pyrophosphate and Joint-Diseases

Pathological (ectopic) mineralization of soft tissues occurs during aging, in several common conditions such as diabetes, hypercholesterolemia, and renal failure and in certain genetic disorders. Pseudoxanthoma elasticum (PXE), a multi-organ disease affecting dermal, ocular, and cardiovascular tissues, is a model for ectopic mineralization disorders. ABCC6 dysfunction is the primary cause of PXE, but also some cases of generalized arterial calcification of infancy (GACI). ABCC6 deficiency in mice underlies an inducible dystrophic cardiac calcification phenotype (DCC). These calcification diseases are part of a spectrum of mineralization disorders that also includes Calcification of Joints and Arteries (CALJA). Since the identification of ABCC6 as the "PXE gene" and the development of several animal models (mice, rat, and zebrafish), there has been significant progress in our understanding of the molecular genetics, the clinical phenotypes, and pathogenesis of these diseases, which share similarities with more common conditions with abnormal calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into inorganic pyrophosphate (PPi) and adenosine by the ectonucleotidases NPP1 and CD73 (NT5E). PPi is a potent endogenous inhibitor of calcification, whereas adenosine indirectly contributes to calcification inhibition by suppressing the synthesis of tissue non-specific alkaline phosphatase (TNAP). At present, therapies only exist to alleviate symptoms for both PXE and GACI; however, extensive studies have resulted in several novel approaches to treating PXE and GACI. This review seeks to summarize the role of ABCC6 in ectopic calcification in PXE and other calcification disorders, and discuss therapeutic strategies targeting various proteins in the pathway (ABCC6, NPP1, and TNAP) and direct inhibition of calcification via supplementation by various compounds.

Topics: 5'-Nucleotidase; Animals; ATP-Binding Cassette Transporters; Calcification, Physiologic; Calcinosis; Diphosphates; GPI-Linked Proteins; Humans; Joint Diseases; Mice; Multidrug Resistance-Associated Proteins; Phosphoric Diester Hydrolases; Pseudoxanthoma Elasticum; Pyrophosphatases; Rats; Vascular Calcification; Vascular Diseases

Pyrophosphate arthropathy is a clinical syndrome that is recognized as a consequence of calcification of aging tissues. This syndrome, with emphasis on its presentation in the knees of elderly persons, is reviewed. Comments on the epidemiology, clinical presentation with criteria of diagnosis, radiology, synovial fluid findings, differential diagnosis, pathogenesis, and treatment are offered.

Topics: Diagnosis, Differential; Diphosphates; Humans; Joint Diseases; Knee Joint; Radiography

The chemistry and molecular bonding characteristics of the CaPPi family of compounds are very complex. The unique molecular flexibility of the PPi anion and the potential variability of Ca coordination geometries have allowed for a broad spectrum of CaPPi type structures. The structure of t-CPPD has the smallest P-OB-P angle of the known CaPPi structures, both Ca atoms are 7 coordinate which is the maximum allowable contacts for Ca atoms, and the two water molecules of crystallization not only serve to fill molecular space, but they are also involved in direct contact to the PPi anions and the Ca atoms. The structure of t-CPPD appears to be very stable and the structural characteristics support the observation that the crystals are sparingly soluble in an aqueous environment. Unfortunately, the structure of m-CPPD is not known and comparisons cannot be made. The solution model studies have resulted in the observation that t-CPPD and m-CPPD crystals can be grown in an aqueous environment at conditions far less harsh than those required for the standard synthetic procedure. However, the synthetic procedure, in contrast to the solution models, yields the prismatic crystal growth morphology of t-CPPD and the rod morphology of m-CPPD observed in vivo. The solution models showed that increasing Mg or Pi retarded crystal formation. At physiologic levels of Mg and Pi, a-CaPPi formed, but neither t-CPPD nor m-CPPD would form. In all solution studies, the final Ca and PPi were not determined and therefore a correlation could not be made between the ionic concentrations and crystal type formed. The gel models using silica, polyacrylamide, and biologic grade gelatin all highlighted that the time of incubation of Ca and PPi ions was a critical parameter in determining the type of crystal formed. The biologic grade gelatin model studies that we conducted indicated that the formation of the two in vivo crystals was mediated by the formation of intermediate crystalline materials and the subsequent dissolution of those species. This formation/dissolution/reformation mechanism allows for a very localized ionic concentrating process to occur. In our model system, we measured the final Ca and PPi levels at all points of crystallization and could map the ionic concentration gradients and compare them to the crystal type formed with respect to the time of incubation. However, the crystal growth morphologies for t-CPPD and m-CPPD still did not match the morphologies observed in

