Does High-Resolution Computed Tomography Image Analysis of Distal Radius Provide Information Independent of Bone Mass?

This study aimed to investigate the usefulness of computed tomography (CT) image analysis of the distal radius for comparing two groups of postmenopausal women matched for age and bone mineral density at both the lumbar spine and femoral neck. The first one consisted of 16 women with at least one vertebral fracture and the second consisted also of 16 women without disease affecting bone mass or bone metabolism. Eight slices were selected in each patient: four consecutive coronal slices and four consecutive axial slices. Bone texture analysis was performed using structural methods leading to the measurement of 24 features. Most of the structural variables derived from histomorphometric parameters and were measured after segmentation from a binary or a skeletonized image. Nine variables were significantly different between the two groups on axial slices: valley number, valley surface area, apparent bone volume/tissue volume (BV/TV), apparent trabecular separation, apparent trabecular number, trabecular bone pattern factor, trabecular skeletal length, node count, and node-to-node strut count. Also four variables were significantly different between osteoporotic women and controls on coronal slices: apparent BV/TV, trabecular partition, node-to-node strut count, and terminus-to-terminus strut count. In conclusion this study suggests that bone texture analysis could yield additional data on bone mass for explaining bone strength and therefore could be used for improving the prediction of fracture risk.     

Computed Tomography Image Analysis of the Calcaneus in Male Osteoporosis

The present study aimed to characterize bone microarchitecture assessed by computed tomography (CT) at the calcaneus in male subjects suffering from osteoporosis. Seventy-nine subjects were assessed (45 with osteoporosis and 34 control subjects matched for age). Osteoporosis was defined according to the World Health Organization classification either at the lumbar spine or at the femoral neck. Thirty-three subjects (73%) had a past history of low-energy fracture mainly represented by vertebral fractures (24/33). Nine axial sections (1 mm in width and 2 mm apart) were selected for each subject. Bone microarchitecture analysis was performed using structural (binary and skeletonized images but also skeletonization from gray levels) and fractal analyses. Bone densitometry by dual-energy X-ray absorptiometry (DXA) at the calcaneus was also performed in 73 cases. Bone mineral density (BMD) was decreased in osteoporotic patients compared with controls both at the lumbar spine and hip and also at the calcaneus (p<0.01). Also 14 microarchitectural features among 25 measured were significantly different between the two groups (p<0.01). The odds ratio for fracture per 1 control group standard deviation decrease were also significant for 13 structural features but also for BMD at the calcaneus. The odds ratios after adjustment for BMD at the calcaneus were significant for the following features (p<0.05): number of valleys, 2.8 (1.2–6.9); trabecular partition, 3.3 (1.3–7.9); apparent trabecular spacing, 1.8 (1.0–3.1); trabecular bone pattern factor, 2.2 (1.1–4.3); Euler number, 3.0 (1.1–8.7); node-to-terminus strut count, 3.3 (1.4–7.8); terminus-to-terminus strut count, 2.9 (1.2–6.9); and fractal dimension, 3.7 (1.5–9.7). Few and weak correlations were found between BMD at the calcaneus measured with DXA and features obtained from CT, suggesting that these two methods give different information about bone status. In conclusion, male osteoporosis is a disease characterized by decreased bone mass but also by microarchitectural deterioration of bone tissue which is partly independent of BMD. Received: 24 April 2001 / Accepted: 6 July 2001     

The Effect of Androstenedione/Estrone Supplementation on Cortical and Cancellous Bone in the Young Intact Female Monkey: A Model for the Effects of Polycystic Ovarian Disease on the Skeleton?

