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     

Vitamin D and Bone Mineral Density in Ambulatory Women Living in Buenos Aires, Argentina

The aim of this study was to determine possible associations between bone mineral density (BMD), 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (PTH). In a retrospective study we examined the case notes of free-living postmenopausal women living in our city (34° S). We also report a low prevalence of vitamin D deficiency (25(OH)D <25 nmol/l, 5.6%) and of secondary hyperparathyroidism (intact PTH >65 pg/ml, 7.5%). Age was correlated with BMD at the lumbar spine (r=−0.25, p = 0.00038) and femoral neck (r=−0.252, p = 0.0003). Body mass index (BMI) was correlated with BMD at the femoral neck (r= 0.177, p = 0.021) but not at the lumbar spine. 25(OH)D was positively correlated with BMD at the femoral neck (r = 0.149, p=0.036) but not at the lumbar spine. PTH was positively correlated with age (r= 0.279, p = 0.012) and negatively correlated with 25(OH)D (r=−0.322, p = 0.0036). PTH was also negatively correlated with BMD at the lumbar spine (r=−0.258, p=0.02) and the femoral neck (r=−0.282, p = 0.011). Forward stepwise multiple regression showed that BMI, age and 25(OH)D made significant contributions to BMD at the femoral neck. PTH also showed a significant contribution to BMD at both sites. In conclusion, weak correlations found between PTH and 25(OH)D and BMD suggest these biochemical variables, among other factors, contribute to lumbar spine and femoral neck BMD. Received: 19 February 2000 / Accepted: 20 June 2000     

Household Tobacco Smoke Exposure is Negatively Associated with Premenopausal Bone Mass

Subjects exposed to environmental tobacco smoke have been found to be at increased risk for several health problems. Whether exposure to passive tobacco smoke is associated with reduced bone mineral density (BMD) is unknown. In order to examine this, we measured BMD in 154 healthy premenopausal women (age range 40–45 years). BMD of the total hip, femoral neck, lumbar spine and total body was measured by dual-energy X-ray absorptiometry (DXA). Data were collected on exposure to household tobacco smoke from age 10 years to the present as well as on other lifestyle factors related to bone mass. We found that 67.5% of the subjects had a history of household tobacco smoke exposure. Subjects exposed to household tobacco smoke had a mean adjusted BMD that was significantly lower at the total hip (p= 0.021) and femoral neck (p= 0.018) compared with subjects who were not exposed. In addition, duration of household tobacco smoke exposure was negatively associated with BMD at the total hip (p = 0.010), femoral neck (p= 0.004), lumbar spine (p = 0.037) and total body (p = 0.031). Subjects exposed to household tobacco smoke for 15 years or more had mean adjusted BMD that was 4% lower at the total body, and more than 8% lower at the total hip, femoral neck and lumbar spine, compared with subjects who were not exposed. In conclusion, household tobacco smoke exposure during adolescence and young adulthood was found to be negatively associated with BMD at the total hip and femoral neck, and duration of exposure was negatively associated with BMD at the total hip, femoral neck, lumbar spine and total body in premenopausal women. Received: 17 December 2001 / Accepted: 16 February 2002     

Regular Physical Exercise and Bone Mineral Density: A Four-Year Controlled Randomized Trial in Middle-aged Men. The DNASCO Study

The aim of the study was to investigate the effects of regular aerobic exercise training on bone mineral density (BMD) in middle-aged men. A population based sample of 140 men (53–62 years) was randomly assigned into the exercise and reference groups. BMD and apparent volumetric BMD (BMD_vol) of the proximal femur and lumbar spine (dual-energy X-ray absorptiometry, DXA) and anthropomorphic measurements were performed at the randomization and 2 and up to 4 years later. The participation rate was 97% and 94% at the second and third BMD measurements, respectively. As another indication of excellent adherence and compliance, the cardiorespiratory fitness (aerobic threshold) increased by 13% in the exercise group. The 2% decrease in the reference group is regarded as an age-related change in cardiorespiratory fitness. Regardless of the group, there was no association between the increase in aerobic threshold and change in BMD. In the entire group, age-related bone loss was seen in the femoral neck BMD and BMD_vol (p<0.01). BMD and BMD_vol values increased with age in L2–L4 (p<0.004). An increased rate of bone loss at the femoral neck was observed in men with a low energy-adjusted calcium intake (p = 0.003). Men who increased their alcohol intake during the intervention showed a decrease in the rate of bone loss at the femoral neck (p = 0.040). A decrease in body height associated with decreased total femoral BMD (r= 0.19, p = 0.04) and the change in body height was a predictor of bone loss in the femoral neck (β= 0.201). Long-term regular aerobic physical activity in middle-aged men had no effect on the age-related loss of femoral BMD. On the other hand, possible structural alterations, which are also essential for the mechanical strength of bone, can not be detected by the DXA measurements used in this study. The increase seen in lumbar BMD reflects age-related changes in the spine, thus making it an unreliable site for BMD follow-up in men. Received: August 2000 / Accepted: November 2000     

