Evaluation of calcaneus bone densitometry against hip and spine for diagnosis of osteoporosis.

Dual X-ray absorptiometry (DXA) is now widely available as a method for assessing bone density. However, the place of peripheral bone densitometry in clinical practice for diagnosis of osteoporosis is not yet clear. To examine the potential use in our district general hospital setting, we compared calcaneus measurements with conventional DXA of the hip and spine in 100 patients referred for assessment following identification of risk factors for osteoporosis. Measurements were made on both heels and the results were found to be similar but not completely interchangeable. Use of receiver operating characteristic curves confirmed that a threshold T-score of -1.6 could be used to identify many of the high risk subjects. However, there was only moderate agreement between fracture risk classifications derived from heel T-scores, and diagnostic classification (osteoporosis/osteopenia/normal) derived from axial DXA. The specificity of heel measurements was high, but sensitivity was poorer. Heel measurements could therefore be valuable in some circumstances for finding patients for whom treatment of osteoporosis would be appropriate, such as in a population with a low prevalence of osteoporosis. They may also be of value in a population with a high prevalence of disease, particularly if there were no alternative means of bone densitometry. However, with an intermediate prevalence, the relatively high risk of false negative values would mean that false reassurance could be given to many of those classed as "low risk". This could be a major drawback in clinical practice if heel densitometry were used as the initial investigation and axial measurements were also available, since they would give conflicting results for a substantial proportion of these patients.

Necrotising fasciitis in a patient receiving infliximab for rheumatoid arthritis.

A case of necrotising fasciitis in a patient receiving infliximab, an antitumour necrosis factor alpha (TNF-alpha) agent for rheumatoid arthritis, is presented. A widespread confluent, erythematous, pustular skin rash was the presenting sign. There was no fever throughout this admission. beta-Haemolytic group A streptococcus was isolated from blood cultures and skin swabs. The adductor muscles and fascia around the site of a previous hip arthroplasty were necrotic on exploration. The case highlights the risk of severe sepsis in patients on anti-TNF-alpha treatment.

The long-term effects of non-steroidal anti-inflammatory drugs in osteoarthritis of the knee: a randomized placebo-controlled trial.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat osteoarthritis (OA), though their long-term efficacy is uncertain. We report a comparison of the symptomatic responses to therapy with tiaprofenic acid, indomethacin and placebo over 5 yr. METHODS: A parallel-group, randomized, single-blind trial of patients with knee OA recruited 812 patients from 20 centres; 307 patients received tiaprofenic acid (300 mg b.d.), 202 indomethacin (25 mg t.d.s.) and 303 matching placebo for up to 5 yr. At the end of the parallel-group study, patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo, both given for 2 weeks. Assessments were at baseline, 4 weeks, then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study. They comprised pain scores, duration of morning stiffness, patients' global assessments, paracetamol consumption, adverse reactions, withdrawals and functional outcomes. RESULTS: There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase. Thereafter there were no advantages favouring active therapy. In the cross-over phase, pain scores were significantly lower in patients receiving tiaprofenic acid than placebo. Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa. Adverse events were reported by 61% of patients receiving tiaprofenic acid, 63% on indomethacin and 51% on placebo. Potentially severe side-effects were rare; for example, there were only three cases of gastrointestinal bleeding on NSAIDs. The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study; at 48 weeks 53% of the patients remained on tiaprofenic acid, 50% on indomethacin and 54% on placebo. CONCLUSIONS: NSAIDs significantly reduce overall pain over 4 weeks. This short-term responsiveness is retained, and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo. Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy.

The levels of collagenase, tissue inhibitor of metalloproteinases-1 (TIMP-1), collagenase approximately TIMP-1 complexes and glycosaminoglycan (GAG) in sequential samples of synovial fluid aspirated from patients with osteoarthritis.

OBJECTIVE: Collagen turnover in connective tissues is thought to be controlled by the balance between the levels of interstitial collagenase and tissue inhibitor of metalloproteinases (TIMP-1). The aim of this study was to measure the level of total collagenase (MMP-1), TIMP-1, collagenase approximately TIMP-1 complex and glycosaminoglycan (GAG) in sequential samples of osteoarthritic knee synovial fluid from well documented patients to determine if these parameters changed with time and correlated with clinical indices. METHODS: Twenty-one patients were recruited and randomly allocated to receive tiaprofenic acid, indomethacin or naproxen. Total collagenase, TIMP-1, collagenase approximately TIMP-1 complex and GAG were measured in 80 osteoarthritic synovial fluids taken over a period of six months. RESULTS: The majority of fluids contained a molar excess of TIMP-1 over collagenase, although in seven fluids collagenase was present in excess; six of these samples were from a single patient. GAG levels were relatively unchanged over the six months studied. CONCLUSION: The levels of collagenase and TIMP-1 varied between patients and over time in individual patients. No collagenase approximately TIMP-1 complex was found in any fluid. There was no significant difference in the median levels of collagenase, TIMP-1 or GAG in the different treatment groups. High levels of collagenase were found in one patient with a crystal related disease. These immunoassays give valuable information on the levels of collagenase and TIMP-1 in individual patients with time and may help to determine the mechanisms controlling the turnover of cartilage collagen in different arthritides.

A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' capsules) in the treatment of osteoarthritis.

