Prevalence of non-fracture short vertebral height is similar in premenopausal and postmenopausal women: the osteoporosis and ultrasound study.

UNLABELLED: We observed similar prevalence of short vertebral height without endplate depression (SVH) in young women aged 20-39 years and older women aged 55-79 years. There was no association between SVH and low bone density. In older women, therefore, SVH may be largely long standing and not indicative of osteoporotic fracture. INTRODUCTION: Algorithm-based qualitative (ABQ) definition of osteoporotic vertebral fracture (VF) requires evidence of endplate fracture, and there is no minimum threshold for apparent 'reduction' in vertebral height. In older women, SVH without endplate fracture identified on baseline assessment may be long standing and unrelated to VF. If this is so, we would expect to see a similar prevalence of SVH in younger women. We aimed to compare the prevalence of pre- and postmenopausal women with SVH and the characteristics of women with and without SVH. METHODS: We used the ABQ method to classify baseline vertebral images (DXA-based imaging) from 257 premenopausal and 1,361 postmenopausal women participating in the population-based Osteoporosis and Ultrasound Study. Images were classified as follows: normal (no VF, no SVH), SVH (no VF) or VF (with/without SVH in unfractured vertebrae). We compared proportions of women with SVH (chi-squared test) and compared age, height, weight and bone mineral density (BMD) by ABQ classification (two-sample t test/analysis of variance). RESULTS: The prevalence of pre- and postmenopausal women with SVH was 37% and 33%, respectively (P>0.05). Compared to women without SVH, premenopausal women with SVH were older (P<0.001) and heavier (P=0.05), and postmenopausal women with SVH were taller (P<0.05), with higher spine BMD (P<0.01). Postmenopausal women with VF were older (P<0.001) and shorter (P<0.01) with lower BMD (P<0.001) than women without VF. CONCLUSIONS: Short vertebral height without endplate fracture is equally prevalent in pre- and postmenopausal women and not associated with low bone density.

Association between incident and baseline vertebral fractures in European women: vertebral fracture assessment in the Osteoporosis and Ultrasound Study (OPUS).

UNLABELLED: Vertebral fracture assessment (VFA) with densitometric devices uses less radiation than spinal radiography. We assessed risk of new vertebral fracture (VF) in women with baseline fracture identified on VFA using algorithm-based qualitative diagnosis. Women with VF had significantly greater risk of VF after 6 years compared to those without baseline fracture. INTRODUCTION: Prevalent VFs predict future fracture and are identifiable on vertebral fracture assessment (VFA) using bone densitometry devices. We have previously performed cross-sectional, but not longitudinal, VFA using the algorithm-based qualitative method (ABQ). We aimed to examine the prevalence and incidence of VF and test the association between prevalent and incident VF identified by ABQ VFA. METHODS: We used ABQ to assess vertebral images obtained at baseline and 6 years (Hologic devices) in 674 women at ages 39 to 80 years participating in the Osteoporosis and Ultrasound Study. Criteria for prevalent and incident VF were endplate fracture, with/without cortical fracture. We compared proportions (chi-squared test) and characteristics (two-sample t tests and analysis of variance) of women with and without VF and calculated odds ratios for incident VF in women with prevalent VF (logistic regression). RESULTS: Prevalent VF was identified in one premenopausal woman and 41 postmenopausal women. Incident VF was identified in 18 postmenopausal women. Odds ratios (95% CI) for incident VF in postmenopausal women with prevalent VF were 7.8 (2.8, 22.1) (unadjusted) and 4.3 (1.4, 13.7) (adjusted for age and bone mineral density, BMD). Women with prevalent or incident VF were older (P < 0.01), with lower hip BMD (P < 0.001) compared to women without VF. CONCLUSIONS: Population-based postmenopausal women had relatively low prevalence and incidence of VF analysed with the ABQ method applied to VFA. Women with prevalent fracture had a significantly greater risk of incident VF than women without prevalent fracture.

Effects of calcium-fortified ice cream on markers of bone health.

