Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication in established ankylosing spondylitis (AS). It is known that inflammatory activity in rheumatic diseases (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. The aim of this study was to analyze whether inflammatory activity and an alteration of the vitamin D metabolism play a substantial role in the loss of bone mass in AS. In this cross-sectional study, 58 patients with established AS and an age- and sex-matched control group were examined. The vitamin D status was investigated, as was, in parallel, the relationship to disease activity (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), markers of bone metabolism (parathyroid hormone [PTH], 1.25 vitamin D3, 25 vitamin D3), calcium, bone alkaline phosphatase (bone-AP), urine cross-links, and plasma tumor necrosis factor alpha (TNFalpha). Bone mineral density was measured by quantitative computed tomography (QCT) of the lumbar spine. Osteoporosis was diagnosed in early as well as in progressive stages of AS (23/58=39.6%). Furthermore, serum levels of 1.25 vitamin D3 and PTH were negatively correlated with disease activity and TNFalpha. The excretion of cross-links showed a positive correlation with disease activity and TNFalpha, and 1.25 vitamin D3 and PTH were positively correlated with bone-AP. TNFalpha also positively correlated with disease activity. AS patients with osteoporosis showed significantly increased CRP, ESR, cross-links and PTH and a significantly decreased 1.25 D3. Osteoporosis is frequent in AS and high disease activity is associated with an alteration in vitamin D metabolites and increased levels of bone resorption in active AS. Our findings propose a close association of BMD, bone metabolism and inflammatory activity, possibly related to vitamin D inflammation interactions.
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PMID:Association of 1.25 vitamin D3 deficiency, disease activity and low bone mass in ankylosing spondylitis. 1617

Secondary osteoporosis is common among patients being evaluated for osteoporosis. All men and premenopausal women with unexplained bone loss or a history of a fragility fracture should undergo a work-up for secondary osteoporosis. Also, postmenopausal women with risk factors for secondary osteoporosis should be carefully evaluated. The evaluation should include a thorough history, physical examination, bone mineral density testing, and laboratory testing. While there is no consensus for a cost-effective laboratory evaluation, some recommendations include: 25-hydroxyvitamin D, parathyroid hormone (PTH), serum and urine calcium, phosphate, creatinine, liver function tests, a complete blood count, testosterone in men, and thyroid-stimulating hormone. After a thorough review of the evaluation for secondary osteoporosis, this chapter reviews the pathophysiology and treatment of secondary osteoporotic disorders, including vitamin D insufficiency, osteomalacia, the osteoporosis of erosive inflammatory arthritis, ankylosing spondylitis, systemic lupus erythematosus, and osteoporosis related to anti-androgenic therapy for prostate cancer and aromatase inhibitor therapy for breast cancer. Physicians have a significant responsibility to evaluate and treat the underlying medical problem that is the cause of secondary osteoporosis and to optimize bone health in the individual patient.
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PMID:The management of secondary osteoporosis. 1630 Nov 95

Bisphosphonates have the potential to reduce osteolysis, a phenomenon that has been postulated to play a key role in aseptic loosening of total joint replacements. Bisphosphonates may contribute to the in vivo longevity of total joint replacements. Some authors have suggested there are decreases in flexural strength and flexural modulus of the cured cement when a liquid form of disodium pamidronate is added to a commercially available acrylic bone cement (Palacos R). We proposed that it is comparatively easier to blend a bisphosphonate in powder form into an acrylic bone cement than it is when the drug is in liquid form; and that the cement's fatigue life is decreased when the bisphosphonate is added in liquid rather than in solid form. The bisphosphonate and bone cement used were alendronate sodium and Cemex XL, respectively. The fatigue tests were done using phosphate buffered saline solution at 37 degrees +/- 1 degrees C. The data supported both hypotheses. Our findings should guide orthopaedic surgeons when using bisphosphonate-impregnated acrylic bone cements in total joint replacements. Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom replaces the central oxygen atom. These therapeutic agents may be classified into nitrogen and non-nitrogen containing types. Some examples are alendronate, pamidronate, ibandronate, risedronate, etidronate, clodronate, and zoledronate. There are many targets and mechanisms of action of this family of drugs, therefore making them efficacious against diverse clinical conditions such as osteoporosis, periprosthetic bone loss subsequent to total joint replacement, tumor cell proliferation, apoptosis and angiogenesis, Charcot neuroarthropathy, rheumatoid arthritis, ankylosing spondylitis and spondyloarthropathies, and arterial calcification. It has been proposed that some bisphosphonates are effective against the mechanisms that have been suggested as being implicated in aseptic loosening of total joint replacements, these being osteoclast-mediated bone resorption and wear particle-induced osteolysis. A meta-analysis of randomized controlled trials showed that alendronate and pamidronate had beneficial effects maintaining periprosthetic bone for as much as 1 year after a total joint replacement.
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PMID:Alendronate in bone cement: fatigue life degraded by liquid, not by powder. 1644 96

