE. Annual bone loss rates in the tibia and calcaneus of players were significantly smaller than those values in the controls. However, the bone loss rates in the lumbar spine did not differ significantly between the groups. The bone loss rate in the calcaneus was significantly related to the current number of training hours per week and YSM. The rate of bone loss in the tibia was related to BMI. These data indicated that the total number of years participating in exercise activity during adulthood have positive effects on lumbar and calcaneus BMDs and the cortical structure of the tibia. Habitual volleyball exercise apparently did not alleviate the menopause-related bone loss in the lumbar spine. Received: 3 September 1999 / Accepted: 10 July 2000     

Relation of Statin Use and Bone Loss: A Prospective Population-Based Cohort Study in Early Postmenopausal Women

Recent experimental and epidemiologic studies have suggested that the lipid-lowering drugs, statins, may have bone-protective effects. We studied the effects of statin use on the change in bone mineral density (BMD) in a prospective 4.5-year cohort study based on subjects from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study, Finland. Six hundred and twenty women aged 53–64 years were divided into four groups: 55 women reported continuous and 63 women occasional statin use during the follow-up; 142 non-users of statins reported hypercholesterolemia whereas 360 non-users did not. Spinal and femoral BMDs were measured by dual-energy X-ray densitometry in 1995–1996 and 1999–2000 and the BMD changes of the four groups were compared. Characteristics of the study population were obtained with postal inquiries. The mean annual spinal and femoral BMD changes of the study groups were 0.29% and −0.50% for the continuous statin users, 0.19% and −0.57% for the occasional statin users, 0.52% and −0.29% for the hypercholesterolemic non-users of statins, and 0.39% and −0.33% for the non-users of statins without hypercholesterolemia, (p= 0.398 and p = 0.404) respectively. The corresponding BMD changes adjusted for age, years since menopause, body mass index, BMD at baseline, calcium intake, estrogen and cortisone therapy, duration of follow-up and statin use before the baseline were −0.20% and −0.47%, 0.19% and −0.54%, 0.54% and −0.32%, 0.47% and −0.33% (p= 0.134 and p= 0.628), respectively. Our results suggest that statins do not protect from early postmenopausal bone loss. Randomized trials are needed to confirm these results. Received: 11 October 2001 / Accepted: 3 January 2002     

Cut-off Values Determined for Vertebral Fracture by Peripheral Quantitative Computed Tomography in Japanese Women

In spite of the benefits of bone mass measurement by dual-energy X-ray absorptiometry (DXA), the use of DXA has limitations. It is unable to assess a true bone density, and cannot discriminate between the trabecular and cortical bone compartments. Ultradistal radius bone density was measured using peripheral quantitative computed tomography (pQCT) to determine reference values for total bone density (BD), trabecular bone density (TBD), polar strength strain index (pSSI), total bone mineral content (BC), trabecular bone mineral content (TBC), cortical bone density (CBD), cortical bone mineral content (CBC) and polar cross-sectional moment of inertia (pCSMI) in the Japanese female population, and to ascertain the cut-off values of the measured indicators that could most efficiently discriminate osteoporotic subjects with vertebral fractures. A total of 5266 healthy Japanese women aged 20–89 years were included in this study to determine Japanese reference values. Additionally, 621 who had undergone radiographic examination of the thoracic and lumbar spine at the time of pQCT measurement were selected to determine the cut-off values of BD, TBD, pSSI and other indicators for vertebral fractures. All the healthy subjects were divided into 5 year age groups. The BD showed nonsignificant changes from the 20–24 year age group to the 45–49 year age group, and fell significantly thereafter. The TBD maintained a plateau until the 40–44 year group, which corresponds to the young adult mean (YAM) values of the lumbar spine, femoral neck and radius BMDs measured using DXA. The TBD decreased significantly thereafter. The pSSI did not change significantly from the 20–24 year age group to the 45–49 year age group, and decreased slightly in the 50–54 year age group and markedly after 55–59 years. The cut-off values for the discrimination of vertebral fractures were obtained by the calculation of sensitivities, specificities and the area under the curves obtained using age-adjusted receiver operating characteristics (ROC) analysis. Odds ratios and 95% confidence limits (CL) were calculated using age-adjusted logistic analysis. The cut-off values for vertebral fractures, the area under the ROC curves (AUC) and odds ratios were 270.1 mg/cm³ (−2.2 SD, 66.6% of YAM), 0.689 ± 0.025, 2.10 (1.63, 2.70) for BD, 104.8 mg/cm³ (−2.2 SD, 53.5% of YAM), 0.699 ± 0.023, 2.17 (1.69, 2.77) for TBD and 192.8 mm³ (−1.9 SD, 59.8% of YAM), 0.631 ± 0.028, 1.72 (1.34, 2.21) for pSSI, respectively. These findings suggest that ultradistal radius BMD measured using pQCT can be used to discriminate women with vertebral fractures. Received: 3 August 2000 / Accepted: 5 March 2001     

