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ID PMID Title PublicationDate abstract
18173920 Tryptase enhances release of vascular endothelial growth factor from human osteoarthritic 2007 Nov OBJECTIVE: A contribution of mast cells and its mediators in the pathogenesis of arthritis has been postulated. We aimed to clarify the role of mast cell-derived serine protease tryptase and proteinase activated receptor (PAR)-2-mediated signaling in chondrocytes. METHODS: Human articular cartilage specimens were obtained from patients with osteoarthritis (OA), rheumatoid arthritis (RA) and with traumatic fracture without arthritis (PT; as controls) who underwent joint surgery. Isolated chondrocytes were cultured in vitro by monolayer, and confluent cells were incubated with recombinant human lung Beta tryptase or with a PAR-2 agonist peptide. The secreted level of vascular endothelial growth factor (VEGF) in culture supernatant was measured using commercially available ELISA kits, and expression of VEGF mRNA was analyzed using real-time PCR. RESULTS: The tryptase-stimulated chondrocytes from OA or RA, but not from PT patients, produced significantly higher amount of VEGF in their supernatants. The response was blocked by a G-protein receptor inhibitor pertussis toxin, however, was not reproduced by incubation of cells with the PAR-2 agonist, suggesting a presence of non-PAR-2 dependent signals for the VEGF induction. In addition, actinomycin D and cycloheximide did not exert significant inhibition, indicating a regulation of VEGF release by tryptase. CONCLUSION: The inflammatory mediator, mast cell-derived protease tryptase may modulate chondrocyte metabolism through induction of VEGF release.
16816753 Comparison of the anatomical risk for vertebral artery injury associated with the C2-pedic 2006 Jul 1 STUDY DESIGN: We evaluated the trajectories of atlantoaxial transarticular and C2-pedicle screws in 3 dimensions using computerized tomography. OBJECTIVE: To compare the anatomic risk for vertebral artery injury associated with C2-pedicle and atlantoaxial transarticular screws. SUMMARY OF BACKGROUND DATA: The atlantoaxial fixation technique using C1-lateral mass screws combined with C2-pedicle screws is considered a safer technique for preventing vertebral artery injury than atlantoaxial transarticular fixation. However, few reports have compared the anatomic risk of vertebral artery injury associated with C2-pedicle screws with that of transarticular screws. METHODS: A total of 62 consecutive patients with cervical lesions were evaluated using 3-dimensional images reconstructed by a computer-assisted navigation system. We compared the maximum possible diameters of the atlantoaxial transarticular screw and C2-pedicle screw trajectories, and examined whether the maximum possible diameters were limited by the height or width of the bony structure in screw trajectories < or = 4 mm in diameter. RESULTS: Mean maximum possible diameters did not differ significantly between the trajectories of 124 atlantoaxial transarticular and 124 C2-pedicle screws. In screw trajectories < or = 4 mm in diameter, 57.1% of transarticular screw trajectories were limited by the height of the bony structure, and all pedicle screw trajectories were limited by the width. CONCLUSIONS: C2-pedicle screw placement has nearly the same anatomic risk of vertebral artery injury as transarticular screw placement. Preoperative 3-dimensional evaluation may be useful for choosing the best surgical technique.
18094329 The specificity of JAK3 kinase inhibitors. 2008 Feb 15 PF-956980 is a selective inhibitor of JAK3, related in structure to CP-690550, a compound being evaluated in clinical trials for rheumatoid arthritis and prevention of allograft rejection. PF-956980 has been evaluated against a panel of 30 kinases, and found to have nanomolar potency against only JAK3. Cellular and whole blood activity of this compound parallels its potency and selectivity in enzyme assays. It was effective in vivo at inhibiting the delayed type hypersensivity reaction in mice. We compared 2 commercially available JAK3 inhibitors (WHI-P131 and WHI-P154) in the same panel of biochemical and cellular assays and found them to be neither potent nor selective for JAK3. Both were found to be nanomolar inhibitors of the EGF receptor family of kinases. As these compounds have been used in numerous publications in the transplant and autoimmune disease literature, their specificity should be considered when interpreting these results.
