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     

Effect of Long-Term Growth-Hormone Substitution Therapy on Bone Mineral Density and Parameters of Bone Metabolism in Adult Patients with Growth Hormone Deficiency

Reduced bone mineral density (BMD) and the prevalence for osteoporotic vertebral fractures are symptoms of growth hormone deficiency (GHD) syndrome, and GH replacement therapy is now available for GH-deficient adults. We investigated the long-term effects of GH replacement therapy on bone mineral density (BMD) and bone metabolism in 19 adult patients with GHD over a period of 18 months. In response to GH treatment, the initially decreased IGF-I concentrations rose significantly during 18 months of therapy to levels within the normal range (matched for sex and age) (mean change 158.1 ± 50.8 ng/ml, P < 0.001). Parameters of bone formation such as osteocalcin (OC) and procollagen I-C-Peptide (PICP) showed a significant increase in the first 6 months of therapy, followed by a slight decrease in the next months. Markers of bone resorption (Crosslaps^R and deoxypyridinoline (D-Pyr) also increased significantly with a peak value after 6 months and all parameters except PICP remained above baseline values after 18 months. BMD of the femoral neck (FN) showed an increase after 18 months of therapy (mean change 0.01 ± 0.03 g/cm² after 18 months, n.s.). However, the increase in BMD was significant only in the lumbar spine (LS) (mean change 0.03 ± 0.04 g/cm², P < 0.05 after 18 months). We conclude that GH replacement therapy in adult patients with GHD over a period of 18 months causes a pronounced increase in bone turnover mainly during the first 12 months of therapy and increases BMD of the lumbar spine and the femoral neck after 18 months. Received: 13 March 1997 / Accepted: 7 August 1997     

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     

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     

Biochemical Markers of Bone Turnover and Bone Loss at the Lumbar Spine and Femoral Neck: The Taiji Study

The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40–79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P= 0.009), and that of BGP was found to be significant in women (P= 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making. Received: 26 January 1998 / Accepted: 9 July 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     

Dissimilar Spine and Femoral Z-Scores in Premenopausal Women

The purpose of this study was to determine if differences exist in premenopausal women between z-scores for lumbar spine and proximal femoral bone mineral densities (BMD). Participants were 237 women ranging in age from 20 to 45 years. BMDs of the lumbar spine and proximal femur (femoral neck, Ward's area, and trochanter) were assessed using dual-energy X-ray absorptiometry (Lunar DPX). Mean (±SD) age, height, and weight of the participants were 29.4 ± 6.9 years, 164.4 ± 6.1 cm, and 64.9 ± 12.1 kg, respectively. Lumbar spine BMD and BMD at the femoral neck, Ward's area, and trochanter were significantly correlated with large SEEs (r = 0.59–0.65; SEE = 0.09–0.11). No positive correlation with age and BMD at any site was seen in this population but a significant negative correlation with age was seen in the proximal femur beginning at age 30. Twenty to 24% of the 20–29-year-olds exhibited a difference in z-scores of greater than 1 between the spine and sites in the proximal femur. This percentage increased to 32–46% in the 30–45-year-olds but the nature of the observed differences changed. The differences in spine and proximal femoral z-scores that are seen in the older age group appear to be the result of the earlier onset of bone loss in the proximal femur rather than an initial difference in peak bone mass which has been maintained. Received: 28 August 1996 / Accepted: 25 April 1997     

Relationships Between Bone Mass Measurements and Lifetime Physical Activity in a Swedish Population