Modeling of Cross-sectional Bone Size, Mass and Geometry at the Proximal Radius: A Study of Normal Bone Development Using Peripheral Quantitative Computed Tomography

It is becoming increasingly accepted that bone size is an important determinant of bone mass. Studies on the development of bone size may therefore promote a better understanding of the basis of diseases which are due to low bone mass. Here, we characterize the temporal changes in cross-sectional bone size, geometry and mass at the radial diaphysis in healthy subjects from 6 to 40 years of age (n= 469; 273 females). Peripheral quantitative computed tomography was used to measure total and cortical cross-sectional area, bone mineral content (BMC) and volumetric bone mineral density (BMD) at the site of the forearm whose distance from the ulnar styloid process corresponded to 65% of forearm length. Over the age range of the study, total cross-sectional area increased by 39 mm² (50%) in females and by 85 mm² (116%) in males. Cortical area increased to a similar extent in both sexes. Between 6–7 years and adulthood, BMC increased by 52 mg/mm (111%) in females and by 73 mg/mm (140%) in males and was significantly higher in males after the age of 15 years. Volumetric BMD increased by 246 mg/cm³ (48%) in females but by only 132 mg/cm³ (23%) in males and was significantly higher in women than in men. In summary, these data show that BMC in men is higher than in women, because periosteal modeling continues longer in boys than in girls. Volumetric BMD is higher in women, partly because the size of the marrow cavity does not increase in girls as it does in boys. Received: 11 May 2000 / Accepted: 11 January 2001     

Age-Related Bone Mineral Density, Accumulated Bone Loss Rate and Prevalence of Osteoporosis at Multiple Skeletal Sites in Chinese Women

We investigated the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) and the prevalence of osteoporosis at different skeletal sites in Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral spine (areal BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD at the middle region [MVD] and total region [TVD]), hip (femoral neck [FN], trochanter [Troc] and Ward’s triangle [Ward’s]) and forearm (radius + ulna ultradistal [RUUD], 1/3 region [RU1/3] and total region [RUT]) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 2702 females aged from 5 to 96 years old. Data were analyzed by eight different regression models. We found that the cubic regression model was the best for describing age-related changes in BMD. The coefficients of determination (R ²) of the fitting curve were 0.398 to 0.612 (p= 0.000). The data were then analyzed by 5-year age groups. This showed that the earliest peak BMD was at the age of 20–24 years at Troc and Ward’s, and the latest at the age of 40–44 years at RU1/3 and RUT of the distal forearm. Compared with BMD, the ABLRs were highest at Ward’s (−66.2%) and the lowest at RU1/3 of the distal forearm (−31.3%) in subjects over 80 years old. The prevalence of osteoporosis at at least one site in these women was 0.5 ± 0.4% in those 30–39, 4.6 ± 4.4% in those 40–49, 23.9 ± 13.3% in those 50–59, 56.3 ± 20.3% in those 60–69, 71.8 ± 16.7% in those 70–79 and 83.2 ± 12.1% those over 80 years of age, respectively. The prevalence of osteoporosis in these women was 8.6–11.1% at the age of 40–49 and 36.5–40.6% at the age of 50–59 at the lateral spine regions (mLat, Lat, MVD and TVD), and 0.5–3.7% at the age of 40–49 and and 3.9–21.7% at the age of 50–59 years at the other skeletal sites (AP, FN, Troc, Ward’s, RUUD, RU1/3 and RUT). Significant differences were found in the prevalence of osteoporosis between the lateral spine regions and other skeletal sites (p<0.001) at the age of 40–59 years. In summary, we demonstrated significant age-related differences in peak BMD, ABLR and osteoporosis prevalence among various skeletal sites. Our data suggest that the supine lateral spine is the most sensitive site for the diagnosis of osteoporosis, especially in the early menopausal period, although the prevalence of osteoporosis varied with age and with different sites measured. Received: 20 November 2001 / Accepted: 13 February 2002     

