Non-association of Estrogen Receptor Genotypes with Bone Mineral Density and Bone Turnover in Korean Pre-, Peri-, and Postmenopausal Women

Estrogen is known to play a critical role in both skeletal maturity and the rate of bone loss. This suggests the possibility that the estrogen receptor (ER) gene is one of the candidate genes that determines peak bone density and/or bone turnover rate. We investigated two established restriction fragment length polymorphisms (RFLPs) in intron 1 at the ER gene, represented as PvuII and XbaI. In 598 healthy Korean women aged 20–74 years, we examined the association of these ER genotypes with bone mineral density (BMD) and bone turnover status. The distribution of the PvuII and XbaI RFLPs was as follows: pp 205 (34.3%), Pp 308 (51.5%), PP 85 (14.2%) and xx 384 (64.2%), Xx 180 (30.1%), XX 34 (5.7%), respectively (where capital letters signify the absence of, and lower-case letters signify the presence of, the restriction site of each RFLP). No significant genotypic differences were found in BMD and bone markers. We grouped the subjects into three categories according to their menstrual status: 104 premenopausal women with regular menstruation, 182 perimenopausal women who had amenorrhea of not less than 3 months and not more than 12 months’ duration, and 312 postmenopausal women whose last menstruation was at least 12 months previously. No significant genotypic difference in either BMD or bone markers was found in any of these three groups. Furthermore we categorized women in peri- and postmenopause into a high loser group and a normal loser group according to the level of bone resorption markers. There was no difference in genotypic proportions between the high and normal loser groups. Our data suggest that these ER polymorphisms are not associated with BMD or bone turnover in Korean women. Received: 16 March 1998 / Accepted: 17 August 1998     

The New Selective Estrogen Receptor Modulator MDL 103,323 Increases Bone Mineral Density and Bone Strength in Adult Ovariectomized Rats

Selective estrogen receptor modulators (SERMs) can prevent the bone loss induced by ovariectomy (OVX), but it is not established whether they can increase bone mass and strength in a curative protocol in ovariectomized osteopenic animals. We investigated the influence of a SERM of the new generation, MDL 103,323, on areal bone mineral density (BMD), as measured by dual-energy X-ray absorptiometry, bone strength and remodeling in OVX osteopenic rats. Nine weeks after OVX, 8-month-old rats were divided into six groups of 10 animals. MDL 103,323 was given by gavage at doses of 0.01, 0.1 or 0.6 mg/kg body weight, 5 days a week. The effect of MDL 103,323 was compared with that of the bisphosphonate pamidronate (APD), which was injected subcutaneously at a dose of 1.6 mmol/kg body weight for 5 days every 4 weeks. Lumbar spine (LS), femoral neck (FN), proximal tibia (PT) and midshaft tibia (MT) BMD, bone strength, and proximal tibia histomorphometry, serum osteocalcin, urinary total deoxypyridinoline and serum insulin-like growth factor I (IGF-I) were measured. After 16 weeks of treatment, BMD changes (means ± SEM) were −11.4 ± 2.2, +4.0 ± 2.1 and +6.4 ± 1.0% respectively in OVX controls, in rats treated with 0.1 mg/kg MDL 103,323 (p<0.05) and in APD-treated rats (p<0.02) at the level of LS; −0.4 ± 1.1, +6.7 ± 1.4, +7.2 ± 1.8% (p<0.01 and NS) at the level of FN; and −2.6 ± 1.2%, +5.8 ± 1.2, +6.9 ± 1.4% (p<0.03 and 0.01) at the level of PT. MDL 103,323-treated animals had a higher trabecular bone volume, a higher number of trabeculae and smaller intertrabecular spaces compared with OVX controls. Vertebral body ultimate strength was 186 ± 13, 292 ± 16, 249 ± 23 N (p<0.05) in OVX controls, MDL 103,323-treated rats and APD-treated rats, respectively. The administration of 0.6 mg/kg of MDL 103,323 did not further increase BMD or bone strength, indicating a bell-shaped dose–response curve. MDL 103,323 lowered plasma osteocalcin concentration and urinary deoxypyridinoline excretion. In rats treated with 0.1 mg/kg MDL 103,323, plasma IGF-I was increased as compared with OVX controls (664 ± 36 ng/ml vs 527 ± 39 ng/ml, p<0.05). In conclusion, these results indicate that this new SERM positively influences BMD and lumbar spine bone strength in estrogen-deficient rats. Received: 30 October 1998 / Accepted: 12 April 1999     