The goal of this study was to determine the effects of chronically elevated blood androstenedione and estrone levels on the quality and quantity of both cancellous (trabecular) and cortical bone in a young (mean age 9.4 years) female primate model (M. fascicularis). Thirteen intact female monkeys received continuous androstenedione/estrone supplementation via subcutaneous implants over a 24-month period to simulate the human condition known as polycystic ovarian disease (PCOD). A group of 16 untreated intact age-matched female monkeys served as controls. Lumbar spine and whole body bone mineral density (BMD) status was determined mid-study by dual photon absorptiometry (DPA); subsequent analysis of the bone related to data obtained following the 2-year treatment period without further BMD measurement. Bone markers, including serum acid phosphatase, total bone alkaline phosphatase, bone gla protein and tartrate-resistant acid phosphatase were measured at the end of the study. At necropsy, the lumbar vertebrae and femora were recovered in order to analyze the bone mineral quality and quantity of cancellous and cortical bone respectively and to compare these with the control group. Mineralization profiles of the vertebrae and femora were obtained using the density fractionation technique. Chemical analysis of the three largest fractions retrieved by density fractionation was performed to evaluate differences in %Ca, %P, Ca/P ratio and mineral content (%Ca+%PO₄) between control and experimental groups. In addition, unfractionated bone powder was examined by X-ray diffraction to identify any changes in crystal size. Coronal sections of vertebrae were analyzed for structural parameters using histomorphometry and image analysis. Cross-sections taken at the midshaft diaphyseal femora were analyzed for structural macroscopic and intracortical parameters. There was a significant increase in BMD at the L2–L4 region in the treatment group compared with the control groups (p<0.005) as measured at 1 year into the trial. Serum acid phosphatase was significantly lower (p<0.05) in the treatment group compared with the controls near study termination. A nonsignificant shift in the mineralization profile of the vertebrae towards less dense bone was observed in the treatment group, while there was a significant shift in the mineralization profile towards more dense bone in the treated femora compared with controls (p<0.05) after a 2-year period. There was no difference between treatment and control groups in terms of size/strain of the cortical or cancellous bone crystal as detected by X-ray diffraction. There was a significant increase in cancellous bone area (B.Ar.) (p<0.02) and a significant increase (p<0.05) in mean trabecular width with a corresponding decrease in trabecular separation (p<0.03) in the experimental group compared with the controls. There were no significant changes in osteoid parameters (perimeter, area or width) or eroded perimeter measurements in the experimental group compared with the controls. In the experimental group, trabecular strut analysis showed a significant increase in the number of nodes (p<0.02) and in the total strut length (p<0.003) compared with the controls. There was also a significant increase in the node to node (p<0.04) and node to terminus (p<0.004) strut length in the treatment group compared with the controls. A significant increase in B.Ar. without concurrent indices of ongoing remodeling differing from controls suggests that cancellous bone of the vertebral body in the treated young female primate had been receptive to the anabolic stimulus of androstenedione/estrone supplementation over the 2-year period. In contrast, macroscopic parameters of cortical bone such as perimeter, area and width were preserved over the 2-year course, while intracortical remodeling was evident with increased percent porosity (p<0.001), osteonal bone (p<0.01) and osteonal density (p<0.01) observed in the treatment group compared with the controls. The endocrine profile of both elevated androstenedione and estrone levels in an intact female primate of reproductive age may identify differential effects of the condition known as polycystic ovarian disease on the skeletal compartments. Received: 24 November 1999 / Accepted: 4 April 2000     

Fractal Analysis of Trabecular Bone Texture on Calcaneus Radiographs: Effects of Age, Time Since Menopause and Hormone Replacement Therapy

An analysis of trabecular bone texture based on fractal mathematics, when applied to trabecular bone images on plain radiographs, can be considered as a reflection of trabecular bone microarchitecture. It has been shown to be able to distinguish postmenopausal osteoporosis cases from controls. This cross-sectional study was carried out to investigate the influence of age, time since menopause and hormone replacement therapy (HRT) on the fractal dimension of trabecular bone texture at the calcaneus in a sample of 537 healthy women. Fractal analysis of texture was performed on calcaneus radiographs and the result expressed as the Hmean parameter (H = 2–fractal dimension). Total hip, femoral neck and lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. There was a statistically significant Hmean parameter decrease with age (p<0.0001) but the degree of correlation was low (r=–0.2) compared with the correlation between age and BMD (r=–0.36 to –0.61 according to the BMD site). We found a weak but statistically significant correlation between time since menopause and Hmean (r=–0.14, p= 0.03) in the 241 postmenopausal women included in the study. Hmean was significantly lower in a group of postmenopausal women without HRT (n= 110) compared with a group of age-matched postmenopausal women with HRT (n = 110): respectively 0.683 ± 0.043 and 0.695 ± 0.038 (p= 0.03). In conclusion, this study suggests that there is a menopause- and age-related decrease in the Hmean parameter and that HRT interferes with the results of the fractal analysis of trabecular bone texture on calcaneus radiographs. Received: 2 March 2001 / Accepted: 2 October 2001     

