Axial and Total-Body Bone Densitometry Using a Narrow-Angle Fan-Beam

We assessed a new dual-energy bone densitometer, the PRODIGY, that uses a narrow-angle fan-beam (4.5°) oriented parallel to the longitudinal axis of the body (i.e., perpendicular to the usual orientation). High-resolution scans across the body can be stepped at 17 mm intervals. The energy-sensitive array detector uses cadmium zinc telluride, which allowed rapid photon counting. Spine and femur scans required 30 s, and total-body scans required 4–5 min; the dose was only 3.7 mrem and 0.04 mrem respectively, or about 5 to 10 times lower than conventional fan-beam densitometry. We found only a small influence of soft-tissue thickness on bone mineral density (BMD) results. There was also a small ( ± 1%) influence of height above the tabletop on BMD results. A software correction for object height allowed a first-order correction for the large magnification effects of position on bone mineral content (BMC) and area. Consequently, the results for BMC and area, as well as BMD, with PRODIGY corresponded closely to those obtained using the predecessor DPX densitometer, both in vitro and in vivo; there was a generally high correlation (r= 0.98–0.99) for BMD values. Spine and femur values for BMC, area and BMD averaged within 0.5% in vivo (n= 122), as did total-body BMC and BMD (n= 46). PRODIGY values for total-body lean tissue and fat also corresponded within 1% to DPX values. Regional and total-body BMD were measured with 0.5% precision in vitro and 1% precision in vivo. The new PRODIGY densitometer appears to combine the low dose and high accuracy of pencil-beam densitometry with the speed of fan-beam densitometers. Received: 2 April 1999 / Accepted: 27 July 1999     

Bone Mineral Content and Density in Professional Tennis Players

Total and regional bone mineral content (BMC) as well as lean and fat mass were measured in nine male professional tennis players (TPs) and 17 nonactive subjects; dual-energy X-ray absorptiometry (DXA) was used for measuring. The mean (±SD) age, body mass, and height were 26 ± 6 and 24 ± 3 years, 77 ± 10 and 74 ± 9 kg, and 180 ± 6 and 178 ± 6 cm for the TP and the control group (CG), respectively. The whole body composition for BMC, lean mass, and fat of the TP was similar to that observed in the CG. The tissue composition of the arms and legs was determined from the regional analysis of the whole-body DXA scan. The arm region included the hand, forearm, and arm, and was separated from the trunk by an inclined line crossing the scapulo-humeral joint. In the TP, the arm tissue mass (BMC + fat + lean mass) was about 20% greater in the dominant compared with the contralateral arm because of a greater lean (3772 ± 500 versus 3148 ± 380 g, P < 0.001) and BMC (229.0 ± 43.5 versus 188.2 ± 31.9 g, P < 0.001). In contrast, no significant differences were observed either in BMC or BMD between arms in the CG. Total mass, lean mass, and BMC were greater in the dominant arm of the TP than in the CG (all P < 0.05). In the TP, BMD was similar in both legs whereas in the CG, BMD was greater in the right leg. Lumbar spine (L2–L4) BMD, adjusted for body mass and height, was 15% greater in the TP than in the CG (P < 0.05). Femoral neck BMDs (femoral neck, Ward's triangle, greater trochanter, and intertrochanteric regions) adjusted for body mass and height were 10–15% greater in the TP (all P < 0.05). Ward's triangle BMD was correlated with the maximal leg extension isometric strength (r = 0.77, P < 0.05) even when adjusted for body mass (r = 0.76, P < 0.05) and height (r = 0.77, P < 0.05). In summary, the participation in tennis is associated with increased BMD in the lumbar spine and femoral neck. These results may have implications for devising exercise strategies in young and middle-aged persons to prevent involutional osteoporosis later in life. Received: 29 April 1997 / Accepted: 14 November 1997     

