Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

Vertebral Fracture Assessment using the Lateral Scoutview of Computed Tomography in Comparison with Radiographs

Semiquantitative vertebral fracture assessment was compared between lateral computed tomography (CT) scoutviews and conventional thoracolumbar spinal radiographs. Vertebral levels T4–L4 were assessed by both techniques in a group of 56 women (mean age 60 + 13 years). In order to compare inter- and intra-observer variabilities for the two techniques, the images were analyzed twice by two independent observers, and percentage agreement and kappa statistics were measured both between readings and between observers. Percentage agreement and kappa statistics were also used to quantify differences between techniques. In the CT scoutviews, noise and artifacts from overlying tissues in the thoracic spinal levels rendered 3.4% of the vertebrae unreadable for the first observer and 8.3% for the second observer. For the CT scoutviews the agreement between readings was 98.1%, 97.3% and 100% (k = 0.87, 0.83 and 1.0) on T4–L12, T4–12 and L1–4, respectively for the first observer, and 97.8%, 97.1% and 99.5% (k = 0.79, 0.73 and 0.92) for the second observer. For the lateral radiographs, the agreement between readings was 97.7%, 96.9% and 100% (k = 0.87, 0.85 and 1.0) on T4–L12, T4–12 and L1–4, respectively for the first observer, and 98.4%, 97.7% and 99.5% (k = 0.86, 0.82 and 0.95) for the second observer. The agreement between observers was 96.1%, 94.4% and 100% (k = 0.68, 0.58 and 1.0) on T4–L12, T4–12 and L1–4, respectively for the CT scout-views and 96.8%, 95.9% and 99.0% (k = 0.79, 0.76 and 0.91) for the lateral radiographs. The inter-technique was 95.8%, 94.2% and 99.5% (k = 0.73, 0.68 and 0.95) on T4–L12, T4–12 and L1–4, respectively for the first observer and 95.6%, 94.2% and 99.0% (k = 0.64, 0.55 and 0.90) for the second observer, with the scoutview technique detecting, on average, 23% fewer fractures than the lateral radiographs. Although the vertebral fracture detection in lumbar spine is quite comparable to that of conventional radiographs, given its reduced sensitivity for vertebral fracture detection in thoracic spine, the lateral CT scoutview technique should not be substituted for conventional radiographs where diagnosis of all vertebral fractures is of primary importance. Received: 26 August 1997 / Accepted: 28 Augustr 1997     

Peripheral Quantitative Computed Tomography of the Femoral Neck in 60 Japanese Women

Peripheral quantitative computed tomography (pQCT) is able to evaluate trabecular and cortical bone separately, and to determine geometric properties from cross-sectional images for noninvasive assessments of mechanical strength. In order to assess the diagnostic value of pQCT of the femoral neck, 60 healthy women were examined with a new pQCT machine, XCT-3000 (Norland-Stratec, Germany), which is suitable for direct measurement of the hip. The region of interest chosen was the center of the femoral neck. pQCT of the distal radius and dual energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck were also performed. The study demonstrated that total bone mineral density (BMD) (femoral MD) and trabecular BMD (femoral-TBD) decreased with advancing age. Percent cortical area showed a small but significant decrease with advancing age and % trabecular area increased slightly. Both the endosteal perimeter and the periosteal perimeter were relatively constant with aging. Bone strength index (BSI) and stress-strain index (SSI), which reflect the mechanical strength of bone, declined with advancing age, especially after menopause. Femoral TBD correlated strongly with femoral neck BMD by DXA and L2-L4 BMD by DXA but femoral-CBD did not correlate with femoral neck BMD by DXA. Volumetric BMD of the femoral neck and distal radius were closely correlated. It is concluded that (1) cortical thinning occurs with aging by endocortical resorption and loss of femoral-TBD; (2) loss of femoral-CBD occurred at a slower rate than radial CBD, perhaps due to the weight-bearing effect; (3) biomechanical parameters such as the BSI and SSI may reflect increasing fragility of the femoral neck in pre- and postmenopausal women; (4) pQCT of the femoral neck had diagnostic value at least equivalent to that of DXA or pQCT of the distal radius. Received: 23 June 1998 / Accepted: 1 July 1999     