Estimation of the Prevalence of Low Bone Density in Canadian Women and Men Using a Population-Specific DXA Reference Standard: The Canadian Multicentre Osteoporosis Study (CaMos)

The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10 061 women and men aged ≥25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged ≥50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 ± 0.121 g/cm² for women and 1.058 ± 0.127 g/cm² for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 ± 0.125 g/cm² for women and 0.910 ± 0.125 g/cm² for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged ≥50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%. Received: 23 April 1999 / Accepted: 14 April 2000     

Determinants of Bone Mineral Density in Middle Aged Men: A Population-Based Study

Osteoporosis is a growing health problem not only in women but also in men. To assess determinants of bone mineral density (BMD) at the spine and proximal femur, a randomly selected sample of 140 Finnish men aged 54–63 years was measured using fan beam dual-energy X-ray absorptiometry. Isometric muscle strength was measured using a computerized measurement system and cardiorespiratory fitness was assessed with maximal oxygen uptake (VO₂max) using breath-by-breath respiratory gas analyses during an incremental bicycle ergometer exercise. Intakes of calcium and energy were estimated using 4-day food records. Smoking habits and alcohol consumption were assessed from an interview and a 4 week diary, respectively. Isometric muscle strength of triceps and biceps brachii, extensors and flexors of thigh and rectus abdominis correlated significantly with BMD (r= 0.18–0.35, p= 0.02–0.000). Calcium intake correlated positively with femoral (r= 0.19–0.28, p= 0.03–0.003), but not with lumbar BMD. In addition, calcium intake adjusted for dietary energy content (mg/MJ) correlated with femoral BMD (r= 0.25–0.36, p= 0.03–0.000). Smoking had no effect on BMD, whereas alcohol intake correlated positively with BMD at L2–L4 (r = 0.19, p= 0.031). In the multiple linear regression analysis adjusted calcium intake predicted BMD in every site measured, while strength of abdominal muscles predicted BMD at Ward’s triangle and femoral neck. Body weight was a predictor of trochanteric BMD. Body height was the best predictor of lumbar and femoral neck area. We conclude that low dietary calcium intake, weak muscle strength and low body weight are risk factors for low BMD in men. Received: 30 August 1999 / Accepted: 29 December 1999     

Vitamin D Receptor Gene Polymorphisms, Bone Mass, Bone Loss and Prevalence of Vertebral Fracture: Differences in Postmenopausal Women and Men

Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of vertebral fractures in a population-based sample of both sexes (n = 326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry. Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck, and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p= 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related to bone mass and bone loss in women; also a trend in the prevalence of vertebral fractures was observed in postmenopausal women but not in men. Received: 8 June 1998 / Accepted: 7 December 1998     

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     

Areal and volumetric bone density in Hong Kong Chinese: a comparison with Caucasians living in the United States

