pyrophosphate and Chondrocalcinosis

Extracellular inorganic pyrophosphate (ePPi) both inhibits and promotes different forms of pathologic mineralization. Basic calcium phosphate (BCP) deposition results from depressed levels of ePPi while excess levels of ePPi leads to calcium pyrophosphate dihydrate crystal deposition (CPPD) disease. These crystals are also often identified in patients with osteoarthritis, the most prevalent form of arthritis causing significant morbidity.. The two primary hypotheses for generation of ePPi, export of inorganic pyrophosphate through the multipass transmembrane protein ANK and generation of ePPi by ectoenzyme activity, continue to be supported and better understood through animal models and study of families with CPPD deposition disease.. As the pathophysiology of crystal formation in both articular cartilage and synovial fluid is better understood, the opportunity for prevention and treatment of pathologic mineralization increases. In particular, a more complex understanding of the ank gene, ectoenzyme PC-1, and the transglutaminase enzyme family may eventually translate into therapeutic application for both BCP deposition and CPPD deposition disease.

Topics: Calcium Phosphates; Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Chondrocytes; Crystallization; Diphosphates; Extracellular Space; Humans; Phosphoric Diester Hydrolases; Pyrophosphatases; Synovial Fluid; Transglutaminases

Familial calcium pyrophosphate dihydrate deposition (CPPD) disease is a chronic condition in which CPPD microcrystals deposit in the joint fluid, cartilage, and periarticular tissues. Two forms of familial CPPD disease have been identified: CCAL1 and CCAL2. The CCAL1 locus is located on the long arm of chromosome 8 and is associated with CPPD and severe osteoarthritis. The CCAL2 locus has been mapped to the short arm of chromosome 5 and identified in families from the Alsace region of France and the United Kingdom. The ANKH protein is involved in pyrophosphate metabolism and, more specifically, in pyrophosphate transport from the intracellular to the extracellular compartment. Numerous ANKH gene mutations cause familial CCAL2; they enhance ANKH protein activity, thereby elevating extracellular pyrophosphate levels and promoting the formation of pyrophosphate crystals, which produce the manifestations of the disease. Recent studies show that growth factors and cytokines can modify the expression of the normal ANKH protein. These results suggest a role for ANKH in sporadic CPPD disease and in CPPD associated with degenerative disease.

Topics: Animals; Ankylosis; Chondrocalcinosis; Diphosphates; Homozygote; Humans; Membrane Proteins; Mice; Mutation; Phosphate Transport Proteins

Topics: Arthrography; Chondrocalcinosis; Diphosphates; Global Health; Gout; Humans; Pedigree; Rheumatic Diseases

CPPD deposition occurs in a wide variety of clinical settings, most commonly as an age-related phenomenon in the absence of other joint abnormality. Although our knowledge of CPPD and other intra-articular particles has increased in the last decade, the role of CPPD remains unclear. The paradox of asymptomatic deposition of phlogistic crystals, the wide spectrum of clinical presentation, and the lack of disease specificity, however, have challenged recognition of pyrophosphate arthropathy (PA) as a separate, distinct disease entity and led to reappraisal of earlier concepts of crystal deposition disease. In this article, clinical aspects of PA will first be presented; the validity of PA as a discrete arthropathy will then be discussed.

Topics: Arthritis; Calcinosis; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Joint Diseases

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

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Hypercalcemia; Synovial Fluid

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Chronic Disease; Diagnosis, Differential; Diphosphates; Humans; Joint Diseases; Radiography

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

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

Calcium pyrophosphate deposition disease (CPDD) is a condition in which calcium pyrophosphate dihydrate crystals are deposited in joint articular cartilage, menisci, and synovium. The main clinical presentations of CPDD are chondrocalcinosis--calcification of cartilage, pseudogout--acute joint inflammation due to crystal-induced synovitis, and pyrophosphate arthropathy--degenerative joint disease similar to osteoarthritis associated with calcium pyrophosphate crystal deposition. The clinical importance of CPDD for the arthroscopist is the ability to recognize the condition so that appropriate treatment can be instituted. Arthroscopy is valuable for diagnosis as well as lavage and intraarticular debridement or meniscectomy. Tissue removed for microscopic examination should be sent to the laboratory in saline, since formalin dissolves the crystals. Postarthroscopy treatment of CPDD should include oral antiinflammatory medication. Asymptomatic chondrocalcinosis does not require treatment.

Topics: Aged; Anti-Inflammatory Agents; Arthroscopy; Calcium Pyrophosphate; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Female; Humans; Joint Diseases; Male; Middle Aged; Terminology as Topic

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Hyperparathyroidism; Hypothyroidism; Radiography

Topics: Alkaline Phosphatase; Animals; Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Extracellular Space; Humans; Hydrolysis; Intracellular Fluid; Solubility; Tissue Distribution

Topics: Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Male; Neutrophils; Phagocytosis; Sex Factors; Synovial Fluid; Uric Acid; X-Ray Diffraction

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

Topics: Arthritis; Calcinosis; Calcium; Cartilage, Articular; Chemical Phenomena; Chemistry; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Geriatrics; Gout; Humans; Joint Diseases; Radiography; X-Ray Diffraction

To explore the lived experience of people with calcium pyrophosphate deposition (CPPD) disease and the impact of this condition on their daily lives.. Patients with CPPD and their caregivers were invited to take part in a one-to-one (patient only) or paired (patient and caregiver) semi-structured interview. Interviews covered patients' diagnosis and treatment experiences, and the impact of CPPD on their daily lives. Transcribed interviews were analysed using inductive thematic analysis.. 28 patient interviews, six of which included a caregiver, were conducted across five countries. Acute CPP crystal arthritis flares resulted in temporary but profound disability for most patients, disrupting their ability to go about day-to-day activities, and they sought immediate medical attention. CPPD+OA and chronic CPP crystal inflammatory arthritis presented patients with longer term limitations in daily lives. Patients and their caregivers described these disruptions and limitations, which included a reduced ability or inability to complete household and self-care tasks, exercise, socialise, work and drive. They also described how arthritis pain and resulting limitations adversely impacted upon patients' psychological wellbeing. Delays in referral to specialists and diagnostic uncertainty were described by many. Lack of appropriate treatment or access to treatments only upon worsening of symptoms impacted upon the length of time some patients spent in pain and with functional limitations.. This study is the first to demonstrate the wide-ranging impact of CPPD, and highlights the need for improved diagnosis, physician training, as well as greater emphasis upon finding targeted therapies to specifically treat CPPD.

Topics: Calcinosis; Calcium Pyrophosphate; Caregivers; Chondrocalcinosis; Diphosphates; Humans

ANKH mutations are associated with calcium pyrophosphate deposition disease and craniometaphyseal dysplasia. This study investigated the effects of these ANKH mutants on cellular localisation and associated biochemistry. We generated four ANKH overexpression-plasmids containing either calcium pyrophosphate deposition disease or craniometaphyseal dysplasia linked mutations: P5L, E490del and S375del, G389R. They were transfected into CH-8 articular chondrocytes and HEK293 cells. The ANKH mutants dynamic differential localisations were imaged and we investigated the interactions with the autophagy marker LC3. Extracellular inorganic pyrophosphate, mineralization, ENPP1 activity expression of ENPP1, TNAP and PIT-1 were measured. P5L delayed cell membrane localisation but once recruited into the membrane it increased extracellular inorganic pyrophosphate, mineralization, and ENPP1 activity. E490del remained mostly cytoplasmic, forming punctate co-localisations with LC3, increased mineralization, ENPP1 and ENPP1 activity with an initial but unsustained increase in TNAP and PIT-1. S375del trended to decrease extracellular inorganic pyrophosphate, increase mineralization. G389R delayed cell membrane localisation, trended to decrease extracellular inorganic pyrophosphate, increased mineralization and co-localised with LC3. Our results demonstrate a link between pathological localisation of ANKH mutants with different degrees in mineralization. Furthermore, mutant ANKH functions are related to synthesis of defective proteins, inorganic pyrophosphate transport, ENPP1 activity and expression of ENPP1, TNAP and PIT-1.

Topics: Alkaline Phosphatase; Autophagy; Bone Diseases, Developmental; Carrier Proteins; Chondrocalcinosis; Chondrocytes; Craniofacial Abnormalities; Diphosphates; HEK293 Cells; Humans; Hyperostosis; Hypertelorism; Microscopy, Confocal; Mutation; Phosphate Transport Proteins; Phosphoric Diester Hydrolases; Protein Domains; Pyrophosphatases; Transcription Factor Pit-1

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

Familial articular chondrocalcinosis (CC) was first reported in 1963. It is characterised by multiple calcifications of hyaline and fibrous cartilage in the joints and intervertebral discs. Mutations in ANKH have been identified in several pedigrees as a monogenic cause for this disorder. ANKH is a key protein in pyrophosphate metabolism and is involved in pyrophosphate transport across the cell membrane. The objective of this work was to screen ANKH and ENPP1, two key genes in pyrophosphate metabolism, in Slovakian kindreds with familial CC. DNA samples from 25 individuals (10 affected, 15 unaffected) from 8 families were obtained. The promoter, coding regions and intron-exon boundaries of ANKH and ENPP1 were sequenced. Twelve DNA sequence variants, six in each gene, were identified. All the variants had been previously identified. None segregated with the disease. Our results suggest that neither ANKH nor ENPP1 mutations are the cause of CC in these families, indicating that possibly other major genes are involved in the aethiopathogenesis of this condition in these families.

