D. Diacinti

Vertebral morphometry: current methods and recent advances

Vertebral fractures are the hallmark of osteoporosis and are associated with increased morbility and mortality. Because a majority of vertebral fractures often occur in absence of specific trauma and are asymptomatic, their identification is radiographic. The two most widely used methods to determine the severity of vertebral fractures are the visual semiquantitative (SQ) assessment and the morphometric quantitative approach, involving the measurements of vertebral body heights. The measurements may be made on conventional spinal radiographs (MRX: morphometric X-ray radiography) or on images obtained from dual X-ray absorptiometry (DXA) scans (MXA: morphometric X-ray absorptiometry).The availability of a rapid, low-dose method for assessment of vertebral fractures, using advanced fan-beam DXA devices, provides a practical method for integrated assessment of BMD and vertebral fracture status. The visual or morphometric assessment of lateral DXA spine images may have a potential role for use as a prescreening tool, excluding normal subjects prior to performing conventional radiographs.

Annual skeletal balance and metabolic bone marker changes in healthy early postmenopausal women: results of a prospective study

The aim of this study was to establish the duration and annual rate of menopause-related bone loss and to investigate the relationship between bone turnover and bone loss in early healthy postmenopausal women. The rate of change in bone mineral density (BMD) at the lumbar spine and in bone turnover was measured twice at the exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) and by the determination of plasma alkaline phosphatase levels (ALP) and fasting urinary hydroxyproline/creatinine ratio (OHPr/Cr), respectively, in 123 healthy premenopausal and postmenopausal women 45-60 years of age. The subjects were divided into nine groups according to their menstrual status and years since menopause (YSM). Annual bone loss at the lumbar spine of women who were menopausal for 1, 2, 3, 4, and 5 years was -2.62 +/- 0.37 (95% confidence interval -3.66, -1.58), -3.87 +/- 0.96 (-6.02, -1.73), -2.50 +/- 0. 37 (-3.29, -1.70), -2.86 +/- 0.73 (-4.44, -1.27), and -1.54 +/- 0.41 (-2.42, -0.66), respectively, and was significantly less than zero. But, the annual bone loss of women who were premenopausal or menopausal for 6, 7, and 8 years was -0.76 +/- 0.60 (-2.04, +0.53), -1.16 +/- 0.68 (-2.61, +0.29), 0.24 +/- 0.48 (-0.78, +1.26), and 0. 16 +/- 0.63 (-1.18, -1.49), respectively, and was not significantly different from zero. These results demonstrate that the early hormone-dependent bone loss commences in the first year after menopause and is arrested within 6 years after the onset of menopause. The overall bone loss for this phase is estimated to be approximately 15%. Annual change in ALP and OHPr/Cr seems to indicate that bone resorption prevails on bone formation in the first 2 YSM, whereas osteoblastic activity relatively prevails from YSM 3 to YSM 5, which explains the progressive repairing of the imbalance between bone resorption and formation.

Aging changes in vertebral morphometry

We analyzed the vertebral morphometry of healthy premenopausal women and their changes with age and menopause in order to better define the reference population for the clinical and epidemiological evaluation of vertebral fractures. Vertebral morphometry has been performed on lateral thoracic and lumbar spine films from 50 premenopausal and 76 postmenopausal normal women, age range 39–74 years. Vertebral heights and the anterior height/posterior height ratio are significantly lower in postmenopausal compared with premenopausal women. Vertebral anterior height decreases about 1.5 mm/year, whereas middle and posterior height decreases about 1.3 and 1.2/mm year, respectively. A statistically significant reduction of vertebral heights by around 1 mm/vertebra was observed in postmenopausal (n=16) compared with premenopausal women (n=20) of the same age (P<0.05). The results demonstrate that vertebral heights are lower with advancing age and menopause and that the vertebral heights difference in elderly people is not only the consequence of a cohort effect. The results also contribute to better defining the reference population to be chosen for evaluatin vertebral deformation.