It is a common perception that Asians have lower bone density than Caucasians. However, such relationships could be confounded by bone size. In this study, the skeletal status of a convenience sample of 482 men and 887 women living in Hong Kong is compared with published data for Caucasians living in Rochester, Minnesota. Areal bone mineral density (BMD, g/cm²) and volumetric bone mineral apparent density (BMAD, g/cm³) were determined for the lumbar spine and proximal femur, using the Hologic QDR 2000 instrument. Cross-calibration was performed by measuring a common phantom, and the Hong Kong data were adjusted by a multiplication factor. Lumbar spine and femoral neck BMD and BMAD of Chinese men and women were all significantly lower (P<0.001 by t-test) than those of Caucasians, but the differences in BMAD were on average only about half the size of the differences in BMD. For instance, in postmenopausal Chinese women, BMD at the femoral neck and lumbar spine were 15.2% and 18.8% lower respectively, but BMAD at the femoral neck and lumbar spine were only 7.8% and 12.4% lower respectively. Similar trends were observed in men. After adjusting for age, body height and weight, the difference in BMAD between Caucasians and Chinese was further reduced and only statistically significant among postmenopausal women and among men younger than age 50 years for the lumbar spine. For instance, the adjusted BMAD in postmenopausal Chinese women at the femoral neck and lumbar spine were 3.9% (P=0.03 by ANCOVA) and 7.3% (P<0.001 by ANCOVA) lower respectively, while the adjusted BMAD at the lumbar spine for Chinese men younger than 50 years was 11.7% lower (P<0.01 by ANCOVA). Predictors of BMAD in Hong Kong Chinese women include body weight, age at menarche, cigarette smoking, and oral contraceptive use (P<0.001), while body weight was the only independent predictor of BMAD in Hong Kong Chinese men (P<0.001). We conclude that bone density is lower in Hong Kong Chinese men and women than in Caucasians, although such differences were attenuated by adjustments for bone size, body weight and height.     

A Comparative Study of Computed Digital Absorptiometry and Conventional Dual-Energy X-ray Absorptiometry in Postmenopausal Women

The aim of the study was to evaluate whether computed digital absorptiometry (CDA) of the hand might be a useful screening technique for identifying patients with postmenopausal osteoporosis and to compare the results of CDA with those of dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck. We studied 230 postmenopausal women (mean age 58.4 ± 7.9 years). For CDA, bone mineral density (BMD) was measured with an AccuDEXA Schick densitometer in the third middle phalanx of the nondominant hand. For DXA, BMD of the lumbar spine and upper femur was assessed using a DXA Hologic QDR-1000 densitometer. We did a comparative analysis (ANOVA) and linear correlation tests. Sensitivity and specificity of CDA and receiver operating characteristic (ROC) curves for the diagnosis of osteoporosis were calculated. The mean BMD with CDA was 0.445 ± 0.084 (T-score: −1.27 ± 1.29). The mean BMD (g/cm²) with DXA at the lumbar spine was 0.877 ± 0.166 (T-score: −1.52 ± 1.59) and 0.708 ± 0.127 at the femoral neck (T-score: −1.12 ± 1.25). BMD at the lumbar spine and femoral neck correlated positively with CDA of the hand (r= 0.66 and r= 0.65 respectively, p<0.001). When using as cut-off a T-score of −2.5, according to WHO criteria, 76 women (33%) had osteoporosis of the lumbar spine and/or femoral neck with DXA and 42 (18%) with CDA (p<0.001). The kappa score for osteoporosis was 0.33 for CDA versus spinal DXA and 0.35 for CDA versus femoral DXA. With the cut-off level used, sensitivity and specificity of CDA in detecting osteoporosis at the lumbar spine were 0.39 and 0.90, respectively; sensitivity and specificity of CDA in identifying osteoporosis at the femoral neck were 0.58 and 0.87, respectively. The positive predictive value of CDA for osteoporosis was 69% and the negative predictive value was 75%. The area under the ROC curve for osteoporosis was 0.822 ± 0.028. We conclude that: (a) CDA assessment has a moderate correlation with BMD measured by DXA at the lumbar spine and femoral neck; (b) CDA has a low sensitivity for the diagnosis of osteoporosis compared with spinal and femoral DXA; and (c) predictive values for osteoporosis at both the lumbar spine and femoral neck are acceptable. Received: September 2000 / Accepted: January 2001     

Osteocalcin Gene Polymorphism is Related to Bone Density in Healthy Adolescent Females

