Joint Mobilization of the Hands of Patients With Rheumatoid Arthritis: Results From an Assessor-Blinded, Randomized Crossover Trial.

OBJECTIVE: The purpose of this study was to assess the clinical feasibility and effectiveness of manual mobilization of the hands of patients with rheumatoid arthritis (RA). METHODS: A total of 320 individual hand joints were evaluated after recruiting an experimental research group of 12 participants with RA and, for clinical comparability, 8 participants with hand osteoarthritis (OA). One hand per participant was randomized to receive weekly low-grade (I-II) Kaltenborn manual mobilization, using passive sustained stretch of the metacarpophalangeal (MCP) joints II to V by licensed manual therapists. After 2 weeks, the randomized treated hand was crossed over to control (untreated) during weeks 3 to 4 and vice versa. Final assessment was at 2 months, which was 1 month after the last treatment at week 4. Primary hand outcomes included pain by visual analog scale, tender or swollen joint count, and presence of Doppler signal or synovial fluid and radiographic joint space by musculoskeletal ultrasound. RESULTS: In the RA group, both the initially randomized treated hand and the contralateral hand improved significantly from baseline to crossover to follow-up at 2 months (pain outcomes and Doppler signal, P < .050; synovial fluid and MCP joint space, P ≤ .001). Hand pain and MCP joint space also improved significantly in OA. There were no dropouts or reported adverse events in either the RA or OA group. CONCLUSION: In this study, manual mobilization of the hands of patients with RA was shown to be feasible, safe, and effective to integrate into specialized healthcare.

Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

OBJECTIVE: To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). METHODS: MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. RESULTS: Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. CONCLUSION: In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

Is there a role for Digital X-ray Radiogrammetry as surrogate marker for radiological progression and imaging of structural integrity in rheumatoid arthritis?

INTRODUCTION: The established scoring techniques based on radiographs present limitations in the evaluation of structural integrity due to high effectiveness of innovative therapeutic strategies. The aim of this study was to evaluate the periarticular mineralisation as detected by Digital X-ray Radiogrammetry (DXR) as surrogate marker for structural integrity during the course of rheumatoid arthritis (RA). METHODS: 11 centers throughout Germany contributed data of 94 patients with verified RA. The patients were treated with leflunomide or methotrexate during a mean observation period of 22 months. All patients underwent complete computerized calculations of bone mineral density (BMD) and metacarpal index (MCI) by DXR using digitized hand radiographs. The radiological assessment of disease progression was estimated by the Sharp Score. RESULTS: The Sharp Score revealed no significant change during the study period. DXR-BMD revealed minimal decrease of -1.4 % (leflunomide group) versus a higher reduction of -4.3 % (methotrexate group). Regarding DXR-MCI, a reduction of -2.2 % (leflunomide group) and -4.9 % (methotrexate group) was observed. CONCLUSION: Quantitative data of hand bone mass estimated by the presented DXR-technique may be a complementary precise tool in the identification of RA-related radiographic changes and in the assessment of structural integrity.

Ultrasound imaging of the trapeziometacarpal articular cavity to investigate the presence of intraarticular gas bubbles after chiropractic manipulation.

OBJECTIVE: The purpose of this study was to investigate the presence of intraarticular gas bubbles in the trapeziometacarpal joint cavity after chiropractic manipulation with audible cavitation and to assess the state of the gas bubbles after a 20-minute refractory period. METHODS: This investigation included 18 asymptomatic male and female participants between the ages of 21 and 26 years. High-resolution (15 MHz) sonograms of the trapeziometacarpal articular cavity were obtained by an experienced musculoskeletal ultrasonographer at 3 intervals: premanipulation, within 30 seconds postmanipulation, and at 20 minutes postmanipulation. The sonograms were saved as digital copies for subsequent reports that were correlated with reports compiled during dynamic visualization of the articular cavity. Data were extracted from the reports for analysis. RESULTS: The premanipulative sonograms showed that 27.78% of joints contained minute gas bubbles, also known as microcavities, within the synovial fluid before the joint was manipulated. The remaining 72.22% of joints contained no intraarticular microcavities. All of the postmanipulative sonograms revealed numerous large conspicuous gas bubbles within the synovial fluid. The postrefractory sonograms showed that, in 66.66% of the synovial fluid, gas bubbles were still visible, whereas the remaining 33.34% had no presence of gas bubbles or microcavities, and the synovial fluid had returned to its premanipulative state. CONCLUSION: The findings of this study suggest that synovial fluid may contain intraarticular microcavities even before a manipulation is performed. Numerous large intraarticular gas bubbles are formed during manipulation due to cavitation of the synovial fluid and were observed in the absence of an axial distractive load at the time of imaging. In most cases, these gas bubbles remained within the joint for longer than 20 minutes.

Relationship of focal erosions, bone mineral density, and parathyroid hormone in rheumatoid arthritis.