Quantitative Assessment of Experimental Fracture Repair by Peripheral Computed Tomography

An experimental fracture model was used to assess bone mineral density at the fracture site by peripheral computed tomography and to compare the model with biomechanical, histological, and radiographic methods for the quantification of the fracture repair process. Transverse osteotomies in the mid-diaphysis of 28 tibia of sheep were externally fixed and mineral densities, cross-sectional areas, flexural rigidities, tissue composition, and projected callus area were calculated after 9 weeks of healing time. BMD measured by pQCT was strongly correlated with histologically determined percentages of mineralized tissue in the osteotomy gap (R ²= 0.71) and in the periosteal callus (R ²= 0.62). The percentage of mineralized tissue in the osteotomy gap was the best predictor of the flexural rigidity of the tibiae (R ²= 0.74). Because of high correlations with the histological findings, the volumetric BMD at the level of the osteotomy gap was also strongly correlated with the biomechanical findings (R ²= 0.70). Neither the cross-sectional area in pQCT nor the projected callus area in plane film radiography were positively correlated to the flexural rigidity of the tibiae. Quantitative computed tomography proved to be a successful estimator for the prediction of the mechanical stability of healing bones. The noninvasive procedure is a reliable tool for the quantification of the fracture repair process in experimental studies and may be useful for treatment decisions in particular clinical situations. Received: 2 May 1996 / Accepted: 24 June 1996     

Estimation of the Architectural Properties of Cortical Bone Using Peripheral Quantitative Computed Tomography

We assessed the volumetric bone mineral density (vBMD) and cross-sectional architecture of cortical bone at the distal radius by peripheral quantitative computed tomography (pQCT). The volumetric bone mineral density [integral bone mineral density (BMDi), trabecular bone mineral density (BMDt) and cortical with subcortical bone mineral density (BMDsc)] and the architectural parameters [cortical bone area (CBA), cortical thickness (C-th), moment of inertia (Im) and polar moment of inertia (Ip)] were measured in 115 healthy premenopausal women, 48 osteoporotic postmenopausal women and 78 age-matched healthy postmenopausal women. Age-matched healthy women had higher values of vBMD and architectural parameters at the distal radius than osteoporotic women. Premenopausal women had higher values of vBMD and architectural parameters at the distal radius than postmenopausal women. The differences in the architectural parameters between age-matched healthy women and osteoporotic women were more pronounced when only the high density area (threshold 0.70 cm^–1) was included. However, the differences in architectural parameters between premenopausal women and postmenopausal women were significant using even the lowest threshold value of 0.50 cm^–1 in the calculation. Receiver operating characteristic (ROC) curves were constructed and the areas under the curves calculated to evaluate the discriminating power of vBMD and architectural parameters. Comparison of the different ROC curves showed no statistical significance. In conclusion, our results suggest that both the density and mass distribution of the radius were clearly different between the healthy women and osteoporotic women. The differences in architectural parameters were more useful for studying the pathopysiology of osteoporosis than for contributing to the diagnosis. Determination of the cross-sectional mass distribution of bone combined with BMD should offer more information than BMD alone in the study of the pathophysiology of osteoporosis. Received: 22 December 1998 / Accepted: 2 June 1999     