Topics: Anions; Calcinosis; Calcium Pyrophosphate; Chemical Phenomena; Chemistry, Physical; Collagen; Crystallization; Crystallography; Diphosphates; Gels; Humans; Joint Diseases; Models, Biological; Models, Chemical

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

Varying combinations of acute inflammatory and/or chronic degenerative arthritis have been found to be associated with crystals of calcium pyrophosphate dihydrate (CPPD) and/or basic calcium phosphates (BCPs). Since the arthropathies associated with CPPDs and/or BCPs occur in older individuals, while diagnosis and treatment for monosodium urate monohydrate crystal deposition disease (gout) have become extremely precise and effective, joint problems associated with calcium crystals have become more common than those associated with monosodium urate monohydrate crystals. The classification, pathogenesis, clinical manifestations, and treatment of CPPD and BCP crystal deposition are discussed.

Topics: Aged; Anti-Inflammatory Agents; Arthritis; Calcium Phosphates; Calcium Pyrophosphate; Colchicine; Crystallization; Diphosphates; Female; Humans; Hyperplasia; Inflammation; Joint Diseases; Methods; Peptide Hydrolases; Radiography; Shoulder Joint; Syndrome; Synovial Membrane

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

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: 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: Antibodies, Antinuclear; Bacteria; Blood Coagulation Tests; Calcium; Cholesterol; Complement System Proteins; Diphosphates; Glucose; Humans; Inclusion Bodies; Joint Diseases; Knee; Leukocyte Count; Leukocytes; Mucins; Proteins; Radiography; Rheumatoid Factor; Sodium; Staining and Labeling; Synovial Fluid; Uric Acid; Viscosity

Topics: Adult; Aged; Arthritis; Calcinosis; Diphosphates; Female; Gout; Humans; Joint Diseases; Male; Middle Aged; Phagocytosis; Synovial Fluid; Synovitis; Terminology as Topic; Uric Acid

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

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

Pyrophosphate arthropathy (PA) has been reported in association with a number of diseases, usually occurring in the older age group. We report a 40-year-old female with untreated X-linked hypophosphataemic rickets who presented with PA.

Topics: Adult; Diphosphates; Female; Humans; Joint Diseases; Phosphates; Rickets

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

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

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

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

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

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

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

Using transmission electron microscopy, selected area electron diffraction, and micro x-ray diffraction techniques, we studied calcium pyrophosphate dihydrate (CPPD) deposits from 23 patients with chondrocalcinosis affecting the femoral head to delineate the cellular and matrix environment in which CPPD crystals form, to determine the sequence of crystal deposition, and to address the question of coexistent calcium apatite crystal deposition. We found 2 types of CPPD crystal deposits with few transitional forms. First, small collections of crystals were seen at the border of the territorial matrix at the articular and subarticular poles of the chondron. CPPD crystal deposits were unassociated with collagen or matrix vesicles. Second, and more frequently, large collections of randomly arranged crystals (agglomerates) were observed, the smallest replacing the chondrocyte and adjacent pericellular matrix. Chondrocytes adjacent to crystal deposits were intact. Coexistent apatite crystal deposition was demonstrated in only 2 of 23 cartilages ultrastructurally examined, providing evidence that mixed crystal deposits are possible but not common in CPPD crystal arthropathy.

Topics: Aged; Aged, 80 and over; Calcinosis; Calcium Pyrophosphate; Cartilage; Crystallization; Diphosphates; Electron Probe Microanalysis; Female; Humans; Joint Diseases; Male; Microscopy, Electron

Of 200 consecutive patients with confirmed pyrophosphate arthropathy, clinically significant median nerve entrapment was found in 14 (14%) of those with wrist involvement. Three of these had electromyographically confirmed combined median and ulnar nerve entrapment at the wrist (bilateral in 2). Chondrocalcinosis, but not changes of arthropathy, was closely associated with the presence of entrapment (p less than 0.001), implying that soft tissue factors are important in causation. Treated hypothyroidism was more common in those with nerve entrapment (p less than 0.01), suggesting a possible interaction of multiple factors in the pathogenesis of nerve entrapment.

