Osteoporosis in rheumatic diseases

Rheumatic diseases, characterized by chronic inflammation and damage to various organs and systems, include systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis and other connective tissue diseases. Bone is a target in many inflammatory rheumatic diseases. In recent years, the survival of patients with rheumatic diseases has increased markedly and the relationship between rheumatic diseases and osteoporosis (OP) has become more prominent. OP and related fragility fractures increase the morbidity and mortality of rheumatic disease. The cause of OP in rheumatic diseases is complex. The pathogenesis of OP in rheumatic diseases is multifactorial, including disease and treatment-related factors. Osteoimmunology, a crosstalk between inflammatory and bone cells, provides some insight into the pathogenesis of bone loss in systematic inflammatory diseases. The aim of this article is to review different risk factors in rheumatic diseases. Several factors play a role, such as chronic inflammation, immunological factors, traditional factors, metabolism and drug factors. Chronic inflammation is the most important risk factor and drug treatment is complex in patients with OP and rheumatic disease. Attention should be paid to bone loss in rheumatic disease. Optimal treatment of the underlying rheumatic disease is the first step towards prevention of OP and fractures. Apart from that, a healthy lifestyle is important as well as calcium and vitamin D supplementation. Bisphosphonates or denosumab might be necessary for patients with a low T score.     

Aortic valve insufficiency in patients with chronic rheumatic diseases

Aortic valve lesions are often found in patients with rheumatic diseases, but their clinical significance has not been properly evaluated. In the present study, the echocardiographic files of the cardiology unit of the Oulu University Hospital were screened for a diagnosis of aortic insufficiency (AI). The aetiology of the valve disease and specific details of the rheumatic disease were evaluated in 160 patients. Twenty-eight patients (18%) had a history of rheumatic fever. Rheumatic disease was found in 14 patients (8.8%) with AI, which is significantly more than the prevalence of rheumatic diseases (1.8%) in the corresponding age group (35–100 years) in Finland. Rheumatoid arthritis or juvenile rheumatoid arthritis was found in seven patients (4.4%), whereas ankylosing spondylitis or seronegative spondylarthropathy were found in four patients (2.5%). Other rheumatic diseases included Takayasu's arteritis (two patients) and scleroderma (one patient). When 38 patients with pure AI without other possible aetiology were analysed, rheumatic disease was found in five patients (13%). Patients with rheumatic disease as a potential aetiology of AI often had symptomatic valve disease, which required surgical treatment, although great differences between different aetiologies were not found.     

Health-related quality of life in patients with common rheumatic diseases referred to a university clinic

The aim of the present study was to assess the health-related quality of life (HRQoL) in patients with common rheumatic diseases referred to a rheumatology clinic and to compare it to the HRQoL of the general population. All patients with a new referral to the Department of Rheumatology of the Helsinki University Central Hospital were asked to participate in the study during the period from May 2002 to April 2003. A total of 295 patients with various rheumatic diseases were included in the analysis: 99 patients with rheumatoid arthritis (RA), 47 with arthralgia and fibromyalgia, 43 with other chronic arthritis (spondyloarthritis, psoriatic arthritis, enteropathic arthritis), 44 with osteoarthritis (OA), 22 with active reactive arthritis (ReA), 17 with systemic rheumatic diseases, 9 adults with juvenile idiopathic arthritis (JIA) and 14 with other diagnoses. HRQoL was measured by a disease specific instrument, the Stanford health assessment questionnaire (HAQ) and by a generic instrument, 15D. The mean baseline 15D score of the 295 included patients (0.822, SD 0.114) was significantly lower than of the general population (0.903, SD 0.098). Patients with OA and chronic arthritis reported the poorest HRQoL scores (both 0.810 on a 0-1 scale). In patients with RA and ReA the 15D score improved in a statistically significant and clinically important manner during the 8-month follow-up. Discomfort and symptoms caused by the disease were alleviated in a statistically significant manner in patients with RA as well as in those with arthralgia and fibromyalgia, chronic arthritis, ReA and systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. The HRQoL of patients with common rheumatic diseases at referral to rheumatology clinic is significantly lower than the HRQoL of age-standardized general population. The most affected patients are those with OA, chronic arthritis and RA. A significant improvement in HRQoL with conventional interventions was achieved in patients with RA and ReA.     

Microbes,helminths, and rheumatic diseases

There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood.The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.     