16969149 Removal of methotrexate by peritoneal dialysis and hemodialysis in a single patient with e 2006 Sep BACKGROUND: Although methotrexate is highly bound to albumin, it is thought to be removed by hemodialysis and not by peritoneal dialysis. We are not aware of any direct comparison in the same patient. CASE REPORT/METHODS: A 60-year-old patient on continuous ambulatory peritoneal dialysis was admitted to the East Alabama Medical Center for stomatitis and pancytopenia after being given 10 mg of methotrexate for his rheumatoid arthritis. Measurements of total methotrexate levels were made before, during, and after sequential peritoneal and hemodialysis treatments. RESULTS: We found that the clearance of methotrexate measured in the dialysate was equal in the first hour of dialysis for both types of dialysis, although serum levels were markedly lower in hemodialysis compared to peritoneal dialysis. CONCLUSION: Methotrexate was cleared by peritoneal dialysis in the first hour of an exchange and was not associated with a rebound in serum levels. Hemodialysis was associated with lower serum levels; however, there was also a significant rebound 2 hours after the procedure ended. Since neither procedure was able to preclude the death of the patient, other more effective means of methotrexate elimination should be employed.
19150000 [Clinical evaluation of the ceramic femoral component used for reconstruction of total kne 2008 Dec PURPOSE OF THE STUDY: The study evaluates mid-term results of total knee replacement with a zirconia ceramic (ZrO2) femoral component. MATERIAL: The evaluated group comprised 20 knees in 19 patients (4 men and 15 women). In one patient the replacement was performed bilaterally. Two patients had in the contralateral knee the same type of prosthesis with a femoral chrome-cobalt component.The mean age at the time of operation was 65.2 years (range, 38-81 years).The primary indication was 14 times osteoarthritis and 5 times rheumatoid arthritis. The average follow-up period was 6.5 years (range, 2.1-8.5 years). METHODS: Patients included in the study regardless of age, body mass and the basic diagnosis, agreed with the use of the ceramic femoral component. The evaluation covered a range of motion, mechanical axis, joint stability, pain, swelling, ability to walk on level ground and on stairs, subjective satisfaction (EULAR Knee Chart). Radiograph were assessed at one year intervals in two projections to identify the incidence of radiolucency around the implant. The Kaplan-Meier survival curve was used and compared with the survival curve in identical chrome-cobalt implants. RESULTS: At he final follow-up, 14 knees were evaluated, because 3 patients died without any connection with the implant, in one case the tibial component migrated due to necrosis of the tibial condyle in a patient with RA and two implants had to be revised and replaced due to polyethylene wear. No infection or negative tissue reaction was recorded in the evaluated group. The average flexion range was 109 degrees. All knees were stable and without swelling, in two cases there occurred slight femoropatellar pain. Twelve patients were fully satisfied, 2 patients were satisfied with a certain reservation. The differences in the course of the survival curves of chrome-cobalt and ceramic implants were statistically insignificant. DISCUSSION: Although the use of zirconia ceramics in vitro reduces the amount of polyethylene wear, the clinical outcomes of total knee replacements as compared to the hip are not convincing. One of the causes may be the substantially different and more complex biomechanics of the knee. Tribology improvement of the femoral ceramic component cannot compensate the deficiencies in the joint balancing in flexion and extension. The economically and technologically demanding production of these implants may be justified in patients with allergies caused by chrome-cobalt components. CONCLUSIONS: The results of mid-term follow-up of the use of zirconia ceramic femoral components proved no impact on the improvement of the period of survival of the knee implant. No adverse response to the material or mechanical failure of the ceramic components was encountered. Key words: total knee replacement, zirconia ceramic femoral component, TKR mid-term results, ceramic knee survival curve.
18576312 A broad analysis of IL1 polymorphism and rheumatoid arthritis. 2008 Jul OBJECTIVE: It has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well-powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA. METHODS: Key coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single-nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case-control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects. RESULTS: No fully significant associations were observed. Analysis of the discovery case-control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case-control samples. No association with rheumatoid factor, anti-cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here. CONCLUSION: In spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA.