Topics: Chondrocalcinosis; Diphosphates; Exons; Female; Gene Frequency; Humans; Introns; Male; Mutation; Pedigree; Phenotype; Phosphate Transport Proteins; Phosphoric Diester Hydrolases; Pyrophosphatases; Slovakia

Transforming growth factor (TGF)-β1 stimulates extracellular PP(i) (ePP(i)) generation and promotes chondrocalcinosis, which also occurs secondary to hyperparathyroidism-induced hypercalcemia. We previously demonstrated that ANK was up-regulated by TGF-β1 activation of ERK1/2 and Ca(2+)-dependent protein kinase C (PKCα). Thus, we investigated mechanisms by which calcium could affect ePP(i) metabolism, especially its main regulating proteins ANK and PC-1 (plasma cell membrane glycoprotein-1). We stimulated articular chondrocytes with TGF-β1 under extracellular (eCa(2+)) or cytosolic Ca(2+) (cCa(2+)) modulations. We studied ANK, PC-1 expression (quantitative RT-PCR, Western blotting), ePP(i) levels (radiometric assay), and cCa(2+) input (fluorescent probe). Voltage-operated Ca(2+)-channels (VOC) and signaling pathways involved were investigated with selective inhibitors. Finally, Ank promoter activity was evaluated (gene reporter). TGF-β1 elevated cCa(2+) and ePP(i) levels (by up-regulating Ank and PC-1 mRNA/proteins) in an eCa(2+) dose-dependent manner. TGF-β1 effects were suppressed by cCa(2+) chelation or L- and T-VOC blockade while being mostly reproduced by ionomycin. In the same experimental conditions, the activation of Ras, the phosphorylation of ERK1/2 and PKCα, and the stimulation of Ank promoter activity were affected similarly. Activation of SP1 (specific protein 1) and ELK-1 (Ets-like protein-1) transcription factors supported the regulatory role of Ca(2+). SP1 or ELK-1 overexpression or blockade experiments demonstrated a major contribution of ELK-1, which acted synergistically with SP1 to activate Ank promoter in response to TGF-β1. TGF-β1 promotes input of eCa(2+) through opening of L- and T-VOCs, to potentiate ERK1/2 and PKCα signaling cascades, resulting in an enhanced activation of Ank promoter and ePP(i) production in chondrocyte.

Topics: Animals; Calcium; Calcium Channels; Cartilage, Articular; Cells, Cultured; Chondrocalcinosis; Chondrocytes; Diphosphates; ets-Domain Protein Elk-1; Gene Expression Regulation; Ion Transport; Ionomycin; Ionophores; Male; Mitogen-Activated Protein Kinase 3; Phosphate Transport Proteins; Phosphoric Diester Hydrolases; Promoter Regions, Genetic; Protein Kinase C-alpha; Pyrophosphatases; ras Proteins; Rats; Rats, Wistar; Signal Transduction; Sp1 Transcription Factor; Transforming Growth Factor beta1

Pathological mineralization is induced by unbalance between pro- and anti-mineralization factors. In calcifying osteoarthritic joints, articular chondrocytes undergo terminal differentiation similar to that in growth plate cartilage and release matrix vesicles (MVs) responsible for hydroxyapatite (HA) or calcium pyrophosphate dihydrate (CPPD) deposition. Inorganic pyrophosphate (PP(i)) is a likely source of inorganic phosphate (P(i)) to sustain HA formation when hydrolyzed but also a potent inhibitor preventing apatite mineral deposition and growth. Moreover, an excess of PP(i) can lead to CPPD formation, a marker of pathological calcification in osteoarthritic joints. It was suggested that the P(i)/PP(i) ratio during biomineralization is a turning point between physiological and pathological mineralization. The aim of this work was to determine the conditions favoring either HA or CPPD formation initiated by MVs.. MVs were isolated from 17-day-old chicken embryo growth plate cartilages and subjected to mineralization in the presence of various P(i)/PP(i) ratios. The mineralization kinetics and the chemical composition of minerals were determined, respectively, by light scattering and infrared spectroscopy.. The formation of HA is optimal when the P(i)/PP(i) molar ratio is above 140, but is completely inhibited when the ratio decreases below 70. The retardation of any mineral formation is maximal at P(i)/PP(i) ratio around 30. CPPD is exclusively produced by MVs when the ratio is below 6, but it is inhibited for the ratio exceeding 25.. Our findings are consistent with the P(i)/PP(i) ratio being a determinant factor leading to pathological mineralization or its inhibition.

Topics: Animals; Cartilage; Cells, Cultured; Chick Embryo; Chondrocalcinosis; Cytoplasmic Vesicles; Diphosphates; Durapatite; Extracellular Matrix; Growth Plate; Homeostasis; Microscopy, Electron; Phosphates

We investigated the role of two genes, ANKH and TNAP, in patients with cuff tear arthropathy. These genes encode proteins which regulate the extracellular concentration of inorganic pyrophosphate, fluctuations of which can lead to calcium crystal formation. Variants were detected by direct sequencing of DNA and their frequencies compared with healthy controls. The effect of variants on protein function was further studied by in vitro approaches. Variant genotypes were observed more frequently in the cases when compared with controls in ANKH (45% and 20%) and TNAP (32% and 9%). Variants in ANKH altered inorganic pyrophosphate (PPi) concentrations in transfected human chondrocytes. There was a higher mean serum concentration of TNAP detected in female patients compared with normal ranges. Cuff tear arthropathy is associated with variants in ANKH and TNAP that alter extracellular inorganic pyrophosphate concentrations causing calcium crystal deposition. This supports a theory that genetic variants predispose patients to primary crystal deposition which when combined with a massive rotator cuff tear leads to the development of arthritis.

Topics: Alkaline Phosphatase; Carrier Proteins; Cells, Cultured; Chondrocalcinosis; Chondrocytes; Diphosphates; Female; Genetic Predisposition to Disease; Humans; Male; Phosphate Transport Proteins; Polymorphism, Single Nucleotide; Rotator Cuff Injuries; Sequence Analysis, DNA; Sex Factors; Shoulder Joint; Transfection

ANK is a multipass transmembrane protein transporter thought to play a role in the export of intracellular inorganic pyrophosphate and so to contribute to the pathophysiology of chondrocalcinosis. As transforming growth factor-beta-1 (TGF-beta1) was shown to favor calcium pyrophosphate dihydrate deposition, we investigated the contribution of ANK to the production of extracellular inorganic pyrophosphate (ePPi) by chondrocytes and the signaling pathways involved in the regulation of Ank expression by TGF-beta1. Chondrocytes were exposed to 10 ng/mL of TGF-beta1, and Ank expression was measured by quantitative polymerase chain reaction and Western blot. ePPi was quantified in cell supernatants. RNA silencing was used to define the respective roles of Ank and PC-1 in TGF-beta1-induced ePPi generation. Finally, selective kinase inhibitors and dominant-negative/overexpression plasmid strategies were used to explore the contribution of several signaling pathways to Ank induction by TGF-beta1. TGF-beta1 strongly increased Ank expression at the mRNA and protein levels, as well as ePPi production. Using small interfering RNA technology, we showed that Ank contributed approximately 60% and PC-1 nearly 20% to TGF-beta1-induced ePPi generation. Induction of Ank by TGF-beta1 required activation of the extracellular signal-regulated kinase (ERK) pathway but not of p38-mitogen-activated protein kinase or of protein kinase A. In line with the general protein kinase C (PKC) inhibitor calphostin C, Gö6976 (a Ca2+-dependent PKC inhibitor) diminished TGF-beta1-induced Ank expression by 60%, whereas a 10% inhibition was observed with rottlerin (a PKCdelta inhibitor). These data suggest a regulatory role for calcium in TGF-beta1-induced Ank expression. Finally, we demonstrated that the stimulatory effect of TGF-beta1 on Ank expression was inhibited by the suppression of the Ras/Raf-1 pathway, while being enhanced by their constitutive activation. Transient overexpression of Smad 7, an inhibitory Smad, failed to affect the inducing effect of TGF-beta1 on Ank mRNA level. These data show that TGF-beta1 increases ePPi levels, mainly by the induction of the Ank gene, which requires activation of Ras, Raf-1, ERK, and Ca2+-dependent PKC pathways in chondrocytes.

Topics: Animals; Base Sequence; Cells, Cultured; Chondrocalcinosis; Chondrocytes; Diphosphates; DNA Primers; Extracellular Signal-Regulated MAP Kinases; Humans; Kinetics; Male; MAP Kinase Signaling System; Membrane Proteins; Phosphate Transport Proteins; Phosphoric Diester Hydrolases; Proto-Oncogene Proteins c-raf; Pyrophosphatases; ras Proteins; Rats; Rats, Wistar; RNA, Messenger; RNA, Small Interfering; Transforming Growth Factor beta1

Certain mutations in ANKH, which encodes a multiple-pass transmembrane protein that regulates inorganic pyrophosphate (PPi) transport, are linked to autosomal-dominant familial chondrocalcinosis. This study investigated the potential for ANKH sequence variants to promote sporadic chondrocalcinosis.. ANKH variants identified by genomic sequencing were screened for association with chondrocalcinosis in 128 patients with severe sporadic chondrocalcinosis or pseudogout and in ethnically matched healthy controls. The effects of specific variants on expression of common markers were evaluated by in vitro transcription/translation. The function of these variants was studied in transfected human immortalized CH-8 articular chondrocytes.. Sporadic chondrocalcinosis was associated with a G-to-A transition in the ANKH 5'-untranslated region (5'-UTR) at 4 bp upstream of the start codon (in homozygotes of the minor allele, genotype relative risk 6.0, P = 0.0006; overall genotype association P = 0.02). This -4-bp transition, as well as 2 mutations previously linked with familial and sporadic chondrocalcinosis (+14 bp C-to-T and C-terminal GAG deletion, respectively), but not the French familial chondrocalcinosis kindred 143-bp T-to-C mutation, increased reticulocyte ANKH transcription/ANKH translation in vitro. Transfection of complementary DNA for both the wild-type ANKH and the -4-bp ANKH protein variant promoted increased extracellular PPi in CH-8 cells, but unexpectedly, these ANKH mutants had divergent effects on the expression of extracellular PPi and the chondrocyte hypertrophy marker, type X collagen.. A subset of sporadic chondrocalcinosis appears to be heritable via a -4-bp G-to-A ANKH 5'-UTR transition that up-regulates expression of ANKH and extracellular PPi in chondrocyte cells. Distinct ANKH mutations associated with heritable chondrocalcinosis may promote disease by divergent effects on extracellular PPi and chondrocyte hypertrophy, which is likely to mediate differences in the clinical phenotypes and severity of the disease.