UNLABELLED: Premenopausal women with low calcium intakes consumed calcium-fortified ice cream daily for 28 days. Bone markers, NTX, CTX and PTH decreased significantly by 7 days, with some evidence of a calcium dose-dependent effect. Bone marker responses were observed within 1 h of consuming ice cream. Body weight remained constant over 28 days. INTRODUCTION: Dietary calcium is important for lifelong bone health. Milk is a good source of bioavailable calcium, but consumption has declined among young adults. The aims were to determine whether calcium-fortified ice cream, a palatable source of calcium, produces significant, sustainable changes in bone turnover markers and parathyroid hormone (PTH) in premenopausal women with calcium intake below recommended UK levels. METHODS: Eighty women, ages 20-39 years (calcium intake <750 mg/day) were randomised to consume lower saturated fat/sugar ice cream containing 96, 244, 459 or 676 mg calcium daily for 28 days. Urinary NTX/Cr, serum CTX, PINP, 1,25D and PTH were measured (baseline, days 1, 7 and 28). Acute changes in CTX and PTH were measured over 5 h (n = 29 women). RESULTS: There were significant mean decreases by 7 days in NTX/Cr, CTX, PTH and 1,25D and increases in PINP (one sample t tests), with a significant dose-dependent effect on CTX analysis of covariance. Only CTX remained suppressed at 28 days. Serum CTX and PTH decreased within 1 h. Body weight did not change significantly between baseline and 28 days. CONCLUSIONS: Daily consumption of calcium-fortified ice cream by premenopausal women may significantly reduce levels of the bone resorption marker serum CTX, without stimulating weight gain. The ice cream could be incorporated into the diet to replace low-calcium snacks and thus help individuals with habitually low calcium intakes to meet recommended intakes. The 244 mg calcium preparation would provide more than a quarter of the UK daily recommended nutrient intake for premenopausal women.

Is short vertebral height always an osteoporotic fracture? The Osteoporosis and Ultrasound Study (OPUS).

INTRODUCTION AND HYPOTHESIS: Diagnosis of prevalent osteoporotic vertebral fracture is complicated by normal or developmental variation in vertebral shape or size and non-osteoporotic deformities that appear to have 'reduced' height. Using our visual approach, the algorithm-based qualitative method (ABQ) a vertebra with apparent "reduced" height without evidence of osteoporotic endplate depression is classified as non-osteoporotic short vertebral height (SVH). We aimed to determine whether ABQ classification of SVH represents true or false negative diagnosis of osteoporotic vertebral fracture, by testing the associations with clinical outcomes of osteoporosis or vertebral fracture. METHODS: The ABQ method was used to assess spinal radiographs acquired at baseline for a subset of 904 postmenopausal women participating in the Osteoporosis and Ultrasound Study (OPUS). The sample was enriched with vertebral fracture cases. Subjects were categorized by ABQ diagnosis as (i) normal, (ii) non-osteoporotic short vertebral height (SVH) or (iii) osteoporotic vertebral fracture. RESULTS: Women were classified by ABQ as follows: osteoporotic vertebral fracture, n=231; SVH, n=376 and normal, n=297. Women with vertebral fracture were older, with lower height, weight and height loss than those classified as SVH or normal. Women with SVH were heavier and older, with greater historical height loss than normal women. Age-adjusted SD units (z-scores) for BMD were lower than expected among women with osteoporotic vertebral fracture, but not among those with SVH. There was a significant association between diagnosis of osteoporotic vertebral fracture and history of low-trauma non-vertebral and vertebral fracture (p<0.001, odds ratios=3.2 and 20.6, respectively). There was also an association between diagnosis of SVH and previous low-trauma non-vertebral fracture (p<0.05, odds ratio=1.7). CONCLUSIONS: Short vertebral height without evidence of central endplate fracture in postmenopausal women is largely unrelated to osteoporosis. Quantitative morphometry should not be used alone for the assessment of vertebral fracture in clinical decision making: we recommend differential diagnosis of morphometric vertebral deformities by an expert reader to rule out non-osteoporotic deformities with short vertebral height.