Prediction of Bone Loss Rate in Healthy Postmenopausal Women

Prevention of fractures is the only way to drastically reduce osteoporosis-related health expenditures. In order to optimize the cost/benefit ratio of a strategy of prevention, it is essential to identify, as early as possible, women who will develop fractures later in their life. Therefore, and since postmenopausal bone loss is an asymptomatic process, screening procedures should detect, at the time of the menopause, women whose postmenopausal bone loss is higher than the mean, and will, a couple of years later, exhibit a low mineral content and a subsequent high risk for fractures. For 3 years we have followed a cohort of 92 healthy women who had undergone menopause less than 36 months previously. By a multivariate discriminant analysis based on the differences in lumbar bone density, assessed by dual photon absorptiometry, and in a few routine biochemical parameters (serum phosphorus, estrone, androstenedione, and urine calcium) observed during the first 6 months of the study, we have been able to correctly predict the rate of spinal bone loss, observed at the end of the 3 years, in 76% of the subjects. All of the women who presented a bone loss higher than 10% over the 3 years were correctly isolated by our discriminant functions after 6 months of follow-up. We conclude that a measurement of lumbar bone mineral density coupled with a few routine biochemical determinations, repeated twice at a 6-month interval in healthy postmenopausal women, can isolate 100% of postmenopausal ``fast bone losers' with an overall specificity of 76%. Received: 22 December 1995 / Accepted: 23 September 1996     

Bone Mineral Density of Opposing Hips Using Dual Energy X-Ray Absorptiometry in Single-Beam and Fan-Beam Design

Bone densitometry focuses on bone mineral area density (BMD in g/cm²) of the proximal femur and spine in anterior-posterior (AP) projections. Artifacts, such as osteoarthritis and osteophytic calcifications (OC) influence spine BMD, especially in AP scans. If only two sites are measured, as is usual in clinical practice, there may be advantages to measuring both femora rather than one femur and the spine. This would not be useful, however, if there was strong symmetry between the two sides. Furthermore, fan beam (FB) techniques have become available for measuring BMD with less data acquisition time. We compared densitometry of opposing femora in 421 patients (369 women, mean age 59.0 ± 4.8; 52 men, mean age 56.9 ± 7.4) using dual-energy X-ray absorptiometry (DXA): both single-beam (SB) and FB modes were evaluated. The precision errors in vivo (short- and midterm) of total BMD were 0.7% for both SB and FB. The total BMD and BMC of the left hip (0.817 ± 0.124 g/cm², 31.3 ± 6.4 g) were significantly (P < 0.001) higher (2–3%) than the corresponding values of the right hip (0.801 ± 0.125 g/cm², 30.3 ± 6.3 g) in both SB and FB (left BMD 0.802 ± 0.117 g/cm², BMC 30.0 ± 6.2 g versus right BMD 0.795 ± 0.117 g/cm², BMC 29.3 ± 6.3 g) modes. However, BMD of the femoral neck and Ward's triangle were not significantly (P > 0.05) different between the two sides. The FB results were generally 2% lower than SB results. There were highly significant (P < 0.001) correlations (r > 0.9) between both hips using both SB and FB. For diagnostic procedures and longitudinal studies, one should consider that there are bilateral differences of femur BMD, as well as differences between FB and SB scan modes.     

Measurement of Bone Density Around Total Knee Arthroplasty Using Fan-Beam Dual Energy X-ray Absorptiometry

The clinical survival of joint arthroplasties is clearly associated with the quality of surrounding bone environment. Bone mineral density (BMD) is an important measure of bone strength and quality. Periprosthetic BMD can be measured by using dual-energy X-ray absorptiometry (DXA) with special software algorithms. We studied short-term reproducibility of the periprosthetic BMD measurements after total knee arthroplasty (TKA) in 30 patients with primary osteoarthrosis. The operated knees and the contralateral control knees were measured twice and the results were expressed as a coefficient of variation (CV%). The average precision error was 3.1% in femoral regions of interest (ROI) and 2.9% in tibial ROIs after TKA. In the prosthesis-free control knees, CV% were similar; 3.2% and 2.5%, respectively. The best precision was found in the femoral diaphyses above the implant (1.3%), whereas the least reproducible BMD was determined in the patellar region of the TKA knees (6.9%). Our results confirm that DXA measures precisely small bone mineral changes around TKA and makes it possible to follow bone remodeling DXA and may provide a feasible method for monitoring TKA in the future. Received: 16 September 1998 / Accepted: 29 February 2000     