Topics: 5' Untranslated Regions; Cell Line, Transformed; Chondrocalcinosis; Chondrocytes; Diphosphates; DNA Mutational Analysis; Gene Expression; Genetic Predisposition to Disease; Guanine; Humans; Membrane Proteins; Middle Aged; Phosphate Transport Proteins; Point Mutation; Polymorphism, Genetic; Thymine; Transfection

We describe the pattern of early childhood seizures within a family with autosomal dominant chondrocalcinosis (CCAL, which causes adult-onset arthritis). All affected family members with CCAL experienced seizures in early childhood, usually, but not always, associated with fever. Similarities exist to the syndrome of generalized epilepsy with febrile seizures plus (GEFS+). A mutation within the ANKH gene on chromosome 5p has been found previously in this family; other patients with familial CCAL (but without seizures) have mutations in the same gene. ANKH codes for a transmembrane protein involved in the regulation of extracellular pyrophosphate ion levels, although its precise mechanism of action remains unclear. It is highly expressed in the brain, and its expression may be influenced by seizure activity. The mutation within this family creates a premature initiation codon, adding four amino acids to the N-terminus of the protein. We postulate that this may lead to a gain of function, causing seizure susceptibility as well as chondrocalcinosis. Mutations within this gene may underlie other forms of genetic epilepsy and febrile seizures.

Topics: Arthritis; Child, Preschool; Chondrocalcinosis; Codon, Initiator; Diphosphates; Epilepsy, Generalized; Female; Gene Expression; Genetic Predisposition to Disease; Humans; Infant; Male; Membrane Proteins; Mutation; Pedigree; Phosphate Transport Proteins; Seizures; Seizures, Febrile

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

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondrocalcinosis; Diphosphates; Female; Finger Joint; Humans; Meloxicam; Radiography; Thiazines; Thiazoles; Treatment Outcome; Wrist Joint

Articular cartilage affected by calcium pyrophosphate dihydrate (CPPD) crystal deposition contains abnormal chondrocytes with morphologic similarities to the terminally differentiated hypertrophic chondrocytes that mineralize in growth plate cartilage. These chondrocytes also elaborate high levels of extracellular inorganic pyrophosphate (PPi), an essential component of the CPPD crystal. Several factors that stimulate articular chondrocyte PPi elaboration also induce terminal differentiation in growth plate chondrocytes. We hypothesized that factors such as thyroid hormones (T3 and T4) that are potent stimulants of growth plate chondrocyte hypertrophy might also stimulate articular chondrocyte hypertrophic differentiation. We also hypothesized that like transforming growth factor-beta (TGF-beta), ascorbate, and retinoic acid, thyroid hormones would increase chondrocyte PPi elaboration.. We determined the effects of T3, T4, and TGF-beta on markers of the hypertrophic phenotype such as alkaline phosphatase (ALPase) activity and type X collagen production; and the effects of T3 and T4 on processes implicated in CPPD crystal formation including PPi elaboration and nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity in adult porcine articular chondrocytes in culture.. ALPase activity increased 3-fold with T3 and T4 and 1.3-fold with TGF-beta. Type X collagen levels also increased with thyroid hormone treatment. [125I]T3 binding studies proved the existence of saturable T3 receptors on chondrocytes. Media [PPi] and cellular NTPPPH activity significantly increased in cultures treated with 1-10 nM T3 or 100-500 nM T4.. Increased PPi elaboration is an additional and previously unrecognized feature of hypertrophic differentiation in articular chondrocytes. These terminally differentiated chondrocytes may play a pathogenic role in CPPD crystal deposition disease.

Topics: Alkaline Phosphatase; Animals; Binding Sites; Calcium Pyrophosphate; Cell Differentiation; Cell Size; Cells, Cultured; Chondrocalcinosis; Chondrocytes; Collagen; Diphosphates; Phenotype; Pyrophosphatases; Swine; Thymidine; Thyroxine; Transforming Growth Factor beta; Triiodothyronine; Tritium

Topics: Adjuvants, Immunologic; Chondrocalcinosis; Diphosphates; Humans; Hyaluronic Acid; Injections, Intra-Articular

The elaboration of excess extracellular inorganic pyrophosphate (ePPi) by cartilage contributes to calcium pyrophosphate dihydrate (CPPD) crystal deposition disease. Transforming growth factor-beta 1 (TGF beta 1) is the only defined physiologic stimulant of cartilage ePPi elaboration. The mechanism of ePPi generation by chondrocytes is unknown, but current evidence suggests that TGF beta 1 induced ePPi is made intracellularly. An active transport mechanism such as an anion transporter would then be necessary to export ePPi to the matrix where crystals form. We determined the effect of probenecid (PB), an anion transport inhibitor, on TGF beta 1 induced ePPi elaboration.. Porcine hyaline articular chondrocytes in high density monolayer cultures were exposed to serum-free media with and without TGF beta 1 and/or PB. ePPi was measured in the media after 48-96 h of exposure. Cell injury was measured by examining the release of 3H-deoxyglucose from chondrocytes. The activity of the ePPi generating ectoenzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH) and media lactate concentrations were measured with standard colorimetric assays. As PB may inhibit phosphodiesterase (PDE), its effects on ePPi generation were compared with isobutylmethylxanthine (IBMX), a specific PDE inhibitor.. PB inhibited TGF beta 1 induced ePPi elaboration by chondrocytes. PB did not cause membrane injury or decrease NTPPPH activity. Lactate production was decreased by PB but did not correlate with the effects of PB on ePPi elaboration. IBMX did not inhibit TGF beta 1 effect on ePPi elaboration.. PB blocks TGF beta 1 induced ePPi elaboration. This effect is independent of cell membrane injury, decreased NTPPPH activity, or PDE inhibition. Our data implicate a role for anion transport in TGF beta 1 induced ePPi elaboration, and suggest a potential therapy for CPPD disease.

Topics: 1-Methyl-3-isobutylxanthine; Animals; Cartilage, Articular; Chondrocalcinosis; Diphosphates; Knee Joint; Lactates; Lactic Acid; Probenecid; Pyrophosphatases; Swine; Transforming Growth Factor beta

Microcrystalline arthropathies of the wrist include three main forms of microcrystalline pathology: gout, chondrocalcinosis and apatite calcifications. Gout of the wrist is now rare and may be missed, particularly in its chronic form, occasionally associated with tophi and large, often asymmetrical erosions on the X-rays. Chondrocalcinosis is frequent and easy to diagnose in the wrist and may be responsible for a very typical arthropathy predominantly involving the radiocarpal joint, while the frequency and specificity of scapho-trapezoid involvement are controversial. Apatite deposits in the wrist involve various tendons and ligaments, especially the tendon of flexor carpi ulnaris, but may also be responsible for intra-articular pathology.

Topics: Apatites; Arthritis, Gouty; Carpal Bones; Chondrocalcinosis; Diphosphates; Humans; Joint Loose Bodies; Radiography; Wrist Joint

The association between calcium pyrophosphate dihydrate (CPPD) crystal deposition and ageing is unexplained. Levels of inorganic pyrophosphate (PPi) and activity of nucleoside triphosphate pyrophosphatase (NTPP) were estimated in synovial fluid from 91 asymptomatic normal knees, including five with isolated CPPD crystal deposition (70 subjects; median age 47, range 22-83 years). In non-crystal fluids, PPi levels and NTPP activities were low (median, interquartile range: 9.5, 7.6-12.3 microM, and 1, 0.4-2 microM/30 min/mg protein, respectively: n = 50) and a generalized increase with age was not demonstrated. Higher values for PPi and NTPP in all five subjects with isolated CPPD deposition supports involvement of altered PPi metabolism, unrelated to ageing per se, in crystal formation. Presumed cartilage fragments were identified by morphological characteristics in 70% of normal fluids: metachromatic staining and electron microscopy, undertaken in a limited number, supported identification of such particles as cartilage. This finding supports dynamic turnover of healthy matrix, and questions the usefulness of identification, without quantification, cartilage fragments as a measure of cartilage damage.

Topics: Adult; Aged; Aged, 80 and over; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Male; Microscopy, Electron; Middle Aged; Pyrophosphatases; Reference Values; Synovial Fluid

Familial predisposition to chondrocalcinosis (CC) due to calcium pyrophosphate dihydrate (CPPD) crystal deposition is described in five English kindreds. Two families were characterized by premature-onset polyarticular CC with little associated structural arthropathy. In one of these families, recurrent childhood fits were strongly associated with subsequent development of CC. Affected members of the other three families resembled sporadic disease in showing predominantly late-onset, oligoarticular CC with mild arthritis and destructive change in only one case. Knee synovial fluid levels of inorganic pyrophosphate (PPi) and nucleoside triphosphate pyrophosphate (NTPP) did not differ from those of 59 sporadic cases of CC due to CPPD, although PPi and NTPP levels in both groups were higher than in normal knee synovial fluid (P less than 0.0001). Urinary PPi levels were not different from normal controls. Screening for other metabolic abnormality was negative in all cases. This is the first report of familial CC in the UK, and the first to associate this condition with childhood fits. Absence of overt primary abnormality of PPi metabolism suggests that other factors relating to crystal nucleation/growth may be more relevant to predisposition in these cases.

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Knee Joint; Male; Pedigree; Pyrophosphatases; Radiography; Synovial Fluid

To define the patterns of calcium pyrophosphate dihydrate (CPPD) crystal deposition in the triangular fibrocartilage complex (TFCC), we examined the wrists of five adult, fresh-frozen cadavers using light and scanning electron microscopy and the wrist radiographs of 10 patients with a clinical diagnosis of CPPD disease. The radiographs consistently showed mineral deposits near or on the proximal and distal surfaces of the radial half of the TFCC. Light and electron microscopy showed that CPPD crystals formed distinct clusters sharply demarcated from uninvolved fibrocartilage. The density of crystal packing within clusters varied with the sharpness of demarcation of the clusters from the surrounding tissue. TFCC defects were consistently found in the vicinity of CPPD crystals, and degeneration of the articular cartilage on the ulnar half of the proximal surface of the lunate was associated with CPPD crystal deposition in the radial half of the TFCC. These observations suggest that degenerative tears of the TFCC and degeneration of the articular cartilage of the lunate are associated with CPPD crystal deposits in the TFCC.