Standardised quantitative morphometry: a modified approach for quantitative identification of prevalent vertebral deformities.

UNLABELLED: Our approach for the quantitative identification of vertebral deformity (standardised quantitative morphometry, SQM) reduces problems associated with obtaining reference intervals from populations with high prevalence of fracture. In women with osteoporosis, agreement with radiological diagnosis (surrogate gold standard) was better for SQM than QM using the Eastell-Melton method. INTRODUCTION: Use of reference intervals for quantitative vertebral morphometry (QM) derived by statistical trimming can be problematic in reference populations with high prevalence of deformity. We have developed a modified approach known as standardised quantitative morphometry (SQM), whereby vertebral height is standardised to eliminate variation between individuals. The aims of this study were to compare SQM to QM (Eastell-Melton method) for identification of prevalent vertebral deformities, using qualitative radiological diagnosis as the gold standard, and automate the process. METHODS: Our study populations were a clinic-based sample of 80 women ages 48 to 87 years with a high prevalence of vertebral deformity and a general practice (GP)-based sample of 372 women ages 50 to 85 years. Agreement with the gold standard was tested for SQM and QM. RESULTS: Agreement was better for SQM (kappa = 0.80) than for QM (kappa = 0.14) in the clinic sample using clinic-based reference data. The agreement was improved for QM using the GP-based reference data, kappa = 0.63. In the GP population, agreement was good for both SQM and QM (kappa = 0.59 and 0.54 respectively). CONCLUSIONS: In our population with a high prevalence of vertebral fracture, SQM performs better than the Eastell-Melton method.

Identification of vertebral fractures: an update.

Osteoporotic vertebral fracture is associated with increased morbidity and mortality. As a powerful predictor of future fracture risk, the identification of vertebral fracture helps target individuals who will benefit from anti-fracture therapy. The identification of vertebral fractures is problematic because (1) "normal" radiological appearances in the spine vary greatly both among and within individuals; (2) "normal" vertebrae may exhibit misleading radiological appearances due to radiographic projection error; and (3) "abnormal" appearances due to non-fracture deformities and normal variants are common, but can be difficult to differentiate from true vertebral fracture. Various methods of vertebral fracture definition have been proposed, but there is no agreed gold standard. Quantitative methods of vertebral fracture definition are objective and reproducible, but the major limitation of these methods is their inability to differentiate between vertebral deformity and vertebral fracture. The qualitative visual approach draws on the expertise of the reader, but it is a subjective method with poor interobserver agreement. Semiquantitative assessment of vertebral fracture is a standardized visual method, which is commonly applied in research studies as a surrogate gold standard. This method is more objective and reproducible than a purely qualitative approach, but can be difficult to apply. The established methods focus primarily on the identification of "reduced" or short vertebral height as an indication of vertebral fracture, but this is also a feature of some non-fracture deformities and normal variants. A modified visual approach known as algorithm-based qualitative assessment of vertebral fracture (ABQ) has recently been introduced, and this focuses on radiological evidence of change at the vertebral endplate as the primary indicator of fracture. Preliminary testing of the ABQ method has produced promising results, but the method requires further evaluation. Vertebral imaging by means of dual energy X-ray absorptiometry (DXA) scanner produces images of near-radiographic quality at a fraction of the radiation dose incurred by conventional radiography. There is growing interest in vertebral fracture assessment using this technique as a means of assessing a patient's fracture risk. Given the increasing availability of new technology and the importance of accurate diagnosis of vertebral fracture, there is an urgent need for better awareness of and training in the definition of vertebral fracture. Methods of vertebral fracture definition should be validated by testing the association with clinical outcomes of vertebral fracture, in particular the prediction of incident fractures.

Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis.

