Alendronate in rheumatoid arthritis patients treated with methotrexate and glucocorticoids

Rheumatoid arthritis (RA) is a systemic inflammatory disease. Along with synovial joint inflammation, extra-articular involvement is a common feature of RA. Periarticular and generalized osteoporosis are seen both as an extra-articular feature of the disease itself and due to various medications like glucocorticoids and methotrexate (MTX). In this study, we investigated the effects of oral alendronate in RA patients treated with MTX and prednisolone by comparing the effects of “alendronate+calcium” and “only calcium” on bone mineral density (BMD). Fifty RA patients classified according to American Rheumatism Association (ARA) criteria were included in the study. The control group consisted of 20 postmenopausal osteoporotic patients. The RA patients were divided randomly into two groups. All patients were started on MTX 7.5 mg/week, 2.5-mg daily folic acid, and 7.5-mg daily prednisolone. The first group, consisting of 25 female RA patients, was also given 10-mg daily alendronate and 1000-mg daily calcium. The second group also consisted of 25 female patients and was given only 1000-mg calcium per day. The postmenopausal control group was given daily 10-mg alendronate and 1000-mg calcium. Bone mineral densities were measured by dual-energy x-ray absorptiometry (DEXA) and again at the end of the sixth month. At the end of the study, RA patients given only calcium had reduced mean BMD, and patients treated with alendronate and calcium showed increased mean BMD almost in all regions. This increase was significant in the L2 and L1–4 total regions. In postmenopausal osteoporotic patients, we saw statistically significant increases in BMD in all regions. The increase in BMD values in RA patients treated with alendronate was smaller than in those of the control group of postmenopausal osteoporosis patients. In conclusion, RA itself has a risk factor for osteoporosis in addition to the risks of the medications like corticosteroids and MTX. In the prevention and treatment of RA-associated osteoporosis, alendronate and calcium therapy is effective and well tolerated. Received: 16 June 2000 / Accepted: 20 August 2000     

Influence of perception of glucocorticoids on compliance of treatment in patients with rheumatoid arthritis and systemic lupus erythematosus

BackgroundGlucocorticoids (GCs) are alleged as hazardous medications among Egyptian patients and their relatives.Aim of the workTo highlight the beliefs held about GCs and the effect of these beliefs on adherence to GCs treatment.Patients and methodsThe study included 70 systemic lupus erythematosus (SLE) patients, 70 rheumatoid arthritis (RA) patients and 140 GC-naïve subjects as the control. The demographic and socioeconomic standards of the patients and control as well as the GCs use experience in patients were recorded. GCs perception was assessed by Beliefs about medication Questionnaire (BMQ). Adherence was assessed by Compliance Questionnaire of Rheumatology (CQR).ResultsGCs were significantly perceived as harmful and of low benefit by the control (p < 0.001, p < 0.001, respectively), a beneficial drug by SLE patients, while RA patients had significantly higher harm scores (p = 0.015 and p = 0.003 respectively). Most of SLE and RA patients were non-adherent (57.1% and 65.7%, respectively). Higher general-BMQ harm scores were significantly associated with a lower odd of adherence (OR: 0.25, 95%CI: 0.1–0.63). Reduced OR of necessity > concern was associated with higher socioeconomic standards and maximum oral GCs dose (OR:0.09 and 0.96, respectively). Increased OR of high necessity was significantly associated with number of currently used disease modifying anti-rheumatic drugs (DMARDs) (OR:5.54, p = 0.025). High OR of harm perception was significantly associated with higher socioeconomic standards (OR: 5.12, p = 0.016).ConclusionGCs are perceived as pillars in management by SLE and RA patients. Concerns about side effects and dependency are still troublesome. Improvement of patients’ GCs perception impacts level of adherence to treatment.     