The Effects of Pregnancy and Lactation on Bone Mineral Density

We performed a prospective study of bone mineral density (BMD) in 38 women during their first full-term pregnancy until 12 months postpartum. BMD measurements at lumbar spine [L2–L4 (LS)] and forearm [distal 33% (RD) and ultradistal (RUD) region of the radius] were made within 3 months before conception, after delivery, and at 6 and 12 months postpartum. In mid-pregnancy the DXA examination was carried out only at the forearm. Patients were grouped according to duration of lactation as group I, II or III (0–1, 1–6, 6–12 months respectively). During pregnancy there was a significant difference between baseline and delivery (p< 0.001) in the LS, RUD and RD BMD values. In group I there was no statistically significant difference in LS BMD between visits following pregnancy. The RUD BMD loss was recovered by 6 months postpartum (PP6). Group II showed continuous bone loss from delivery until PP6 at LS and RUD. In group III the LS BMD loss continued throughout the lactation period. The RUD BMD dropped (4.9%) until PP6 then increased by 3.0% as measured at 12 months postpartum (PP12). There was no significant change in RD BMD in any of three groups during lactation. At LS bone loss between delivery and PP12 correlated well with the duration of lactation (r=−0.727; p<0.001). We suggest that calcium needed for fetal skeletal growth during pregnancy was gained from maternal trabecular and cortical sites and that calcium needed for infant growth during lactation was drawn mainly from the maternal trabecular skeleton in our patients. The effect of pregnancy and lactation on the maternal bone mass was spontaneously compensated after weaning. Received: 13 July 2000 / Accepted: 19 April 2001     

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 Mineral Density of the Lebanese Reference Population

We determined the bone mineral density (BMD) of normal Lebanese subjects and compared results with US/European reference data. The investigation was conducted at one center, and included 858 women and 165 men aged 20–79 years. Spine, femoral and radial BMD measurements were made using dual-energy X-ray absorptiometry. Age-related changes in BMD were similar in form to those of US/European reference data. However, BMD values of Lebanese were generally lower than US/European values. Spine BMD of Lebanese women was about 8% lower than US/European values between ages 20 and 59 years, and 5–6% lower for ages 60–79 years. Femoral neck BMD values for Lebanese women were 8% lower in the young adult years (age 20–39 years), but only 2–3% lower in the postmenopausal years, compared with US/European women. There were smaller postmenopausal decreases in femoral and radial BMD in Lebanese women compared with US/European women, which led to a convergence of BMD after age 70 years. The BMD of Lebanese men was 5–8% lower than US/European values throughout the age range (20–79 years). The effect of weight on BMD ranged from 0.2% to 0.4% per kilogram. Height was not significantly associated with BMD when both height and weight were entered in multiple regression analyses. The prevalence of osteoporosis appeared to be overestimated if the US/European reference data, rather than Lebanese reference data, were used to calculate T-scores. Received: 25 February 1999 / Accepted: 9 March 2000     

