Long-term in-vitro precision of direct digital X-ray radiogrammetry

Digital X-ray radiogrammetry (DXR) calculates peripheral bone mineral density (BMD) from hand radiographs. The short-term precision for direct DXR has been reported to be highly satisfactory. However, long-term precision for this method has not been examined. Thus, the aim of this study was to examine the long-term in-vitro precision for the new direct digital version of DXR. The in-vitro precision for direct DXR was tested with cadaver phantoms on four different X-ray systems at baseline, 3 months, 6 months, and in one machine also at 12 months. At each time point, 31 measurements were performed. The in-vitro longitudinal precision for the four radiographic systems ranged from 0.22 to 0.43% expressed as coefficient of variation (CV%). The smallest detectable difference (SDD) ranged from 0.0034 to 0.0054 g/cm(2). The in vitro long-term precision for direct DXR was comparable to the previous reported short-term in-vitro precision for all tested X-ray systems. These data show that DXR is a stable method for detecting small changes in bone density during 6-12 months of follow-up

Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: Subanalysis of the PREMIER study

<p>Abstract</p> <p>Background</p> <p>Anti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response. This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA.</p> <p>The objective of this study was to examine if treatment with the TNF-α inhibitor adalimumab also could reduce periarticular bone loss in RA patients independent of disease activity.</p> <p>Methods</p> <p>RA patients were recruited from the PREMIER study and included 214 patients treated with methotrexate (MTX) plus adalimumab and 188 patients treated with MTX monotherapy. Periarticular bone loss was assessed by digital X-ray radiogrammetry metacarpal cortical index (DXR-MCI). Change in DXR-MCI was evaluated in patients with different levels of clinical response, as assessed by changes in DAS28 score at 52 weeks and in mean C-reactive protein (CRP) levels during follow-up.</p> <p>Results</p> <p>In the MTX group, there was a greater median DXR-MCI loss among patients with moderate and high disease activity compared to those in remission or with low disease activity (-3.3% vs. -2.2%, p = 0.01). In contrast, periarticular bone loss was independent of disease activity (-1.9% vs. -2.4%, p = 0.99) in the combination group. In the MTX group patients with a mean CRP of ≥ 10 mg/l lost significantly more DXR-MCI than patients with low CRP (-3.1% vs. -1.9%, p <0.01) whereas in the combination group no significant differences between the two CRP groups was seen (-2.4% vs. -2.0%, p = 0.48).</p> <p>Conclusion</p> <p>Adalimumab in combination with MTX reduces periarticular bone loss independently of clinical response. These results support the hypothesis that TNF-α stimulates the osteoclast not only by the inflammatory pathway but do also have a direct effect on the osteoclast.</p> <p>Trial Registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT001195663">NCT001195663</a></p

Automatic image analysis for decision support in rheumatoid arthritis and osteoporosis

Low-energy trauma and fragility fractures represent a major public health problem. The societal cost of the fragility fractures that occurred in Sweden 2010 has been estimated at €4 billion. In rheumatoid arthritis (RA), patient outcomes have improved greatly in recent years. However, the therapeutic decision making is still hampered by a lack of effective validated biomarkers. The cost of RA in Sweden 2010 has been estimated at €600 million, of which biologic drugs was €180 million. Digital X-ray radiogrammetry (DXR) is a method to measure bone mineral density (BMD) in the metacarpals of the hand. It can be applied opportunistically in several workflows where a person is already at an X-ray machine, including fracture repositioning follow up, mammography screening and hand imaging in RA. This thesis explored DXR-BMD as a marker to identify individuals who would benefit from anti-osteoporotic treatment, change rate of DXR-BMD as a biomarker in RA and under what conditions historical X-ray images can be used to estimate DXR-BMD. An automated method for measurement of joint space width in metacarpophalangeal and interphalangeal joints was also developed and evaluated as a biomarker in RA. Low DXR-BMD was predictive for hip fractures and predicted fragility fractures to a comparable degree as other BMD measurement sites. Rapid decrease of DXR-BMD was a strong and independent predictor for progression of radiographic damage in RA when manual radiographic progression scores were not available. Change of metacarpal joint space width was a statistically significant but weak predictor of joint space narrowing score progression. Guidelines and considerations for use of historical X-ray radiographs for DXR-BMD measurements in clinical trials have been developed and published

