Prevalence of symptomatic hip and knee osteoarthritis: a two-phase population-based survey.

OBJECTIVE: Osteoarthritis (OA) epidemiologic data are scarce in Europe. To estimate the prevalence of symptomatic knee and hip OA in a multiregional sample in France. DESIGN: A two-phase population-based survey was conducted in six regions in 2007-2009. On initial phone contact using random-digit dialing, subjects 40-75 years old were screened with a validated questionnaire. Subjects screened positive were invited for ascertainment: physical examination and hip and/or knee radiography (Kellgren-Lawrence grade≥2). Multiple imputation for data missing not-at-random was used to account for refusals. RESULTS: Of 63,232 homes contacted, 27,632 were eligible, 9621 subjects screened positive, 3707 participated fully in the ascertainment phase, and 1010 had symptomatic OA: 317 hip, 756 knee. Hip OA prevalence according to age class ranged from 0.9% to 3.9% for men and 0.7-5.1% for women. Knee OA ranged from 2.1% to 10.1% for men and 1.6-14.9% for women. Both differed by geographical region. The hip and knee standardized prevalence was 1.9% and 4.7% for men and 2.5% and 6.6% for women, respectively. CONCLUSIONS: This confirmed the feasibility of using a screening questionnaire for eliciting population-based estimates of OA. In France, it increases with age and is greater among women above the age of 50. The geographical disparity of hip and knee OA parallels the distribution of obesity. Study registration ID number 906297 at http://www.clinicaltrials.gov/.

EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis.

OBJECTIVE: To develop evidence-based recommendations for the diagnosis of knee osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 12 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched systematically. Whenever possible, the sensitivity, specificity and likelihood ratio were calculated for individual diagnostic indicators and a diagnostic ladder was developed using Bayes' method. Secondary analyses were undertaken to test directly the recommendations using multiple predictive models in two populations from the UK and the Netherlands. Strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Recommendations covered the definition of knee OA and its risk factors, subsets, typical symptoms and signs, the use of imaging and laboratory tests and differential diagnosis. Three symptoms (persistent knee pain, limited morning stiffness and reduced function) and three signs (crepitus, restricted movement and bony enlargement) appeared to be the most useful. Assuming a 12.5% background prevalence of knee OA in adults aged > or =45 years, the estimated probability of having radiographic knee OA increased with increasing number of positive features, to 99% when all six symptoms and signs were present. The performance of the recommendations in the study populations varied according to the definition of knee OA, background risk and number of tests applied. CONCLUSION: 10 key recommendations for diagnosis of knee OA were developed using both research evidence and expert consensus. Although there is no agreed reference standard, thorough clinical assessment alone can provide a confident rule-in diagnosis.

Screening for hip and knee osteoarthritis in the general population: predictive value of a questionnaire and prevalence estimates.

OBJECTIVE: To study the feasibility and validity of a two-step telephone screening procedure for symptomatic knee and hip osteoarthritis (OA) in the general population. METHOD: The screening questionnaire was based on signs and symptoms, previous diagnosis of OA and validated OA criteria. A random sample of telephone numbers was obtained and, at each number, one person aged 40-75 years was included. A physical examination and knee or hip radiographs were offered when the screen was positive. A sample of subjects with negative screens was also examined. The diagnosis of hip/knee OA was based on the American College of Rheumatology criteria for signs and symptoms and Kellgren-Lawrence radiographic stage 2 or greater. Prevalence rates were estimated with correction for the performance of the screening procedure. RESULTS: Of 1380 subjects, 479 had positive screens, among whom 109 were evaluated; symptomatic radiographic OA was found in 50 subjects, at the knee (n = 35) or hip (n = 20). Corrected prevalence estimates of symptomatic OA were 7.6% (6.4%-8.8%) for the knee and 5% (3.9%-6.1%) for the hip. The screening procedure had 87% (95% CI 79% to 95%) sensitivity and 92% (95% CI 91% to 93%) specificity for detecting knee OA and respectively 93% (95% CI 86% to 100%) and 93% (95% CI 92% to 94%) for hip OA. CONCLUSION: This study establishes the feasibility of telephone screening for symptomatic knee/hip OA, which could be used for a nationwide prevalence study. Pain and previous OA diagnosis were the best items for detecting symptomatic OA.

