Efficiency of Quantitative Ultrasound Measurements as Compared with Dual-Energy X-ray Absorptiometry in the Assessment of Corticosteroid-Induced Bone Impairment

Bone loss due to corticosteroid treatment differs from that of postmenopausal osteoporosis with regard to bone structure. Corticosteroids affect both horizontal and vertical trabeculae while horizontal trabeculae are damaged in postmenopausal osteoporosis. Dual-energy X-ray absorptiometry (DXA) is the gold standard to evaluate bone loss. The place of quantitative ultrasound (QUS), a technique that could theoretically provide information on bone structure, is not well established in corticosteroid-induced bone impairment. The aim of the study was to determine the usefulness of QUS in the assessment of corticosteroid-induced bone impairment. We hypothesized that the relationship between QUS and DXA could be influenced by changes in bone structure and thus differ with regard to corticosteroid treatment. Seventy-seven women with inflammatory diseases chronically treated with corticosteroids (dose: 7.5–15 mg/day), 29 without corticosteroids and 100 controls were investigated. Bone mineral density at the lumbar spine (BMDL) was measured by DXA and QUS parameters were measured at the calcaneus. Both the QUS parameters (SOS, BUA, Stiffness) and BMDL were significantly lower (by 1.3% for SOS, 5.8% for BUA, 12.7% for Stiffness and 11% for BMDL) in patients treated with corticosteroids compared with patients not taking corticosteroids and with controls (p<0.001, ANCOVA, with age and height as covariates). Multiple linear regressions of Stiffness, SOS and BUA as dependent variables on age, BMDL, corticosteroid treatment and a computed new variable designed to test the interaction between BMDL and the treatment group showed that Stiffness, SOS and BUA were dependent on age and BMDL (p<0.001); BUA and Stiffness were dependent on treatment group. Taking into account the age of the patients, a significant difference was observed in the relation between BUA and BMDL according to treatment with corticosteroids. A similar difference was found in the subgroup of patients without fractures. SOS and BUA were strongly correlated but their relation did not differ according to treatment. Thus, QUS is useful in the assessment of corticosteroid-associated bone loss. Furthermore, the observation of a significant difference in the relationship between BUA and BMDL with regard to corticosteroid treatment might support the hypothesis that QUS, especially BUA, could give additional information about bone structure. Received: 24 August 1998 / Accepted: 4 March 1999     

Effects of Cigarette-Smoking on Bone Mass as Assessed by Dual-Energy X-ray Absorptiometry and Ultrasound

In order to elucidate the influence of nicotine smoking on bone mass in elderly women, bone mass was cross-sectionally assessed by dual energy X-ray absorptiometry (DXA) in total body, hip and lumbar spine, as well as with ultrasound of calcaneus and phalanges of the hand. Subjects were 1,042, 75-year old women, recruited on a population basis (Osteoporosis Prospective Risk Assessment (OPRA) study). We found bone mineral density (BMD) to be lower in hip (0.71 vs. 0.76 g/cm², p<0.0001 for femoral neck) and total body (0.96 vs. 1.02 g/cm², p<0.0001) in current smokers compared to never-smokers. There was no difference in BMD of the lumbar spine between current smokers and never-smokers. Bone mass as assessed by ultrasound of the calcaneus was lower for speed of sound (p<0.01), broadband ultrasound attenuation (p<0.0001) and stiffness (p<0.0001) in current smokers than in never-smokers. No differences were found for ultrasound measurements of the phalanges between smokers and never-smokers. Also, weight and current physical activity as assessed by a questionnaire differed significantly between current smokers and never-smokers.  There was no evident difference between former smokers and never-smokers in any of the skeletal regions assessed by DXA or ultrasound.  After correcting for differences in weight and physical activity, current smokers had lower BMD in all hip sites (p<0.05) and total body (p<0.01) compared to never-smokers. Ultrasound and BMD spine did not differ between these two groups after correction for weight and physical activity.  We conclude that nicotine smoking has a negative influence on bone mass independent of differences in weight and physical activity. This difference is detected by DXA but not by ultrasound measurements of the calcaneus or the phalanges. The present data are encouraging since no bone mass differences were found between former and never-smokers. Received: 29 March 2002 / Accepted: 2 July 2002     