17124600 Differing distributions of CXCR3- and CCR4-positive cells among types of interstitial pneu 2007 Jan Interstitial pneumonia (IP) is an important complication in collagen vascular diseases (CVDs). We examined the distribution of helper T cell subsets in lung biopsies of cases of IP associated with CVD (CVD-IP). The tissues from 27 CVD-IP patients with rheumatoid arthritis (RA), 8 with polymyositis or dermatomyositis (PM/DM), and 8 with systemic sclerosis (SSc) were compared with those from 10 patients with idiopathic pulmonary fibrosis (IPF) in our previous study. The expressions of CXCR3 and CCR4 (chemokine receptors associated in vitro with Th1 and Th2 cells, respectively) in the mononuclear infiltrate were analyzed immunohistochemically. The positive cells were semiquantified in fibrosing areas of the CVD-IP and IPF cases. The number of CXCR3-positive cells was significantly greater in RA-IP than in PM/DM-IP, SSc-IP, or IPF, whereas there were fewer CCR4-positive cells in RA-IP, PM/DM-IP, and SSc-IP than in IPF. The CXCR3-/CCR4-positive cells ratio was significantly higher in RA-IP and PM/DM-IP (but not in SSc-IP) than in IPF. These results support previous reports of the dominance of Th2 cells in some SSc-IP and IPF cases. However, Th1-type immune responses may predominate in RA-IP and PM/DM-IP. Our findings suggest that the pathogenesis of CVD-IPs differs with the helper T cell subset.
16568327 Blood loss in total knee arthroplasty: an analysis of risk factors. 2007 Feb The amount of blood loss in a primary cemented total knee arthroplasty (TKA) seems to vary in different reported studies. We carried out a prospective study to determine the factors affecting the peri-operative blood loss, hidden blood loss and blood transfusion requirements in a primary cemented total knee arthroplasty. The factors analysed were gender, diagnosis, tourniquet time and body mass index (BMI). We included a total of 66 consecutive patients who underwent primary TKA by a single surgeon (A.M). There was significantly more peri-operative blood loss in male patients than in females (p=0.001, Student's t test). The patients with rheumatoid arthritis did not show any statistical difference in peri-operative blood loss compared with that in patients with osteoarthritis. The tourniquet time and the surgical time showed a positive correlation with peri-operative blood loss. The BMI did not show any correlation with peri-operative blood loss. The incidence of blood transfusion was significantly higher in patients with rheumatoid knees as their pre-operative haemoglobin value was low. The amount of hidden blood loss in our series was 38%. We concluded that gender and tourniquet time plays a role in blood loss in TKA, but diagnosis (advanced osteoarthritis [OA] or rheumatoid arthritis (RA) does not. The blood transfusion depends on both pre-operative haemoglobin value and intra-operative blood loss. The post-operative transfusion trigger can be brought to 8.0 g% in a haemodynamically stable patient.
18062565 [Statins--are they potentially useful in rheumatology?]. 2007 Sep For more than 30 years statins have been successfully used in patients with hypercholesterolemia and cardiovascular diseases. Recently, there is a growing body of evidence, that statins exert effects by much exceeding the effect of cholesterol level decrease. Inhibition of earlier stages of cholesterol biosynthesis pathway (not influencing the very cholesterol level) results in blocking the intermediate metabolite synthesis; isoprenoids (farnesyl phosphate and geranyl phosphate), which play a regulatory function in cells. Statins have antiatherosclerotic, antiinflammatory, antioxidant, immunomodulatory and antithrombotic effects. It applies equally to diseases of chronic inflammation type, as to those, where bone metabolism is disturbed. It is well known that statins decrease bone fracture risk; through bone formation intensification, and inhibition of bone tissue resorption. Slowing down the atherosclerosis progression is a very important effect, considering that in rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE) we are dealing with premature and rapid progression of atherosclerotic lesions. In this paper statins pathways of action in rheumatic diseases (including pleiotropic effects), and their potential use in rheumatology have been discussed. Though there is lack of reliable data enabling statins introduction to standard complementary therapy in rheumatic diseases, the results however of completed studies allow concluding of their utility. The statins that were most frequently evaluated in clinical studies were simvastatin and atorvastatin. Studies on statins have been performed in RA, SLE, osteoporosis and systemic vasculotos.
17938531 A case of bucillamine-induced interstitial pneumonia with positive lymphocyte stimulation 2007 A 64-year-old woman with rheumatoid arthritis and treated with bucillamine presented with a productive cough. No obvious infiltration was detected in chest radiography, but CT revealed patchy ground glass opacities in bilateral lung fields. Her serum KL-6 level was elevated and transbronchial lung biopsy showed interstitial pneumonia. Drug lymphocyte stimulation test (DLST) for bucillamine was negative for blood lymphocytes, but positive for bronchoalveolar lavage (BAL) lymphocytes. The pneumonitis improved after the cessation of bucillamine. We therefore made a diagnosis of bucillamine-induced interstitial pneumonia. DLST with BAL lymphocytes is thus suggested to be useful for such diagnoses.
