pyrophosphate and Arthritis--Rheumatoid

Topics: Aged; Arthritis; Arthritis, Rheumatoid; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diagnosis, Differential; Diphosphates; Humans; Knee Joint; Middle Aged

Topics: Aged; Arthritis, Rheumatoid; Chondrocalcinosis; Colchicine; Crystallization; Diphosphates; Female; Gout; Humans; Indomethacin; Joint Diseases; Male; Phenylbutazone; Probenecid; Sulfinpyrazone; Synovial Fluid; Uric Acid; X-Ray Diffraction

It is now well recognized that osteoarthritis (OA) synovial membrane presents inflammatory components. The aim of this work is to provide evidence that similar inflammatory mechanisms exist in synovial membrane (n = 24) obtained from three pathologies presenting altogether an inflammatory gradient: OA, chronic pyrophosphate arthropathy (CPPA) and rheumatoid arthritis (RA). Synovial biopsies were first characterized by a histological score based on synovial hyperplasia and infiltration of lymphocytes, plasma cells, polymorphonuclear and macrophages. All biopsies were also analyzed by 2D-nano-UPLC-ESI-Q-Orbitrap for protein identification and quantification. Protein levels were correlated with the histological score. Histological score was in the range of 3 to 8 for OA, 5 to 13 for CPPA and 12 to 17 for RA. Of the 4,336 proteins identified by mass spectrometry, 51 proteins were selected for their strong correlation (p < 0.001) with the histological score of which 11 proteins (DNAJB11, CALR, ERP29, GANAB, HSP90B1, HSPA1A, HSPA5, HYOU1, LMAN1, PDIA4, and TXNDC5) were involved in the endoplasmic reticulum (ER) stress. Protein levels of S100A8 and S100A9 were significantly higher in RA compared to OA (for both) or to CPPA (for S100A8 only) and also significantly correlated with the histological score. Eighteen complement component proteins were identified, but only C1QB and C1QBP were weakly correlated with the histological score. This study highlights the inflammatory gradient existing between OA, CPPA and RA synovitis either at the protein level or at the histological level. Inflamed synovitis was characterized by the overexpression of ER stress proteins.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Biomarkers; Chondrocalcinosis; Diphosphates; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Female; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Osteoarthritis; Proteins; Proteome; Retrospective Studies; Synovitis

The presence of matrix metalloproteinase-2 and -9 (MMP-2, MMP-9), gelatinase A and B, in synovial fluid is typical in inflammatory connective tissue diseases especially rheumatoid arthritis (RA). Because MMPs are synthesized as latent proforms, a pathophysiologic understanding of MMP regulation has focused on mechanisms of activation that remain to date largely unresolved.. Synovial fluid was collected by aseptic aspiration from RA patients and incubated with and without physiologic levels of calcium and other modifiers (pyrophosphate, bisphosphonates, and the tissue inhibitors of MMPs (TIMPs), under conditions that activate MMPs. MMP-2 and -9 were then characterized by substrate gel electrophoresis (gelatin zymography) to resolve both latent and activated 'partially proteolyzed' forms.. Gelatin zymography revealed that RA synovial fluid contained latent neutrophil MMP-9 (92, 130, 225 kDa) and fibroblast MMP-2 (72 kDa). A small amount of activated MMP-2 (64 kDa) was also noted. Incubation of synovial fluid without calcium resulted in MMP-9 activation to 87, 116, and 209 kDa forms. MMP-9 activation was, however, substantially delayed in the presence of physiologic calcium (2.5 mmol/l). MMP-2 did not demonstrate any appreciable activation with or without physiologic calcium. MMP-9 activation likely occurred via an autoactivation mechanism since it was susceptible to inhibition by the tissue inhibitor of MMP-9 (TIMP-1). Pyrophosphate and bisphosphonates (alendronate and risedronate) were ineffective in blocking synovial fluid MMP-9 autoactivation. Some early MMP-9 activation was noted with alendronate despite the presence of physiologic calcium.. Although RA synovial fluid contained abundant MMP-2 and MMP-9, only MMP-9 underwent autoactivation to lower molecular weight forms. MMP-9 was transiently stable in the presence of physiologic calcium concentration, whereas autoactivation was more pronounced without exogenous calcium. The apparent lack of MMP-2 autoactivation with or without calcium, likely resulted from the coexistence of its bound endogenous inhibitor, TIMP-2. The role of differential autoactivation of MMPs activity in inflammatory arthritic disease is discussed.

Topics: Aged; Arthritis, Rheumatoid; Calcium; Diphosphates; Diphosphonates; Enzyme Activation; Female; Humans; Inflammation; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Molecular Structure; Synovial Fluid

To quantify inorganic pyrophosphate (PPi) production from extracellular adenosine triphosphate (ATP) by human synovial fluids (SF).. Serial measurements of ATP hydrolysis rate (t1/2) were performed by the luciferase method from a starting concentration of 500 nM in 21 pathologic and one normal cell-free SF samples incubated under physiologic conditions. ATP was then pumped into a sample of each fluid, using the rate constant derived from the t1/2 of that fluid, to provide steady state levels simulating those reported in SF. Trace [32P] gamma ATP was added at the start of the infusion; conversion to [32P] Pi and to [32P] PPi was determined by precipitation of Pi as reduced phosphomolybdate before and after treatment with yeast inorganic pyrophosphatase. Finally, the pumping experiment was repeated and PPi production was calculated from direct measurement of PPi at time zero and at 60 min. PPi hydrolysis was measured in each fluid by [32P] Pi precipitation from [32P] PPi tracer added at time zero.. ATP was hydrolyzed by all SF. The mean t1/2 (seconds) in 8 osteoarthritis (OA) samples was 72 s, in 5 calcium pyrophosphate dihydrate (CPPD) 30 s (p < 0.02), in 3 rheumatoid arthritis (RA) 1160 s, in normal 86 s, in 3 olecranon bursal (OB) 54 s, and in 2 total knee replacement fluid samples 17 and 121 s. The major product of ATP hydrolysis was PPi in all but 2 fluids (1 RA, 1 OB), even at lower than steady state levels. At simulated in vivo steady state ATP levels, mean conversion of APT to PPi was stoichiometric in OA and CPPD fluids. PPi hydrolysis was < 4% in all noninflammatory fluids.. PPi is the major product of extracellular ATP catabolism in most SF. Hydrolysis rates were significantly faster in SF containing CPPD crystals. Mean PPi production by these fluids at simulated in vivo steady state levels was 6-fold that of OA SF (p < 0.01). Hydrolysis of extracellular ATP by ectonucleotide pyrophosphohydrolases can account for all PPi produced by joint issues previously estimated from [32P] PPi pool and turnover studies in human knee joints.

