Bone Density in an Immigrant Population from Southeast Asia

The epidemiology of bone loss in populations of Asian heritage is still poorly known. This study compared the skeletal status of a convenience sample of 396 Southeast Asian immigrants (172 Vietnamese, 171 Cambodians and 53 Laotians) residing in Rochester, Minnesota in 1997 with 684 white subjects previously recruited from an age-stratified random sample of community residents. Areal bone mineral density (BMD, g/cm²) and volumetric bone mineral apparent density (BMAD, g/cm³) were determined for lumbar spine and proximal femur using the Hologic QDR 2000 instrument for the white population and the QDR 4500 for Southeast Asian subjects; the machines were cross-calibrated from data on 20 volunteers. Lumbar spine BMD was 7% higher in white than Southeast Asian women ( p < 0.001), and similar results were observed for the femoral neck; lumbar spine BMD was 12% higher in white than nonwhite men ( p < 0.001). Race-specific discrepancies were reduced by calculating BMAD: for premenopausal women, lumbar spine and femoral neck differences between whites and Southeast Asians were eliminated; for postmenopausal women the lumbar spine differences persisted ( p < 0.0001), while femoral neck BMAD was actually higher for Southeast Asians. There were no race-specific differences in femoral neck BMAD among men of any age ( p= 0.312), but lumbar spine BMAD was less for younger ( p= 0.042) but not older ( p= 0.693) Southeast Asian men. There were differences among the Southeast Asian subgroups, but no clear pattern emerged. Predictors of lumbar spine BMAD in Southeast Asian women were age ( p < 0.001), weight ( p= 0.015) and gravidity ( p= 0.037). Even after adjusting for bone size using BMAD, 32% and 9% of Southeast Asian women and men, respectively, would be considered to have osteoporosis at the femoral neck and 25% and 4%, respectively, at the lumbar spine. These findings indicate a need for culturally sensitive educational interventions for Southeast Asians and for physicians to pursue diagnosis and treatment to prevent osteoporosis-related disabilities in this population. Received: 12 October 2000 / Accepted: 15 February 2001     

Variations in Bone Density among Persons of African Heritage

The epidemiology of bone loss in populations of African heritage is still poorly known. We compared a convenience sample of 47 African-American (AA) residents of Rochester, Minnesota (32 women, 15 men) and 66 recent immigrants from Somalia (all women) with 684 white subjects (349 women, 335 men) previously recruited from an age-stratified random sample of community residents. Areal bone mineral density (BMD, g/cm²) and volumetric bone mineral apparent density (BMAD, g/cm³) were determined for lumbar spine and proximal femur using the Hologic QDR 2000 for white subjects and the QDR 4500 for the others; the instruments were cross-calibrated from data on 20 volunteers. Lumbar spine BMD was 18% higher in AA (p<0.001) and 4% lower in Somali (p= 0.147) than white women. Femoral neck BMD was 27% higher in AA women but also 11% greater in Somali women (both p<0.001) compared with whites. Lumbar spine BMD was 6% higher (p= 0.132) and femoral neck BMD 21% higher (p<0.001) in AA than white men. No Somali men were studied. After correcting for bone size differences, both lumbar spine (p<0.01) and femoral neck BMAD (p<0.001) were greater for Somali than white women, but the difference between Somali and AA women persisted. Lumbar spine and femoral neck BMAD values also remained significantly greater for AA women (both p<0.001) and men (p<0.05; p<0.001) compared with whites. Weight was associated with BMAD at both skeletal sites in all groups, but adjustment for differences in weight did not reduce the discrepancy in BMAD values between Somali and AA women or between the latter group and whites. This heterogeneity among different ethnic groups of African heritage may provide an opportunity for research to better explain race-specific differences in bone metabolism. Received: 4 September 2001 / Accepted: 11 January 2002     

Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women

Risk factors that are associated with lower bone mineral density (BMD) may not necessarily be associated with increased bone loss among premenopausal and perimenopausal women. We determined risk factors for lower premenopausal and perimenopausal BMD while simultaneously determining risk factors for increased 6-year rate of bone loss among women aged 24–50 years within a population-based prospective cohort study. BMD of the lumbar spine and femoral neck, reported as t scores, were measured five times within the 6-year study among 614 women who were between the ages of 24 and 44 in 1992/1993. Rates of bone loss were calculated from the repeated BMD measurements. Risk factors for lower BMD over time at the lumbar spine included history of any fracture (P=0.005). The major risk factor for lower BMD over time at the femoral neck was family history of osteoporosis (P<0.002). The major protective factor for greater BMD over time at both skeletal sites was additional body weight (P<0.0001). Other protective factors for greater BMD over time at the femoral neck were modest alcohol consumption (P=0.0002) and high-school sports participation (P=0.002). Risk factors for greater bone loss at either skeletal site included postmenopausal status (P<0.0001 at the lumbar spine; P=0.01 at the femoral neck), and the reporting of a reproductive cancer (P<0.0001 at the lumbar spine; P=0.0008 at the femoral neck). Body weight was protective against bone loss at both skeletal sites (P<0.0001). Baseline age, calcium intake, smoking, and current physical activity were not associated with BMD or bone loss. The understanding of the relative importance of risk factors for both low BMD and bone loss may assist in the identification of women at greater risk for subsequent low postmenopausal BMD.     

Differences in mineral homeostasis, volumetric bone mass and femoral neck axis length in black and white South African women

In South Africa, appendicular and lumbar spine bone mineral density (BMD) have been found to be similar in black and white women. However, femoral BMD has been found to be higher in black than in white women. Two different techniques were used to recalculate BMD to eliminate the possible confounding influence of ethnic differences in height on areal BMD measurements. Volumetric bone mineral apparent density (BMAD) values were calculated and bone mineral content (BMC) was corrected for body and bone size. This report analyses differences in BMD (corrected for height and weight), BMAD, BMC (corrected for body and bone size), femoral neck axis length (FNAL), mineral homeostasis and bone turnover (BT) in a group of 20 to 49-year-old premenopausal (105 whites and 74 blacks) and 45 to 64-year-old postmenopausal (50 whites and 65 blacks) female South African nurses. The corrected BMD and BMC findings were congruous, showing that both pre- and postmenopausal blacks and whites have similar distal radius and lumbar spine bone mass but that whites have lower femoral neck bone mass than blacks. In contrast, BMAD findings suggest that pre- and postmenopausal whites have lower bone mass at the lumbar spine and femoral neck than blacks but similar bone mass at the distal radius to blacks. There is a greater rate of decline in BMD in postmenopausal whites than in blacks. BMD at the femoral neck was 12.1% lower in premenopausal whites and 16.5% lower in postmenopausal whites than in blacks. There was a positive association between femoral neck BMD and weight in premenopausal blacks (R ²=0.5,p=0.0001) but not in whites. Blacks had shorter FNAL than whites in both the pre- and postmenopausal groups. Blacks had lower serum 25-hydroxyvitamin D (25-(OH)D) and higher 1,25-dihydroxyvitamin D (1,25-(OH)₂D) levels than whites. There were no ethnic differences in biochemical markers of bone formation (serum alkaline phosphatase and osteocalcin) or bone resorption (urine hydroxyproline and pyridinoline), or in dietary calcium intake in either the pre- or postmenopausal groups. In the postmenopausal group, whites had higher ionized serum calcium (p=0.003), similar serum albumin, lower serum parathyroid hormone (p=0.003) and higher urinary calcium excretion (p=0.0001) than blacks. These results suggest that the higher peak femoral neck BMD in South African blacks than in whites might be determined by greater weight-bearing in blacks and that the significantly lower femoral neck BMD in postmenopausal whites than in blacks is determined by lower peak femoral neck BMD and a faster postmenopausal decline in BMD in whites. The higher incidence of femoral neck fractures in South African whites than in blacks is probably determined by the lower femoral neck BMD and longer FNAL in whites. The greater rate of decline in BMD in postmenopausal whites than in blacks is associated with an increase in urinary calcium excretion in whites. Measurement of biochemical markers of BT has not contributed to the understanding of ethnic differences in BMD and skeletal metabolism in our subjects.     