Arthritis Research &amp;amp

Abstract Introduction: The aim of this study was to investigate the role of hand bone mineral density (BMD) loss analyzed with digital X-ray radiogrammetry (DXR) in early rheumatoid arthritis (RA) as a predictor for progression of joint damage

Potential sources of quantification error when retrospectively assessing metacarpal bone loss from historical radiographs by using digital X-ray radiogrammetry : an experimental study

During the past 15 yr, digital X-ray radiogrammetry (DXR) has been used to measure metacarpal bone mineral density (BMD). BMD is often measured in existing cohorts where X-ray images were not acquired in accordance with the DXR imaging protocol (DIP). The purpose of the present study was to analyze how deviations from DIP in historical radiographs may affect the reproducibility of DXR-BMD measurements. Cadaver hand phantoms were used to conduct repeat measurements of deviations from DIP with respect to voltage, exposure, lateral displacement, supination, combination of lateral displacement and supination or rotation, extension of the wrist, and edge enhancement. Direct digital radiography (Aristos; Siemens Healthcare, Erlangen, Germany) was used for image acquisition and dxr-online (Sectra, Linkoping, Sweden) for DXR-BMD measurements. The influence of the tested deviations from DIP ranged from 0 to 32.5 mg/cm(2) (0-6.8%). On repetition with the same specimen, none of the deviations resulted in a within-specimen reproducibility error greater than 2 mg/cm(2) (0.4%, equivalent to a T-score of 0.042). Among the tested deviations, all except tube voltage had a magnitude greater than the normal measurement noise for the technique and must therefore be considered when planning a study based on historical images

Does digital X-ray radiogrammetry have a role in identifying patients at increased risk for joint destruction in early rheumatoid arthritis?

Introduction The aim of this study was to investigate the role of hand bone mineral density (BMD) loss analyzed with digital X-ray radiogrammetry (DXR) in early rheumatoid arthritis (RA) as a predictor for progression of joint damage. Methods In 379 patients with early RA, baseline and one-year hand BMD was measured with DXR and the hand bone loss (HBL) was analyzed using the smallest detectable change (HBLsdc) and tertiles (HBLtertiles). Joint damage in hands and feet were scored according to the Sharp van der Heijde (SHS) method at baseline and at one, two, five and eight years. At the same time-points Disease Activity Score (DAS28) was calculated and functional disability assessed. Rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed at baseline. Results Sixty-six percent of the patients had hand BMD loss in the first year of RA determined by HBLsdc and 65% by HBLtertiles. Radiographic progression after two, five and eight years was associated with hand bone loss defined by HBLsdc. By HBLtertiles there were significant associations at all time-points except at eight years. The change in DXR at one year (ChDXR1yr) correlated significantly and inversely with the change in SHS (ChSHS) at two, five and eight years. Multivariate analysis showed that only change in SHS during the first year and the presence of anti-CCP were independent predictors of long-term progressive joint damage. If radiographic scores were not included, DXR-BMD loss was an independent predictor. Patients with great bone loss by HBLtertiles had significantly more often high disease activity after two years. However, neither bone loss by HBLsdc or HBLtertiles nor by ChDXR1yr was an independent predictor of remission after two, five and eight years. Conclusions This study confirms previous reports of an association of decrease in DXR-BMD during the first disease year with progression of radiographic joint damage over an extended period of time. This association was independent in a regression model only when radiological findings were excluded suggesting a possible predictive role of DXR-BMD in clinical practice when radiographic evaluation is not available. However, further studies are required before this can be established

Potential sources of quantification error when retrospectively assessing metacarpal bone loss from historical radiographs by using digital X-ray radiogrammetry : an experimental study

During the past 15 yr, digital X-ray radiogrammetry (DXR) has been used to measure metacarpal bone mineral density (BMD). BMD is often measured in existing cohorts where X-ray images were not acquired in accordance with the DXR imaging protocol (DIP). The purpose of the present study was to analyze how deviations from DIP in historical radiographs may affect the reproducibility of DXR-BMD measurements. Cadaver hand phantoms were used to conduct repeat measurements of deviations from DIP with respect to voltage, exposure, lateral displacement, supination, combination of lateral displacement and supination or rotation, extension of the wrist, and edge enhancement. Direct digital radiography (Aristos; Siemens Healthcare, Erlangen, Germany) was used for image acquisition and dxr-online (Sectra, Linkoping, Sweden) for DXR-BMD measurements. The influence of the tested deviations from DIP ranged from 0 to 32.5 mg/cm(2) (0-6.8%). On repetition with the same specimen, none of the deviations resulted in a within-specimen reproducibility error greater than 2 mg/cm(2) (0.4%, equivalent to a T-score of 0.042). Among the tested deviations, all except tube voltage had a magnitude greater than the normal measurement noise for the technique and must therefore be considered when planning a study based on historical images