Effect of Soy Protein on Bone Metabolism in Postmenopausal Japanese Women

We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2–4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2–4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2–4 BMD (r= 0.23, p = 0.038) and UDPYR (r =−0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2–4 BMD (β= 0.225, p = 0.04) and UDPYR (β=−0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms. Received: 17 September 1999 / Accepted: 29 February 2000     

Diagnostic Sensitivity of Peripheral Quantitative Computed Tomography Measurements at Ultradistal and Proximal Radius in Postmenopausal Women

Peripheral quantitative computed tomography (pQCT) is a bone densitometry technique that is able to provide real volumetric bone density values not only of the total but also of trabecular and cortical bone separately. Normal reference curves were constructed with cross-sectional data obtained in 275 postmenopausal women (50–85 years), measured at 4% of the ulnar length (ultradistal region), and data for total, trabecular, and cortical bone density were obtained. In these postmenopausal subjects, continuously significant (p < 0.0001) age-dependent declines in bone density of 1.14%, 1.1%, and 0.57% for total, trabecular, and cortical bone, respectively, were observed while similar declines of 0.9%, 0.9%, and 0.4% per year since menopause, respectively, were found. The estimated mechanical stability index also showed linear dependencies with decreases of 0.84%/year and 0.6%/year since menopause (p < 0.0001). A more proximal acquisition at 15% of the ulnar length, an almost pure cortical region, resulted in linear declines of 0.41%/year and 0.27%/year (p < 0.0001) for the cortical bone and the mechanical stability index with significant changes of −0.27% and −0.23% per year, respectively, since menopause. Covariance analysis showed similar age dependencies of the different bone indices obtained in both regions of interest except for the stability index. A significant size adaptation of the bone with age was also observed, which was seen in the relationships of the trabecular and cortical bone areas to age and to bone density. Diagnostic sensitivity of all parameters for established osteoporosis was assessed by receiver operating characteristic (ROC) curves, comparing 99 patients with at least one fracture to the reference population. The area under these curves was highest in the ultradistal pure trabecular density of the radius (75%), followed by stability index (72%) and the area of cortical bone (65%) of the proximal site. No distinguishing power was seen for the cortical bone density values obtained in either the ultradistal (51%) or proximal radius (52%).     