Not All Postmenopausal Women on Chronic Steroid and Estrogen Treatment are Osteoporotic: Predictors of Bone Mineral Density

Chronic steroid use results in osteoporosis, and postmenopausal women are believed to be at a high risk for steroid-induced bone loss. The purpose of this study was to determine predictors of bone mineral density (BMD) in postmenopausal women on both chronic steroid and hormone replacement therapy. Seventy-six postmenopausal women (≥3 years postmenopausal, ≥2 years of steroid treatment of ≥5 mg/day of prednisone, and ≥1 year of hormone replacement therapy) were recruited into this study. Measurements of BMD of the lumbar spine and femoral neck were obtained in all subjects. Risk factors for osteoporosis were obtained by questionnaire. Discriminant analysis was performed to determine predictors of BMD. Osteoporosis, defined by a T score of <−2.5, was present in the lumbar spine or femoral neck in 34 of the 76 subjects. Based on these criteria, women with osteoporosis were significantly older, were more years postmenopausal, and had a lower body mass index (BMI) than women who did not have osteoporosis. Predictors of osteoporosis for both the femoral neck and spine included a low BMI (P < 0.05), more years postmenopausal (P < 0.01), and more years on steroids (P < 0.01). Low BMI was the only significant predictor of osteoporosis in the lumbar spine (P < 0.05), whereas for the femoral neck both years on steroids (P < 0.05) and BMI (P < 0.05) were significant predictors of low BMD. In summary, not all postmenopausal women on chronic steroid and hormone replacement therapy are osteoporotic but a low BMI, more years on steroids, and more years postmenopausal were significant predictors of osteoporosis in these subjects. Received: 8 November 1997 / Accepted: 21 May 1997     

Racial/ethnic differences in bone mineral density among older women

The epidemiologic information regarding international differences in bone mineral density (BMD) in women is currently insufficient. We compared BMD in older women across five racial/ethnic groups in four countries. The femoral neck, total hip, and lumbar spine BMD were measured in women (aged 65–74 years) from the Study of Osteoporotic Fractures (SOF) (5,035 Caucasian women and 256 African American women in the US), the Tobago Women’s Health Study (116 Afro-Caribbean women), the Ms Os Hong Kong Study (794 Hong Kong Chinese women) and the Namwon Study (1,377 South Korean women). BMD was corrected according to the cross-site calibration results for all scanners. When compared with US Caucasian women, the age adjusted mean BMD measurements at the hip sites were 21–31 % higher among Tobago Afro-Caribbean women and 13–23 % higher among African American women. The total hip and spine BMD values were 4–5 % lower among Hong Kong Chinese women and 4–7 % lower among South Korean women compared to US Caucasians. The femoral neck BMD was similar in Hong Kong Chinese women, but higher among South Korean women compared to US Caucasians. Current/past estrogen use was a significant contributing factor to the difference in BMD between US versus non-US women. Differences in body weight partially explained the difference in BMD between Asian versus non-Asian women. These findings show substantial racial/ethnic differences in BMD even within African or Asian origin individuals, and highlight the contributing role of body weight and estrogen use to the geographic and racial/ethnic variation in BMD.     

Bone mineral density and prevalent vertebral fractures in men and women

To test the hypothesis that the association between bone mineral density (BMD) and estimated volumetric BMD and prevalent vertebral fractures differs in men and women, we studied 317 Caucasian men and 2,067 Caucasian women (average age 73 years). A total of 43 (14%) men and 386 (19%) women had a vertebral fracture identified on lateral spine radiographs using vertebral morphometry. Hip and spine areal BMD was about 1/3 standard deviation lower among men and women with a vertebral fracture. A 0.10 g/cm² decrease in areal BMD was associated with 30–40% increased odds of having a fracture in men and 60–70% increased likelihood in women. Low bone mineral apparent density (BMAD) was also associated with 40–50% increased odds of a vertebral fracture in both genders. The probability of a man having a fracture was observed at higher absolute areal BMD values than observed for women (P=values for interaction of BMD × gender: trochanter, P=0.05; femoral neck, P=0.10; total hip, P=0.09). In contrast, the probability of fracture was similar in men and women across the range of estimated volumetric BMD (BMAD). In conclusion, low BMD and low BMAD are associated with increased odds of vertebral fracture in both men and women. Measures of bone mass that partially correct for gender differences in bone size may yield universal estimates of fracture risk. Prospective studies are needed to confirm this observation.     