Digital X-ray radiogrammetry in the study of osteoporotic fractures: Comparison to dual energy X-ray absorptiometry and FRAX

Osteoporosis is often underdiagnosed and undertreated. Screening of post -menopausal women for clinical risk factors and/or low bone mineral density (BMD) has been proposed to overcome this. Digital X-ray radiogrammetry (DXR) estimates hand BMD from standard hand X-ray images and have shown to predict fractures and osteoporosis. Recently, digital radiology and the internet have opened up the possibility of conducting automated opportunistic screening with DXR in post -fracture care or in combination with mammography. This study compared the performance of DXR with FRAX (R) and DXA in discriminating major osteoporotic fracture (MOF) (hip, clinical spine, forearm or shoulder), hip fracture and femoral neck osteoporosis. This prospective cohort study was conducted on 5278 women 65 years and older in the Study of Osteoporotic Fractures (SOF) cohort Baseline hand X-ray images were analyzed and fractures were ascertained during 10 years of follow up. Age -adjusted area under receiver operating characteristic curve (AUC) for MOF and hip fracture and for femoral neck osteoporosis (DXA FN BMD T -score &amp;lt;= -2.5) was used to compare the methods. Sensitivity to femoral neck osteoporosis at equal selection rates was tabulated for FRAX and DXR. DXR-BMD, FRAX (no BMD) and lumbar spine DXA BMD were all similar in fracture discriminative performance with an AUC around 0.65 for MOF and 0.70 for hip fractures for all three methods. As expected femoral neck DXA provided fracture discrimination superior both to other BMD measurements and to FRAX. AUC for selection of patients with femoral neck osteoporosis was higher with DXR-BMD, 0.76 (0.74-0.77), than with FRAX, 0.69 (0.67-0.71), (p &amp;lt; 0.0001). In conclusion, DXR-BMD discriminates incident fractures to a similar degree as FRAX and predicts femoral neck osteoporosis to a larger degree than FRAX. DXR shows promise as a method to automatically flag individuals who might benefit from an osteoporosis assessment (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Funding Agencies|Sectra AB, Linkoping, Sweden; National Institutes of Health; National Institute on Aging (NIA) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576]</p

Does digital X-ray radiogrammetry have a role in identifying patients at increased risk for joint destruction in early rheumatoid arthritis?

Introduction The aim of this study was to investigate the role of hand bone mineral density (BMD) loss analyzed with digital X-ray radiogrammetry (DXR) in early rheumatoid arthritis (RA) as a predictor for progression of joint damage. Methods In 379 patients with early RA, baseline and one-year hand BMD was measured with DXR and the hand bone loss (HBL) was analyzed using the smallest detectable change (HBLsdc) and tertiles (HBLtertiles). Joint damage in hands and feet were scored according to the Sharp van der Heijde (SHS) method at baseline and at one, two, five and eight years. At the same time-points Disease Activity Score (DAS28) was calculated and functional disability assessed. Rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed at baseline. Results Sixty-six percent of the patients had hand BMD loss in the first year of RA determined by HBLsdc and 65% by HBLtertiles. Radiographic progression after two, five and eight years was associated with hand bone loss defined by HBLsdc. By HBLtertiles there were significant associations at all time-points except at eight years. The change in DXR at one year (ChDXR1yr) correlated significantly and inversely with the change in SHS (ChSHS) at two, five and eight years. Multivariate analysis showed that only change in SHS during the first year and the presence of anti-CCP were independent predictors of long-term progressive joint damage. If radiographic scores were not included, DXR-BMD loss was an independent predictor. Patients with great bone loss by HBLtertiles had significantly more often high disease activity after two years. However, neither bone loss by HBLsdc or HBLtertiles nor by ChDXR1yr was an independent predictor of remission after two, five and eight years. Conclusions This study confirms previous reports of an association of decrease in DXR-BMD during the first disease year with progression of radiographic joint damage over an extended period of time. This association was independent in a regression model only when radiological findings were excluded suggesting a possible predictive role of DXR-BMD in clinical practice when radiographic evaluation is not available. However, further studies are required before this can be established