The identification of vertebral fracture in osteoporosis is based mainly on the identification of abnormal variation in vertebral shape, but this can be misleading in the presence of a non-fracture deformity or normal variant of vertebral shape. Qualitative identification of vertebral fracture (Qual) is influenced by the subjectivity of the approach, and although more objective, the semiquantitative method (SQ) can be difficult to apply. In addition, there has been little independent evaluation of SQ in relation to other approaches. We aimed to evaluate a new algorithm-based approach for the qualitative identification of vertebral fracture (ABQ) and to compare it with SQ and Qual. Two radiologists reported spinal radiographs for 372 postmenopausal women using Qual (reader 1), and SQ and ABQ (reader 2). Non-fracture deformities and normal variants were also reported using Qual and ABQ. The prevalence of vertebral fracture by subjects was higher for SQ (24%) than for Qual (11%) and ABQ (7%). Agreement was poor between SQ and the other methods, and moderate between Qual and ABQ. Twenty-two women with vertebral fracture were agreed by all three methods, similar to the total identified by ABQ (25 women). Seventeen women diagnosed with fracture by Qual, had non-fracture deformity or normal variant (but no fracture) according to ABQ. Of the women with SQ fractures, 53% and 70% were identified negative for fracture but positive for non-fracture deformity or normal variant by ABQ and Qual. The main sources of discrepancy between SQ and the other methods were Scheuermann's disease, normal variation, and degenerative change accompanied by short anterior vertebral height. For all methods, bone mineral density (BMD) and BMD Z-scores were lower in women with vertebral fractures than in those with no fractures. Bone mineral density and BMD Z-scores were also lower at the lumbar spine and total body in women with vertebral fractures according to Qual and ABQ than they were for SQ, and were lower in women with SQ fractures agreed by Qual and ABQ, compared with those diagnosed negative for fracture by Qual and ABQ (p<0.01). We conclude that poor agreement between methods arises mainly from difficulties in differentiating true fracture from non-fracture deformity. Our new approach attempts to address this problem but requires further testing in a larger study population.

Visual identification of vertebral fractures in osteoporosis using morphometric X-ray absorptiometry.

Visual identification of vertebral fractures from spinal radiographs (visual XR) makes use of the reader's expertise in ruling out non-fracture deformities or normal variants. Scan images of the spine acquired by DXA may be analyzed quantitatively (morphometric X-ray absorptiometry [quantitative MXA]) or visually (visual MXA). The aims of this study were to compare visual and quantitative MXA with visual XR for the identification of vertebral fractures. Spinal radiographs and MXA scans were acquired at baseline and 1 year in 70 women referred with osteoporosis. These were assessed visually by two expert readers (observer A, a radiologist; observer B, a physician with expertise in osteoporosis) for evidence of prevalent and incident vertebral fractures. Observer C (a radiographer with expertise in vertebral morphometry) performed visual and quantitative assessments of the MXA scans. Visual assessment of spinal radiographs by observer A was used as the gold standard for comparison of methods. Sensitivity for the identification of prevalent fractures by MXA was best for visual MXA by observer A (92%), whereas quantitative MXA had the lowest sensitivity (82%). Specificity was >90% for both visual and quantitative MXA. Kappa scores for agreement for identification of prevalent fractures between visual XR (observer A) and visual MXA (all three observers), and between visual XR and visual MXA performed by reader B were similar (kappa = 0.85-0.87). Agreement with visual XR performed by observer A was slightly lower for quantitative MXA (kappa = 0.77). Interobserver agreement between the two expert readers (observers A and B) was the same for both visual XR and visual MXA (kappa = 0.86). Seven incident vertebral fractures were identified in four patients at follow-up. All four patients were identified by visual MXA, and three patients were identified by quantitative MXA. Observers A and B identified all seven incident fractures by visual MXA, and observer C missed one fracture that was also missed by quantitative MXA. An incident fracture of vertebra T6 was excluded from analysis by quantitative MXA because of poor image quality. We conclude that visual identification of vertebral fractures from MXA scans is superior to quantitative assessment. Used as a screening tool for conventional radiography, this approach could help reduce the radiation dose to the patient in the diagnosis and monitoring of osteoporosis.

Longitudinal evaluation of morphometric X-ray absorptiometry for the identification of vertebral deformities.

