Metacarpal bone loss in patients with rheumatoid arthritis estimated by a new Digital X-ray Radiogrammetry method - initial results.

BACKGROUND: The Digital X-ray Radiogrammetry (DXR) method measures the cortical bone thickness in the shafts of the metacarpals and has demonstrated its relevance in the assessment of hand bone loss caused by rheumatoid arthritis (RA). The aim of this study was to validate a novel approach of the DXR method in comparison with the original version considering patients with RA. METHOD: The study includes 49 patients with verified RA. The new version is an extension of the BoneXpert method commonly used in pediatrics which has these characteristics: (1) It introduces a new technique to analyze the images which automatically validates the results for most images, and (2) it defines the measurement region relative to the ends of the metacarpals. The BoneXpert method measures the Metacarpal Index (MCI) at the metacarpal bone (II to IV). Additionally, the MCI is quantified by the DXR X-posure System. RESULTS: The new version correctly analyzed all 49 images, and 45 were automatically validated. The standard deviation between the MCI results of the two versions was 2.9% of the mean MCI. The average Larsen score was 2.6 with a standard deviation of 1.3. The correlation of MCI to Larsen score was -0.81 in both versions, and there was no significant difference in their ability to detect erosions. CONCLUSION: The new DXR version (BoneXpert) validated 92% of the cases automatically, while the same good correlation to RA severity could be presented compared to the old version.

Digital X-ray radiogrammetry and its sensitivity and specificity for the identification of rheumatoid arthritis-related cortical hand bone loss.

Digital X-ray radiogrammetry (DXR) is a computer-assisted diagnosis technique for quantifying cortical hand bone mineral density (BMD) as well as the metacarpal index (MCI) in the metacarpal bones from radiographs. The objective was to compare DXR-BMD and DXR-MCI between healthy individuals and patients with rheumatoid arthritis (RA) and verify the sensitivity and specificity of this technique for the identification of cortical hand bone loss as an additional diagnostic approach in RA. 618 patients were enrolled and divided into two groups: those with RA (n = 309) and a healthy control group (n = 309) as a reference database. DXR-BMD and the DXR-MCI were measured by DXR using hand radiographs. The severity of RA was evaluated by the modified Larsen score. Mean values for DXR-BMD and DXR-MCI in RA patients were significantly lower compared to healthy subjects (-20.7 and -21.1 %, respectively). Depending on the severity of RA-related joint damage, DXR-BMD revealed a significant reduction of -28.1 % and DXR-MCI -28.2 %, comparing score 1 and score 5 of the modified Larsen score. Both DXR-BMD and DXR-MCI had a high sensitivity (DXR-BMD 91 %, DXR-MCI 87 %) and a moderate specificity (DXR-BMD 47 %, DXR-MCI 49 %) to identify RA-related cortical hand bone loss. The DXR technique seems to be able to quantify RA-related periarticular bone loss as a characteristic feature in the course of RA. Consequently, periarticular osteoporosis seems to function as a reliable diagnostic approach comparable to erosions and joint space narrowing in the diagnosis of RA and as a surrogate marker for the progression of bone loss in RA.

Psoriatic arthritis is associated with bone loss of the metacarpals.

BACKGROUND: BoneXpert (BX) is a newly developed medical device based on digital X-ray radiogrammetry to measure human cortical bone thickness. The aim of this study was to quantify cortical bone loss of the metacarpals in patients with psoriatic arthritis (PsA) and compare these findings with other radiological scoring methods. METHODS: The study includes 104 patients with verified PsA. The BX method was used to measure the Metacarpal Index (MCI) at the metacarpal bones (II-IV). Additionally, the T-score of the MCI (T-scoreMCI) was calculated. Radiographic severity was determined by the Psoriatic Arthritis Ratingen Score (Proliferation Score and Destruction Score) as published by Wassenberg et al. and the Psoriatic Arthritis modified van der Heijde Sharp Score (Joint Space Narrowing Score and Erosion Score). RESULTS: For the total PsA study cohort, the T-scoreMCI was significantly reduced by -1.289 ± 1.313 SD. The MCI negatively correlated with the Proliferation Score (r = -0.732; p < 0.001) and the Destruction Score (r = -0.771; p < 0.001) of the Psoriatic Arthritis Ratingen Score. Lower coefficients of correlations were observed for the Psoriatic Arthritis modified van der Heijde Sharp Score. In this context, a severity-dependent and PsA-related periarticular demineralisation as measured by the MCI was quantified. The strongest reduction of -30.8 % (p < 0.01) was observed for the MCI in the Destruction Score. CONCLUSIONS: The BX MCI score showed periarticular demineralisation and severity-dependent bone loss in patients with PsA. The measurements of the BX technique were able to sensitively differentiate between the different stages of disease manifestation affecting bone integrity and thereby seem to achieve the potential to be a surrogate marker of radiographic progression in PsA.

Differential regulation by cyclic nucleotides of the CNGA4 and CNGB1b subunits in olfactory cyclic nucleotide-gated channels.

Olfactory cyclic nucleotide-gated (CNG) ion channels are essential contributors to signal transduction of olfactory sensory neurons. The activity of the channels is controlled by the cyclic nucleotides guanosine 3',5'-monophosphate (cGMP) and adenosine 3',5'-monophosphate (cAMP). The olfactory CNG channels are composed of two CNGA2 subunits, one CNGA4 and one CNGB1b subunit, each containing a cyclic nucleotide-binding domain. Using patch-clamp fluorometry, we measured ligand binding and channel activation simultaneously and showed that cGMP activated olfactory CNG channels not only by binding to the two CNGA2 subunits but also by binding to the CNGA4 subunit. In a channel in which the CNGA2 subunits were compromised for ligand binding, cGMP binding to CNGA4 was sufficient to partly activate the channel. In contrast, in heterotetrameric channels, the CNGB1b subunit did not bind cGMP, but channels with this subunit showed activation by cAMP. Thus, the modulatory subunits participate actively in translating ligand binding to activation of heterotetrameric olfactory CNG channels and enable the channels to differentiate between cyclic nucleotides.