Topics: Adult; Aged; Aged, 80 and over; Arthrography; Calcium Pyrophosphate; Crystallization; Diphosphates; Electromyography; Female; Humans; Joint Diseases; Male; Median Nerve; Middle Aged; Nerve Compression Syndromes; Wrist

Topics: Calcium Pyrophosphate; Cartilage, Articular; Cell Membrane; Crystallization; Diphosphates; Forecasting; Humans; Joint Diseases; Minerals

Clinical features of calcium pyrophosphate dihydrate crystal deposition disease (CPPD c.d.d.) were studied and the following results were obtained. The prevalence of CPPD c.d.d. was 9.7% in 300 persons aged 50 or older, who stayed or worked at an old-age home. The most common type of CPPD c.d.d. was the asymptomatic type. Comparative studies between the patients with CPPD c.d.d. and subjects without it revealed that scoliosis of the lumbar spine, osteoarthritis-like changes of the knee, subchondral bone cyst and patella wrapped around the femur were statistically more frequent in the former. The clinical study of 50 patients with CPPD c.d.d. revealed calcification not only in the articular cartilage but also in periarticular tissues and ligamentum flavum. The histological study demonstrated frequent destructive changes of the tissues around the site of CPPD crystal deposition. Formation of CPPD crystals appeared to be initiated by degenerating chondrocytes and metaplastic chondrocytes.

Topics: Age Factors; Aged; Blood Chemical Analysis; Calcinosis; Calcium Pyrophosphate; Crystallization; Diphosphates; Female; Humans; Joint Diseases; Knee Joint; Ligaments; Lumbar Vertebrae; Male; Middle Aged; Radiography

Topics: Aged; Calcium Pyrophosphate; Crystallization; Diphosphates; Durapatite; Female; Humans; Hydroxyapatites; Joint Diseases; Radiography; Shoulder Joint

A simple, rapid screening method using alizarin red S stain and ordinary light microscopy to detect microcrystalline or noncrystalline calcium phosphate salts was used on wet drop preparations of synovial fluids. This proved to be helpful in detecting apatite crystal clumps and small calcium pyrophosphate dihydrate (CPPD) crystals missed by polarized light. The staining was positive in 100% of synovial fluids from patients later proven to have apatite and/or CPPD deposition diseases. Apatite and CPPD crystals were commonly found together in the same fluids. In addition, some synovial fluids from patients with osteoarthritis, renal failure dialysis, rheumatoid arthritis, and gout also exhibited positive staining. The correlation of positive alizarin red S staining with radiologic evidence of osteoarthritis suggests that apatite crystals might be related to articular cartilage degeneration in different rheumatic diseases.

Topics: Anthraquinones; Apatites; Arthrography; Calcium Pyrophosphate; Crystallization; Diphosphates; Electron Probe Microanalysis; Humans; Joint Diseases; Microscopy, Electron; Staining and Labeling; Synovial Fluid; X-Ray Diffraction

Radiographic features of hand and wrist involvement in 26 patients with hemochromatosis and in 26 patients with idiopathic calcium pyrophosphate dihydrate (CPPD) crystal deposition disease were compared. Two radiologists independently examined the radiographs without knowledge of the specific group to which the patient belonged. The results of this study clearly establish that structural joint diseases in the two disorders are not identical. Characteristic findings allow the radiologist to favor one diagnosis over the other. These radiographic differences indicate that the arthropathy of hemochromatosis is related to factors additional to the presence of CPPD crystals, specifically, the more prevalent narrowing of the metacarpophalangeal joint spaces, including those in the fourth and fifth digits, peculiar hook-like osteophytes on the radial aspect of the metacarpal heads, and less prevalent separation of the scaphoid and the lunate.

Topics: Adult; Aged; Calcium Metabolism Disorders; Calcium Pyrophosphate; Diagnosis, Differential; Diphosphates; Female; Hand; Hemochromatosis; Humans; Joint Diseases; Male; Metacarpophalangeal Joint; Middle Aged; Radiography; Wrist Joint

The post-mortem examination of an unsuspected case of alkaptonuria revealed extensive ochronosis. Histological examination of undecalcified sections of tracheal, costal, femoral and patellar cartilage revealed, in addition to ochronotic pigment, extensive calcium pyrophosphate dihydrate (CPPD) deposition. Similar deposits were present in intervertebral discs and were related to ossification of the discs resulting in partial or complete ankylosis. The calcific deposits were present around chondrocytes in the articular cartilage and this may be an important factor in the initiation of the osteoarthrotic process which characterises ochronotic arthropathy as it affects large diarthrodial joints.

Topics: Aged; Calcium Pyrophosphate; Cartilage; Cartilage, Articular; Diphosphates; Femur Head; Hip Joint; Humans; Intervertebral Disc; Joint Diseases; Male; Ochronosis; Trachea

Calcium pyrophosphate dihydrate crystal deposition disease and HA crystal deposition disease are two common disorders that may come to the attention of a physician because of a variety of clinical symptomatology patterns. In CPPD crystal deposition disease, characteristic radiologic features include articular and periarticular calcification and an arthropathy consisting of joint space narrowing, bone sclerosis, often prominent subchondral cyst formation, occasional severe and progressive destructive bone changes, and variable osteophyte formation. These findings are often seen in a characteristic distribution with involvement of non-weight-bearing as well as weight-bearing joints and with involvement of distinctive intraarticular sites such as the patellofemoral compartment of the knee and the radiocarpal compartment of the wrist. In HA crystal deposition disease, characteristic radiologic features consist of calcific tendinitis and periarthritis as well as a more recently described arthropathy. Awareness of the distinctive roentgenographic appearance of these two diseases should allow a specific diagnosis to be made, and an understanding of their pathologic features should aid in appropriate therapy and guide future investigation of possible etiologic factors.