Recognition of Vertebral Fracture in a Clinical Setting

Osteoporosis-related vertebral fractures have important health consequences for older individuals, including disability and increased mortality. Because these fractures can be prevented with appropriate medications, recognition and treatment of high-risk patients is warranted. A cross-sectional survey was carried out in a large, regional hospital in New England to examine the frequency with which vertebral fractures are identified and treated by clinicians in a population of hospitalized older women who have radiographic evidence of fractures. The study population consisted of 934 women aged 60 years and older who were hospitalized between October 1, 1995 and March 31, 1997, and who had a chest radiograph obtained. Vertebral fractures in the thoracic region were identified by two radiologists. Discharge diagnoses, medical record notes and radiology reports were compared with the results of the radiologists’ readings to determine the frequency with which fractures were identified and appropriate, osteoporosis-preventing medications prescribed. Moderate or severe vertebral fractures were identified for 132 (14.1%) study subjects, but only 17 (1.8%) of the 934 participants had a discharge diagnosis of vertebral fracture. Of these 132, only 17% had fracture noted in the medical record or discharge summary; 50% of contemporaneous radiology reports identified a fracture as present; and 23% of the time it was found in the radiologist’s summary impression. Only 18% of medical records indicated that fracture patients had been prescribed calcium, vitamin D, estrogen replacement or an antiresorptive agent. Relatively few hospitalized older women with radiographically demonstrated vertebral fractures were thus identified or treated by clinicians, suggesting a need for improved recognition. Received: 15 November 1999 / Accepted: 23 December 1999     

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

Prevalence of Vertebral Deformity and its Associations with Physical Impairment among Japanese Women: The Hizen-Oshima Study

Vertebral fractures are a hallmark of postmenopausal osteoporosis and an important end point in trials of osteoporosis treatment, but the clinical significance of vertebral deformities remains uncertain. We examined the prevalence of vertebral deformity and associations of vertebral deformities and other characteristics with physical functioning among 584 Japanese women ages 40 to 89 years. Lateral spine radiographs were obtained and radiographic vertebral deformities were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. A self-administered questionnaire was used to survey participants about difficulty in performing selected basic and instrumental activities of daily living (ADL). Overall, 15% of women had at least one vertebral deformity, and 8% had 2 or more. The prevalence of vertebral deformities increased progressively with age. Half of women ages 80 and over had vertebral deformities. Impaired function was defined as difficulty performing 3 or more ADLs. After adjusting for age, the odds of impaired function were increased by 1.4 times (95% CI: 0.7, 2.9) in women with a single vertebral deformity, and 3.1 times (1.4, 6.8) in those with two or more deformities. Additional adjustment for number of painful joints, number of comorbidities, body mass index, and back pain did not materially alter these findings. In conclusion, women with multiple vertebral deformities had significantly greater impaired function. The association was independent of age, back pain and the number of painful joints, suggesting that deformities may impair function even when back pain is not present. Received: 29 October 2001 / Accepted: 11 April 2002     

Vertebral Fracture and Cortical Bone Changes in Corticosteroid-Induced Osteoporosis

Despite an intriguing understanding of trabecular bone dynamics, little is known about corticosteroid-induced cortical bone loss and fractures. Recently, we verified a steroid-induced decrease in cortical bone volume and density using peripheral quantitative computed tomography (pQCT) in adult asthmatic patients given oral corticosteroids. Subsequently, the pQCT parameters and presence of vertebral fractures were investigated to further clarify the role of cortical bone quality in fractures in 86 postmenopausal (>5 years after menopause) asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone) (steroid group) and 194 age-matched controls (control group). Cortical and trabecular bone was subjected to measurement of various parameters using pQCT (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the cortical area by the total bone area. Strength Strain Index (SSI) was determined in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. Patients treated with high doses of oral steroid (>10 g cumulative oral prednisolone) were found to have an increased risk of fracture compared with control women receiving no steroid medication (odds ratio, 8.85; 95% CI, 4.21–18.60) after adjustment was made for years since menopause, body mass index and RCV. In both groups, the diagnostic and predictive ability of the pQCT parameters for vertebral fracture was assessed by the areas under their receiver operating characteristic (ROC) curves. All parameters were found to be significant predictors (p<0.0001) in the control group. In the steroid group, however, the cortical bone mineral density (BMD) (p= 0.001), RCV (p<0.0001) and SSI (p= 0.001) were found to be significant predictors, but not trabecular BMD (p= 0.176). For comparison between the two groups, thresholds of all parameters for vertebral fracture were also calculated by the point of coincidence of sensitivity with specificity in ROC testing and the 90th percentile value. Although a rise in fracture threshold in the steroid group was suggested, considerable difference in the values obtained by the two methods of calculation precluded any conclusion. High-dose oral steroid administration was associated with an increased risk of fracture. Cortical bone parameters obtained by pQCT could play a role as good predictors of future corticosteroid-induced vertebral fractures. Received: 30 November 2001 / Accepted: 28 February 2002     

