pyrophosphate and Osteoarthritis

In the progression of osteoarthritis, pathological calcification in the affected joint is an important feature. The role of these crystallites in the pathogenesis and progression of osteoarthritis is controversial; it remains unclear whether they act as a disease initiator or are present as a result of joint damage. Recent studies reported that the molecular mechanisms regulating physiological calcification of skeletal tissues are similar to those regulating pathological or ectopic calcification of soft tissues. Pathological calcification takes place when the equilibrium is disrupted. Calcium phosphate crystallites are identified in most affected joints and the presence of these crystallites is closely correlated with the extent of joint destruction. These observations suggest that pathological calcification is most likely to be a disease initiator instead of an outcome of osteoarthritis progression. Inhibiting pathological crystallite deposition within joint tissues therefore represents a potential therapeutic target in the management of osteoarthritis.

Topics: Apoptosis; Bursa, Synovial; Calcinosis; Calcium; Cartilage; Chondrocytes; Collagen; Diphosphates; Extracellular Matrix; Extracellular Vesicles; Humans; Meniscus; Mitochondria; Osteoarthritis; Phosphates; Proteoglycans; Pyrophosphatases; Severity of Illness Index

Topics: Anti-Inflammatory Agents, Non-Steroidal; Apatites; Calcium Pyrophosphate; Crystallization; Diphosphates; Humans; Osteoarthritis; Pain; Pain Management; Synovial Fluid; Synovial Membrane

Calcium pyrophosphate and apatite crystals are common in osteoarthritic knee effusions. One or the other crystal was found in 60 percent or more of cases. These crystals offer the potential for mechanical effects in cartilage but are also often phagocytized by synovial cells. A low-grade inflammation with release of proteases and other mediators of inflammation may be an important factor in the pain and joint damage of osteoarthritis. Crystal-associated changes may merit specific attention in any future approach to therapy.

Topics: Apatites; Calcium Pyrophosphate; Crystallization; Diphosphates; Humans; Inflammation; Knee Joint; Microscopy, Electron; Osteoarthritis; Phagocytosis; Synovial Fluid; Synovial Membrane

Topics: Aged; Arthritis; Bone and Bones; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Durapatite; Female; Gout; Humans; Hydroxyapatites; Male; Osteoarthritis

Topics: Animals; Arthropathy, Neurogenic; Calcium Pyrophosphate; Cartilage, Articular; Cholesterol; Chondrocalcinosis; Crystallization; Diphosphates; Disease Models, Animal; Durapatite; Hand; Hemochromatosis; Humans; Hydroxyapatites; Knee Joint; Menisci, Tibial; Ochronosis; Osteoarthritis; Postoperative Complications; Radiography; Shoulder Joint; Uric Acid

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

Mesenchymal stem cells (MSCs) can protect against cartilage breakdown in osteoarthritis (OA) via their immunomodulatory capacities. However, the optimization strategy for using MSCs remains challenging. This study's objective was to identify the in vivo effects of metformin-stimulated adipose tissue-derived human MSCs (Ad-hMSCs) in OA. An animal model of OA was established by intra-articular injection of monosodium iodoacetate into rats. OA rats were divided into a control group and two therapy groups (treated with Ad-hMSCs or metformin-stimulated Ad-hMSCs). Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1β, and IL-6 expression. Metformin increased the migration capacity of Ad-hMSCs with upregulation of chemokine expression. In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1β-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3. The antinociceptive activity and chondroprotective effects were greater in OA rats treated with metformin-stimulated Ad-hMSCs than in those treated with unstimulated Ad-hMSCs. TGF-β expression in subchondral bone of OA joints was attenuated more in OA rats treated with metformin-stimulated Ad-hMSCs. Our findings suggest that metformin offers a promising option for the clinical application of Ad-hMSCs as a cell therapy for OA.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Cell Movement; Cells, Cultured; Chondrocytes; Cytoprotection; Diphosphates; Disease Models, Animal; Humans; Imidazoles; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interleukin-10; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Metformin; Nociception; Osteoarthritis; Rats; Rats, Wistar

Topics: Adipose Tissue; Autophagy; Bone and Bones; Diphosphates; Humans; Multiple Myeloma; Musculoskeletal Diseases; Osteoarthritis; Osteoporosis, Postmenopausal; Pain

Osteoarthritis (OA) is a whole-joint disease characterized by cartilage degradation and mineralization associated with chondrocyte phenotype changes, subchondral bone sclerosis and mild synovial inflammation. The extracellular levels of inorganic phosphate (ePi) and pyrophosphate (ePPi) are major regulators of the mineralization process but also play a role in the maintenance of the differentiated chondrocyte phenotype. Four membrane proteins control the balance between ePi and ePPi: the transporters ANK (exporting PPi outside the cells) and PiT-1 (importing ePi into the cells), and the enzymes PC-1 (generating ePPi from nucleotides) and Tissue Non-specific Alkaline Phosphatase (TNAP, hydrolyzing ePPi into ePi). In the present work, we investigated the ability of specific microRNAs (miR) to modulate activity and level of the mRNA coding for the regulatory proteins of the ePi/ePPi balance in chondrocytes. The 4 following microRNAs, let7e, miR-9, miR-188 and miR-219, were selected by bioinformatics for their ability to putatively target the mRNA 3'UTRs of these regulators. In IL-1β-stimulated human chondrocytes, chosen as a model of differentiated phenotype loss implicating the PPi transporter ANK, miR-9, miR-188 and let7e levels increased. However, luciferase reporter assays and transient miR overexpression in the ATDC5 chondrogenic cell line only support that miR-9 was a negative post-transcriptional regulator of PC-1, Pit-1 and TNAP mRNAs. This suggests that miR-9 could contribute to the acquirement of an altered chondrocyte phenotype by disrupting the ePi/ePPi balance.