Lifetime occupational and leisure time activities were assessed by a questionnaire in order to evaluate their relationship to bone mass measurements and biochemical markers of bone metabolism in a population of 61 women and 61 men, randomly selected from a Swedish population register, to represent ages between 22 and 85 years. We also considered possible confounders by using questions about smoking habits, milk consumption, hormone replacement therapy (HRT), and menopausal age. Bone mineral density (BMD) and bone mineral content (bone mass, BMC) of the total body, lumbar spine, and proximal femur (neck, trochanter, Ward's triangle) were measured by dual energy X-ray absorptiometry (DXA), and BMD of the forearm with single energy X-ray absorptiometry (SXA). In addition, both DXA and SXA provided information on bone area. Quantitative ultrasound measurements (QUS) at the heel were performed to assess the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Fasting blood samples were analyzed for biochemical markers of bone metabolism as well as parathyroid hormone (PTH) and total serum calcium. After adjustment for confounding factors, neither BMD nor QUS measurements were consistently related to lifetime leisure time or occupational activities; nor were there any consistent patterns relating biochemical markers of bone metabolism to bone mass measurements. However, physical activity seemed to influence bone mass, area, and width more than density. In men, high levels of leisure time activity were associated with raised values for lumbar spine area (6.2%) and width (3.3%) as well as for femoral neck area (5.5%) compared with their low activity counterpart. Men exposed to high levels of occupational activity demonstrated lower lumbar spine BMD (10.9%) and area (5.3%) than men with low activity levels. Within an unselected Swedish population, estimation of lifetime occupational and sport activities as well as bedrest, using a questionnaire, demonstrated no major effects on bone density. However, the association between high levels of lifetime activity and raised values for bone mass, area, and width indicate that geometrical changes in bone may provide better estimations of mechanically induced bone strength than bone density, at least in men. Received: 20 May 1997 / Accepted: 15 October 1997     

Biochemical Markers as Predictors of Bone Mineral Density Changes After GnRH Agonist Treatment

To evaluate bone biochemical markers as predictors of the efficacy of a hormone replacement therapy (HRT), we studied the bone changes induced by the cessation and return of ovarian function in 28 patients treated for 6 months with a GnRH agonist. This model reproduced the effects observed in postmenopausal women with high bone turnover treated with HRT. At the end of the treatment, Z scores were 1.8 ± 0.3 for Crosslaps (CTx) and deoxypyridinoline (D-Pyr), and 1.1 ± 0.2 for bone alkaline phosphatase (B-ALP) and osteocalcin (OC). This indicated an imbalance in bone remodeling with a high bone resorption. Bone mineral density (BMD) fell by 4.2 ± 2.5%. The changes in BMD between the 6th and 12th months were 0.34 ± 2.24 and −1.73 ± 3.25% at the lumbar spine and the femoral neck, respectively. Biochemical markers except urinary calcium and hydroxyproline measured at 6 months were positively correlated with the BMD changes at the lumbar spine. After the resumption of menstruation, 13 of 28 women displayed positive spine BMD changes between the 6th and 12th months; in this group, bone biochemical markers measured at 6 months were significantly higher (P= 0.02). Stepwise regression analysis showed that the association of B-ALP and D-Pyr measured at 6 months explained 40% of BMD variance and the association of B-ALP, PTH, and estradiol 56%. We conclude that measuring individual biochemical bone markers can help to predict the bone effect of an increase in the circulating estradiol in women with ovarian deficiency. Received: 16 January 1997 / Accepted: 17 June 1997     