Differential Effects of Primary Hyperparathyroidism on Ultrasound Properties of Bone

Primary hyperparathyroidism (PHPT) may result in greater cortical than trabecular bone loss. Ultrasound is able to predict osteoporotic fracture risk independent of densitometric measurements, but little is known about the changes in ultrasound variables with PHPT. The aim of our study was to examine the effect of PHPT on ultrasound variables and bone density measurements at cortical (hand) and trabecular (lumbar spine and heel) sites, and to evaluate their reversibility following surgical treatment. We recruited 25 postmenopausal women diagnosed with PHPT ages 51–76 years (mean 62 years) and 95 postmenopausal controls ages 57–80 years (mean 67 years). Measurements were made at baseline and 1 year. Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of the heel were measured using the Lunar Achilles (LA+) and McCue CUBA Clinical (CC). Amplitude-dependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI) of the fingers were measured using the IGEA DBM Sonic. Bone mineral density (BMD) of the hand and lumbar spine (LS) were measured by dual-energy X-ray absorptiometry (DXA). At baseline, hand BMD, LS BMD and heel BUA were significantly lower and finger UBPI significantly higher in the PHPT patients compared with controls (p<0.001). There were no differences in Stiffness Index, heel SOS or finger AD-SoS between control and PHPT subjects. At 1 year postoperatively, there was a mean (±SD) increase in LS and hand BMD of 3 ± 1% (p<0.01). BUA at the heel increased (11 ± 5%, p<0.001), and UBPI of the fingers decreased (17 ± 7%, p<0.001) probably reflecting different modes of attenuation in trabecular (scattering) and cortical (absorption) bone. Stiffness Index, SOS of the heel and AD-SoS of the fingers did not change. BUA, UBPI and BMD returned towards normal postmenopausal values following surgery. There were no changes in BMD or QUS variables at 1 year in the control group. Quantitative ultrasound (QUS) measurements provide different information about bone structure than densitometric measurements and cannot be regarded as simply reflecting bone density. With further research the combined use of BMD and QUS could improve the assessment of skeletal status in patients with PHPT before and after surgery. Received: 10 September 2001 / Accepted: 31 January 2002     

Longitudinal Alveolar Bone Loss in Postmenopausal Osteoporotic/Osteopenic Women

The purpose of this 2-year longitudinal clinical study was to investigate alveolar (oral) bone height and density changes in osteoporotic/osteopenic women compared with women with normal lumbar spine bone mineral density (BMD). Thirty-eight postmenopausal women completed this study; 21 women had normal BMD of the lumbar spine, while 17 women had osteoporosis or osteopenia of the lumbar spine at baseline. All subjects had a history of periodontitis and participated in 3- to 4-month periodontal maintenance programs. No subjects were current smokers. All patients were within 5 years of menopause at the start of the study. Four vertical bitewing radiographs of posterior sextants were taken at baseline and 2-year visits. Radiographs were examined using computer-assisted densitometric image analysis (CADIA) for changes in bone density at the crestal and subcrestal regions of interproximal bone. Changes in alveolar bone height were also measured. Radiographic data were analyzed by the t-test for two independent samples. Osteoporotic/osteopenic women exhibited a higher frequency of alveolar bone height loss (p<0.05) and crestal (p<0.025) and subcrestal (p<0.03) density loss relative to women with normal BMD. Estrogen deficiency was associated with increased frequency of alveolar bone crestal density loss in the osteoporotic/osteopenic women and in the overall study population (p<0.05). These data suggest that osteoporosis/osteopenia and estrogen deficiency are risk factors for alveolar bone density loss in postmenopausal women with a history of periodontitis. Received: 9 April 1998 / Accepted: 18 August 1998     

Trabecular Bone Architecture in the Distal Radius Using Magnetic Resonance Imaging in Subjects with Fractures of the Proximal Femur