Topics: Algorithms; Amino Acid Sequence; Animals; Cell Differentiation; Cell Line, Tumor; Chondrocytes; Diphosphates; Gene Expression Regulation; Gene Targeting; HeLa Cells; Humans; Membrane Proteins; Mice; MicroRNAs; Molecular Sequence Data; Osteoarthritis; Phenotype; Phosphates

Mineralization of growth plate cartilage is a critical event during endochondral bone formation, which allows replacement of cartilage by bone. Ankylosis protein (Ank), which transports intracellular inorganic pyrophosphate (PP(i)) to the extracellular milieu, is expressed by hypertrophic and, especially highly, by terminally differentiated mineralizing growth plate chondrocytes. Blocking Ank transport activity or ank expression in terminally differentiated mineralizing growth plate chondrocytes led to increases of intra- and extracellular PP(i) concentrations, decreases of alkaline phosphatase (APase) expression and activity, and inhibition of mineralization, whereas treatment of these cells with the APase inhibitor levamisole led to an increase of extracellular PP(i) concentration and inhibition of mineralization. Ank-overexpressing hypertrophic nonmineralizing growth plate chondrocytes showed decreased intra- and extracellular PP(i) levels; increased mineralization-related gene expression of APase, type I collagen, and osteocalcin; increased APase activity; and mineralization. Treatment of Ank-expressing growth plate chondrocytes with a phosphate transport blocker (phosphonoformic acid [PFA]) inhibited uptake of inorganic phosphate (P(i)) and gene expression of the type III Na(+)/P(i) cotransporters Pit-1 and Pit-2. Furthermore, PFA or levamisole treatment of Ank-overexpressing hypertrophic chondrocytes inhibited APase expression and activity and subsequent mineralization. In conclusion, increased Ank activity results in elevated intracellular PP(i) transport to the extracellular milieu, initial hydrolysis of PP(i) to P(i), P(i)-mediated upregulation of APase gene expression and activity, further hydrolysis and removal of the mineralization inhibitor PP(i), and subsequent mineralization.

Topics: Alkaline Phosphatase; Amino Acid Sequence; Animals; Anthraquinones; Biological Transport; Blotting, Northern; Cartilage; Cell Differentiation; Cells, Cultured; Chickens; Chondrocytes; Cloning, Molecular; Diphosphates; DNA-Binding Proteins; Electrophoresis, Polyacrylamide Gel; Gene Expression Regulation; Immunoblotting; Immunohistochemistry; Membrane Proteins; Models, Biological; Molecular Sequence Data; Osteoarthritis; Phosphates; Retroviridae; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Sequence Homology, Amino Acid; Signal Transduction; Time Factors; Transcription Factor Pit-1; Transcription Factors; Tretinoin; Up-Regulation

The study of our team was driven by a clinical problem of age-dependent chronic degenerative disease of skeleton that includes osteoporosis (OP) and osteoarthritis (OA)-related phenotypes. The major aims of the study included evaluation of the putative genetic factors determining the rate and pattern of the bone and cartilage loss and identification of the specific genes involved in this process. In addition, we examined genetic effects on circulating molecular factors involved in bone and cartilage metabolism. The skeletal phenotypes were assessed from hand radiographs, in total on about 1200 individuals belonging to ethnically homogeneous nuclear and complex three-generational pedigrees of European origin. The results obtained until now can be divided into three sections: (1) genetic analysis of bone mass/size/geometry characteristics (OP) and traits related to hand OA; (2) pedigree-based investigation of circulating levels of calciotropic hormones, growth factors, cytokines, and biochemical indices of bone and cartilage remodelling; (3) linkage and linkage disequilibrium study of several candidate genes, such as estrogen receptor alpha, collagen type I alpha 1, genes related to extracellular inorganic pyrophosphate transport and OP/OA phenotypes, including biochemical variables. The study provides compelling evidence to suggest strong involvement of the genetic factors in determination of variation of the majority of the examined OP- and OA-related phenotypes.

Topics: Age Factors; Aging; Biological Transport; Bone and Bones; Bone Remodeling; Cartilage; Cohort Studies; Collagen Type I; Collagen Type I, alpha 1 Chain; Diphosphates; Estrogen Receptor alpha; Female; Genetic Linkage; Genetic Predisposition to Disease; Genotype; Humans; Likelihood Functions; Linkage Disequilibrium; Male; Models, Biological; Osteoarthritis; Osteoporosis; Pedigree; Phenotype; Risk Factors; Statistics as Topic; Time Factors

Periarticular calcification is a common attendant symptom of generalized arterial calcification of infancy, a rare Mendelian disorder caused by mutations of the gene coding for ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). This prompted us to perform a family-based association study to test the hypothesis that genetic variation at the ENPP1 locus is involved in the etiology of osteoarthritis of the hand. The study population comprised 126 nuclear families with 574 adult individuals living in small villages in the Chuvasha and Bashkirostan autonomies of the Russian Federation. The extent of osteoarthritis was determined by analyzing plain hand radiographs. The outcome of a principal component analysis of osteoarthritis scores of a total of 28 joints of both hands was used as a primary phenotype in this study. Maximum likelihood estimates of the variance component analysis revealed a substantial contribution of genetic factors to the overall trait variance of about 25% in this homogeneous population. Three short tandem repeat (STR) polymorphisms--one intragenic and two flanking markers--and four single-nucleotide polymorphisms were tested. The markers tagged the ENPP1 locus at nearly equal intervals. We used three different transmission disequilibrium tests and obtained highly significant association signals. Alleles of the upstream microsatellite marker as well as several single-nucleotide polymorphism haplotypes consistently revealed the association. Thus, our data highlights variability of ENPP1 as an important genetic factor in the pathogenesis of idiopathic osteoarthritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Bashkiria; Chromosomes, Human, Pair 6; Crystallization; Diphosphates; Ethnicity; Female; Genetic Predisposition to Disease; Genotype; Hand Bones; Haplotypes; Humans; Linkage Disequilibrium; Male; Microsatellite Repeats; Middle Aged; Osteoarthritis; Pedigree; Phosphoric Diester Hydrolases; Polymorphism, Single Nucleotide; Pyrophosphatases; Radiography; Regulatory Sequences, Nucleic Acid; Russia; White People

A genetic association of the ENPP1 gene with primary hand osteoarthritis was recently reported in this journal. ENPP1 encodes an enzyme that regulates soft tissue calcification. The study as it stands is far from complete because the actual causal variant(s) within ENPP1 has not been identified and no functional study on the activity of the enzyme in hand osteoarthritis was presented. Nevertheless, the study stimulates interest and will encourage others in the field to test ENPP1 as a possible osteoarthritis susceptibility gene in their cohorts. The genetic basis of osteoarthritis is slowly being uncovered, and this report constitutes another interesting find.