Bone Mineral Measurements: A Comparison of Delayed Gamma Neutron Activation, Dual-Energy X-ray Absorptiometry and Direct Chemical Analysis

A system in vitro consisting of a femur from a cadaver and soft-tissue equivalent material was used to test the agreement between several techniques for measuring bone mineral. Calcium values measured by delayed gamma neutron activation (DGNA) and bone mineral content (BMC) by Lunar, Hologic and Norland dual-energy X-ray absorptiometers (DXA) were compared with calcium and ash content determined by direct chemical analysis. To assess the effect of soft-tissue thickness on measurements of bone mineral, we had three phantom configurations ranging from 15.0 to 26.0 cm in thickness, achieved by using soft-tissue equivalent overlays. Chemical analysis of the femur gave calcium and ash content values of 61.83 g ± 0.51g and 154.120 ± 0.004 g, respectively. Calcium measured by DGNA did not differ from the ashed amount of calcium at any of the phantom configurations. The BMC measured by DXA was significantly higher, by 3–5%, than the amount determined by chemical analysis for the Lunar densitometer and significantly lower, by 3–6%, for the Norland densitometer (p<0.001–0.024), but only 1% lower (not significant) for the Hologic densitometer. DXA instruments showed a decreasing trend in BMC as the thickness increased from 20.5 to 26.0 cm (p<0.05). However, within the entire thickness range (15.0–26.0 cm), the overall influence of thickness on BMC by DXA was very small. These findings offer insight into the differences in these currently available methods for bone mineral measurement and challenge the comparability of different methods. Received: 27 July 1998 / Accepted: 9 January 1999     

Disproportionate, Age-Related Bone Loss in Long Bone Ends: A Structural Analysis Based on Dual-Energy X-ray Absorptiometry

The width of long bone diaphyses apparently increase with age, a phenomenon that is suggested to have some positive impact on bone strength. On the other hand, these changes in size that are site-specific may cause a deterioration in the local mechanical integrity of the whole bone. Physical activity and calcium intake are known to be able to modify bone mass and size. It is, however, not known whether these lifestyle habits can modify the postulated disproportionate changes in bone size. To address this question, bone mineral content (BMC)-derived estimates of cross-sectional areas (CSA) of femur and radius in 158 premenopausal (mean age 43, standard deviation 2 years) and 134 postmenopausal (63 (2) years), clinically healthy women with contrasting long-term histories in physical activity and calcium intake were determined from dual-energy X-ray absorptiometry (DXA) data. The DXA-obtained BMC correlated strongly with the actual CSA (r= 0.94) determined with peripheral quantative computed tomography. The ratios between functionally interrelated CSA data (i.e., (radial shaft CSA/distal radius CSA), (trochanter CSA/femoral neck CSA), (femoral shaft CSA/trochanter CSA) and (femoral shaft CSA/femoral neck CSA)) were considered primary outcome variables. Neither physical activity nor calcium intake separately or interactively were associated with any CSA ratio. Age showed no interaction with physical activity or calcium intake but was independently associated with all CSA ratios, except the ratio of femoral shaft CSA to trochanteric CSA. This study indicated clearly that a preferential reduction in the cross-sectional area occupied by bone mineral occurs disproportionately at the long bone ends as compared with diaphyseal sites, and this apparently inherent, age-associated relative loss seems not to be prevented by physical activity or calcium intake. In particular, given the utmost clinical relevance of the proximal femur region, an observed loss in femoral neck CSA of about 10% in contrast to about a 5% loss in trochanteric CSA warrants further investigation regarding its potential role as a predictor for hip fracture. Not only the local differences in bone composition but also the biomechanical aspects are important factors underlying these apparent changes in CSA at the studied skeletal sites. Received: 10 September 1998 / Accepted: 17 March 1999     

Comparison insight dual X-ray absorptiometry (DXA), histomorphometry,ash weight,and morphometric indices for bone evaluation in an animal model (the orchidectomized rat) of male osteoporosis

