Mammography and osteoporosis screening--clinical risk factors and their association with digital X-ray radiogrammetry bone mineral density.

The aim of this study was to study the association between digital X-ray radiogrammetry (DXR) T-score and clinical risk factors for osteoporosis. Women were recruited 2 d per wk at a single mammography screening center between year 2010 and 2012. Included women answered a questionnaire about risk factors for osteoporosis, and a radiograph of the nondominant hand was obtained for DXR analysis. Univariate associations between DXR T-score and risk factors were examined. A generalized linear regression model was fitted to independent variables with univariate associations at p<0.05. The multivariable model was reduced through manual backward elimination, with p>0.1 as the exclusion criterion. Seventy-six percent of the women chose to participate in the study (n=8810). The difference in number of daily mammograms performed on study vs nonstudy days was not significant. All univariate associations between DXR T-score and potential risk factors were highly significant. The multivariable model included height, weight, age, right-handedness, menopause before age 45, alcohol consumption, cortisone treatment, rheumatic disease, and age×smoking status. The coefficient of determination of the model was 0.37. The association between risk factors for osteoporosis and DXR T-score is similar to previously reported associations with dual-energy X-ray absorptiometry.

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, Linköping, 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.

Loss of metacarpal bone density predicts RA development in recent-onset arthritis.

OBJECTIVE: Serum samples taken before the onset of RA suggest that one of the first features of RA is BMD loss. We determined the ability of radiographic BMD loss to predict RA development and arthritis persistency in patients with early undifferentiated arthritis (UA). METHODS: Five hundred and seventeen patients with early UA, included in the Leiden Early Arthritis Clinic, were assessed. Of these, 101 had hand radiographs made at first visit as well as after 6 months. BMD loss was measured using digital X-ray radiogrammetry (DXR) online. The outcome measures fulfilled the 1987 ACR criteria for RA after 1 year and arthritis persistency during a mean follow-up of 7 years. Additionally, it was assessed whether BMD measurements improved predictions compared with a validated prediction rule. RESULTS: A total of 53.8% of UA patients developed RA and 67.5% had persistent disease after 7 years follow-up. Highly elevated BMD loss (≥2.5 mg/cm2/month) was present in 16.3% of patients and associated with RA development [odds ratio (OR) 6.1, 95% CI 1.2, 29.2, positive predictive value (PPV) 85%, negative predictive value (NPV) 52%, sensitivity 26%, specificity 95%]. BMD loss may have an independent effect of anti-CCP when tested in a logistic regression analysis (OR 4.1, 95% CI 0.8, 21.2), although the CI is large. All UA patients that were unclassified with the prediction rule and had highly elevated BMD loss progressed to RA. BMD loss was not significantly associated with arthritis persistency (HR = 0.56, 95% CI 0.14, 2.29). CONCLUSION: Present data suggest that BMD loss predicts RA development. These findings need to be verified in larger studies.

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

BACKGROUND: 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.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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT001195663.

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

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Metacarpal bone diameter increases constantly in adult females, but escalated resorption of the inner surface at menopause explains the observed decreased bone mineral density at digital X-ray radiogrammetry.

OBJECTIVE: To assess how bone morphology and mineralization changes with age, in women by digital X-ray radiogrammetry (DXR). DXR has potential as a screening tool for osteoporosis, as it can evaluate bone mineralization similarly to dual-energy X-ray absorptiometry. METHODS: The nondominant hand was analyzed with DXR in 13,285 women ages 40-74 years undergoing mammography. 1,556 women attended two consecutive examinations with 18 to 24 months interval. Changes in bone parameters were calculated and compared in 5-year age groups. Regression analysis and ANOVA tests were performed. RESULTS: Univariate linear regression showed no significant difference in age or bone size between the groups with single or consecutive measurements. In the group with consecutive measurements, the average inner diameter (DXR-ID) of the metacarpals significantly increased with age from 0.38 cm in the 40-45 years age span to 0.47 cm in the 65+ age group (P < 0.001), whereas DXR bone mineral density (DXR-BMD) decreased from 0.59 g/cm2 to 0.50 g/cm2 in the same age groups (P < 0.001). Intraindividual measurements showed a fourfold increase in yearly DXR-ID increase and concurrent DXR-BMD loss between 50 and 59 years of age (P < 0.001). The outer diameter only increased significantly between the youngest and oldest age group (P < 0.001). CONCLUSIONS: The faster decrease in DXR-BMD observed during and after menopause is caused by resorption of the inner cortical surface, not matched by outer diameter increase. We speculate that most bones in the human body grow in the same pattern as observed in the metacarpals, partly explaining decreasing BMD at DXR and dual-energy X-ray absorptiometry.

Video Summary:http://links.lww.com/MENO/A832 .

Short-time in vitro and in vivo precision of direct digital X-ray radiogrammetry.

Digital X-ray radiogrammetry (DXR) calculates peripheral bone mineral density (BMD) from hand radiographs. The aim of this study was to examine in vitro and in vivo precision for the new direct digital version of DXR, a development of the conventional DXR. The in vitro precision for direct DXR was tested on 4 different X-ray equipment, based on 31 radiographs of the same phantom. The in vivo precision was based on duplicate hand radiographs from both hands in 39 individuals. For the 4 X-ray equipment, in vitro precision ranged from 0.14% to 0.30%, expressed as coefficient of variations (CV%) and from 0.0012 to 0.0028 g/cm2, expressed as smallest detectable difference (SDD). The precision was correlated to the resolution of the radiographic equipment (r=0.95, p=0.05). The corresponding values for the in vivo precision for mean values of both hands were: CV%=0.46%; SDD=0.0046 g/cm2, and least significant change (LSC%)=1.28%. The DXR-BMD for 1 of the X-ray equipment differed 1.1% from the overall mean. The precision for direct DXR was highly satisfactory both in vitro and in vivo. DXR-BMD values may differ between the radiographic equipment, and follow-up measurements should be performed with the same X-ray equipment.