Topics: Adult; Aged; Aged, 80 and over; Arthrography; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Joint Diseases; Microscopy, Electron, Scanning; Middle Aged; Tomography; Wrist Joint

Topics: Adult; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Male; Mandible; Temporomandibular Joint Disorders; Tomography, X-Ray Computed

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: Animals; Calcium Pyrophosphate; Carpus, Animal; Chondrocalcinosis; Diphosphates; Dog Diseases; Dogs; Forelimb; Hypothyroidism; Male

Cervical Myelopathy is a rare manifestation of calcium pyrophosphate dihydrate (C.P.P.D.) deposition disease. A case is presented where radiographically noncalcified extradural masses containing C.P.P.D. crystals were present at the C7 level, producing cord compression and neurological symptoms. These masses are thought to represent para-articular deposits related to the adjacent facet joints.

Topics: Aged; Aged, 80 and over; Calcium Metabolism Disorders; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Male; Neck; Spinal Cord Compression; Tomography, X-Ray Computed

Topics: Adult; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Male; Microscopy, Electron; Radiography; X-Ray Diffraction

A report of two patients in which a soft tissue mass, initially regarded as a malignant tumor, was shown to be the result of calcium pyrophosphate deposition disease. The first case, a woman aged 71 years, presented with a mass involving the right fifth finger. In the second case, also a woman aged 71 years, the lesion involved the tissues adjacent to the right hip. Each lesion consisted of a mass of highly cellular tissue containing deposits of calcium pyrophosphate dihydrate crystals. The clinical, radiological, and pathological features of the two cases are compared with those of seven similar cases reported in the literature.

Topics: Aged; Bone Neoplasms; Calcium Pyrophosphate; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Electron Probe Microanalysis; Female; Fingers; Hip; Humans; Microscopy, Electron, Scanning; Radiography; X-Ray Diffraction

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

Inorganic pyrophosphate elaboration by articular cartilage may favor calcium pyrophosphate dihydrate crystal deposition. Frequently crystal deposits form in persons affected with metabolic diseases. The cartilage organ culture system was used to model these metabolic conditions while measuring the influence on extracellular pyrophosphate elaboration. Alterations of ambient pH, thyroid stimulating hormone levels, and parathyroid hormone levels did not change pyrophosphate accumulation in the media. However, subphysiologic ambient calcium concentrations (25, 100, 500 microM) increased pyrophosphate accumulation about chondrocytes 3- to 10-fold. Low calcium also induced release of [14C]adenine-labeled nucleotides from chondrocytes, potential substrates for generation of extracellular pyrophosphate by ectoenzymes. Exposing cartilage to 10% fetal bovine serum also enhanced by 50% the egress of inorganic pyrophosphate from the tissue.

Topics: Animals; Calcium; Cartilage, Articular; Chondrocalcinosis; Diphosphates; Hydrogen-Ion Concentration; In Vitro Techniques; Iron; Parathyroid Hormone; Pyrophosphatases; Sulfates; Swine; Thyrotropin

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

Authors describe the case of a 43 years old male patient with complaints and restriction of motions since years, localized on the talocrural joint. In the background of the disease, responding inadequately to the therapy, calcium pyrophosphate depositions were found in the joint tissues. As the pathomechanism of the disease is even presently not cleared authors summarize our present knowledge referring to this problem.

Topics: Adult; Ankle Joint; Arthritis; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Male; Synovial Fluid

We demonstrated the histologic localization of lipid in the articular cartilage, meniscus, and synovium in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, by staining with Sudan III. Almost all the sites of tophus-like deposits of CPPD crystals and the degenerated matrix containing low concentrations of scattered CPPD crystals stained strongly with Sudan III. Transmission electron microscopy demonstrated round or oval lipid droplets in more than half of the chondrocytes around the crystals in each of these tissues. Small lipid droplets were also seen on or around the crystals. These findings suggest that lipids are abundant at the site of CPPD crystal deposition and may be involved in CPPD crystal formation.

Topics: Aged; Azo Compounds; Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Diphosphates; Female; Humans; Lipid Metabolism; Male; Menisci, Tibial; Microscopy, Electron; Staining and Labeling; Synovial Membrane

The authors describe three cases of cervical radiculomyelopathy caused by calcium pyrophosphate dihydrate crystal deposition disease (CPPDcdd). Radiological investigations revealed nodular calcifications, 5 to 7 mm in diameter, in the cervical ligamentum flavum compressing the spinal cord. Light microscopic, scanning electron microscopic, and x-ray diffraction studies were performed on all three surgical specimens obtained by laminectomy. In two of the cases x-ray microanalysis and transmission electron microscope studies were also performed. This study defined the presence of two patterns of crystal deposition in the ligamentum flavum. One is a nodular deposit, in which hydroxyapatite crystals are seen in the central part of the nodules, with calcium pyrophosphate dihydrate (CPPD) being distributed thinly around them. The other pattern is a linear deposit seen in multiple ligaments and composed of pure CPPD, which causes minimal thickening of the ligaments. A transitional pattern between the two types was also observed. This study revealed details of the nodular deposition of crystals in the ligamentum flavum and demonstrates that CPPDcdd and so-called "calcification of the ligamentum flavum" are the same disease: namely, CPPDcdd. Hydroxyapatite is assumed to have been transformed from CPPD.

Topics: Aged; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Ligaments; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Neck; Radiography; Spine; X-Ray Diffraction

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

To determine the physical-chemical effects of [Fe++] and [Fe ] on calcium pyrophosphate dihydrate (CPPD) crystal formation de novo, we studied CPPD crystal formation in an established model aqueous solution mixture system using physiological concentrations of Na+, Mg++, Ca++, C1-. We found that [Fe++] greater than 1 microM or [Fe ] greater than or equal to 100 microM inhibits CPPD crystal formation under conditions of [Ca++] = 1.5 mM, [Pi] = 0.1 mM, and [PPi] = 0.1 mM that simulate CPPD formation in vivo. These experiments suggest that at biological concentrations, Fe++ acts to inhibit CPPD formation but that [Fe++] depletion therapy by removal of inhibition effects may facilitate CPPD crystal formation in articular tissues.

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Ferric Compounds; Ferrous Compounds; Hemochromatosis; Humans

Three patients were found to have calcium pyrophosphate dihydrate deposition disease (CPPD) as the cause of prolonged fever and elevated sedimentation rate. All responded to treatment. CPPD should be considered in evaluating patients with fever and high sedimentation rate.

Topics: Aged; Aged, 80 and over; Blood Sedimentation; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diagnosis, Differential; Diphosphates; Female; Fever; Humans

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

Formation of calcium pyrophosphate dihydrate (CPPD) crystals in native collagen gels represent an in vitro model system for the study of pathological cartilage calcification. The conditions under which CPPD forms in collagen gels have been determined. At low Ca X pyrophosphate product, CPPD forms directly. At high Ca X pyrophosphate product, CPPD forms via the amorphous intermediate calcium magnesium pyrophosphate (CMPP). Chondroitin sulfate (CS) inhibits formation of CPPD by both pathways, but apparently by different mechanisms. Direct CPPD formation is inhibited with low potency by CS, apparently by binding of Ca2+ ions. Indirect formation of CPPD is inhibited with high potency by CS, apparently by stabilization of the CMPP intermediate. Comparison of the inhibition of direct CPPD formation by the two glycosaminoglycan species occurring in cartilage proteoglycan showed that CS is a more potent inhibitor than keratan sulfate (KS), in agreement with the greater Ca2+-binding affinity of CS. The increase in KS/CS ration which occurs in human hyaline cartilage with aging may facilitate deposition of CPPD crystals by decreasing the exclusion of pyrophosphate anions.

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Chondroitin Sulfates; Collagen; Crystallization; Diphosphates; Gels; Glycosaminoglycans; Microscopy, Electron; Models, Biological; Time Factors

Electron microscopy was used to investigate the characteristics of calcium pyrophosphate dihydrate (CPPD) crystals in chondrocalcinosis (pseudogout syndrome). Crystals in midzone cartilage were frequently seen adjacent to chondrocytes. Great variation in crystal size and shape was observed. Most of the pyrophosphate crystals that had been phagocytosed by polymorphonuclear leukocytes of synovial fluid from patients with acute pseudogout were small (less than or equal to 1 micron), indicating that small crystals can cause intense inflammation. Large numbers of polymorphonuclear leukocytes became attached to the eroded articular surface and phagocytosed microcrystals. Interaction of polymorphonuclear leukocytes with CPPD crystals in the superficial region of articular cartilage may stimulate the release of inflammatory mediators.

Topics: Aged; Calcium Pyrophosphate; Cartilage; Chondrocalcinosis; Crystallography; Diphosphates; Humans; Inflammation; Microscopy, Electron; Middle Aged; Neutrophils

Topics: Aged; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Humans; Ligaments, Articular; Radiography; Synovitis; Wrist Joint

Calcium pyrophosphate dihydrate crystal deposition disease is a clinical condition characterised by Gout-like synovitis (pseudogout), calcification on and around the joints and an arthropathy that is radiologically similar to osteoarthritis (chronic pyrophosphate arthropathy). Though all these radiological clinical aspects may coexist in the same patient this is often not the case. An examination of the X-ray data on the 68 cases studied which were diagnosed on the basis of the criteria proposed by McCarty, shows that the disease is relatively common especially in the over-fifties. When chronic pyrophosphate arthropathy is the only clinical manifestation of the disease differential diagnosis from the osteoarthrosis so common in the elderly is difficult and depends on the greater severity and progression of the joint damage that may often affect joints not subjected to weight such as the shoulder, unlike what happens in osteoarthritis.