Generalized osteoporosis in non-steroid treated rheumatoid arthritis

Summary To investigate the presence of reduced bone mineral density (BMD) and to assess determinants of bone loss in rheumatoid arthritis, 45 female patients suffering from non-steroid treated rheumatoid arthritis were submitted to dual photon absorptiometry of the lumbar spine and to laboratory tests for calcium metabolism. The rheumatoid arthritis patients were divided into two groups according to anatomic grade and functional class; no abnormalities in calcium metabolism were defected whereas BMD was significantly lower in the third and fourth grade and in the third and fourth class patients (P<0.005 versus controls, versus grades I and II and versus classes 1 and 2). BMD was significantly correlated with age (P<0.001) and years postmenopausal (P<0.01), but not with duration of disease. By multiple inear regression we derived an equation predictive of BMD. Osteoporosis in rheumatoid arthritis is observed even in non-corticosteroid treated patients; articular lesions with subsequent reduction in physical activity appear to play an important role in axial bone loss in rheumatoid arthritis.     

Knee deformity in rheumatoid arthritis is closely correlated with generalized osteoporosis

To examine the relationship between knee deformity and osteoporosis in women with rheumatoid arthritis (RA), bone mineral density (BMD) in the lumbar spine and distal radius was measured using dual X-ray absorptiometry, and knee deformity (valgus or varus deformity) was measured using plain radiograms in 55 women with RA. Associations between knee deformity and BMD, disease related variables, including RA stage, RA duration, age, cumulative doses of administered glucocorticosteroids, body mass index, or postmenopausal period were evaluated. Cut-off values of the BMD defining RA patients with knee deformity were very close to the BMD value corresponding to 70% of young adult mean in the lumbar spine and distal radius. The femorotibial alignment was significantly correlated with age and deformity of the proximal tibia. Deformity of the proximal tibia was negatively correlated with the radial BMD and lumbar BMD. Deformity of the proximal tibia showed a significant difference between the groups of less than 5 years after menopause and the group of 5–10 years after menopause. We concluded that knee deformity in RA derived from deformity of the proximal tibia, and it was closely correlated with generalized osteoporosis.     

Structural mechanisms of bone loss in iliac biopsies: comparison between rheumatoid arthritis and postmenopausal osteoporosis

To assess the mechanisms that cause generalized osteoporosis in rheumatoid arthritis (RA), 40 postmenopausal women with RA (46–74 years) and 40 age-matched controls with osteopenia underwent iliac bone biopsies. A structural analysis of histomorphometry and two-dimensional strut analysis were performed As compared to those with primary osteoporosis, there were a few unique characteristics in those with RA. Trabecular thickness and wall thickness declined with age, and this decline was especially accelerated by glucocorticoids. Decreased connectivity of the trabecular (Nd.Nd) was more prominent than the disappearance of the nodes. The connectivity of cortical bone to the nodes (Ct.Nd) and cortical thickness significantly decreased with age. With glucocorticoid therapy, the disappearance of the nodes was accelerated. In the case of vertebral compression fractures, the parameters of Nd.Nd and Ct.Nd significantly decreased. Although a bone biopsy is needed to analyze strut, this method is useful to evaluate the quality or intensity of the bone. Received: 19 October 1998 / Accepted: 17 December 1998     

Osteoporosis evaluation and treatment recommendations in rheumatoid arthritis

In this chapter, we emphasize among rheumatoid arthritis (RA) patients, whom and how to screen for osteoporosis. We highlight certain modalities, advancements in technology, secondary osteoporosis workup, and laboratory testing as well as their caveats. Finally, we discuss current guidance on how to direct the laboratory and radiology testing in the context of the individual patient with RA to guide and select from the osteoporosis treatment options currently available.     

The relation between joint erosion and generalized osteoporosis and disease activity in patients with rheumatoid arthritis