Accuracy and Precision of 62 Bone Densitometers Using a European Spine Phantom

Dual-energy absorptiometry (DXA) is widely used for bone mineral density measurements. Different types of devices are available. Differences between devices from either the same manufacturer or different manufacturers can lead to difficulties in clinical practice when patients are followed on different machines. We calculated the accuracy and precision of 62 DXA devices from two manufacturers (51 Hologic, 11 Lunar) using a European Spine Phantom (ESP, semi-anthropomorphic). The ESP was measured 5 times on each device without repositioning. Accuracy was assessed by comparing bone mineral density (BMD, g/cm²) values measured on each device with the actual value of the phantom. Precision was assessed by the coefficient of variation (CVsd), using the root mean square average. The limits of agreement were estimated from the differences between each replicate measurement of BMD and the estimated true value for a particular manufacturer, according to Bland and Altman. The results confirm the difference between devices from different manufacturers (18.5%). Mean CVsd values were 0.57% and 0.64% for Hologic and Lunar respectively. The limits of agreement among devices from the same manufacturer were 0.026 g/cm² and 0.025 g/cm² for Hologic and Lunar respectively. Differences in extreme results between devices from the same manufacturer were on average 5.4% and 3.6% for Hologic and Lunar respectively. Results of different devices from the same manufacturer are highly comparable, although unpredictable differences exist that may be clinically relevant. Received: 12 June 1998 / Accepted: 20 November 1998     

Evaluation of Bone Mineral Density Using Three-Dimensional Solid State Phosphorus-31 NMR Projection Imaging

A solid state magnetic resonance imaging technique is used to measure true three-dimensional mineral density of synthetic hydroxyapatite phantoms and specimens of bone ex vivo. The phosphorus-31 free induction decay at 2.0 T magnetic field strength is sampled following application of a short, hard radiofrequency excitation pulse in the presence of a fixed amplitude magnetic field gradient. Multiple gradient directions covering the unit sphere are used in an efficient spherical polar to Cartesian interpolation and Fourier transform projection reconstruction scheme to image the three-dimensional distribution of phosphorus within the specimen. Using 3–6 Gauss/cm magnetic field gradients, a spatial resolution of 0.2 cm over a field of view of 10 cm is achieved in an imaging time of 20–35 minutes. Comparison of solid state magnetic resonance imaging with dual energy X-ray absorptiometry (DXA), gravimetric analysis, and chemical analysis of calcium and phosphorus demonstrates good quantitative accuracy. Direct measurement of bone mineral by solid state magnetic resonance opens up the possibility of imaging variations in mineral composition as well as density. Advantages of the solid state magnetic resonance technique include avoidance of ionizing radiation; direct measurement of a constituent of the mineral without reliance on assumptions about, or models of, tissue composition; the absence of shielding, beam hardening, or multiple scattering artifacts; and its three-dimensional character. Disadvantages include longer measurement times and lower spatial resolution than DXA and computed tomography, and the inability to scan large areas of the body in a single measurement, although spatial resolution is sufficient to resolve cortical from trabecular bone for the purpose of measuring bone mineral density. Received: 13 March 1997 / Accepted: 4 November 1997     

Bone Density and Body Composition in Japanese Women

Total body bone mineral content (BMC_TB in g) and density (BMD_TB in g/cm²) and body composition were measured in 1006 healthy Japanese women aged 20–79 years using dual X-ray absorptiometry. Peak BMD_TB was 1.11 ± 0.05 g/cm² in women 20–49 years, and mean BMD_TB was 1.019 g/cm² in the 6th decade, 0.956 g/cm² in the 7th decade, and 0.900 g/cm² in the 8th decade. BMD_TB declined by 0.007 g/cm²/year in women after age 50. This age-related decline in BMD showed a similar pattern to that seen for the lumbar spine and femoral neck, but the actual rate of loss was lower for BMD_TB than for these other measurement sites. There was no significant difference between a eumenorrheic premenopausal group and a group with irregular menses. BMC_TB and BMD_TB were associated with body build, lean tissue mass, and fat mass (r = 0.29 ∼ 0.65 and 0.26 ∼ 0.41, respectively). Bone mass and density decreased significantly in older women of all body builds. Premenopausal Japanese women had a 5% lower BMD_TB than U.S. and European whites, but the difference was several times greater in postmenopausal than in premenopausal women. Received: 1 June 1995 / Accepted: 3 March 1997     