Bone Loss from the Hand in Women Following Distal Forearm Fracture

Bone loss occurs after distal forearm fracture, but it is unclear if this bone loss is fully recovered. We designed a cross-sectional study to evaluate the time course of the bone loss from the hand after distal forearm fracture. We identified 40 women who had a fracture of the distal forearm within the previous 4.5 years. Their ages ranged from 42 to 81 (mean 64 years) and time since fracture 6 to 54 (mean 28 months). These were compared with 95 women (mean age 67, range 57 to 80 years) from a population-based cohort. Lumbar spine (LS) and hand bone mineral density (BMD) were measured in all subjects using a Hologic QDR 1000/W densitometer. Ultrasound of the fingers of both hands was measured in the forearm fracture group using a DBM Sonic 1200 R model. Compared to controls, LS BMD was decreased by 6.4% (p<0.001), non-fractured hand by 3.2% (p<0.001) and the fractured hand by 6.1% (p<0.001) in the forearm fracture group. The mean differernce in bone density between the fractured and non-fractured hand was 0.0207 g/cm², the average value for the non-fractured hand being 0.304 g/cm². The decement in hand BMD was equivalent to 6.2% (p<0.0001). The difference in hand BMD between the fractured and non-fractured side was greatest when the time since fracture was short; there was no further difference in hand BMD after 2 years. Ultrasound showed a mean difference of 18.7 m/s in amplitude-dependent speed of sound (AD-SoS) with the average value being 1893 m/s. A 1.0% decrease was observed in the fractured hand AD-SoS (p<0.05). A strong relationship was observed between AD-SoS and BMD in both hands (r= 0.70, p<0.001). We conclude that distal forearm fracture results in a significant decrease in hand BMD that is partially reversible. The decrease in hand BMD is reflected in the ultrasound properties of the finger phalanx. Received: 26 July 2000 / Accepted: 5 January 2001     

Bone Sialoprotein is a Specific Biochemical Marker of Bone Metabolism in Postmenopausal Women: A Randomized 1-Year Study

Accelerated bone remodeling after the menopause is associated with increased bone loss that can be abolished using hormone replacement therapy (HRT). Biochemical markers of bone metabolism are known to correlate closely with changes in bone histomorphometry and osteodensitometry. Bone sialoprotein (BSP), a major constituent of bone matrix, is almost exclusively found in mineralized tissues and therefore considered a potential marker of bone metabolism. In 82 postmenopausal women, randomly allocated to either low-dose sequential HRT or no HRT, serum BSP was measured and compared with established specific biochemical markers of bone resorption [urinary deoxypyridinoline (DPD), pyridinoline (PYD) and amino-terminal telopeptide (NTx)] and markers of bone formation [serum osteocalcin (Oc) and bone-specific alkaline phosphatase (bALP)]. Longitudinal analysis showed a marked response of BSP levels following commencement of HRT, resulting in a 52% reduction after 12 months compared with initial values. The changes of BSP levels over time were at least as strong as in conventional markers of bone formation and resorption and paralleled their changes. A moderate to close correlation was found between BSP and both markers of bone resorption (r= 0.57 for NTx; r= 0.38 for DPD) and formation (r= 0.55 for Oc; r= 0.39 for bALP; p<0.0001, respectively). Our data demonstrate a cause and effect relationship between commencement of HRT and a change in serum BSP. In conclusion, serum BSP circumvents some of the limitations of urinary measurements and appears valuable for the quantitative monitoring of the skeletal response to HRT in healthy postmenopausal women. Received: 5 October 1999 / Accepted: 30 March 2000     

Withdrawal of Hormone Replacement Therapy is Associated with Significant Vertebral Bone Loss in Postmenopausal Women

This study aimed to assess the changes in vertebral bone mineral density (BMD) after cessation of hormone replacement therapy (HRT) in postmenopausal women who had been treated on a long-term basis. Fifty healthy postmenopausal women who had been followed both during the course of HRT and after cessation of treatment in our menopause clinic were included in this study. All women had started HRT within the first 3 years after the postmenopause and had received HRT (either 1.5 mg/day of 17β-estradiol given percutaneously or 50 μg/day of 17β-estradiol given as a transdermal patch, combined in all women with natural progesterone or a 19-norprogesterone derivative) for a mean 5 ± 2.4 years. In all women, vertebral BMD was assessed during the course of HRT up to the last 6 months before estrogen withdrawal, then at least once within the first 18 months after cessation of treatment. Of the initial population, 30 women were additionally reviewed later on and up to 8 years after cessation of treatment (mean duration of follow-up for the whole population: 3.9 ± 1.7 years). Rates of changes in vertebral BMD were compared with those determined in a group of healthy untreated women who had been followed within the first years of postmenopause during the same time period as the study population. In the study group, bone loss was found to accelerate within the first 2 years after HRT withdrawal and the annual rate of loss was identical to that which occurs within the first 2 years of postmenopause in untreated women (−1.64%± 1.3% vs −1.52 ± 0.9%, NS). Beyond this first 2-year time period, the annual rate of bone loss decreased as a function of time following cessation of treatment, as was observed following the menopause in untreated women (between 3 and 5 years: −0.83%+ 1.35% in the study group vs −0.70%± 0.8% in the control group, NS). On average, 3 years after cessation of HRT mean vertebral BMD when expressed as a Z-score was significantly higher (−0.13 vs −0.89, p<0.01) than at baseline, before HRT was started, which suggested a lasting beneficial effect on bone mass. However, even though our findings do not support the hypothesis that bone loss might continue to be accelerated several years after cessation of treatment we cannot fully address the question as to whether any residual benefit on bone mass over a longer period of time may be observed. In conclusion, the pattern of bone loss observed after cessation of estrogen therapy was found to be comparable to that which occurs in younger women within the first years after the menopause. Such a pattern needs to be kept in mind when the decision to stop HRT is taken, especially in women who were given HRT to prevent osteoporosis. The issue of assessing their risk of fracture several years after cessation of treatment thus needs to be addressed. Received: 25 July 2000 / Accepted: 5 December 2000     