To determine whether magnetic resonance (MR)-derived measures of trabecular bone architecture in the distal radius are predictive for prevalent hip fractures, 20 subjects with hip fractures and 19 age-matched postmenopausal controls were studied. Bone mineral density (BMD) measures at the hip (dual-energy X-ray absorptiometry, DXA) and the distal radius (peripheral quantitative computed tomography, pQCT) were also obtained. We compared the MR-based structural measures derived in the radius with those in the calcaneus of the same patients. In the radius, images were acquired at an in-plane resolution of 156 μm and a slice thickness of 0.5 mm. Stereologic measures such as the apparent trabecular thickness (app. Tb.Th), fractional trabecular bone volume (app. BV/TV), trabecular spacing (app. Tb.Sp) and trabecular number (app. Tb.N) were derived from the images. Measures of app. Tb.Sp and app. Tb.N in the distal radius showed significant (p<0.05) differences between the two groups, as did hip BMD measures. However, radial trabecular BMD measures showed only a marginal difference (p= 0.05). Receiver operating curve analysis was used to determine the diagnostic efficacy of BMD, structural measures and a combination of the two. The area under the curve (AUC) for total hip BMD was 0.73, and for radial trabecular BMD was 0.69. AUC for most of the measures of trabecular bone structure at the distal radius was lower than for hip BMD measures; however, AUC for app. Tb.N at the radius was 0.69, comparable to trabecular BMD using pQCT. The AUC for combined BMD (hip) and structure measures was higher (0.87) when radius and calcaneus structure was included. Measures of trabecular architecture derived from MR images combined with BMD measures improve the discrimination between subjects with hip fractures and normal age-matched controls. Received: 22 December 1998 / Accepted: 12 February 1999     

Ultrasound Measurements of Proximal Phalanges in Polish Early Postmenopausal Women

The aim of this cross-sectional study was to evaluate skeletal status in Polish early postmenopausal women using ultrasound measurement at the proximal phalanges of the hand. We assessed the ability of the method to discriminate between healthy and osteoporotic individuals, the influence of age and menopause on ultrasound values, the impact of hormone replacement therapy and the relationships between ultrasound measurement and type of fracture. Five hundred and three early postmenopausal women were divided into three groups: (1) healthy (n= 398, mean age 53.4 years), (2) fractured (n= 43, mean age 53.9 years), (3) treated with estrogens (n= 62, mean age 53.5 years). Groups were matched for age and years since menopause (YSM). Group 2 was subdivided into those with and without wrist fracture. No drugs except estrogens were used by the subjects studied and no diseases known to affect bone metabolism were observed. Bone status was assessed by a DBM Sonic 1200 (Igea, Italy), a device that measures amplitude-dependent speed of sound (AD-SoS) at the proximal phalanges II–V of the hand. AD-SoS had the highest value in estrogen-treated women (1996.5 ± 66.5 m/s), the lowest in fractured persons (1883.6 ± 77.1 m/s) and a medium value in healthy women (1949.2 ± 78.0 m/s). All values were significantly different from each other (p <0.0001). AD-SoS values for the subgroups of group 2 were 1873.0 ± 80.6 m/s for those with wrist fracture and 1914.0 ± 73.0 m/s for those without; they were not statistically different. The hypothesis that AD-SoS at the proximal phalanges might be more sensitive to wrist fracture was not confirmed by Fisher's exact test for frequencies. Linear regression showed age-related changes, with r values –0.4 (p <0.00001), –0.47 (p <0.005), –0.37 (p <0.005), and YSM-related changes, with r values of –0.44 (p <0.00001), –0.32 (p <0.005), and –0.18 (NS) in groups 1, 2 and 3, respectively. It is concluded that: (1) ultrasound measurements of the proximal phalanges were able to discriminate between healthy and osteoporotic individuals; (2) the method is useful in detecting age and postmenopause-related changes within the skeleton; and (3) hormone replacement therapy significantly reduced the impact of the menopause on bone loss as detected by ultrasound. Received: 28 February 1997 / Revised: 4 March 1998     

Cross-sectional Area of Lumbar Vertebrae in Peri- and Postmenopausal Patients With and Without Osteoporosis

