Osteoporosis: Adams JE

Engelke K, Adams JE, Armbrecht G, Augat P, Bogado CE, Bouxsein ML, Felsenberg D, Ito M, Prevrhal S, Hans DB, Lewiecki EM. · Institute of Medical Physics, University of Erlangen, Germany; Synarc, Hamburg, Germany. <> · J Clin Densitom. · Pubmed #18442757 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) has developed Official Positions for the clinical use of dual-energy X-ray absorptiometry (DXA) and non-DXA technologies. While only DXA can be used for diagnostic classification according to criteria established by the World Health Organization, DXA and some other technologies may predict fracture risk and be used to monitor skeletal changes over time. ISCD task forces reviewed the evidence for clinical applications of non-DXA techniques and presented reports with recommendations at the 2007 ISCD Position Development Conference. Here we present the ISCD Official Positions for quantitative computed tomography (QCT) and peripheral QCT (pQCT), with supporting medical evidence, rationale, controversy, and suggestions for further study. QCT is available for bone mineral density measurements at the spine, hip, forearm, and tibia. The ISCD Official Positions presented here focus on QCT of the spine and pQCT of the forearm. Measurements at the hip may have clinical relevance, as this is an important fracture site; however, due to limited medical evidence, definitive advice on its use in clinical practice cannot be provided until more data emerge.

Guglielmi G, Diacinti D, van Kuijk C, Aparisi F, Krestan C, Adams JE, Link TM. · Department of Radiology, University of Foggia, Viale Luigi Pinto, 1, 71100 Foggia, Italy. · Eur Radiol. · Pubmed #18351350 No free full text.

Abstract: 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.

Link TM, Guglielmi G, van Kuijk C, Adams JE. · Department of Radiology, University of California, San Francisco, 400 Parnassus Ave., A 367, P.O. Box 0628, San Francisco, CA, 94143-0628, USA. · Eur Radiol. · Pubmed #15841380 No free full text.

Abstract: As populations age osteoporosis becomes an increasingly important public health issue. Among osteoporotic fractures vertebral fractures are of particular relevance: they are the most common fractures, frequently are asymptomatic but have an important influence on prognosis and morbidity in the osteoporotic patient. Previous studies have suggested that these fractures are frequently not diagnosed and that radiologists miss a high percentage of osteoporotic, vertebral fractures present on lateral chest radiographs. The aims of this review are (1) to emphasize the important role that radiologists play in the accurate and clear reporting of vertebral fractures, (2) to provide guidance in assessing these fractures in radiographs, MRI and computed tomography imaging of the vertebral spine and (3) to sensitize the radiologist in diagnosing fractures in chest radiographs.

Adams JE. · Imaging Science and Biomedical Engineering, University of Manchester, England. · Semin Dial. · Pubmed #12356010 No free full text.

Abstract: The bone disease associated with end-stage renal failure (ESRD) and treatment are complex and multifactorial, and has changed in both clinical and imaging features over the past three decades. Whereas previously features of vitamin D deficiency (rickets/osteomalacia) and intense, and prolonged, secondary hyperparathyroidism (bone resorption, osteosclerosis, metastatic calcification) predominated, these features are now rarely evident radiologically. This has occurred through the better understanding of vitamin D metabolism and improvements in therapeutic management. However, metastatic calcification in soft tissues and 'adynamic" bone continue to be problematic. New complications have developed as a consequence of treatment (dialysis and transplantation), including amyloid deposition, noninfective sponyloarthropathy, osteonecrosis, and osteopenia/osteoporosis). Radiographs remain the most widely used imaging technique in examining for skeletal disease in patients with ESRD on maintenance dialysis. Occasionally, more sophisticated imaging (CT, MRI, nuclear medicine scanning) are helpful (parathyroid tumor localization, differentiation between infection and amyloid deposition). Developments in quantitative methods to assess bone density enable the effects of ESRD and treatment to be studied and monitored. Technical developments in computed tomography (rapid, multislice scanning) allow quantitation and monitoring of metastatic cardiac calcification in patients on hemodialysis, which has relevance to prognosis.

Adams JE. · Clinical Radiology, Imaging Science and Biomedical Engineering, University of Manchester, United Kingdom. · Kidney Int Suppl. · Pubmed #10633462 No free full text.

Abstract: The bone disease associated with chronic renal impairment is complex and multifactorial, and has changed over past decades. Whereas originally features of vitamin D deficiency (rickets/osteomalacia) and secondary hyperparathroidism (erosions, osteosclerosis, brown cysts) predominated, improvement in management and therapy have resulted in such readiographic features being present in a minority of patients. Metastatic calcification and "adynamic" bone develop as a complication of disease (phosphate retention) and treatment (phosphate binders). New complications (amyloid deposition, noninfective spondyloarthropathy, osteonecrosis) are now seen complicating long-term hemodialysis and/or renal transplantation. Radiographs remain the most important imaging technique, but occasionally other imaging and quantitative techniques (CT, MRI, bone densitometry) are relevant to diagnosis and management.