Osteoporosis has received increasing attention as a potential complication of inflammatory bowel disease (IBD). The first population-based data on incidence of fractures in an IBD population were published this past year. The incidence of fractures was one per 100 patient years. Compared with the general population, the fracture rate was increased; however, the relative risk was 1.4 and, therefore, not as high as might be expected from the myriad of studies reporting high rates of osteopenia measured by dual energy x-ray absorptiometry (DXA). Another area receiving increasing attention is that of the enhanced risk of venous thrombosis in patients with IBD. The first population-based incidence rates of venous thrombosis in IBD were also published this past year and showed that IBD patients are affected by venous thrombosis at a rate of approximately one per 200 patient years. The relative risk for venous thrombosis compared with the general population was 3.5. Several studies have reported on associated risk markers or genetic clotting abnormalities, but no clear paradigm has emerged to account for those patients who will suffer a clot. Finally, the first North American population-based study was published, quantifying the prevalence rates of extraintestinal manifestations in patients with IBD for at least 10 years. Some gender- and disease-specific findings emerged. This study found that iritis and uveitis were more common in female patients with ulcerative colitis (3.2%), primary sclerosing cholangitis (PSC) was most common in male patients with ulcerative colitis (3%), ankylosing spondylitis was most common in male patients with Crohn disease (2.7%), and erythema nodosum was most likely to occur in female patients with Crohn disease (1.9%).
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PMID:Osteoporosis and other complications of inflammatory bowel disease. 1703 17

Conflicting data have been published about osteoporosis and bone turnover markers in patients with ankylosing spondylitis (AS). The aim of this study was to determine bone mineral density (BMD) of the lateral lumbar spine in a group of male patients with AS and to investigate the relationship between clinical parameters and markers of bone turnover. Thirty-two consecutive AS patients with a mean disease duration of 14.8 years and 32 control subjects were included. Demographic and clinical characteristics were recorded. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to determine the activity of disease. BMD was determined for the lateral lumbar spine in both patients and control groups. Serum osteocalcin and urinary N-telopeptide were measured as bone turnover markers in patient and control groups. Although the mean values of lumbar BMD in AS patients tended to be lower than in the control group, the difference was not statistically significant. Osteoporosis was observed in 11 (34.3%) of AS patients and in 2 (6.2%) of the control group. Osteocalcin levels were significantly higher in AS patients in comparison with control subjects (p < 0.05). In the subgroup analysis according to the activity of the disease, erythrocyte sedimentation rate and N-telopeptide levels were significantly higher in the severely active group when compared with that in mild or moderate disease groups. Active AS patients compared with the control group had significantly lower BMD and significantly higher N-Telopeptide levels (p < 0.05). The levels of BASDAI scores and N-telopeptide values correlated significantly with each other. The incidence of osteoporosis is high in AS patients, and patients with active disease are especially at risk for developing osteoporosis. The monitoring of bone turnover markers and disease activity indices may help to predict patients at risk. Prophylactic and therapeutic strategies are needed to struggle against bone loss in patients with this disabling condition.
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PMID:Bone mineral density and bone turnover markers in a group of male ankylosing spondylitis patients: relationship to disease activity. 1704 10