Recently a polymorphism was found in the human osteocalcin gene, and its association with bone mass was investigated in healthy postmenopausal Japanese women. The osteocalcin gene allelic variant HH was found to be overrepresented in women with osteopenia. The purpose of this study was to investigate whether the previously demonstrated polymorphism of the osteocalcin gene was related to bone mineral density (BMD; g/cm²) or osteopenia in a group of 97 healthy Caucasian adolescent females (aged 16.9 ± 1.2 years, mean ± SD). BMD of the left humerus, right femoral neck, lumbar spine and total body was measured using dual-energy X-ray absorptiometry. The relation between the allelic variants and bone density was analyzed as presence or absence of the H allele. Presence of the H allele was found to be related to a lower BMD of the humerus (0.97 vs 1.02, p = 0.03). There was also a strong tendency towards significance at the femoral neck (p = 0.06) and total body (p = 0.11). Using a multiple linear regression and including physical activity, weight, height and years since menarche, presence of the H allele was found to be an independent predictor of humerus BMD (β=−0.21, p<0.05) and femoral neck BMD (β=−0.23, p<0.01). Using logistic regression, presence of the H allele was also independently associated with a 4.5 times increased risk of osteopenia (p = 0.03) in the whole group. Osteopenia was defined as at least 1 SD lower bone density than the mean for the whole group of at least one of the BMD sites measured. We have demonstrated that the osteocalcin HindIII genotype is independently related to bone density in healthy adolescent females. The present study also suggests that presence of the H allele is predictive of osteopenia at an early age. Received: 31 January 2000 / Accepted: 25 April 2000     

Determinants of Bone Loss in Elderly Men and Women: A Prospective Population-Based Study

While several studies have described the rate and pattern of involutional bone loss in women, far less information is available for men. Furthermore, the roles of lifestyle and body build in determining bone loss rate in both sexes have been largely extrapolated from cross-sectional studies. We addressed this issue in a population-based longitudinal study which sought to ascertain rates of bone loss at the femoral neck and lumbar spine in a cohort of men and women aged 60–75 years at baseline, and to relate this loss to anthropometric and lifestyle variables. We additionally investigated the capacity of biochemical markers of bone turnover to predict bone loss rates in these subjects. Women lost bone at all sites; this ranged from 0.20%/year at the lumbar spine to 1.43%/year at the femoral trochanteric region. By contrast, men lost only 0.20%/year at the trochanteric region, and gained at the lumbar spine (0.33%/year) and at Ward’s triangle (0.27%/year) over the 4-year period. Anthropometric measurements were associated with bone loss in both sexes; lower baseline body mass index (BMI) and a greater rate of loss of adiposity over the follow-up period were both associated with greater bone loss at all proximal femoral sites. These attained statistical significance after Bonferroni correction at the total proximal femur among both men (r= 0.29), p<0.01) and women (r= 0.31, p<0.05). Lifestyle factors associated with lower rates of bone loss (after adjustment for BMI) included alcohol consumption at the femoral neck among women (p= 0.007) and physical activity at the lumbar spine among men (p = 0.05). Serum parathyroid hormone, 25-hydroxyvitamin D and biochemical markers of bone turnover did not predict bone loss after adjustment for adiposity. Received: 8 December 1998 / Accepted: 8 April 1999     

Ethnic and Gender Differences in Bone Mineral Density and Bone Turnover in Young Adults: Effect of Bone Size

Generally, the incidence of osteoporotic fracture is lower in black populations and in men. These effects of ethnicity and gender may result from differences in peak bone mineral density (PBMD) and bone turnover (BT), which in turn are affected by bone size. Therefore, the aims of this study were to examine the effects of ethnicity and gender on bone mineral density (BMD) and BT in young African-Caribbean and Caucasian adults, and to adjust for the effect of bone size on BMD and BT. BMD was measured at the lumbar spine, L2–L4 (LS), total body (TB) and femoral neck (FN) by dual-energy X-ray absorptiometry in 44 blacks (16 men, 28 women) and 59 whites (28 men, 31 women) ages 20–37 years. We measured serum bone-specific alkaline phosphatase (BAP) and serum osteocalcin (OC) as markers of bone formation and urinary immunoreactive free deoxypyridinoline (ifDpd) and crosslinked N-telopeptide of type I collagen (NTx) as markers of bone resorption. To adjust the data for any differences in bone size, we calculated: (a) bone mineral apparent density (BMAD), an estimated volumetric bone density which attempts to normalize BMD measurements for bone size; and (b) bone resorption markers as a ratio to total body bone mineral content (TB BMC). Two-way analysis of variance was used to compare the effects of race and gender, and to test for any interaction between these two factors. Blacks had higher BMD compared with whites at the TB (p<0.001), LS (p= 0.0001) and FN (p= 0.0005). This increase remained significant at the LS only after calculating BMAD. Men had higher BMD at all sites (except at the LS). This increase was no longer significant at the FN after calculating BMAD, and LS BMAD was actually greater in women (p<0.0001). Blacks and whites had similar concentrations of turnover markers, but men had higher bone turnover markers than women (BAP, p<0.0001; OC, p= 0.002; ifDpd, p= 0.03; NTx, p<0.0001). This increase in bone resorption markers was no longer significant after adjusting for TB BMC (except for NTx in whites). We conclude that the skeletal advantage in blacks during young adulthood is not explained by bone size. However, it seems probable that bone size effects partially explain gender differences in BMD and bone turnover. Received: 2 February 1999 / Accepted: 2 December 1999     