Link TM, Majumdar S, Grampp S, Guglielmi G, van Kuijk C, Imhof H, Glueer C, Adams JE. · Department of Clinical Radiology, University of Muenster, D-48129 Muenster, Germany. · Eur Radiol. · Pubmed #10602950 No free full text.

Abstract: Osteoporosis is a metabolic bone disorder that is characterized by reduced bone mass and a deterioration of bone structure which results in an increased fracture risk. Since the disease is preventable, diagnostic techniques are of major importance. Standard techniques determine bone mineral density, whereas some of the newer techniques focus on trabecular structure. This article reviews structure analysis techniques in the diagnosis of osteoporosis. Imaging techniques applied to the assessment of trabecular bone structure include conventional radiography, magnification radiography, high-resolution CT (HRCT) and high-resolution MR imaging (HRMRI). The best results were obtained using high-resolution tomographic techniques. The highest spatial resolutions in vivo were achieved using HRMRI. The most common texture analysis techniques that have been used are morphological parameters (analogous to bone histomorphometry). Fractal dimension, co-occurrence matrices, mathematical filter techniques and autocorrelation functions are more complex techniques. Most of the studies evaluating structure analysis show that texture parameters and bone mineral density both predict bone strength and osteoporotic fractures, and that combining both techniques yields the best results in the diagnosis of osteoporosis.

Caulton JM, Ward KA, Alsop CW, Dunn G, Adams JE, Mughal MZ. · The Manchester School of Physiotherapy, Manchester Royal Infirmary, Manchester, UK. · Arch Dis Child. · Pubmed #14736627 links to  free full text

Abstract: BACKGROUND: Severely disabled children with cerebral palsy (CP) are prone to low trauma fractures, which are associated with reduced bone mineral density. AIMS: To determine whether participation in 50% longer periods of standing (in either upright or semi-prone standing frames) would lead to an increase in the vertebral and proximal tibial volumetric trabecular bone mineral density (vTBMD) of non-ambulant children with CP. METHODS: A heterogeneous group of 26 pre-pubertal children with CP (14 boys, 12 girls; age 4.3-10.8 years) participated in this randomised controlled trial. Subjects were matched into pairs using baseline vertebral vTBMD standard deviation scores. Children within the pairs were randomly allocated to either intervention (50% increase in the regular standing duration) or control (no increase in the regular standing duration) groups. Pre- and post-trial vertebral and proximal tibial vTBMD was measured by quantitative computed tomography (QCT). RESULTS: The median standing duration was 80.5% (9.5-102%) and 140.6% (108.7-152.2%) of the baseline standing duration in the control group and intervention group respectively. The mean vertebral vTBMD in the intervention group showed an increase of 8.16 mg/cm3 representing a 6% mean increase in vertebral vTBMD. No change was observed in the mean proximal tibial vTBMD. CONCLUSION: A longer period of standing in non-ambulant children with CP improves vertebral but not proximal tibial vTBMD. Such an intervention might reduce the risk of vertebral fractures but is unlikely to reduce the risk of lower limb fractures in children with CP.

Nackaerts O, Horner K, Jacobs R, Karayianni K, Mitsea A, Berkas L, Mastoris M, Lindh C, van der Stelt PF, Marjanovic E, Adams JE, Pavitt S, Devlin H. · Oral Imaging Centre, Katholieke Universiteit Leuven, Leuven, Belgium. · Eur J Oral Sci. · Pubmed #19196312 No free full text.

Abstract: The aim of this study was to determine whether alcohol consumption would predict mandibular bone quality and quantity in a large European female population. In total, 672 middle-aged and elderly women (45-70 yr of age; standard deviation = 6) were recruited in the study. Alcohol consumption was recorded through a self-reported questionnaire. Mandibular cortical width was measured, by five observers, in the mental foramen region on panoramic radiographs. Mandibular bone density, expressed as aluminium thickness, was recorded on intra-oral radiographs. Alcohol consumption was associated with a reduction of mandibular bone density and cortical width. This association was higher in subjects with excessive alcohol consumption, defined in the present study as > 14 units consumed per week. This study showed reduced jaw-bone quality in older individuals and in those with increased alcohol consumption.

Geraets WG, Verheij JG, van der Stelt PF, Horner K, Lindh C, Nicopoulou-Karayianni K, Jacobs R, Marjanovic EJ, Adams JE, Devlin H. · Department of Oral and Maxillofacial Radiology, Academic Centre for Dentistry Amsterdam, Louwesweg 1, 1066 EA Amsterdam, The Netherlands. · Dentomaxillofac Radiol. · Pubmed #18812598 No free full text.