不同国家和地区各种族人群骨密度参考值及其相互比较

目的了解各种族之间骨密度(BMD)参考值的差异。方法收集科学引文索引(SCI)收录杂志发表的20多个国家和地区不同种族人群的BMD参考值,并进行分类整理和比较分析。结果BMD拟合参考曲线显示,各种族女性和男性人群不同骨骼部位的峰值BMD(PBMD),绝大多数发生在20~30岁,日本女性股骨颈达到PBMD的年龄最早(15岁),中国香港男性腰椎达到PBMD的年龄最晚(40岁)。中国人群的PBMD和BMD参考曲线显著低于其他种族,黑人BMD显著高于所有种族。在腰椎、股骨颈和总体髋部,中国女性的PBMD比美国白人女性分别低6.7%、4.9%和6.1%;美国黑人女性股骨颈和总体髋部的PBMD比中国长沙女性分别高13.9%和13.7%,比美国白人女性分别高10.4%和8.8%;墨西哥女性股骨颈的PBMD与北欧女性人群一致。美国黑人男性股骨颈的PBMD与中国香港男性人群的差异最大,为20.9%。结论不同国家和地区各种族人群之间的BMD参考值绝大多数存在种族或地域差异。     

Comparison of broadband ultrasound attenuation to single X-ray absorptiometry measurements at the calcaneus in postmenopausal women

Broadband ultrasound attenuation (BUA), a radiation-free and portable technology, may be useful in assessing bone density and fracture risk. In this study, we compared cross-sectional BUA measurements to the more established single energy X-ray absorptiometry measurements of bone mineral density (BMD) at the calcaneus in 259 healthy postmenopausal women, aged 45–76 years. Paired measurements with repositioning of the subject's dominant heel were made consecutively by each method. A coefficient of variation (CV) for each method was calculated for each individual from the paired scans. BUA and BMD of the heel were also compared with BMD of the lumbar spine and femoral neck, as measured by dual energy X-ray absorptiometry. BUA was significantly correlated with BMD at the calcaneus (r=0.66, P<0.01). Heel BUA was also correlated with lumbar spine BMD (r=0.43, P<0.01) and femoral neck BMD (r=0.43, P<0.01) but the correlations were lower than those between heel BMD and spine (r=0.63, P<0.01) or femoral neck BMD (r=0.62, P<0.01). The mean CV for heel BUA (3.60±3.50%) was significantly greater than that for heel BMD (1.06±0.99%, P<0.01). The moderate correlation of calcaneal BUA and BMD, the lower correlations of BUA than heel BMD with both spine and hip BMD, and lower precision of BUA indicate BUA does not predict bone density as effectively as absorptiometry, the current standard methodology.The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.     

Association of red blood cell 5-methyltetrahydrfoate folate with bone mineral density in postmenopausal Iranian women

Recent studies have suggested that hyperhomocystenemia and low plasma folate are associated with fracture and also bone mineral density (BMD) and that they may contribute to the pathogenicity of osteoporosis in postmenopausal women. However, as plasma total homocysteine (tHcy) and plasma folate can be regarded as short-term markers when compared to a long-term variable such as BMD, in this study we tested the hypothesis that low red blood cell 5-methyltetrahydrofolate (RBC 5-MTHFR) as a long-term marker of the folate status may be a better predictor of BMD than plasma 5-MTHF, and its deficiency may contribute to the pathogenecity of osteoporosis in postmenopausal Iranian women. The BMD at the femoral neck and lumbar spine (measured by dual-energy X-ray absorptiometry, DXA) together with anthropometric and biochemical components of the homocysteine re-methylation pathway including plasma tHcy, 5-MTHF and vitamin B12, RBC 5-MTHF and creatinine were determined in 366 postmenopausal women. RBC 5-MTHF was more highly correlated with BMD at the lumbar spine ( r =0.21, P =0.001) and femoral neck ( r =0.19, P =0.004) than was plasma 5-MTHF (lumbar spine; r =0.14, P =0.03 and femoral neck; r =0.17, P =0.006). Stepwise multiple linear regression analyses revealed that RBC 5-MTHF was one of the predictors of BMD explaining 4.3 and 4.0% variance of BMD at the lumbar spine and femoral neck, respectively, whereas plasma 5-MTHF was excluded in the model and not determined to be a predictor of BMD at both the lumbar spine and femoral neck when adjusted for age, BMI, years since menopause and RBC 5-MTHF. This study suggests that RBC 5-MTHF is a better predictor of BMD than plasma 5-MTHFR when compared to a long-term marker such as BMD, and its deficiency is associated with low BMD that may contribute to the pathogenecity of osteoporosis in postmenopausal women.     