The mechanical properties of dentin are largely determined by the intertubular dentin matrix, which is a complex composite of type I collagen fibers and a carbonate-rich apatite mineral phase. We performed a small angle X-ray scattering (SAXS) study on fully mineralized human dentin to quantify this fiber/mineral composite architecture from the nanoscopic through continuum length scales. The SAXS results were consistent with nucleation and growth of the apatite phase within periodic gaps in the collagen fibers. These mineralized fibers were perpendicular to the dentinal tubules and parallel with the mineralization growth front. Within the plane of the mineralization front, the mineralized collagen fibers were isotropic near the pulp, but became mildly anisotropic in the mid-dentin. Analysis of the data also indicated that near the pulp the mineral crystallites were approximately needle-like, and progressed to a more plate-like shape near the dentino-enamel junction. The thickness of these crystallites, approximately 5 nm, did not vary significantly with position in the tooth. These results were considered within the context of dentinogenesis and maturation.     

The Contribution of Cortical and Cancellous Bone to Dual-Energy X-ray Absorptiometry Measurements in the Female Proximal Femur

Dual-energy X-ray absorptiometry (DXA) is the most common method for determining bone mineral density (BMD) in the proximal femur. However, there remain questions concerning the contribution of cortical and cancellous bone to this technology in the proximal femur. The purpose of this investigation was to identify structural and compositional characteristics of human bone in the proximal femur that significantly influence DXA BMD measurements. Twenty-four femora were obtained at autopsy from Caucasian females ranging in age from 17 to 92 years (mean ± SD, 61 ± 25 years). DXA scans were performed on each specimen with a Hologic QDR-2000 densitometer. Direct measurements were determined from proximal femoral sections for cancellous bone (volume fraction, ash fraction, cancellous cross-sectional area and percent cancellous cross-sectional area), cortical bone (thickness, ash fraction, porosity, cortical cross-sectional area and percent cortical cross-sectional area) and anteroposterior thickness. These parameters were compared with the associated DXA measurements by means of simple and multiple regressions. Cancellous volume fraction was the best predictor of variability of DXA measurements for both the neck and trochanter, with an R ² of 0.87 and 0.76, respectively (p<0.0001). There was only a minor influence of cortical factors such as thickness (neck and trochanter R ²= 0.51 and 0.42, respectively, p<0.001) and trochanteric cross-sectional area (R ²= 0.21, p<0.05). Although the accuracy for determining specific components of the proximal femur was low, the DXA BMD measurement was a strong predictor of cancellous bone factors, but not cortical bone factors that have been shown to change significantly with age. Received: 2 February 2000 / Accepted: 7 September 2000     

In Situ Femoral Dual-Energy X-ray Absorptiometry Related to Ash Weight, Bone Size and Density, and its Relationship with Mechanical Failure Loads of the Proximal Femur

The objective of this study was to directly compare in situ femoral dual-energy X-ray absorptiometry (DXA) and in vitro chemical analysis (ash weight and calcium) with mechanical failure loads of the proximal femur, and to determine the influence of bone size (volume) and density on mechanical failure and DXA-derived areal bone mineral density (BMD, in g/cm²). We performed femoral DXA in 52 fixed cadavers (age 82.1 ± 9.7 years; 30 male, 22 female) with intact skin and soft tissues. The femora were then excised, mechanically loaded to failure in a stance phase configuration, their volume measured with a water displacement method (proximal neck to lesser trochanter), and the ash weight and calcium content of this region determined by chemical analysis. The correlation coefficient between the bone mineral content (measured in situ with DXA) and the ash weight was r= 0.87 (standard error of the estimate = 16%), the ash weight allowing for a better prediction of femoral failure loads (r= 0.78; p<0.01) than DXA (r= 0.67; p<0.01). The femoral volume (r= 0.61; p<0.01), but not the volumetric bone density (r= 0.26), was significantly associated with the failure load. The femoral bone volume had a significant impact (r= 0.35; p< 0.01) on the areal BMD (DXA), and only 63% of the variability of bone volume could be predicted (based on the basis of body height, weight and femoral projectional bone area. The results suggest that accuracy errors of femoral DXA limit the prediction of mechanical failure loads, and that the influence of bone size on areal BMD cannot be fully corrected by accounting for body height, weight and projected femoral area. Received: 26 April 1999 / Accepted: 25 October 1999     

Body Composition by Dual-Energy X-ray Absorptiometry in Black Compared with White Women