Abstract: OBJECTIVES: A previous study showed that the trabecular pattern on dental radiographs correlates with femoral and spinal bone mineral density (BMD). The objective of this study was to determine if the correlation is affected by the size and location of the region of interest (ROI). METHODS: In a European research project on osteoporosis, BMD was measured at the left hip and the lumbar spine of 525 women. From all subjects, intraoral radiographs were made of the premolar region in the upper and lower jaws. Two ROIs were indicated manually on each scanned image. The smallest region involved only trabecular bone and the largest also included parts of the neighbouring teeth. The ROIs were subjected to automatic image analysis, yielding 26 measurements per ROI. Stepwise linear regression was used to predict femoral and spinal BMD. RESULTS: Inner and outer regions predicted BMD equally well. The radiographs of lower and upper jaw also predicted BMD equally well. Combining inner and outer regions did not improve the prediction of femoral and spinal BMD, but combining lower and upper jaws did. CONCLUSIONS: This study shows that it is possible to include parts of neighbouring teeth in the ROI used to assess the trabecular pattern and predict BMD. This simplifies the process of selecting the ROIs because no efforts have to be made to exclude neighbouring teeth. Combining ROIs of lower and upper jaws significantly improves the prediction of BMD.

Nackaerts O, Jacobs R, Devlin H, Pavitt S, Bleyen E, Yan B, Borghs H, Lindh C, Karayianni K, van der Stelt P, Marjanovic E, Adams JE, Horner K. · Oral Imaging Center, Department of Dentistry, Faculty of Medicine, KU Leuven, Belgium. · Dentomaxillofac Radiol. · Pubmed #18606750 No free full text.

Abstract: OBJECTIVES: To determine the diagnostic accuracy of mandibular and maxillary bone density in detecting osteoporosis using receiver operating characteristic (ROC) analysis. METHODS: 671 women between 45 years and 70 years of age underwent dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine. This was the gold standard for diagnosing osteoporosis. Intraoral radiography of the upper and lower right premolar region was performed, using an aluminium wedge as a densitometric reference. Jaw bone density was determined using dedicated software. Observer differences and ROC curves were analysed. RESULTS: For detecting osteoporosis using jaw bone density, the area under the ROC curve (A(z)) was 0.705. For separate analysis of mandibular and maxillary films, sensitivity varied from 33.9% to 38.7% and specificity from 83.5% to 85.3% when using a threshold of 4.3 mm Al equivalent. CONCLUSIONS: Density of the premolar region reaches a fair diagnostic accuracy, which might improve when including additional factors in the analysis and refining the densitometric tool.

Williams AL, Al-Busaidi A, Sparrow PJ, Adams JE, Whitehouse RW. · Department of Radiology, Manchester Royal Infirmary, Oxford Road, Manchester, UK. · Eur J Radiol. · Pubmed #17913429 No free full text.

Abstract: PURPOSE: Osteoporotic vertebral fractures are frequently asymptomatic. They are often not diagnosed clinically or radiologically. Despite this, prevalent osteoporotic vertebral fractures predict future osteoporotic fractures and are associated with increased mortality and morbidity. Appropriate management of osteoporosis can reduce future fracture risk. Fractures on lateral chest radiographs taken for other conditions are frequently overlooked by radiologists. Our aim was to assess the value of computed tomography (CT) in the diagnosis of vertebral fracture and identify the frequency with which significant fractures are missed. MATERIALS AND METHODS: The thoracic CT scans of 100 consecutive male and 100 consecutive female patients over 55 years were reviewed. CT images were acquired on General Electric Lightspeed multi-detector (MD) CT scanners (16 or 32 row) using 1.25mm slice thickness. Midline sagittal images were reconstructed from the 3D volume images. The presence of moderate (25-40% height loss) or severe (>40% height loss) vertebral fractures between T1 and L1 was determined using an established semi-quantitative method and confirmed by morphological measurement. Results were compared with the formal CT report. RESULTS: Scans of 192 patients were analysed (95 female; 97 male); mean age 70.1 years. Thirty-eight (19.8%) patients had one or more moderate to severe vertebral fractures. Only 5 (13%) were correctly reported as having osteoporotic fractures in the official report. The sensitivity of axial CT images to vertebral fracture was 0.35. CONCLUSION: Incidental osteoporotic vertebral fractures are under-reported on CT. The sensitivity of axial images in detecting these fractures is poor. Sagittal reformations are strongly recommended to improve the detection rate.

Geraets WG, Verheij JG, van der Stelt PF, Horner K, Lindh C, Nicopoulou-Karayianni K, Jacobs R, Harrison EJ, Adams JE, Devlin H. · Academic Centre for Dentistry Amsterdam (ACTA), Department of Oral and Maxillofacial Radiology, Louwesweg 1, 1066 EA Amsterdam, The Netherlands. · Bone. · Pubmed #17317351 No free full text.

