Ragnhild E. Ørstavik

Effects of rheumatoid arthritis on bone

The effects of rheumatoid arthritis on bone include structural joint damage (erosions) and osteoporosis. The latter may lead to increased risk for fractures, which are associated with increased morbidity and mortality. Osteoporosis in rheumatoid arthritis is characterized by a complexity of risk factors, including primary osteoporosis risk factors in addition to inflammation, immobilization, and use of corticosteroids. Quantitative assessment of periarticular and generalized bone loss in rheumatoid arthritis may be reliable indicators of future disease course and potential response variables in intervention studies. The osteoclast cell in rheumatoid arthritis plays a crucial role in the development of erosions and periarticular and generalized osteoporosis, suggested to be mediated through the osteoprotegerin/receptor activator of Nuclear Factor (NF)-&kgr;&bgr;/receptor activator of NF-&kgr;&bgr; ligand signaling system. Based on an improved understanding of this biology, new treatment opportunities exist.

Self reported non-vertebral fractures in rheumatoid arthritis and population based controls: incidence and relationship with bone mineral density and clinical variables

Objective: To compare the incidence of self reported non-vertebral fractures after RA diagnosis between female patients with RA and control subjects, and to explore possible associations between non-vertebral fractures and bone mineral density (BMD), disease, and demographic factors. Methods: 249 women (mean age 63.0 years) recruited from a county register of patients with RA and population controls (nu200a=u200a249) randomly selected after matching for age, sex, and residential area were studied. Data on previous non-vertebral fractures were obtained from a detailed questionnaire, and BMD was measured at the hip and spine. Results: 53 (21.3%) patients with RA had had 67 fractures after RA diagnosis, the corresponding numbers for controls were 50 (20.1%) and 60 (odds ratio (OR) for paired variables for overall fracture history 1.09, 95% CI 0.67 to 1.77). The overall fracture rates per 100 patient-years were 1.62 and 1.45, respectively, but self reported hip fractures were increased in RA (10 v 2, OR 9.0, 95% CI 1.2 to 394.5). Patients with a positive fracture history had longer disease duration, were more likely to have at least one deformed joint, and had lower age and weight adjusted BMD than those with no fracture history. In logistic regression analysis, fracture history was independently related to BMD only. Conclusions: With the probable exception of hip fractures, non-vertebral fractures do not seem to be a substantial burden in RA. Similar independent relationships between levels of BMD and fracture history were found in patients with RA and in population based controls.

Clinical decision rules in rheumatoid arthritis: do they identify patients at high risk for osteoporosis? Testing clinical criteria in a population based cohort of patients with rheumatoid arthritis recruited from the Oslo Rheumatoid Arthritis Register

Background: Preliminary clinical criteria based on age, inflammation, and immobility have been proposed to identify which patients with rheumatoid arthritis (RA) should be examined by dual energy x ray absorptiometry (DXA) to diagnose osteoporosis. The three item criteria have not been evaluated in male patients with RA or in the entire female RA population. Objectives: (1) To test the proposed criteria in a cohort of men and women thought to be representative of the entire underlying RA population. (2) To develop clinical decision rules, which could be applied to all patients with RA irrespective of corticosteroid use. Methods: Clinical and demographic data were collected from a total of 287 representative patients with RA (235 (82%) women, 52 (18%) men, age range 25.3–73.1 years) from the Oslo RA register (completeness 85%). Bone mineral density (BMD) was measured in spine L2–4 (anterior-posterior view) and femoral neck by DXA. The criteria were applied and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: Mean age (SD) for the women and men with RA was 56.8 (11.0) years and 61.5 (10.2) years; disease duration was 15.5 (9.5) years and 14.7 (8.6) years. Of the women 163 (69%) were postmenopausal. One hundred and seventeen (50%) women and 28 (54%) men fulfilled the three item criteria. For the diagnosis of osteoporosis (T score ≤−2.5) using the original three item criteria sensitivity in women and men was 74% and 67%, specificity 57% and 50%, PPV 32% and 29% and NPV 89% and 83%, and including weight and ever use of corticosteroids in a five item criteria sensitivity increased to 82% and 83%, specificity decreased to 45% and 45%, PPV was 29% and 31%, and NPV was 90% and 90% respectively. Conclusion: The novel five item criteria (age, weight, inflammation, immobility, and ever use of corticosteroids) are a more accurate tool to identify patients with RA and osteoporosis than the original three item criteria (age, inflammation, and immobility). The clinical decision rules have an acceptable sensitivity and provide a practical tool for the doctor to identify patients with RA who should have a DXA measurement performed.