Topics: Adenosine Triphosphate; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Calcium Pyrophosphate; Cell-Free System; Diphosphates; Female; Humans; Hydrolysis; In Vitro Techniques; Knee Prosthesis; Male; Middle Aged; Osteoarthritis; Pyrophosphatases; Synovial Fluid

The enzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH) is present in all joint fluids and on intraarticular cells. It generates inorganic pyrophosphate (PPi) from nucleoside triphosphate substrate, thus serving as a potential source of the PPi which forms in the cartilages of patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition. NTPPPH is also important in matrix vesicle induced calcification with basic calcium phosphate (BCP) crystals. An articular substrate for this enzyme was sought. ATP was measured in the joint fluids from 107 patients with various forms of arthritis. Synovial fluid ATP levels were higher in patients with CPPD deposits than in osteoarthritis (p less than 0.02) or rheumatoid arthritis (p less than 0.002). ATP also correlated with PPi concentration (p less than 0.05) and with the presence of BCP crystals (p less than 0.05), but not with cellularity of the fluid, NTPPPH activity, or age of the donor. This substrate for NTPPPH may contribute to CPPD crystal deposition by generating PPi and may stimulate matrix vesicle induced formation of BCP crystals in several forms of arthritis.

Topics: Adenosine Triphosphate; Arthritis, Rheumatoid; Calcium Pyrophosphate; Cartilage; Diphosphates; Humans; Osteoarthritis; Pyrophosphatases; Synovial Fluid

Deposition of intra-articular calcium pyrophosphate is associated with both aging and arthropathy; increased concentrations of free pyrophosphate (PPi) may contribute to such deposition. Free pyrophosphate and nucleoside triphosphate pyrophosphatase (NTPase) were estimated in synovial fluids from 50 subjects with normal knees and from 44 patients with rheumatoid arthritis, 61 with pyrophosphate arthropathy, and 59 with osteoarthritis. For arthropathic knees clinically assessed inflammation was classified as active or inactive using a summated score of six clinical features. The order of PPi (mumol/l) and NTPase (mumol PPi/30 min/mg protein) was pyrophosphate arthropathy greater than osteoarthritis greater than rheumatoid arthritis (median PPi, NTPase respectively: for pyrophosphate arthropathy 15.9, 0.45; for osteoarthritis 9.3, 0.25; for rheumatoid arthritis 4.4, 0.18), with significant differences between all groups. In pyrophosphate arthropathy both PPi (mumol/l) and NTPase (mumol PPi/30 min/mg protein) were higher than normal (15.9, 0.45 v 8.6, 0.2 respectively), but findings in osteoarthritis did not differ from normal. The inflammatory state of the knee had a distinct but variable effect on synovial fluid findings in rheumatoid arthritis and pyrophosphate arthropathy, but not in osteoarthritis. There was no correlation of either PPi or NTPase with age, or between PPi and NTPase in any group. This study provides in vivo data for synovial fluid PPi and NTPase. It suggests that factors other than PPi need to be considered in a study of crystal associated arthropathy. Clinical inflammation, as well as diagnosis, is important in synovial fluid studies.

Topics: Adult; Aged; Aged, 80 and over; Arthritis; Arthritis, Rheumatoid; Calcium Pyrophosphate; Diphosphates; Female; Humans; Joint Diseases; Knee Joint; Male; Middle Aged; Osteoarthritis; Pyrophosphatases; Synovial Fluid

Scintigraphic examination of the joints and spine was performed in 42 children with Bekhterev's disease and rheumatoid arthritis to establish different accumulation of 99mTc-pyrophosphate. In Bekhterev's disease, elevated concentration of the radio-indicator was detected was detected in the joints of the lower limbs, including hip joints, in the sacroiliac parts of the spine and in heels. In rheumatoid arthritis, it was mainly detectable in the joints of the upper limbs and sometimes in the cervical part of the spine. Scintigraphy of the joints may be helpful in differential diagnosis of the above-indicated disease entities.

Topics: Adolescent; Arthritis, Rheumatoid; Child; Diagnosis, Differential; Diphosphates; Female; Humans; Male; Radionuclide Imaging; Spondylitis, Ankylosing; Technetium; Technetium Tc 99m Pyrophosphate

Three thousand synovial fluids (1312 patients: chronic pyrophosphate arthropathy (CPA), 41%; osteoarthritis (OA), 12%; rheumatoid arthritis (RA), 16%) were examined for crystals, including calcium pyrophosphate dihydrate (CPPD), by polarized microscopy (score 0-3); calcific particles, by alizarin red positivity (ARP; 0-3); and total cell count. For 1150 fluids, local joint inflammation was assessed as 'active' or 'inactive' using a summated score of six clinical variables. CPPD and ARP scores did not correlate, but each showed positive correlation with age (P less than 0.01, P less than 0.02 respectively). Pseudogout had the highest mean CPPD score (P less than 0.001); intermittent CPPD positivity (range 8-100%) was seen in serially aspirated CPA joints, and there was no difference in CPPD positivity or score between active and inactive CPA. ARP was most frequent in OA subsets (72% of CPA, 46% of OA, 31% of RA; P less than 0.001). ARP was more frequent in active than inactive OA (P less than 0.05) but showed no association with inflammation in CPA or RA. Cell counts were higher in RA and pseudogout compared to OA and CPA, and in active compared to inactive RA. No correlation was found between ARP or CPPD scores and cell count. Cholesterol crystals were uncommon (0.2%) and showed no disease or joint predilection. In arthritic joints, CPPD and calcific particles particularly associate with the OA process and ageing. CPPD may contribute to acute and other calcific particles to chronic inflammation in OA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anthraquinones; Arthritis; Arthritis, Rheumatoid; Calcium Pyrophosphate; Child; Chondrocalcinosis; Coloring Agents; Crystallography; Diphosphates; Female; Humans; Male; Middle Aged; Osteoarthritis; Synovial Fluid