Type II benign osteopetrosis (Albers-Schönberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations.

AbstractA 16-year-old male patient with type II autosomal dominant benign osteopetrosis (ADO) was genotyped and found to harbor a novel mutation in exon 25 of the gene encoding for the osteoclast-specific chloride channel, CLCN7, inherited from the father, who was asymptomatic. The patient had normal biochemical findings and acid-base balance, except for increased serum levels of creatine kinase, lactic dehydrogenase, and the bone formation markers bone alkaline phosphatase isoenzyme, osteocalcin and N-terminal type I collagen telopeptide/creatinine ratio. Unusual generalized osteosclerosis was observed together with a canonical increase in vertebral and pelvis bone mass. An affected first grade cousin presented with normal biochemical findings and a milder osteosclerotic pattern of the pelvis. At the cellular level, cultured osteoclasts from the patient showed increased motility, with lamellipodia, membrane ruffling and motile pattern of podosome distribution, all of which could have contributed to functional impairment of bone resorption. The present report documents a novel mutation of the CLCN7 gene causing osteopetrosis in a radiologically uncertain form of the diseases, with apparent incomplete penetrance.

A new predictive index for vertebral fractures: the sum of the anterior vertebral body heights.

UNLABELLED Evaluation of osteoporotic vertebral fracture risk is currently based on measurement of bone mineral density (BMD), but bone strength depends also on bone quality parameters. Aim of this study was to evaluate the validity of a new vertebral morphometric index, the Anterior Vertebral Heights sum (AHs) in discriminating women at high risk of vertebral fracture, comparing its diagnostic accuracy with that of BMD measured at lumbar spine (LS-BMD) and femoral neck (FN-BMD). MATERIALS AND METHODS A total of 163 Caucasian post-menopausal women (age range 46-74 years, mean age+/-SD=63.8+/-7.1 years), who did not present prevalent fractures at baseline evaluation, were observed at longitudinal follow-up. X-ray of the thoracic and lumbar spine, LS-BMD and FN-BMD measurements were obtained in all patients at baseline and repeated at the second follow-up visit 18-24 months later (mean 21+/-1.7 months). Radiographs of spine were analysed in order to identify vertebral fractures using a visual semiquantitative method (SQ) and vertebral morphometry as well as by calculating the AHs morphometric index. RESULTS During follow-up, 21/163 patients (12.9%) sustained a new vertebral fracture; 95.2% (20/21) of fractured patients but only 4.9% (7/142) of non-fractured women had reduced AHs values. As regarding BMD, 66.6% (14/21) and 61.9% (13/21) of women with incident fracture were osteoporotic at lumbar spine and femoral neck baseline evaluation , whereas among non-fractured women, 38% (54/142) at LS-BMD and 33.1% (47/142) at FN-BMD were osteoporotic . Analyses of Receiver Operating Characteristic (ROC) curves showed that AHs discriminated vertebral fractures almost perfectly (AUC 0.97; 95% CI 0.95-0.99). On the other hand, the AUC for LS-BMD was only 0.73 (95% CI 0.64-0.81) and for FN-BMD was 0.72 (95%CI 0.63-0.80), showing that the diagnostic accuracy of AHs was significantly higher compared to that of LS-BMD (p<0.001) or FN-BMD (p<0.001). A modified Poisson regression model for binary data was used to assess the independent role of AHs in predicting vertebral fracture. The effect of AHs remained statistically significant (p<0.001) after adjusting by FN-BMD, age, weight and body height. CONCLUSIONS Results of this study indicate the validity of this new morphometric index in evaluating the risk of osteoporotic vertebral fractures thus suggesting that AHs should be considered a valid parameter in clinical practice to assess the need for primary prevention of vertebral fractures.