Mortality in the rheumatic diseases

Objective. To review mortality data in published studies of various rheumatic diseases. Methods. A MEDLINE search of the literature on the rheumatic diseases, including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, polymyositis, and vasculitis. Results. Mortality rates higher than expected have been reported in most rheumatic conditions, considerably higher for inflammatory rheumatic diseases. The mortality rates in patients with systemic lupus erythematosus, scleroderma, polymyositis, and vasculitis are often comparable to mortality rates seen in patients with neoplastic or cardiovascular diseases, although the causes of death often are not identified as the rheumatic disease. Conclusion. Mortality has been found to be predicted in most instances by more severe clinical status, and therefore death should not be considered as “unrelated” to the rheumatic disease. These observations may have important implications for clinical care and health policies regarding patients with rheumatic diseases.     

Metabolic abnormalities in patients with inflammatory rheumatic diseases

Patients with rheumatoid arthritis (RA) experience an increased cardiometabolic risk factor burden that is substantially driven by systemic inflammation. This occurs less consistently in patients with ankylosing spondylitis (AS). Psoriatic arthritis most strongly associates with excess adiposity and metabolic risk. RA patients also often have systemic inflammation-induced proinflammatory high-density lipoprotein (HDL) cholesterol particles and lean/muscle mass loss in association with increased adiposity, a condition termed rheumatoid cachexia, which further enhances cardiovascular risk. The presence of proinflammatory HDL and lean mass loss was also reported in patients with AS. Individualized aerobic and resistance exercise programs can improve body composition and metabolic risk factor profiles in RA and AS. Future studies should assess how long-term lifestyle changes can be effectuated and if these can influence cardiovascular events in inflammatory rheumatic diseases. Herein, we review the current evidence on metabolic abnormalities in inflammatory arthritis. We propose management strategies and a research agenda.     

Orofacial manifestations in patients with inflammatory rheumatic diseases

The main orofacial manifestation of the inflammatory rheumatic diseases is that of Sjögren's syndrome. In addition, there is a constellation of orofacial manifestations of the inflammatory rheumatic diseases, many of which are extra-articular with some constituting presenting signs of the underlying rheumatic disease. This review will discuss the orofacial manifestations in a variety of connective tissue diseases and will also allude to the oral adverse drug reactions that may occur as a consequence of therapy.     

Assessment of fatigue and functional impairment in patients with rheumatic diseases

Aim of the workTo assess fatigue and functional impairment in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS) and fibromyalgia (FM) patients and their correlation with the corresponding clinical characteristics and determine their predictors.Patients and methods150 patients (40 RA, 40 SLE, 40 primary FM and 30 AS) and 80 matched controls were studied. All patients underwent full clinical examination and laboratory investigations to score disease activity and severity. Fatigue was assessed by the short form-36 (SF-36) and the visual analogue scale (VAS) of fatigue. Functional status was assessed by the modified health assessment questionnaire (mHAQ).ResultsThe patients were 112 females and 38 males and the mean age was 36.7 ± 12.2 years. Fatigue and functional impairment were significantly higher in all patients compared to control. The highest frequency of fatigue was found in FM (100%) and the lowest in AS (60%). Functional impairment was 100% in FM and lowest in SLE (27.5%). Fatigue and functional impairment were more severe in RA and SLE females and in AS males. Fatigue and functional impairment significantly correlated with disease activity and severity for all the studied diseases. On regression, disease activity and severity in RA and SLE as well as severity in FM and activity in AS were predictors of fatigue and functional impairment.ConclusionsFatigue and functional impairment are common in rheumatic diseases and strongly related to disease activity and severity. Good control of fatigue and functional impairment can be achieved through early control of disease activity and severity.     

The clinical application of etanercept in Chinese patients with rheumatic diseases