Acute and Long-Term Increase in Fracture Risk after Hospitalization for Vertebral Fracture

The aims of this study were to determine the magnitude of the increase in risk of further fracture following hospitalization for vertebral fracture, and in particular to determine the time course of this risk. The records of the Swedish Patient Register were examined from 1987 to 1994 to identify all patients who were admitted to hospital for thoracic or lumbar vertebral fractures. Vertebral fractures were characterized as due to high- or low-energy trauma. Patients were followed for subsequent hospitalizations for hip fracture, and for all fractures combined. A Poisson model was used to determine the absolute risk of subsequent nonvertebral fracture and compared with that of the general population. We analyzed 13.4 million hospital admissions from which 28.869 individuals with vertebral fracture were identified, of which 60% were associated with low-energy trauma. There was a marked increase in subsequent incidence of hip and all fractures within the first year following hospitalization for vertebral fracture in both men and women. Thereafter, fracture incidence declined toward, but did not attain, baseline risk. Increased risks were particularly marked in the young. The increase in fracture risk was more marked following low-energy vertebral fracture than in the case of high-eneergy trauma. We conclude that the high incidence of new fractures within a year of hospitalization for vertebral fractures, irrespective of the degree of trauma involved, indicates that such patients should be preferentially targeted for treatment. It is speculated that short courses of treatment at the time of first vertebral fracture could provide important therapeutic dividends. Received: 6 June 2000 / Accepted: 28 September 2000     

Baseline BMD and Bone Loss at Distal Radius Measured by Peripheral Quantitative Computed Tomography in Peri- and Postmenopausal Hong Kong Chinese Women

The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal (n = 26) and postmenopausal (n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM (r ranges from −0.283 to −0.502; p<0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss ≥3%), normal bone losers (with annual tBMD loss ≥ 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence. Received: 12 November 2001 / Accepted: 18 July 2002     

Comparative Assessment of Bone Mineral Measurements Using Dual X-ray Absorptiometry and Peripheral Quantitative Computed Tomography

A measurement of bone mass is the single most important determinant of future fracture. However, controversy exists as to which technique (dual X-ray absorptiometry (DXA) or peripheral quanitative computed tomography (pQCT)), and which site of skeletal measurement (axial vs appendicular) provides the best prediction of fracture risk. The aims of this study were: (1) to determine the ability of pQCT to predict bone mass of the lumbar spine, proximal femur, and distal forearm measured using DXA, and (2) to compare the ability of DXA and pQCT to discriminate prevalent fractures in women with established osteoporosis. One hundred and sixty-five women were studied, including 47 with established osteoporosis (vertebral, hip or Colles' fractures) as well as 118 who had bone mass measurements to assess osteoporosis risk. Each subject had bone mass measured by DXA at the lumbar spine and femoral neck, and at the distal radius by both DXA and pQCT. In women with fractures, bone mass, when expressed as a standardized score, was in general lower using DXA compared with the appendicular skeleton measured using pQCT. Bone mass determinations at all sites were significantly correlated with each other. The highest correlation coefficients were observed within the axial skeleton. In women with fractures, the highest odds ratios were observed at skeletal regions measured using DXA. Likewise, the areas under the receiver-operating characteristic (ROC) curves were comparable at all skeletal regions measured using DXA; and were significantly greater than the areas under the ROC curves for pQCT measurements. In summary, the strongest discriminators of prevalent fractures were measurements using DXA. Measurements of bone mass at the appendicular skeleton, using either DXA or pQCT, were poorly associated with axial bone mass. PQCT has the poorer ability to discriminate persons with fractures, and appears to be less sensitive than measurements using DXA. Received: 15 September 1997 / Accepted: 17 February 1998     

