CPPD Crystal Research Articles

E062 Calcium pyrophosphate dihydrate crystal in operated rheumatoid arthritis of the knee

Abstract Background/Aims Calcium pyrophosphate dihydrate (CPPD) crystals are also one of the common types of crystals causing crystal-induced inflammatory arthritis. Several studies have elucidated important aspects of the molecular and cellular mechanisms of CPPD crystal formation. CPPD crystal deposition disease is a common arthritic disorder in mainly elderly patients. CPPD crystals are found in multiple joints (e.g. knee, wrist joints) in association with severe cartilage degeneration in osteoarthritis. However, there are few reports concerning about CPPD crystals in patients with rheumatoid arthritis (RA). In this study, I investigated the relationship between CPPD crystal and operated RA of the knee. Methods Seventy-seven total knee arthroplasties were performed for RA knees from January 2016 to September 2021. I defined the lower extremity alignment (LEA) base on the femorotibial angle (FTA) as valgus (FTA<170°), neutral (170°≤FTA<180°), and varus (FTA≥180°). I also defined the osteophyte formation degree (OFD) in the knee (grade 0-3). At the operation, joint fluids were collected from 70 knees (average age 71.6; male 8; female 72 body mass index (BMI) 24.4kg/m2,; C-reactive protein (CRP) 1.20mg/dL; erythrocyte sedimentation rate (ESR) 49.5mm/h; matrix metalloprotease (MMP)-3 289.5ng/dL; OFD (0/1/2/3) 0/38/25/7; FTA 177.9°; LEA: varus 35; neutral 22; valgus 13). We evaluated the relationship between CPPD crystals and age, gender, FTA, BMI, CRP, ESR, MMP-3, OFD and LEA. When I analyzed the risk factors using the logistic regression method, LEA were defined as valgus (FTA<175°) and varus (FTA≥176°). Results CPPD crystals were detected from 19 RA knees (27.1%). There were no significant differences between CPPD(+) and (-) groups about age, gender, FTA, BMI, CRP, ESR and MMP-3. The more severe osteophyte formation showed higher CPPD(+) rate tendency; however, there was no significance. CPPD(+) rates were 34.2% in varus knees, 23.1% in valgus knees and 18.2% in neutral knees, respectively. We reported that age, valgus knee, severe osteophyte and low BMI were the risk factors of CPPD(+) in operated osteoarthritis (OA) knees, previously. In this study, there was no difference between CPPD(+) and (-) groups about these factors. Especially, CPPD(+) rate in RA valgus knees was one third of that of OA valgus knees. Conclusion It may be suggested that CPPD production mechanism in RA knees is different from that in OA knees. Disclosure M. Nishikawa: None.

A case of Tophaceous Pseudogout: A Rare Crystalopathy Particularly Afflicting the Temporomandibular Joint

<h3>Introduction</h3> Tophaceous pseudogout is a rare variant of CPPD crystal deposition disease presenting with a soft- tissue calcified mass. Temporomandibular joint is a common site of involvement of tophaceous pseudogout. Mu- tations in gene ANKH (inorganic phosphate transport regulator) are involved in crystal related inflammatory reac- tions. <h3>Materials and Methods</h3> We report a case of Tophaceous CPPD crystal deposition disease. A 77-year old female with no pertinent past medical or drug history, presented with persistent dull pain in her left TMJ and gradual change in occlusion over two years with intermittent trismus. Clinical examination revealed a left pre-auricular swelling with compression of the left EAC. CT imaging showed a radiopaque expansile mass encompassing the left TMJ. Surgical removal was performed together with alloplastic reconstruction using a TMJ Concepts Total Joint Replacement prosthesis. <h3>Results</h3> Microscopic examination revealed a low-grade cartilaginous proliferation with intensely basophilic calcified crys- tal deposits which were rhomboidal in appearance and polarized weakly. Few areas showed atypical, occasional binucleated chondrocytes interpreted as chondroid metaplasia. No significant bone or soft tissue invasion was identified. The clinical, histological and radiographic findings were consistent with tophaceous pseudogout (mas- sive CPPD deposition with cartilaginous metaplasia). Post-operatively the patient was pain-free with normalized occlusion and function. <h3>Conclusions</h3> Distinction from other benign chondroid neoplasms such as osteochondroma, synovial chondromatosis which may mimic CPPD disease is important. Low grade chondrosarcoma should be excluded, especially in decalcified sec- tions from which the CPPD crystals may be lost leaving behind only the atypical features in metaplastic chondro- cytes. Tophi of gout needs to be discriminated too, where monosodium urate crystals are more needle shaped and negatively birefringent under polarized light microscopy, besides hydroxyapatite crystals which appear as non- birefringent clumps. Correct identification of the type of crystal deposition is paramount to the treatment of crystal arthropathy as the underlying metabolic disturbances may be quite specific.