Associations of vitamin C, calcium and protein with bone mass in postmenopausal Mexican American women

We investigated the associations of vitamin C, calcium and protein intakes with bone mass at the femoral neck and lumbar spine in postmenopausal Mexican American women. Bone mass was measured by dual-energy X-ray absorptiometry (DXA) and expressed as areal (BMD, g/cm²) and volumetric (bone mineral apparent density or BMAD, g/cm³) bone mineral density. Diet was assessed using a modified version of the National Cancer Institute Food Questionnaire, which was administered by trained bilingual interviewers familiar with Mexican dietary practices. Data gathered from 125 subjects were analyzed using multiple linear regression analysis with age, body mass index (BMI), acculturation, years of estrogen use, physical activity, total energy intake, and the nutrient of interest as independent variables. Neither calcium nor calcium/protein ratio was associated with bone mineral density. There was evidence of a positive association between dietary vitamin C intake and femoral neck BMD (β=0.0002 g/cm² per mg/day, SE=0.0001,p=0.07) and BMAD (β=0.0001 g/cm³ per mg/day, SE=0.00006,p<0.05), but vitamin C was not associated with lumbar spine bone mass. Further investigation of the role of vitamin C in skeletal health is warranted.     

Bone Mass and Markers of Bone and Calcium Metabolism in Postmenopausal Women Treated with 1,25-Dihydroxyvitamin D (Calcitriol) for Four Years

To evaluate the long-term effect of calcitriol treatment on bone mineral density (BMD) of the femoral neck and lumbar spine and the parameters of calcium and bone metabolism in elderly women, 55 healthy, postmenopausal women, all aged 66 years, were enrolled in the study. Eighteen started a 4-year supplementation with 0.5 μg of calcitriol daily and 37 served as controls. Calcium intake of all the subjects was adjusted to 800 mg daily. In 4 years femoral neck BMD increased by 3.0% in the calcitriol group, but decreased by 1.6% in the control group (P= 0.009). The respective changes in lumbar spine BMD were +2.3% and +0.9% (P= 0.067). Two years' treatment with calcitriol increased the intestinal absorption of strontium by 57% (P < 0.001), doubled the urinary excretion of calcium (P < 0.001), and decreased the mean parathyroid hormone (PTH) level by 32% (P < 0.01). In the calcitriol group the marker of bone formation, serum osteocalcin, decreased by 27% (P < 0.01), and the marker of bone resorption, serum C-telopeptide of type I collagen (CTx), by 33% (P= 0.05) after 2 years. In two subjects the calcitriol dose had to be reduced because of hypercalciuria. We conclude that calcitriol treatment increases bone mass at the femoral neck and lumbar spine, the increases being maintained for up to 4 years. The gain in bone mass results from reduced bone turnover which is partly a consequence of the enhanced intestinal absorption of calcium and suppressed serum PTH levels. Received: 8 January 1999 / Accepted: 29 February 2000     

Influence of duration of total breast-feeding on bone mineral density in a Turkish population: does the priority of risk factors differ from society to society?

Introduction Despite numerous studies on risk factors for osteoporosis the effect of breast-feeding on bone mineral density (BMD) is unclear. In this study our aim was to determine the influence of total duration of breast-feeding on BMD, and subsequent risk of osteoporosis. Methods A total of 1,486 postmenopausal women over the age of 40 were included in the study. Women with diseases or who were under drug treatments known to affect bone metabolism were excluded. The BMD of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry technique, using either the Norland XA-26 or Lunar DPX-IQ densitometers and were transferred to standard values. Patients were placed in groups of five with respect to the duration of their breast-feeding as never, 1–12 months, 12–24 months, 24–60 months, >60 months. Results One-way ANOVA test showed a significant difference between the lumbar spine and femoral neck BMD of these groups of women (p<0.001, p<0.001). Post hoc Bonferroni correction revealed that both the lumbar spine and femoral neck BMD results of women with longer duration of total breast-feeding were significantly lower than those of women with less duration of total breast-feeding. In subsequent analysis other potential risk factors were also considered in a multiple linear stepwise regression model. Years since menopause (p<0.001), weight (p<0.001), total duration of breast-feeding (p<0.001), and body mass index (p=0.001) were found to be the most important predictors for lumbar spine BMD; and age (p<0.001), weight (p<0.001), years since menopause (p<0.001), and total duration of breast-feeding (p<0.001) for femoral neck BMD. Conclusions This study showed significant associations between total duration of breast-feeding and BMD. In conclusion, total duration of breast-feeding might be an important risk factor besides age, weight, and years since menopause in postmenopausal osteoporosis.     