Bone mineral density in patients with hand osteoarthritis compared to population controls and patients with rheumatoid arthritis

Objectives: Several studies have revealed increased bone mineral density (BMD) in patients with knee or hip osteoarthritis, but few studies have addressed this issue in hand osteoarthritis (HOA). The aims of this study were to compare BMD levels and frequency of osteoporosis between female patients with HOA, rheumatoid arthritis (RA) and controls aged 50–70 years, and to explore possible relationships between BMD and disease characteristics in patients with HOA. Methods: 190 HOA and 194 RA patients were recruited from the respective disease registers in Oslo, and 122 controls were selected from the population register of Oslo. All participants underwent BMD measurements of femoral neck, total hip and lumbar spine (dual-energy x ray absorptiometry), interview, clinical joint examination and completed self-reported questionnaires. Results: Age-, weight- and height-adjusted BMD values were significantly higher in HOA versus RA and controls, the latter only significant for femoral neck and lumbar spine. The frequency of osteoporosis was not significantly different between HOA and controls, but significantly lower in HOA versus RA. Adjusted BMD values did not differ between HOA patients with and without knee OA, and significant associations between BMD levels and symptom duration or disease measures were not observed. Conclusion: HOA patients have a higher BMD than population-based controls, and this seems not to be limited to patients with involvement of larger joints. The lack of correlation between BMD and disease duration or severity does not support the hypothesis that higher BMD is a consequence of the disease itself.

Incidence of vertebral deformities in 255 female rheumatoid arthritis patients measured by morphometric X-ray absorptiometry

To date, no studies have been published on incident deformities in patients with rheumatoid arthritis (RA). Morphometric X-ray absorptiometry (MXA) is an alternative to conventional X-rays for identifying vertebral deformities. The aim of the present study was to describe the incidence of vertebral deformities in 255 female RA patients measured by MXA, and the relationship between incident deformities and clinical and demographic variables. MXA is still under evaluation for its ability to identify deformities, so we explored four different cut-off thresholds including fixed percentage reduction and the principle of least significant change (LSC). MXA (T4–L4) and BMD (L2–L4 and total hip; Lunar Expert) were performed on 255 patients (mean age 54.3, range 29.2–70.8 years) at baseline and after a mean period of 2.3 years. MXA scans were analyzed pairwise by the same trained technician, and incident deformities calculated applying LSC with a 99.9% and 99.99% confidence limit, and a fixed reduction of 20% and 25% for anterior, middle or posterior heights. Long term precision (%CV) of height measurements for all vertebrae combined (T4–L4) were 4.8, 4.8 and 4.4, respectively. Frequency and distribution of incident deformities varied from 39 deformities in 33 patients (fixed 20% reduction) to 17 deformities in 15 patients (fixed 25% reduction), and quality control analyses revealed a high number of presumed false deformities. Incidence per 100 patient years varied from 2.9 to 6.7 deformities according to method, and was comparable to those obtained from intervention studies in corticosteroid-induced osteoporosis. Patients with incident deformities were significantly older, had lower BMD, higher disability and more often a previous non-vertebral fractures than those without incident deformities Incident deformities by MXA need further evaluation in secondary osteoporosis. It seems, however, that older patients with previous limb fractures and low BMD are especially prone to this complication.

Comparison of ultrasound and X-ray absorptiometry bone measurements in a case control study of female rheumatoid arthritis patients and randomly selected subjects in the population

Abstract.To compare quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA) bone measurements in female rheumatoid arthritis (RA) patients and controls were randomly selected from the population; secondly, to examine disease and demographic factors associated with these bone measurements. In a total of 115 RA patients (mean age 63.0xa0years) and 115 age- and gender-matched controls demographic and clinical variables were collected and heel QUS parameters [speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI)] as well as DXA bone mineral density (BMD) at spine and hip were measured. The differences in QUS and DXA measurements between RA patients and controls were tested both on a group and on an individual level. Univariate and multivariate statistical tests were applied to explore for associations to the bone measurements. In the RA patients mean disease duration was 16.6xa0years, erythrocyte sedimentation rate 23.6xa0mm/h, M-HAQ 1.68, 28-swollen joint count 7.7, 18-deformed joint count 4.5, 50.0% were rheumatoid factor (RF) positive and 44.2% were current users of prednisolone. All bone measurements were reduced in RA patients compared with controls (SOS 1.9%, BUA 9.4%, SI 19.5%, femoral neck BMD 7.4%, total hip BMD 7.5%, spine L2–L4 BMD −3.0%). Only at spine was the BMD reduction not statistically significant (P=0.21). In the subgroup of never users of prednisolone SOS was decreased by 1.4%, BUA by 3.7%, SI by 11.0, femoral neck BMD by 2.7%, and total hip BMD by 0.6%, whereas for spine L2–L4 BMD was increased by 4.3% and only for SOS and SI was the decrease statistically significant. The QUS discriminated better than DXA between patients and controls on a group level, but this difference in favor of QUS disappeared on an individual level when the measurement errors were taken into account. Age, BMI, RF and deformed joint count, but not corticosteroids, were independently associated with at least one of the QUS and one of the DXA measures; however, the association between disease-related variables was stronger with the QUS bone measures than with the DXA bone measures. The results for the quantitative QUS bone measures seem to mainly reflect bone mass. Disease-related variables in multivariate analysis remained independently associated with all QUS measures even when adjusting for DXA bone measures. Further studies are needed to examine if QUS may reflect other aspects than bone mass and be a potential better predictor for fracture risk in RA and corticosteroid-induced osteoporosis.