The efficacy and side-effect profiles of two formulations of indomethacin were compared in a multi-centre, double-blind, crossover study in 77 patients with osteoarthritis. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times daily for a period of 4 weeks, after which patients were crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by the investigator and patient indicate that controlled-release indomethacin tablets, 75 mg given at night, were as efficacious as immediate-release indomethacin capsules, 25 mg given 3-times daily, in the treatment of osteoarthritis. The side-effect profiles of the two formulations were similar.

Reduction of prostaglandin E2 concentrations in synovial fluid of patients suffering from rheumatoid arthritis following tiaprofenic acid or indomethacin treatment.

Prostaglandin E2 (PGE2) is a potent stimulator of inflammation, and the inhibition of its synthesis is one possible mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs). We have investigated patients suffering from rheumatoid arthritis to determine how synovial fluid levels of PGE2 are affected by tiaprofenic acid or indomethacin medication. Ten patients suffering from rheumatoid arthritis were studied, with 5 patients receiving tiaprofenic acid and 5 indomethacin for a 1-week period. Synovial fluid and serum samples were collected over an 8-hour period on days 1 and 8; these were then assayed for PGE2 and active drug concentrations. The concentration of PGE2 in the synovial fluid fell consistently as the concentration of each drug rose, and low levels of PGE2 persisted on continuation of the medication. Tiaprofenic acid appeared to cause a faster onset of inhibition of PGE2 synthesis than indomethacin.

A controlled trial of tiaprofenic acid against indomethacin in patients with rheumatoid arthritis.

A multicentre double-blind crossover study of tiaprofenic acid 600 mg daily against indomethacin 75 mg daily was carried out in 68 patients with rheumatoid arthritis to compare short-term efficacy and tolerance. There were no significant differences in efficacy between the two treatments, but significantly fewer C.N.S. side-effects were associated with tiaprofenic acid treatment. Five patients withdrew during the course of the study due to side-effects and all were receiving indomethacin.

Phototoxic reactions to piroxicam, naproxen and tiaprofenic acid.

Photosensitivity investigations have been carried out using an irradiation monochromator on 31 patients taking one of seven different nonsteroidal anti-inflammatory agents for the treatment of rheumatoid and osteoarthritis. Six patients, who were taking either piroxicam, naproxen or tiaprofenic acid, experienced adverse immediate reactions of erythema and flaring, together with an urticarial response in four of these six patients. No phototoxic response was observed in patients taking either indomethacin, ketoprofen, benorylate or ibuprofen, although firm conclusions about the non-phototoxic nature of these four drugs cannot be drawn from this pilot study because of the small numbers of patients investigated.

Side effects of benoxaprofen.

A study was made of adverse dermatological reactions to the non-steroidal anti-inflammatory agent benoxaprofen. Photosensitivity was seen in several patients, confined to wavelengths less than 340 nm. Other cutaneous side effects were erythema multiforme, the Stevens-Johnson syndrome, milia, and onycholysis. One case of pancytopenia and toxic epidermal necrolysis was reported. patients were not rechallenged with the drug, but these reactions appear to be true side effects of benoxaprofen.

Short-term efficacy and tolerance of tiaprofenic acid ('Surgam') in rheumatoid arthritis and osteoarthritis: multi-centre, placebo-controlled trials.

Two multi-centre, placebo-controlled, crossover trials of tiaprofenic acid were conducted to an identical design: one in 80 patients suffering from rheumatoid arthritis, the other in 60 patients suffering from osteoarthritis. After a washout period, each patient received 600 mg tiaprofenic acid daily and placebo each for 1 week. The results were similar for both trials. Tiaprofenic acid was more effective than placebo in both rheumatoid arthritis and osteoarthritis and differences in all the assessments of efficacy used were statistically significant. This significance was attained from the first day in rheumatoid arthritis and from the second day in osteoarthritis. Tiaprofenic acid was as well tolerated as placebo. Routine laboratory tests revealed no adverse effects. Possible side-effects, which were predominantly mild and related to the gastro-intestinal system, were reported by 23% patients with tiaprofenic acid and 21% patients with placebo. The 2 patients withdrawn for possible side-effects were both receiving placebo.

A controlled trial of tiaprofenic acid versus ibuprofen in rheumatoid arthritis.

Tiaprofenic acid, 200 mg three times a day, was compared with ibuprofen, 400 mg three times a day, in 41 patients suffering from rheumatoid arthritis and already receiving nonsteroidal anti-inflammatory drugs in a double-blind controlled study. The degree of disability expressed as functional class was significantly improved on tiaprofenic acid. There were no other significant differences from initial values on either treatment in any other clinical measure of therapeutic efficacy. Side-effects were few and minor and there were no significant differences between the drugs in this respect.

Diminished mixed lymphocyte response in ankylosing spondylitis.

A diminished mixed lymphocyte response was reported by Nikbin et al. (1976) among patients with ankylosing spondylitis, their asymptomatic relatives and also normal controls carrying the B27 antigen. In the present communication, the responses in 48 ankylosing spondylitis patients and 45 controls were examined in mixed lymphocyte cultures tested against a 'standard stimulator' made up of pooled lymphocytes. A significantly diminished response is confirmed among the ankylosing spondylitis patients, but not in the control group carrying the B27 antigen. The diminished mixed lymphocyte response therefore appears to be more directly associated with the disease than with the B27 antigen, and possibly represents a specific T-cell defect associated with the pathogenesis of the disease.