Adverse events of computed tomography colonography: An Italian National Survey ☆

AIM To retrospectively study the frequency and magnitude of complications associated with computed tomography (CT) colonography in clinical practice. METHODS A questionnaire on complications of CT colonography was sent to Italian public radiology departments identified as practicing CT colonography with a reasonable level of training. The frequency of complications and possible risk factors were retrospectively determined. Responses were collated and row frequencies determined. A multivariate analysis of the factors causing adverse events was also performed. RESULTS 40,121 examinations were performed in13 centers during the study period. No deaths were reported. Bowel perforations occurred in 0.02% (7 exams). All perforations were asymptomatic and occurred in patients undergoing manual insufflation. Five perforations (71%) occurred in procedures performed following a recent colonoscopy. There was no significant difference between perforations associated with rectal balloon (0.017%) and those that were not (0.02%). Complications related to vasovagal reaction (either with or without spasmolytic) occurred in 0.16% (63 exams). All vasovagal reactions resolved in less than 3h, without any sequelae. CONCLUSIONS Perforation rate at CT colonography in Italy is comparable with elsewhere in the world, occurring regardless of the experience of radiology centers. Although the risk is very small, it may not be negligible when compared with the risk of diagnostic colonoscopy.

Vertebral morphometry by dual-energy X-ray absorptiometry (DXA) for osteoporotic vertebral fractures assessment (VFA)

PurposeThis study was done to evaluate the diagnostic accuracy of dual-energy X-ray absorptiometry (DXA) compared with conventional radiography for identifying vertebral fractures.Materials and methodsA total of 930 postmenopausal women underwent conventional radiography and DXA imaging of the spine. The images were evaluated by two expert skeletal radiologists using the semiquantitative (SQ) method for conventional radiography and the morphometric vertebral fracture assessment (VFA) for DXA.ResultsThe SQ method for radiography (SQ-Rx) analysed 99.1% of vertebrae, identifying 442 vertebral fractures; VFA analysed 97.5% vertebrae, detecting 420 vertebral fractures. Agreement between SQ-Rx and VFA reached 98.76%, and the κ-score was 0.96 [95% confidence interval (CI), 0.95–0.98]. Assessing the grading of vertebral fractures, agreement reached 97.5% and the κ-score was 0.841 (95% CI, 0.821–0.891). Considering SQ-Rx method as “gold standard”, VFA had a sensitivity of 97.85 % and a specificity of 99.81%. The negative (NPV) and positive (PPV) predictive value for VFA were 99.83 % and 98.15%, respectively. Fractures were identified in 251 (27 %) and 242 (26 %) of patients on SQ-Rx and VFA, respectively. On a per-patient basis, the agreement between the two methods was 97% and the κ-score was 0.95 (95% CI, 0.920–0.968). The diagnostic parameters for VFA were 97.23% sensitivity, 98.86% specificity, 97.60% PPV and 98.84% NPV.ConclusionsThis study demonstrated that VFA with DXA may reach a high level of accuracy for diagnosing vertebral fractures, suggesting that VFA should be introduced in the screening of individuals with a risk of osteoporosis and in the follow-up of osteoporotic patients receiving treatment.RiassuntoObiettivoScopo del presente lavoro è stato valutare l’accuratezza diagnostica della tecnica assorbimetrica a raggi X a doppia energia (DXA) a confronto con la radiologia convenzionale per la identificazione delle fratture vertebrali.Materiali e metodiNovecentotrenta donne in postmenopausa sono state sottoposte ad esame radiologico convenzionale e ad esame DXA del rachide. Le immagini sono state valutate da due radiologi esperti dello scheletro utilizzando rispettivamente il metodo semiquantitativo per l’esame radiologico (SQ-Rx) e la valutazione morfometrica vertebrale (VFA) per l’esame DXA.RisultatiIl metodo SQ-Rx ha analizzato il 99,1% delle vertebre, identificando 442 fratture vertebrali; VFA ha analizzato il 97,5% delle vertebre identificando 420 fratture vertebrali; la concordanza tra i due metodi è risultata pari al 98,76% con k-score di 0,96; [95% intervallo di confidenza (CI) 0,95–0,98]. Valutando il grado delle fratture vertebrali, la concordanza tra SQRx e VFA è risultata 97,5% con k-score 0,84 (95% CI 0,821–0,891). Considerando il metodo SQ-Rx come riferimento, la VFA aveva una sensibilità del 97,85% ed una specificità 99,81%. Il valore predittivo negativo (VPN) ed il valore predittivo positivo (VPP) erano 99,83% e 98,15%, rispettivamente. Duecentocinquantuno (27%) e 242 (26%) dei pazienti sono stati giudicati fratturati con il metodo SQ-Rx e con il metodo VFA, rispettivamente. Nella valutazione per paziente la concordanza tra le due tecniche era 97% (k-score: 0,948; 95% CI 0,920–0,968). I parametri diagnostici della VFA sono risultati: sensibilità 97,2%; specificità 98,9%; VPP 97,60%; VPN: 98,84%.ConclusioniQuesto studio dimostra che la VFA mediante la tecnica DXA può avere una elevata accuratezza per la diagnosi delle fratture vertebrali, suggerendone l’introduzione nello screening dei soggetti a rischio di osteoporosi e nel follow-up terapeutico di pazienti osteoporotici.