Spine and femur BMD by DXA in patients with varying severity spinal osteoporosis

Summary Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1:-3SD deformations only; group 2: one-4SD deformation; group 3: two-four-4SD deformations; and group 4: 5 or more-4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20–40 years) and 109 postmenopausal normal women (average age 64, range 60–70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm² (P<0.01) and Ward's triangle 0.059 g/cm² (P<0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this crosssectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.     

Endogenous sex steroids and bone mineral density in healthy Greek postmenopausal women

The aim of this study was to assess the association of endogenous sex steroids with bone mineral density (BMD) in healthy postmenopausal women not on hormone therapy. A total of 884 postmenopausal women aged 42–71 years were studied in a cross-sectional design. Parameters assessed were follicle-stimulating hormone, luteinizing hormone, estradiol, total testosterone, sex hormone-binding globulin, free estrogen index (FEI), free androgen index (FAI), Δ4-androstendione (Δ4A), dehydroepiandrosterone sulfate (DHEAS), bone alkaline posphatase, and bone mineral density at the lumbar spine (L-BMD) and femoral neck (N-BMD). Estradiol and FEI associated positively with both L-BMD and N-BMD (r = 0.21–0.47, P < 0.01). These associations remained significant after adjustment for age, years since menopause, and body mass index. FAI correlated positively with both L-BMD and N-BMD (r = 0.18 and 0.33, respectively; P < 0.01). At the multivariate analysis, however, FAI remained the significant determinant only for N-BMD. Δ4A associated positively with N-BMD (r = 0.27, P = 0.001), whereas DHEAS showed no association with BMD at either site. Thus, endogenous steroids are significant determinants of postmenopausal BMD. Endogenous estradiol may be more important for lumbar spine BMD, whereas endogenous androgens are associated mainly with femoral neck BMD.     

The relationship between bone mineral density and ultrasound in postmenopausal and osteoporotic women

The aim of this cross-sectional study was to use a novel method of data analysis to demonstrate that patients with osteoporosis have significantly lower ultrasound results in the heel after correcting for the effect of bone mineral density (BMD) measured in the spine or hip. Three groups of patients were studied: healthy early postmenopausal women, within 3 years of the menopause (n=104, 50%), healthy late postmenopausal women, more than 10 years from the menopause (n=75, 36%), and a group of women with osteoporosis as defined by WHO criteria (n=30, 14%). Broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were measured using a Lunar Achilles heel machine, and BMD of the lumbar spine and left hip was measured using dual-energy X-ray absorptiometry (DXA). SOS, BUA and Stiffness were regressed against lumbar spine BMD and femoral BMD for all three groups combined. The correlation coefficients were in the range 0.52–0.58, in agreement with previously published work. Using a calculated ratio R, analysis of variance demonstrated that the ratio was significantly higher in the osteoporotic group compared with the other two groups. This implied that heel ultrasound values are proportionately lower in the osteoporotic group compared with the other two groups for an equivalent value of lumbar spine and femoral neck BMD. We conclude that postmenopausal bone loss is not associated with different ultasound values once lumbar spine or femoral neck BMD is taken into account. Ultrasound does not give additional information about patterns of bone loss in postmenopausal patients but is important in those patients with osteoporosis and fractures.     

A Prospective Study of Bone Loss in Menopausal Australian-Born Women

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46–59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14–41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n= 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of 70.9% (0.4%) at the lumbar spine and 70.7% (0.6%) at the femoral neck (both p50.05 compared with women who remained premenopausal). In the women who became postmenopausal (n= 42) the mean annual changes in BMD were 72.5% (0.2%) at the lumbar spine and 71.7% (0.2%) at the femoral neck (both p50.0005), and in the women who remained postmenopausal (n= 60) they were 70.7% (0.2%) per year and 70.5% (0.3%) per year respectively (both p50.05), compared with women who remained premenopausal. In the 1–3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p50.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n= 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p50.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p50.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine. Received: 23 June 1997 / Accepted: 5 November 1997     

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects (n=400) were selected by sex and age stratum from the full list of residents born in 1910–1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects (P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.     