Abstract

Over a 2-year period, to evaluate the efficacy and safety of biologic agents, etanercept (25?mg twice per week, s.c.) was used to treat 57 rheumatoid arthritis (RA) patients, 9 ankylosing spondylitis (AS) patients, 6 psoriatic arthritis (PSA) patients, and 4 juvenile rheumatoid arthritis (JRA) patients. In addition to inflammatory arthritis, I have used this tumor necrosis factor (TNF) blocker in other rheumatic diseases including idiopathic thrombocytopenic purpura (ITP), Behçet's disease with intractable oral ulcer, fibromyalgia syndrome, and systemic lupus erythematosis with intractable pleural effusion and acute lumbar disc herniation. For RA, after 6 months of etanercept treatment, all the parameters including number of swollen joints, number of tender joints, disease activity score, erythrocyte sedimentation rate, C-reactive protein, and global health status were rapidly improved (P < 0.001 or P < 0.0001). The anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor also significantly declined. For spondyloarthropathy, it also gave a similar effect as to RA. Both Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index also improved. One of the two cases with Behçet's disease with intractable oral ulcer had a long-term remission after etanercept. The other Behçet's disease patient with oral ulcer and another with ITP obtained a good response temporarily. The short-term use of etanercept (<3 months) did not bring a significant effect for cases of fibromyalgia syndrome, pleural effusion, and lumbar disc herniation. In conclusion, a dramatic and rapid clinical response in different kinds of arthritis patients can be achieved by etanercept. Moreover, the TNF-α inhibitor also can treat other severe rheumatic-related symptoms. In general, except for a few cases with infection and two cases with malignancy, etanercept was safe in our arthritis patients. We need to study a larger number of patients in order to better understand the efficacy and safety of etanercept.     

Prevalence of rheumatic diseases and disability in China

The objective of this study was to provide a single source for the best available estimates of the national prevalence of common rheumatic disorders and rheumatic disability by reviewing the epidemiological surveys conducted in China. Relevant publications were retrieved by search engines in both the English and the Chinese language web sites. Only community-based surveys conducted in China were included. A pooled prevalence with 95% confidence interval was calculated. Forty-one surveys met the inclusion criteria. Prevalence of rheumatic pain varied from 11.6 to 46.4%, with significantly higher rate in northern China in comparison to the southern part. Prevalence of rheumatic disability, however, did not increase with higher latitude. Limitation to daily life and work was 1–2 and 3–6%, of general population, respectively. The pooled prevalence of rheumatoid arthritis, ankylosing spondylitis, and undifferentiated spondylarthropathy is 0.37, 0.22 and 0.57%, respectively. The estimated prevalence is 37.7/100,000 for systemic lupus erythematosus, and 0.45% for primary Sjögren’s syndrome. In the past decade, prevalence of gout and hyperuricemia was 0.22–0.43 and 12.1–25.2%, respectively. In elderly Chinese age ≥60, prevalence of symptomatic cervical OA, lumbar OA, knee OA and hand OA was 14.5, 24.0, 19.4, and 5.0%, respectively. Symptomatic hip OA was rare. Rheumatoid arthritis and gout are less frequent in Chinese than in Caucasians. The prevalence of ankylosing spondylitis, systemic lupus erythematosus and primary Sjögren’s syndrome is comparable to that in Caucasians. In comparison to the whites, the Chinese population has a higher prevalence of knee OA, a lower prevalence of hand OA, and a much lower prevalence of hip OA.     

The clinical application of etanercept in Chinese patients with rheumatic diseases

Over a 2-year period, to evaluate the efficacy and safety of biologic agents, etanercept (25?mg twice per week, s.c.) was used to treat 57 rheumatoid arthritis (RA) patients, 9 ankylosing spondylitis (AS) patients, 6 psoriatic arthritis (PSA) patients, and 4 juvenile rheumatoid arthritis (JRA) patients. In addition to inflammatory arthritis, I have used this tumor necrosis factor (TNF) blocker in other rheumatic diseases including idiopathic thrombocytopenic purpura (ITP), Behçet's disease with intractable oral ulcer, fibromyalgia syndrome, and systemic lupus erythematosis with intractable pleural effusion and acute lumbar disc herniation. For RA, after 6 months of etanercept treatment, all the parameters including number of swollen joints, number of tender joints, disease activity score, erythrocyte sedimentation rate, C-reactive protein, and global health status were rapidly improved (P < 0.001 or P < 0.0001). The anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor also significantly declined. For spondyloarthropathy, it also gave a similar effect as to RA. Both Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index also improved. One of the two cases with Behçet's disease with intractable oral ulcer had a long-term remission after etanercept. The other Behçet's disease patient with oral ulcer and another with ITP obtained a good response temporarily. The short-term use of etanercept (<3 months) did not bring a significant effect for cases of fibromyalgia syndrome, pleural effusion, and lumbar disc herniation. In conclusion, a dramatic and rapid clinical response in different kinds of arthritis patients can be achieved by etanercept. Moreover, the TNF-α inhibitor also can treat other severe rheumatic-related symptoms. In general, except for a few cases with infection and two cases with malignancy, etanercept was safe in our arthritis patients. We need to study a larger number of patients in order to better understand the efficacy and safety of etanercept.     

Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) and non-RA rheumatic diseases

Abstract

Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA–PCP patients were found to have a higher mortality rate than non-RA–PCP patients (3/7 vs. 0/12, respectively; p = 0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p = 0.036) despite lower mean levels of serum beta-d-glucan (314 ± 214 vs. 1139 ± 1114 pg/ml, respectively; p = 0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia.     

Clinical and epidemiological features of rheumatic diseases in patients attending the university hospital in Kinshasa

The aim of the present retrospective and hospital-based study was to describe epidemiological and clinical features of rheumatic diseases in patients attending the University Hospital of Kinshasa (UHK). Rheumatic complaint was a reason for consultation in 12.1% of outpatients attending the Department of Internal Medicine of the UHK. Osteoarthritis was the most common rheumatic disease (59.2%), followed by soft tissue rheumatism (16.1%), gout (9.3%), and spondylarthropathies (7.5%). The cumulative frequency of autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and mixed connective tissues disease) and the frequency of osteoporosis were 5.2 and 2.7%, respectively. Lumbar spine was the part of the skeleton mostly affected by osteoarthritis. Pathological fractures in osteoporosis, subcutaneous nodules, rheumatoid factor, and erosive bone lesions in rheumatoid arthritis were rarely found. Compared to the previous studies performed in the same hospital, our results disclose a threefold increase of rheumatic outpatients. The paucity of erosive arthritis and extra-articular manifestations suggest the less severity of rheumatoid arthritis in our patients. Likewise, the absence of femoral and wrist osteoporotic fractures and the scarcity of advanced vertebral crush fractures suggest the mildness of osteoporosis.     

Neutrophil gelatinase levels in plasma and synovial fluid of patients with rheumatic diseases

To examine the clinical significance of neutrophil gelatinase in rheumatic diseases, plasma and synovial fluid (SF) gelatinase levels were determined in 62 patients with rheumatoid arthritis (RA), 12 patients with ankylosing spondylitis (AS), 18 patients with osteoarthritis (OA) and 17 healthy controls. The gelatinase level was measured by enzyme-linked immunoassay (ELISA). The assay had a sensitivity of 1 ng/ml and a working range of 5–25 ng/ml. Gelatinase levels were significantly higher in the plasma of patients with RA and of patients with RA complicated by amyloidsis or vasculitis as compared to those of healthy controls. Moreover, the mean value of gelatinase in the plasma of patients with RA complicated by vasculitis was found to be significantly higher than that of RA patients without vasculitis. A significant increase in gelatinase concentration was also observed in the plasma of AS patients but not in the plasma of patients with OA. The concentration of gelatinase in the RA SF samples was much higher (18-fold) than the level of the enzyme in the plasma of RA patients. There was also a higher concentration of gelatinase (fourfold) in OA SF compared with OA plasma. The results suggested that circulating gelatinase may reflect some degree of neutrophil activation in patients with inflammatory arthritis, especially in those with RA complicated by vasculitis. However, the results did not allow a differentiation between chronic and acute inflammation.     

Use of alternative therapies by patients with rheumatic disease in Guadalajara,Mexico: Prevalence,beliefs, and expectations

Objective . To assess the prevalence, practices, beliefs, and expectations of patients with rheumatic diseases in relation to the use of alternative therapies. Methods . We conducted a cross-sectional survey of 300 consecutive patients with rheumatic diseases at 3 outpatient rheumatic disease clinics in Guadalajara, Mexico to evaluate the use of alternative therapies. A face-to-face structured interview was administered by a trained assistant to evaluate the prevalence of use and patient beliefs, perceptions, and expectations in relation to alternative therapies. Results . Two hundred fifty patients (83%) had used a total of 1,386 alternative therapies (range 1–19); 203 (68%) patients had used alternative therapy in the previous 12 months. Sixty-one percent received at least one alternative treatment before the first rheumatology consultation, but an additional 18% initiated these therapies after their initial contact with a rheumatologist at our clinics. Only 66 (26%) of the patients using alternative therapy notified their rheumatologist about their use. Thirty-six patients (14%) discontinued formal treatment at least on one occasion in order to receive alternative therapies, and only 8 (22%) notified their rheumatologist. Alternative therapy practitioners recommended discontinuation of conventional therapy on 57% of the occasions when formal treatments were discontinued. Mean expenditures per patient for fees to alternative therapy providers were equivalent to 28 days of the official minimum daily wage, and per patient costs for the remedies themselves were equivalent to 13 days of the official minimum daily wage. Patients who used alternative therapy in the past 12 months had lower education (7 versus 10 years, P > 0.001) and were slightly more disabled (1.7 versus 1.5, modified Health Assessment Questionnaire, P > 0.01). Conclusions . In this survey most patients used alternative therapies for the treatment of their rheumatic disease. Alternative therapies were costly and appeared to decrease adherence to conventional therapy. Health care providers should openly discuss the use of alternative therapy in patients with rheumatic diseases.     

Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy

Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers {osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)]}. The daily glucocorticoid dose was 10 mg prednisone equivalent (median), and the cumulative dose was 12 g prednisone equivalent (median). None of the patients had previously taken medication for osteoporosis. Osteoporosis was demonstrated in 35.3% of the patients, osteopenia in 47.5%, and a normal BMD in 17.2%. The results of tandem-MP ostase correlated with the BMD of the lumbar spine and of the femoral neck. The values for N-terminal telopeptide and pyridinoline correlated only with the bone density of the femoral neck. All results were statistically significant, although the correlation coefficients were low. After classification of the patients according to their BMD values (osteoporosis, osteopenia and normal BMD), there were significantly more patients with bone markers above the norm in the osteoporosis group and in the osteopenia group than in the group with normal bone density. All bone markers recorded behaved similarly in relation to the bone density values. The same analysis was also undertaken for the different disease groups. In these subgroups there was also a correlation between ostase/crosslinks with BMD, but the correlation coefficients were low. A general recommendation for the routine use of a specific bone marker in patients with rheumatic diseases on glucocorticoid therapy cannot be made from a cost-benefit point of view mainly because of limited predictive power (low correlation coefficients, incomplete correlation with different sites of BMD measurement).     

Leukocytapheresis for rheumatic disease

Leukocytapheresis (LCAP) is an apheresis technique for depleting pathogenic leukocytes from the circulating blood to improve the condition of the patient. LCAP sensu lato has been applied for the treatment of various rheumatic diseases: other treatments include thoracic duct drainage, photopheresis, centrifugal LCAP, granulocytapheresis (GCAP) and filtration LCAP. Among these modalities, GCAP and filtration LCAP are most commonly used in Japan for two reasons; the equipment and procedure are simple and practical and adverse events are rare and minor. In this article, LCAP, in particular filtration LCAP, for the treatment of rheumatic diseases is reviewed.     

Domain reactivity of autoantibodies to calpastatin in patients with systemic rheumatic diseases

Autoantibodies to calpastatin (endogenous inhibitor of calpain, a calcium-dependent neutral proteinase) have been detected in sera of patients with rheumatoid arthritis (RA) and other diseases. We investigated the epitope reactivity of anticalpastatin autoantibodies in patients with rheumatic diseases. cDNAs encoding each calpastatin domain (L, I, II, III, and IV) were amplified by PCR and ligated into an expression vector. The fusion proteins were expressed in E. coli. The presence of autoantibodies specific for each calpastatin domain was assayed in sera of patients with various rheumatic diseases by immunoblotting the fusion proteins with these sera. Of the RA patient sera, 81% reacted with at least one calpastatin domain. This reaction was significantly greater than with sera from patients with systemic lupus erythematosus (46%), scleroderma (32%), polymyositis/dermatomyositis (43%), and normal controls (13%). Domains I and II were recognized by RA patient sera significantly more than by other patient sera, whereas domains III and IV reacted almost equally among all patient sera. Although, collectively, sera from RA and lupus patients reacted equally with all domains, scleroderma sera tended to react with only domains I and IV and myositis sera tended to recognize only domains III and IV. Patients with RA positive for anticalpastatin antibodies exhibited more active disease (i.e., a higher erythrocyte sedimentation rate and C-reative protein level) than antibody-negative patients. Our results suggest that anticalpastatin antibodies were detected in RA with the highest frequency and that different domain reactivity was shown among different diseases. The presence of these antibodies in sera may be related to the type of disease and, in RA, with disease activity, suggesting their importance in rheumatic disorders. Received: September 11, 1999 / Accepted: November 20, 1999