Relation between the knee arthritis of CPPD crystal deposition disease and the osteoarthritis using X-ray findings and joint fluid analysis

Relation between the knee arthritis of CPPD crystal deposition disease and the osteoarthritis using X-ray findings and joint fluid analysis

AB0067 CHONDROCALCINOSIS IS ASSOCIATED WITH A SPECIFIC EFFECT ON THE CHONDROCYTE PHENOTYPE THAT MARKEDLY DIFFERS FROM OA

Background:Calcification of cartilage with BCP crystals is a common finding during osteoarthritis (OA) and is directly linked to the severity of the disease and hypertrophic differentiation of chondrocytes. Chondrocalcinosis (CC) is associated with CPPD crystal formation. There is only little knowledge about the effect of CPPD crystals on chondrocytes.Objectives:The aim of this study was to investigate the chondrocyte phenotype in CC cartilage and the effect of CPPD crystals on chondrocytes.Methods:Cartilage samples of patients with CC were used and compared with samples of severe OA patients without chondrocalcinosis and healthy cartilage samples served as control. Radiological presence of chondrocalcinosis was evaluated using standard X-ray pictures, as well as macroscopically inspection. The cartilage samples were stained using von Kossa/Safranin-orange staining. These stainings were used for OA severity scoring using the Chambers-Score. FTIR analyses was performed to distinguish CPPD and BCP crystals in cartilage. Chondrocyte differentiation markers were evaluated using Collagen 2 and X, as well as Sox9 and aggrecan as markers for chondrocyte hypertrophic differentiation in immunohistochemistry and qRT-PCR. TUNEL staining was performed to investigate cell death. In vivo results were validated using qRT-PCR for the expression of the respective genes after stimulation of C28 chondrocytes with CPPD and BCP crystals.Results:Radiologically detectable cartilage calcifications were evident in chondrocalcinosis patients, but absent in OA patients without CC. CPPD crystals were detected on the cartilage surface, whereas BCP crystals were detected in the pericellular matrix of hypertrophic chondrocytes. CC cartilage exhibited an increased collagen X expression compared to healthy cartilage, as well as to severe OA cartilage containing BCP calcification. Interestingly, aggrecan and collagen 2 were not reduced in CC cartilage, but markedly reduced in OA cartilage. TUNEL positive cells were significantly increased in CPPD cartilage compared to OA cartilage, although the histological OA severity was lower. qRT-PCR indicated no relevant influence of CPPD crystals on hypertrophic marker genes, whereas BCP crystals significantly induced hypertrophic differentiation.Conclusion:BCP and CPPD crystals seem to trigger differential effects on the chondrocyte phenotype. BCP crystals induce hypertrophic differentiation, which is not induced by CPPD crystals.Acknowledgments:The project was funded by theDeutsche Rheumastifung by the sponsor Dr. Sigrid Schuler.Disclosure of Interests:Franziska Meyer: None declared, Miriam Bollmann: None declared, Uwe Kornak: None declared, Jessica Bertrand Grant/research support from: Pfizer, Speakers bureau: Pfizer

Tendonitis of the ring finger with flexion contracture associated with CPPD crystal deposition disease; a case report

Tendonitis of the ring finger with flexion contracture associated with CPPD crystal deposition disease; a case report

AB0842 A Simple Method for the Microscopic Identification of Calcium Pyrophosphate Dihydrate and Hydroxyapatite Deposits in Metabolic and Crystal Induced Diseases

BackgroundArthropathy induced by calcium pyrophosphate dihydrate [Ca2P2O7.2H2O] (CPPD) crystals (chondrocalcinosis, pseudogout, pyrophosphate arthropathy) and arthropathy induced by hydroxyapatite [Ca5(PO4)3(OH)] (HA) crystals (apatite rheumatism) are separate entities.CPPD and HA crystals may...