Abstract: There is consensus to use the bone mineral density (BMD) for the operational definition of the degree of osteoporosis and the risk of osteoporotic fractures. Dual X-ray absorptiometry (DXA) is the common technique to determine BMD. Because of high costs and limited availability of DXA equipment it is worthwhile to look for alternative diagnostic techniques. As part of a larger study, the Osteodent project, we investigated if the trabecular pattern on dental radiographs can be used to predict BMD and to identify the subjects with osteoporosis and increased risk of osteoporotic fractures. In four clinical centers 671 women with an average age of 55 years were recruited. BMD values were measured by DXA equipment at the femoral neck, total hip, and spine. One panoramic and two intraoral radiographs were made. From 525 women a complete set of BMD values and radiographs was obtained. Four regions of interest on the radiographs were selected manually and then processed automatically. On all regions of interest mean and standard deviation of the gray values were measured and several features describing the shape of the binarized trabecular pattern. Multiple regression was used to predict BMD of total hip and spine by means of the radiographic measurements combined with age. It was found that age accounts for 10% of the variation in total hip BMD and 14% of the variation in spinal BMD. When all measurements on the dental radiographs are used the explained variation increases to 22% and 23%. The areas under the ROC curves are comparable to those of commonly used screening instruments for osteoporosis. It is concluded that prediction of DXA measurements of BMD by means of quantitative analysis of the trabecular pattern on dental radiographs is feasible.

Devlin H, Allen PD, Graham J, Jacobs R, Karayianni K, Lindh C, van der Stelt PF, Harrison E, Adams JE, Pavitt S, Horner K. · School of Dentistry, University Dental Hospital, Higher Cambridge Street, Manchester, M15 6FH, UK. · Bone. · Pubmed #17188590 No free full text.

Abstract: General dental practitioners use a vast amount of panoramic radiography in their routine clinical work, but valuable information about patients' osteoporotic status is not collected. There are many reasons for this, but one of the prime reasons must be the disruption involved in clinical routine with lengthy manual radiographic assessment. We have developed computer software, based on active shape modeling that will automatically detect the mandibular cortex on panoramic radiographs, and then measure its width. Automatic or semi-automatic measurement of the cortical width will indicate the osteoporotic risk of the patient. The aim of our work was to assess the computer search technique's ability to measure the mandibular cortical width and to assess its potential for detection of osteoporosis of the hip, spine and femoral neck. Mandibular cortical width was measured using the manually initialized (semi-automatic) method and, when assessed for diagnosing osteoporosis at one of the three measurement sites, gave an area under the ROC curve (A(z))=0.816 (95% CI=0.784 to 0.845) and for the automatically initialized searches, A(z)=0.759 (95% CI=0.724 to 0.791). The difference between areas=0.057 (95% Confidence interval=0.025 to 0.089), p<0.0001. For diagnosing osteoporosis at the femoral neck, mandibular cortical width derived from the manually initialized fit gave an area under the ROC curve (A(z))=0.835 (95% CI=0.805 to 0.863) and for the automatically initialized searches A(z)=0.805 (95% CI=0.773 to 0.835). The difference in A(z) values between active shape modeling search methods=0.030 (95% CI=-0.010 to 0.070), and this was not significant, p=0.138. We concluded that measurement of mandibular cortical width using active shape modeling is capable of diagnosing skeletal osteoporosis with good diagnostic ability and repeatability.

Karayianni K, Horner K, Mitsea A, Berkas L, Mastoris M, Jacobs R, Lindh C, van der Stelt PF, Harrison E, Adams JE, Pavitt S, Devlin H. · Dental School, University of Athens, Greece. · Bone. · Pubmed #16979965 No free full text.

Abstract: Clinical questionnaires and dental radiographic findings have both been suggested as methods of identifying women at risk of having osteoporosis and who might benefit from bone densitometry. The aim of this study was to measure the diagnostic accuracy of a combination of mandibular cortical width (MCW) measured from dental panoramic radiographs (DPRs) and the osteoporosis index of risk (OSIRIS) in the diagnosis of osteoporosis. 653 women (age range 45-70 years, mean age 54.95 years) in four European centres underwent standardised dual X-ray energy absorptiometry (DXA) to provide reference data on osteoporosis status. Each subject was interviewed to derive OSIRIS scores and underwent DPR examination. MCW was measured directly by five observers. Receiver Operating Characteristic (ROC) curve analysis was used to calculate sensitivities and specificities of the clinical and radiographic tests for the diagnosis of osteoporosis. 512 (78.4%) of the study population were classified as having normal BMD and 141 (21.6%) as having osteoporosis. Using ROC analysis, OSIRIS gave a ROC curve area (A(z)) of 0.838, with a sensitivity of 70.9% and a specificity of 79.5% at a diagnostic threshold of <or=+1. MCW on DPRs gave Az values for the five observers ranging from 0.71 to 0.78, providing sensitivities between 41.0% and 59.6% and specificities of between 81.8% and 90.3% at a diagnostic threshold of a 3 mm MCW and sensitivities between 94.2% and 99.3% and specificities of between 9.8% and 23.7% at a diagnostic threshold of a 4.5 mm MCW. Inter-observer repeatability was less than 2.15 mm for 95% of subjects. Combining clinical and radiographic tests had the effect of improving specificity at the expense of a fall in sensitivity. Diagnostic thresholds for MCW and OSIRIS can be chosen to provide the sensitivity and specificity combination that best suits locally determined needs. However, the addition of OSIRIS as a stepwise 'follow-up' test to radiographic assessment of MCW should only be performed if the aim is to have a test for which the highest achievable specificity is desired.