Ultrasound Velocity Through the Phalanges in Normal and Osteoporotic Patients

Quantitative ultrasound (US) measurements have been shown to be a new technique assessing bone status. This study aimed to assess a new US instrument, the DBM Sonic 1200? (IGEA) which permits the measurement of the speed of sound in the proximal phalanges (SOSp) of the hand. The results obtained were compared with DXA (SOPHOS) and US measurements at the calcaneus (Achilles? LUNAR). The in vivo precision expressed by coefficient of variation was 0.91%. Ultrasound measurements of phalanges were significantly correlated with BMD in the entire group of 90 subjects: osteoporotic patients (n = 47) and controls (n = 43) (r = 0.44, femoral neck and 0.45, lumbar spine, P < 0.01). A significant correlation was also found in the control group (r = 0.33, lumbar spine and 0.38, femoral neck, P < 0.05) but not in the osteoporotic group (r = 0.3, lumbar spine and 0.17, femoral neck, P > 0.05). Mean values for 31 postmenopausal, osteoporotic women and age-matched controls showed a significant decrease in US measurements at the phalanges (P < 0.05) and the calcaneus (P < 0.01) as well as bone mineral density (BMD) at the spine and femoral neck (P < 0.01) in the osteoporotic group. A decision threshold for a sensitivity of 80% for osteoporotic fractures resulted in a specificity value of only 37% for SOSp, between 53 to 65% for calcaneus US measurements and 45 to 56% for BMD. The Z score, the odds ratio, the ROC curves, and areas under the curves plotted for the subgroup of 31 fractures and their healthy controls showed poorer values for SOSp than BMD and calcaneus US measurements. In conclusion, US measurements of phalanges seem to be less efficient than calcaneus US and BMD measurements to distinguish osteoporotic from healthy women. Other studies and also prospective studies are required to assess the interest in fracture risk assessment. Received: 23 September 1996 / Accepted: 25 November 1997     

Long-Term Vegetarian Diet and Bone Mineral Density in Postmenopausal Taiwanese Women

This study examined bone density among postmenopausal Buddhist nuns and female religious followers of Buddhism in southern Taiwan and related the measurements to subject characteristics including age, body mass, physical activity, nutrient intake, and vegetarian practice. A total of 258 postmenopausal Taiwanese vegetarian women participated in the study. Lumbar spine and femoral neck bone mineral density (BMD) were measured using dual-photon absorptimetry. BMD measurements were analyzed first as quantitative outcomes in multiple regression analyses and next as indicators of osteopenia status in logistic regression analyses. Among the independent variables examined, age inversely and body mass index positively correlated with both the spine and femoral neck BMD measurements. They were also significant predictors of the osteopenia status. Energy intake from protein was a significant correlate of lumbar spine BMD only. Other nutrients, including calcium and energy intake from nonprotein sources, did not correlate significantly with the two bone density parameters. Long-term practitioners of vegan vegetarian were found to be at a higher risk of exceeding lumbar spine fracture threshold (adjusted odds ratio = 2.48, 95% confidence interval = 1.03–5.96) and of being classified as having osteopenia of the femoral neck (3.94, 1.21–12.82). Identification of effective nutrition supplements may be necessary to improve BMD levels and to reduce the risk of osteoporosis among long-term female vegetarians. Received: 10 May 1996 / Accepted: 9 August 1996     

Low Bone Mass Density at Multiple Skeletal Sites, Including the Appendicular Skeleton in Amenorrheic Runners

The aim of this study was to investigate any difference in bone mass at different sites between female long-distance runners with amenorrhea and those with eumenorrhea. We compared 10 amenorrheic and 10 eumenorrheic athletes to determine whether athletes with amenorrhea have lower BMD in multiple skeletal regions, including weight-bearing lower limbs. The amenorrheic group had experienced menstrual dysfunction ranging from 3 to 43 months. As a further control group, 16 eumenorrheic soccer players were compared with the former two running groups regarding their BMD measurements. The two groups were matched for age, height, and amount of training. Areal bone mineral density (BMD) was measured and was found to be significantly lower in the total body, humerus, spine, lumbar spine, pelvis, femoral neck, trochanter, total femur, femur diaphysis, tibia diaphysis and in the nonweight-bearing head of the femur in the amenorrheic group. Body weight, BMI, fat mass, and body fat percent were significantly lower in the amenorrheic group. The differences in the BMD of the head, humerus, femoral neck, total femur, femur diaphysis, and tibia diaphysis disappeared when adjusted for body weight. Compared with the soccer group, the amenorrheic subjects had significantly lower BMD values at all sites except for the head, Ward's triangle, and femur diaphysis. Blood samples were obtained in the two running groups for analysis of osteocalcin, carboxy terminal telopeptide (ICTP), procollagen I (PICP), and estradiol. There were no significant differences between the groups but there was a strong tendency towards a lower estradiol level and a higher osteocalcin level in the amenorrheic group. A free estradiol index (FE₂) was derived as the ratio of estradiol to sex hormone binding globulin (SHBG) and was significantly lower in the amenorrheic group. No difference in their daily intake of total energy, protein, carbohydrates, fiber, calcium, and vitamin D was observed. However, both groups showed a surprisingly low energy intake in relation to their training regimens. Stepwise regression analyses revealed that weight was the best predictor of spine BMD in both groups. Estradiol and FE₂ were significant predictors of the BMD of the proximal femur in the eumenorrheic group, but did not predict any BMD site in the amenorrheic group. In conclusion, amenorrhea in athletic women affects trabecular and cortical bone in both axial and appendicular skeleton. However, some of the discrepancy can be explained by a lower body weight. Physical weight-bearing activity does not seem to completely compensate for the side effects of reduced estrogen levels even in weight-bearing bones in the lower extremity and spine. Received: 15 November 1997 / Accepted: 9 July 1998     