AB0989 Relationship between calcium pyrophosphate dihydrate crystal and osteoarthritis of the knee

BackgroundCalcium pyrophosphate dihydrate (CPPD) is one of the common crystals that causes crystal induced arthritis. But the relation between CPPD crystal and osteoarthritis (OA) remains controversy1. Is the crystal directly...

The detection of calcium pyrophosphate crystals in the synovial fluid of patients with rheumatoid arthritis using the cytospin technique: prevalence and clinical correlation

There are only a few studies dealing with the detection and clinical impact of calcium pyrophosphate (CPPD) crystals in patients with rheumatoid arthritis (RA) published to date. In particular, data determined by the cytospin technique, which is an effective tool to enhance the crystal detection rate, are lacking. The objectives of this study were to determine the prevalence of CPPD crystals in the synovial fluid (SF) of patients with RA and to investigate whether the detection of CPPD crystals is correlated with demographic, clinical and serological features. We examined 113 consecutive SF samples of patients with RA, obtained from therapeutic arthrocentesis of knee joints. After cytocentrifugation, the sediments were examined by polarized microscopy for the occurrence of CPPD crystals. Demographic, clinical and serological data, acquired from the medical records, were compared between crystal-positive and crystal-negative subjects. CPPD crystals were observed in 20 of the 113 cases, representing 17.7 %. CPPD-positive and CPPD-negative subjects did not differ significantly in sex, duration of disease, Steinbrocker radiologic stage, disease activity score 28, as well as serum rheumatoid factor and anti-CCP positivity. Patients positively tested for CPPD crystals had a significantly higher age than CPPD-negative patients (p < 0.0001). An age-independent association of long-time treatment with diuretics and CPPD crystal formation was not found. In conclusion, demographic, clinical and serological characteristics of patients with RA were not associated with the occurrence of CPPD crystals. Age was the only significant influencing factor on CPPD crystal formation in patients with RA.

CPPD crystal deposition disease of the cervical spine: A common cause of acute neck pain encountered in the neurology department

BackgroundCalcium pyrophosphate dihydrate (CPPD) crystal deposition disease is one of the most common forms of crystal-associated arthropathy in the elderly. However, CPPD deposition on the cervical spine is less well known, and only a limited number of cases have been reported to date. Here, we report our recent clinical experience with CPPD crystal deposition disease of the cervical spine and describe the clinical features of this disease. MethodsFourteen patients with clinically diagnosed CPPD crystal deposition disease of the cervical spine at our department during the period from January 2005 to December 2008 were analyzed retrospectively. ResultsPatients ranged in age from 54 to 92 (mean±SD, 77.5±8.5). Chief symptoms of patients were acute posterior neck pain and fever. All patients had markedly restricted neck rotation. Serum CRP level was highly elevated in all patients (10.16±5.35mg/dL). Computed tomography of the cervical spine demonstrated linear calcific deposits in the transverse ligament of atlas (crowned dens syndrome) in all patients. Calcific deposits were also found in other periodontoid structures and the ligamenta flava in some patients. Posterior neck pain, fever, and increased serum inflammatory indicators were relieved within 1 to 3weeks by nonsteroidal antiinflammatory drugs (NSAIDs) or a combination of NSAIDs and prednisolone. Most of the patients were misdiagnosed as having other diseases before consultation. ConclusionsCPPD crystal deposition disease of the cervical spine is one of the most common underrecognized causes of acute neck pain in the neurology department, especially in elderly patients.

Dexamethasone Promotes Calcium Pyrophosphate Dihydrate Crystal Formation by Articular Chondrocytes

Calcium pyrophosphate dihydrate (CPPD) crystals are commonly found in osteoarthritic joints and correlate with a poor prognosis. Intraarticular corticosteroids, such as dexamethasone (Dxm), are commonly used therapies for osteoarthritis with or without CPPD deposition. Dxm has variable effects in mineralization models. We investigated the effects of Dxm on CPPD crystal formation in a well established tissue culture model. Porcine articular chondrocytes were incubated with ATP to generate CPPD crystals. Chondrocytes incubated with or without ATP were exposed to 1-100 nM Dxm in the presence of 45Ca. Mineralization was measured by 45Ca uptake in the cell layer. We also investigated the effect of Dxm on mineralization-regulating enzymes such as alkaline phosphatase, nucleoside triphosphate pyrophosphohydrolase (NTPPPH), and transglutaminase. Dxm significantly increased ATP-induced mineralization by articular chondrocytes. While alkaline phosphatase and NTPPPH activities were unchanged by Dxm, transglutaminase activity increased in a dose-responsive manner. Levels of Factor XIIIA mRNA and protein were increased by Dxm, while type II Tgase protein was unchanged. Transglutaminase inhibitors suppressed Dxminduced increases in CPPD crystal formation. These findings suggest a potential for Dxm to contribute to pathologic mineralization in cartilage and reinforce a central role for the transglutaminase enzymes in CPPD crystal formation.