16137814 Economic valuation of informal care: lessons from the application of the opportunity costs 2006 Feb This paper reports the results of the application of the opportunity costs and proxy good methods to determine a monetary value of informal care. We developed a survey in which we asked informal caregivers in The Netherlands to indicate the different types of time forgone (paid work, unpaid work and leisure) in order to be able to provide care. Moreover, we asked informal caregivers how much time they spent on a list of 16 informal care tasks during the week before the interview. Data were obtained from surveys in two different populations: informal caregivers and their care recipients with stroke and with rheumatoid arthritis (RA). A total of 218 care recipients with stroke and their primary informal caregivers completed a survey as well as 147 caregivers and their care recipients with RA. The measurement of care according to both methods is more problematic compared to the valuation. This is especially the case for the opportunity costs method and for the housework part in the proxy good method. More precise guidelines are necessary for the consistent application of both methods in order to ensure comparability of results and of economic evaluations of health care.
18306275 Intra-articular depot formulation principles: role in the management of postoperative pain 2008 Nov The joint cavity constitutes a discrete anatomical compartment that allows for local drug action after intra-articular injection. Drug delivery systems providing local prolonged drug action are warranted in the management of postoperative pain and not least arthritic disorders such as osteoarthritis. The present review surveys various themes related to the accomplishment of the correct timing of the events leading to optimal drug action in the joint space over a desired time period. This includes a brief account on (patho)physiological conditions and novel potential drug targets (and their location within the synovial space). Particular emphasis is paid to (i) the potential feasibility of various depot formulation principles for the intra-articular route of administration including their manufacture, drug release characteristics and in vivo fate, and (ii) how release, mass transfer and equilibrium processes may affect the intra-articular residence time and concentration of the active species at the ultimate receptor site.
15940474 Inadvertent C2-C3 union after C1-C2 posterior fusion in adults. 2006 Mar INTRODUCTION: Some authors pointed out that there were more than a few patients with inadvertent C2-C3 union after C1-C2 posterior fusion, although few detailed studies of C2-C3 union have been reported. The purpose of this study was to clarify whether C2-C3 union accelerated adjacent C3-C4 disc degeneration after C1-C2 posterior fusion and to investigate the related factors for C2-C3 union. METHODS: Sixteen patients with rheumatoid arthritis (RA group) (4 males, 12 females, mean age 60 years, mean follow-up period 4 years and 3 months) and fifteen patients without RA (non-RA group) (11 males, 4 females, mean 52 years, mean follow-up period 3 years and 10 months) who underwent C1-C2 posterior fusion were radiologically assessed. The C2-C3 union was defined as trabecular bone formation at C2-C3 interlamina in lateral radiograph. C3-C4 disc height was measured to evaluate the disc degeneration. RESULTS: C2-C3 union rate was 56% and 60% in RA group and non-RA group, respectively. In RA group, postoperative C3-C4 disc height was lower (Student's t-test, P = 0.029) and the decrease rate of C3-C4 disc height was higher (Student's t-test, P = 0.015) in patients with C2-C3 union than in patients without C2-C3 union. In non-RA group, the age at operation was older (Student's t-test, P = 0.0007), and the C1-C2 fusion angle (Student's t-test, P = 0.012) was smaller in patients with C2-C3 union than in patients without C2-C3 union. CONCLUSIONS: C2-C3 union after C1-C2 posterior fusion occurred in more than half of both groups. Inadvertent C2-C3 union should be considered a radiological complication and a potential risk factor due to acceleration of C3-C4 disc degeneration in RA.