Modeling of Cross-sectional Bone Size, Mass and Geometry at the Proximal Radius: A Study of Normal Bone Development Using Peripheral Quantitative Computed Tomography

It is becoming increasingly accepted that bone size is an important determinant of bone mass. Studies on the development of bone size may therefore promote a better understanding of the basis of diseases which are due to low bone mass. Here, we characterize the temporal changes in cross-sectional bone size, geometry and mass at the radial diaphysis in healthy subjects from 6 to 40 years of age (n= 469; 273 females). Peripheral quantitative computed tomography was used to measure total and cortical cross-sectional area, bone mineral content (BMC) and volumetric bone mineral density (BMD) at the site of the forearm whose distance from the ulnar styloid process corresponded to 65% of forearm length. Over the age range of the study, total cross-sectional area increased by 39 mm² (50%) in females and by 85 mm² (116%) in males. Cortical area increased to a similar extent in both sexes. Between 6–7 years and adulthood, BMC increased by 52 mg/mm (111%) in females and by 73 mg/mm (140%) in males and was significantly higher in males after the age of 15 years. Volumetric BMD increased by 246 mg/cm³ (48%) in females but by only 132 mg/cm³ (23%) in males and was significantly higher in women than in men. In summary, these data show that BMC in men is higher than in women, because periosteal modeling continues longer in boys than in girls. Volumetric BMD is higher in women, partly because the size of the marrow cavity does not increase in girls as it does in boys. Received: 11 May 2000 / Accepted: 11 January 2001     

Relationship Between Structural Parameters, Bone Mineral Density and Fracture Load in Lumbar Vertebrae, Based on High-Resolution Computed Tomography, Quantitative Computed Tomography and Compression Tests

Different noninvasive techniques for the assessment of the individual fracture risk in osteoporosis are introduced, and the relation between structural properties of high-resolution computed tomography (HR-CT) images of vertebral bodies, their bone mineral density (BMD) and the fracture load is analyzed. In 24 unfractured lumbar vertebrae with different degrees of demineralization from six specimens, the trabecular and cortical BMD was determined using quantitative CT. A lateral X-ray image revealed the number of fractures in the entire spine. A structural analysis of spongy and cortical bone was performed based on the HR-CT images. In the spongiosa, the fractal dimension was calculated as a function of the threshold value. In the cortical shell, the maximum number of clusters of low BMD was determined at varying threshold values. After the CT measurements the vertebrae were excised and compressed until fractured. On the basis of the spongiosa BMD and the number of fractures, 3 cases were found to be severely osteoporotic; the other 3 cases showed osteopenia. The average fracture loads were determined as 3533 N for the non-osteoporotic cases (range 2602–5802 N) and 1725 N for the osteoporotic cases (range 1311–2490 N). The parameters were determined as follows: average spongiosa BMD 115.2 mg/ml (101.8–135.3 mg/ml) for the non-osteoporotic cases, 46.2 mg/ml (34.8–57.6 mg/ml) for the osteoporotic cases; average cortical BMD 285.1 mg/ml (216.4–361.9 mg/ml) for the non-osteoporotic cases, 136.1 mg/ml (142.5–215.2 mg/ml) for the osteoporotic cases; spongiosa structure: average 0.5 (range 0.32–0.75) for the non-osteoporotic cases, average 1.05 (range 0.87–1.24) for the osteoporotic cases; cortical structure: average 81 (range 55–104) for the non-osteoporotic cases), average 136 (range 102–159) for the osteoporotic cases. Single parameters (BMD and structure) and weighted sums of these parameters were correlated with the fracture load, resulting in correlation coefficients of r _sBMD= 0.82 (spongiosa BMD), r _cBMD= 0.82 (cortical BMD), r _sStr=–0.75 (spongiosa structure) and r _cStr=–0.86 (cortical structure). The weighted sum of cortical and spongiosa BMD resulted in r _BMD= 0.86, of cortical and spongiosa structure in r _Str=–0.86. A weighted combination of all four parameters correlates with the fracture load at r ₄= 0.89, all correlations being statistically significant (p<0.0001). The four individual parameters show only a slight overlap between non-osteoporotic and osteoporotic subjects. The high correlation of the cortical BMD and the structural parameter in cortical bone indicates the important contribution of the cortical shell to vertebral stability. A weighted sum of multiple parameters results in a higher correlation with the fracture load and does not show an overlap between the two groups. It is best suited to estimate the individual fracture risk. The presented methods are generally applicable in vivo; and allow an improvement of the diagnosis of osteoporosis compared with the measurement of the BMD alone. Received: 7 November 1997 / Accepted: 28 September 1998     

Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis

The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n= 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p= 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p= 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease. Received: 29 September 1999 / Accepted: 10 November 1999     

Spinal Performance and Functional Impairment in Postmenopausal Women with Osteoporosis and Osteopenia without Vertebral Fracture

Previous studies have paid much attention to the impact on functional impairment or quality of life from vertebral fractures secondary to osteoporosis, but little research has addressed the function of osteoporotic women without fractures. The purposes of this study were: (1) to describe spinal performance and functional impairment in postmenopausal women with osteoporosis and osteopenia without vertebral fracture, and (2) to investigate the relationship between them. Thirty postmenopausal women diagnosed as having osteoporosis or osteopenia were recruited who fulfilled the following criteria: (1) menopause for at least 6 months; (2) no vertebral fracture; (3) no medication that would interfere with calcium intake. Measurements included assessment of functional impairment and spinal performance including trunk extension/flexion isokinetic strength, spinal range of motion (ROM) and movement velocity in three planes (sagittal, frontal and transverse). The results showed that spinal ROM and velocity were significantly reduced in the osteoporosis group compared with the osteopenia group (p<0.05), but no significant difference in trunk strength was shown. Functional impairment level showed a slight difference between the two groups (p= 0.042). There was a significant correlation between spinal ROM and motion velocity with bone mineral density; however, functional impairment correlated with motion velocity only in the transverse plane (trunk rotation) (p<0.05). Spinal strength did not show any correlation with other parameters. It was concluded that spinal motion performance declined and functional impairment increased in relation to the severity of bone mineral loss in postmenopausal women without vertebral fracture, but their physical performance was not correlated with functional impairments. Received: 13 March 2001 / Accepted: 23 November 2001     

FDG-PET Findings of Vertebral Compression Fractures in Osteoporosis: Preliminary Results

The aim of this study was to evaluate FDG-PET findings in patients with osteoporosis or preclinical osteoporosis and acute vertebral compression fractures in order to determine whether FDG-PET has a value for distinction of pathological from osteoporotic vertebral fractures. 17 patients with a spontaneous compression fracture of the spine were evaluated by bone scanning with Tc-99m HDP, positron emission tomography with fluorine-18 deoxyglucose (FDG-PET) and magnetic resonance imaging (MRI). Osteoporosis had been established in all cases by X-ray and osteodensitometry. PET and bone scan images were scored independently from 0 (no pathological uptake) to 4 (definitive pathological uptake) by two blinded nuclear medicine physicians. The results of the blinded scoring were compared to MRI findings which served as gold standard. In 13 out of 17 patients, MRI demonstrated a vertebral fracture generating from osteoporosis. In 12 of these 13 cases, PET scans were scored with 0 or 1 and categorized as true negative. Standard uptake values (SUV) ranged between 1.1 and 2.4. In one of the 13 patients, PET was interpreted false positive with an uptake score of 3 (SUV = 2.9). Of the 17 patients, MRI revealed a pathological fracture caused by spondylodiscitis in three patients and by plasmacytoma in one patient. In these patients, all PET scans were highly positive with a score of 3 and 4 and SUV values between 3.8 to 9.8. The bone scans of all 17 patients were positive with scores of 3 or 4 but a differentiation between osteoporotic and pathological fractures was not possible. Our preliminary results indicate that acute vertebral fractures that originated from osteoporosis or preclinical osteoporosis tend to have no pathologically increased FDG uptake. Since a high FDG uptake is characteristic for malignant and inflammatory processes, use of FDG-PET may have potential value for differentiation between osteoporotic and pathological vertebral fractures. Received: 18 October 2001 / Accepted: 25 April 2002     

