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Objectives: Inflammatory rheumatic and musculoskeletal diseases (iRMDs) are associated with increased systemic bone loss that is mediated by chronic inflammation, treatment with glucocorticoids (GCs) and other factors. Our objective was to analyse the impact of variables that influence osteoporosis (OP) in patients with iRMD treated with GC., Methods: Rh-GIOP (acronyme) is a prospective observational cohort study investigating bone health in consecutive patients with iRMD and current or prior GC treatment. We present an analysis of the patients' baseline data here. Bone mineral density (BMD) measured by dual X-ray absorptiometry was the primary outcome. Multivariable linear regression models were performed to identify variables associated with BMD., Results: Data from 1066 patients with iRMD were analysed. GC doses of <5 mg prednisone equivalent per day, cumulative dose and duration of GC therapy were not associated with negative effects on BMD. Dosages of ≥5 mg/day lost their negative association with BMD after adjustment for confounders. When subanalysing patients with exactly 5 mg/day, no negative effect was seen. For patients with rheumatoid arthritis (RA), GC doses of >7.5 mg/day showed a negative association with BMD overall, but this effect seemed to be specific only to patients with moderate or high disease activity (Disease Activity Score 28-C reactive protein >3.2)., Conclusions: GCs of ≤5 mg/day did not seem to be associated with a reduction of BMD in patients with iRMD and current or prior exposure to GC. This is most likely due to the dampening of inflammation by GC, which exerts a mitigating effect on the risk of OP. In RA, current GC doses of >7.5 mg/day were negatively associated with BMD, but only in patients with moderate to high disease activity., Trial Registration Number: NCT02719314., Competing Interests: Competing interests: EW reported consultancy fees, honoraria and travel expenses from Medac and Novartis. DH reported receiving travel expenses from Shire. TB received consultancy fees and honoraria from Roche, Novartis, Sanofi and GSK. RB reported receiving consultancy fees, honoraria and travel expenses from Novartis. GRB reported receiving consultancy fees, honoraria and travel expenses from Roche and Sanofi and grant support from Medac. MB received consulting fees from Novartis. JS reported receiving consulting fees from AbbVie, ChemoCentryx, Sanofi, Spruce, Zenas, Bristol-Myers Squib, Sana, Q32Bio, Novartis, Kyverna, Horizon, Steritas and Argenx. CD reported receiving consultancy fees and honoraria from MSD, Pfizer, UCB, AbbVie, Roche, Novartis, Lilly, Sanofi and Galapagos. FB reported receiving consultancy fees, honoraria and travel expenses from Abbvie, Horizon Therapeutics, Pfizer and Roche, and grant support from Horizon Therapeutics, Roche and Abbvie., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To prove the feasibility and measure the diagnostic accuracy of contrast-enhanced ultra-low-dose CT (ULD-CT) for the depiction of inflammatory soft-tissue changes (synovitis, tenosynovitis and peritendonitis) in patients with arthritis of the hand., Materials and Methods: In this institutional review board-approved study, 36 consecutive patients over the age of 50 with suspected rheumatoid arthritis underwent ULD-CT (estimated radiation exposure <0.01  mSv) and MRI of the hand with weight-adapted intravenous contrast administration. ULD-CT subtraction and MR images were assessed for synovitis, tenosynovitis and peritendonitis by three readers using a modified Rheumatoid Arthritis MRI Score (RAMRIS). Patients were asked which modality they would prefer for future examinations. Sensitivity and specificity of ULD-CT for detection of inflammatory changes were calculated using MRI as standard of reference. The sum scores were correlated using Pearson's r., Results: All 36 patients showed synovitis in MRI. ULD-CT had 69% sensitivity on the patient level and 65% on the joint level with 87% specificity. Sensitivity was higher in patients with more severe inflammation (80% for MRI RAMRIS >1). There was almost perfect correlation between the modified RAMRIS sum scores of ULD-CT and MRI (Pearson's r=0.94). Regarding preferences for future examinations, 85% preferred ULD-CT over MRI. ULD-CT detected more differential diagnoses than MRI (8 vs 2/12)., Conclusion: Contrast-enhanced ULD-CT of the hand allows for depiction of soft-tissue inflammation at the hand and can be achieved using very low radiation exposure (<0.01 mSv). ULD-CT may evolve to a fast and comfortable alternative to MRI, although it is not as sensitive as MRI for detecting mild disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. We investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints., Methods: CD14 + cells from BM and peripheral blood (PB) of patients with RA and osteoarthritis (OA) were profiled with GeneChip microarrays. Detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and mobilisation. Cytometric profiling determined monocyte subsets of CD14 ++ CD16 - , CD14 ++ CD16 + and CD14 + CD16 + cells in BM, PB and synovial fluid (SF) and ELISAs quantified the release of activation markers into SF and serum., Results: Investigation of genes differentially expressed between RA and OA monocytes with reference transcriptomes revealed gene patterns of early myeloid precursors in RA-BM and late myeloid precursors along with reduced terminal differentiation to CD14 + CD16 + monocytes in RA-PB. Patterns associated with tumor necrosis factor/lipopolysaccharide (TNF/LPS) stimulation were weak and more pronounced in RA-PB than RA-BM. Cytometric phenotyping of cells in BM, blood and SF disclosed differences related to monocyte subsets and confirmed the reduced frequency of terminally differentiated CD14 + CD16 + monocytes in RA-PB. Monocyte activation in SF was characterised by the predominance of CD14 ++ CD16 ++ CD163 + HLA-DR + cells and elevated concentrations of sCD14, sCD163 and S100P., Conclusion: Patterns of less mature and less differentiated RA-BM and RA-PB monocytes suggest increased turnover with accelerated monocytopoiesis, BM egress and migration into inflamed joints. Predominant activation in the joint indicates the action of local and primary stimuli, which may also promote adaptive immune triggering through monocytes, potentially leading to new diagnostic and therapeutic strategies., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To analyse the function of nucleotide pyrophosphatase phosphodiesterase (NPP1), a member of the pyrophosphate pathway, in osteoarthritis (OA)., Methods: mRNA expression of NPP1, ANK ankylosing protein and tissue non-specific alkaline phosphatase was assessed by quantitative PCR. NPP1 protein levels were analysed in mouse and human cartilage samples. Bone metabolism was analysed by F18-positron emission tomography-scanning and µCT in ttw/ttw mice. Ttw/ttw mice are mice carrying a loss-of-function mutation in NPP1. Calcification of articular cartilage was assessed using von Kossa staining and OA severity using the Mankin score. Cartilage remodelling was investigated by type X collagen immunohistochemistry., Results: Expression of NPP1, but not the other members of this pathway, inversely correlated with cartilage calcification and OA severity in mouse and humans. Proinflammatory cytokines downregulated the expression of NPP1, demonstrating an influence of inflammation on matrix calcification. Ttw/ttw mutant mice, carrying a loss-of-function mutation in NPP1, exhibit increased bone formation process in joints compared with wild types. Ttw/ttw mice also developed spontaneous OA-like changes, evaluated by histological analysis and in vivo imaging. Ectopic calcifications were associated with increased expression of collagen X in the cartilage., Conclusion: The authors conclude that OA is characterised by the reactivation of molecular signalling cascades involving proinflammatory cytokines, thereby regulating the pyrophosphate pathway which consequently leads to cartilage ossification, at least in part resembling endochondral ossification.