Topics: Adult; Bashkiria; Chromosomes, Human, Pair 6; Crystallization; Diphosphates; Ethnicity; Genetic Predisposition to Disease; Genotype; Hand Bones; Humans; Linkage Disequilibrium; Microsatellite Repeats; Osteoarthritis; Pedigree; Phosphoric Diester Hydrolases; Polymorphism, Single Nucleotide; Pyrophosphatases; Radiography; Regulatory Sequences, Nucleic Acid; Russia

Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals.. Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage.. Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes or cartilage extracts. Both CILP and ANK mRNA expression and ePPi elaboration were stimulated by TGFbeta1 and inhibited by IGF-1 in chondrocytes from all sources.. CILP and ANK mRNA expression correlates with chondrocyte ePPi accumulation around CPPD and OA chondrocytes, and all respond similarly to growth factor stimulation. These findings suggest that up-regulated CILP and ANK expression contributes to higher ePPi accumulation from CPPD crystal-forming cartilage.

Topics: Adult; Aged; Cartilage, Articular; Chondrocalcinosis; Chondrocytes; Diphosphates; Extracellular Matrix Proteins; Extracellular Space; Growth Substances; Humans; Hyalin; In Vitro Techniques; Membrane Proteins; Middle Aged; Osteoarthritis; Phosphate Transport Proteins; Pyrophosphatases; Up-Regulation

A new study on page 265 of this issue suggests that a genetic defect in mice causes the joint's cartilage cells to pump insufficient amounts of pyrophosphate--a natural water softener--into the joint cleft, and this in turn leads to the formation of bony spurs that eventually stiffen the joints completely. Because humans have an almost identical gene, and disorders such as osteoarthritis also feature an abnormal outgrowth of bones, some arthritis researchers are hopeful that these new findings may point the way toward a new class of pyrophosphate-based drugs similar to the antiscaling chemicals in washing powders and toothpaste. But, as many of the researchers point out, the numerous roads that lead to human joint degradation make a single cure-all unlikely.

Topics: Animals; Arthritis; Cartilage; Diphosphates; Humans; Joints; Membrane Proteins; Mice; Mice, Mutant Strains; Mutation; Osteoarthritis; Phosphate Transport Proteins

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

To test the hypothesis that high concentrations of extracellular inorganic pyrophosphate (PPi), which associate with increased cell synthesis and turnover in cartilage, may act as a marker for structural outcome in knee osteoarthritis (OA).. One hundred and thirty five consecutive patients referred to hospital with knee OA (59 men, 76 women; mean age 71 years, range 41-88) were followed prospectively for a median of 2.5 years (interquartile range 1.75-3.0). Synovial fluid (SF) aspirated at presentation (202 OA knees: 68 bilateral, 66 unilateral) was assessed for PPi content by radiometric assay. Knee radiographs at presentation and at final review were assessed for change in global (Kellgren) and individual features (narrowing, osteophyte, sclerosis, cyst, attrition) of OA.. The median SF PPi level was 10.5 mumol (range 0.07-72.4). At baseline, high PPi was significantly associated with presence of calcium pyrophosphate crystals, chondrocalcinosis, and bone attrition. Radiographic change was observed in 164 knees. High PPi levels were negatively associated with change in Kellgren and Lawrence grade, further narrowing, and increase in osteophyte, but positively associated with development of attrition. In the 68 patients from whom bilateral data were obtained, there was correlation between right and left knees for PPi levels, all baseline radiographic scores, and changes in radiographic features. Multiple logistic regression analysis for PPi as a continuous variable (age, gender, and patient number included in model) showed a negative correlation with change in global Kellgren and Lawrence grade (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95 to 0.99) and a positive correlation with attrition (OR 1.04, 95% CI 1.02 to 1.07).. High SF levels of PPi are associated with favourable radiographic outcome in terms of progressive change in Kellgren grade. Such elevated PPi levels, however, may inhibit new bone formation and remodelling in knee OA.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Diphosphates; Female; Follow-Up Studies; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Prognosis; Prospective Studies; Radiography; Sensitivity and Specificity; Synovial Fluid

Topics: Diphosphates; Humans; Joint Diseases; Osteoarthritis; Radiography; Tibia

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

In order to evaluate the effect of calcium pyrophosphate dihydrate (CPPD) deposition on articular cartilage catabolism, the proteoglycans released into normal synovial fluid were compared with those in synovial fluid obtained from patients with osteoarthritis (OA), chronic pyrophosphate arthropathy (CPA) and acute pyrophosphate arthropathy (APA). Keratan sulphate (KS) was measured by the modified 1,9-dimethylmethylene blue (DMB) assay in synovial fluids treated with chondroitin ABC lyase. This enzyme was found to eliminate all of the sulphated glycosaminoglycans in synovial fluid except KS. In OA, CPA and APA the concentrations of KS were found to be significantly higher than in normal synovial fluid (NSF) (P less than 0.01). Similar KS concentrations were observed in CPA and APA. In CPA they were significantly higher than in OA (P less than 0.02). The size distribution of proteoglycan fragments varied between different patients with the same disease, but only minor differences were observed in patients with OA and CPA who were matched for age, sex and disease severity. Furthermore, the size distribution of proteoglycan fragments in the acute and chronic phases of pyrophosphate arthritis was similar. Thus although in pyrophosphate arthritis the rate at which proteoglycans are released from the cartilage may be greater than in OA or normal joints, the fundamental processes governing the release of these macromolecules may be the same.