OBJECTIVE: To investigate the relationship among focal bone erosions and bone mineral density (BMD), 25(OH) vitamin D (25OHD), and parathyroid hormone (PTH) values in patients with rheumatoid arthritis (RA). METHODS: The study included 1191 RA patients (1014 women, 177 men, mean age 58.9 ± 11.1 yrs) participating in a multicenter, cross-sectional study. RESULTS: Radiographic evidence of typical bony erosions on hands or forefeet was found in 64.1% of patients. In those with bone erosions as compared to those without, mean BMD Z score values were significantly lower at both the spine (-0.74 ± 1.19 vs -0.46 ± 1.31; p = 0.05) and the hip (-0.72 ± 1.07 vs -0.15 ± 1.23; p < 0.001). In the subgroup of patients not taking vitamin D supplements, PTH levels were significantly higher in those with erosive arthritis (25.9 ± 14.0 vs 23.1 ± 11.6 pg/ml; p = 0.01); whereas the 25OHD concentrations were very similar in the 2 groups. The mean differences for BMD and PTH among the erosive and nonerosive RA remained statistically significant when values were simultaneously adjusted for all disease and mineral metabolism factors (i.e., age, sex, menopause, disease duration, Disease Activity Score 28-joint count, Health Assessment Questionnaire, activities of daily living, Steinbrocker functional state, glucocorticoid therapy, body weight, and bisphosphonate treatment). CONCLUSION: Our results suggest that the presence of bone erosions in RA correlates with low BMD levels and high PTH levels, and that these associations are independent of the degree of functional impairment and other common determinants of bone mass and mineral metabolism in adults with RA. These findings suggest that treatments to prevent bone loss or suppress PTH levels might positively affect the progression of bone erosions in RA.

Vitamin K in hand osteoarthritis: results from a randomised clinical trial.

OBJECTIVES: Vitamin K has bone and cartilage effects, and previously shown to be associated with radiographic osteoarthritis. We evaluated vitamin K's effect on hand osteoarthritis in a randomised controlled trial. METHODS: This was an ancillary study to a randomised controlled trial assessing the effects of phylloquinone supplementation (vitamin K arm) versus placebo on bone loss and vascular calcification among older adults regardless of their vitamin K status. At the final 3-year study visit, we assessed the effects of vitamin K versus placebo on hand x-ray features of osteoarthritis using logistic regression and intention to treat, and also restricted analysis to the subgroup that had insufficient vitamin K concentrations at baseline. RESULTS: This ancillary study had 378 participants (193 in vitamin K arm, 185 in placebo arm). There were no effects of randomisation to vitamin K for radiographic osteoarthritis outcomes. Those with insufficient vitamin K at baseline who attained sufficient concentrations at follow-up had trends towards 47% less joint space narrowing (p = 0.02). CONCLUSIONS: There was no overall effect of vitamin K on radiographic hand osteoarthritis. SUBJECTS: that were insufficient in vitamin K at baseline who attained sufficient concentrations at follow-up may have had a benefit in joint space narrowing. A clinical trial in those who are vitamin K insufficient may be warranted. TRIAL REGISTRATION NUMBER: NCT00183001.

Computerized digital imaging techniques provided by digital X-ray radiogrammetry as new diagnostic tool in rheumatoid arthritis.

PURPOSE: Our study evaluates digital x-ray radiogrammetry (DXR) and Radiogrammetry Kit (RK) as a new diagnostic method for the measurement of disease-related osteoporosis including quantification of joint space narrowing dependent on the severity of rheumatoid arthritis (RA). MATERIALS AND METHODS: A total of 172 unselected patients with RA underwent computerized measurements of bone mineral density (BMD) and metacarpal index (MCI) by DXR, as well as a semiautomated measurement of joint space distances at the metacarpal-phalangeal articulation (JSD-MCP 2-5), both were analyzed from plain radiographs of the nondominant hand. RESULTS: Correlations between DXR-BMD and DXR-MCI vs. parameters of RK were all significant (0.34 < R < 0.61; p < 0.01). An expected negative association was observed between RK parameters and the different scoring methods (-0.27 < R < -0.59). The maximum relative decrease in BMD vs. MCI as measured by DXR between the highest and lowest RA severity group was -27.7% vs. -27.5% (p < 0.01) for the modified Larsen Score, whereas the minimal value of relative DXR-BMD and DXR-MCI reduction could be documented for the Sharp Erosion Score (-20.8% vs. -26.8%; p < 0.01). The relative reduction of mean JSD-MCP using RK significantly varied from -25.0% (Sharp Erosion Score) to -41.2% (modified Larsen Score). In addition, an excellent reproducibility of DXR and RK could be verified. CONCLUSION: DXR in combination with RK could be a promising, widely available diagnostic tool to supplement the different scoring methods of RA with quantitative data, allowing an earlier and improved diagnosis and more precision in determining disease progression.