The proposed method of sequential scintigraphy of the kidneys and joints in a single administration of 99mTc-pyrophosphate permits obtaining objective information on function and topography of the kidneys and pyodestructive processes in the joints. Dynamic scintigraphy helps to assess visually renal hemodynamics and the antomotopographic position of the kidney and to obtain exhaustive information on accumulative-evacuatory function of each kidney individually. Scintigraphy also helps to investigate all the joints and to detect pyoinflammatory changes in them. The proposed method considerably reduces the time of investigation and lessens radiation exposure of patients, permitting repeated investigations to assess and correct the treatment of patients with rheumatic arthritis.

Topics: Adult; Arthritis, Rheumatoid; Diphosphates; Evaluation Studies as Topic; Female; Humans; Joint Diseases; Joints; Kidney; Kidney Diseases; Male; Middle Aged; Radionuclide Imaging; Suppuration; Technetium; Technetium Tc 99m Pyrophosphate

Recent advances in technology have lead to the development of a high-definition microfocal X-ray unit allowing macroradiographic examination of different parts of the body at x 5 to x 10 magnification and with a high spatial resolution. Its applications in the study of a number of arthritides, metabolic and some other bone diseases are described in terms of early detection of diagnostic features. Emphasis is placed on the advantages of direct accurate measurement of these features, providing a precise evaluation of disease progression and response to therapy.

Topics: Arthritis, Rheumatoid; Bone and Bones; Child; Diphosphates; Humans; Hyperparathyroidism; Male; Osteoarthritis; Radiation Dosage; Radiography; Scleroderma, Systemic; X-Ray Intensifying Screens

Application of a complex of clinical, thermography and radionuclide methods in 79 patients with rheumatoid arthritis has demonstrated high sensitivity of scintigraphy with the use of osteotropic radiopharmaceuticals (99mTc-pyrophosphate, 99mTc-phosphone) as well as a possibility of diagnosing preclinical injuries to the joints. The thermography and scintigraphic parameters depended on the degree of inflammation, permitting an objective evaluation of the treatment effect.

Topics: Adult; Arthritis, Rheumatoid; Chronic Disease; Combined Modality Therapy; Diphosphates; Female; Follow-Up Studies; Humans; Joints; Male; Middle Aged; Prognosis; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate; Thermography

C3 degradation products (C3dg/d) were estimated in 288 synovial fluid (SF) samples (rheumatoid arthritis (RA) 93, osteoarthritis (OA) 68, chronic pyrophosphate arthropathy 80, acute pseudogout 20, others 27) from knees of 138 patients (bilateral 67, serial sampling on two to six occasions 40). At each aspiration knees were defined as 'active' or 'inactive' by single observer global assessment using six clinical parameters of inflammation. Lack of correlation between paired SF and plasma C3dg/d implied local C3 activation within joints. Raised SF C3d levels were found in active compared with inactive RA joints (mean (range) 51 (15-105) and 6 (0-15) units/ml respectively). Low SF C3dg/d levels were found in OA (mean (range) 0.8 (0-7) units/ml) and chronic pyrophosphate arthropathy (mean (range) 4 (0-16) units/ml), irrespective of clinical activity. In contrast, very high levels (mean (range) 61 (16-126) units/ml) were present in all cases of pseudogout. These differences remained after correction for SF C3 or albumin. This study is the first to show a positive correlation between SF C3dg/d and local inflammation in RA joints. It further suggests that C3 activation is a constant feature of pseudogout but not an accompaniment of inflammation associated with chronic crystal associated synovitis or OA.

Topics: Adult; Aged; Aged, 80 and over; Arthritis; Arthritis, Rheumatoid; Chondrocalcinosis; Complement C3; Complement C3b; Complement C3d; Diphosphates; Female; Gout; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Peptide Fragments; Synovial Fluid

We studied synovial fluid (SF) collagenase in 10 women with severe rheumatoid arthritis (RA), 10 with pyrophosphate arthropathy, and 10 with idiopathic destructive disease of the shoulder conforming to a pattern recently described. SF cell counts were highest in the RA group. Particles were detected by polarized light microscopy and alizarin red staining. Crystals were seen in fluids from all 3 groups; pyrophosphate predominated in the pyrophosphate arthropathy group and alizarin red-positive particles in the idiopathic disease group. Collagenase and tissue inhibitor of metalloproteinase levels were estimated in SF after gel filtration. Tissue inhibitor of metalloproteinase activity was detected in all fluids, but tended to be highest in the RA group. Collagenase activity was detected in 3 RA fluids only. In no sample was collagenase found in an active form. These findings support the clinical concept of an aggressive destructive process which sometimes occurs in the shoulder joints of elderly women. Because we were not able to detect free collagenase in SF from any of the patients with idiopathic shoulder disease, the data suggest that high levels of active collagenase are not characteristic of this group of patients.

Topics: Apatites; Arthritis; Arthritis, Rheumatoid; Crystallization; Diphosphates; Enzyme Inhibitors; Female; Humans; Microbial Collagenase; Radiography; Shoulder Joint; Synovial Fluid; Tissue Inhibitor of Metalloproteinases

Synthetic calcium pyrophosphate dihydrate crystals and, to a lesser extent, synthetic hydroxyapatite crystals increased the amount of interleukin-1/mononuclear cell factor released by human blood monocytes, as measured by collagenase and prostaglandin E2 production by rabbit chondrocytes, human dermal fibroblasts, and adherent rheumatoid synovial cells. The same crystals also directly induced collagenase and prostaglandin E2 secretion by rabbit chondrocytes, and potentiated the action of interleukin-1/mononuclear cell factor on chondrocytes. These mechanisms may be important in the pathogenesis of the destructive arthropathies associated with these crystals.