Clinical and densitometric efficacy of the association of interferon alpha and pamidronate in the treatment of osteoporosis in patients with systemic mastocytosis.

Osteoporosis accompanying severe mastocytosis leads to numerous compressed vertebrae. We treated four patients (mean age 52 years) with severe osteoporosis and mastocytosis proven by bone marrow biopsy (more than 40 mast cells/mm3), according to the following protocol: interferon alpha (IFN) 3 million units (MU) three times a week, reduced to 1.5 MU three times a week in the event of intolerance, and pamidronate (Pam) 90 mg/month in infusion. This treatment was given for 2 years. It was followed by Pam alone at a dose of 90 mg/month. After 3 or 4 years of treatment, no patient presented new vertebral or extravertebral fractures. The mean increase in bone mineral density (BMD) with IFN and Pam was 16.05+/-6.12% at the spine, 5+/-2.24% at the femoral neck, and 4.12+/-3.03% for the whole body; the increase or loss of BMD with Pam alone was +0.2+/-2.13% at the spine, -2.25+/-2.78% at the femoral neck, and -0.1+/-3.35% for the whole body. In one patient, the IFN dose was halved because of a flu-like syndrome, and in another IFN was discontinued at one year for the same reason. The association of IFN and Pam led to a major increase in bone marrow density in osteoporosis with concomitant mastocytosis and this gain was then maintained by monthly infusions of Pam.

Comparison of the analgesic efficacy of pamidronate and synthetic human calcitonin in osteoporotic vertebral fractures: a double-blind controlled study.

Our aim was to compare the analgesic efficacy of pamidronate (PAM) and synthetic human calcitonin (CT) in intravenous infusion for recent painful benign vertebral compression in a randomised prospective double-blind study. Twenty-seven patients aged 49-85 years with painful benign non-traumatic vertebral compression were included in the study. They received either PAM (1 mg/kg) or synthetic human CT (1.5 mg) as an intravenous infusion. Pain and functional disability were evaluated before infusion, and 4 and 30 days afterwards. The pain score assessed on a visual analogue scale at day 0 was 5.94+/-2.47 in patients treated with PAM and 6.27+/-2.50 in patients treated with CT (p=0.74); at day 4, 4.8+/-2.80 with PAM vs 3.9+/-2.68 with CT (p=0.37); and at day 30, 3.6+/-3.13 with PAM vs 3.10+/-2.76 with CT (p=0.70). Spinal function scores were 18.21+/-3.17 at day 0 in patients treated with PAM vs 17.23+/-4.42 in patients treated with CT (p=0.69) and at day 30, 13.7+/-5.36 with PAM vs 12.33+/-3.22 with CT (p=0.68). We found no advantage of PAM over CT in a single intravenous infusion for the treatment of painful recent benign vertebral compression. Since CT is ten times less costly, its use should be preferred.

Do new therapeutic approaches (autotransplants, thalidomide, dexamethasone) improve the survival of patients with multiple myeloma followed in a rheumatology department?