17435840 [Anakinra, a recombinant human IL-1 receptor antagonist, in clinical practice. Outcome in 2007 Jan OBJECTIVE: We evaluated both the efficacy and safety of anakinra in daily routine rheumatoid arthritis clinical practice. METHODS: We studied 60 cases, including patients with previous anti-TNFalpha exposure, treated with anakinra (100 mg/daily s.c.) in combination with methotrexate (7.5-10 mg/week i.m.) or leflunomide (20 mg/die) in a two year observational study. Efficacy measures were assessed using the American College of Rheumatology (ACR) response criteria. Safety was evaluated according to a modified World Health Organization adverse reaction term dictionary. RESULTS: At week 14, ACR 20% response criteria have been fulfilled by 53 (91.3%) out of 58 patients, 51 (87.9%) of them achieving also an ACR 50%and 15 (25.8%) an ACR 70%response. Thirteen patients touched 102 weeks of treatment: ACR 20% response was achieved in 92.3%, while ACR 50% and ACR 70% were respectively found in 84.6% and 38.4% of the cases. The mean decrease in HAQ score was 0.38, p<0.001. Of the 16 patients who were previously treated with anti-TNFalpha blockers, 81.2% responded to anakinra. There was no significant difference in the ACR response between groups with and without previous anti-TNFalpha exposure. Seventeen patients (28.3%) stopped anakinra because of side-effects (5%) or failure to respond (23.3%). Only 4 cases of pulmonitis, of which 2 have been hospitalised, and 1 case with tuberculosis (previously treated with infliximab) were observed. CONCLUSIONS: Our clinical experience confirms that anakinra is effective and safe in the treatment of rheumatoid arthritis. Anakinra seems also useful in patients with previous anti-TNFalpha blockers failures. Even though major adverse events were rare, clinicians should be aware of such a possibility.
17456948 Endogenous endophthalmitis in a rheumatoid patient on tumor necrosis factor alpha blocker. 2007 May The development of anti-tumor necrosis factor (TNF) therapies is a milestone in the therapy of rheumatic diseases. It is of concern whether all potential undesired complications of therapy have been evaluated within clinical trials which have led to treatment approval. Specialists prescribing TNF blockers should be aware of the unusual and severe complications that can occur. We describe a case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.
17045814 Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic proce 2007 Mar OBJECTIVE: The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo. DESIGN: Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis factor alpha (TNFalpha) and oncostatin M (OSM). Supernatants were assessed for changes in biochemical markers, N-terminal propeptide of type II (PIINP) collagen and fragments of C-telopeptide of type II collagen (CTX-II). Matrix metalloproteinases (MMP) were added to metabolic inactivated cartilage and evaluated by the two biochemical markers for formation or degradation, respectively. Finally, urinary CTX-II and PIINP were evaluated for assessment of type II collagen turnover in patients with rheumatoid arthritis (RA). RESULTS: In the bovine articular cartilage explants, IGF-I induced an increase in PIINP level up to 4.8+/-1.1[ng/ml]/mg cartilage whereas CTX-II remained below 0.1+/-0.1[ng/ml]/mg cartilage. In the catabolic stimulated explants both PIINP and CTX-II were released to the supernatant, reaching concentrations of 9.0+/-1.4 and 9.1+/-2.2[ng/ml]/mg cartilage, respectively. RA patients had significantly lower serum concentrations of PIINP (3.4+/-3.7 ng/ml) compared with those healthy individuals (18.7+/-12.41 ng/ml, P<0.001). In contrast, RA patients had significantly higher urinary CTX-II (0.8+/-0.8 mg/mmol) compared to the healthy controls (0.1+/-0.08 mg/mmol, P=0.004). CONCLUSIONS: This study is the first to demonstrate that precursors and degradation products of type II collagen released into the supernatant can effectively reflect the anabolic and catabolic activities of stimulated cartilage explants.
18797940 Risk factors for opportunistic infections in infliximab-treated patients: the importance o 2009 Apr We sought to determine factors associated with opportunistic infections (OI) in infliximab-treated patients. A retrospective study cohort (1999-2004) was examined. Nine OI were diagnosed in 94 infliximab-treated patients: tuberculosis (four), visceral leishmaniasis (one), pyogenic muscular abscess (one Salmonella spp. and one Streptococcus pneumoniae), and two viral infections (hepatitis B virus [HBV] and zoster ophthalmicus). The risk for OI was significantly higher in the first year of treatment (odds ratio [OR] 8; 95% confidence interval [CI] 2-50). Previous treatment with more than two immunosuppressive drugs was the only factor related to OI (OR 8.686; 95% CI 1.889-39.943). We identified the subset of patients treated with infliximab who had a higher risk for OI. The screening of latent infections is key to diminishing the incidence of these infections.