Topics: Animals; Arthritis, Rheumatoid; Biological Products; Calcium Pyrophosphate; Cartilage, Articular; Cell Adhesion; Cells, Cultured; Crystallization; Dinoprostone; Diphosphates; Durapatite; Fibroblasts; Humans; Hydroxyapatites; Interleukin-1; Leukocytes, Mononuclear; Microbial Collagenase; Monokines; Plasminogen Activators; Prostaglandins E; Rabbits; Synovial Membrane

Diagnostic potentialities of investigation of the kidneys using 99mTc-pyrophosphate were studied in 34 patients with rheumatoid arthritis (RA) for articular scintigraphy. The results obtained were compared with those of radionuclide renography with 131I-hippuran and excretory urography. A possibility of investigation of the kidneys with 99mTc-pyrophosphate for the assessment of parenchyma function and kidney urodynamics was shown. Taking into account a high prevalence of nephropathy in RA patients, dynamic renal scintigraphy and clearance registration were recommended at the first stage of articular scintigraphy with 99mTc-pyrophosphate in order to obtain information on the anatomotopographic site and accumulation-evacuatory function of the kidneys.

Topics: Adult; Aged; Arthritis, Rheumatoid; Diphosphates; Female; Humans; Iodohippuric Acid; Joints; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Radioisotope Renography; Technetium; Technetium Tc 99m Pyrophosphate; Time Factors; Tomography, Emission-Computed

Topics: Arthritis, Rheumatoid; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Femur; Humans; Radiography

Monosodium urate crystals are clearly related to acute attacks of gout and to the hard tissue destruction of chronic tophaceous gout. Fortunately, the acute attacks are readily treated with anti-inflammatory drugs, and destructive changes due to tophi may be prevented or reversed, at least in part, by the intelligent control of serum urate levels. Control of gout is one of the premier success stories of modern medicine. In contrast, the number of patients who have arthritis associated with crystals that contain calcium appears to be rising--perhaps a function of better recognition, perhaps related to the aging of the population. CPPD and BCP crystals can be associated with acute or subacute inflammation, but as in acute gout, it is easily controlled with anti-inflammatory drugs or by local injections of corticosteroids. A direct relationship of BCP and CPPD crystals to the associated destructive arthropathies has been hypothesized and is supported by clinical observations, animal studies, and in vivo experiments. Unlike gout, which is usually associated with a systemic metabolic abnormality (i.e., hyperuricemia), calcium crystals deposition seem to be a localized phenomenon, although numerous local sites in several joints are often involved in a given patient. Tissue degeneration in gout clearly follows (tophaceous) crystal deposition. Calcium crystal deposition may follow, rather than precede, destructive joint changes. Alternatively, both destructive changes and crystal deposition may derive independently from a common, still obscure, biochemical abnormality of joint tissues. P. A. Dieppe and colleagues believe that calcium crystal deposition follows either primary or secondary tissue degeneration but that the crystals exert a positive feedback effect (amplification loop) that accelerates degeneration. Each of those formulations of a pathogenetic role for crystals may be true in a given case, analogous to the etiology of primary and secondary forms of hyperuricemia and to sodium urate crystal deposition coexistent with osteoarthritis (tophus formation in Heberden's nodes). Conclusive proof of a significant role for BCP or CPPD crystals in the pathogenesis of human joint tissue damage depends on interrupting the postulated disease mechanism and showing that this prevents joint deterioration and leads to significant repair of existing damage. Our current position is somewhat analogous to that of our colleagues who had to contend with management of gouty a

Topics: Aged; Arthritis, Rheumatoid; Calcium Phosphates; Calcium Pyrophosphate; Crystallization; Diphosphates; Gout; Humans; Male; Middle Aged

Synovial fluid from 16 normal subjects was compared with that from 149 patients with a variety of rheumatic disorders. Normal fluid had fewer cells and a lower content of beta-glucuronidase than osteoarthritic samples. Particles, including occasional birefringent crystals, were seen in normal fluids as well as pathological samples. Alizarin red staining particles (presumed to contain apatite) were seen in all diagnostic groups; their numbers showed some correlation with radiological calcification in and around the joints and with a hypertrophic subchondral bone response. Lactate levels were highest in septic arthritis. No assay showed disease specificity.

Topics: Adult; Anthraquinones; Arthritis; Arthritis, Infectious; Arthritis, Rheumatoid; Cell Count; Diphosphates; Female; Glucuronidase; Humans; Knee Joint; Male; Microscopy, Polarization; Middle Aged; Osteoarthritis; Physical Exertion; Radiography; Staining and Labeling; Synovial Fluid; Viscosity

The synovial fluid ferritin level in 49 patients (57 joints) with various rheumatic diseases was analysed. In rheumatoid arthritis (n = 22) the geometric mean ferritin level was 528 micrograms/l (range 56-3 100 micrograms/l), in other inflammatory arthritides (n = 12) 339 micrograms/l (105-2 835 micrograms/l) (p greater than 0.5), in calcium pyrophosphate arthropathy (n = 14) 507 micrograms/l (180-4 230 micrograms/l) (p greater than 0.5) and in non-inflammatory osteoarthritis (n = 9) 167 micrograms/l (14-725 micrograms/l) (p less than 0.05). Synovial fluid/serum ferritin ratios did not differ significantly in the four diagnostic groups; 4 patients had ratios less than 1.0. Synovial fluid ferritin was not correlated to total fluid cell count or differential cell count. Although ferritin content was significantly greater in inflammatory than in noninflammatory fluid (p less than 0.05), the wide scatter of the values and marked overlap between the different groups limit the value of measuring synovial fluid ferritin as a differential diagnostic test for rheumatic diseases.