Oral Contraceptives and Bone Mineral Density in White and Black Women in CARDIA

To examine whether exposure to oral contraceptives (OCs) is associated with bone mineral density (BMD) in young women, we studied, cross-sectionally and longitudinally, 216 white and 260 black women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Spine, hip and whole body BMDs were measured by dual-energy X-ray absorptiometry (DXA) when the women were aged 25–37 years, and whole body BMD was remeasured in 369 of the women 3 years later. A comprehensive history of OC use, including dose of ethinyl estradiol (estrogen) and duration of use, was determined from an interviewer-administered questionnaire. After adjustment for other relevant variables, we found that cumulative estrogen from OCs (mg) explained 4.0% of the variation in spine BMD (p = 0.024) among white women, but did not explain any of the variance in BMD in black women. Cumulative OC estrogen was associated with a decreased risk for low bone density (lowest quartile) at the spine, hip and whole body in white women. The odds ratios (95% CIs) comparing women in the highest quartile of cumulative OC estrogen with those in the lowest quartile were, at the spine: 0.08 (0.02, 0.46); at the hip: 0.23 (0.06, 0.87); and at the whole body: 0.37 (0.11, 1.26). OC exposure was not related to low bone density in black women. OCs did not predict longitudinal changes in whole body BMD in either race. These results suggest that exposure to the estrogen from OCs during the premenopausal years may have a small beneficial effect on the skeleton in white women. Benefit is proportional to the cumulative estrogen exposure, suggesting that previous cross-sectional studies that considered OC use as a dichotomous variable may have lacked the power to detect an association. Received: 22 January 2002 / Accepted: 25 April 2002 Correspondence and offprint requests to: Kristin L. Cobb, Division of Epidemiology, HRP Redwood Building, Stanford University, Stanford, CA 94305, USA. Tel: +1 (650) 498 6784. Fax: +1 (650) 725 6951. e-mail: kcobb@stanford.edu     

Total Body and Regional Bone Mineral Density in Men: Effect of Age

Bone density is related to the risk of fracture, with a decrease in bone density resulting in an increased risk of fracture. The aims of this study were to characterize the relationship between bone mineral density (BMD) and age at different skeletal sites in men, and to determine whether the BMD pattern with age reflects the pattern of fracture in men. We studied 178 healthy Caucasian men, ages 20–79 years (approximately 30 per decade) from a general practitioner register. Spinal radiographs were obtained from men over 50 years of age and graded by a radiologist for spinal osteoarthritis by the method of Kellgren. BMD was measured by dual-energy X-ray absorptiometry at the anteroposterior (AP) lumbar spine, femoral neck, Ward’s triangle, trochanter, ultradistal forearm and total body (providing estimates for the pelvis, head, arms, legs, trunk, ribs and spine). Severe osteoarthritis (grades 3 and 4) was associated with increased spine BMD, and therefore individuals with severe osteoarthritis were excluded from analysis of the spine. There was a decrease in height of vertebrae L2–4 in men between 20 and 79 years of age (4%), resulting in a decrease in projected area. The change in BMD in standard deviation units (T-score) between 20 and 79 years was calculated: there were significant decreases at the femoral neck (–1.6), Ward’s triangle (–2.4), total body (–0.6), and its subregions the pelvis (–1.4), trunk (–0.8), ribs (–0.7) and legs (–0.7). There was no change in BMD with age at the AP lumbar spine, ultradistal forearm, or the total body subregion of the head. Similar results were found after adjusting for height and weight. Thus, there was only a small decrease in total body BMD across life, but a substantial decrease in BMD of the pelvis and proximal femur, sites rich in trabecular bone. These are the same sites associated with substantial increases in fracture incidence in men with aging. Received: 31 March 1998 / Accepted: 25 November 1998     

The Sp1 COLIA1 Gene Polymorphism, and Not Vitamin D Receptor or Estrogen Receptor Gene Polymorphisms, Determines Bone Mineral Density in Postmenopausal Greek Women