Harrison EJ, Adams JE. · Clinical Radiology, Imaging Science and Biomedical Engineering, The University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. · Calcif Tissue Int. · Pubmed #16969598 No free full text.

Abstract: A method proffered for the interpretation of measurements from peripheral dual energy X-ray absorptiometry (pDXA) is a triage approach to stratify patients into one of three risk categories; (i) high-treat, (ii) medium-refer for central DXA and (iii) low-reassure. The aim of this study was to apply the triage approach to measures from peripheral scanners and risk indices and stratify patients into one of three risk categories (i), (ii) or (iii). 207 post-menopausal women had central DXA from which they were categorised as non-osteoporotic or osteoporotic. Additional peripheral scans of the left calcaneus were performed on three scanners (GE Lunar Achilles and PIXI, McCue CubaClinical). From demographic details four risk indices were calculated and algorithms combining measures from peripheral scanners and one risk index were obtained. All peripheral measures, risk indices and combination algorithms were good at identifying women at risk of osteoporosis (ROC areas: 0.67-0.82). Each tool stratified varying numbers of osteoporotic and non-osteoporotic women into each risk category using the triage approach. One combination algorithm (PIXI & osteoporosis indices of risk (OSIRIS)) performed best by minimising misclassification (10% non-osteoporotic, 10% osteoporotic) and reducing requirement for central DXA to 36%. However the cost of implementing the triage approach for PIXI & OSIRIS was greater (263%) than central DXA (100%) scanning all women. Although the triage approach was an effective tool at identifying women at risk of osteoporosis the unnecessary treatment of non-osteoporotic women in the high risk category make it impractical. Therefore an alternative more cost-effective method has been suggested.

Eastell R, Hannon RA, Cuzick J, Dowsett M, Clack G, Adams JE, Anonymous00169. · Bone Metabolism Group, Division of Clinical Sciences (North), University of Sheffield, UK. · J Bone Miner Res. · Pubmed #16869719 No free full text.

Abstract: Aromatase inhibitors reduce estrogen levels in postmenopausal women with breast cancer. Residual estrogen is an important determinant of bone turnover. Adjuvant anastrozole was associated with significant BMD loss and increased bone remodeling, whereas tamoxifen reduced bone marker levels. INTRODUCTION: In the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial after a median follow-up of 68 months, a significant improvement in disease-free survival was observed with anastrozole treatment (hazard ratio [HR], 0.87; 95% CI, 0.78-0.97; p = 0.01). Anastrozole was also associated with tolerability benefits compared with tamoxifen, but with higher fracture rates. The HR of anastrozole compared with tamoxifen after 60 months of treatment was 1.49 (95% CI, 1.25-1.77). MATERIALS AND METHODS: This prospectively designed subprotocol (n = 308) of ATAC assessed changes in BMD and bone turnover markers in postmenopausal women with invasive primary breast cancer receiving anastrozole 1 mg/day, tamoxifen 20 mg/day, or combination treatment with both agents for 5 years. Patients with osteoporosis were excluded (osteopenia permitted at the investigators discretion). Lumbar spine and total hip BMD was assessed at baseline and after 1 and 2 years; bone turnover markers (serum C-telopeptide, urinary N-telopeptide [NTX], free deoxypyridinoline, serum procollagen type-1 N-propeptide, bone alkaline phosphatase [ALP]) were assessed at baseline and after 3, 6, and 12 months. Results were expressed as median percentage change. RESULTS: After 2 years of anastrozole treatment, BMD was lost at lumbar spine (median 4.1% loss) and total hip (median 3.9% loss) sites; increases of 2.2% and 1.2%, respectively, were observed with tamoxifen. After 1 year of anastrozole treatment, increased bone remodeling was observed (NTX, +15%; 95% CI, 3-25%; bone ALP, +20%; 95% CI, 14-25%); decreased bone remodeling was observed with tamoxifen (NTX, -52%; 95% CI, -62% to -33%; bone ALP, -16%; 95% CI, -24% to -11%). CONCLUSIONS: Anastrozole is associated with significant BMD loss and a small increase in bone turnover, whereas tamoxifen (and the combination) is associated with increased BMD and decreased remodeling. These data may explain the increased fracture risk observed with anastrozole treatment in the ATAC trial. The impact of anastrozole on bone should be weighed against its overall superior efficacy and tolerability as observed in the main ATAC trial.