Topics: Arthritis, Rheumatoid; Diphosphates; Female; Ferritins; Humans; Male; Osteoarthritis; Rheumatic Diseases; Synovial Fluid

Topics: Aged; Arthritis, Rheumatoid; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Knee Joint; Middle Aged; Radiography

99mTc-polyphosphate joint imaging of the hand has been performed in 18 patients, with evidence of inflammatory joint disease, but without any significant radiographic lesions, which might be related to rheumatoid arthritis. The hand scans were compared to clinical and radiographic data. An year after, the same subjects were re-examined, with both the radionuclide imaging and radiography. Scintigraphy has been shown to be significantly more sensitive for detecting inflammatory joint disease than x-ray, especially in the early stage of rheumatoid arthritis. Although radionuclide imaging is non specific (activity is increased also in osteoarthritis, trauma, metabolic bone disease, infarction, etc.). Radiography is highly specific but relatively non sensitive.

Topics: Adult; Aged; Arthritis, Rheumatoid; Diagnosis, Differential; Diphosphates; Diphosphonates; Female; Hand; Humans; Male; Middle Aged; Polyphosphates; Radiography; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Technetium Compounds; Technetium Tc 99m Pyrophosphate

A negative correlation between rheumatoid arthritis (RA) and calcium pyrophosphate dihydrate (CPPD) crystal deposition was demonstrated in separate controlled radiographic and synovial fluid surveys of RA patients aged 55-75 years. Knee chondrocalcinosis was detected in 14% of 135 normal controls and 28% of 87 post-meniscectomy ("joint damage") controls (P less than 0.05), but only 3% of 100 RA and 75 osteoarthritis patients revealed CPPD crystals in 1% and 23%, respectively (P less than 0.01). Ten subjects with coexistent RA and CPPD deposition were also studied; 7 showed radiographic features atypical of RA, including patchy, asymmetric disease, retained bone density, prominent osteophytosis, well-corticated cysts, and paucity of progressive erosive disease. It is suggested that rheumatoid joint damage, unlike that in osteoarthritis, is not conducive to CPPD crystal formation. When RA and CPPD coexist, atypical radiographic features reflecting a hypertrophic reparative response may occur.

Topics: Aged; Arthritis, Rheumatoid; Arthrography; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Synovial Fluid

The retention of 99mTc-labeled pyrophosphate (PPi) at 24 h was measured in 235 patients, 119 of whom had a normal bone metabolism. The mean retention in the group of normal subjects is 52% of the injected dose. Reproducibility of the measurement in a given person is 5.5% coefficient of variation (CV). The value depends strongly on sex (higher in males) and age (higher with increasing age, especially in cortical bone). Retention increases slowly with the decrease in glomerular filtration rate (GFR) between 50 and 120 ml/min; it rises very rapidly with values below 50 ml/min. The slowing down of the GFR with age does not account for the increase in PPi retention with age. When expressed as a percentage of the expected value for sex and age, retention is frequently low in osteoporosis (P less than .001), more so when urinary hydroxyproline is low; it is normal or high in osteomalacia, and in some cases rises after vitamin D treatment is started; it is high in hyperparathyroidism (P less than .01). The PPi retention is correlated with bone calcium accretion rate, alkaline phosphatase level, and above all, the urinary hydroxyproline level. The lower the bone mineralization (Ca/hydroxyproline ratio in biopsy), the higher the retention value. We conclude that the PPi retention is an index of bone metabolism when GFR is higher than 50 ml/min. It allows for classification of metabolic bone diseases according to the bone turnover rate. It has the advantage over the usual biologic examinations in that it affords better observation of highly localized bone disorders and can be used in combination with a morphologic record, the bone scintigraphy.

Topics: Adolescent; Adult; Aged; Aging; Arthritis, Rheumatoid; Bone and Bones; Bone Diseases; Child; Child, Preschool; Diphosphates; Female; Glomerular Filtration Rate; Humans; Hydroxyproline; Male; Middle Aged; Technetium; Technetium Tc 99m Pyrophosphate

The inflammatory response to intradermal injections of urate, pyrophosphate and hydroxyapatite crystals in human forearm skin is described. Patients with rheumatoid arthritis responded normally to urate crystals, and patients with osteoarthritis or pyrophosphate arthropathy responded normally to hydroxyapatite and pyrophosphate crystals respectively. These results suggest that variation in host response to crystals cannot explain the different patterns of crystal-induced disease seen in man. The model, however, is recommended as a safe, simple ethical and reproducible test of inflammation in human subjects.

Topics: Arthritis, Rheumatoid; Calcium Pyrophosphate; Diphosphates; Gout; Humans; Hydroxyapatites; Intradermal Tests; Osteoarthritis; Skin; Uric Acid

Serum enzymes and articular radionuclide tests have a restricted application in solving the current diagnostic and differential-diagnostic problems of present-day rheumatology. The enzyme tests became positive in case of a high activity of rheumatoid arthritis, not objectivizing the articular degeneration. Their correlation with radionuclide tests of the patients with osteoarthrosis and the patients with rheumatoid arthritis is not elucidated. A juxtaposition was made of the serum enzymes with the articular radionuclide quantitative indices in 88 patients with rheumatoid arthritis with various clinical-laboratory activity, 88 patients with osteoarthrosis in various X-ray stages and 22 healthy controls. A correlation dependence was established between LDH, CPK, acid phosphatase, clearance effectiveness of articular cavity and the deposition of 99mTc-pyrophosphate in knee joints of the patients with osteoarthritis and between gamm-GT, alkaline phosphatase, acid phosphatase and radionuclide articular indices of the patients with rheumatoid arthritis. Those characteristics enabled the earlier overcoming of the diagnostic difficulties in those two basic rheumatic diseases.

Topics: Adult; Arthritis, Rheumatoid; Clinical Enzyme Tests; Diphosphates; Enzyme Activation; Humans; Knee Joint; Middle Aged; Osteoarthritis; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Technetium Tc 99m Pyrophosphate; Xenon Radioisotopes

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease can lead to many clinical syndromes. One syndrome simulates rheumatoid arthritis and is thus called "pseudo-rheumatoid arthritis." Since some patients have true rheumatoid arthritis with CPPD crystal deposition disease, the clinician may have difficulty differentiating those patients from others who have the pseudo-rheumatoid syndrome. Such a diagnostic problem can be solved radiographically. Eleven patients with CPPD crystal deposition disease were studied; five had true rheumatoid arthritis and six had pseudo-rheumatoid arthritis. Because osseous erosions were not apparent in the arthropathy of uncomplicated CPPD crystal deposition disease, the detection of skeletal erosive changes indicated a true rheumatoid arthritis process.