The acute as well as chronic clinical features of ankylosing spondylitis (AS) are a burden to the patient and society. Apart from the axial and articular manifestations, extraarticular AS-related comorbidities such as uveitis, inflammatory bowel disease, and psoriasis contribute to the burden of the disease. In addition, a large proportion of patients have osteoporosis or osteopenia, which may be associated with fractures and contribute to kyphosis. All these features result in decreased quality of life. Moreover, patients with AS have an increased mortality rate. The impact of this disease also can be seen in various aspects of workforce participation, from requiring more assistance at paid work to withdrawal from the workforce. Further, patients with AS and, subsequently, society are affected by substantial healthcare costs related to medications and healthcare provider expenses. Early diagnosis and management of patients will likely prevent functional disability and improve patient outcomes.
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PMID:The burden of ankylosing spondylitis. 1704 55

Since healthcare resources are scarce, choices have to be made on how they will be allocated. The use of economic evaluations using cost-effectiveness analyses has increased rapidly as policymakers have realized their value in maximizing the population's benefits (in terms of length of life and health status) within a given budget. Following efforts by OMERACT to create reference case definitions for the conduct of economic evaluation in rheumatoid arthritis, osteoporosis, and osteoarthritis, we review various methodological areas and research decisions that could benefit from a consensus between researchers, clinicians, and drug developers in terms of an ankylosing spondylitis (AS) reference case. Ten methodological issues are presented that will be important for future development of evaluations. Tentative proposals to define the issues in a reference case for AS are made, along with recommendations for further research.
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PMID:Considerations and preliminary proposals for defining a reference case for economic evaluations in ankylosing spondylitis. 1747 83

To date there is no definite cure for ankylosing spondylitis. However, modern treatment improves the quality of life and the final outcome for most patients. Patient education and physiotherapy form the basis of treatment. In pharmacotherapy, nonsteroidal anti-inflammatory drugs have a central role. Second-line drugs such as sulfasalazine, immunomodulating agents and other antirheumatic disease-modifying drugs should be applied if the disease is active. Corticosteroids are used mainly intra-articularly. The problem of osteoporosis in ankylosing spondylitis is gaining more interest, and efforts to prevent or treat it will increase. It is critical to make an early diagnosis of ankylosing spondylitis and in active cases start intensive therapy before irreversible damage takes place.
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PMID:Ankylosing spondylitis: current approaches to treatment. 1802 May 95

For many bone and joint diseases in humans, including postmenopausal osteoporosis, rheumatoid arthritis, and ankylosing spondylitis, an immune-mediated etiology has either been proven or is considered as a co-factor in pathogenesis. The identification of the receptor activator of nuclear factor kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG)-interplay and the in-depth characterization of the signaling pathways induced upon RANK activation, including molecules such as TNF receptor-associated factor 6 (TRAF6), nuclear factor-kappaB (NF-kappaB), and signal transducer and activator of T cells (STAT)-3, now promise to give the opportunity to target osteoclastogenesis specifically. Additionally, many byways influencing osteoclastogenesis have been elucidated, thus giving rise to additional therapeutic approaches. These are based mainly upon the effects of diverse cytokines on osteoclast differentiation with interleukin (IL)-17 and interferone (IFN)-gamma being most prominent at the moment. The same applies for the recently established signaling pathways in osteoblastogenesis, which have attracted much attention in the recent years. In this respect, much attention has been attributed towards bone morphogenetic proteins (BMPs) and the Wnt signaling cascade. In this review, an overview on the key molecules, which (could) serve as promising targets for novel therapeutic interventions with the aim of enhancing osteoblast formation or suppressing osteoclast development, is given. Further on, antibody-based therapeutical schemes as well as methodologically novel, albeit predominantly theoretical at the moment, strategies in the fight against immune-mediated osteopathologies are discussed.
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PMID:Strategies for novel therapeutic approaches targeting cytokines and signaling pathways of osteoclasto- and osteoblastogenesis in the fight against immune-mediated bone and joint diseases. 1822 Jul 68

This report details a case of multiple implant failure (so-called 'cluster phenomenon') in a patient with ankylosing spondylitis and considers some factors for implant failure including reduced bone density. It highlights the relationship between ankylosing spondylitis and osteoporosis although no direct link is made between these conditions and the implant failures in this case.
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PMID:Case report of multiple implant failure in a patient with ankylosing spondylitis. 1846 21


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