Topics: Adult; Aged; Aged, 80 and over; Arthritis; Calcium Pyrophosphate; Chromatography, Gel; Diphosphates; Female; Humans; Keratan Sulfate; Male; Middle Aged; Osteoarthritis; Proteoglycans; 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

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

Topics: Arthritis; Calcium Phosphates; Calcium Pyrophosphate; Diphosphates; Humans; Osteoarthritis; Synovial Fluid

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

Synovial, meniscal, articular cartilage, and other connective tissue from fifty-seven patients who had calcium pyrophosphate dihydrate crystal-deposition disease was examined by light microscopy, electron microscopy, and electron-probe microanalysis. Safranin O-positive hypertrophic chondrocytes that contained proteoglycans were observed in the tissues of each patient. Microcrystals that were suggestive of early precipitation of crystals were found in the degenerating matrix surrounding hypertrophic chondrocytes. The matrix contained electron-dense amorphous material, including proteoglycans and debris of cellular components. The microcrystals were often seen in contact with degenerating collagen fibers. There was never any histological evidence of formation of crystal in the areas that had no hypertrophic chondrocytes. Chondrocytes of this kind, surrounded by characteristic degenerating matrix, were never observed in the articular tissue from sixty-one patients who had only osteoarthritis. On the basis of our results, we speculate that electron-dense amorphous material containing proteoglycans and debris of cellular components, and the degenerating collagen fibers that were seen around the hypertrophic chondrocytes, may play important roles in the formation of calcium pyrophosphate dihydrate crystals.

Topics: Adult; Aged; Aged, 80 and over; Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Electron Probe Microanalysis; Female; Humans; Male; Microscopy, Electron, Scanning; Middle Aged; Osteoarthritis

We measured levels of cartilage proteoglycan (PG) fragments in knee joint synovial fluid obtained from patients with previous trauma of the knee, early gonarthrosis, or pyrophosphate synovitis, and in age-matched control subjects. During the initial 3-4 weeks after rupture of the anterior cruciate ligament or the meniscus (confirmed by arthroscopy), markedly increased PG fragment levels were found. At later times after trauma (up to 4 years), many of these patients still had significantly elevated levels of cartilage PG fragments in the joint fluid. In a group of older patients with gonarthrosis, these levels were only moderately elevated, while in patients with acute pseudogout, greatly increased levels were observed. Although longitudinal studies are needed to validate the significance, PG fragments in joint fluid may be a marker for early posttraumatic arthrosis.

Topics: Adolescent; Adult; Cartilage; Chondrocalcinosis; Diphosphates; Female; Humans; Knee Injuries; Male; Middle Aged; Osteoarthritis; Peptide Fragments; Proteoglycans; Synovial Fluid; Synovitis; Time Factors

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

Synovial fluid (SF) inorganic pyrophosphate (PPi) concentration is elevated in calcium pyrophosphate dihydrate (CPPD) crystal deposition arthropathy. Since CPPD and basic calcium phosphate (BCP) crystals often are present in the same joints, we determined [PPi] and activity of the PPi-generating enzyme, nucleotide pyrophosphohydrolase (NPPH), in SF from the joints of patients with various arthropathies, including those with BCP crystals. We found elevated SF [PPi] in joints with BCP crystals, as well as in joints with CPPD crystals. The presence of BCP crystals in synovial fluids was also predictive of elevated NPPH activity.

Topics: Calcium Phosphates; Crystallization; Diphosphates; Humans; Joint Diseases; Osmolar Concentration; Osteoarthritis; Preservation, Biological; Pyrophosphatases; Shoulder Joint; Syndrome; Synovial Fluid

A comparison of synovial fluid lactate levels has been made in cases of chronic pyrophosphate arthropathy (PA) with and without joint destruction, acute PA and osteoarthritis. No statistically significant difference could be observed between results of chronic PA and osteoarthritis. By contrast, synovial fluid lactate levels were significantly higher in acute PA in comparison with the two other groups. These data suggest that hypoxia is unlikely to play a role in destructive arthropathy commonly found in chronic PA.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Chondrocalcinosis; Chronic Disease; Diphosphates; Humans; Knee Joint; Lactates; Middle Aged; Osteoarthritis; Synovial Fluid

Calcium pyrophosphate dihydrate deposition disease is a spectrum of disease including asymptomatic chondrocalcinosis, pseudogout, and chronic arthropathy. Its frequency increases with advancing age and is found very commonly in the aged. Underlying metabolic illnesses are occasionally identifiable. Differentiation from other causes of arthritis that it may mimic is often important and possible on clinical grounds, radiographic examination, and synovial fluid analysis. Prognosis is variable and treatment may include analgesics, nonsteroidal anti-inflammatory drugs, colchicine, and intra-articular corticosteroids.

Topics: Aged; Aging; Anti-Inflammatory Agents, Non-Steroidal; Calcium Pyrophosphate; Chondrocalcinosis; Colchicine; Diagnosis, Differential; Diphosphates; Female; Humans; Male; Osteoarthritis; Prognosis; Radiography; Synovial Fluid

Topics: Aged; Bursitis; Calcinosis; Calcium Pyrophosphate; Diphosphates; Female; Hip Joint; Humans; Osteoarthritis

Radiographs and synovial fluids from 66 knees representing 59 patients with symptomatic osteoarthritis were evaluated to determine the pattern of radiographic abnormalities associated with basic calcium phosphate (BCP), calcium pyrophosphate dihydrate (CPPD), or both crystals together. Crystals were found in 71% of fluids. In general, CPPD crystals correlated with patient age, while BCP crystals correlated with joint degeneration. Synovial fluid BCP and CPPD crystals were found together more often than either alone. Joint compartment narrowing and osteophytes in three compartments are often associated with BCP crystals.

Topics: Aged; Calcium Phosphates; Calcium Pyrophosphate; Crystallization; Diphosphates; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Radiography; Synovial Fluid

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

Apatite crystals, calcium pyrophosphate dihydrate crystals, or both were observed in knee joint effusions from 60% of 100 consecutive osteoarthritis (OA) patients. Crystals were mor common in patients with more severe OA and in joints that had received previous intraarticular steroid injections. Whether the latter was predominantly related to an effect of the steroid or to the fact that steroids were used in more severe cases was not clear. Crystals existed in many effusions without elevated synovial fluid leukocyte counts. A subgroup of 7 patients had both types of crystals, more crystal phagocytosis, and more severe OA.