The aim of this study is to investigate the correlation between joint erosion and osteoporosis in patients with rheumatoid arthritis (RA). Fifty-one patients with RA were included for the study. Hand radiograms of all patients were evaluated by the Larsen modified Sharp and carpometacarpal ratio methods. Bone mineral density (BMD) measurements were performed at the femur, lumbar, and forearm regions. Disease activity was assessed clinically by the health assessment questionnaire (HAQ), visual analog scale, erythrocyte sedimentation rate, C-reactive protein (CRP), and the rheumatoid factor (RF). There was no statistically significant difference in terms of the BMD values at L1-4 between the patients with RA and the control group. The BMD measurements at the right forearm and the right hip were statistically significantly lower in the patient group. For radiological scoring, hand radiograms were evaluated by three different methods. There was a significant correlation between the duration of disease and the radiological evaluation methods. HAQ scores, Larsen and Sharp methods 1/3 distal and mid-distal (MID), and BMD measurements of the forearm were correlated. Moreover, 1/3 distal, MID, and ultra-distal BMD showed significant correlations with CRP levels. Radiogram continues to have an important role in determining and following-up the joint erosion seen in patients with RA. However, we believe that as establishing periarticular osteoporosis in the early term by performing BMD measurements on the forearm is correlated with disease activity, it may be useful in the early diagnosis of RA and its objective results will be efficient in predicting the progression of disease     

Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis

To elucidate the pathology of osteoporosis associated with rheumatoid arthritis (RA), bone mass measurements were performed in 146 female patients with RA and compared with those in 150 age-matched female patients with osteoarthritis (OA) and postmenopausal osteoporosis (OP). Bone mineral density (BMD) was measured at the lumbar spine (L-BMD), the mid-radius (MR-BMD) and the calcaneus (C-BMD) by dual-energy X-ray absorptiometry (DXA), and at the distal radius by peripheral quantitative computed tomography (pQCT). The RA group showed significantly lower BMD at all sites, except L-BMD, than the OA group. Compared with the OP group, the RA group showed a significantly higher L-BMD but no difference at other sites. BMD in RA decreased with disease severity at all sites and lean body mass was highly correlated with L-BMD and C-BMD. Cross-sectional analysis revealed early bone loss at the distal radius and a decrease of L-BMD, MR-BMD, and C-BMD with disease duration. Longitudinal analysis showed that the annual loss of L-BMD, MR-BMD and C-BMD tended to be lower with increasing disease duration. Glucocorticoid administration had no influence on L-BMD, MR-BMD or C-BMD. We concluded that, unlike postmenopausal osteoporosis, osteoporosis associated with RA is characterised by relatively preserved bone mass in the axial bone and marked loss in the peripheral bone. The risk factors for generalised osteoporosis are a long disease duration, severity of disease, and decreased lean body mass. Received: 8 May 2001 / Accepted: 18 September 2001     

Risk factors for osteoporosis and fractures in rheumatoid arthritis

People with rheumatoid arthritis (RA) have both disease-specific risk factors for osteoporosis and fractures in addition to those that affect the general population. Disease specific risks include directly pathogenic auto-antibodies, chronic exposure to systemic inflammation, and joint damage causing early disability. Risk factors that affect the general population which may have a higher prevalence in RA include smoking, calcium and vitamin D deficiency as well as hypogonadism. Additionally, chronic exposure to glucocorticoids results in reduced bone mineral density and body composition changes which can further increase fracture risk. In this review we discuss these risk-factors for osteoporosis as well as factors that may impact fall and fracture risk in people with RA.     

Association of bone mineral density and vertebral deformity in patients with rheumatoid arthritis

The aim of this study was to investigate the association of vertebral deformities developed as a result of osteoporosis in female patients with rheumatoid arthritis (RA) with bone mineral density (BMD) and disease activity parameters. In the study, 100 female patients with the diagnosis of RA and 56 healthy subjects were recruited. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) tests were performed and the number of swollen and tender joints, level of pain and health assessment questionnaire (HAQ) were recorded in order to evaluate disease activity. Anteroposterior and lateral thoracic and lumbosacral roentgenograms of all patients were taken for radiological examination and deformities of vertebrae were assessed. BMD measurements of patients were performed on vertebrae L1–4 of lumbar region and on total hip, femur neck, trochanter and Ward’s triangle of the right side. Vertebral deformity was established in 30% of RA patient group and 7.1% of control group and this was statistically significant. In the statistical analysis, no statistically significant difference was found between BMD measurements of RA and control groups. Patients with RA were divided into two subgroups with regard to using corticosteroids (CS) or not. Vertebral deformity was 32.4% in the subgroup using CS and 24.1% in the subgroup not using CS, and the difference was not statistically significant. There was a correlation between number of deformed joint and age and vertebral deformity incidence. RA is a risk factor on its own for the development of osteoporosis and vertebral deformity and this risk increases by age, excess number of deformed joints and severe course of disease. We think that precautions should be taken immediately to suppress the disease activity as well as to protect the quality and density of bone and to prevent the development of vertebral deformity and fracture while planning the treatment of patients with RA.     