Inappropriate Reference Range for Peak Bone Mineral Density in Dual-energy X-ray Absorptiometry: Implications for the Interpretation of T-scores

An inappropriate reference range for peak bone mineral density (BMD) may result in identification of an incorrect proportion of subjects with osteopenia and osteoporosis at dual-energy X-ray absorptiometry (DXA). In this study, we assessed the prevalence of low BMD in Turkish young adults with respect to local population reference range T-scores and the US reference range T-scores. The BMD values of lumbar spine (L1–L4) and proximal femur (femoral neck, intertrochanter, trochanter, Ward”s triangle and total) were measured by DXA in 323 healthy young adults (171 women, 152 men) aged 19–25 years. The World Health Organization criteria for the diagnosis of osteopenia (−2.5 <T-score <−1) and osteoporosis (T-score ≤−2.5) were applied. In women, the means of the US reference range T-scores were significantly lower than zero at the spine and proximal femoral sites (p<0.0001). In men, the means of the US reference range T-scores were significantly lower than zero at the spine, femoral neck, intertrochanter, total femur (p<0.0001) and trochanter (p<0.05), but not at Ward”s triangle (p=0.92). When the diagnoses were based on local population reference range T-scores instead of the US reference range T-scores, the prevalence of low BMD (T-score <−1) in women fell from 50.3% to 14.0% at the lumbar spine and from 60.8% to 14.6% at the femoral neck, and in men from 42.8% to 15.8% at the lumbar spine and from 30.9% to 17.1% at the femoral neck. Our data suggest that individual populations should use their own reference range T-scores to avoid misdiagnoses of osteopenia and osteoporosis by DXA. Received: 4 November 1999 / Accepted: 29 March 2000     

Identification of Women with Reduced Bone Density at the Lumbar Spine and Femoral Neck using BMD at the Os Calcis

We assessed the clinical usefulness of bone density measurements at the os calcis as a screening tool to identify patients with low bone density at the lumbar spine and femoral neck. Bone mineral density (BMD) was recorded in 443 women (mean age 60 years) referred to a bone densitometry service. Measurements were made at the lumbar spine and femoral neck using a Lunar DPXL and at the right os calcis using a Peripheral Instantaneous X-ray Imaging (PIXI) dual-energy X-ray absorptiometry system. Average T-scores derived using the manufacturer”s data were: 1.59 for the lumbar spine, −1.41 for the femoral neck and −0.87 for the os calcis. The prevalence of osteoporosis using WHO criteria (T-scores of −2.5 or less) was 36% for the lumbar spine or femoral neck but only 9.7% for the os calcis. BMD of the os calcis correlated with that at the lumbar spine (r= 0.69, p<0.001) and femoral neck (r= 0.67, p<0.001). The area under the receiver operator characteristics curve was 0.836 (standard error 0.020) for the os calcis related to osteoporosis at the lumbar spine or femoral neck. Optimal accuracy was obtained at a T-score of ≤−1.3 (BMD 0.39 g/cm²) when the sensitivity was 69.6% (95% confidence interval 65.3, 73.9%) and specificity 82.6% (95% confidence interval 79.1, 86.1%). However, the probability of diagnosing low bone density from a given BMD at the os calcis varied by age and site scanned. Accordingly, for informing management strategies, the choice of a single cutoff BMD at the os calcis may not be appropriate and several thresholds may be adopted based on age, the site of interest (lumbar spine or femoral neck) and consideration of associated clinical features. Thus, the use of heel bone density scanners could reduce the number of axial bone density measurements required. The advantages of portability, low cost and shorter scan times should reduce the cost of detection and provide a greater opportunity for identification of women at risk of fracture. Received: 18 June 1999 / Accepted: 30 March 2000     

In Vivo MRI Measurements of Bone Quality in the Calcaneus: A Comparison with DXA and Ultrasound