Morphometric X-ray absorptiometry (MXA) has not been evaluated for the identification of incident vertebral deformities. The reliability of longitudinal measurements in quantitative vertebral morphometry is influenced by the precision of the technique. Long-term precision in vitro (weekly MXA phantom scans) assessed by retrospective cumulative sum (Cusum) analysis, detected one event during a 6-month period when the measurement process was 'out of control'. Inspection of service records revealed that repair work was performed around this timepoint. The coefficient of variation (CV) for long-term precision (vertebral heights) in a population-based sample of postmenopausal women ages 56 to 83, mean 65+/-6 years (n = 48), was 4.0% for morphometric radiography (MRX), 2.9% for MXA using the compare facility for analysis of serial scans, and 3.2% when 'compare' was not used. In women with osteoporosis ages 49 to 87, mean 67+/-9 years (n = 50). the CV was 5.0% for MRX, 4.1% for MXA using 'compare' and 8.5% without 'compare'. Precision errors for height ratios (MRX and MXA) were greater than for vertebral heights. Incident deformities were identified by MRX and MXA in the women with osteoporosis, using point prevalence, 20% minimum reduction in vertebral height, and percent least significant change (LSC) in vertebral heights and height ratios. Semiquantitative analysis of radiographs by a radiologist (Genant method) was used as the gold standard. The results were similar for MRX and MXA, and all morphometric criteria identified a similar proportion of true incident deformities, although the false positive rate was generally greater for the height ratio approaches. MXA has good long-term precision and is comparable to MRX for the identification of incident deformities when scans are analyzed with the compare facility.

Short-term precision for morphometric X-ray absorptiometry.

Morphometric X-ray absorptiometry (MXA) is a low-radiation technique used for the identification of vertebral deformities. The reliability of MXA measurements is dependent on the precision of the technique, and this is influenced by system error, variability associated with morphometric analysis, and variability within study populations. Short-term precision in vivo affects the identification of prevalent deformities, and may vary according to the age and health status of the study population. The aims of this study were to measure short-term precision in vitro and in vivo for MXA, and to compare intraoperator variability for repeat marking of radiographs in morphometric radiography (MRX) and scan images in MXA. For short-term precision in vitro (based on 30 consecutive MXA phantom scans), the coefficient of variation (CV) was approximately 1%. Intraoperator variability for repeat marking of baseline radiographs and MXA scans (marked without the compare facility) in a population-based group of 32 postmenopausal women, was significantly lower for MRX (CV for vertebral heights = 1.5%) than for MXA (CV = 2.9%). The CV for duplicate same-day MXA scans performed in subjects with osteoporosis (n = 20) was 2.2% for vertebral heights between T8 and L4 using the compare facility, and 4.8% when scans were analyzed without the compare facility. We conclude that short-term precision for MXA is good for vertebrae T8 to L4, but the technique is limited due to poor image resolution in the upper thoracic vertebrae. Intraoperator variability for repeat marking was lower for MRX, but the error associated with marking MXA scans remained below the minimum change required for identification of a vertebral deformity.

Vertebral wedge angle measured by morphometric X-ray absorptiometry.

Vertebral wedge angle is greater in older men than in women of similar age, and increases with age in men. Wedge angle may depend less on bone size than other methods (for example, height ratios), and thus could be more effective at identifying wedge deformities. We aimed to compare mean wedge angle measured by morphometric X-ray absorptiometry (MXA) in young men and women, to assess the effect of age on wedge angle in women, and to compare wedge angle and anterior-posterior (ha/hp) height ratios for the identification of vertebral deformities. Mean wedge angle was similar in normal men (n = 46) and women (n = 106) ages 22-50 years, and did not change significantly with age in normal women ages 22-83 years (n = 222). MXA reference intervals for ha/hp ratios (trimmed mean minus 3.0 SD) and wedge angle (trimmed mean +/- 3.0, 2.5 and 2.0 SD) were used to identify vertebral wedge deformities in 83 women with osteoporosis, ages 49-87 years. For agreement with semiquantitative assessment of radiographs (SQ), kappa (kappa) = 0.76 for wedge angle mean plus 2.0 SD, and 0.74 for ha/hp height ratio mean minus 3.0 SD. Sensitivity was marginally better for wedge angle plus 2.0 SD than for ha/hp when all SQ grades of deformity were included, but there was no difference between methods for detection of moderate to severe deformities (grades 2 to 3). Diagnostic values for the two approaches were broadly similar. The results of this analysis do not provide strong evidence for the preferential use of the wedge angle approach.