Bone Remodeling and Structure in Postmenopausal Women Treated with Long-Term, High-Dose Estrogen Therapy

Conventional hormone replacement therapy preserves bone mass predominantly by reducing bone turnover but does not exert significant anabolic skeletal effects. In contrast, high doses of estrogen have been shown to increase bone formation in animals and we have recently reported high bone mineral density values in women treated long-term with estradiol implant therapy. The aim of this study was to investigate the mechanisms by which high doses of estrogen may increase bone mass in postmenopausal women. Iliac crest biopsies were obtained from 12 women who had received long-term treatment with estradiol implants (at least 14 years), on demand, following hysterectomy and bilateral salpingo-oophorectomy. Indices of bone turnover, remodeling balance and cancellous bone structure were assessed by image analysis and compared with those of premenopausal women. Mean wall width was significantly higher in women treated with estradiol therapy than in premenopausal women (44.8 ± 4.8 vs 38.8 ± 2.8 mm; mean ± SD; p = 0.001) and eroded cavity area was significantly lower in the implant-treated women (3612 ± 956 vs 5418 ± 1404 mm²; p = 0.001). Bone formation rate at tissue level and activation frequency were lower in the women treated with implants, although the differences were not statistically significant. Indices of cancellous bone structure were generally similar between the two groups. These results provide the first direct evidence that high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women and indicate that these are achieved by stimulation of osteoblastic activity. Received: 18 August 1998 / Accepted: 9 December 1998     

Commencing, Continuing and Stopping Brisk Walking: Effects on Bone Mineral Density, Quantitative Ultrasound of Bone and Markers of Bone Metabolism in Postmenopausal Women

Regular walking is associated with reduced risk of fracture and, in our recent randomized trial, reduced calcaneal bone loss relative to controls. The present follow-up study compared the effects on dual-energy X-ray absorptiometry, ultrasound and biochemical indices of bone density and metabolism of (i) taking up (ii) continuing with and (iii) ceasing brisk walking for exercise. Subjects were 68 postmenopausal women aged 60–70 years. Twenty previously sedentary women remained sedentary (Sed/Sed) whilst 17 took up brisk walking (Sed/Walk). Fifteen women who had been walking regularly for 1 year returned to their former sedentary lifestyle (Walk/Sed), whilst 16 continued brisk walking over a second year (Walk/Walk). Bone mineral density (BMD), broadband ultrasonic attenuation (BUA), and biochemical markers of bone formation (serum osteocalcin, C-terminal propeptide of type I collagen and bone alkaline phosphatase) and resorption (urinary deoxypyridinoline) were assessed at baseline and 12 months. Women in the Sed/Walk and Walk/Walk groups completed a mean (SEM) of 16.9 (0.7) and 20.8 (1.2) min of brisk walking per day, respectively. Changes in BMD did not differ significantly between groups. Calcaneal BMD decreased significantly in Walk/Sed women [by 2.7 (1.4)%; p= 0.01] whilst changes in other groups were not significant. Calcaneal BUA increased significantly (p= 0.02) in Sed/Walk women [by 7.4 (3.3)%] relative to other groups. Urinary deoxypyridinoline increased over the year in the Sed/Sed group but there were no significant changes in biochemical markers in other groups. Women taking up brisk walking for exercise showed no change in BMD but a significant increase in calcaneal BUA. There was no significant effect on BMD or BUA of continuing brisk walking but calcaneal BMD declined on ceasing brisk walking. Bone resorption increased in sedentary women but not exercisers, suggesting the effect on exercise on bone in postmenopausal women could be through amelioration of this increased turnover. Received: 12 September 2000 / Accepted: 13 February 2001     