Dual-energy X-ray absorptiometry (DXA) has recently been applied to the measurement of body composition using a three-compartment model consisting of fat, lean and bone mineral. The mass of skeletal muscle may be approximated by measurement of the lean tissue mass of the extremities. In addition, body fat distribution can be estimated by determining the ratio of fat in the trunk to the fat in the extremities. In the current study, DXA was used to compare body composition and fat distribution between black (n= 162) and white women (n= 203). Black women had a higher mineral mass and a higher skeletal muscle mass. The ratio of mineral to muscle mass was higher in black women, even when the data were adjusted for age, height and weight. Both total body bone mineral and muscle mass declined with age in both races, with evidence for an accelerated loss of bone mineral after menopause. Body size (height and weight) was generally a significant variable in developing regressions of each compartment against age. Their higher musculoskeletal mass may lead to misclassification of 12% of black women as obese if body mass index is used as an index of obesity. Body fat distribution (trunk/leg) did not differ between races in the raw data. However, for women of the same age, height and weight, white women have a significantly higher trunk/leg fat ratio. Body composition values for fat, lean and bone mineral obtained from DXA should be adjusted not only for gender but also for age, height, weight and ethnicity. Received: 23 September 1998 / Accepted: 4 January 1999     

The Effect of Weight Change on Total Body Dual-Energy X-ray Absorptiometry: Results from a Clinical Trial

In the past decade dual-energy X-ray absorptiometry (DXA) scanning has assumed an important role in the evaluation of new treatments for osteoporosis. Although the spine and hip are the sites usually chosen for monitoring bone mineral density (BMD) changes, total body DXA is also of interest because of the comprehensive view it gives of the whole skeleton. However, recent studies have reported anomalies in total body DXA in subjects undergoing weight change, suggesting that the technique may not be valid in this circumstance. The present study evaluated total body DXA in a trial of cyclical etidronate therapy in which many subjects underwent significant weight change. The study population was 152 postmenopausal women who had spine, hip and total body DXA scans performed at baseline, 1 and 2 years. The total body scans were analyzed using two software options referred to as “standard” and “enhanced”. The following variables were studied: total body BMD, total body bone mineral content (BMC), and subregional BMD values for the following seven sites: lumbar spine, thoracic spine, pelvis, head, ribs, arms and legs. The percentage change from baseline was analyzed in a multivariate regression analysis to derive the treatment effect (defined as the difference in changes between the etidronate and placebo groups) and a coefficient that described the effect of weight change on the total body DXA variable. Mean weight change after 2 years was +1.1 kg (range −9.3 to +16.8 kg). Results for the weight change coefficient were significantly different from zero for five of nine total body variables using the standard analysis and seven of nine for the enhanced analysis with values (and standard errors) that varied from +0.67 (0.04) %/kg for standard total body BMC to −0.32 (0.11) %/kg for enhanced arm BMD. Results for the treatment effect at 2 years were significantly different from zero for total body BMD, total body BMC and for the lumbar spine, thoracic spine and pelvis BMD subregions, but were not significant for head, rib, arm or leg BMD. Findings for the standard and enhanced analyses agreed closely and the size of the treatment effect was related to the proportion of trabecular bone at the measurement site. We conclude that in a randomized study the effects of weight change can be corrected and total body DXA can give useful information about the response to treatment across the whole skeleton. Received: 18 February 2000 / Accepted: 12 April 2000     

A Comparison of the Longitudinal Changes in Quantitative Ultrasound with Dual-Energy X-ray Absorptiometry: The Four-Year Effects of Hormone Replacement Therapy