CD38 is associated with premenopausal and postmenopausal bone mineral density and postmenopausal bone loss

One goal of osteoporosis research is to identify the genes and environmental factors that contribute to low bone mineral density (BMD) and fracture. Linkage analyses have identified quantitative trait loci (QTLs), however, the genes contributing to low BMD are largely unknown. We examined the potential association of an intronic polymorphism in CD38 with BMD and postmenopausal bone loss. CD38 resides in 4p15, where a QTL for BMD has been described. CD38−/− mice display an osteoporotic phenotype at 3 months, with normalization of BMD by 5 months. The CD38 polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 457 postmenopausal and 173 premenopausal Caucasian women whose spine and hip BMD was measured by dual energy X-ray absorptiometry (DXA). Influence of the CD38 polymorphism on bone loss was analyzed in 273 postmenopausal women over a follow-up of 2.94 ± 1.50 years. The CD38-PvuII polymorphism was significantly associated with premenopausal and postmenopausal (P = 0.001) lumbar spine BMD. Women homozygous for the G allele had >14% lower spinal BMD than women with GC/CC genotypes. An allele dose effect was observed at the spine in premenopausal (P = 0.002) and postmenopausal (P < 0.001) cohorts. The CD38-PvuII polymorphism was significantly associated with femoral neck BMD in pre- and postmenopausal women (P = 0.002 and P = 0.011, respectively). However, significance was lost following adjustment of hip BMD for covariates in the postmenopausal cohort (P = 0.081). The CD38-PvuII polymorphism was weakly associated with bone loss at the spine (P = 0.024), in postmenopausal women not taking hormone replacement therapy. We suggest that the CD38-PvuII polymorphism may influence the attainment and maintenance of peak BMD and postmenopausal bone loss.     

Idiopathic osteoporosis in premenopausal women

Although osteoporosis predominantly affects older postmenopausal women, low bone mineral density also occurs in men and younger women. In men, it is often unexplained by recognized secondary causes. These men with idiopathic osteoporosis have reductions in serum IGF-I as well as indices of reduced bone formation. Younger women also experience bone loss of unknown etiology (IOP). Whether premenopausal women with IOP have similar decreases in IGF-I levels and reduced indices of bone formation is unknown. We prospectively evaluated a group of premenopausal women with unexplained low bone mass and compared them to normal premenopausal women with respect to serum concentrations of IGF-I. Thirteen premenopausal women (34.2±2.3 years) with low bone density (mean lumbar spine T-score –2.26±0.20) were compared with 13 premenopausal women (35.7±1.7 years) with normal bone density of similar age, height and ethnic composition. Body mass index (BMI) was lower in subjects than controls (20.5±0.7 versus 25.2±1.1 kg/m², P<0.01). A family history of osteoporosis and a history of fragility fractures were found more frequently in subjects than controls (P0.05). Calciotropic hormones did not differ between the two groups. In contrast to our observations in men with idiopathic osteoporosis, mean serum IGF-I concentrations did not differ between subjects and controls (subjects: 22.5±2.2 nmol/l versus controls: 20.8±1.6 nmol/l; NS). Moreover, serum IGF-I levels did not correlate significantly with serum estradiol or with BMD at either the lumbar spine or femoral neck. However, lower follicular phase serum estradiol levels among non-oral contraceptive users were found in subjects as compared to controls (subjects: 124.1±13 pmol/l versus controls 194.9±24 pmol/l, P=0.06). Calculated free, bioavailable estradiol levels were significantly lower overall in subjects than controls (0.6±0.1 versus 1.2±0.2 pmol/l, P<0.05). Total serum estradiol levels correlated with BMD at the femoral neck (r=+0.50; P<0.05). Free, bioavailable estradiol correlated with BMD and BMAD at the lumbar spine (r=+0.54, P<0.01 and r=+0.54, P<0.05, respectively) and femoral neck (r=+0.60 and r=+0.55 respectively, both P<0.01). Urinary NTX excretion, although within the normal premenopausal range, was 45% higher in subjects than controls (41.6±5.9 nmol BCE/l versus 28.3±2.4 nmol BCE/l; P<0.05). Bone-specific alkaline phosphatase activity was also higher (17.4±1.6 ng/ml versus 14.7±0.8 ng/ml), although the difference was not statistically significant. These results suggest differences in the pathogenesis of idiopathic osteoporosis in women as compared to men with IOP.