Survival of patients with multiple myeloma (MM) showed no improvement between the 1960s and 1990s. During the last decade, new therapeutic approaches seemed likely to offer hope of prolonging survival. The aim of this study was to examine if this survival increased with the usage of new treatments. The method involves a retrospective study of 123 patients with MM, diagnosed between 1975 and 1999, all receiving treatment. They were divided into two groups: group 1 included 55 patients given the so-called "old treatments" [melphalan-prednisone, cyclophosphamide-prednisone, polychemotherapy (vincristine, melphalan, cyclophosphamide, prednisone (VMCP), VMCP-VBAP)], and group 2 included 68 patients receiving at least one of the so-called "new treatments" (dexamethasone, thalidomide, high-dose chemotherapy followed by autotransplants, bisphosphonates, interferon). The two groups were similar in terms of age, sex ratio and renal impairment, and the percentage of light-chain MM was identical in both groups. Patients who had been given a "new" treatment (group 2) had longer median survival than the patients in group 1 (54 vs 42 months). Independent analysis of each treatment modality showed increased median survival in MM patients treated using autotransplantation compared with untreated patients (125 vs 45 months). Survival was also longer in MM patients treated with thalidomide than in untreated patients (72 vs 42 months). On the other hand, neither bisphosphonates, interferon-alpha nor dexamethasone result in improved survival. Our findings emphasize the increased survival of the MM patients treated with new therapeutic approaches.

Multiple intraosseous meningiomas.

In our knowledge, we are the first to report an observation on multiple osteomeningioma.

T-cell receptor variable region of the beta-chain gene use in peripheral blood and multiple synovial membranes during rheumatoid arthritis.

In order to look for a site-specific T-cell response in RA SM, PCR analyses using oligonucleotide primers specific for 24 TCRBV (V beta) families were performed to compare the respective usage of each TCRBV gene by T cells present in PB and SM of 13 patients with RA. In four patients, SM cells from two or three sites of inflammation were subjected to analysis. In one patient, synovial tissue was studied at two different phases of the disease, resulting in a total number of 19 samples of SM cells, which were compared with paired samples of PB cells. The results showed that whereas all 24 TCRBV gene families could be detected in both PB and SM cells, there was some skewing of increased or decreased usage frequencies of particular TCR V beta genes among SM cells. Three TCRBV families were often overexpressed in SM: V beta 3, V beta 17, and V beta 22. Moreover, V beta 4 was often decreased in SM (7 out of 13). This decrease was statistically significant in the RA population studied. SM from different joints of a given patient showed similar variations of T-cell repertoire compared to PB, even 6 months later in the course of the disease. These results demonstrate a biased TCRBV gene utilization in RA SM. This bias appears to be similar in different joints and at different times in the course of the disease. No correlation was found between the bias of TCR repertoire in SM and the HLA typing of these patients.

Maintenance treatment with recombinant alpha interferon after autologous bone marrow transplantation for aggressive myeloma in first remission after conventional induction chemotherapy.

Twenty patients (median age 57 years) with high tumor mass myeloma in first remission after conventional chemotherapy received a two-phase treatment: autologous bone marrow transplantation (ABMT) using a preparative regimen of high dose melphalan plus total body irradiation followed by maintenance treatment with recombinant alpha interferon. Before ABMT all patients were in partial remission, while after ABMT 10 (50%) achieved complete remission, and 10 remained in partial remission (with a 90% decrease in measurable paraprotein in 7/10). With a median follow-up of 19.8 months (12.2-33.5) after diagnosis and 13 months (4-25) after ABMT, the Kaplan-Meier 2-year post-ABMT probability of progression-free survival was 85% (95% CI = 58.7-95.8%). None of the 10 patients in complete remission has relapsed. No toxic death occurred. Alpha interferon was introduced early after ABMT (2.7 months) and was well tolerated. This strategy may represent an advance in the management of aggressive myeloma.

Direct extraction and assay of collagenase from human osteoarthritic articular cartilage.

A method has been developed for the direct extraction of collagenase from small quantities (5 mg) of human osteoarthritic articular cartilage. The enzyme, which was not detected in normal cartilage, was entirely in a latent form and demonstrated typical properties of mammalian collagenase after activation by trypsin.

Increased concentrations of endogenous 13-cis- and all-trans-retinoic acids in diffuse idiopathic skeletal hyperostosis, as demonstrated by HPLC.