Topics: Aged; Apatites; Calcium Pyrophosphate; Crystallization; Diphosphates; Female; Humans; Injections, Intra-Articular; Leukocyte Count; Male; Middle Aged; Osteoarthritis; Steroids; Synovial Fluid

Topics: Aged; Diphosphates; Female; Hip Joint; Humans; Male; Middle Aged; Osteoarthritis; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Technetium Tc 99m Pyrophosphate

Adenosine triphosphate pyrophosphohydrolase (ATPPPH) and neutral inorganic pyrophosphatase activities were assayed in synovial fluids (SF) from 37 patients with a variety of arthropathies. ATPPPH activity was detected in all fluids, but was highest in patients with chronic chondrocalcinosis; its activity in patients with osteoarthritis was higher than that in patients with rheumatoid arthritis, gout, or pseudogout. ATPPPH activity correlated positively with SF pyrophosphate concentration and negatively with SF white blood cell count. Pyrophosphatase activity did not correlate with diagnosis, pyrophosphate level, or white blood cell count.

Topics: Adenosine Triphosphatases; Adult; Aged; Calcinosis; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Male; Middle Aged; Osteoarthritis; Pyrophosphatases; Synovial Fluid

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

Topics: Adult; Aged; Diagnosis, Differential; Diphosphates; Female; Femur Head Necrosis; Hip Fractures; Hip Joint; Humans; Male; Middle Aged; Osteoarthritis; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Calcium pyrophosphate (CPPD) and apatite crystals are associated with several types of arthritis. Using transmission electron microscopy both the tiny apatite-like crystals and larger CPPD can be seen to be associated with granular materials. With the ferritin bridge technique immunoglobulins and complement are seen in the material with the apatite but not the CPPD. Immunoprotein is seen both intracellularly and extracellularly. Further study of these coatings is needed to ascertain if they have consistent patterns on all crystals and how they affect the ability of the crystals to induce inflammation.

Topics: Calcinosis; Calcium Pyrophosphate; Crystallization; Diphosphates; Durapatite; Humans; Hydroxyapatites; Microscopy, Electron; Osteoarthritis; Proteins; Synovial Fluid

Naturally occurring deposition of calcium pyrophosphate has been identified in six rhesus monkeys following acute episodes of trauma and various septicemias. Scanning electron microscopy with energy-dispersive X-ray analytical system and single crystal electron diffraction studies were used to identify the crystals within the articular cartilage. The osteoarthritis grading system was used to determine the degree of cartilage degenerative changes.

Topics: Animals; Calcium Pyrophosphate; Cartilage Diseases; Cartilage, Articular; Diphosphates; Female; Knee Joint; Macaca mulatta; Male; Microscopy, Electron, Scanning; Monkey Diseases; Osteoarthritis; Synovitis; X-Ray Diffraction

Radionuclide joint imaging with the technetium-99m-labeled phosphates is a sensitive technique for the detection of inflammatory articular disease, although it is nonspecific as to the cause of the increased uptake and offers poor resolution in comparison to conventional radiography. There does not appear to be any place for the routine use of joint imaging of the peripheral joints, as there is little evidence that it benefits patient management. Scintigraphy is of benefit in the detection of osteomyelitis, Legg-Perthes' disease, and osteonecrosis, where changes may antedate roentgenologic abnormalities. Technetium-99m-phosphates may have an increasing role in the evaluation of knee and hip prosthetic joint loosening and infection, especially regarding the femoral components. Scintigraphy may be useful in excluding synovitis and allaying concern in selected patients with chronic articular pain in whom a conventional diagnostic evaluation is unrewarding. Attempts have been made to use radionuclide joint imaging to quantitate the degree of synovitis present in individual joints, particularly the sacroiliac joints. To date, reliable methods that distinguish normal from abnormal joints have not been established, although this remains an area of potential usefulness and active research. Scintigraphy with 99mTc-phosphates is useful in the detection of spinal fracture and pseudoarthrosis in individuals with ankylosing spondylitis.

Topics: Adult; Arthritis; Bone Neoplasms; Child; Diphosphates; Diphosphonates; Female; Gallium Radioisotopes; Humans; Joint Diseases; Legg-Calve-Perthes Disease; Male; Middle Aged; Osteoarthritis; Osteomyelitis; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Spondylitis, Ankylosing; Synovitis; Technetium; Technetium Compounds; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate

The relationship between osteoarthritic change and amyloid degeneration was studied in 116 joint capsules from osteoarthritic hip joints. Twenty-seven (23%) contained amyloid deposits. Twenty-eight joint capsules showed chondroid metaplasia in the fibrous part. Significantly more amyloid degeneration was found among these. Six joint capsules contained pyrophosphate crystals. Five of these were positive for amyloid. Chronic inflammation of the joint capsule was found in 80% of the cases and was negatively correlated with amyloid degeneration, which is in good agreement with the biphasic theory for the pathogenesis of amyloid. Further investigation is necessary to decide how chondroid metaplasia takes part in the production of amyloid.

Topics: Adult; Aged; Amyloid; Chondroma; Diphosphates; Female; Hip Joint; Histocytochemistry; Humans; Lymphocytes; Male; Metaplasia; Microscopy, Electron; Middle Aged; Osteoarthritis; Synovial Membrane

Incubation of minced, focally calcified, chondromatosis tissue obtained at operation from a patient with Milwaukee shoulder (rotator cuff defect and glenohumeral osteoarthritis associated with synovial fluid, hydroxyapatite crystals in microspheroidal masses, collagenase, and neutral protease) with partially purified mammalian synovial cell collagenase released masses of hydroxyapatite crystals of the same size as those originally found in the patient's synovial fluid. Incubation of mineral articular cartilage obtained from a shoulder joint at arthroplasty for a destructive arthropathy in a patient with generalised calcium pyrophosphate dihydrate (CPPD) crystal deposition with partially purified synovial cell collagenase freed CPPD crystals from their matrix. These data are compatible with a previously postulated mechanism linking microcrystals to destructive arthropathies, that is, crystal endocytosis by synovial cells stimulating collagenase secretion with subsequent enzymatic crystal "strip-mining', releasing additional crystals into the synovial fluid in a self-perpetuating cycle.