Relationship Between Spine Bone Mineral Density and Vertebral Body Heights

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

Vertebral morphometry by X-ray absorptiometry: Which reference data for vertebral heights?

INTRODUCTION The recent improvement in the resolution of dual-energy X-ray absorptiometry (DXA) images enables most vertebral levels to be seen adequately and thus DXA may be a worthwhile alternative to radiologic morphometry for the identification of vertebral fractures (VF). In this multicenter study, we have derived reference data for vertebral heights and their ratios in Italian women using morphometric X-ray absorptiometry (MXA). METHODS DXA scans were acquired in 1254 consecutive pre- and postmenopausal women, (mean age 63.7 ± 11.3, range 26-88 yrs), referred to six osteoporosis centers. MXA analysis of these images was performed by the same operator measuring vertebral heights and height ratios from L4 to T4. We calculated measures of central tendency and dispersion of vertebral heights and vertebral ratios using different approaches (mean and standard deviation as well as median and interquartile range of raw data, mean and standard deviation of trimmed data using an iterative algorithm, and mean and standard deviation of not fractured vertebrae). RESULTS Independently of the approach that we used, all the measures of central tendency were similar, while significant differences were found when compared with reference ranges in other populations. The vertebral heights of our sample at every vertebral level were significantly smaller than both Rea population and the Lunar reference values, even after normalization. Splitting data according to age groups, there was a decrease in the vertebral heights and ratios between the younger and older women. CONCLUSIONS This study demonstrates that reference data for MXA should be population specific and age matched.

Cyclical behavior of bone remodeling and bone loss in healthy women after menopause: results of a prospective study

Annual changes in lumbar bone mineral density (LBMD) and bone remodeling markers were measured in 238 healthy pre- and postmenopausal women, aged 45-74 years. The subjects were divided into groups according to their menstrual status and years since menopause. The results obtained indicate that bone loss is not a constant process over time but rather exhibits cyclical damping oscillations. When the log-linear trend of LBMD decrement was transformed into a constant by considering annual percentage changes, the presence of a cyclical component of 7 years was evident. By employing a harmonic regression model, the cyclical component was also statistically significant on baseline data. The cyclical behavior of LBMD decrement corresponded to an analogous behavior of the bone remodeling markers. These results suggest that a lack of estrogen acts as a synchronizer on bone remodeling by triggering a latent cyclical rhythm of bone loss that persists throughout life after menopause. The existence of a chronobiological rhythm of bone loss starting after menopause, if confirmed, could have important clinical implications.