The purpose of this study was to analyze the midvertebral area of lumbar vertebrae in osteoporotic and nonosteoporotic female patients and to find out whether the midvertebral area may be used as an additional parameter in the diagnosis of osteoporosis. In 195 peri- and postmenopausal patients (average age 51.7 ± 5.2 years) trabecular and cortical bone mineral density (BMD) were determined using quantitative CT (QCT) in L2–4. In addition, midvertebral cross-sectional area was measured in a standardized fashion on the CT sections and the height of the second lumbar vertebra was determined on the lateral digital radiographs. Body height and weight were obtained and vertebral fracture status was determined. According to WHO criteria 29 patients (average age 57.2 years) were considered osteoporotic, 93 osteopenic (average age 52.2 years) and 73 normal (average age 48.6 years). Body weight and size did not show significant differences between the individual groups. Average midvertebral area was 1278 ± 173 mm² in the osteoporotic patients, 1186 ± 125 mm² in the osteopenic patients and 1126 ± 127 mm² in the normals. A correlation of r=−0.39 (p<0.05) was obtained between BMD and area. Thirty-six of 195 patients showed osteoporotic vertebral fractures. Midvertebral area in these patients was 1266 ± 171 mm² versus 1159 ± 133 mm² in the nonfractured females (p<0.05). We therefore conclude that the lumbar midvertebral area is larger in osteoporotic and osteopenic patients compared with women with normal BMD. In contrast to biomechanical considerations midvertebral area seems not to be suited as an additional measure of bone strength in vivo. Received: 8 March 1999 / Accepted: 15 September 1999     

Bone Densitometry: A New, Highly Responsive Region of Interest in the Distal Forearm to Monitor the Effect of Osteoporosis Treatment

The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone. The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n= 69), a 1-year trial with ibandronate (n= 141) and a 2-year trial with HRT (n= 121). Bone mineral density (BMD) at the distal forearm revealed a highly statistically significant dose-related response and increased 3–5% per year with 2.5 mg ibandronate, 10 mg alendronate or HRT, whereas the decrease in the placebo groups was 1–3% (p<0.001). The response at the distal forearm was similar to the response at the lumbar spine and hip. In conclusion, trabecular bone at the distal forearm is as responsive to antiresorptive treatment as trabecular bone in other skeletal regions. Bone densitometry at the new region of interest in the distal forearm has comparable performance characteristics to more expensive and technically demanding methods. The method is more accessible clinically and has potential as an alternative for monitoring bone mass changes during antiresorptive treatment. Received: 9 February 1998 / Accepted: 30 July 1998     

Ultrasound Velocity and Attenuation in Cancellous Bone Samples from Lumbar Vertebra and Calcaneus

We report a study of ultrasound velocity and broadband ultrasound attenuation (BUA) in human cancellous bone samples. The influence of density and microarchitecture on ultrasound propagation in cancellous bone was examined. A total of 20 samples from vertebra L1 and 21 from calcanei were studied. The direction of ultrasound propagation was anteroposterior in the vertebra and lateromedial in the calcaneus. The relationships between ultrasonic parameters and density of bone samples, apparent ash density, trabecular bone volume (BV/TV) and trabecular thickness (Tb.Th) were analyzed using a simple linear model and a multiple regression model. Velocity of ultrasound and BUA were positively correlated with density and morphometric parameters, in both vertebra and calcaneus. The best correlation was found between velocity and bone sample density in vertebra (r= 0.961, p < 0.0001) and the worst between velocity and trabecular thickness in calcaneus (r= 0.632, p= 0.002). The best correlation for BUA was with BV/TV in vertebra (r= 0.960, p < 0.0001). Using the stepwise regression procedure, BV/TV only was selected as significant for BUA and apparent ash density with Tb.Th for velocity, in both vertebra and in calcaneus. The possible influence of trabecular configuration on ultrasonic parameters is discussed, emphasizing the different slopes of regression lines obtained for vertebra and calcaneus, sites with different architecture of trabecular bone. Received: 9 April 1997 / Accepted: 27 April 1998     

Image-Based Assessment of Spinal Trabecular Bone Structure from High-Resolution CT Images