Topics: Calcium Pyrophosphate; Cartilage, Articular; Diphosphates; Etidronic Acid; Humans; Hydroxyapatites; Male; Microbial Collagenase; Microscopy, Electron, Scanning; Middle Aged; Osteoarthritis; Synovial Membrane

The pathologic features of calcium pyrophosphate crystal deposition disease (CPDD), particularly the synovial abnormalities, have not been adequately described or depicted in textbooks or journals; this report details the findings in 12 cases. Attention is drawn to the practical reasons for distinguishing CPDD arthropathy from other arthropathies, particularly osteoarthritis; clinical and gross pathologic features that should suggest CPDD arthropathy in cases that are not suspected preoperatively; and characteristics of the tophaceous deposits in CPDD.

Topics: Aged; Apatites; Arthroplasty; Biopsy; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Foot; Hand; Humans; Joint Diseases; Knee Joint; Male; Middle Aged; Osteoarthritis; Synovial Membrane; X-Ray Diffraction

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

One abnormality in calcium pyrophosphate deposition disease (CPDD) which fosters consistently high synovial fluid pyrophosphate ion (PPi) and large accumulations of calcium pyrophosphate dihydrate crystals (Ca pyrophosphate) might be an aberration in chondrocytes involving elaboration of PPi and failure of its hydrolysis within cartilage matrix. Exploration of this hypothesis required further information on the phosphohydrolases in relevant human articular cartilages. Triton X-100 extracts of whole homogenized cartilage from 18 patients with primary osteoarthritis (OA), 10 patients with CPDD and secondary OA, as well as 6 "normal" subjects were partially purified by DE-52 chromatography and eluates studied for phosphohydrolase activity in a variety of substrates, inhibitors, and environmental conditions. Almost all the protein as well as crude alkaline phosphatase and pyrophosphatase activities were clustered in peaks designated I and II. Findings in CPDD cartilage not observed in OA controls were: 1) consistent alkaline phosphatase activity in the void volume of DE-52 columns, 2) high levels of 5'nucleotidase activity, 3) abundant generation of PPi by CPDD cartilage during in vitro incubation of cartilage extract fractions with ATP. This enzymatic behavior is likely to bear a regulatory relationship to PPi production by chondrocytes in CPDD.

Topics: Adenosine Triphosphate; Aged; Alkaline Phosphatase; Calcium Pyrophosphate; Cartilage Diseases; Cartilage, Articular; Cations, Divalent; Chromatography; Diphosphates; Female; Humans; Hydrogen-Ion Concentration; Kinetics; Male; Middle Aged; Nucleotidases; Osteoarthritis; Phosphoric Monoester Hydrolases; Pyrophosphatases

Pyrophosphate and capsular chondromatosis were demonstrated histologically in 15 cases, 14 of which also exhibited local deposition of amyloid. A systematic examination of the joint capsule in 57 consecutive hip replacement operations for osteoarthritis revealed these changes in 6 of the cases (10.5 per cent). Microscopic examination which was done if intraarticular calcifications were grossly visible at operation, showed the same changes in 8 knees, 4 with osteoarthritis and 4 with meniscal disease. The changes were also seen in the menisci. Only one patient was suffering from chronic, polyarticular pyrophosphate arthritis. In the other cases neither change had been expected a priori, and the patients had no signs of systemic articular disease or amyloidosis. Most of them were elderly, but in good health.

Topics: Adult; Aged; Amyloid; Chondrocalcinosis; Diphosphates; Female; Humans; Joints; Male; Middle Aged; Osteoarthritis

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

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

The possibilities of the complex radionucleid joint investigations in the diagnosis of ostheoarthrosis are discussed. The investigation covered 104 patients with osteoarthrosis, aged 471 +/- 2.0 and 22 control subjects, aged 43.9 +/- 3.1. The time for half-elimination of 133Xenon injected in the knee joint is 154.8 minutes for the healthy subjects and 122.2 minutes for those suspected of narrowing of the joint cavity resp., 105.4 minutes for the patients with II X-ray stage and 77.7 minutes for III-IV X-ray stage of osteoporosis. The accumulation of 99MTc-pertechnetate is 115.3 per cent for the control group and 134.9 per cent, 127.7 per cent and 143.0 per cent for the patients with I, II and III-IV X-ray stage of osteoarthrosis. The accumulation of 99MTc-pyrophosphate is 115.7 per cent in the sound joints and 144.8 per cent; 158.1 per cent and 170.7 per cent resp., according to X-ray stage of the diseases. With the progress of bonetissue destruction the effektiveness of Xenon clearance is improved as well as of 99MTc-pyrophosphate in the joints investigated. High reactivity of joint structure (synovial membrane and bone epiphysis) was established in the early and late stages of osteoarthrosis. The radionucleid constellation of an intensified joint clearance, high pyrophosphate test and light fluctuating pertechnetate joint index are indicative for a diagnostic test of the disease prior to the manifestation of confirmed X-ray data. Catabolic osseous destruction is coordinated, according to rate, with the effectiveness of the j oint 133Xenon clearance and with the accumulation of 99MTc-pyrophosphate in the joints with arthrosis alterations.

Topics: Adult; Diphosphates; Humans; Knee Joint; Middle Aged; Osteoarthritis; Radiography; Radionuclide Imaging; Technetium; Xenon Radioisotopes

The methodologic variables of the UDPG pyrophosphorylase method for analysis of inorganic pyrophosphate (PPi) levels in biologic fluids are described. Use of a tourniquet in collection of blood specimens elevated plasma PPi levels from 35% to 55% above control values and may explain the differences in published normal values. The sodium pyrophosphate decahydrate used to prepare the standard solution lost 8 waters of hydration after dessication, which could result in the calculation of spuriously elevated PPi levels. Normal plasma PPi concentration was 2.18 muM with a range (95% confidence limits) of 0.58-3.78 muM. Comparison of plasma PPi in normal subjects, patients with primary osteoarthritis, and patients with calcium pyrophosphate dihydrate deposition disease revealed no significant intergroup differences.