Endogenous 13-cis- and all-trans-retinoic acids have been quantitated in human serum using a solvent extraction procedure followed by isocratic reversed phase high performance liquid chromatography and UV detection. In healthy adults, after an overnight fasting period, the concentrations of 13-cis- and all-trans-retinoic acids yielded 5.3 +/- 2.43 nmol/l and 11.8 +/- 3.3 nmol/l, respectively (mean +/- SD). The method has been successfully applied to the analysis of both isomers in serum from patients with idiopathic skeletal hyperostosis in whom, the 13-cis- as well as all-trans-retinoic acid levels were raised as compared to the control group.

Osteoporosis with lymphoid nodules and hematopoietic marrow hyperplasia.

OBJECTIVE: In 1983 Vigorita reported 3 cases of osteoporosis associated with intramedullary lymphoid nodules. We present 8 patients with osteoporosis and lymphoid nodules (LN) in whom we studied the clinical, biological and histological features and the course of the disease. METHODS: Three men (mean age 52 yrs., range 43-68 yrs.) and 5 women (mean age 60 yrs., 49-66 yrs.), 6 of them with osteoporosis with fracture and 2 with osteoporosis on bone densitometry (T score < -2.5 SD) were enrolled in this study. The following parameters were studied: immunobinding with IG determination, phosphorus and calcium levels, PTH, 25 and 1-25 OH D3, osteocalcin, urinary deoxypyridinoline, histomorphometry, tests for autoanti-bodies, HIV, HTLV, EBV and CMV serology. The results were compared with those of 20 patients with osteoporosis but without LN. Five patients underwent a second BMB a mean of 2 years after the first. RESULTS: Five patients had asthenia, 4 had joint pain and 3 had hyperlymphocytosis. Immunologic and virologic investigations were negative in all cases. Bone marrow was hypercellular (59.9 +/- 5.3 vs 40.1 +/- 13%, p: 0.001). At the second BMB, LN were absent but bone marrow was still hypercellular. In all cases, no cause of demineralization was found and osteoporosis progressed rapidly (an average of 3 vertebral compression fractures in three months, with increased resorption (ES 6.5 +/- 1.6 vs 3 +/- 1.2, p: 0.05) with decreased calcification rate (CR 0.62 +/- 0.07 vs 0.79 +/- 0.1, p: 0.04). CONCLUSION: Some interesting questions are raised by this study. Did an undiscovered viral infection cause the asthenia and joint pain via cytokines or PTHrp in our patients, and can activated lymphocytes perhaps modify bone remodeling?

Bone mineral decrease in the leg with unilateral chronic occlusive arterial disease.

OBJECTIVE: The links between osteoporosis and arteriosclerosis have been established by numerous epidemiological studies. Could arteriosclerosis induce bone mineral loss via ischemia or other pathological process? We carried out a comparative study of bone mineral density in both legs of patients with unilateral arterial disease of the lower limbs. METHODS: We studied 25 patients, 22 men and 3 women, whose mean age was 62.3 years (range 35-88 years). These patients had unilateral lower limb arterial disease of at least 3 months duration with a systolic index at least 50% lower on the affected than on the healthy side. Bone mineral content (BMC) and bone mineral densities (BMD) of the femoral neck, femur, tibia, foot and ankle of the affected and the unaffected legs were measured by dual x-ray absorptiometry (Lunar DPXL) and the results compared. RESULTS: Bone mineral density was significantly lower in the femur (-3.7%, p = 0.04), the foot and the ankle (-3%, p = 0.05) of the affected leg. There was a non-significant decrease in BMD of the whole femoral neck (-1.2%) and the trochanter (-4.4%, p = 0.08) on the affected side. Tibial bone mineral density was identical in both legs. Bone mineral content was lower on the affected side (-5.3%, p = 0.05) whereas fat mass and muscle mass were the same in both legs. CONCLUSION: The ischemia resulting from arterial disease of the lower limbs appears to have a direct deleterious effect on bone mineralization.