The goal of this study was to assess whether a high-resolution CT measure of trabecular bone structure can enhance the discrimination between subjects with or without a vertebral fracture and having overall low hip or spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Sixty-one women with low BMD by DXA (T-score <–2.5 at hip or spine) were examined. Twenty women had sustained a vertebral fracture. Quantitative CT (QCT) BMD and high-resolution CT spinal scans were performed on a whole-body CT scanner. For the high-resolution images (0.31 mm pixel, 1.5 mm thick slice), trabecular bone was segmented from marrow using an adaptive threshold, region growth and skeletonization step. From the processed image we measured the apparent trabecular bone fraction (BV/TV), apparent trabecular thickness (I.Th) and apparent trabecular spacing (I.Sp). We also assessed the connectivity of the marrow space using region growing to derive a mean (H_A) and maximum (H_M) hole size. Despite the fact that the study population was preselected to have a low BMD by DXA, QCT BMD was highly associated with (p <0.005) with fracture status. All structural parameters were correlated (r ~ 0.64 to 0.79) with BMD with p <0.003 and showed significant differences between the fracture and non-fracture group. However, except for H_A, this difference did not remain significant after adjustment for BMD. When BMD and then H_A was entered into a paired linear regression model to predict fracture outcome, H_A contributed with p= 0.03 and BMD with p= 0.86. ROC analysis was applied and showed that H_A, BMD, I.Th and I.Sp discriminated the two groups with areas of 0.76, 0.75, 0.71 and 0.68, respectively. These findings suggest that an assessment of vertebral trabecular structure from high-resolution CT images is useful in discriminating subjects with vertebral fractures and potentially useful for predicting future fractures. Received: 10 October 1997 / Accepted: 4 December 1997     

Changes in Bone Mass and Bone Turnover Following Ankle Fracture

Bone loss and increased bone turnover are recognized local changes after a fracture, but the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following ankle fracture. Fourteen subjects (7 postmenopausal women and 7 men, mean age 63 years) were recruited following fracture of the distal tibia and fibula. Bone mineral density (BMD) of the ankle and proximal femur were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the calcaneus at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and QUS. There was a significant decrease in BMD at the ultradistal ankle (p<0.001), the trochanteric region of the hip (p<0.01) and QUS of the heel after ankle fracture. This bone loss was maximal for ultradistal ankle BMD by 6 weeks at 13% (p<0.001) and for the trochanter by 26 weeks at 3% (p<0.01). The ankle BMD returned to baseline at 52 weeks but the trochanter BMD did not. Velocity of sound (VOS) decreased at 6 weeks by 2% (p<0.01) and broadband ultrasound attenuation (BUA) by 15% (p<0.01). VOS recovered completely by 52 weeks, but BUA did not return to baseline. Bone formation markers increased significantly between 1 and 4 weeks by 11–78% (p<0.01), and iBAP returned to baseline at 52 weeks but PINP and Oc remained elevated. Bone resorption markers did not increase and NTx was decreased at 52 weeks. We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Ankle BMD and heel VOS recovered at 52 weeks (trochanteric BMD and heel BUA did not) and the bone turnover markers returned toward baseline. Received: 27 January 1999 / Accepted: 19 April 1999     

Changes in Bone Mass and Bone Turnover Following Distal Forearm Fracture

Bone loss occurs close to a fracture and is associated with increased bone turnover. Fracture healing itself results in increased markers of bone turnover. But the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following distal forearm fracture. Twenty women (mean age 63 years) were recruited following fracture of the distal radius and ulna. Bone mineral density (BMD) of the hand and forearm were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the fingers was measured at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), free deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and amplitude-dependent speed of sound (AD-SoS). There was a decrease in BMD at the hand and in AD-SoS of the fingers after forearm fracture (p<0.001). This bone loss was maximal for BMD by 6 weeks at 9% (p<0.001) and remained decreased at 52 weeks. AD-SoS decreased at 12 weeks by 3% (p<0.01) and recovered completely by 52 weeks. Bone formation markers increased between 2 and 4 weeks by 13–52% (p<0.001), and were still elevated at 52 weeks. Bone resorption markers increased between 2 and 6 weeks by 18–35% and returned to baseline at 52 weeks (TRAcP remained elevated). We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Bone loss after distal forearm fracture did not recover by 52 weeks and most bone turnover markers did not return to baseline. Received: 27 January 1999 / Accepted: 19 April 1999     