Quantitative ultrasound (QUS) has been proposed as a tool which can measure both the quantitative and qualitative aspects of bone tissue and can predict the future risk of osteoporotic fractures. However, the usefulness of QUS in long-term monitoring has yet to be defined. We studied a group of early postmenopausal women over a 4-year period. Thirty subjects were allocated to hormone replacement therapy and 30 selected as controls matched for age, years past the menopause (YPM) and bone mineral density (BMD) at the anteroposterior spine (AP spine). The mean age of the subjects was 52.4 years (SD 3.9 years), mean YPM 4.0 years (SD 3.2) and all subjects had a BMD T-score above −2.5 SD (number of standard units related to the young normal mean population). BMD was measured at baseline and annually by dual-energy X-ray absorptiometry (DXA) at the AP spine and total hip, and QUS carried out at the calcaneus, measuring broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness. Mean percentage changes from baseline were assessed at 2 and 4 years. The overall treatment effect (defined as the difference in percentage change between the two groups) was: AP spine BMD, 11.4%; total hip BMD, 7.4%; BUA, 6.4%; SOS, 1.1%; and Stiffness, 10.4% (p<0.01). To compare the long-term precision of the two techniques we calculated the Standardized Precision, which for QUS was approximately 2–3 times that of DXA, for a given rate of change. The ability of each site to monitor response to treatment was assessed by calculating the Treatment Response Index (Treatment Effect/Standardized Precision), which was: AP spine BMD, 10.4; total hip BMD, 3.9; BUA, 3.1; SOS, 0.3; and Stiffness, 4.2. This was then normalized for AP spine BMD (to compare the role of QUS against the current standard, AP Spine BMD), which was: total hip BMD, 0.38; BUA, 0.30; Stiffness, 0.40 (p<0.01); and SOS, 0.03 (NS). In summary, QUS parameters in the early menopause showed a similar rate of decline as AP spine BMD and total hip BMD measured by DXA. Hormone replacement therapy results in bone gain at the AP spine and total hip, and prevents loss in BUA and SOS measured by QUS at the calcaneus. QUS has a potential role in long-term monitoring, although presently the time period to follow individual subjects remains 2–3 times that for DXA, for a given rate of change. Anteroposterior spine remains the current optimal DXA monitoring site due to its greater rate of change and better long-term precision. Received: 20 January 1999 / Accepted: 14 June 1999     

Normal Changes in Spinal Bone Mineral Density in a Chinese Population: Assessment by Quantitative Computed Tomography and Dual-Energy X-ray Absorptiometry

This study was designed to determine age- and gender-based normative values for spinal bone mineral density (BMD) in a Chinese population. In addition, we compared our data with those of other countries and populations. Four hundred and forty-three healthy Chinese subjects, aged 10–79 years (189 males, mean age 46.9 years; 254 females, mean age 45.7 years) were recruited for BMD assessment. BMD was measured by quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA), including postero-anterior DXA (PA-DXA), lateral DXA (L-DXA) and midlateral DXA (mL-DXA). For both genders, BMD values peaked in the 10–19 year age group when measured by QCT, and in the 30–39 year age group when measured by PA-DXA. BMD values decreased with age after reaching peak bone density in males and females for all measurements, except for PA-DXA in males. Male BMD values by DXA tended to increase beginning with the 60–69 age group through the 70–79 age group whether by PA-DXA, or L-DXA and mL-DXA. However, male QCT data showed stable BMD values among these two older groups. Comparative results showed female QCT data were higher in the 20–39 age group and lower after the 40–49 age group compared with American females. The peak BMD value by PA-DXA in Chinese females was reached in the same age group as American and European females and was similar in magnitude (p > 0.05). However, the peak BMD value for Chinese females was reached earlier and was significantly higher than that observed in Japanese females (p < 0.001). We conclude that the age group in which the peak BMD values are reached is different depending on the technique used, as is the calculated age-related rate of bone loss. It can be speculated that such differences reflect different timing for bone maturation in cancellous and cortical bone. Received: 21 February 1998 / Accepted: 28 May 1998     

Longitudinal Study of Bone Loss in Pre- and Perimenopausal Women: Evidence for Bone Loss in Perimenopausal Women

Bone loss before and around the time of menopause is not well characterized by longitudinal studies. We measured bone mineral density at various skeletal sites – total body, femoral neck, trochanter, anteroposterior (AP) and lateral spine, and forearm – with dual-energy X-ray absorptiometry in a large prospective cohort of 272 untreated pre- and perimenopausal women aged 31–59 years, at 1 year intervals for 3 years. Sex steroids and the following markers of bone remodeling were measured: serum osteocalcin (OC), procollagen I carboxyterminal extension peptide, bone alkaline phosphatase (BAP) and urinary crosslinks (CTX and NTX). Seventy-six women were classified as perimenopausal and 196 as premenopausal. Over the 3 years, premenopausal women had no significant bone loss at any site and a small but significant increase in bone mineral density at the trochanter, total hip, AP spine and radius. Perimenopausal women significantly lost bone from cancellous and cortical sites, i.e., the femoral neck, trochanter and lumbar spine. In perimenopausal women with increased follicle stimulating hormone, the rate of bone loss at the femoral neck correlated negatively with OC and BAP. In perimenopausal women, serum estradiol levels decreased during the 3 years of follow-up and bone loss from the trochanter and the AP spine was correlated with serum estradiol after 3 years. In conclusion, among premenopausal women there is no bone loss. In contrast, there is a rapid and diffuse bone loss in perimenopausal women, related to decreased estrogen secretion. Bone markers may be useful to identify these women losing bone. Received: 13 October 1997 / Accepted: 19 October 1998     