Bone Quality Parameters of the Distal Radius as Assessed by pQCT in Normal and Fractured Women

The aim of this study was to test the ability of some indicators of different aspects of bone quality (assessed by peripheral quantitative computed tomography in the distal radius) to discriminate between fractured and nonfractured individuals. The study compared 214 women aged 45–85 years, free of any bone-affecting treatment, of whom 107 had suffered a Colles” fracture in the previous 6 months and 107 did not. The determinations included bone tissue or mineral “mass” indicators (trabecular, cortical and total volumetric mineral content, cortical bone area); bone “density” estimates (trabecular, cortical and total volumetric mineral density), and the Cartesian (rectangular) and polar moments of inertia as influences of cross-sectional architecture on resistance to bending and torsional loads, respectively.  The influences of body height, weight and age on the tomographic indicators were minimized by adjusting the data according to the partial coefficients of multiple stepwise regressions. The adjusted values of all the indicators were lower in fractured than in nonfractured groups. The prevalence of fractures was directly related to the actual values of the indicators, rather than the age or body habitus of the individuals. The significance of these differences between the assessed indicators decreased in the following order: trabecular “mass” > trabecular “density” > cortical or total “mass” > cortical architecture > total or cortical “density” indicators. Within the same type of bone, the tissue or mineral “mass” indicators performed better than the “density” indicators. The cortical bone density did not give useful information, probably because of technical difficulties. Odds-ratios and receiver-operating characteristic (ROC) analyses confirmed those features. The selected “cut-off” values of the indicators as determined by the ROC curves (very close to those determined by the inflexion points of the logistic reression curves) may indicate reference limits to detect persons at risk of fracture according to the type of information provided by each variable. These results show that these tomographic indicators discriminate well between fractured and nonfractured individuals, and should be suitable to assess how total, cortical and trabecular bone strength in the distal radius could affect different kinds of strength regardless of the age or body habitus of the individual. Their ability to estimate fracture risk from different biomechanical points of view should be assessed by adequately designed, prospective studies. Received: June 2000 / Accepted: January 2001     

Multisite Quantitative Ultrasound: Colles’ Fracture Discrimination in Postmenopausal Women

Distal forearm fractures are the most common perimenopausal fracture and are generally associated with osteoporosis. The aim of this study was to evaluate the capability of speed of sound (SOS) measurements in cortical bone at the phalanx, radius, tibia and metatarsal to discriminate Colles’ fracture cases from controls in postmenopausal women and to compare this with bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA). Sixty-three postmenpausal Colles’ fracture cases and 191 postmenopausal controls had SOS measurements of the radius, tibia, phalanx and metatarsal using a semi-reflection ultrasound technique and BMD measurements of the lumbar spine and proximal femur using DXA. The age-adjusted odds ratios (ORs) for fracture for the SOS measurement sites were 1.50 [95% CI 1.07–2.10] for the radius, 1.23 [0.86-1.76] for the tibia, 1.85 [1.06–3.23] for the phalanx and 1.74 [1.12–2.71] for the metatarsal site. For the BMD measurements the ORs were 1.95 [1.34–2.85] for the lumbar spine, 2.21 [1.43–3.40] for the femoral neck and 2.62 [1.69–4.08] for the total hip. The benefits of combining sites either by taking their average Z-score or by using the manufacturer’s ORI algorithm were evaluated. The two methods yielded similar results and the ORs for the combination of the radius and phalanx were 2.00 [1.21–3.33], for the radius and metatarsal 1.67 [1.05–2.67], for the phalanx and metatarsal 1.86 [1.11–3.08] and for the radius, phalanx and metatarsal 1.81 [1.07–3.06]. Combinations of DXA sites gave 2.22 [1.44–3.41] for the lumbar spine and femoral neck and 2.41 [1.57–3.70] for the lumbar spine and total hip. In conclusion, semi-reflection ultrasound measurements at the radius, phalanx or metatarsal demonstrated an ability to discriminate fracture cases from controls in postmenopausal Colles’ fracture patients, although the odds ratios were lower than with spine and femur BMD. Received: 6 July 2001 / Accepted: 11 December 2001     