Topics: Aged; Arthritis, Rheumatoid; Calcium Pyrophosphate; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Female; Humans; Joint Diseases; Male; Middle Aged; Radiography

Soluble pyrophosphate was measured in the plasma and synovial fluid of various groups of patients and in the plasma of two control groups. The two control groups consisted of 13 healthy subjects and 19 patients suffering from benign lumbar back pain. The other group of patients had rheumatoid arthritis (RA) (14 plasma and 19 synovial fluid examinations), osteoarthrosis (OA) (19 plasma and 26 synovial fluids) and articular chondrocalcinosis (ACC) (27 plasma and 43 synovial fluids). The level of soluble pyrophosphate in the plasma was 3.5 mumol/l in healthy subjects, 4.0 mumol/l in patients with lumbar back pain, 4.1 mumol/l in individuals having OA and 3.5 mumol/l in the group suffering from RA as well as for those with ACC. The differences between these values are not significant statistically. In the synovial fluid the values were 4.6 mumol/l for the group with RA, 12.7 mumol/l for those with OA and 34.2 mumol/l in the group having ACC. If a normal distribution of these values is assumed and the average values and standard deviations recalculated for each group after elimination of cases more than 3 standard deviations above the mean, then we obtain 9.8 mumol/l for the group with OA and 23.8 mumol/l for those with ACC. The difference between the group with RA and that with OA is highly significant (p greater than 0.0001). Even more significant is the difference between the group with RA and ACC (p less than 0.0005). The difference between the OA and the ACC is also highly significant (p less than 0.001). On the basis of these observations various mechanisms leading to the pyrophosphage crystal deposition disease are discussed.

Topics: Arthritis; Arthritis, Rheumatoid; Back Pain; Chondrocalcinosis; Diphosphates; Humans; Osteoarthritis; Solubility; Synovial Fluid

Hydroxyapatite (HA) and calcium pyrophosphate dihydrate (CPPD) crystals were phagocytosed when added to cultured human rheumatoid or normal canine synovial cells. Collagenase and neutral protease secretion into the culture medium was increased 5- to 8-fold over control values in the presence of HA and increased 3-fold in the presence of CPPD crystals. HA but not CPPD crystals induced a 300-fold increase in human rheumatoid synovial cell culture fluid prostaglandin (PG) E2 levels and an 8-fold increase in PGF alpha levels. This mechanism may be important in the pathogenesis of the destructive arthropathies associated with HA and CPPD crystals.

Topics: Animals; Arthritis, Rheumatoid; Calcium Pyrophosphate; Cell Line; Cells, Cultured; Diphosphates; Dogs; Humans; Hydroxyapatites; L-Lactate Dehydrogenase; Microbial Collagenase; Peptide Hydrolases; Prostaglandins; Synovial Membrane

Topics: Arthritis, Rheumatoid; Diphosphates; Humans; Joints; Radioactivity; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Adolescent; Adult; Arthritis, Rheumatoid; Diphosphates; Humans; Knee Joint; Middle Aged; Recurrence; Synovectomy; Technetium; Time Factors; Tomography, Emission-Computed

Topics: Arthritis, Rheumatoid; Cartilage, Articular; Collagen; Diphosphates; Humans; Hydroxyapatites; Joints; Necrosis; Osteoporosis

The knee joints of 88 patients with rheumatoid arthritis and 22 healthy subjects were examined via a complex radiometric method. The time for half-elimination of 133xenon, injected into the joints, is 154.8 minutes for the control group and 118.7 min, 81.6 min and 39.2 min according to the graded activity of rheumatoid arthritis. The accumulation of 99mTc-pertechnetate is 115.3% for the controls and 131.0%, 151.0% and 178.0% for the joints with inflammatory reaction. The accumulation of 99mTc-pyrophosphate is 115.7% and 133.0%, 149.9% and 170.7% respectively in the patients with I, II and III degree of rheumatoid arthritis activity. The manifestation of X-ray signs of osteo-articular destruction is combined with higher radionuclide indices than those corresponding to rheumatic activity. The results reveal an enhanced reactivity of all articular structures (synovial sac, bone-epiphyses) in the patients with rheumatoid arthritis. The following radio-isotope constellation is indicated for the early diagnostics and differential diagnosis in case of that disease: high effectiveness of articular 133xenon clearance, equivalence of figure expression and similarity in the changes of the depots 99mTc-pertechnetate and 99mTc-pyrophosphate in the knee joints of patients with rheumatoid arthritis.

Topics: Adult; Arthritis, Rheumatoid; Diphosphates; Half-Life; Humans; Knee Joint; Radionuclide Imaging; Synovial Membrane; Technetium; Xenon Radioisotopes

Scintigraphic and radiometric investigation with 99mTc-pyrophosphate was carried out on the sacro-iliac joints of 79 patients: 48 with positive form of Behterev disease, 26 -- with probable form of the disease, 2 -- with Reiter syndrome and 2 -- with rheumatoid arthritis. Scintigraphy was combined with radiometric investigation (determination of sacro-iliac -- sacral index) with a view to obtaining quantitative information about the degree of accumulation of pyrophosphate in sacro-iliac joints. The data from the scintigraphic and radiometric investigations were juxaposed to clinical laboratory and X-ray investigations. Forty of the patients examined were HLA-B27 positive and 38 of them-HLA-B27 negative. Sacro-iliac index, determined in 13 healthy subjects (26 sacro-iliac joints) was within the limits of 1.18 +/- 0.094. The average value of the index of the 78 patients examined was 1.41 +/- 0.20. The index, during the first and second X-ray stage was 1.43 +/- 0.13 and 1.45 +/- 0.19 resp. The values decreased to 1.39 +/- 0.18 during the third X-ray stage, whereas in the fourth stage with completely ankylosis of the joints, the index was 1.20 +/- 0.07, being close to that of the control group of healthy subjects.