Associations with subregional BMD-measurements in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have bone loss to various degrees at different skeletal sites. The subregional bone mineral density (BMD) of the hand and the correlation of BMD to other regional bone losses, parameters of inflammation or bone resorption was evaluated in 421 patients with RA and controls. RA patients had significantly (P < 0.01) lower BMD values in the carpus (0.405 ± 0.004 g/cm²), metacarpal joint II (0.318 ± 0.036 g/cm²) and metacarpal joint III (0.326 ± 0.022 g/cm²) compared to controls. There was no difference in bone density at the lumbar spine or hip. Significant (P < 0.001) correlations were found between BMD total of the hand, its subregions, the forearm and hip. Parameters of inflammation correlated significantly (P < 0.001) with pyridinolines (r = 0.378), desoxypyridinolines (r = 0.183), forearm (r = −10, P < 0.05), MCP II (r = −0.190, P < 0.001), MCP III (r = 0.204, P < 0.001) and carpus (r = 0.191, P < 0.001).     

Predictors of bone density testing in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) are at increased risk of low bone density and fractures. This study identifies predictors of initiation of dual energy X-ray absorptiometry (DXA) testing in RA. We identified RA patients from the CORRONA registry with ≥1 year follow-up without reported DXA at study entry. The primary outcome was report of DXA in the first year of follow-up (DXA initiation). Variables associated with DXA initiation were considered for the multivariate model. Stepwise logistic regression identified independent predictors. Of the 2,717 RA patients without DXA documented at enrollment, 297 (11%) reported DXA initiation. Independent predictors of DXA initiation included age, female sex, history of fracture, steroid use, and physician’s assessment of RA activity. In conclusion, DXA initiation in RA patients in the CORRONA cohort is low despite increased risk of osteoporosis. Predictors of DXA initiation include fracture, common risk factors for osteoporosis, and RA-associated factors. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis

Rheumatoid arthritis (RA) is commonly associated with decreased bone mineral density (BMD) due to numerous factors. BsmI polymorphism of the vitamin D receptor (VDR) gene has been implicated in the pathogenesis of osteoporosis. Vitamin D has several immunomodulatory effects and thus may play a role in the course of arthritis. However, little data is available on the possible relationship between RA and VDR gene polymorphisms. In this study, the frequency of BsmI polymorphism genotypes were compared with that found in other countries. In this study, 64 RA patients and 40 healthy controls were tested for VDR gene BsmI polymorphism genotypes. Frequencies of B and b alleles were associated with markers of bone metabolism and RA. Among control subjects, the frequency of the BB genotype is relatively high (27.5%). In RA with secondary osteopenia/osteoporosis the BB genotype was more rare, the bb was more common than in control subjects. Markers of bone metabolism were associated with the B allele. RA patients carrying the B allele had lower BMD and increased bone loss over 1 year. The B allele was also correlated with increased osteoclast and osteoblast function, as determined by the assessment of biochemical markers of bone metabolism. Rheumatoid factor titer, which is an independent marker for disease progression in RA, was higher in bb patients. Our data suggest, that the imbalance in B and b allele expression may be involved in the pathogenesis of RA-associated osteoporosis. The possible involvement of vitamin D and VDR gene polymorphisms in the development and progression of RA needs further elucidation.Financial support: ETT 314/96 and ETT 60/2001 grants from the Medical Research Council of Hungary (Z.S.), and FKFP 18/2000 grant from the Research and Development in Highest Education Council (Z.S.).     

Risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis

Objective. No available anti-osteoporotic medication has been shown to completely prevent declines in bone mineral density (BMD) and the resulting increased risk of fracture. The objective of this study was to investigate the risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis (RA).

Methods. A retrospective cohort study of 103 patients with RA and osteoporosis was conducted. Patients were divided into two groups for comparison: those whose osteoporosis treatment was effective and those whose treatment failed. Risk factors for treatment failure were identified by univariate and multivariate logistic regression using variables that differed significantly between the groups.

Results. Osteoporosis treatment failed in 66 of 103 patients (64.1%). During 14.01 months of follow-up, non-adherence to bisphosphonate use was the most powerful risk factor for treatment failure. Daily glucocorticoid dosage ≥ 7.5 mg/day before the first BMD measurement, immobilization > 3 months, and Disease Activity Score in 28 joints (DAS28) ≥ 3.2 were also significantly related to treatment failure.

Conclusion. Our findings indicate that osteoporosis treatment fails frequently in RA patients and adherence to bisphosphonate use, daily glucocorticoid dosage, immobilization, and DAS28 score should be taken into consideration when treating osteoporotic patients with RA.     

Rare copresent rheumatoid arthritis and gout: comparison with pure rheumatoid arthritis and a literature review

Copresent rheumatoid arthritis (RA) and gout is seldom reported. This study summarizes the findings of eight cases of copresent RA and gout and compares them with 31 pure RA cases. Additional reported cases were retrieved from the current literature by Medline search. Patients with copresent RA and gout were older (p = 0.014) and predominantly male (p < 0.01). Synovial fluid, positive for urate crystals, was aspirated most frequently from the knee (five out of eight), followed by the first metatarsophalangeal joint (three out of eight). Serum creatinine and urate levels in the copresent group were significantly higher (p < 0.01, both), and serum hemoglobin was lower (p = 0.04) than those with pure RA. Copresent subjects had much lower percentage of positive rheumatoid factor (RF) tests than patients with pure RA (37.5 vs 80.6%). Only one copresent subject had both RF and anti-cyclic citrullinated peptide antibody. Of copresent subjects, 75% had gouty arthritis before diagnosis of RA, which is consistent with earlier reports. Seven copresent subjects had gout attacks under disease-modifying antirheumatic drug use. This study revealed that polyarthritis negative for RF in a previously gouty patient may be RA and vice versa. This combination occurs more frequently in males. Moreover, anti-CCP antibody examination is not helpful for this diagnosis. Therefore, physicians must obtain synovial fluid for analysis in joints with intense swelling, especially in old RA subjects with renal insufficiency or involvement of lower extremities. Conversely, RA must be considered in gouty patients with polyarticular involvement.     

The bone mineral density effects of calcitonin and alendronate combined therapy in patients with rheumatoid arthritis

Aim The bone mineral density (BMD) effects of calcitonin (CT) and alendronate (ALEN) therapy either alone or in combination were evaluated in patients with rheumatoid arthritis (RA). Method Eighty out of 100 patients with RA using methotrexate 5–12.5 mg/week and prednisone 5–10 mg/day were included in the study. These were randomly divided into four groups: the first group was given ALEN 70 mg/week; the second was given 200 IU/day CT nasal spray; and the third group was given combined therapy of 70 mg/week ALEN and 200 IU/day CT nasal spray. The fourth group (control) as well as the other three groups were given 600 mg calcium and 400 IU vitamin D. Dual‐energy X‐ray absorptiometry BMD of lumbar, hip and forearm regions and laboratory investigations were performed before and at the 12th month of the therapy. Reuslts Only the combined therapy group displayed significant decreases of alkaline phosphatase levels, pointing out that the high bone turnover seen in RA patients can only be normalized by combination therapy. Also the combined therapy group showed significant increases at the lumbar and hip regions, whereas at the forearm regions BMD values stabilized. Conclusion We recommend the use of CT and ALEN combined therapy, especially in severe active cases of RA, but further prospective studies consisting of larger patient populations are needed to confirm the additive effects of this combined therapy on fracture risk in these patients.     