Effect of Calcium Supplementation as a High-Calcium Mineral Water on Bone Loss in Early Postmenopausal Women

It is generally agreed that an adequate calcium intake is necessary for the maintenance of bone health and that calcium supplementation reduces the rate of bone loss in postmenopausal women. Mineral waters are calorie free, and some, with relatively high calcium levels, might be significant sources of calcium. We studied the effect of mineral water in 45 early postmenopausal women randomly assigned to receive a high-calcium (Ferrarelle, Italy) or a low-calcium mineral water. On the basis of the dietary regimen, women were divided in two clusters (A = 23 subjects, B = 22 subjects) significantly different only for calcium intake (CI) and for dietary consumption of calories (energy). At the end of the study period (13 ± 1 months), bone mineral density at the distal radius showed a significant decrease (P < 0.001) only in cluster with low CI. The difference between the clusters was significant (P < 0.05). Furthermore, the cluster with high CI showed a significant (P < 0.05) reduction in osteocalcin serum levels after 3 months. This study provides further evidence to support the use of a high calcium mineral water as an effective prophylaxis against postmenopausal bone loss. Received: 24 October 1995 / Accepted: 28 January 1996     

Determinants of Bone Mineral Density and Spinal Fracture Risk in Postmenopausal Japanese Women

The present study analyzed the factors that determine bone mineral density (BMD) and predict spinal fracture risk in postmenopausal Japanese women. Two hundred and five postmenopausal Japanese women aged 48–84 years (mean age 64 years) were enrolled in the cross-sectional study. BMD of the lumbar spine, femoral neck and total body as well as body composition were measured by dual-energy X-ray absorptiometry (DXA). Mid-radial BMD was measured by single-photon absorptiometry. We also determined serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-2, -3 and osteocalcin as well as urinary levels of pyridinoline (Pyr), deoxy-Pyr (D-Pyr) and growth hormone. Multiple regression analysis revealed that lean body mass (LBM) was positively correlated with BMD at all sites. In contrast, femoral neck BMD was highly related to fat mass as well as LBM, although fat mass was not an independent correlate of total body and mid-radial BMD. LBM and urinary D-Pyr were crucial determinants at all sites except the mid-radius in stepwise regression analysis. Fat mass and serum IGF-I were determinants of femoral neck and mid-radial BMD, respectively. In terms of reproductive history, parity affected lumbar BMD. Factors affecting BMD differed according to the site. On the other hand, lumbar BMD as well as serum levels of IGF-I and albumin were selected as predictors of spinal fracture risk in multiple logistic regression analysis. Lumbar BMD, serum IGF-I and LBM were selected in women with lumbar BMD above 0.727 g/cm². In conclusion, the present study indicates that LBM is a more important determinant of BMD than fat mass at any site except the femoral neck. Age, serum IGF-I and urinary D-Pyr were also determinants of BMD, dependent on the regions measured. Lumbar BMD and LBM as well as serum levels of IGF-I and albumin were useful markers which predicted the risk of osteoporotic spinal fractures in postmenopausal Japanese women. Received: 6 June 2000 / Accepted: 11 January 2001