Abnormal T cell receptor V beta gene expression in the peripheral blood and synovial fluid of rheumatoid arthritis patients.

OBJECTIVE: The aim of this study was to assess T cell receptor V beta-gene expression in the peripheral blood and synovial fluid of rheumatoid arthritis patients. METHODS: Cytometric analysis was performed on peripheral blood and synovial fluid lymphocytes from 12 patients using a restricted set of V beta-specific monoclonal antibodies (to V beta 5.1-3, V beta 6.7 and V beta 8). In 5 patients the expression of the V beta 1 through V beta 20 gene families was also analysed, using a recently described method based on a one-side-specificity polymerase chain reaction coupled to reverse dot hybridization. RESULTS: Cytometric analysis failed to show any consistent difference in the expression of V beta 5, 6 and 8 between the two compartments on the one hand, or between the peripheral blood of normal individuals and patients on the other hand. The PCR/dot hybridization method did not demonstrate a significant difference in the V beta repertoires between peripheral blood and synovial fluid samples from arthritis patients. However, in all patients the V beta 6, 13 and/or 14 families were expressed to a high level, so that these families frequently represented over 40% of the V beta 1-20 repertoire in both compartments, instead of the approximately 20% seen in normal peripheral blood samples. CONCLUSION: We conclude that V beta 6, 13 and 14 are overexpressed in both the peripheral blood and synovial fluid of rheumatoid arthritis patients compared to normal samples.

Is camptocormia a primary muscular disease?

STUDY DESIGN: This study analyzed computed tomographic scans, magnetic resonance images, and biopsies of the paravertebral muscles of patients with camptocormia and age-matched patients with lumbar interapophyseal osteoarthritis or lumbar vertebral stenosis. OBJECTIVES: To define the muscular lesions and clarify their nature in this particular disorder. SUMMARY OF BACKGROUND DATA: Progressive lumbar kyphosis or camptocormia, a rare disease of the elderly characterized by inability to immobilize the lumbar spine in relation to the pelvis appears to be a result of weakness of the paraspinal muscles. The features presented by these patients do not correspond to any myopathy previously described. METHODS: Twenty-seven patients (5 men and 22 women) mean age 69 years, with camptocormia were compared to fifteen age-matched patients without camptocormia but with posterior interapophyseal osteoarthritis and to nine elderly patients operated for narrowing of lumbar canal. Computed tomographic scans, magnetic resonance images, light microscopy, histochemistry, and electron microscopy of paraspinal muscles were obtained in both groups. RESULTS: In patients with camptocormia, computed tomographic scans and magnetic resonance imaging showed heterogeneous appearance of the spinal muscles with areas of low density. These features were distinct from those of patients with interapophyseal osteoarthritis and were similar to the features described in primary muscular dystrophies. The main microscopic change in camptocormia was the increase of fibrous tissue, frequently with a lobular pattern, not seen in osteoarthritic patients. Familial history of the disorder was frequent (20 out of the 27 patients). CONCLUSION: Camptocormia, disappearing in the recumbent position, is thus very probably linked to muscle involvement. That there is often a family history of such disorder is in favor of a genetically transmitted condition. Magnetic resonance images and computed tomographic scan appearance seems to be in favor of primary muscular disease, restricted to the spinal muscles.

Stenosis of the lumbar spinal canal in vertebral ankylosing hyperostosis.

Certain morphologic features frequently observed in radiography or computed tomography (CT) scan in patients with hyperostosis led us to study the association between a narrowed spinal canal and vertebral hyperostosis. Twenty-eight items were selected and studied by three different investigators (two rheumatologists and one radiologist) in radiographs and CT scans of 100 patients with acquired stenosis of the lumbar canal, with or without hyperostosis (46 and 54 cases, respectively). The most distinctive points that we suggest can be used as diagnostic criteria of the hyperostotic narrowed lumbar canal are anterior or posterior lateral marginal somatic osseous proliferations, proliferations of the nonarticular aspects of the posterior apophyses, and ossifications of the posterior articular capsule and of the ligaments (yellow ligament, posterior longitudinal ligament, and the supraspinal ligament). Four of these six criteria should be present to establish the diagnosis of hyperostotic lumbar stenosis. The appearance of lumbar hyperostosis on X-ray or CT scans differs from that of simple degenerative changes due to arthrosis, and the hyperostosis can be held responsible for dural compression.