Several genetic polymorphisms are implicated as determinants of bone mineral density (BMD) in postmenopausal women. These include the Sp1 polymorphism of the collagen type Iα 1 (COLIA1) gene, the FokI and BsmI polymorphisms of the vitamin D receptor (VDR) gene, and the PvuII and XbaI polymorphisms of the estrogen receptor (ER) gene. The relative importance and the independence of these genetic effects have not been studied simultaneously in the same population. We evaluated the effects of these polymorphisms on lumbar spine BMD among 154 postmenopausal Greek women. BMD tended to differ across Sp1 genotypes (mean 0.842 g/cm² in SS, 0.851 g/cm² in Ss, 0.763 in ss, age-adjusted p = 0.056), mostly because ss homozygotes had lower BMD (p = 0.018 compared with SS and Ss). No other polymorphisms were associated with BMD in this population (p= 0.53 for FokI, p= 0.94 for BsmI, p = 0.80 for PvuII, p = 0.91 for XbaI). In multivariate modeling, the effect of ss homozygosity was clinically and statistically significant (–0.105 g/cm², p= 0.013) after adjusting for age, weight, height, hormone replacement use, and the other four polymorphisms. None of the other four polymorphisms was retained as an independent predictor of BMD in a backward elimination model and no significant synergistic effects were observed when gene interactions were tested. When all five polymorphisms are considered simultaneously, the Sp1 COLIA1 polymorphism seems to have the most unequivocal effect on BMD, at least in postmenopausal women. Received: 3 July 2000 / Accepted: 14 November 2000     

Vitamin D and Estrogen Receptor Polymorphisms and Bone Mineral Changes in Postpartum Women

BsmI restriction fragment length polymorphism (RFLP) of the vitamin D receptor (VDR) gene and PvuII RFLPs of the estrogen receptor (ER) gene and their relation to changes in areal bone mineral density (BMD) were examined in 43 healthy postpartum Finnish women aged 31.3 (SD 4.7) years. BMD was measured by dual energy X-ray absorptiometry at lumbar spine, right femoral neck, and dominant distal radius immediately after delivery, 1 month after resumption of menses, and 1 year thereafter. The RFLPs were represented as Bb (BsmI) and Pp (PvuII), the capital letters denoting the absence of and the small letters the presence of the restriction sites. The frequency of VDR alleles was as follows: bb (20.9%), Bb (60.5%), and BB (18.6%), and that of ER alleles was pp (39.5%), Pp (51.2%), and PP (9.3%). Altogether, BMD decreased significantly during postpartum amenorrhea at all sites [the mean bone loss ranging from −1.2 (SD 3.6)% at the distal radius to −3.7 (2.9)% at the femoral neck], and increased after resumption of menses [the 1-year follow-up BMD values ranging from −1.0 (2.4)% at the femoral neck to +3.3 (4.0)% at the lumbar spine as compared with baseline]. No obvious genotype-related differences were found between these changes. These results suggest that the BsmI and PvuII polymorphisms may not have substantial influence on BMD changes postpartum. Received: 20 November 1998 / Accepted: 30 September 1999     

Updated Data on Proximal Femur Bone Mineral Levels of US Adults

This paper describes data on bone mineral levels in the proximal femur of US adults based on the nationally representative sample examined during both phases of the third National Health and Nutrition Examination Survey (NHANES III, 1988–94), and updates data previously presented from phase 1 only. The data were collected from 14646 men and women aged 20 years and older using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in four selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter and total. These variables are provided separately by age and sex for non-Hispanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). NHW in the southern United States had slightly lower BMD levels than NHW in other US regions, but these differences were not sufficiently large to prevent pooling of the data. The updated data provide valuable reference data on femur bone mineral levels of noninstitutionalized adults. The updated data on BMD for the total femur ROI of NHW have been selected as the reference database for femur standardization efforts by the International Committee on Standards in Bone Measurements. Received: 18 August 1997 / Accepted: 23 February 1998     

Measurement of Bone Mineral Density in Mother–Daughter Pairs for Evaluating the Family Influence on Bone Mass Acquisition: A GRIO Survey