Total-Body Calcium Estimated by Delayed Gamma Neutron Activation Analysis and Dual-Energy X-ray Absorptiometry

Total body calcium (TBCa) in 270 black and white women age 21–79 years was measured concurrently by delayed gamma neutron activation analysis (DGNA) and dual-energy X-ray absorptiometry (DXA). The mean value for TBCa calculated from DXA was 933 g compared with 730 g for DGNA. By regression, TBCa_DXA(g)= 1.35 × TBCa_DGNA(g)−54 (r= 0.90, r ²= 81.4%, SEE = 66.9 g). This remarkable difference of 203 g suggests that one or both these methods is not accurate. Adjustment of the regression of DXA versus DGNA for body mass index or trunk thickness explained 8.5–10% of the variability between methods. The unadjusted slope for the DXA values regressed against the DGNA values was 1.35, indicating significant discordance between the methods. There is greater agreement between the two DGNA facilities (Brookhaven National Laboratory and Baylor College of Medicine) and between the various DXA instruments. Either DGNA underestimates TBCa or DXA overestimates total-body bone mineral content. Resolution of these disparate results may possibly be achieved by concurrent measurement of whole human cadavers of different sizes with chemical determination of the calcium content of the ash. In the interim, cross-calibration equations between DGNA and standardized values for DXA for total-body bone mineral content may be used, which will permit reporting of consistent values for TBCa from the two technologies. Received: 28 December 1998 / Accepted: 20 May 1999     

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     

Histomorphometric Evaluation of the Effects of Ovariectomy on Bone Turnover in Rat Caudal Vertebrae

The purpose of this study was to learn whether caudal vertebrae can be used to evaluate the effects of ovariectomy (OVX) in rats. Seven-month-old female Wistar rats were divided into two groups: the OVX group and the untreated control group. All rats were killed at 8 weeks and their 4th lumbar (L4), 1st caudal (C1), 3rd caudal (C3), and 5th caudal (C5) vertebrae were processed undecalcified and sectioned with Villanueva bone stain for quantitative bone histomorphometry. Both length of vertebral bodies and the cancellous tissue area in C1 were similar in size to L4 but significantly bigger than C3 and C5. Within the groups, cancellous bone volume (BV/TV) and trabecular thickness in both groups gradually increased in caudal vertebrae in relation to the distal direction. Between the groups, OVX rats exhibited a significantly lower BV/TV relative to control rats at L4 and C1, however, no significant difference were seen at C3 and C5. Bone formation-related parameters such as osteoid and mineralizing surface, and eroded surface were higher in the OVX group than in the control group in caudal as well as in lumbar vertebrae. By quantitative analysis of bone marrow composition, yellow marrow volume in C3 and C5 was significantly higher than that in L4 and C1, in both groups. Our results suggest that C1 is similar to L4 in size, bone turnover, and bone marrow composition. However, further experiments are needed to evaluate the possibility that C1 vertebra could be used as an alternative site for histomorphometric evaluation of bone changes in OVX rats. Received: 12 August 1997 / Accepted: 11 May 1998     

Reference Data and Predictive Diagnostic Models for Calcaneus Bone Mineral Density Measured with Single-Energy X-ray Absorptiometry in 7428 Chinese