Magnetic resonance imaging (MRI) has shown promise in the assessment of bone architecture. The precision and feasibility of MRI measurements in osteoporosis in vivo have been assessed in this study. T2′ was calculated from measurements of T2 and T2* in the calcaneus of 32 postmenopausal women using a gradient-echo sequence PRIME (Partially Refocused Interleaved Multiple Echo). This sequence allows the measurement of T2 and T2* in one acquisition. In vivo measurements of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were made in the calcaneus, spine and femoral neck. The ultrasound parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were also measured in the calcaneus. These three techniques have not previously been compared in the same study population. The precision of the MRI technique was poor relative to the DXA and ultrasound techniques, with a CV of 6.9%± 4.4% for T2′ and 5.5%± 3.6% for T2*. Approximately 4% of this is due to system error as determined by phantom measurements. The postmenopausal women were classified as having low BMD if they had a lumbar spine (L2–4) BMD of less than 0.96 g/cm² (more than 2 standard deviations below normal peak bone mass). Calcaneal T2′ was significantly correlated with calcaneal BMD (r = –0.79, p <0.0001), BUA (r = –0.59, p = 0.0004) and SOS (r = –0.58, p = 0.0006). T2′ was significantly different in postmenopausal women with normal BMD and those with low BMD (p <0.01). However, the difference was of only borderline significance (p <0.06) after adjustment for age and years since menopause. Received: 8 July 1997 / Accepted: 29 April 1998     

Association of VDR and Estrogen Receptor Genotypes with Bone Mass in Postmenopausal Caucasian Women: Different Conclusions with Different Analyses and the Implications

Much work has been done on the association between vitamin D receptor (VDR) genotypes and bone mineral density (BMD). Despite considerable effort, the results are inconsistent. While the VDR association remains unresolved, studies have expanded to other candidate genes (i.e., estrogen receptor (ER) genotypes), also yielding inconsistent results. A few studies have suggested that interaction effects between VDR and ER genotypes significantly affect BMD. We assessed associations of BMD with VDR BsmI genotypes, and ER XbaI and PvuII polymorphisms (denoted as ERX and ERP respectively) with spine, femoral neck, distal radius BMD, and with total body bone mineral content (tbBMC) in 108 US Mid-western postmenopausal Caucasian women. We statistically controlled for confounding factors such as height, weight, etc., in the analysis. No significant association was detected for ER genotypes with spine and radius BMD, or for VDR genotypes with femoral neck and radius BMD and tbBMC. No significant interaction between VDR and ER genotypes was detected in our sample. However, the VDR genotypes are significantly (p = 0.004) associated with *5.8% spine BMD variation. Both ERX and ERP genotypes are significantly (p = 0.02) associated with *3.5% femoral neck BMD variation. ERX genotypes are significantly (p = 0.03) associated with *2.4% tbBMC variation. However, if the data were analyzed by simple ANOVA as in some previous studies, without adjusting statistically for confounding factors, all the significant results we found here would have gone undetected. Our findings suggest that: (1) VDR and ER genotypes may have different effects on BMD at different sites and on tbBMC; and (2) if significant factors influencing bone are not appropriately controlled, true significant associations can easily be missed. These findings may offer a partial explanation for some of the earlier inconsistent results of association studies on BMD with VDR and ER genotypes. Received: 4 August 1998 / Accepted: 2 November 1998     

Effects of Alendronate on Bone Density in Men with Primary and Secondary Osteoporosis

Alendronate has been reported to increase bone mineral density (BMD) and reduce fracture risk in women with osteoporosis. As there are no proven safe and effective treatments available for men with osteoporosis, we compared the effects of alendronate (10 mg/day) on BMD, measured using dual-energy X-ray absorptiometry, in a 12-month prospective, controlled, open label study involving (i) men with primary (n= 23) or secondary osteoporosis (n= 18), (ii) postmenopausal women with primary (n= 18) or secondary (n= 21) osteoporosis, and (iii) 29 male and 14 female untreated controls matched by age, height and weight. The patients had one or more vertebral fractures and ranged in age from 34.6 to 85.1 years. BMD was detectably increased relative to baseline by 6 months, and increased by comparable amounts in males and females with primary or secondary osteoporosis. At 12 months, lumbar spine BMD was 5.4%± 1.1% to 7.0%± 2.2% higher in the treated groups compared with baseline and controls (p<0.05 to 0.0001). Trochanteric BMD increased by 2.6%± 1.5% and 3.7%± 1.7% in treated men with primary and secondary osteoporosis, respectively (p = 0.06 to 0.08), and by 3.9%± 1.3% in treated women with primary osteoporosis (p<0.01) after 12 months. No significant changes were detected at the femoral neck or Ward’s triangle. BMD remained unchanged in controls. We infer that alendronate has comparable incremental effects on BMD in men and women with primary and secondary osteoporosis within 12 months of treatment. The changes are in the order of 0.5 SD – effects associated with a clinically worthwhile reduction in fracture risk. The data provide room for optimism regarding the role of alendronate in the treatment of osteoporosis in men. Randomized, double-masked and placebo-controlled trials are needed to confirm these preliminary findings and demonstrate antifracture efficacy using vertebral and nonvertebral fracture rates as the primary endpoint. Received: 23 February 1999 / Accepted: 2 June 1999     