The relative influence of genetic and environmental determinants on bone mass is still unclear. Using an original multicentric mode of recruitment, based on absorptiometry current practice, the hypothesis of a familial predisposition to low bone mineral content was assessed. The study was based on dual-energy X-ray absorptiometry (DXA) measurements of lumbar and femoral neck bone mineral density (BMD), using daughters of women with a low BMD (case mothers). These BMD values were compared with those of control daughters of women with a normal BMD. Case mothers (n= 72) aged 54.3 ± 4.8 years were recruited on the basis of a questionnaire and a vertebral Z-score < – 2 SD. Their healthy daughters of more than 20 years (n= 77) aged 28.2 ± 4.9 years had their vertebral and femoral BMD Z-score determined. The control groups were composed of mothers aged 54.1 ± 4.7 years, paired by age ± 2 years to the case mothers, and of their daughters of more than 20 years old, aged 27.7 ± 5.8 years. For daughters, a significant difference was found between the mean vertebral Z-scores (–0.82 ± 1.08 for cases and 0.01 ± 1.14 for controls, p < 0.0001). The difference was in the same direction but was not statistically significant for mean femoral Z-scores (–0.58 ± 1.15 for cases and –0.22 ± 1.33 for controls, p <0.073). These findings confirm the hypothesis of a familial predisposition to low BMD. Received: 18 June 1997 / Accepted: 16 January 1998     

Comparison of Bone and Total Alkaline Phosphatase and Bone Mineral Density in Postmenopausal Osteoporotic Women Treated with Alendronate

Alendronate therapy in osteoporotic women decreases bone turnover and increases bone mineral density (BMD). Optimal patient management should include verification that each patient is responding to therapy. Markers of bone turnover and BMD have both been proposed for this purpose. We have investigated changes resulting from alendronate therapy with an enzyme immunoassay for bone alkaline phosphatase (BAP) and compared it with total alkaline phosphatase (TAP) and BMD of the lumbar spine, hip, and total body. Subjects were drawn from a multicenter randomized, placebo-controlled trial of alendronate in postmenopausal women with osteoporosis. BAP and TAP levels were measured at baseline and following 3, 6 and 12 months of therapy with either placebo (n= 180) or alendronate 10 mg/day (n= 134). All subjects also received 500 mg/day supplemental calcium. BMD was measured at baseline and following 3, 6, 12, 18, 24 and 36 months of therapy. To compare BAP, TAP and BMD at each site for identifying women that experienced a skeletal effect of alendronate, we calculated least significant change (LSC) values from the long-term intraindividual variability in each placebo-treated woman. Median levels of BAP decreased by 34%, 44% and 43% at 3, 6 and 12 months, respectively, in alendronate-treated women (p<0.0001 compared with baseline and with placebo). These changes were significantly greater (p<0.0001) than changes observed for TAP. Following 6 months of alendronate therapy, 90% of the women had experienced a decrease in BAP exceeding the LSC compared with only 71% for TAP. The greatest number of women similarly identified with BMD at any site (i.e. a gain in BMD exceeding the LSC) was 81% for spinal BMD at 36 months. All other sites were less than 70% at 36 months. Short-term changes in BAP and TAP were modestly associated with subsequent changes in BMD at all sites (Spearman’s rho −0.22 to −0.52, p<0.05). Compared with TAP and BMD, BAP testing rapidly and sensitively identified skeletal effects of alendronate thus enabling appropriate drug monitoring of osteoporotic women. Though BAP and TAP changes were modestly predictive of BMD changes, the value of the bone marker tests is their ability to detect rapidly a skeletal effect of therapy. Received: 19 May 2000 / Accepted: 31 October 2000     