Calcaneus bone mineral density (BMD) of 7428 Chinese (4126 women, 3302 men; aged 22–94 years) was measured using single-energy X-ray absorptiometry (SXA). A reference range of calcaneus BMD values for healthy Chinese men and women was established and the usefulness of this method for screening and diagnosis in osteoporosis was evaluated. The peak BMD occurred at 20–24 years old and peak BMD in women was significantly lower than in men. BMD loss in the calcaneus started at the age of 35 years for women, and at 63 years in men. BMD loss rate was 1.2%/year for women and 0.56 %/year for men after 50 years. The young normal reference for calcaneus BMD was 442.1±69.6 mg/cm² for men and 388.3±61.7 mg/cm² for women calculated from the mean BMD value of subjects whose age ranged from 20 to 49 years. The accumulated BMD loss in the calcaneus is similar to that of Ward’s triangle. Multiple linear regression showed that both age and weight were important factors. The incidence of osteoporosis in older men and women (≥60 years) is 6.6% and 32.1% respectively. We conclude that calcaneus BMD measurement is useful and sensitive for the screening and diagnosis of osteoporosis. A predictive diagnostic model for osteoporosis based on the calcaneus was constructed using multiple linear regression and the WHO criteria for diagnosing osteoporosis can be applied to calcaneus BMD. Received: 16 August 2000 / Accepted: 20 March 2001     

Quantitative Ultrasound of Bone in Male Osteoporosis

Quantitative ultrasound (QUS) measurement, a different approach to bone fragility assessment, has already been attempted in women with osteoporosis but rarely in men. In order to test its value and ability to identify osteoporotic men, a case–control prospective study was conducted using the Lunar Achilles, a device that measures attenuation and velocity parameters. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), a composite parameter, were assessed through the heel of 66 osteoporotic patients, and compared with the results in 35 controls. Patients had sustained a low-trauma fracture and/or had a lumbar and/or femoral bone mineral density (BMD) more than 2.5 SD below the young male reference value. As expected, all QUS parameters were statistically lower in patients, as were the dual-energy X-ray absorptiometry (DXA) measurements at the hip and lumbar spine. The two methods were compared for their ability to predict the risk of osteoporotic fractures. The odds ratios (ORs), with their 95% confidence limits, for fractures per 1 SD decrease were significant, especially for SOS and SI (OR = 2.3 [1.4–3.6] and 2.1 [1.3-3.3] respectively) and to a lesser extent for BUA (1.6 [1.0–2.4]). Our study suggests that QUS is associated with a history of low-trauma fracture in men; sensitivity is, however, less than when results are compared with BMD measurements (OR = 2.8 [1.6–5.0] and 3.4 [1.6–7.0] for lumbar spine and hip, respectively). Prospective studies are required before QUS can be recommended for clinical use in male osteoporosis. Received: 11 June 2001 / Accepted: 16 November 2001     

Pregnancy and Lactation Confer Reversible Bone Loss in Humans

The influence of pregnancy on bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) in 73 women (mean age 29 years, range 20–44 years) postpartum. Fifty-five age-matched women served as controls. The influence of lactation was evaluated in 65 of the delivered women who were followed with repeated measurements, a mean of 4.5 ± 0.1 and 11.5 ± 0.1 months after the delivery. The influence of multiple pregnancies was evaluated in 39 premenopausal women (mean age 38 years, range 31–54 years) with a minimum of four pregnancies (range 4–7). Fifty-eight age-matched healthy premenopausal women with a maximum of two pregnancies (range 0–2) served as controls. Data are presented as mean ± SEM. BMD data are adjusted for differences in total fat mass and total lean mass. Lumbar spine BMD was 7.6 ± 0.1% and total body BMD 3.9 ± 0.1% lower in women postpartum compared with controls (both p<0.001). BMD did not decrease significantly in non-breastfeeding mothers. Mothers breastfeeding for 1–6 months decreased femoral neck BMD by 2.0 ± 1.0% during the first 5 months postpartum (p<0.001). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 1.3 ± 0.8% lower than after delivery in mothers breastfeeding for 1–6 months (p= 0.05). Mothers breastfeeding for more than 6 months decreased Ward’s triangle BMD by 8.5 ± 1.0% and lumbar spine BMD by 4.1 ± 0.8% during the first 5 months postpartum (both p<0.05). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 4.0 ± 1.1% lower and Ward’s triangle BMD 5.3 ± 1.9% lower than after delivery in mothers breastfeeding for more than 6 months (both p<0.05). BMD loss was higher during the first 5 months following delivery in the lactating women compared with the non-lactating women (p< 0.05 comparing lumbar spine BMD loss in lactating mothers versus non-lactating mothers). However, in women with a minimum of four pregnancies the BMD was no lower than in age-matched women with fewer pregnancies. Total duration of lactation was not correlated with the present BMD. In summary, pregnancy seem to confer a low BMD with additional BMD loss during 5 months of lactation. Even if complete restoration in BMD was not reached within 5 months of weaning, women with four pregnancies or more had a BMD no lower than women with two pregnancies or fewer. We conclude that neither an extended lactation period nor multiple pregnancies could be used as a risk factor when predicting women at risk for future osteoporosis. Received: 15 November 2000 / Accepted: 21 March 2001     