Fully automated joint space width measurement and digital X-ray radiogrammetry in early RA.

OBJECTIVES: To study fully automated digital joint space width (JSW) and bone mineral density (BMD) in relation to a conventional radiographic scoring method in early rheumatoid arthritis (eRA). METHODS: Radiographs scored by the modified Sharp van der Heijde score (SHS) in patients with eRA were acquired from the SWEdish FarmacOTherapy study. Fully automated JSW measurements of bilateral metacarpals 2, 3 and 4 were compared with the joint space narrowing (JSN) score in SHS. Multilevel mixed model statistics were applied to calculate the significance of the association between ΔJSW and ΔBMD over 1 year, and the JSW differences between damaged and undamaged joints as evaluated by the JSN. RESULTS: Based on 576 joints of 96 patients with eRA, a significant reduction from baseline to 1 year was observed in the JSW from 1.69 (±0.19) mm to 1.66 (±0.19) mm (p<0.01), and BMD from 0.583 (±0.068) g/cm2 to 0.566 (±0.074) g/cm2 (p<0.01). A significant positive association was observed between ΔJSW and ΔBMD over 1 year (p<0.0001). On an individual joint level, JSWs of undamaged (JSN=0) joints were wider than damaged (JSN>0) joints: 1.68 mm (95% CI 1.70 to 1.67) vs 1.54 mm (95% CI 1.63 to 1.46). Similarly the unadjusted multilevel model showed significant differences in JSW between undamaged (1.68 mm (95% CI 1.72 to 1.64)) and damaged joints (1.63 mm (95% CI 1.68 to 1.58)) (p=0.0048). This difference remained significant in the adjusted model: 1.66 mm (95% CI 1.70 to 1.61) vs 1.62 mm (95% CI 1.68 to 1.56) (p=0.042). CONCLUSIONS: To measure the JSW with this fully automated digital tool may be useful as a quick and observer-independent application for evaluating cartilage damage in eRA. TRIAL REGISTRATION NUMBER: NCT00764725.

Can secondary osteoporosis be identified when screening for osteoporosis with digital X-ray radiogrammetry? Initial results from the Stockholm Osteoporosis Project (STOP).

OBJECTIVES: To identify causes of low age-adjusted bone mass at digital X-ray radiogrammetry (DXR) in individuals attending an osteoporosis screening program. STUDY DESIGN: In a descriptive observational cohort study, women aged 40-75 years who attended a general mammography screening program had their bone mass investigated with DXR and answered a questionnaire regarding several clinical risk factors for osteoporosis. Each month the 2% with the lowest Z-scores were selected for further clinical examination with DXA of the hip and lumbar spine and pre-defined blood tests. MAIN OUTCOME MEASURE: Causes of secondary osteoporosis determined by clinical and laboratory evaluation. RESULTS: 14,783 women attended mammography screening and had their bone mass evaluated. In total, 327 women had a low DXR BMD and 281 accepted further DXA examination. Of these, 93 (33.1%) had osteoporosis. The diagnosis was new in 79 cases (84.9%) and in 32 (34.4%) a potential underlying cause was identified. Primary hyperparathyroidism was found in 8.6% and secondary hyperparathyroidism in 13.5%. Several self-reported risk factors for osteoporosis, including rheumatic disease, insulin-treated diabetes, cortisone treatment, smoking, reduced mobility, hyperparathyroidism, and malabsorption, were significantly more common among those selected for DXA referral than in the total cohort. For example, rheumatic disease and insulin-treated diabetes were reported 3.4 and 2.3 times as often, respectively. CONCLUSION: The prevailing potential cause of secondary osteoporosis according to DXR was primary and secondary hyperparathyroidism. Most of the women with these conditions were previously undiagnosed, indicating that further follow-up of patients with low age-adjusted DXR BMD is justified.

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® 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 65years and older in the Study of Osteoporotic Fractures (SOF) cohort. Baseline hand X-ray images were analyzed and fractures were ascertained during 10years 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 ≤-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<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.

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.

The effect of fat on the measurement of bone mineral density by digital X-ray radiogrammetry (DXR-BMD).

OBJECTIVE: We have previously shown that surrounding fat causes an increase of up to 21% in bone mineral density (BMD) measured by Lunar 'Intelligent DXA' (iDXA), one of the latest generation dual energy X-ray absorptiometry (DXA) scanners [1]. The purpose of our study was to see if it was possible to avoid this artifact when measuring the BMD of metacarpals II, III, and IV by digital X-ray radiogrammetry (DXR). METHODS: We took X-rays of the bones of a cadaveric left hand which were immobilized in a wooden cradle to preserve an approximate in vivo configuration. The X-rays were digitized into Digital Imaging and Communications in Medicine (DICOM) files which were analyzed using dxr-online (dxr-online, Sectra, Sweden) which uses the same DXR-BMD algorithm previously used by Pronosco X-posure v2 and Sectra Osteoporosis package. The X-rays were repeated four times. We then surrounded the bones with a layer of lard, and again X-rayed four times. This process was repeated with the bones were covered by two layers, and then three layers of lard. RESULTS: The measured DXR-BMD increased by a maximum of 0.44% when the metacarpals were covered by either two or three layers of lard compared with when the metacarpals were not covered by lard. CONCLUSION: The measurement of metacarpal BMD measured by DXR is minimally affected by surrounding lard. The measurement of metacarpal BMD by DXR seems to be a way of avoiding the artifactual change in BMD caused by fat, when it is measured by DXA.