Discordance Between Ultrasound of the Calcaneus and Bone Mineral Density in Black and White Women

Black women have 40% of the incidence rate for hip fracture and have a higher bone mineral density (BMD) than white women. The possibility was raised that bone quality may be disproportionately greater than the advantage in bone density in protection against osteoporotic fractures in black versus white women. Ultrasound (US) of the calcaneus is believed to measure properties of bone in addition to its density. We performed bone density measurements and US of the calcaneus in 108 black and 177 healthy white women, aged 20–70 years. The highest correlation was seen between total body bone density and speed of sound (r = 0.75). The interracial differences in BMD were all statistically significant and varied from 3.4 to 7.6%. The US measurements had lesser interracial differences than the bone density measurements, with velocity barely different between races. These findings suggest that US of the calcaneus measures properties of bone different from density. Fracture prediction data using US from prospective data in white women should not be extrapolated to black women because of the discordance between bone density and US measurements. Prospective studies are needed comparing US measurements in black women to the occurrence of osteoporotic fractures. Received: 30 May 1997 / Accepted: 8 January 1998     

Absence of Correlation Between BMP-4 Polymorphism and Postmenopausal Osteoporosis in Italian Women

Several studies have demonstrated that bone has the power of regeneration and repair. BMPs (bone morphogenetic proteins) are involved in the determination of osteoblast phenotype and bone turnover, therefore genes coding for these proteins, like BMP-4, could be considered potential candidate genes for osteoporosis. We investigated the association of BMP-4 gene polymorphism with osteoporosis in a cohort of 72 osteoporotic, postmenopausal women and 82 unrelated controls. We failed to detect any significant association between this genetic marker and the disease. Received: 9 August 1999 / Accepted: 3 February 2000     

Relationship Between Spine Bone Mineral Density and Vertebral Body Heights

The aim of this study was to investigate the correlation between lumbar spine bone mineral density (LS-BMD) and the vertebral body heights with advancing age and years since menopause. One hundred and sixty-three women ages 39–74 years (77 normal premenopausal, ages 39–54, and 86 normal postmenopausal, ages 46–74 years) were studied. LS-BMD was measured by dual energy X-ray absorptiometry. Vertebral heights were evaluated, using morphometry, as the sum of anterior (AHs), middle (MHs), and posterior (PHs) vertebral body heights from T₄ to L₅. The AHs/PHs ratio at the same level was also calculated. AHs, MHs, PHs, and AHs/PHs ratio directly correlated with LS-BMD; the correlations are AHs r = 0.80, P < 0.0001, MHs r = 0.75, P < 0.0001, PHs r = 0.76, P < 0.0001, and AHs/PHs r = 0.66, P < 0.001. Both LS-BMD and AHs are inversely correlated with age, and the regressions fit with both linear and cubic curves. The statistical significance of the correlations persists while maintaining age constant. The linear regression curve of AHs with age indicates that the spine height decrement rate is 2.12 mm/year, corresponding to 7.4 cm in 35 years. AHs decreases immediately after menopause fitting with a cubic curve model, with a decrement rate of about 3 cm in the first 5 years after menopause. We conclude that the measurement of the sum of vertebral body heights could usefully integrate LS-BMD evaluation in the clinical and epidemiological investigation of osteoporosis. Received: 30 May 1997 / Accepted: 14 November 1997     

Volumetric bone density of the lumbar spine is related to fat mass but not lean mass in normal postmenopausal women

We have previously found that fat mass but not lean body mass is related to bone mineral density (BMD) in women. In these and most other studies of the dependence of BMD on body composition, areal rather than volumetric bone density was measured. It is possible that the dependence of this variable on body size introduced a scale artifact that contributed to the previous findings. The present study addresses this issue by measuring thevolumetric density of the third lumbar vertebra from simultaneous anteroposterior (AP) and lateral scans using dual-energy X-ray absorptiometry in 119 normal postmenopausal women. Whole body fat and lean body mass were also measured using this technique. In the AP projection, BMD was similarly related to body weight and to fat mass (r=0.44,p<0.0001 for both) but not to lean body mass (r=0.17, NS). BMD in the lateral projection was less closely related to body composition than was AP BMD, but the greater impact of fat (r=0.25,p<0.01) than lean body mass (r=0.09, NS) was still evident. When AP or lateral BMDs were divided by height, arm span or the square root of the scan area to produce an index with the dimensions of volumetric density, the dependence of BMD on body weight and fat mass were not affected but the relationship to lean body mass was eliminated (–0.02<r<0.09). Similarly, the volumetric density of the third lumbar vertebra was related to fat mass (r=0.21,p=0.02) but not to lean body mass (r=0.01). It is concluded that BMD is related to fat mass and that previously reported associations between lean body mass and BMD are probably contributed to by a scaling factor arising from failure to measure volumetric bone density.     