Bone Mineral Density in the Long Term after Liver Transplantation

Hepatic osteodystrophy is a complication of chronic liver disease and bone mass is known to decline further in the first year after liver transplantation. The present study focused on bone mineral density (BMD) between 1 and 15 years after liver transplantation under a prednisolone- and azathioprine-based immunosuppressive regimen. Three groups of adult patients were studied: group 1, 45 patients with a follow-up of 5–9 years after transplantation, had BMD measurements done at 1, 2 and 5 years after transplantation; group 2, 17 patients with a follow-up of 10–14 years, had BMD measurements done at 5 and 10 years; group 3, 4 patients with a follow-up of more than 15 years, had BMD measurements done at 10 and 15 years. BMD of lumbar spine (L1–L4) and proximal femur was measured using dual-energy X-ray absorptiometry, and at the same time radiographs of the spine and hips were made. Spinal BMD increased significantly, during the second post-transplant year; subsequently no significant changes were seen. Proximal femur BMD decreased slightly, but significantly during the second year, and remained stable afterwards. About one-third of patients had a BMD below the fracture threshold (= 0.798 g/cm² for the lumbar spine and 0.675 g/cm² for the hip) during the follow-up. In 5 of the 66 patients studied, new vertebral fractures occurred. No fractures or avascular necrosis of the hips were seen. Furthermore, after transplantation lower Z-scores of the hip were found in patients with pre-transplant cholestatic liver diseases, and lower Z-scores of the lumbar spine were found in men compared with women. Long-term follow-up of BMD up to 15 years after transplantation revealed an improvement mainly in the second postoperative year with no deterioration afterwards. Nevertheless a substantial number of patients (around one-third) kept a BMD below the fracture threshold, and new fractures may occasionally occur. The overall outcome appeared somewhat less favorable in men and patients transplanted for cholestatic liver diseases. Received: 15 July 1999 / Accepted: 11 January 2000     

Bone Mineral Density and Metabolism in Familial Dysautonomia

Familial dysautonomia (FD) patients suffer from multiple fractures and have reduced bone pain, which defers the diagnosis. The pathogenesis of bone fragility in FD is unknown. This study aimed to characterize bone mineral metabolism and density in FD. Seventy-nine FD patients aged 8 months to 48 years (mean age 13.9 ± 10.4 years, median 12.3) were studied. Clinical data included weight, height, bone age, weekly physical activity and history of fractures. Bone mineral density (BMD) of the lumbar spine (n= 43), femoral neck (n= 26), total hip (n= 22) and whole body (n= 15) were determined by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D₃, osteocalcin, bone alkaline phosphatase (B-ALP), parathyroid hormone and urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined in 68 patients and age- and sex-matched controls. Forty-two of 79 patients (53%) sustained 75 fractures. Twenty-four of 43 patients had a spine Z-score <–2.0, and 13 of 26 had a femoral neck Z-score <–2.0. Mean femoral neck BMD Z-score was lower in patients with fractures compared with those without (–2.5 ± 0.9 vs –1.5 ± 1.0, p= 0.01). Mean body mass index (BMI) was 16 kg/m² in prepubertal patients and 18.4 kg/m² in postpubertal patients. Bone age was significantly lower than chronological age (75.5 vs 99.3 months in prepubertal patients, p<0.001; 151 vs 174 in post-pubertal patients, p<0.05). NTx and osteocalcin levels were higher in FD patients compared with controls (400 ± 338 vs 303 ± 308, BCE/mM creatinine p<0.02; 90 ± 59.5 vs 61.8 ± 36.9 ng/ml, p<0.001, respectively). B-ALP was lower in FD patients compared with controls (44.66 ± 21.8 vs 55.36 ± 36.6 ng/ml, p<0.04). Mean spine Z-score was significantly lower in physically inactive compared with active patients (–3.00 ± 1.70 vs –1.77 ± 1.3, respectively, p= 0.05). We conclude that fractures in FD patients are associated with reduced BMD. FD patients have increased NTx and osteocalcin. Contributing factors include reduced BMI, failure to thrive and reduced physical activity. Preventive therapy and early diagnosis are essential. Received: 21 May 2001 / Accepted: 27 November 2001     