Pye SR, Reid DM, Adams JE, Silman AJ, O'Neill TW. · ARC Epidemiology Unit, University of Manchester, Oxford Road, Manchester M13 9PT, UK. · Ann Rheum Dis. · Pubmed #16014671 links to  free full text

Abstract: OBJECTIVES: To determine the association between individual radiographic features of lumbar disc degeneration and bone mineral density (BMD) at the spine and hip. METHODS: SUBJECTS: were recruited from a population register for a screening survey of vertebral osteoporosis. BMD was assessed at the spine and hip using dual energy x ray absorptiometry. Lateral spinal radiographs were evaluated for features of lumbar disc degeneration. Each vertebral level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes, end plate sclerosis, and disc space narrowing. Linear regression was used to determine the association between each of these features and BMD at the spine and hip, with adjustments for age, body mass index, and levels of physical activity. Analyses were done separately in men and women. RESULTS: 250 women and 256 men (mean age around 65 years) were studied. At the lumbar spine, after age adjustment there was an increase in BMD with increasing grade for all radiographic features of disc degeneration in both men and women. At the femoral neck, after age adjustment there was an increase in BMD with increasing osteophyte and end plate sclerosis grade though not disc space narrowing. Adjusting for body mass index and physical activity did not influence the strength of the associations. CONCLUSIONS: Radiographic features of lumbar disc degeneration are associated with an increase in BMD at the spine. Osteophytes and end plate sclerosis, but not disc space narrowing, are associated with an increase in BMD at the hip.

Blake GM, Harrison EJ, Adams JE. · Guy's, King's and St Thomas' School of Medicine, St Thomas Street, London, SE1 9RT, UK. · Calcif Tissue Int. · Pubmed #15037973 No free full text.

Abstract: The high precision and stable calibration of dual X-ray absorptiometry (DXA) scanners have led to their widespread use in longitudinal studies for research and the follow-up of individual patients who are receiving treatment for osteoporosis. However, difficulties in maintaining the continuity of the bone mineral density (BMD) calibration scale can arise when an old DXA system is replaced by a newer model. We report the results of an in vivo cross-calibration study performed when a GE-Lunar Prodigy fan-beam system replaced a DPX-L pencil-beam scanner. Lumbar spine and hip DXA scans were performed in 133 patients (104 female, 29 male) attending long-term BMD monitoring. On average, lumbar spine BMD measurements on the two systems agreed closely, with Prodigy values 1% lower than those on the DPX-L. However, after allowing for this difference, the root mean square error (RMSE) of 0.037 g/cm2 was larger than in previous cross-calibration studies reported in the literature, and was 3 times the value expected from the precision of the BMD measurements. Mean femoral neck BMD also agreed closely between the two systems, although for Prodigy, the spread of measurements was 10% smaller than that for the DPX-L. For the trochanter and Ward's triangle regions, mean BMD was 4% and 6% lower, respectively, on the Prodigy system, and the results were affected by a similar compression of the range of values. RMSE values were 0.037 g/cm2, 0.044 g/cm2, and 0.044 g/cm2, respectively, for the femoral neck, trochanter, and Ward's triangle sites. When the high value of the RMSE was investigated, it was found that for lumbar spine BMD, patient body weight and the difference between the two systems in the percentage fat reported in the soft tissue reference region explained 40% of the variance. This enabled equations to be developed that significantly improved the agreement between scans performed on the two systems. Smaller improvements were obtained for the femur BMD measurements.

Ward KA, Cotton J, Adams JE. · Department of Clinical Radiology, Imaging Science and Biomedical Engineering, University of Manchester, M13 9PT Manchester, UK. · Osteoporos Int. · Pubmed #12730766 No free full text.

Abstract: Skeletal assessment by morphometry at peripheral sites (e.g. metacarpal index), although simple to perform and widely available, was limited by poor precision and technical aspects of radiogrammetry. Digital X-ray radiogrammetry (DXR) uses the principles of this long-established method but applies more sophisticated methodology to overcome these problems. The aims of this study were to (a) investigate the effects of radiographic technique on bone mineral density (BMD) measurement by DXR, (b) compare DXR to dual-energy X-ray absorptiometry (DXA) and single-energy X-ray absorptiometry (SXA) and (c) determine the applicability of DXR in identifying individuals who most appropriately might be referred for axial DXA. Different radiographers performing the radiograph do not adversely affect precision. Precision, unstandardised (CV%) and standardised (sCV%), is good with both double (DF)- and single (SF)-sided emulsion radiographic film, but better with SF (CV% 0.92 vs 1.12 DF; SCV% 1.76 vs 2.93 DF). Repeat analysis precision was determined on SF (CV% 0.24, sCV% 0.55). A significant ( p<0.001), systematic difference was found between BMD measured from DF and SF (mean difference 0.017 g/cm(2)). The overall percentage difference between the methods was 2.98% (range 0.18-5.78%). Correlations between DXR BMD and DXA were moderately good (r=0.56-0.77, p<0.001); with SXA of the forearm they were excellent (r=0.91, p<0.001). The sensitivity and specificity of DXR for detecting women with osteopaenia or osteoporosis (DXA T-score less than -1; World Health Organisation) was determined at the spine [area under curve (AUC)=0.82, standard error (SE)=0.04], femoral neck (AUC=0.84, SE=0.04) and total hip (AUC=0.84, SE=0.04). Based on femoral neck BMD for detection of osteopaenia, a DXR T-score threshold of -1.05 would be appropriate for detection of patients who might benefit most from axial DXA measurements. The DXR is quick and simple to use, having potential for application in a variety of settings as analysis can be performed in a central unit, with radiographs taken in sites over a wide geographical area. Retrospective analysis may also be performed, e.g. on radiographs taken to monitor rheumatoid arthritis. The technique may also provide a simple, widely available and relatively inexpensive method to assess patients at risk of osteopaenia or osteoporosis, and who most appropriately could be referred for axial DXA. This may be particularly relevant in those who suffer low-trauma fractures and attend accident and emergency or fracture clinics, where investigation for osteoporosis is often overlooked.