Uneven Deficits in Vertebral Bone Density in Postmenopausal Patients with Primary Hyperparathyroidism as Evaluated by Posterior–Anterior and Lateral Dual-Energy Absorptiometry

This investigation was undertaken to determine whether the preservation of bone mass in patients with mild primary hyperparathyroidism (PHPT) could be detected when measuring spine density in the lateral projection. We compared the bone mineral density (BMD) of L2–L4 utilizing the posterior–anterior (PA) and lateral projections in postmenopausal patients with PHPT and in a group of 27 postmenopausal normal women. Thirty-three consecutive postmenopausal patients with PHPT were studied; 25 were asymptomatic whereas the remaining 8 suffered complications related to the disease. Based upon the criteria established by the Consensus Conference on the Management of Asymptomatic PHPT, only 10 of the 25 asymptomatic patients could be considered affected by mild disease; the remaining patients were classified as having moderate disease. Patients with mild disease had mean lateral total BMD values (0.682 ± 0.113 g/cm²) significantly higher than normal women (0.588 ± 0.076, p<0.02) and patients with moderate disease (0.599 ± 0.077, p<0.05). There were significant differences among the three groups in both PA L2–L4 and L1–L4 levels: patients with mild disease had significantly higher mean BMD values than patients with moderate disease and normal women, when either three or four vertebrae were considered. Interestingly, at this latter site, patients with moderate disease had significantly (p<0.05) lower values than normal women. Our results indicate that patients with mild PHPT have a preservation of vertebral mass when compared with the other hyperparathyroid patients and normal women, when taking into account both the mainly trabecular portion and the whole vertebra. The finding that when the PA projection was assessed, BMD values of patients with moderate disease were significantly lower than those of normal women, might be attributed to the detrimental effect of raised parathyroid hormone levels on the cortical component of the vertebral body. Received: 20 October 2001 / Accepted: 26 February 2002     

Bone Loss and Recovery in Regional Migratory Osteoporosis

Regional migratory osteoporosis (RMO) is a migrating arthralgia of the weight-bearing joints of the lower limb associated with focal osteoporosis. Little information is available on a quantitative assessment of systemic or local osteoporosis. In this study, we report three cases of RMO in which spine, hip and whole body serial assessments of bone mass have been evaluated to outline their extent and time course of changes. Systemic osteoporosis, with a prevalent involvement of the mainly trabecular skeletal sites, was present in all the patients, with T-scores below −2.5 at both the lumbar spine and femoral neck. Bone loss in acute episodes ranged from −75.5% to −14.7% and appeared related to the severity of the episode. In acute episodes the demineralizing process affected the whole limb from the hemipelvis to the foot: the bone loss ranged from −33.6% to −3.5% at sites with prevalent trabecular composition and from −19.1% to −1.1% at sites with prevalent cortical composition. Bone recovery was complete in one episode out of six. In the other five cases, the average residual bone loss was 26% (range 13.9–32.7%). Our observations suggest that RMO occurs in subjects with systemic osteoporosis and densitometric assessment may aid in the clinical management. Received: 12 February 2002 / Accepted: 17 June 2002 Correspondence and offprint requests to: Carlo Trevisan, MD, Clinica Ortopedica, Università degli Studi di Milano Bicocca, Azienda Osp.S.Gerardo, Via Donizetti, 106-20052 Monza (MI), Italy. Tel: +39 039 2332322. Fax +39 039 2302905. e-mail: trevisan@progetto3000.it