Topics: Aged; Aged, 80 and over; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Male; Middle Aged; Radiography; Synovial Membrane

A case of 64-year-old Japanese woman with cervical radiculomyelopathy caused by the deposition of both calcium pyrophosphate dihydrate (CPPD) and hydroxyapatite crystals in the cervical ligamentum flavum is reported. The patient developed paresthesia in her both hands and gait disturbance in the previous six months. Neurological examination revealed generalized hyperreflexia and hypesthesia in the C7 region. Neuroradiologically, two nodular opacifications were shown in the C3-4 and C5-6 level. CT scan revealed linear and symmetrical calcifications in the C3-4 and nodular calcifications in the C5-6 level. En bloc laminectomy was performed and the patient was discharged from the hospital with improvements of neurological symptoms. Specimens of the spinal laminae and ligamenta flava were studied by light microscopy, scanning electron microscopy (SEM), energy dispersive X-ray microanalysis (X-MA) on SEM, and an X-ray diffraction study was carried out on the crystals. The results showed A. CPPD crystal depositions throughout the ligamenta flava together with a minimal thickening of the ligaments. The deposition was seen in the midzone of the ligaments forming a plate-like distribution and forming lines in the cut surface, the latter coincided well with the CT finding at the C3-4 level. B. The nodule (7 X 6 X 6 mm in size) at the C5-6 level was composed of two crystals, CPPD and hydroxyapatite, the latter being encased by the former. The thickness of the CPPD layer was quite thin varying from 10 to 100 mu. Myelographically, the spinal cord was most severely compressed by the C5-6 nodule. C. Because of the absence of family histories and predisposing factors, the case was considered one of primary or idiopathic CPPD crystal deposition disease. The origin of the deposition of mixed crystals was discussed and it appeared likely that the central part of CPPD crystal deposition had transformed to hydroxyapatite at the C5-6 level. In the literature a considerable number of cases have been reported under the title, "Calcification of the Ligamentum Flavum", and some of them have been shown to have hydroxyapatite deposition. Considering the great similarities in clinical, radiological and histological findings between the so-called "calcification of the lig. fl." and CPPD crystal deposition disease, the present case was the first to clearly indicate that these two conditions belong to a single category, i.e. CPPD crystal deposition disease.(ABSTRACT TRUNCATED AT 400 WOR

Topics: Calcium Pyrophosphate; Cervical Vertebrae; Chondrocalcinosis; Diphosphates; Female; Humans; Ligaments; Middle Aged

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

Topics: Adult; Aged; Anti-Inflammatory Agents; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Middle Aged

A man developed acute monoarticular ankle arthritis caused by calcium pyrophosphate dihydrate (CPPD) crystals. The clinical syndrome resembled that of a pyogenic arthritis. Synovial fluid analysis revealed a glucose concentration of 13 mg/dL and 99,000 white blood cells/mm3. Only one other report of an extremely low synovial fluid glucose associated with pseudogout could be found. The diagnosis of pseudogout was initially suggested when rhomboidal forms were seen during synovial fluid Gram stain examination. Synovial fluid examination with polarized microscopy was initially negative, but revealed numerous CPPD crystals when repeated on the third hospital day. This case serves to illustrate how pseudogout can mimic pyogenic arthritis in both clinical presentation and low synovial fluid glucose concentration. The examination of Gram-stained synovial fluid can reveal the rhomboidal forms of CPPD crystals. The appearance of these crystals is documented in this report.

Topics: Arthritis, Infectious; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diagnosis, Differential; Diphosphates; Glucose; Humans; Male; Middle Aged; Staining and Labeling; Synovial Fluid

Topics: Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Diphosphates; Humans; Proteoglycans

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

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: Aged; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Elbow Joint; Humans; Male; Radiography; Recurrence

Pyrophosphate arthropathy is an age-related disease rarely seen in those under 45 years of age. We report 2 patients with early onset pyrophosphate arthropathy in joints previously affected by juvenile chronic arthritis. This previously undescribed association supports the hypothesis that joint damage may predispose to calcium pyrophosphate dihydrate crystal deposition and lead to secondary pyrophosphate arthropathy.

Topics: Adult; Arthritis, Juvenile; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Humans; Knee Joint; Male; Radiography

Topics: Aged; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Hypothyroidism

Topics: Adult; Aged; Blood Platelets; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans; Middle Aged

Topics: Aged; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Humans; Sacroiliac Joint

The relationship between ambient ionic conditions that favor pyrophosphate (PPi) versus phosphate (Pi) biomineralization is important to understanding the pathogenesis of chondrocalcinosis. We studied aqueous solutions at pH 7.4, 37 degrees C, [Na+] = 140 mM, [Mg+ +] = 0.5 mM, [Ca+ +] = 1.0 or 1.5 mM over a range of pyrophosphate and phosphate concentrations to determine the effect of different ambient concentrations and ratios of Pi/PPi on calcium pyrophosphate dihydrate (CPPD) and calcium hydroxyapatite (HA) crystal formation. We found that the Pi/PPi ratio is an extremely important determinant of the crystal product formed. At low [Pi], CPPD crystal formation is partially inhibited by Pi; at higher [Pi], calcium pyrophosphate, calcium phosphate and calcium pyrophosphate-phosphate complexes amorphous to x-ray diffraction are formed; whereas at still higher [Pi], HA crystal formation partially inhibited by PPi. We conclude that CPPD forms when the ratio [Pi]/[PPi] less than 3 and HA forms when [Pi]/[PPi] greater than 100.

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Durapatite; Hydroxyapatites; Phosphates

The initial rates of oxygen consumption and of glucose oxidation via the hexose monophosphate shunt were measured during the phagocytosis of sodium urate and calcium pyrophosphate microcrystals. By applying the kinetics of an enzyme-catalyzed reaction, the affinity of the polymorphonuclear leukocytes for crystals, Km, and the maximum rate, Vmax, were determined. When the comparisons are made between the two kinds of crystals, the differences in Vmax are always significant (p less than 0.02). The lesser phlogistic properties of pyrophosphate crystals stem probably in part from different crystal-protein interactions. The influence of the donor is less marked. Part of the weakly depressed phagocytic activity observed with pseudogouty PMN may be attributed to antiinflammatory drugs.

Topics: Adult; Aged; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Glucose; Gout; Humans; Middle Aged; Neutrophils; Oxidation-Reduction; Oxygen Consumption; Phagocytosis; Uric Acid

Topics: Aged; Arthritis; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diagnosis, Differential; Diphosphates; Female; Humans; Radiography

A clinical and radiographic survey of 110 members of 2 families with hereditary pyrophosphate arthropathy was performed. The mode of inheritance was autosomal, dominant with a variable penetrance. Twenty-two percent of the family members had joint involvement related to pyrophosphate arthropathy, 47% of those over 50 years of age had experienced acute attacks of arthritis and/or had joint calcifications. The majority of individuals with both arthritis and joint calcifications suffered from chronic pain that resulted in early retirement. A high frequency of back pain was observed, but no ankylosis or deformity. Surgery was performed for parathyroid hyperplasia on the propositus in 1 family, and several members of her family suffered from symptoms that suggested a disturbance of calcium phosphate metabolism. There were several differences between our patients and 50 cases of sporadic pyrophosphate arthropathy from the same area of Sweden. Familial cases had an earlier onset, a greater number of involved joints, and peripheral joint involvement more often. Back pain was more frequent, and calcifications of intervertebral discs were found only in the hereditary cases.

Topics: Adult; Age Factors; Aged; Arthritis; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Genes, Dominant; Humans; Male; Middle Aged; Pedigree; Prognosis; Radiography; Sweden

We studied a case of long-standing chondrocalcinosis that after 40 years affected almost all fibrocartilages, hyaline cartilages, and articular cavities within the subject. Massive deposits of dihydrocalcium pyrophosphate (CPP) were also found in nonfissured nucleus pulposus of the vertebral disks. To our knowledge, this is the first report of CPP deposits in these disks.

Topics: Aged; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Intervertebral Disc; Male; Radiography

Genealogical links between three Swedish families with hereditary pyrophosphate arthropathy were found in the 18th century, indicating a possible founder effect, similar to earlier findings in Slovakia, France and Chile. However, no connection between the Swedish and other European families with the disease has so far been found. In accordance with other reported familial aggregations of pyrophosphate arthropathy, the transmission of the disease in the Swedish families appeared to be autosomal dominant with incomplete penetrance and variable expressivity. Severe symptoms related to homozygotic cases reported in some other families were not found in Sweden.

Topics: Adult; Chondrocalcinosis; Diphosphates; Female; Genes, Dominant; Genetics, Population; Humans; Male; Pedigree; Phenotype; Selection, Genetic; Sweden

A case of olecranon bursitis in an 81-year-old patient is presented. Analysis of the bursal fluid revealed positive birefringent crystals; radiographs showed calcifications in the distal triceps tendon. A bursectomy was performed. X-ray diffraction analyses demonstrated calcium pyrophosphate dihydrate patterns in a subcutaneous "tophus" and in a specimen of the tendon. On histologic examination, there was a bursitis with positive birefringent crystals on the bursa's inner surface; histologic images of "chondrocalcinosis" were observed in and around the tendon. It is concluded that bursitis may be part of the extraarticular manifestations of calcium pyrophosphate dihydrate crystal deposition disease.

Topics: Aged; Bursitis; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Elbow Joint; Humans; Male; Radiography; Tendons

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 association of hypophosphatasia and pyrophosphate arthropathy in an adult patient has been described on 1 previous occasion. We report a further 2 patients with this disease combination. One patient suffers from the type of hypophosphatasia that presents in adult life, with fractures that are either spontaneous or the result of minimal trauma. The other patient suffered from the severe type of hypophosphatasia that presents in infancy but survived longer than is usual; the necropsy findings on this patient are reported.