Topics: Adolescent; Adult; Arthritis, Reactive; Arthritis, Rheumatoid; Diphosphates; Female; HLA Antigens; Humans; Male; Middle Aged; Radionuclide Imaging; Sacroiliac Joint; Spondylitis, Ankylosing; Technetium

Topics: Arthritis, Rheumatoid; Crystallization; Diphosphates; Gout; Humans; Hydroxyapatites; Joint Diseases; Leukocyte Count; Microscopy, Electron; Microscopy, Polarization; Osteoarthritis; Phagocytosis; Synovial Fluid

Bone scintigraphs obtained with both Technetium-99m polyphosphate and Technetium-99m pyrophosphate have been abnormal at the sacroiliac joints of 44 patients with definite ankylosing spondylitis (AS). Because of the normal registration of the sacroiliac joints on bone scintigraphy, it has been necessary to develop a profile-scan technique to quantify the abnormality that proves to be significantly different from the normal finding. In 17 patients with a strong clinical suspicion of AS but normal radiographs, the sacroiliac joints have frequently been abnormal. This finding is meaningful because there is a common occurence in this group of the histocompatibility antigen HL A-B27, known to be a marker of AS. We also note the frequency of abnormal sacroiliac scinitigrams in 26 patients with rheumatoid arthritis and in a group of other diseases-Crohn's disease, uveitis, psoriasis, ulcerative colitis, and Reiter's disease-all of which share some of the manifestations of AS.

Topics: Adult; Animals; Arthritis, Reactive; Arthritis, Rheumatoid; Cats; Colitis, Ulcerative; Crohn Disease; Diphosphates; Evaluation Studies as Topic; Humans; Psoriasis; Radionuclide Imaging; Sacroiliac Joint; Spondylitis, Ankylosing; Technetium; Uveitis

Topics: Adult; Aged; Arthritis, Rheumatoid; Diphosphates; Female; Humans; Middle Aged

Bone-to-bone, iliosacral joint-to-os sacrum and joint-to-joint ratios were computed using the region-of-interest technique 2 to 3 hrs. after injection of 99mTc Sn-methylene-diphosphonate or 99mTc Sn-pyrophosphate in 139 patients with skeletal diseases (bone tumours, degenerative changes of the spine and joints, inflammatory changes of joints) as well as in 123 patients with normal skeletal states. In the latter group, iliosacral joint-to-os sacrum ratios decreased with increasing age of the patients. In patients with osseous metastases of the spine ratios of 0.80 to 4.0 occurred ( reference area second vertebra below or above the affected vertebra). In degenerative changes of the spine values of 0.80 to 1.69 were computed. These results show, that 74% of the spine metastases could not be differentiated from benign changes of the spine by determining their relative amounts of bone uptake. In bone tumours of the extremities and in rheumatoid or gouty arthritis of the small joints (hands and feet) the highest ratios, i.e. contrasts, occurred referring to a contralateral reference area. Osteoarthritic and inflammatory alterations of the big joints could not be differentiated because of percentual distribution of the increased joint-to-joint ratios turned out to be nearly identical.

Topics: Adult; Aged; Arthritis; Arthritis, Rheumatoid; Bone Diseases; Bone Neoplasms; Colonic Neoplasms; Diphosphates; Diphosphonates; Extremities; Femur; Gout; Hemangiosarcoma; Humans; Hypertrophy; Lumbar Vertebrae; Melanoma; Middle Aged; Neoplasm Metastasis; Osteoarthritis; Radionuclide Imaging; Spinal Neoplasms; Spinal Osteophytosis; Spondylolisthesis; Technetium

Five cases of hemochromatosis arthropathy are presented and the distinctive radiological features of the disease are described. Although the condition is typically degenerative, showing subchondral cyst formation, sclerosis, and thinning of cartilage, its distribution is characteristic. Selective degenerative changes of the second and third metacarpophalangeal joints are striking, particularly in the hands, while abnormalities in the intercarpal joints are variable and the interphalangeal joints are spared. Chondrocalcinosis involving both fibrous and hyaline cartilage is frequently seen as well, particularly in the large joints. The calcification is due to deposition of calcium pyrophosphate crystals, perhaps resulting from iron inhibition of pyrophosphatase.

Topics: Adult; Aged; Arthritis; Arthritis, Rheumatoid; Calcium Phosphates; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Elbow Joint; Finger Joint; Hemochromatosis; Hip Joint; Humans; Joint Diseases; Knee Joint; Male; Middle Aged; Osteoarthritis; Radiography; Shoulder Joint; Spine; Synovial Membrane; Wrist Joint

The solubility of triclinic calcium pyrophosphate dihydrate (CPPD) crystals was measured under varying conditions using 45Ca-labeled crystals, expressing solubility as micromoles per liter of 45Ca in solution. In a 0.1-M Tris-HC1 buffer pH 7.4, the solubility of accurately sized CPPD crystals (37-20mum) was 60muM with maximal solubility being attained after about 8 h incubation at 37degreeC. Reduction in crystal size, decrease in pH, increase in ionic strength, Mg++, citrate, and albumin all increased solubility. The most marked effects on solubility occurred when changing the calcium concentration or by enzymatic hydrolysis of inoganic pyrophosphate to orthophosphate. It was found that decreasing the ionized calcium level below 5 mg/100 ml resulted in a progressive enhancement of solubility. The observed solubility-enhancing effects of albumin could be explained solely on its calcium-binding ability and thereby, altered ionized calcium level. Diffusible calcium in synovial fluid was only 40% of the total calcium concentration, which means most joint fluids are normally near the critical concentration of 5 mg/100 ml of ionized calcium, below which solubility is enhanced. During surgery, especially parathyroidectomy, calcium levels fall, favoring dissolution of CPPD crystals. We speculate that the slight decrease in crystal size during dissolution frees them from their cartilaginous mold, resulting in a dose-dependent inflammatory reaction as they are "shed" into the joint space. Crystal shedding may be reinforced by the modest fall in joint fluid pH accompanying the inflammatory response.

