The detailed three-dimensional assessment of peripheral bone vBMD and geometry of the present study shows a systemically lower trabecular BMD and thinner cortices in RA patients and a localised greater outer bone shaft circumference at the meta-carpal bone.
Trabecular BMD at the third metacarpal bone, the radius and the tibia was lower in RA patients than controls. This was in accordance with earlier studies using DXA where the RA population was found to have lower total BMD at the distal metacarpal bone [7
], at the distal radius [10
], and the hip [11
The metacarpal bone shafts of our RA patients were thinner and had a greater outer bone diameter (Figure ). These results are in good agreement with a recent publica-tion on patients with polyarticular juvenile idiopathic arthritis [14
]. The between-group deficits in trabecular BMD could not be accounted for by adjustment to muscle cross-sectional area (CSA), indicating that the bone deficit in RA patients was greater than what would be expected as a result of their atrophied muscles. The same was true for cortical thickness of the radius and metacarpal shafts. However, at the tibia shaft, differences in cortical thickness disappeared after adjusting for muscle CSA (Table ). It should be noted that the slope of the muscle CSA to cortical thickness relation-ship differed, indicating that the thinning of the tibial cortex with decreasing muscle CSA was amplified in the RA group. In addition, the greater outer metacarpal diame-ter in our RA patients stands in contrast to the smaller muscle CSA. This may indi-cate that while part of the deficit in trabecular BMD and cortical thickness may have been caused by muscle atrophy, other disease related processes further reduced jux-ta-articular trabecular BMD and altered shaft geometry. Two pathomechanisms for decreased cortical thickness and increased outer circumference of the shaft are cur-rently discussed: First, bony apposition is seen as a compensatory mechanism to counterbalance inflammation to induced cortical thinning [14
]. Second, periosteal bone formation is seen as a repair process in inflammation-induced increased bone turnover [27
]. Irrespective of the causality of the greater outer bone shaft diame-ter, the result is an improved bone resistance against bending and torsion [29
We found a significant negative correlation between erosive score and total and tra-becular BMD as well as cortical shaft thickness at all measured bones. This is in ac-cordance with the relationship between development of erosions at the wrist and fin-gers and the loss of areal BMD at the metacarpal bone measured by digital x-ray ra-diogrammetry [1
]. Significantly lower baseline areal BMD at the hip [31
] and spine [33
] was found in early RA patients with erosive development, pointing to a general bone loss as consequence of a systemic inflammatory process. Our data of the radius and tibia support the notion of a systemic inflammatory process. Our more detailed analysis of vBMD and bone geometry showed lower trabecular vBMD at the radius and tibia and a thinner shaft cortical thickness at the radius independent of muscle atrophy, suggesting that systemic inflammatory processes may be involved. However, the greater shaft outer diameter was seen only at the metacarpal bone shaft suggesting RA-specific alterations at the metacarpal bone.
The presented data document a good performance of a newly developed protocol for measuring volumetric BMD and bone geometry by pQCT at the third metacarpal bone. Reproducibility was similar to previous studies measuring metacarpal areal BMD in RA patients by DXA [7
] and in studies using pQCT (XCT 3000) at the ra-dius [35
], tibia [35
], femur [35
] and humerus [35
]. CVs at the metacarpal mid-shaft (50% scan) of our protocol ranged from 0.7% to 1.5%. This is higher than the CV of 0.14% to 0.3% reported for digital X-ray radiogrammetry [38
], and most proba-bly due to the higher susceptibility to malpositioning. We have also performed inter- and intra-operator Intraclass Correlation Coefficients (ICC) and have found all ICCs > 0.85. Indeed, most ICCs were > 0.99, and they were similar between and within the two operators, indicating that the measuring protocol was not operator-sensitive.
A limitation of the present study is the large number of conducted statistical tests. Therefore, even P-values well below 0.05 should be interpreted carefully. However, the main results of this study, namely the between-group differences in tra-becular BMD and cortical thickness of all measured bones had P-values of ≤ 0.005 (except for the tibia shaft cortical thickness with a P-value of 0.03), and total CSA of the metacarpal bone had a P-value of < 0.02. Further, RA patients were on various medications that influence bone metabolism (biologicals, glucocorticoids, bisphosphonates). However, the aim of the present study was to compare a cohort of RA patients treated according to current common practice with healthy controls. Our results highlight that despite the bone protective effects of bio-logicals and bisphosphonates, trabecular BMD and cortical thickness were reduced at all measured skeletal sites in RA patients. While there were no clear associations between bone parameters and use of biological or glucocorticoids, patients on bisphosphonates had significantly lower trabecular BMD at all measured epiphyses (with diagnosis of osteoporosis being the treatment indication)(data not shown).