Body Size Accounts for Most Differences in Bone Density Between Asian and Caucasian Women

We compared bone mineral density (BMD) of the whole body (and subregions: arm, leg, and pelvis), hip, spine, lateral spine, wrist, and forearm among Caucasian and Asian women at four geographic centers (Honolulu, HI; Nottingham, UK; Portland, OR; Copenhagen, Denmark). Data were derived from the baseline examination of 1367 Caucasian and 162 Asian women enrolled in the 1609-subject Early Postmenopausal Interventional Cohort (EPIC) study. After adjusting for age, study site, years postmenopause, and years of estrogen use, BMD was approximately 4–6% lower (P < 0.05) among Asian women at most skeletal sites, but there was no significant difference for wrist or forearm BMD. Adding height, lean body mass, fat mass, and/or quadriceps muscle strength to the regression models reduced the racial differences at most skeletal sites; after these additional adjustments, Asian women had significantly lower BMD only for the lateral spine (−4.4%; P < 0.005), arm (−2.20%; P < 0.05) and leg (−1.65%; P < 0.05), whereas the wrist was significantly greater (4.64%; P < 0.005) for Asian women. Further research is needed to determine why racial differences in BMD persist at certain skeletal sites, but not others, after adjusting for body size. Received: 22 January 1996 / Accepted: 3 May 1996     

Differences in Bone Turnover and Skeletal Response to Thyroid Hormone Treatment Between Estrogen-Depleted and Repleted Rats

This study was undertaken to compare the effect of supraphysiological doses of thyroxine (T4) on bone metabolism in SHAM and OVX young adult rats. Female Sprague Dawley rats (220 ± 2 g, approx. 5 months of age) were divided into four groups of eight animals each. The animals were intraperitoneally injected 6 days per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl (SHAM+Vh and OVX+Vh) or 250 μg of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4 and osteocalcin (BGP), urinary pyridinolines (Pyr), and creatinine (creat) were determined. At the beginning and at end of the experiment, skeletal bone mineral content (BMC), bone mineral density (BMD), and area (A) of the total skeleton, femur, spine, and whole tibia, as well as proximal, middle, and distal areas of the tibia were assessed by dual X-ray absorptiometry (DXA) in an ultra-high-resolution mode. T4 treatment of the SHAM rats did not induce significant changes in BGP level or Pyr/creat excretion compared with the SHAM+Vh control group. However, these two biochemical bone markers significantly increased due to T4 treatment in OVX rats compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and P < 0.001, respectively). The OVX+T4 group had a significantly lower ΔBMD than SHAM+T4 rats in all studied regions (P < 0.05) except for the middle tibia region. OVX+T4 groups presented a significantly lower ΔBMC and ΔA compared with SHAM+T4 animals (P < 0.001). OVX+T4 rats significantly impaired the ΔBMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle (P < 0.05) tibia whereas T4 treatment of SHAM rats only affected, significantly, the whole (P < 0.05) and the proximal tibia region (P < 0.01). T4 treatment affects bone growth in young adult rats. The effect is significantly greater in the estrogen-depleted than in the estrogen-repleted state. The bone site most adversely affected by T4 treatment depends on the estrogen status. The proximal tibia (principally trabecular bone) was the most affected area in estrogen-repleted rats. Conversely, in OVX rats, the middle tibia (principally cortical bone) presented the greatest decrease in bone density. Received: 20 May 1999 / Accepted: 4 February 2000     

Bone Mineral Density Differences at the Femoral Neck and Ward's Triangle: A Comparison Study on the Reference Data Between Chinese and Caucasian Women