Topics: Arthritis, Rheumatoid; Calcium; Chondrocalcinosis; Citrates; Diphosphates; Gout; Humans; Hydrogen-Ion Concentration; Hydrolysis; Joint Diseases; Joints; Magnesium; Osteoarthritis; Pyrophosphatases; Serum Albumin; Solubility; Synovial Fluid

The anatomy and pathology of the radiocarpal compartment of the adult wrist are described in a study of human cadavers and 50 consecutive patients with radiocarpal joint abnormalities. The most frequently encountered diseases were adult onset rheumatoid arthritis (42) and calcium pyrophosphate deposition disease (22%). Features allowing radiographic diagnosis included the degree of symmetry and the presence of demineralization, sclerosis, joint space narrowing, subchondral cysts and erosions. Evaluation of abnormalities in other compartments of the wrist and the ulnar styloid is mandatory.

Topics: Adult; Aged; Arthritis; Arthritis, Juvenile; Arthritis, Rheumatoid; Carpal Bones; Diphosphates; Female; Gout; Humans; Male; Middle Aged; Psoriasis; Radiography; Radius; Spondylitis, Ankylosing; Wrist Joint

Topics: Acromegaly; Acute Disease; Aged; Arthritis, Rheumatoid; Bursitis; Calcium Phosphates; Chondrocalcinosis; Chronic Disease; Colitis, Ulcerative; Crystallization; Diphosphates; Female; Gout; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Pyrophosphatases; Radioisotope Dilution Technique; Synovial Fluid

A rapid and relatively simple method for measurement of inorganic pyrophosphate (PPi) in biological samples has been described. The mean +/-SEM of plasma samples from 94 normal subjects was 1.8+/-0.06 muM, giving a normal range (99% confidence limits) of 0.16 - 3.40 mumol/liter. Analysis of 17 plasma samples in duplicate showed a standard deviation of 0.18, giving a 99% probability that a single determination of plasma PPi would be +/-0.68 muM of the true value. The mean PPi levels in plasma from subjects with osteoarthritis, pseudogout, acromegaly, and uremia were significantly greater than the normal mean (P < 0.01). Samples from rheumatoid arthritis showed PPi levels distributed about a mean identical to the normal mean. Plasma inorganic orthophosphate levels correlated positively with PPi levels in samples from normal subjects and in samples from patients with osteoarthritis, pseudogout, and uremia, but not with acromegaly. This correlation was statistically significant only in the normal samples and in those from patients with osteoarthritis.

Topics: Acromegaly; Adolescent; Adult; Aged; Arthritis, Rheumatoid; Body Fluids; Child; Child, Preschool; Chondrocalcinosis; Colorimetry; Diphosphates; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Osteoarthritis; Phosphorus Isotopes; Pyrophosphatases; Uremia

Topics: Arthritis, Infectious; Arthritis, Rheumatoid; Bone Diseases; Bone Neoplasms; Diphosphates; Drug Combinations; Humans; Joint Diseases; Male; Neoplasm Metastasis; Pelvic Neoplasms; Phosphates; Prostatic Neoplasms; Radionuclide Imaging; Technetium

Topics: Ankle Joint; Arthritis, Rheumatoid; Bone and Bones; Breast Neoplasms; Diphosphates; Female; Humans; Kinetics; Knee Joint; Male; Phosphates; Prostatic Neoplasms; Radionuclide Imaging; Rheumatic Fever; Spondylitis, Ankylosing; Strontium Radioisotopes; Technetium; Whole-Body Counting

Topics: Arthritis, Rheumatoid; Diphosphates; Humans; Methods; Spondylitis, Ankylosing; Strontium Radioisotopes; Subtraction Technique; Technetium

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Biopsy; Connective Tissue; Dermatomyositis; Diphosphates; Gout; Humans; Hyperparathyroidism; Inflammation; Joint Diseases; Lupus Erythematosus, Systemic; Neutrophils; Polyarteritis Nodosa; Psoriasis; Rheumatoid Factor; Salicylates; Sarcoidosis; Spondylitis, Ankylosing; Synovial Fluid; Synovial Membrane; Uric Acid

Topics: Arthritis, Rheumatoid; Calcium; Calcium Phosphates; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Phosphoric Monoester Hydrolases; Synovial Membrane

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Color; Complement System Proteins; Diphosphates; Erythrocytes; Glucose; Gout; Hemophilia A; Humans; Hyaluronic Acid; Immunoglobulins; Joint Diseases; Joints; Leukocytes; Lipids; Proteins; Rheumatoid Factor; Synovial Fluid; Viscosity

Topics: Acetates; Arthritis; Arthritis, Rheumatoid; Betamethasone; Diagnosis, Differential; Diphosphates; Glucocorticoids; Gout; Humans; Injections, Intra-Articular; Methylprednisolone; Microscopy, Electron; Microscopy, Polarization; Synovial Fluid; Triamcinolone Acetonide; Uric Acid

Topics: Arthritis, Rheumatoid; Crystallization; Diphosphates; Eosinophils; Humans; Lysosomes; Macrophages; Microscopy, Electron; Neutrophils; Phagocytosis; Plasma Cells; Synovial Fluid; Uric Acid

Topics: Aged; Arthritis, Rheumatoid; Calcium; Chondrocalcinosis; Crystallization; Diphosphates; Gout; Humans; Male; Methods; Microscopy, Fluorescence; Microscopy, Polarization; Synovial Fluid; Uric Acid

Topics: Aged; Arthritis, Rheumatoid; Calcinosis; Diagnosis, Differential; Diphosphates; Female; Humans; Hyperglycemia; Joint Diseases; Knee Joint; Middle Aged; Radiography; Synovial Fluid; Wrist Joint

Topics: Arthritis; Arthritis, Rheumatoid; Calcinosis; Calcium Phosphates; Cartilage; Cartilage, Articular; Chondrocalcinosis; Classification; Diagnosis, Differential; Diphosphates; Geriatrics; Gout; Humans; Joint Diseases; Knee; Lupus Erythematosus, Systemic; Pathology; Radiography; Rheumatic Diseases; Synovial Fluid