The Relation of Dietary Vitamin C Intake to Bone Mineral Density: Results from the PEPI Study

Ascorbic acid is a required cofactor in the hydroxylations of lysine and proline necessary for collagen formation; its role in bone cell differentiation and formation is less well characterized. This study examines the cross-sectional relation between dietary vitamin C intake and bone mineral density (BMD) in women from the Postmenopausal Estrogen/Progestin Interventions Trial. BMD (spine and hip) was measured using dual energy X-ray absorptiometry (DXA). The PEPI participants (n = 775) included in this analysis were Caucasian and ranged in age from 45 to 64 years. At the femoral neck and total hip after adjustment for age, BMI, estrogen use, smoking, leisure physical activity, calcium and total energy intake, each 100 mg increment in dietary vitamin C intake, was associated with a 0.017 g/cm² increment in BMD (P= 0.002 femoral neck; P= 0.005 total hip). After adjustment, the association of vitamin C with lumbar spine BMD was similar to that at the hip, but was not statistically significant (P= 0.08). To assess for effect modification by dietary calcium, the analyses were repeated, stratified by calcium intake (>500 mg/day and ≤500 mg/day). For the femoral neck, women with higher calcium intake had an increment of 0.0190 g/cm² in BMD per 100 mg vitamin C (P= 0.002). No relation between BMD and vitamin C was evident in the lower calcium stratum. Similar effect modification by calcium was observed at the total hip: the β coefficient in the higher calcium stratum was similar to that for the total sample (β= 0.0172, P= 0.01), but no statistically significant relation between total hip BMD and vitamin C was found in the lower calcium subgroup. Although the relation between vitamin C and lumbar spine BMD was of marginal statistical significance in the total sample, among women ingesting higher calcium, a statistically significant association was observed (β= 0.0199, P= 0.024). These data are consistent with a positive association of vitamin C with BMD in postmenopausal women with dietary calcium intakes of at least 500 mg. Received: 12 September 1997 / Accepted: 27 January 1998     

Changes in Bone Mineral, Lean Body Mass and Fat Content as Measured by Dual Energy X-ray Absorptiometry: A Longitudinal Study

Bone mineral density (BMD) and soft tissue composition were measured by dual energy X-ray absorptiometry (DXA) 3–4 years apart in 273 men and women aged 23–90. We found different rates of BMD loss in different skeletal regions. There were also different rates of BMD loss in different regions within the hip. Average rates of loss for male subjects 50 years of age and above for BMD total body were 0.1%/year and for femoral neck 1.5%/year, whereas lumbar spine (L2–L4) increased by 0.4%/year. Average rates of loss for female subjects 50 years of age and above for BMD total body were 0.0%/year, femoral neck 0.9%/year, and lumbar spine (L2–L4) 0.1%/year. Received: 28 November 1997 / Accepted: 26 July 1999     