Topics: Arthritis; Bone and Bones; Calcium Pyrophosphate; Cartilage, Articular; Child, Preschool; Chondrocalcinosis; Diphosphates; Female; Fractures, Spontaneous; Humans; Hypophosphatasia; Male; Middle Aged

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Humans

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

Topics: Acute Disease; Aged; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Humans; Male; Synovial Fluid

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

The arthropathy of calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is distinctive and may affect lumbar spinal and sacroiliac joints, as well as appendicular joints. Subchondral pseudocysts that are a hallmark of the disease have a variable appearance, but often occur as a typical cluster of subchondral, coalescent lucencies with smudged, sclerotic margins. Structural joint collapse with fragmentation of cartilage and bone may occur and appear to be related, at least in some cases, to antecedent pseudocysts. Characteristic intra-articular osteochondral bodies are often extensive and may affect multiple joints; their pathogenesis is discussed. Articular synovial calcification is common and may be due to calcium hydroxyapatite, as well as CPPD, particularly if advanced degenerative changes are present. Recognition of the radiologic features may be encountered in CPPD crystal deposition disease is important for differential diagnosis.

Topics: Aged; Arthrography; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Humans; Joints; Lumbar Vertebrae; Male; Middle Aged; Sacroiliac Joint

Hereditary pyrophosphate arthropathy has been observed in three Swedish families and in a few other caucasian populations. The inheritance is most probably autosomal dominant with a variable penetrance. The most severe cases have been found in homozygotes among isolates of immigrants in Slovakia and Chile. Studies on genetic and etio-pathogenetic factors in hereditary pyrophosphate arthropathy, and the utilization of new diagnostic techniques for crystal identification, are important approaches towards a further understanding of the disease.

Topics: Adult; Chondrocalcinosis; Diphosphates; Ethnicity; Female; Genes, Dominant; Homozygote; Humans; Male; Middle Aged

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 metabolic and genetic factors leading to deposition of calcium pyrophosphate crystals in cartilage of patients with chondrocalcinosis are not well understood. Analysis of cultured fibroblasts and lymphoblasts from 12 affected members of a large kindred showed a mean concentration of intracellular inorganic pyrophosphate two times greater than that in cells from unaffected family members or normal, unrelated volunteers. Increased intracellular pyrophosphate may, therefore, be a biochemical marker for the heterozygous expression of the chondrocalcinosis gene.

Topics: Cells, Cultured; Chondrocalcinosis; Diphosphates; Fibroblasts; Humans; Lymphocytes

Topics: Bone Cysts; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Fractures, Spontaneous; Humans; Male; Middle Aged; Radiography; Radius Fractures

A gene in the heterozygous state appears responsible for a 2-fold increase in pyrophosphate content of both fibroblasts and lymphoblasts cultured from patients who have dominantly inherited chondrocalcinosis. Cells from unaffected family members of this large kindred showed a pyrophosphate content in the same range as was found in unaffected, unrelated controls. Similar cells from individuals homozygous for the gene would be useful in delineating the precise biochemical abnormality responsible for the increased pyrophosphate content.

Topics: Adult; Aged; Cells, Cultured; Chondrocalcinosis; Diphosphates; Female; Fibroblasts; Humans; Lymphocytes; Male; Middle Aged

Topics: Adult; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Humans; Male; Middle Aged; Pedigree; Radiography; Sweden

Topics: Aged; Arthropathy, Neurogenic; Calcium Pyrophosphate; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Female; Humans; Knee Joint; Radiography; Wrist Joint

A case of cervical radiculomyelopathy caused by multiple calcified nodules in the ligamenta flava is presented. Roentgenological examination of the cervical spine showed radiopaque nodular lesions, 7 x 7 x 5 mm in size, located in the paramedian portion of the posterior spinal canal. The nodules were removed surgically and they were confirmed to be calcifications of ligamenta flava. Microscopic examination of the nodules with the polarized light revealed extensive deposition of crystals. By x-ray diffraction study, the crystal was determined as calcium pyrophosphate dihydrate (CPPD: Ca2P2O7 . 2H2O). Although CPPD deposition in the cartilage has been known as pseudo-gout syndrome, deposition in the ligament has been reported only in a few cases. This is the first case with radiopaque calcified nodules in the ligamenta flava causing spinal cord compression, the composition of which proved to be CPPD.

Topics: Calcium Pyrophosphate; Cervical Vertebrae; Chondrocalcinosis; Diphosphates; Female; Humans; Ligaments; Middle Aged; Radiography; Spinal Canal; Spinal Cord Compression; Spinal Nerve Roots; Spine

A patient with pyrophosphate arthropathy is reported who had no calcifications on joint radiographs, and no crystals were found in polarized light microscopy of the synovial fluid. Using techniques for idenfication of crystals at the ultrastructural level, abundant small (less than or equal to 1 mu) pyrophosphate crystals were recognized and identified. The possibility of "ultramicrocrystal depositions", including pyrophosphate arthropathy, is important to consider in acute arthritides since small crystals might cause more intense inflammation and be the cause of arthritides, hitherto not possible to classify.

Topics: Aged; Bone Diseases; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Joint Diseases; Knee Joint; Male; Microscopy, Electron, Scanning; Synovial Fluid; Synovial Membrane

A 61-year-old man had a tophus on the third finger of his right hand. There was no history of arthritis, no laboratory abnormality, and no chondrocalcinosis. Crystalline material from the tophus was identified as calcium pyrophosphate dihydrate by x-ray diffraction.

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Fingers; Humans; Male; Metabolic Diseases; Middle Aged; X-Ray Diffraction

Little is known about how calcium pyrophosphate dihydrate (CaPPD) crystals form in vivo and give rise to chondrocalcinosis or pseudogout (pyrophosphate arthropathy or calcium pyrophosphate crystal deposition disease). In this study a simple method has been devised to define the conditions necessary for the deposition of crystals in vitro. Crystal formation is monitored by (45)Ca in the presence of 1.5 mmol/l Ca and increasing concentrations of inorganic pyrophosphate (PPi) under simulated physiological conditions of pH and ionic strength. Concentrations of PPi required to initiate crystal formation were about 40 mmol/l in the absence and 175 mmol/l in the presence of 0.5 mmol/l Mg(2+) at pH 7.4. Less PPi was required at higher pH values. The naturally occurring monoclinic and triclinic forms of CaPPD were produced after prolonged incubation in vitro, but the initial deposits were amorphous or orthorhombic. The physiological significance of these observations is discussed. Since much higher concentrations of PPi are required to form crystals in vitro than are found to occur naturally in synovial fluids from patients with pyrophosphate arthropathy, it is suggested that crystals are more likely to deposit initially within cartilage and that nucleating mechanisms may be important in vivo. Since other workers have observed a slow interconversion of other calcium pyrophosphate crystal forms into monoclinic and triclinic allomorphs under laboratory conditions, the reason why only these 2 forms occur under clinical conditions may reflect the long time available in vivo for the formation of crystals.

Topics: Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Hydrogen-Ion Concentration; Magnesium; Synovial Fluid; Time Factors

An erroneous identification of sodium urate and calcium pyrophosphate crystals in synovial fluid may occur when utilizing compensated polarized microscopy with a dual-viewing-head teaching microscope. This is due to alteration of the observed image orientation with respect to the actual orientation of the crystal in space. By viewing a simple geometric figure through each microscope head, two basic types of image alterations are identified: a 180-degree rotation and a mirror-image transformation. Combinations of these two may also occur. This problem is clarified and illustrated and suggestions are offered to avoid erroneous crystal identification.

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diagnosis, Differential; Diphosphates; Gout; Humans; Microscopy, Polarization; Synovial Fluid; Uric Acid

Aspiration of inflamed periarticular tissues in seven patients suspected of having gout on clinical examination revealed positively birefringent calcium pyrophosphate crystals. The identification of calcium pyrophosphate crystals within articular structures and in the surrounding soft tissues and radiologic findings of chondrocalcinosis, in the absence of identifiable uric acid crystals, emphasize the importance of crystal identification in all cases of probable gout and stress the diagnostic role of soft-tissue aspiration in cases of soft-tissue inflammation, especially when arthrocentesis is unsuccessful.

Topics: Adult; Aged; Biopsy, Needle; Birefringence; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diagnosis, Differential; Diphosphates; Gout; Humans; Joints; Male; Middle Aged; Synovial Fluid

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

Pyrophosphate arthropathy has a wide spectrum of clinical symptoms and is a common cause of synovitis in the elderly. The acute "pseudogout" attack is the most commonly recognized, but chronic synovitis might be just as prevalent. Familial pyrophosphate arthropathy with a dominant autosomal heredity is a rare form, with an earlier debut and a more severe prognosis. Another rare expression of pyrophosphate arthropathy is severe joint destruction. The cause of pyrophosphate arthropathy is still unknown. Both individual reactivity and crystal properties determine the intensity of the inflammatory response to crystals.

Topics: Acute Disease; Adult; Aged; Anti-Inflammatory Agents; Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Chronic Disease; Diphosphates; Female; Humans; Intervertebral Disc; Knee Joint; Male; Middle Aged; Radiography; Synovial Fluid; Synovitis

In two cases of Bartter's syndrome with hypomagnesaemia the authors report radiological findings typical of chondrocalcinosis associated with joint symptoms corresponding to this condition. In Bartter's syndrome there is, in addition to hypokalaemic alkalosis, often concomitant magnesium depletion which has marked repercussions with respect to both physiopathology and symptomatology. In particular, hypomagnesaemia could well be important in the pathogenesis of chondrocalcinosis through two simultaneous mechanisms: by reducing the activity of pyrophosphatases and by facilitating the crystallisation of pyrophosphates. These mechanisms could explain the association of Bartter's syndrome and chondrocalcinosis, which is described here for the first time.