The incidence of hip fracture is lower in Chinese women compared with those from western countries, though they usually have lower bone mineral density (BMD). In this study, reference data (from Caucasian women) supplied by the manufacturer of Hologic Inc. was compared with data obtained from healthy women in Changsha, Hunan province, P.R.C. A total of 1488 Chinese women aged 15–95 years were randomly chosen for the study. Measurements of BMD were taken at the hip by dual energy X-ray absorptiometry (DXA) (QDR 4500A, Hologic Inc., USA). The BMD and the BMD decrease rate were somewhat lower than reference curves at all age groups and all sites except for the femoral neck and Ward's triangle. Chinese women reached their peak BMD 5–10 years later than their counterparts, and had a lower BMD decrease rate for about 35 years after peak BMD was attained. The fact that Chinese women take longer time to reach peak BMD and have a lower BMD decrease rate at the neck and Ward's triangle after peak BMD is attained protects them against hip fractures, and is a phenomenon that needs to be studied in the future. Received: 11 May 1999 / Accepted: 29 February 2000     

Water Bath and Contact Methods in Ultrasonic Evaluation of Bone

A recombinant human parathyroid hormone, rhPTH-(1-84), which is currently in Phase II clinical trial, and hPTH-(1-31)NH₂ (Ostabolin) are promising anabolic agents for treating osteoporosis because they can stimulate cortical and trabecular bone growth in osteopenic, ovariectomized (OVX) rats and in osteoporotic, postmenopausal women when injected subcutaneously and intermittently at low doses. We have now found that, despite their different sizes and signaling properties (rhPTH-(1-84) stimulates adenylyl cyclase and phospholipase C; hPTH-(1-31)NH₂ only stimulates adenylyl cyclase), they are equally osteogenic in OVX rats. Thus daily subcutaneous injections of 0.6 nmol/100 g of body weight of rhPTH-(1-84) or hPTH-(1-31)NH₂ into 3-month-old OVX rats for 6 weeks starting 2 weeks after OVX equally reduced the otherwise large OVX-triggered loss of femoral trabecular bone. Daily subcutaneous injections of 0.4 or 0.8 nmol/100 g of body weight of the two agents for 6 weeks also equally increased the mean thickness of the remaining femoral trabeculae in 3-month-old and 1-year-old OVX rats to 20 to 80% above the value in normal animals when started 9 weeks after ovariectomy. Received: 22 December 1995 / Accepted: 20 March 1996     

Comments on the Hypotheses Underlying Fracture Risk Assessment in Osteoporosis as Proposed by the World Health Organization

It was shown in a recent multivariate analysis of lumbar vertebral (L1–L3) CT scans of 171 women without fractures and 57 fractures somewhere in their skeletons, that regional assessment of the spinal mineral distribution can result in the discrimination of the above patient groups with an accuracy of about 90%. This level of discrimination was possible even in those cases with bone densities below the fracture threshold, where the overlap of patients with and without fractures is the greatest and clinically the most significant. In this region this new analytical technique could also identify a subgroup of patients who not yet had a fracture, but for whom all three lumbar vertebrae were classified as osteoporotic. From these results it follows that the osteoporosis model proposed by the World Health Organization (WHO), which assumes that fragility depends only on a single mean value of bone mineral density (BMD) for a patient, is overly simplistic and requires upgrading to include indices representing the distribution of bone mineral. Received: 25 November 1997 / Accepted: 24 June 1998     

Geographic Differences in Bone Turnover: Data from a Multinational Study in Healthy Postmenopausal Women

