Objective Anticitrullinated protein antibodies (ACPA) are a major risk factor for bone loss in rheumatoid arthritis (RA). We have recently shown that ACPA directly induce bone loss by stimulating osteoclast differentiation. As ACPA precede the clinical onset of RA by years, we hypothesised that ACPA positive healthy individuals may already show skeletal changes. Methods We performed a comparative micro-CT analysis of the bone microstructure in the metacarpophalangeal joints of ACPA positive and ACPA negative healthy individuals without clinical signs of arthritis. Results ACPA positive (n=15) and negative (n=15) healthy individuals were not different in age (48.2±4.1 vs 51.4±3.8 years, p=0.57) or gender (eight women and two men in both groups). Bone mineral density was significantly reduced in ACPA positive individuals (mean±SEM 280±11 mg/cm 3 ) compared with controls (327±6). Bone loss was based on cortical bone changes, with significant ( p=0.044) reduction in cortical thickness in the ACPA positive group (mean±SEM 0.22±0.03 mm) compared with controls (0.32±0.03 mm). Areas of cortical porosity were significantly ( p=0.0005) more widespread in ACPA positive (mean±SEM 7.4±1.4%) than in ACPA negative individuals (1.0±0.3%). Discussion Structural bone damage starts before the clinical onset of arthritis in subjects with ACPA. These findings revise the concept that bone damage is an exclusive consequence of synovitis in patients with RA.

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Background Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are both destructive arthritides but may differ substantially in their periarticular bone changes. Objectives To investigate the differences in the structural changes of periarticular bone in patients with PsA and RA by a high-resolution imaging technique designed to visualise the bone architecture. Methods 30 patients with PsA and 58 patients with RA received a μCT scan to compare structural bone changes in the metacarpophalangeal joints of the dominantly affected hand. Number, extent, form and distribution of bone erosions, osteophytes and cortical thinning were recorded. In addition, the size and depth of bone erosions and the size of osteophytes were determined.

ObjectivesTo investigate whether bone erosions in patients with rheumatoid arthritis (RA) show evidence of repair. Methods 127 erosions were identifi ed in metacarpophalangeal joints 2-4 of the right hands of 30 RA patients treated with tumour necrosis factor inhibitors (TNFi) and 21 sex, age and disease activitymatched patients treated with methotrexate. All erosions were assessed for their exact maximal width and depth by high-resolution µCT imaging at baseline and after 1 year. Results All erosions detected at baseline could be visualised at follow-up after 1 year. At baseline, the mean width of bone erosions in the TNFi group was 2.0 mm; their mean depth was 2.3 mm, which was not signifi cantly different from the methotrexate-treated group (width 2.4 mm; depth 2.4 mm). Mean depth of erosions signifi cantly decreased after 1 year of treatment with TNFi (−0.1 mm; p=0.016), whereas their width remained unchanged. In contrast, mean depth and width of erosive lesions increased in the methotrexate-treated group. The reduction in the depth of lesions was confi ned to erosions showing evidence of sclerosis at the base of the lesion. Moreover, deeper lesions in the TNFi group were particularly prone to repair (−0.4 mm; p=0.02) compared with more shallow lesions. Conclusions Bone erosions in RA patients treated with TNFi show evidence of limited repair in contrast to bone erosions in patients treated with methotrexate. Repair is associated with a decrease in the depth of lesions and sclerosis at the bases of the lesions. Repair thus emerges from the endosteal rather than periosteal bone compartment and probably involves the bone marrow.Bone erosion is a central pathophysiological process in rheumatoid arthritis (RA). Growth factors such as monocyte colony stimulating factor as well as cytokines such as receptor activator of nuclear factor kappa B ligand, tumour necrosis factor alpha (TNFα) and interleukin-1 expressed in the synovial tissue stimulate the differentiation of monocytes/ macrophages into osteoclasts, which initiate the resorption of the periarticular bone. 1 2 This resorption process leads to a loss of mineralised tissue along the joints, which can be visualised as bone erosion by conventional radiography. Apart from clinical measurements, the detection and quantifi cation of bone erosion is an important outcome parameter in both clinical studies and clinical practice. 3 4 Virtually all currently used drug therapies have been tested for their ability to retard the bone erosive process in RA, which is suggestive of effective disease control and preservation of the joint architecture.Bone erosion is closely linked to infl ammatory disease activity of RA. The better synovial infl ammation can be controlled by anti-infl ammatory drug therapy, the more likely retardation or arrest of bone erosion is achieved. Despite this link between infl ammation and bone erosions, some treatment regimens are particularly effective to retard structural damage. 5 Inhibition of tumour necrosis factor alpha inhibibors (...

Objective To determine whether there is an additive effect of anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) on the number and size of bone erosions in patients with rheumatoid arthritis (RA) Methods 242 patients with RA received highresolution peripheral quantitative CT (HR-pQCT) scans of the metacarpophalangeal joints. Demographic and disease-specific parameters including ACPA and RF levels were recorded from all patients. Erosion numbers and their size were assessed in 238 patients at 714 individual joints (MCP 2, 3 and 4) and 5712 sites (each 4 quadrants in metacarpal heads and phalangeal bases). The volume of erosions was calculated by a semiellipsoid formula. Results Of the 238 patients, 112 patients showed RF and ACPAs (ACPAs+RF+), 28 only RF (RF+), 29 only ACPAs (ACPA+) and 69 were antibody negative (NEG). Erosion number and size were highest in RF+ACPAs+ patient group with significant differences compared with NEG patients with respect to erosion number ( p=0.001) and to ACPA-negative patients with respect to erosion size ( p<0.001). Results maintained significance in a linear mixed model showing ACPAs+RF+ status and disease duration being associated with higher number ( p=0.017 and p=0.005, respectively), and larger size ( p=0.014 and p=0.013, respectively) of bone erosions. Furthermore, erosion size was influenced by the presence and titre of RF only in ACPA-positive patients with RA but not in ACPA-negative patients. Conclusions ACPAs and RF show an additive effect on erosion number and erosion size. Concomitant presence of ACPAs and RF is associated with higher erosive disease burden in patients with RA. Furthermore, RF influences erosion size only in ACPA-positive but not in ACPA-negative patients.