Topics: Aged; Arthrography; Calcification, Physiologic; Calcium Metabolism Disorders; Calcium Pyrophosphate; Crystallization; Diphosphates; Female; Humans; Hydroxyapatites; Joint Diseases; Male; Middle Aged; Prognosis

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

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

The 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

Topics: Adult; Child; Diphosphates; Femur Head Necrosis; Gallium Radioisotopes; Hip Joint; Humans; Infections; Joint Diseases; Legg-Calve-Perthes Disease; Radionuclide Imaging; Reflex Sympathetic Dystrophy; Technetium; Technetium Tc 99m Pyrophosphate

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

Topics: Calcium Pyrophosphate; Crystallization; Diphosphates; Humans; Hydroxyapatites; Joint Diseases; Joints; Synovial Fluid

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

Topics: Adult; Aged; Cartilage, Articular; Diagnosis, Differential; Diphosphates; Female; Humans; Joint Diseases; Male; Radiography; Synovial Fluid; Synovitis

Topics: Calcium Metabolism Disorders; Calcium Pyrophosphate; Diphosphates; Joint Diseases

Topics: Bone and Bones; Bone Neoplasms; Diphosphates; Humans; Joint Diseases; Ossification, Heterotopic; Osteoma; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

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

After description of etiopathogenetic, anatomopathological and clinical aspects of the disease, the authors relate about a case of ochronotic arthropathy, lining on its typical radiological patterns. Scintigraphic study with 99mTc-pertechnetate and with 99mTc-pyrophosphate, excluding any phlogistic component, agree with dysmetabolic and degenerative nature of this arthropathy.

Topics: Arthritis; Diagnosis, Differential; Diphosphates; Humans; Joint Diseases; Ochronosis; Radiography; Radionuclide Imaging; Technetium

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

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

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

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

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

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

A scanning electron microscopic study of six cases of pyrophosphate arthropathy has been conducted. In the majority of cases the crystals were rectangular. In some cases giant crystals were present. In one case, the crystals were pyramidal. It is concluded that many geometrically different forms of calcium pyrophosphate crystal exist and that the scanning electron microscope is a useful tool in the differentiation of pyrophosphate arthropathy from other forms of crystal synovitis.

Topics: Cartilage, Articular; Diphosphates; Humans; Joint Diseases; Microscopy, Electron, Scanning; Surface Properties; Synovitis

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

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

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

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

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

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

The 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

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

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

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

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

Topics: Age Factors; Alkaline Phosphatase; Calcification, Physiologic; Calcinosis; Diphosphates; Hemochromatosis; Humans; Iron; Joint Diseases

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Arthritis; Calcinosis; Calcium; Chromatography, Ion Exchange; Crystallization; Diphosphates; Electrophoresis; Female; Humans; Hydrolysis; Ion Exchange; Joint Diseases; Male; Middle Aged; Phosphates; Phosphorus Isotopes; Radioisotope Dilution Technique; Solubility; Synovial Fluid

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

Topics: Aged; Alkaline Phosphatase; Calcinosis; Chromatography, Ion Exchange; Diphosphates; Female; Humans; Joint Diseases; Male; Middle Aged; Synovial Fluid

Topics: Aged; Calcinosis; Calcium Phosphates; Diagnosis, Differential; Diphosphates; Female; Gout; Humans; Joint Diseases; Knee Joint; Male; Middle Aged; Synovial Fluid; Synovitis

Topics: Arthritis; Calculi; Cartilage Diseases; Colchicine; Crystallization; Diphosphates; Female; Humans; Joint Diseases; Kidney Failure, Chronic; Knee; Male; Periarthritis; Radiography; Shoulder; Synovial Fluid; Synovitis; Wrist

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; Blood Sedimentation; Calcinosis; Calcium Phosphates; Diphosphates; Female; Hematocrit; Humans; Inhalation; Joint Diseases; Joints; Knee; Leukocyte Count; Male; Middle Aged; Punctures; Radiography; Synovial Fluid; Uric Acid; Wrist

Topics: Calcium; Diet Therapy; Diphosphates; Humans; Joint Diseases; Methods; Phosphorus

Topics: Aged; Calcinosis; Calcium; Diphosphates; Female; Humans; Joint Diseases; Male; Radiography

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

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