Biochemical markers of bone metabolism (bone markers) are used increasingly to monitor response to therapy and may be predictors of bone loss and fractures. The relationship between fracture rates, which differ between countries, and the rate of bone turnover has not been examined. Therefore, we explored the geographic variability of bone turnover in a selected, healthy study population of 619 postmenopausal women, ages 40–61, participating in a clinical trial of raloxifene hydrochloride for osteoporosis prevention. The subjects were distributed among 38 investigative sites in 10 countries (9–211 subjects/country) on four continents (North America, n = 277, Europe, n = 168, Australia, n = 125, and Africa, n = 49). Specimens for serum osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and urine type I collagen fragment/urinary creatinine ratio (CTX) were handled in a uniform fashion and assayed in a central laboratory. Mean levels of OC (P < 0.001), BSAP (P= 0.006), and CTX (P < 0.001) varied significantly by country (ANOVA), with the lowest values typically in German and Spanish subjects and the highest in American and Canadian subjects. The consistent pattern and wide ranges of mean bone marker values (OC 1.6-fold, BSAP 1.7-fold, CTX 3.1-fold) between countries suggest clinically significant differences in bone turnover. Geographic differences in bone markers were not explained by the determined potential confounders of age, years posthysterectomy, total serum cholesterol, and serum follicle stimulating hormone (FSH). We conclude that bone marker values vary substantially by country in this selected study population, suggesting systematic geographic differences in bone metabolism that potentially relate to osteoporotic fracture rates. Received: 28 November 1997 / Accepted: 23 March 1998     

Impact of Spinal Degenerative Changes on the Evaluation of Bone Mineral Density with Dual Energy X-Ray Absorptiometry (DXA)

The purpose of this study is to evaluate degenerative factors in a postmenopausal patient group and differentiate the influence on bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA). The patients and methods included an investigation of 144 postmenopausal women (mean 63.3 years) with PA-DXA of the spine. Degenerative factors (osteophytes, osteochondrosis, scoliosis, and vascular calcification) were evaluated from plain lumbar radiographs, their estimated probability was analyzed as a function of age, and their influence on BMD measured by PA-DXA was determined. The results of the study revealed osteophytes in 45.8%, vascular calcifications in 24.3%, scoliosis in 22.2%, osteochondrosis in 21.5%. The estimated probability for degenerative factors increased from 35 to 80% in the 55- to 70- year age group. Osteophytes and osteochondrosis were associated with up to a 14% increase in BMD values (P < 0.001). Vascular calcifications showed a positive trend, whereas scoliosis did not show a discernible influence. We concluded that degenerative factors, except for scoliosis, showed an influence on BMD as measured by DXA. Their prevalence increased rapidly between 55 and 70 years of age. Interpretation of PA-DXA spine data for subjects of or above this age range should be complemented by plain film radiographs. Received: 30 May 1996 / Accepted: 24 July 1996     

Differing Lumbar Vertebral Mineralization Rates in Ambulatory Pediatric Patients with Osteogenesis Imperfecta

The purpose of this study was to evaluate serial changes in bone mineral density (BMD) of the lumbar spine in individual children and adolescents with untreated osteogenesis imperfecta (OI) using dual X-ray absorptiometry (DXA). Twenty-seven pediatric patients with OI who had no historical or radiographic evidence of lumbar fracture, required no assistive device for mobility, and were taking no medications known to affect skeletal mineralization during the study period comprised the investigational group. Absolute BMD and age- and gender-matched BMD (Z-scores) were assessed relative to standard parameters of growth (height, weight, age, height adjusted for age and gender and body surface area) and severity of disease (lifetime fracture rate). The spinal mineralization rate (SMR) between examinations for 15 patients with more than one measurement (n= 20 intervals) was expressed as the magnitude of the change in BMD Z-score per year. Both BMD and BMD Z-score were closely correlated with height, height Z-score, weight and body surface area and were inversely related to fracture rate (P < 0.001 for all comparisons). BMD was also highly correlated with patient age (P < 0.001). Stepwise regression analysis showed that together height Z-score and lifetime fracture rate improved the prediction of BMD Z-score (r= 0.71; P < 0.001). SMRs ranged from −0.5 to 3.5. The average change in SMR between sequential measurements was 168% for the five children who had more than two DXA examinations. Linear regression showed a significant negative correlation between SMR and height Z-score (r=−0.79, P < 0.001). We conclude that vertebral body size is a critical determinant of BMD and BMD Z-score in OI because DXA results are expressed per unit area, not per unit volume. Pediatric patients with OI mineralize their lumbar vertebrae at rates similar to healthy children but tend to lag behind in overall mineralization. The rate of mineralization at any age appears to be related to the patient's height (adjusted for age- and gender-matched controls) and inversely related to the patient's lifetime rate of fractures. Our data suggest that vertebral mineralization in children with OI is related primarily to rapid increases in vertebral volume and only secondarily to increases in vertebral mineral density. Received: 2 March 1997 / Accepted: 5 June 1997