Identification of vertebral deformities in women: comparison of radiological assessment and quantitative morphometry using morphometric radiography and morphometric X-ray absorptiometry.

Our aim was to compare normal vertebral reference values for morphometric radiography (MRX) and morphometric X-ray absorptiometry (MXA) and to compare these methods for the identification of vertebral deformities. We calculated MXA reference values (Hologic QDR 4500 A) for 327 women (ages 22-88 years) randomly selected from local General Practice lists in Sheffield, U.K. MRX reference values were calculated from spinal radiographs for 123 of these subjects (ages 56-88 years). We used these reference values to identify deformities in the MRX and MXA reference populations and in 83 women with osteoporosis (ages 49-87 years). We observed differences in mean deformity of vertebral height ratios measured by MRX and MXA, especially for the mid-to-posterior ratio. We compared agreement between quantitative methods (MRX and MXA) and qualitative radiological assessment. Severity of deformity was defined by semiquantitative (SQ) assessment. Agreement was moderate for MRX (k = 0.59; 95% CI = 0.43-0.77) and for MXA (k = 0.47; 95% CI = 0.29-0.66) in the reference population. Agreement was good for MRX (k = 0.86; 95% CI = 0.82-0.89) and MXA (k = 0.71; 95% CI = 0.66-0.75) in the osteoporotic population. MRX and MXA correctly identified a greater proportion of moderate or severe deformities compared with mild deformities. Sensitivity, specificity, predictive values, and accuracy were slightly better for MRX than for MXA. Although MXA agrees well with qualitative radiological assessment, the large proportion of vertebrae excluded from analysis because of poor image quality limits the diagnostic value of the technique. Reference intervals should be technique specific.

Identification of vertebral deformities in men: comparison of morphometric radiography and morphometric X-ray absorptiometry.

Osteoporotic vertebral deformities may be detected by morphometric radiography (MR) using spinal radiographs, and by morphometric X-ray absorptiometry (MXA) using dual-energy X-ray absorptiometry. Reference values for MR may not be appropriate for MXA, and reference values may be affected by gender and age. The aims of this study were to (1) compare mean deformity of vertebral height ratios for MR and MXA in men, (2) compare mean deformity for MXA in men and women, (3) compare mean wedge angle measured by MXA in men and women and (4) assess the effect of aging on MXA values in men. We studied a general practitioner sample of 115 men aged 22-81 years (mean 53 years) and 124 women aged 55-89 years (mean 68 years). Subjects had MXA of T4 to L4 using the Hologic QDR 4500A. Women and men over age 50 years had radiographs of the thoraco-lumbar spine. Scans and radiographs were marked in the same way by one operator and vertebral height ratios and mean deformity were calculated for MR and MXA. The mean wedge angle, θ, was calculated for MXA in all subjects. Mean wedge and biconcavity deformity and standard deviation (SD) in men were greater for MXA than for MR. The mean wedge and biconcavity deformity measured by MXA tended to be greater for men than for women. Vertebral deformity in men increased with age, and was associated with degenerative change seen on spinal radiographs. The mean wedge angle was greater for men than for women, and it increased with age in men. We conclude that sex- and age-specific reference ranges should be established separately for MXA.

Gastrointestinal transit in hyperthyroid patients before and after propranolol treatment.

Mean mouth to cecum transit time determined by the hydrogen breath test after oral lactulose in a group of 10 hyperthyroid patients (nine with regular bowel habit and one with diarrhea) was significantly lower than that observed in 10 euthyroid controls [53 min (SD 15) versus 123 min (SD 12.2), p less than 0.01]. After 5 days of propranolol treatment the patients showed a significant reduction of the heart rate but no modification of transit time [51 min (SD 7.3)].