Bone Mineral Density in French Canadian Women

This cross-sectional study investigated bone mineral density (BMD) at the lumbar spine (L2–4) and femoral neck in French Canadian women residing in the Quebec city area. Data collection was initiated in 1988 and completed in 1994. A total of 747 French Canadian Caucasian women (16–79 years of age) with no metabolic bone disease were evaluated. BMD measurements were obtained using dual-photon absorptiometry (DPA) or dual-energy X-ray absorptiometry (DXA). Anthropometric measures such as weight, height and body mass index (BMI) were recorded. Medical files provided information on demographic characteristics, hormonal profile and lifestyle habits. Results show a curvilinear trend of BMD with aging. Furthermore, the peak BMD at the lumbar spine (L2–4) was reached at 29 years followed by a stable phase until 35 years, after which BMD started to decrease. The pattern of bone evolution at the femoral neck was different, peak BMD being achieved earlier, at 21 years, while after age 26 years a significant decrease was already observed. Women older than 60 years showed the lowest BMD. Regression analysis showed that age, weight and height are determinants of BMD at the lumbar spine and explained 33.9% of inter-individual variation. At the femoral neck, 29.1% of variation was explained by age and height only. In conclusion, our data suggest that French Canadian women have a different pattern of bone loss at the femoral neck compared with the lumbar spine, according to their mean BMD values. Received: 21 July 1997 / Accepted: 15 October 1997     

Serum Albumin and Bone Mineral Density in Healthy Older Men and Women: The Rancho Bernardo Study

Serum albumin has been found to be positively correlated with bone mass in small studies of ambulatory men or women with diagnosed osteoporosis. In this study the relation between serum albumin and bone mineral density (BMD) was examined in 1593 white, community-dwelling men and women aged 50–95 years. BMD was determined using single-photon absorptiometry (SPA) at the ultradistal radius and the midshaft radius, and using dual-energy X-ray absorptiometry (DXA) at the hip and spine. Albumin was measured from a fasting blood sample using the Technicon SMA 12 autoanalyzer. Mean albumin levels in both men and women decreased significantly with increasing age. All but four values were within the normal range (3.5–5.0 g/dl). BMD decreased with increasing age at all sites. In both sexes there was weak positive correlation between serum albumin and BMD in the unadjusted model (Pearson's rvalues <0.3, p values <0.005). After age adjustment, however, the relationship was no longer significant (Pearson's r values <0.05, p values >0.18). Men and women were divided into three sex-specific categories – osteoporotic, osteopenic and normal – based on World Health Organization criteria in relation to young adult means (normal, BMD > –1 SD; osteopenia, BMD between –1 SD and –2.5 SD; osteoporosis, BMD <–2.5 SD). Mean albumin values did not differ significantly across the three BMD categories in men or women. BMD levels stratified for albumin levels and calcium supplement status (a marker for osteoporosis awareness) also did not differ. Albumin levels were also not associated with a history of low-trauma fractures. In summary, there was no age-independent association between serum albumin within the normal range and low BMD or fractures in community-dwelling healthy older adults. We conclude that previously reported associations most likely reflect inadequate adjustment for the age-related decrease in albumin levels and the selection of very frail osteoporotic subjects. Received: 7 October 1997 / Revised: 21 January 1998     

Suitability of the T-score for Establishing Bone Mineral Density Categories

The use of different reference ranges may give rise to different T-score values for the same bone mineral density (BMD) value. This study was designed to quantify the differences in the classification of a particular population on the basis of normal ranges obtained from other reference databases. The T-scores obtained in a sample of 148 women by applying the Spanish normal range were compared with the normal range obtained in NHANES III for femoral neck. Significant differences were found when T-scores were compared, but there were no differences in categorizations using the WHO criteria. The application of these reference ranges to a female population aged older than 45 years with known BMD showed significant differences in classification. In conclusion, the T-score can vary according to the normal range used as reference, but it has little influence on the categorization of individual patients. However, it may be important when applied to a general population. Received: 17 November 1999 / Accepted: 29 October 1999     

Soy Product Intake and Serum Isoflavonoid and Estradiol Concentrations in Relation to Bone Mineral Density in Postmenopausal Japanese Women