Topics: Adult; Alkalosis; Bartter Syndrome; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Hyperaldosteronism; Hypokalemia; Magnesium Deficiency; Male; Potassium; Pyrophosphatases

The deposition and ultrastructure of calcium pyrophosphate (CPPD) crystals in joint tissues of pseudogout patients and cadavers were studied. Nine calcified menisci, 2 articular cartilages and 6 samples of synovial fluid were examined by scanning electron microscopy (SEM). Some of them were examined by analytical electron microscopy (EMMA). In the samples of menisci and cartilages, the findings were compared with those in the soft X-ray examinations and polarized light microscopy. The results are summarized as follows: 1) SEM observation of the cut surfaces of calcified menisci and cartilages showed a three-dimensional ultrastructure for the CPPD crystals. The crystals in the synovial fluid taken from pseudogout knees were also clearly demonstrated by this method. The EMMA analysis provided the possibility to examine the structure and content of the crystals simultaneously. 2) Crystal deposition in the meniscus varied with the depth of the tissues; it was diffuse in the collagen framework of the superficial layer, but showed accumulation in the deep layer where a clear line of demarcation between the collagen framework and crystals was seen. 3) The crystals in the meniscus were rod, granular or rectangular in shape, and 0.2-6.5 micro by 0.2-3.5 micro in size. Crystals from the articular cartilage were granular or rod-like in shape, and 0.2-3.5 micro by 0.2-1.0 micro in size. Most of the crystals found in the synovial fluid were rod-shaped. 4) X-ray microanalysis of the meniscus crystals by EMMA showed the same pattern of PK alpha, CaK alpha, and CaK beta content as that of CPPD crystals commercially available. The P/Ca ratio was about 0.7. 5) SEM and EMMA examination can be very useful for accurate identification of the form and content of the tiny crystals in joint tissues and synovial fluid. This can also be useful in proving a diagnosis of crystal-induced synovitis.

Topics: Calcinosis; Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Menisci, Tibial; Microscopy, Electron, Scanning; Synovial Fluid

Topics: Adult; Aged; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Female; Humans; Male; Middle Aged; Terminology as Topic

Topics: Arthritis; Calcium Pyrophosphate; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Electron Probe Microanalysis; Humans; Microscopy, Electron; Microscopy, Electron, Scanning; X-Ray Diffraction

Articular chondrocalcinosis results from the deposits of calcium pyrophosphate microcrystals in the articular hyalin and fibrocartilages, the synovium and at times the tendons. In our area it is seen most frequently as isolated cases in the elderly and may be asymptomatic. When the affected joints present clinical manifestations, they vary from acute to subacute or chronic recurrent arthritis. A marked articular destruction can be observed in some cases. There is a classical radiological picture: linear opacities are most frequently seen localized in the mid-zone layer of the hyalin cartilage running parallel to but at a certain distance from the bone cortex. A part of our research has shown that in contrast to urate gout, articular chondrocalcinosis results from a metabolic disturbance of the calcium pyrophosphate localized almost exclusively in the same articular structures. Precise information is lacking at the present time to explain why calcium pyrophosphate mycrocrystals accumulate in the cartilage, the synovium and at times at the tendons; nor do we understand the precise role played by the pyrophosphate in bone and cartilage destruction.

Topics: Aged; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Humans; Male; Middle Aged

Inorganic pyrophosphatase activity has been partially characterized in joint fluid and determined in patients with sporadic and familial chondrocalcinosis and their controls. Optimal pH was established at 3.5 and Km values were estimated. Ca-2 and Mg-2 did not affect this activity whereas orthophosphate (Pi) strongly inhibited it. In the clinical study no significant differences were found among groups. This suggests that if a pyrophosphatase defect is present it might be localized in joint tissue and not be reflected in synovial fluid.

Topics: Adolescent; Adult; Aged; Calcium; Chondrocalcinosis; Clinical Enzyme Tests; Depression, Chemical; Diphosphates; Female; Humans; Hydrogen-Ion Concentration; Knee Joint; Magnesium; Male; Middle Aged; Phosphates; Pyrophosphatases; Synovial Fluid

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

Topics: Adult; Aged; Arthritis; Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Male; Middle Aged; Radiography; Synovial Fluid

Topics: Aged; Arthritis; Cartilage, Articular; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Elasticity; Female; Humans; Male; Middle Aged

Topics: Adult; Aged; Calcium; Calcium Pyrophosphate; Chondrocalcinosis; Chronic Disease; Crystallization; Diphosphates; Humans; Hydroxyapatites; Joint Diseases; Middle Aged

Topics: Chondrocalcinosis; Diphosphates; Humans

A prospective, controlled study of patients with primary hyperparathyroidism has been carried out to establish the relation of this endocrinopathy to calcium pyrophosphate dihydrate crystal deposition disease. Eight of 26 patients with documented hyperparathyroidism were found to have chondrocalcinosis compared to four of 104 individuals in the control group (p less than 0.01). Two of these eight patients had confirmed pseudogout attacks shortly after parathyroidectomy. Four other patients, including two without chondrocalcinosis, gave a history of typical pseudogout. Patients with hyperparathyroidism and chondrocalcinosis were significantly older than those without the articular lesion (p = 0.006). We could not delineate specific metabolic abnormalities of hyperparathyroidism which contributed to the development of chondrocalcinosis.

Topics: Adult; Aged; Calcium Pyrophosphate; Chondrocalcinosis; Diphosphates; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Organ Size; Parathyroid Glands; Parathyroid Hormone; Prospective Studies; Radiography; 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

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Crystallization; Diphosphates; Humans; Joint Diseases; Kinetics; Male; Radiography; Terminology as Topic

Topics: Calcium Pyrophosphate; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Humans; Radiography; Syndrome

Topics: Adult; Aged; Calcium Phosphates; Chondrocalcinosis; Diphosphates; Female; Humans; Hypothyroidism; Male; Middle Aged; Myxedema; Radiography; Retrospective Studies; Synovial Fluid

Topics: Adolescent; Adult; Age Factors; Aged; Calcium Phosphates; Chondrocalcinosis; Chromosome Mapping; Chromosomes; Crystallography; Diphosphates; Female; Genes, Dominant; HLA Antigens; Humans; Male; Middle Aged; Pedigree; Radiography; Synovial Fluid

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

Deposits taken from an acetabulum and the head of a femur and known to contain crystals of calcium pyrophosphate were examined by selected histological methods for calcium after the application of a variety of solvents. Treatment with 10% ferric chloride removed all calcium salts tested, except a birefringent crystalline component in the pyrophosphate deposits. This corresponds to the previous optical and morphological descriptions of calcium pyrophosphate as found in synovial fluids. Calcium pyrophosphate stains consistently only by the fluorescent morin method.

Topics: Acetabulum; Basophils; Calcium Phosphates; Chondrocalcinosis; Crystallization; Diphosphates; Femur Head; Humans

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

Radiological and morphological findings in advanced arthritis urica and pyrophosphate arthropathy are well known. In contrast, the early changes of synovial membrane in these disturbances of metabolism pose diagnostic problems. With the assistance of various cytological techniques and polarizing microscopical as well as electron microscopical investigation it was examined to what extent needle biopsies can be helpful in the differential diagnosis of gout and pseudogout.. In 8 patients with gout and 11 patients with pseudogout synovial fluid and small tissue specimens could be obtained with the aid of the Parker-Pearson needle. Both fluid and tissue specimens were investigated light and electron microscopically. Cell counts were evaluated in a Rosenthal chamber. The differentiation of the cells in stained smears was done by counting 200-600 cells per case. Crystals were identified by polarizing microscopy in wet preparations of freshly aspirated synovial fluid.. Polarizing microscopy of synovial fluid detected intra- as well as extracellular urate and pyrophosphate crystals. The wedge-shaped urate crystals and the larger partly polygonal pyrophosphate crystals showed different polarizing microscopical properties and a negative birefringence. The absolute cell counts in gout were higher than those in pseudogout. The relative cell counts of the different cell types in synovial fluid showed more variation in gout than in pseudogout. Cases with acute gout developed a relative leukocytosis in contrast to a relative lymphocytosis in chronic gout. A relative leukocytosis was constant in all patients with pseudogout. Sclerosed areas with scarce and plump villi as well as sometimes hyperplastic and polymorphous synovial cell layers could be demonstrated histologically in the tissue specimens of the needle biopsies in cases with gout. Urate crystals were less frequent in specimens fixed in formalin. The histological alterations in pseudogout were uniform, 2-4 rows of slightly pleomorphic synovial cells lined the inner surface of the joint capsule, sclerosing alterations were less frequent. Pyrophosphate crystals and calcified particles were seen within the synovial lining cells, the connective tissue and the enodthelial cells of the blood vessels in pseudogout specimens. Intra- as well as extracellular crystals could also be demonstrated with the aid of scanning electron microscopy in sediments of synovial fluid in gout and pseudogout. Transmission electron microscopical investigations of synovial tissue specimens detected proliferated and pleomorphic synovial lining cells in gout in contrast to a more monomorphic appearance of these cells in pseudogout. The crystals were washed out during the preparation techniques for transmission electron microscopy so that needle-like empty spaces resulted within cytoplasm of the phagocytic cells. These clefts were surrounded by phagosomal structures and densified cytoplasmic ground substance; sometimes they were also lined by membranes...

Topics: Aged; Biopsy, Needle; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Female; Gout; Humans; Leukocyte Count; Male; Microscopy, Electron, Scanning; Microscopy, Polarization; Middle Aged; Phagocytes; Synovial Fluid; Synovial Membrane; Uric Acid

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

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

During a 12-month period, we have treated five patients with acute inflammatory arthritis and synovial fluid leukocyte counts of 65,000 to 100,00/cu mm with 93% to 100% polymorphonuclear cells, calcium pyrophosphate dihydrate crystals in the synovial fluid, and negative cultures. Four of these five were origingally treated for septic joints. We would like to emphasize this relatively uncommon, but important manifestation of pseudogout.

Topics: Arthritis, Infectious; Calcium; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Humans; Leukocyte Count; Male; Synovial Fluid

Pseudogout, or calcium pyrophosphate arthropathy, is a crystalline synovitis, characterised either by acute attacks of joint pain, which usually occur in the large joints, or by a more chronic, progressive form of joint disease. The essential features of the disease are chondrocalcinosis and the presence of pyrophosphate crystals in the synovial fluid. The exact pathogenesis is unknown. Case reports of 2 patients with confiemed pseudogout, and of 1 who is suspected to be suffering from the disease, as well as a summary of the outstanding aspects of the condition, are presented.