Absence of Linkage for Bone Mineral Density to Chromosome 12q12-14 in the Region of the Vitamin D Receptor Gene

Polymorphisms in the region of the gene for the vitamin D receptor (VDR) (chromosome 12q12-14) have been associated with differences in bone mineral density (BMD) in some studies but not in others. Because linkage analysis assesses allele sharing identical-by-descent among relatives instead of the association of a particular allele of an anonymous marker, we have performed a linkage study for bone BMD using microsatellite markers flanking the VDR locus. The present study explores whether or not relatives who share the chromosomal region containing the VDR gene have more similar bone density. Participants in the Framingham Osteoporosis Study (aged 37–89 years) who had undergone BMD testing were used to test for concordance of genotype with phenotype in the hip (femoral neck, Ward's area, trochanter) and lumbar spine (L2-L4) with adjustment for covariates. Multipoint quantitative trait linkage analysis using variance components methods was conducted with microsatellite markers flanking the VDR locus (GATA91H06, GATA5A09, GGAT2G06) in 332 extended families containing 1062 individuals with both bone density measures and marker data. In addition, quantitative trait sib-pair linkage analysis, with a marker (AFM345xf1) in close proximity to the VDR locus, was performed in a second sample of 169 sibships (n = 413), comprising 284 full-sib pairs. Neither analysis revealed evidence for linkage of this region to femoral neck, Ward's area, lumbar spine, and trochanter in age or sex BMI, and height-adjusted bone density measures. Additional adjustment for alcohol intake, caffeine consumption, smoking status, and estrogen supplement (female only) did not alter the results. The present study could not demonstrate linkage of BMD to chromosome 12q12-14. These findings suggest that neither the VDR gene nor other genes at this locus are likely to have a substantial impact upon bone density. Received: 23 February 2000 / Accepted: 3 August 2000 / Online publication: 22 December 2000     

Identification of Metabolic Bone Disease in Patients with Endogenous Hyperthyroidism: Role of Biological Markers of Bone Turnover

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 ± 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L₂–L₄) and femoral neck (FN). Data were expressed as g/cm² and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease. Received: 5 May 1997 / Accepted: 5 June 1997     

Lifestyle Determinants of Bone Mineral: A Comparison Between Prepubertal Asian- and Caucasian-Canadian Boys and Girls

The purpose of this study was to examine the difference in lifestyle and morphometric factors that affect bone mineral and the attainment of peak bone mass in 168 healthy Asian (n = 58) and Caucasian (n = 110) Canadian, prepubertal girls and boys (mean age 8.9 ± 0.7) living in close geographical proximity. DXA (Hologic 4500) scans of the proximal femur (with regions), lumbar spine, and total body (TB) were acquired. We report areal bone mineral densities (aBMD g/cm²) at all sites and estimated volumetric density (νBMD, g/cm³) at the femoral neck. Dietary calcium, physical activity, and maturity were estimated by questionnaire. Of these prepubertal children, all of the boys and 89% of the girls were Tanner stage 1. A 2 × 2 ANOVA demonstrated no difference between ethnicities for height, weight, body fat, or bone mineral free lean mass. Asian children consumed significantly less dietary calcium (35%) on average and were significantly less active (15%) than their Caucasian counterparts (P < 0.001). There were significant ethnicity main effects for femoral neck bone mineral content (BMC) and αBMD (both P < 0.001) and significant sex by ethnicity interactions (P < 0.01). The Asian boys had significantly lower femoral neck BMC (11%), aBMD (8%), and νBMD (4.4%). At the femoral neck, BMFL mass, sex, and physical activity explained 37% of the total variance in aBMD (P < 0.05). In summary, this study demonstrated differences in modifiable lifestyle factors and femoral neck bone mineral between Asian and Caucasian boys. Received: 21 July 1998 / Accepted: 30 September 1999     