Factors affecting drug treatment compliance in patients with rheumatoid arthritis

We prospectively examined 100 rheumatoid arthritis (RA) patients to calculate drug compliance rates, characteristics of compliant and non-compliant patients, and changes in compliance over time. Three assessments were obtained over a one-year follow–up. Detailed drug history of RA and for concomitant disease was queried. Sedimentation rate, C-reactive protein, and rheumatoid factor values, Ritchie articular index, morning stiffness, and health assessment questionnaire were evaluated. Twenty-six patients (30.2%) were consistently compliant and 10 patients (11.6%) were consistently non-compliant. Older age was associated with a greater likelihood of compliance. Comparison of compliant and non-compliant groups revealed no statistically significant difference in distribution of gender, disease duration, and total number of pills taken for RA and/or total number of pills taken for any reason. In conclusion, compliance to drugs in RA patients is a common problem. Clinical and laboratory activity of RA had less influence on drug compliance. Older age is associated with a greater likelihood of compliance.     

Immunological studies in patients with rheumatoid arthritis receiving azathioprine and myocrisin in combination

Summary Thirty-one patients with classical or definite rheumatoid arthritis (RA), on treatment with azathioprine and sodium aurothiomalate in combination were studied. Absolute lymphocyte counts and IgA levels were reduced but this did not reach statistical significance. Lymphocyte transformation with phytohaemagglutinin (PHA) showed no significant difference from a control group. However, antibody dependent cell-mediated cytotoxicity was significantly impaired compared to rheumatoid controls (p<0.001). There was no relation to the degree of impairment of ADCC and the current dose of azathioprine nor to the total dose or duration of therapy. Inhibiting material to cell-mediated cytotoxicity was present in the sera of 23 patients but its presence showed no relation to the degree of cytotoxicity exhibited by cells in the same patient. Our studies of cellular cytotoxicity have revealed alterations in cellular function possibly attributable to azathioprine.     

Height loss rate as a marker of osteoporosis in postmenopausal women with rheumatoid arthritis

Summary The relation between the loss of height and bone mineral density (BMD) at the lumbar spine and proximal femur was determined in 61 women aged 56–70 years suffering from rheumatoid arthritis. Statistically highly significant negative correlations were found between the loss of height and the spinal and femoral BMD. A loss of 4 cm or more in height over 10 years seems to be associated with a significant decrease of BMD, and it can be recommended as a clinical marker of osteoporosis.     

Nailfold capillaroscopic changes in Egyptian patients with psoriatic arthritis in comparison to rheumatoid arthritis

IntroductionNailfold capillaroscopy (NFC) is simple technique for assessment of the microvascular changes recognized in both diseases can be used in helping the differential diagnosis.Aim of the workTo determine the nailfold capillaroscopic changes in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients and their relation to disease activity.Patients and methodsTwenty PsA and 20 RA patients were studied. Disease activity score (DAS28) was assessed. NFC examination was done to all patients.ResultsThere was a significant decrease in capillary density (8.65 ± 1.39 vs 9.5 ± 1/mm; p = 0.02) and increase in mean capillary width (28.4 ± 7.8 μm vs 22.9 ± 4.3 μm; p = 0.01) in PsA than RA patients. Hairpin, organized capillaries were found in all RA patients while in PsA patients tortuous capillaries were found in 100% and disorganized capillaries in 35%. A significant increase in hemorrhages (65% versus 10%; p < 0.0001) was present in PsA compared to RA patients. In PsA patients, there was a significant correlation between the tender joints count (TJC) and the width of the capillaries (r = 0.44, p = 0.047) and inversely with the capillary density (r = ?0.46, p = 0.04). The TJC significantly associated with the capillary disorganization (p = 0.035). A significant negative correlation between CRP titer and arterial diameter of capillaries (r = ?0.45, p = 0.045).ConclusionThe nailfold capillaroscopy in RA patients had no specific changes, While in PsA patients showed low density, dilated, tortuous and disorganized capillaries and hemorrhages. So, Nailfold capillaroscopy can be used in the differentiation between both diseases. NFC abnormalities may be related to the disease activity.