Topics: Acute Disease; Aged; Chondrocalcinosis; Chronic Disease; Diagnosis, Differential; Diphosphates; Female; Humans; Knee; Male; Middle Aged; Radiography; Wrist

Crystal identification is made with a polarizing, color-compensated light microscope. Most microscopes can be easily and inexpensively adapted for crystal identification. The color compensator allows differentiation between the monosodium urate crystals of gout and the crystals of pseudogout, or calcium pyrophosphate deposition disease. All synovial fluid specimens should be examined. The observation of phagocytosis of crystals establishes that they are the etiologic agent responsible for an ongoing acute attack of arthritis.

Topics: Betamethasone; Calcium Phosphates; Cholesterol; Chondrocalcinosis; Color; Crystallography; Diphosphates; Edetic Acid; Gout; Humans; Light; Lipids; Microscopy; Microscopy, Polarization; Oxalates; Physical Phenomena; Physics; Synovial Fluid; Uric Acid

Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group.

Topics: Adult; Aged; Alkaline Phosphatase; Blood Group Antigens; Calcium; Chile; Chondrocalcinosis; Diet; Diphosphates; Emigration and Immigration; Female; Genes, Recessive; Humans; Joint Diseases; Male; Middle Aged; Pedigree; Synovial Fluid; White People

The pseudogout syndrome is usually associated with radiographic evidence of articular cartilage calcification. Eight patients who had joints containing calcium pyrophosphate dihydrate crystals were studied. Extensive radiographic evaluation was obtained in seven patients and a limited evaluation in the other. None had evidence of chondrocalcinosis. Six had distinctive radiographic abnormalities of the wrists consisting of radiocarpal joint space narrowing and sclerosis, and subchondral cystic degeneration of the carpal bones. We conclude that calcium pyrophosphate dihydrate deposition disease and pseudogout can occur without radiographic evidence of chondrocalcinosis and that the diagnosis can be suggested by characteristic radiographic abnormalities of the wrists.

Topics: Adult; Aged; Calcium Phosphates; Chondrocalcinosis; Diphosphates; Humans; Joint Diseases; Male; Metabolic Diseases; Middle Aged; Radiography; Wrist Joint

Twelve patients with severe hypothyroidism and rheumatic signs and symptoms were studied before or within four days of receiving thyroid replacement therapy. Eight patients had synovial effusions. Seven effusions were extremely viscous and six contained calcium pyrophosphate crystals. Leukocyte counts were less than 1,000/mm3, except in two patients during crystal-induced synovitis. "Bulge signs" were present but often sluggish, possibly because of the viscosity of the fluid. Flexor tendon sheath thickening, joint laxity and popliteal cysts were documented. All patients complained of generalized stiffness and two had proximal myopathy. Roentgenograms were obtained in 11 patients, and chondrocalcinosis was identified in seven. Needle synovial biopsy specimens in five patients showed only mild inflammation in the thick synovium. These findings can suggest hypothyroidism, a treatable disease, as the cause of musculoskeletal problems.

Topics: Aged; Calcium Phosphates; Chondrocalcinosis; Diphosphates; Female; Humans; Hyaluronic Acid; Hypothyroidism; Joint Diseases; Male; Middle Aged; Radiography; Rheumatic Diseases; Synovial Fluid; Synovial Membrane; Viscosity

An ultrastructural study of articular cartilage from five patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease was performed. The CPPD crystals, identified by micro X-ray diffraction, were usually found in clusters, located in intercellular areas of the intermediate cartilage layer. The matrix surrounding the clusters either showed a normal morphology or a homogeneous appearance, within which faint cross striations but no distinctly fibrillar outlines could be identified. Another change in the matrix, characterized by an increased electron density and longitudinally fragmented collagen fibres, was also seen. This latter change was generally seen without concomitant CPPD crystal deposition. No specific relationship between the crystals and the collagen fibres or the granular background material of the matrix was encountered.

Topics: Adult; Calcium Phosphates; Cartilage, Articular; Chondrocalcinosis; Collagen; Crystallization; Diphosphates; Humans; Knee Joint; Middle Aged

Topics: Animals; Arthritis; Arthus Reaction; Calcium; Carrageenan; Chondrocalcinosis; Diphosphates; Disease Models, Animal; Guinea Pigs; Immunity, Cellular; Kinetics; Macrophages; Phosphorus; Pleurisy; Rats

Topics: Arthritis; Chondrocalcinosis; Diphosphates; Humans

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: Adult; Aged; Chondrocalcinosis; Diphosphates; Female; Humans; Knee; Knee Joint; Male; Middle Aged; Radiography

Topics: Calcium Phosphates; Chondrocalcinosis; Crystallization; Diphosphates; Gout; Humans; Joint Diseases; Uric Acid

Topics: Aged; Calcium Phosphates; Chondrocalcinosis; Diphosphates; Female; Humans; Middle Aged; Synovial Fluid; Uric Acid

Topics: Adult; Arthritis; Arthroplasty; Calcium Phosphates; Chondrocalcinosis; Chronic Disease; Diphosphates; Female; Humans; Knee; Middle Aged; Radiography; Syndrome; Synovial Fluid

Topics: Adult; Aged; Arthrography; Calcium Phosphates; Chondrocalcinosis; Crystallization; Diphosphates; Female; Humans; Male; Middle Aged; Synovial Fluid

Topics: Arm; Bursitis; Calcinosis; Calcium; Chondrocalcinosis; Collagen Diseases; Diphosphates; Epidermolysis Bullosa; Gout; Humans; Joint Diseases; Leg; Lipodystrophy; Periarthritis; Radiography; Rupture; Synovial Cyst; Synovial Membrane; Tendon Injuries

Topics: Aged; Arthritis; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Gout; Humans; Knee Joint; Leukocytes; Male; Middle Aged; Radiography; Suppuration; Synovial Fluid

Topics: Aged; Calcium Phosphates; Cartilage, Articular; Chondrocalcinosis; Diphosphates; Female; Humans; Male; Synovial Fluid

Topics: Adult; Aged; Cartilage, Articular; Chondrocalcinosis; Chondroitin; Diphosphates; Glycosaminoglycans; Hexosamines; Humans; Middle Aged; Molecular Weight; Sulfates

Topics: Adult; Aged; Arthritis; Calcium; Chondrocalcinosis; Crystallization; Diabetes Complications; Diet Therapy; Diphosphates; Female; Gout; Humans; Hyperparathyroidism; Knee Joint; Leukocytes; Male; Middle Aged; Physical Therapy Modalities; Radiography; Synovial Fluid; Synovitis; Uric Acid

Topics: Acid Phosphatase; Chondrocalcinosis; Diphosphates; Female; Gout; Hemolysis; Humans; Inflammation; Leukocytes; Lysosomes; Male; Membranes; Phagocytosis; Sex Factors; Silicon Dioxide; Uric Acid

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: Allopurinol; Arthritis; Calcium Phosphates; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Gout; Humans; Kidney Diseases; Kidney Tubules; Leukocytes; Macrophages; Myeloproliferative Disorders; Synovial Fluid; Uric Acid

Topics: Age Factors; Aged; Arthritis; Arthrography; Calcium; Calcium Phosphates; Chondrocalcinosis; Crystallization; Diphosphates; Drainage; Exercise Therapy; Humans; Leukocytes; Middle Aged; Phenylbutazone; Synovial Fluid; Synovitis

Topics: Acute Disease; Age Factors; Aged; Calcium; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Female; Hospitals; Humans; Knee Joint; Male; Middle Aged; Postoperative Care; Postoperative Complications; Sex Factors; Syndrome; Synovitis

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

Topics: Adult; Aged; Chondrocalcinosis; Diphosphates; Female; Humans; Knee; Male; Middle Aged; Postoperative Complications; Surgical Procedures, Operative; Synovial Fluid

Topics: Amputation, Surgical; Animals; Chondrocalcinosis; Diphosphates; Dog Diseases; Dogs; Female; Hindlimb; Histocytochemistry; Radiography

Topics: Calcinosis; Calcium Phosphates; Chondrocalcinosis; Diphosphates; Elbow Joint; Hip Joint; Humans; Hydroxyapatites; Intervertebral Disc; Knee Joint; Pubic Symphysis; Radiography; Shoulder Joint; Tarsal Joints; Tendinopathy; Tendons; Toe Joint; Uric Acid; Wrist Joint

Topics: Adult; Biopsy; Bone Matrix; Calcium Phosphates; Cartilage Diseases; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Femur; Histocytochemistry; Humans; Microradiography; Microscopy, Electron; Microscopy, Polarization; Middle Aged; X-Ray Diffraction

Topics: Adult; Aged; Calcium; Chondrocalcinosis; Crystallography; Diphosphates; Female; Humans; Male; Middle Aged; Radiography; Sodium; Synovial Fluid

Topics: Aged; Arthropathy, Neurogenic; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Humans; Knee Injuries; Knee Joint; Male

Topics: Aged; Chondrocalcinosis; Diphosphates; Female; Humans; Male; Synovial Fluid

Topics: Aged; Chondrocalcinosis; Crystallization; Diagnosis, Differential; Diphosphates; Female; Gout; Humans; Indomethacin; Middle Aged; Synovitis; Uric Acid

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

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

Topics: Arthritis; Calcinosis; Calcium; Cartilage, Articular; Chondrocalcinosis; Diagnosis, Differential; Diphosphates; Gout; Humans; Hyaline Cartilage; Joint Diseases; Knee 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

Topics: Arthritis; Calcinosis; Chondrocalcinosis; Diphosphates; Humans; Rheumatic Diseases; Synovitis

Topics: Adrenal Cortex Hormones; Calcification, Physiologic; Cartilage; Chondrocalcinosis; Crystallography; Diphosphates; Gout; Humans; Joint Diseases; Phenylbutazone; Synovitis