Calcaneal Ultrasonometry: Response to Treatment in Comparison with Dual X-ray Absorptiometry Measurements of the Lumbar Spine and Femur

The object of this study was to determine the effectiveness of calcaneal ultrasonometry in the prediction of bone mineral changes in the lumbar spine and femoral neck in response to treatment of osteoporosis. There were 673 women in the study who had one or more follow-up measurements between 1 and 4 years after the initial baseline determination for a total of 881 same-day measurements of the calcaneus, spine, and femur. The LUNAR Achilles and LUNAR DPX (LUNAR Corporation, Madison, WI) were used. Patients were divided into three treatment time groups: Group 1, 1–<2 years, n = 461; Group 2, 2–<3 years, n = 278; Group 3, 3–<4 years, n = 142. There were significant increases in the bone mineral density (BMD) of the lumbar spine, femoral neck, and in the broadband ultrasonic attenuation (BUA) of the calcaneus for the three groups. In contrast, a significant decrease in speed of sound (SOS) was obtained in these time frames and the stiffness index remained unchanged. Spearmen correlations showed an inverse relationship between the percent changes in SOS and BUA, the reasons for which are speculative. Correlations between the percent changes in calcaneal parameters and the BMDs of the lumbar spine and femoral neck were weak, whether significant or not, rho varying from −0.12 to 0.20. There was a subset of 371 patient measurements that registered BMD increases in both the lumbar spine and femoral neck. This was considered to be an objective indication of adequate compliance with prescribed treatment. Analysis of this subset yielded parameter correlations similar to those of the entire group. It is concluded that changes in the calcaneal ultrasound parameters in response to treatment of osteoporosis are not a reflection of mineral changes occurring in the lumbar spine and femoral neck in a given individual, and in this regard, calcaneal ultrasonometry is not a substitute for direct-site dual X-ray absorptiometry (DXA) measurement of the lumbar spine and femur. Received: 19 February 1998 / Accepted: 24 June 1998     

The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN

 We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 42–52 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = −10 for lumbar spine [95% confidence interval (CI): −0.13, −0.06] and r = −0.08 for femoral neck (95% CI: −0.11, −0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multiethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period. Received: 10 September 2001 / Accepted: 8 July 2002 RID="*" ID="*" see Appendix for details     

Correlation of Bone Density to Strength and Physical Activity in Young Men with a Low or Moderate Level of Physical Activity

The objective of this study was to evaluate the relationship among bone mineral density (BMD), physical activity, muscle strength, and body constitution, in young men with a low or moderate level of physical exercise. Another aim was to investigate whether the head is unaffected by physical activity. The subjects consisted of 33 Caucasian healthy men, mean age 24.8 ± 2.3 years. BMDs of the total body, lumbar spine (L2-L4), femoral neck, Ward's triangle and trochanter, humerus, and head were measured using dual-energy-X-ray absorptiometry (DXA). Bivariate correlations were measured among the different BMD sites and age, weight, height, body mass index (BMI), fat mass, lean body mass, amount of physical activity (hours/week), hamstrings strength, and quadriceps strength. Significant predictors were found for all BMD sites except the head. Using all these variables, only 6% of the variation in BMD of the head could be explained, whereas 46% (total body), 31% (humerus), 17% (lumbar spine), 38% (femoral neck, Ward's), and 41% could be explained for the trochanter. Physical activity and muscle strength were found to be independent significant predictors of BMD of the total body and the sites at the proximal femur. These results suggest that at the time of peak bone mass attainment, physical activity is an important predictor of the clinically relevant proximal femur in young men with a low or moderate level of physical activity. Furthermore, since head BMD was not related to the level of physical activity, we suggest that head BMD may be used as an internal standard, to control for selection bias, in studies investigating the effect of physical activity on bone mass. Received: 5 February 1996 / Accepted: 24 September 1996