17619881 Etanercept reduces the serum levels of interleukin-23 and macrophage inflammatory protein- 2007 Dec The purpose of this study was to analyze the effect of the soluble TNF-alpha receptor etanercept on the serum levels of IL-16, IL-17, IL-23, and macrophage inflammatory protein-3alpha (MIP-3alpha) in rheumatoid arthritis (RA) patients. Twenty-two patients with RA were administered etanercept once or twice a week for more than 6 months, and we evaluated clinical and laboratory parameters and serum levels of IL-16, IL-17, IL-23, and MIP-3alpha at the baseline and at 3 and 6 months. Additionally, the production of IL-23 and MIP-3alpha of cultured synovial cells stimulated with TNF-alpha from RA patients was determined by ELISA. We also used ELISA kits to determine synovial fluid (SF) levels of IL-17, IL-23, and MIP-3alpha in patients with RA, osteoarthritis (OA), pseudogouty arthritis (PGA), and gouty arthritis (GA). A significant decrease in serum levels of IL-23 and MIP-3alpha was observed at 3 and 6 months after initial treatment of etanercept. TNF-alpha induced MIP-3alpha but not IL-23 production in cultured synovial cells from RA patients. SF levels of IL-17, IL-23, and MIP-3alpha in RA patients showed significantly higher levels than those of OA, PGA, and GA patients. This study demonstrated that the reduction of IL-23 and MIP-3alpha production in RA patients was a newly determined function of etanercept.
19274866 [Current views on the treatment of upper limb compression neuropathies]. 2008 Nov The article presents current views about upper limb neuropathies, their treatment and clinical manifestations. The following conditions are described: carpal tunnel syndrome(CTS), cubital tunnel syndrome(CUTS), radial tunnel syndrome, and posterior nervus interosseus syndrome.
18266400 Effects of bisphosphonates on fracture incidence and bone metabolism in rheumatoid arthrit 2008 BACKGROUND AND OBJECTIVE: There is a risk that disturbances of activities of daily living (ADL) due to rheumatoid arthritis (RA) are increased by the occurrence of fractures, including vertebral compression fractures and femoral neck fractures, in RA patients receiving oral corticosteroid therapy. Bisphosphonates are most commonly used in the treatment of postmenopausal osteoporosis. In a large-scale, randomized, double-blind, placebo-controlled study that was performed to assess the prophylactic efficacy of bisphosphonates, alendronic acid decreased the incidence of vertebral fractures by approximately 50% compared with placebo in postmenopausal patients. A similar result has also been reported with risedronic acid. The present long-term retrospective study evaluated the effects of alendronic acid and risedronic acid therapy on development of new vertebral/non-vertebral fractures in RA patients receiving long-term oral prednisolone therapy at an average dose of 5 mg/day. METHODS: The subjects were 138 general practice patients aged 50-79 years with RA (alendronic acid group 80; risedronic acid group 58) who received oral prednisolone at a dose of 2-15 mg/day for at least 1 year combined with bisphosphonate therapy (alendronic acid 5 mg/day or risedronic acid 2.5 mg/day) for at least 10 months. Patients with five or more vertebral fractures at the start of bisphosphonate therapy were excluded from the study. Vertebral fractures were detected by obtaining plain x-ray films of the thoracic and lumbar spines at the start of bisphosphonate therapy and on completion of follow-up. We measured the incidence of new fractures, the speed of sound (SOS) at the calcaneus as measured by quantitative ultrasound, and levels of crosslinked N-telopeptide of type I collagen (NTX), a marker of bone resorption. The percentage change at each measuring point was tested using the paired t-test. The incidence of new fractures was compared between groups using the Cox proportional hazard model. RESULTS: The incidence of new vertebral fractures was 6.3% in the alendronic acid group and 13.8% in the risedronic acid group; the incidence of new non-vertebral fractures was 6.3% and 12.1%, respectively. The incidence of any fracture was significantly higher and severe fractures tended to be more common in the risedronic acid group. Analysis by the Cox proportional hazard model revealed a significant difference between the two groups with respect to the cumulative incidence of new fractures (p = 0.0386). The SOS of the calcaneus showed no appreciable difference between the two groups. NTX measurements indicated that antiresorptive activity was maintained from 6 months of treatment onwards in the alendronic acid group but not in the risedronic acid group. CONCLUSION: These findings suggest that alendronic acid has a stronger prophylactic effect against fractures than risedronic acid in RA general practice patients taking long-term corticosteroid therapy.