Forearm Bone Mineral Densitometry Cannot be Used to Monitor Response to Alendronate Therapy in Postmenopausal Women

Alendronate significantly increases bone mass and reduces hip and spine fractures in postmenopausal women. To determine whether forearm densitometry could be used to monitor the efficacy of alendronate, we examined changes in bone mineral density (BMD) at the forearm (one-third distal, mid-distal, ultradistal radius) versus changes at the hip (femoral neck, total hip) and spine (posteroanterior and lateral) in a double-masked, randomized, placebo-controlled clinical trial of 120 elderly women (mean age 70 ± 4 years) treated with alendronate for 2.5 years. We found that among women in the treatment group, BMD increased by 4.0–12.2% at the hip and spine sites (all p<0.001), whereas BMD increased only nominally at the one-third distal radius (1.3%, p<0.001) and mid-radius (0.8%, p<0.05), and remained stable at the ultradistal radius. At baseline, forearm BMD correlated with that of the hip (r= 0.55–0.64, p<0.001), femoral neck (r= 0.54–0.61, p<0.001) and posteroanterior spine (r= 0.56–0.63, p<0.001). Changes in radial BMD after 1 year of therapy were not correlated with changes in hip and spine BMD after 2.5 years of therapy. In contrast, short-term changes in total hip and spine BMD were generally positively associated with long-term changes in total hip, femoral neck and spine BMD (r= 0.30–0.71, p<0.05). Furthermore, long-term BMD changes at the forearm did not correlate with long-term hip and spine BMD changes, in contrast to the moderate correlations seen between spine and hip BMD at 2.5 years (r= 0.38–0.45, p<0.01). We conclude that neither short- nor long-term changes in forearm BMD predict long-term changes in overall BMD for elderly women on alendronate therapy, suggesting that measurements of clinically relevant central sites (hip and spine) are necessary to assess therapeutic efficacy. Received: 18 February 1999 / Accepted: 20 May 1999     

Changes in Bone Density in Patients with Ankylosing Spondylitis: A Two-Year Follow-Up Study

The objectives of the study were to determine the 2 year rate of bone changes in patients with ankylosing spondylitis (AS) and, whether bone loss is related to physical impairment, systemic inflammation, and therapy. Consecutive outpatients fulfilling the modified New York criteria for AS were included. Baseline assessment included age, disease duration, treatment, clinical, radiologic and laboratory data. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were determined every 6 months. Persistent systemic inflammation was defined as mean ESR ≥ 28 mm/h or mean CRP ≥ 15 mg/l. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry, at baseline and year 2. Statistical analysis compared the baseline and 24 month follow-up BMD data, and determined whether baseline data, and persistent systemic inflammation during the 2 years, were related to the 24 month percentage changes in BMD. Fifty-four patients (35 men, 19 women; mean age 37.3 ± 11.3 years, mean disease duration 12.4 ± 8.6 years) were included. After 2 years, BMD did not change at the lumbar spine (+0.75%± 3.5, p= 0.23), and decreased at the femoral neck (–1.6%± 4, p= 0.006). The 24 month percentage change in femoral neck BMD was related to persistent systemic inflammation, defined using ESR (mean percentage change –4.1%± 5.7 and –1.2%± 3.9 in patients with and without persistent inflammation; respectively; p= 0.007). These results suggest that persistent inflammation might be an etiologic factor of bone loss in AS. Received: 15 November 2000 / Accepted: 15 February 2001