To evaluate soy intake and serum concentrations of estradiol and isoflavonoids and their relationship to bone mineral density (BMD) and serum bone-specific alkaline phosphatase (bone ALP) activity, we conducted a cross-sectional study of 87 postmenopausal Japanese women. Soy product and isoflavone intake from soy products and intake of nutrients were assessed with a semiquantitative food-frequency questionnaire. BMD (mg/cm²) was measured by single-energy X-ray absorptiometry at the site of the calcaneus. Serum estradiol (E₂) and the sex hormone-binding globulin (SHBG) were measured by radioimmunoassay. Serum genistein and daidzein concentrations were measured by a high-performance liquid chromatography MS/MS method. A statistically significant correlation was observed between the ratio of E₂ to SHBG and BMD (Spearman r = 0.38, p = 0.0003) after controlling for age, body mass index, smoking status, age at menarche, and intake of vegetable fat, vitamin C and salt. Soy product and isoflavone intake and serum isoflavones were not significantly correlated with BMD after controlling for the covariates. Serum ALP was not significantly correlated with soy product and isoflavone intake, the E₂/SHBG ratio or serum isoflavones. The present study supports the association of BMD with serum estradiol; however, it does not support the association of BMD with soy or isoflavone intake or serum isoflavone levels. Received: 13 August 2001 / Accepted: 30 October 2001     

Bone Mineral Density at the Hip Predicts Mortality in Elderly Men

Low bone density as assessed by calcaneal ultrasound has been associated with mortality in elderly men and women. We examined the relationship between bone density measured at the hip and all cause and cardiovascular mortality in elderly men. Men aged 65–76 years from the general community were recruited from general practices in Cambridge between 1991 and 1995. At baseline survey, data collection included health questionnaires, measures of anthropometry and cardiovascular risk factors, as well as bone mineral density (BMD) measured using dual energy X-ray absorptiometry. All men have been followed up for vital status up to December 1999. BMD was significantly inversely related to mortality from all causes and cardiovascular disease, with decreasing rates with increasing bone density quartile, and an approximate halving of risk between the bottom and top quartile (p <0.002, test for trend all causes and p <0.025, test for trend for cardiovascular deaths). In multivariate analyses using the Cox proportional hazards model, an increase of 1 standard deviation (0.144 g/cm²) in total hip bone density was significantly associated with an age-adjusted 0.77 relative risk (95% CI 0.66–0.91) for all-cause mortality and 0.76 relative risk (95% CI 0.62–0.93) for cardiovascular disease mortality. The association remained significant after adjusting for age, body mass index, cigarette smoking status, serum cholesterol, systolic blood pressure, past history of heart attack, stroke or cancer and other lifestyle factors which included use of alcohol, physical activity and general health status. Low bone density at the hip is thus a strong and independent predictor of all-cause and cardiovascular mortality in older men. Received: 16 August 2000 / Accepted: 27 October 2000     

The Profile of Bone Mineral Density in Chinese Women: Its Changes and Significance in a Longitudinal Study

Bone mineral density (BMD) has been shown to be different in different ethnic groups. When lifestyle and diet evolve, there is a possibility of a change in the normal reference BMD values within an ethnic group over a period of time. As the osteoporotic risk uses the T-score as the bench mark, it is pertinent to evaluate whether such changes do occur. Two measurements, 5 years apart, of the BMD of the spine and the hip were made in a cohort of Chinese women in Hong Kong. A kernel function smoothing method, a nonparametric statistical method, was employed to present the BMD data. The greatest rate of bone loss was found to occur between 50 and 59 years of age, but this rate of loss was reduced from age 60 onwards. The BMD values obtained in these two measurements were different from the previous studies in the same population and were found to be higher at the lumbar spine and neck of femur in women over 65 years of age. Even within the cohort, there seemed to be a reduction in the BMD values of the hip in a span of 5 years, although the differences were statistically insignificant. These studies suggest that BMD values could change in a population for a variety of possible reasons. Hence, the reference BMD values might need to be evaluated at regular intervals for the T-score to be meaningful. Received: 26 April 2000 / Accepted: 8 February 2001