Does the French general practitioner correctly investigate and treat osteoporosis? Groupe Rhumatologique d'Etudes Cliniques de Midi-Pyrénées.

In our region, more than half the patients with osteoporosis are investigated and treated by general practitioners. We carried out two surveys to discover whether the diagnosis and treatment of osteoporosis were correctly carried out by general practitioners in the Midi-Pyrénées region. The first survey concerned 85 patients who had been diagnosed with osteoporosis by their general practitioner. These patients were being seen for the first time in a hospital or private practice setting by a rheumatologist who completed a questionnaire based solely on the history taken from the patient and the records in the patient's possession. For the second survey, 200 general practitioners who had referred patients to the rheumatology department were sent a questionnaire on their management of osteoporosis. Fifty-two physicians completed and returned the questionnaire. More than half the general practitioners started treatment of osteoporosis without fractures on the basis of standard spinal X-rays where the radiologist suggested bone mineral loss. The initial biological investigation was correctly carried out by only 6% of physicians. Treatment was correctly prescribed in only 34% of cases of osteoporosis with fractures, 50% of osteoporosis without fractures and 50% of senile cortical osteoporosis.

Osteonecrosis of the femoral head and pregnancy.

The authors report 7 anatomo-clinical cases of osteonecrosis of the femoral head, the clinical onset of which occurred during pregnancy or in the fortnight after delivery. On the basis of histological data obtained through core-biopsy in these 7 cases they discuss the relationship between osteonecrosis and reflex sympathetic dystrophy of the hip.

Treatment of Paget's disease of bone with (4-chloro-phenyl) thiomethylene bisphosphonate.

Introduction of antiosteoclastic drugs, calcitonin and etidronate, has profoundly changed the treatment of active Paget's disease of bone. Nevertheless, the use of these drugs is limited in some patients by the occurrence of side-effects or by a resistance to therapy. We report the results of an open, nonrandomized study with a new bisphosphonate, (chloro-4 phenyl) thiomethylene bisphosphonate (Cl-TMBP), given orally to 35 patients with active Paget's disease of bone. At two different dosages this new bisphosphonate induced a significant decrease in disease activity. Patients receiving a mean dosage of 5 mg/kg/d (n = 14) showed a significant reduction of serum alkaline phosphatase levels to 43% of pretherapeutic values (from 499 +/- 91 to 214 +/- 41 IU/l) while hydroxyproline/creatinine ratio decreased to 43% of baseline (from 93 +/- 21 to 40 +/- 11). A second group of patients (n = 21) receiving a mean dosage of 11 mg/kg/d exhibited a similar response: serum alkaline phosphatase activity was reduced to 42% of initial values (from 1384 +/- 209 to 584 +/- 111 IU/l) while hydroxyproline/creatinine ratio fell to 48% of baseline (from 144 +/- 27 to 69 +/- 15). This was accompanied by a reduction in radionuclide uptake in pagetic areas. A prolonged beneficial effect was observed in most patients. In patients receiving the highest dosage significant reduction in serum calcium and rise in parathyroid hormone were observed. Otherwise no clinical or biological side-effect occurred throughout the study.

Septic arthritis of the knee due to Neisseria mucosa.

We report a case of septic arthritis of the knee due to Neisseria mucosa a widespread commensal of the oropharynx following an infiltration of the joint. Evolution was favorable in ten weeks, with antibiotics (amoxicillin then erythromycin), and without surgery.