Pacheco EM, Harrison EJ, Ward KA, Lunt M, Adams JE. · Clinical Radiology, Imaging Science and Biomedical Engineering, The University, Oxford Road, Manchester M13 9PT, UK. · Calcif Tissue Int. · Pubmed #11960208 No free full text.

Abstract: The study assessed the precision, sensitivity, and specificity of a recently developed peripheral dual-energy X-ray absorptiometry (DXA) scanner, applied to the calcaneus, in the identification of individuals with osteoporosis at axial sites by DXA. Two hundred and two women, aged 55.2 +/- l3.7 years (mean +/- SD), participated in the study. The precisions (coefficient of variation) of measurements in vitro (0.48%) and in vivo (1.40%) were very good. The in vivo precision was independent of the operator, foot size, foot width, weight, height, and body mass index. Calcaneus BMD correlated moderately (r = 0.494-0.690, P <0.001) with axial BMD measurements by DXA. Using the World Health Organization (WHO) criterion for defining osteoporosis (T score ? -2.5) the specificity of the calcaneus to identify patients with osteoporosis at total hip, femoral neck, spine, or any of these axial sites was excellent (97.0%, 97.0%, 96.5%, and 97.1%, respectively); however, the sensitivity was poor (58.8%, 36.4%, 21.8%, and 20.3%, respectively). Therefore, the WHO criterion is not appropriate for DXA calcaneus. Based on femoral neck BMD for detection of osteoporosis, a more appropriate calcaneus T score threshold would be -1.4 by analyses of receiver-operator characteristic curves; this might serve to select those patients who might appropriately be referred for axial DXA.

Braidman IP, Baris C, Selby PL, Adams JE, Freemont AJ, Hoyland JA. · Musculoskeletal Research Group, University of Manchester Medical School, First Floor, Stopford Building, Oxford Road, Manchester M13 9PT, UK. · J Pathol. · Pubmed #10951405 No free full text.

Abstract: In western countries, osteoporosis affects at least 1 in 12 of all adult males and a third of osteoporotic men have idiopathic disease (MIO). Both oestrogen and testosterone are now known to be important to the male skeleton. As normal oestrogen levels have been found in younger MIO cases, it is hypothesized that, in bone, their responses to gonadal steroids may be defective, through impaired receptor expression. This study therefore compared oestrogen receptor (ER)-alpha and androgen receptor (AR) expression, by indirect immunofluorescence and semi-quantitative image analysis, in undecalcified fresh frozen bone sections from MIO patients (33-56 years), age-matched control men (n=7), and, for reference, ovarian steroid-replete (n=7) and -deficient women (n=6). In normal men, 23%+/-SEM 6% osteoblasts and 14%+/-SEM 2% osteocytes expressed ERalpha protein, similar to hormone-replete women. Although receptor expression decreased in hormone-deficient women, loss of ERalpha protein in MIO patients was more severe (1%+/-SEM 0.5% osteocytes, 2%+/-SEM 1% osteoblasts expressed receptor). In all four groups, there was little osteocyte AR expression, but in the women, a proportion of osteoblasts were receptor-positive. Deficient osteoblast and osteocyte ERalpha protein expression could explain the bone loss in these MIO patients.

Selby PL, Davies M, Adams JE. · University Department of Medicine, Manchester Royal Infirmary, UK. · Osteoporos Int. · Pubmed #10793874 No free full text.

Abstract: When the World Health Organization (WHO) guidelines for the definition of osteoporosis in postmenopausal women were identified similar proposals were not developed for men as there was insufficient evidence about the relationship between bone density and fracture in men. We have therefore examined the relationship between bone density and vertebral fracture in men and women attending for assessment of possible osteoporosis. Two hundred and sixty-four women (age 64 [SD 10] years) and 37 men (age 55 [10] years) were studied. Bone density was measured in the lumbar spine and femoral neck by dual-energy X-ray absorptiometry and expressed both as bone mineral density (BMD; g/cm2) and as T-scores. In both sexes there was a sigmoid relationship between the cumulative frequency of vertebral fracture and bone density at both sites. There was a linear relationship between the log odds of fracture and bone mass for both sexes and both sites (r = 0.97-0.99; p < 0.0001). The slope of these lines was significantly steeper for men than women. The BMD at which there was 50% risk of fracture was higher in men than women (0.908 vs 0.844 g/cm2). The difference between the slopes was similar when the bone mass was expressed as a T-score. However, the T-score associated with 50% prevalence of fracture was similar in the two sexes (F: -2.77 vs M: -2.60). We conclude that although there is a different relationship between bone density and fracture in the two sexes the current WHO definition of osteoporosis in postmenopausal women can be appropriately applied to men.