Prevalent Vertebral Deformity Predicts Incident Hip though not distal Forearm Fracture: Results from the European Prospective Osteoporosis Study

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40 348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1–9.4) and a weak predictor of ‘other’ limb fractures (RR = 1.6; 95% CI 1.1–2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6–1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0–17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and ‘other’ limb fractures; however, they do not predict distal forearm fractures. Received: 23 February 2000 / Accepted: 11 August 2000     

Usefulness of Armspan and Height Comparison in Detecting Vertebral Deformities in Women

The prevalence of vertebral fractures in women increases with age but only about one third of these fractures are symptomatic. On the other hand, the presence of vertebral fractures is an independent risk factor for new osteoporotic fractures. In the present study we examined the hypothesis that differences between armspan and height are related to the presence of vertebral deformities in a cohort of 494 women aged between 55 and 84 years (mean age 67.6 years, SD 8.2 years) who were randomly selected from a large general practice in The Netherlands. Height and armspan were measured and vertebral morphometry of lateral radiographs of the spine was performed. Both height and armspan decreased significantly with age. The correlation between armspan and height was 0.83. Vertebral deformities were present in 32.7% of the women (grade I in 22.4% and grade II in 10.3%). Only the prevalence of grade II deformities rose with age. The variation of the difference between armspan and height in the groups with or without grade II vertebral deformities was comparable and relatively large (range >15 cm). The difference in mean values was small between those groups (1.6 cm) and could not differentiate between women with and without vertebral deformities. Our data show that the presence of vertebral deformities cannot be detected by the difference between armspan and height. Received: 24 December 1997 / Accepted: 20 May 1998     

Metacarpal Radiogrammetry by Computed Radiography in Postmenopausal Women with Colles' Fracture and Vertebral Crush Fracture Syndrome

Based on the hypothesis that the underlying osteoporotic mechanism of Colles' fracture in postmenopausal women is similar to that of other osteoporotic fractures, that is, cortical bone resorption as opposed to cancellous bone resorption, the rate of corticoendosteal bone loss was compared in 40 normal postmenopausal women [average age 68.4 ± 7.1 years; 20 ± 4 years since menopause (YSM)], in 35 postmenopausal women with Colles' fracture (age 69.4 ± 7.5 years, 22 ± 8 YSM), in 35 normal postmenopausal women with vertebral crush fracture (age 69.4 ± 7.5 years, 22 ± 8 YSM, and in 35 normal premenopausal women (age 36.1 ± 7.9 years). Radiogrammetry by digital radiography of the second metacarpal was used to measure external (ED) and internal (ID) diameter, cortical thickness (CCT), cortical area (CA), and the ratio of cortical area to total area (CA/TA). The ID values of the groups of postmenopausal women were subtracted from the ID value of the premenopausal women and the result was divided by YSM to obtain the rate of corticoendosteal resorption/year (ΔC), CA resorption year (ΔCA) and CA/TA resorption/year (ΔCA/TA). ID, ΔC, ΔCA, and ΔCA/TA all were larger in the postmenopausal women with Colles' and vertebral crush fractures than in the normal postmenopausal women (ANOVA: all P < 0.0001). ID, CCT, ΔC, CA, ΔCA, and ΔCA/TA did not differ between the two groups of postmenopausal women with fractures. ΔC was 87% greater in postmenopausal women with vertebral crush fracture and 116% greater in women with Colles' fracture than in normal postmenopausal women. These results indicate that the loss of cortical bone is an important factor in Colles' fracture in postmenopausal women. Received: 10 October 1996 / Accepted: 15 October 1997