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     

Detailed Analyses of Periarticular Osteoporosis in Rheumatoid Arthritis

Periarticular osteopenia is the earliest radiographic sign of rheumatoid arthritis (RA). Recent studies using dual-energy X-ray absorptiometry (DXA) have indicated that the loss of periarticular BMD can be quantified by whole-hand bone mineral density (BMD) measurements. The aim of this study was to analyze periarticular BMD in more detail by DXA and quantitative ultrasound (QUS). In a cross-sectional study 23 women aged 30–76 years with early RA, mean disease duration 26 ± 19 months, and 18 men aged 42–69 years, mean disease duration 24 ± 25 months, were examined. All patients received antirheumatic therapy. The reference population consisted of 103 age-matched controls (68 females, 35 males) and young healthy controls. BMD measurements were performed using a DXA Expert XL densitometer (Lunar). BMD of the whole-hand and two subregions was determined: two subchondral regions of interest (S.CH.) were set within the trabecular bone, distal to the proximal interphalangeal joints of digits II and III excluding the dense subchondral bone of the metacarpophalangeal (MCP) joint and two metacarpal regions of interest (MCP) were set including the entire MCP joint of these fingers. QUS measurements at the proximal phalanges of digits II–V were performed using a DBM Sonic (Igea); amplitude-dependent speed of sound (Ad-SoS) was determined. In comparison with whole-hand BMD measurements, bone loss was pronounced in patients with a disease duration of 18–72 months at the subchondral regions of interest in both genders compared with age-matched controls (women: mean BMD loss S.CH. −23%, p<0.001, whole-hand −16%, p<0.001; men: mean BMD loss S.CH. −19%, p<0.05, whole-hand −12%, p<0.05). The bone changes were also shown by QUS (women: Ad-SOS values of 1950 ± 90 m/s in RA vs 2137 ± 35 m/s in young healthy controls (p<0.005); men AD-SOS 1956 ± 87 m/s in RA vs 2146 ± 41 m/s in young healthy controls (p<0.05)). These results show that BMD and Ad-SOS values are significantly lowered in patients with early RA and indicate that periarticular osteoporosis in early RA might possibly be better detected using detailed hand scan analyses. Received: 2 February 1999 / Accepted: 25 October 1999     

Relationship Between Computed Tomographic Image Analysis and Histomorphometry for Microarchitectural Characterization of Human Calcaneus

The present study aimed to characterize the relationships between several variables reflecting bone microarchitecture assessed by both computed tomographic (CT) image analysis and histomorphometry (conventional CT system) at the calcaneus. A total of 24 cadaveric specimens were studied. The mean age at death was 78 ± 10 years (range, 53–93 years). A total of 15 sagittal sections (1 mm in width and spaced 2 mm apart) were selected for CT analysis; 6 undecalcified sections (7 m) were analyzed for histomorphometry. The histomorphometric analysis was performed on a Leica Quantimet Q570 image analyzer. Features measured by both methods were: bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N), interconnectivity index (ICI), number of nodes (N Nd), number of terminus (N Tm), node-to-node strut count (NNS), node-to-terminus strut count (NTS), terminus-to-terminus strut count (TTS), marrow space star volume (SV), Euler number (EN), and fractal dimension (FD). The coefficient of correlations values (simple linear regression) between histomorphometry and CT image analysis varied according to the parameters selected. R values were high for BV/TV, Tb.N, and Tb.Sp (range, 0.69–0.90; P < 0.01). R values were less significant for some variables also obtained from the binary image: SV (0.5, P < 0.05) and EN (0.43, P < 0.05). Finally R values were also significant for (two) variables obtained from skeletonized images, i.e., N Nd (0.4, P < 0.05) and N Tm (0.61, P < 0.01). Other correlations were not statistically significant. Moreover, for some variables the relationships between the two methods (CT analysis and histomorphometry) seemed best-described by using nonlinear models. For example, a logarithmic model was more appropriate for SV (r = 0.71, P < 0.01), N Nd (r = 0.52, P < 0.01). Finally the relationship between apparent (App) N Tm and N Tm was most satisfying when using an exponential model (r = 0.64, P < 0.01). In conclusion, trabecular bone structure measures determined on CT images show highly significant correlations with those determined using histomorphometry. The level of correlation varies according to the type of method used for characterizing bone structure, however, and the strongest correlations were found for the most basic features (Parfitts parameters). Finally, for some variables, nonlinear models seem more appropriate.     