Topics: Blood Specimen Collection; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Methods; Osteoarthritis; Tourniquets

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

Topics: Aged; Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Diphosphates; Female; Humans; Hydroxyapatites; Male; Microscopy, Electron; Middle Aged; Osteoarthritis

Topics: Apatites; Calcium Pyrophosphate; Crystallization; Diphosphates; Humans; Osteoarthritis; Synovial Fluid

Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD) (pseudogout) are outlined in an investigation of 85 patients with definite or probable disease and available cadaveric and human surgical material. Pyrophosphate arthropathy produced distinctive roentgenographic abnormalities with were most frequent in the knee, wrist and metacarpophalangeal joints. Although the alterations superficially resembled osteoarthritis, they were frequently more severe and progressive with extensive fragmentation of bone, causing intra-articular osseous bodies. Pyrophosphate arthropathy occurred in unusual locations, such as the radiocarpal compartment of the wrist, elbow, and patellofemoral compartment of the knee. These characteristics allow the radiologist to suggest a probable diagnosis of CPPD even in the absence of articular calcification.

Topics: Aged; Calcium Pyrophosphate; Cervical Vertebrae; Chondrocalcinosis; Diphosphates; Female; Hip Joint; Humans; Joint Diseases; Knee Joint; Male; Osteoarthritis; Radiography; Wrist Joint

Lower neck uptake, frequently seen on anterior views of bone scans done with 99mTc-phosphate compounds, was studied in 122 patients to determine its incidence and etiology. Increased uptake was identified in the lower neck anteriorly in 46 patients (38%). In 14 of these, moderately severe to severe arthritis appeared to cause the uptake; metastatic disease was the cause in 8 cases; and in 1 case there was prominent uptake in the thyroid cartilage. Positioning artifact accounted for the uptake in the other 23 cases. Thyroid uptake was never observed.

Topics: Adult; Cervical Vertebrae; Diphosphates; Etidronic Acid; Humans; Laryngeal Cartilages; Neoplasm Metastasis; Osteoarthritis; Radionuclide Imaging; Spinal Diseases; Spinal Neoplasms; Technetium

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

Spontaneous haemarthrosis may occur during the evolution of articular chondrocalcinosis. It occurs mainly in older women and involves the knee in particular. The disorder may recur in the same or in different joints. A study of 11 case histories and counts of red blood corpuscles in samples of synovial fluid confirm that bleeding occurs more readily in chondrocalcinosis than in arthrosis alone. The proposed mechanism of haemarthrosis is only a hypothesis, but it is possible to imagine the onset of microcrystalline flow in a joint that is senile and affected by arthrosis. It is suspected that repeated haemarthrosis favours an oseolytic evolution in certain cases of chondrocalcinosis.

Topics: Aged; Calcium Phosphates; Chondrocalcinosis; Crystallization; Diphosphates; Female; Hemarthrosis; Humans; Inclusion Bodies; Knee Joint; Leg Injuries; Male; Middle Aged; Osteoarthritis; Osteochondritis; Osteolysis; Synovial Fluid

Topics: Alkaline Phosphatase; Cartilage, Articular; Chondrocalcinosis; Diphosphates; Humans; Osteoarthritis

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 authors report the results they obtained by bone scintigraphy using technetium pyrophosphate. In a study of 142 patients with cancer, the authors show, as others have done, that bone scintigraphy makes it possible to find bone metastases that are radiologically undetectable and they emphasize the importance of this discovery. In 7 patients with spondylodiscitis, of whom 1 was without radiological signs at the time the scintigraphy was carried out, the authors always observed localized vertebral hyperfixation and they noted that this examination can be valuable for distinguishing spondylodiscitis from pseudo-Pott's discarthroses and from the lesions of vertebral epiphysitis, which in their experience do not result in isotopic hyperfixation. In 7 patients with epiphyseal osteonecrosis, the authors observed isotopic hyperfixation before the appearance of radiological signs. In 12 patients with osteoporosis, the authors observed hyperfixation in bone in certain compressed vertebrae, whereas other vertebrae that had probably been compressed some considerable time earlier did not fix the isotope excessively. They never observed hyperfixation in vertebrae that were not compressed. Among 5 patients with ankylosing spondylitis with radiological signs of sacro-iliac arthritis, the authors observed sacro-iliac hyperfixation in only 3 cases. Two other patients who had signs indicating ankylosing spondylarthritis, but were without radiological signs of sacro-iliac arthritis did not show sacro-iliac hyperfixation of the isotope. Among 7 patients with Paget's disease, the authors observed hyperfixation in all the bones with radiological signs of disease; in addition, in 3 patients, there was also hyperfixation in certain bones that were radiologically clear.

Topics: Bone Diseases; Bone Neoplasms; Diphosphates; Epiphyses, Slipped; Humans; Joint Diseases; Knee Joint; Neoplasm Metastasis; Osteitis Deformans; Osteoarthritis; Osteoporosis; Radiography; Radionuclide Imaging; Spinal Diseases; Spondylitis; Spondylitis, Ankylosing; Technetium

Recent studies have shown elevated inorganic pyrophosphate (PPi) levels in most knee joint fluid supernates from patients with pseudogout (PG) or osteoarthritis (OA) and more modestly elevated levels in some supernates from patients with gout or rheumatoid arthritis (RA) relative to PPi levels found in the venous blood plasma of normal or arthritic subjects. We measured the intraarticular PPi pool and its rate of turnover to better understand the significance of the joint fluid-plasma PPi gradient. Preliminary studies in rabbits showed that (32-P)PPi passed from joint space to blood and vice versa without detectable hydrolysis. Incubation of natural or synthetic calcium pyrophosphate dihydrate (CPPD) microcrystals with synovial fluid in vitro in the presence of (32P)PPi tracer showed no change in PPi specific activity in the supernate over a 19-h period so that exchange of PPi in solution with that in CPPD microcrystals could be ignored. Clearance rates of (32P)PPi and of (33P)Pi, as determined by serially sampling the catheterized knee joints of volunteers with various types of arthritis over a 3-h period, were nearly identical. The (32P)PPi/(32P)Pi was determined in each sample. A mixture of a large excess of cold PPi did not influence the clearance rate of either nuclide. The quantity of PPi turned over per hous was calculated from the pool size as determined by isotope dilution and the turnover rate. The residual joint fluid nuclide was shown to be (32P)PPi. The PPi pool was generally smaller and the rate of turnover was greater in clinically inflamed joints. The mean plus or minus SEM pool size (mu-moles) and turnover rate (percent/hour) in PG knees was 0.23 plus or minus 0.07 and 117 plus or minus 11.9, hydrolysis rate (%/h) to Pi was 27.7 plus or minus 13.2; in OA knees: 0.45 plus or minus 0.26 and 72 plus or minus 9.2, hydrolysis 6.9 plus or minus 0.9; in gouty knees: 0.8 plus or minus 0.41 and 50 plus or minus 11.6, hydrolysis 9.8 plus or minus 2.8; and in RA knees: 0.14 plus or minus 0.14 and 114 plus or minus 35.8, hydrolysis 236 plus or minus 116. PPi turnover (mumoles/hour) correlated with the degree of OA change present in the joint as graded by radiologic criteria irrespective of the clinical diagnosis. Mean PPi turnover in joints with advanced OA was greater than in those with mild or moderate changes (P smaller than 0.001), but the mild and moderate groups showed no significant difference. We conclude that synovial PPi turnover and elevat