Haworth CS, Freemont AJ, Webb AK, Dodd ME, Selby PL, Mawer EB, Adams JE. · Adult Cystic Fibrosis Unit, Wythenshawe Hospital, Manchester, UK. · Eur Respir J. · Pubmed #10515433 links to  free full text

Abstract: A 25-yr-old male with cystic fibrosis sustained a fragility fracture of the left femoral neck, which required surgical correction. He had several risk factors for the development of low bone density and despite treatment with an oral bisphosphonate, his bone mineral density reduced further. The patient died 2 yrs after sustaining the fracture. Bone specimens obtained at post mortem demonstrated severe cortical and trabecular osteopenia, but the histological features were not typical of osteoporosis or osteomalacia. Osteoporosis is thought to be a common complication of cystic fibrosis. The novel histomorphometric appearances reported here suggest that the bone disease of cystic fibrosis may be more complex and possibly unique. Labelled bone biopsies are required to clarify the bone defect leading to low bone density in cystic fibrosis patients so that appropriate therapeutic strategies can be developed.

Selby PL, Davies M, Adams JE, Mawer EB. · University of Manchester Bone Disease Research Centre, Department of Medicine, Manchester Royal Infirmary, United Kingdom. · J Bone Miner Res. · Pubmed #10234588 No free full text.

Abstract: Celiac disease is a major cause of intestinal malabsorption. Previous studies have demonstrated that celiac disease is associated with significant osteoporotic bone loss. These studies have suggested that successful treatment of the malabsorption is associated with amelioration of the bone loss. Such studies have failed to examine bone mass at peripheral skeletal sites which is more likely to be responsive to changes in parathyroid hormone (PTH) in response to calcium malabsorption. We have examined bone density in the lumbar spine, femoral neck, and distal forearm in 35 patients with celiac disease who had been established on gluten-free diet. In addition, the concentrations of PTH and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Bone density was below that expected for the subject's age and gender at all sites. This was most marked in the distal forearm where the bone density was 1.40 SD below expected (p < 0.0001). In the forearm, there was a negative relationship between bone density and PTH concentration (r = -0.49, p = 0.009). In the forearm and lumbar spine, there was a negative relationship between 1,25(OH)2D concentration and bone density. Bone mass was not related to the concentration of 25-hydroxyvitamin D at any of the skeletal sites measured. Bone density is reduced in the peripheral skeleton in celiac disease and this deficit persists despite treatment with apparent normalization at axial skeletal sites. This reduction in bone mass is related to the presence of secondary hyperparathyroidism which should be sought in all patients with treated celiac disease.

Kröger H, Lunt M, Reeve J, Dequeker J, Adams JE, Birkenhager JC, Diaz Curiel M, Felsenberg D, Hyldstrup L, Kotzki P, Laval-Jeantet A, Lips P, Louis O, Perez Cano R, Reiners C, Ribot C, Ruegsegger P, Schneider P, Braillon P, Pearson J. · Department of Surgery/Orthopaedics, Kuopio University Hospital, FIN-70210 Kuopio, Finland. · Calcif Tissue Int. · Pubmed #10024374 No free full text.

Abstract: We have measured bone mineral density (BMD) using dual X-ray absorptiometry (DXA) of the spine and hip, spinal quantitative computed tomography (QCTspi), and peripheral radial quantitative computed tomography (pQCTrad) in 334 spine and 51 hip fracture patients. The standardized hip and spine BMD for each patient was calculated and compared with the combined reference ranges published previously, each densitometer having been cross-calibrated with the prototype European Spine Phantom (ESPp) or the European Forearm Phantom (EFP). Male and female fracture cases had similar BMD values after adjusting for body size, where appropriate. This suggests that the relationship between bone density (mass per unit volume) and fracture risk is similar between men and women. However, compared with age-matched controls, mean decreases in BMD ranged from 0.78 SD units (women with hip fracture, DXAspi) to 2.57 SD units (men with spine fractures, QCTspi). The proportion of spine and hip fracture patients falling below the cutoff for osteoporosis (T-score <-2.5 SD) proposed by the World Health Organization (WHO) study group varied according to different BMD measurement procedures (range 18-94%). This finding suggests that the WHO definition requires different thresholds when used with non-DXA BMD measurement techniques. Receiver operator characteristic (ROC) analysis was used to compare measurement techniques for their ability to discriminate between cases and controls. Among DXA sites, the proximal femur was preferred when evaluating generalized bone loss, particularly in elderly people. An additional spinal BMD measurement may add clinical value if spine fracture risk assessment has a high priority. Both axial and peripheral QCT techniques performed comparably to DXA in spinal osteoporosis, so investigators and clinicians may use any of the three technologies with similar degrees of confidence for the diagnosis of generalized or site-specific bone loss providing straightforward clinical guidelines are followed.