High-Resolution Computed Tomography for Architectural Characterization of Human Lumbar Cancellous Bone: Relationships with Histomorphometry and Biomechanics

The aim of the present study on human vertebral cancellous bone was to validate structural parameters measured with high-resolution (150 μm) computed tomography (HRCT) by referring to histomorphometry and to try to predict mechanical properties of bone using HRCT. Two adjacent vertical cores were removed from the central part of human L2 vertebral body taken after necropsy in 22 subjects aged 47–95 years (10 women, 12 men; mean age 79 ± 14 years). The right core was used for structural analysis performed by both HRCT and histomorphometry. Two cancellous bone specimens were extracted from the left core: a cube for HRCT and a compression test, and a cylinder for a shear test. Significant correlations were found between HRCT and histomorphometric measurements (BV/TV, trabecular thickness, separation and number, and node-strut analysis), but with higher values for most of the tomographic parameters (BV/TV and trabecular thickness determined by HRCT were overestimated by a factor 3.5 and 2.5 respectively, as compared with histomorphometry). The maximum compressive strength and Young’s modulus were highly correlated (ρ= 0.99, p<0.0005). Significant correlation was obtained between bone mineral density (determined using dual-energy X-ray absorptiometry) and the maximum compressive strength (ρ= 0.64, p= 0.002). In addition the maximum compressive strength and architectural parameters determined by HRCT or histomorphometry showed significant correlations (e.g., for HRCT, BV/TV: ρ = 0.88, p<0.0005, N.Nd/TV: ρ= 0.73, p<0.001). The shear strength was significantly correlated with BV/TV (ρ= 0.62, p= 0.002), Tb.Sp (ρ=−0.58, p= 0.004) and TSL (ρ= 0.55, p= 0.006) measured by HRCT. In conclusion, an HRCT system with 150 μm resolution is not sufficient to predict the true values of the structural parameters measured by histomorphometry, although high correlations were found between the two methods. However, we showed that a resolution of 150 μm allowed us to predict the mechanical properties of human cancellous bone. In vivo peripheral systems with such a resolution should be of interest and would deliver an acceptable radiation dose to the patient. Received: 13 October 1998 / Accepted: 16 March 1999     

Measurement of Bone Adjacent to Tibial Shaft Fracture

Delayed union and non-union are common complications after fracture of the tibial shaft. Response of the surrounding bone as a fracture heals could be monitored using techniques currently used in the study of osteoporosis. The aims of our study were to: (1) evaluate the decrement in bone measurements made close to the fracture using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound (QUS) and peripheral quantitative computed tomography (pQCT); (2) compare values for fractured versus non-fractured leg to determine the duration of decrement in bone measurements; and (3) calculate short-term precision in DXA, QUS and pQCT in order to calculate the ratio of decrement to precision (response ratio, RR) to determine the optimal test for monitoring changes after tibial fracture. The biggest decrement in bone measurements at the ipsilateral limb of 28 patients with tibial shaft fracture was observed at the pQCT tibial trabecular sites (distal = 19%, p<0.0001; proximal 5% = 21%, p<0.001; proximal 10% = 28%, p<0.001) and the ultradistal tibia/fibula measured by DXA (19%, p<0.0001). When comparing Z-scores, the magnitude of decrements at the ipsilateral limb was bigger for variables measured directly at the tibia, both proximal and distal to the fracture. The magnitude of the decrement in ultradistal tibia/fibula BMD decreased as the time since fracture increased (r = 0.55). When response ratios are considered, pQCT measurements at the distal tibia (RR 6–8) and proximal 5% and 10% trabecular sites (RR 5 and 9 respectively) were found to be the most sensitive to change. Therefore, pQCT of the trabecular regions of either the proximal or distal tibia should prove the most sensitive measurement for monitoring changes in bone adjacent to a tibial shaft fracture. Received: 24 January 2002 / Accepted: 23 July 2002