Topics: Adult; Aged; Arthritis; Chondrocalcinosis; Diphosphates; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Phosphorus Radioisotopes; Pyrophosphatases; Synovial Fluid

The concentration of 99mTc-pyrophosphate was determined in the lower extremities of rabbits (normal, abacterial and bacterial affected soft tissues), in osteoarthritis of the hip joint (capsule and muscle) as well as in knee joint effusions. Compared with the 85Sr-concentration, reflecting the calcification capacity, concentrations of 99mTc-pyrophosphate in soft tissues were found to be lower 2 hours p.i., but were up to elevenfold higher 24 hours p.i. These findings should be due to a fixation of 99mTc-pyrophosphate in collagen containing tissues as in the soft tissue tumors (myosarcoma, synvialioma, breast cancer) presented. A mechanism of delayed equilibration could explain augmented uptake in lymph-edema, ascites and effusions in florid osteoarthritis of the knee joint. The possible dependence of 99mTc-pyrophosphate concentration in bone and soft tissue on collagenous contents is discussed.

Topics: Animals; Ascites; Bone and Bones; Breast Neoplasms; Diphosphates; Disease Models, Animal; Extremities; Freund's Adjuvant; Hip; Humans; Joint Diseases; Joint Prosthesis; Joints; Knee; Osteoarthritis; Phosphates; Rabbits; Rhabdomyosarcoma; Sarcoma, Synovial; Strontium; Strontium Radioisotopes; Technetium; Tibial Fractures; Time Factors; Tin

Scintigraphic exploration of the sacroiliac (S.I.) joints by 99 m-technetium pyrophosphate is simple and free of all danger. The fixation of the isotope in the right sacroiliac (R.S.I.) and the "normal" limits of the fixation ratios R.S.I./L.R. and the lumbar rachis (L.R.), visible on the same film. A series of 28 controls having made it possible to calculate the "normal" limits of the fixation ratios R.S.I./L.R. and L.S.I./L.R., the isotopic fixation was measured in 25 patients with sacroiliac inflammation, 21 of whom were rheumatic, 3 infectious. It was shown that scintigraphy could yield useful information on the evolution of sacroiliac inflammation, making an early diagnosis possible, and also contributing to differentiation between rheumatic and infectious inflammation.

Topics: Adult; Aged; Arthritis, Reactive; Back Pain; Bacterial Infections; Bone and Bones; Diphosphates; Female; Humans; Ilium; Joint Diseases; Male; Middle Aged; Osteoarthritis; Psoriasis; Radionuclide Imaging; Rheumatic Diseases; Sacroiliac Joint; Sacrum; Spinal Diseases; Spondylitis, Ankylosing; Staphylococcal Infections; Technetium; Tuberculosis, Spinal

The distribution of calcium pyrophosphate mineral phase, almost exclusively confined to articular cartilage in chondrocalcinosis, and the high level of pyrophosphate (PPi) ion relative to serum in synovial fluid in patients with either chondrocalcinosis or advanced osteoarthritis led to an investigation of whether cartilage cells elaborate PPi ions. Incubates of articular cartilage from young rabbits but not from mature rabbits, as well as growth plates cartilage, released PPi into incubation media during a 4h period. Control rabbit ear cartilage and synovial membrane elaborated negligible amounts of PPi. The PPi was shown to be undialyzable but could be dissociated from the alkaline phosphatase by ultracentrifugation. In 16 patients with osteoarthritis, a substantial output of PPi by samples of articular cartilage from the knee was demonstrated. It is postulated that either rapid cell division and matrix synthesis found in the base of ulcerating osteoarthritic cartilage or remodeling calcified sites are the source of the PPi in such osteoarthritic cartilage. It is further hypothesized that this PPi output accounts at least in part for the elevated PPi levels found in synovial fluid of patients with osteoarthritis.

Topics: Alkaline Phosphatase; Animals; Autoradiography; Calcium; Cartilage; Cartilage, Articular; Cytidine; Diphosphates; DNA; Humans; Osteoarthritis; Rabbits; Synovial Membrane; Thymidine

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

Topics: Arthritis; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Diphosphates; Hodgkin Disease; Humans; Multiple Myeloma; Neoplasm Metastasis; Osteitis Deformans; Osteoarthritis; Osteolysis; Osteomalacia; Osteoporosis; Radionuclide Imaging; Reflex Sympathetic Dystrophy; Rheumatic Diseases; Technetium; Tin

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: Adult; Age Factors; Aged; Arthritis; Calcium Phosphates; Chondrocalcinosis; Diphosphates; Female; Fever; Hemarthrosis; Hemostasis; Humans; Joint Diseases; Male; Middle Aged; Osteoarthritis; Osteochondritis; Sex Factors; Synovial Fluid; Synovial Membrane

Topics: Animals; Bone and Bones; Calcinosis; Calcium Phosphates; Diphosphates; Joint Diseases; Osteoarthritis; Rabbits; Radiography; Synovial Fluid

Topics: Calcinosis; Diphosphates; Humans; Osteoarthritis; Synovial Fluid; Synovitis

Topics: Calcium; Chondrocalcinosis; Crystallization; Diphosphates; Foreign Bodies; Granuloma; Humans; Injections, Intra-Articular; Joint Diseases; Knee Joint; Male; Middle Aged; Osteoarthritis; Steroids; Synovial Membrane; X-Ray Diffraction