Genetic factors in the pathogenesis of CPPD crystal deposition disease

Crystal deposition is a very complex process ruled by numerous factors. A small but important proportion of cases of chondrocalcinosis are monogenic, and many of the genes involved have been identified. These genetic findings strongly point to control of the level of extracellular inorganic pyrophosphate as the primary mechanism for their association with either calcium pyrophosphate dihydrate or hydroxyapatite deposition. However, effects on extracellular inorganic pyrophosphate levels do not explain the mechanism of association in all of these monogenic diseases. Further, there are likely to be several as yet unidentified genes that are important in this common condition. This review highlights what genetic studies have demonstrated about the processes involved in these diverse but related disorders.

Tumoral calcium pyrophosphate dihydrate deposition disease of the ligamentum flavum.

Calcium pyrophosphate dihydrate (CPPD) deposition disease (CPPDD), also known as pseudogout, is rarely known to affect the spine. The purpose of this article is to report our experience with six cases involving massive focal deposition of CPPD crystals in the ligamentum flavum. Between January 1998 and June 2002, we treated six patients with CPPDD involving the ligamentum flavum of the cervical and thoracic spine. Their ages ranged from 45 to 70 years. There were five female patients and one male patient. The cervical spine was involved in two cases and the thoracic spine in four. All except one patient presented with an insidious onset of myelopathy. The remaining patient presented with paraplegia after trauma. None of the patients exhibited any systemic features of CPPDD or other metabolic conditions that can lead to CPPD deposition. Plain x-rays often yielded inconclusive results. Computed tomography and magnetic resonance imaging were useful in confirming the diagnoses. Decompressive laminectomy, with removal of the ossified ligamenta flava, was performed for all patients. Polarized-light microscopic examinations of the excised ligamenta flava revealed the characteristic rod-shaped, birefringent crystals. Five of the six patients experienced significant improvements in their myelopathic symptoms after surgery. The remaining patient experienced improvements in sensations but no appreciable improvement in motor power. During the follow-up periods, which ranged from 7 months to 3 years, none of the patients presented with a recurrence of CPPD crystal deposition at the previously treated level. However, one patient who exhibited improvement after surgery presented 2 years later with a recurrence of myelopathic features attributable to ossification of the ligamentum flavum at a new level. Tumoral CPPDD of the ligamentum flavum is rare. It commonly occurs among middle-age or elderly female patients and presents with progressive myelopathy. Computed tomography and magnetic resonance imaging are complementary in the diagnosis of this condition. Surgery, if performed early, leads to good improvement. However, long-term follow-up monitoring of these patients is necessary, because surgery provides only symptomatic relief and does not treat the underlying disease. With the increasing availability of magnetic resonance imaging, ossification of the ligamentum flavum is being more frequently recognized. In every case of ossified ligamentum flavum, the excised specimen should be examined with polarized-light microscopy. We think that this simple, inexpensive method will lead to the recognition of more cases of spinal CPPDD.

Local deposition of calcium pyrophosphate crystals in evolution of knee osteoarthritis.

The aim of the study was to investigate the frequency of development of local calcium pyrophosphate (CPPD) crystal deposition in patients with knee OA initially found negative for these crystals, as well as to discover whether prognostic indicators for this subset of patients can be found. A clinical follow-up of records of outpatients with idiopathic knee OA was established. An anteroposterior plain radiography of the knee joints was made initially and at the end of the observation period. The follow-up period needed to be more than 1 year. Patients were divided into two groups. The first included patients with knee OA who did not develop intra-articular CPPD crystal deposition during the observation period (OA group). The second included those patients whose X-rays or synovial fluid (SF) analysis in the follow-up showed these crystal deposits to be present (OA + CPPD group). There were 59 patients (42 women, 17 men) who met the selection criteria. During the observation period (8.1 + 7.4 years in the OA group, 10.4 +/- 6 years in the OA + CPPD group), intra-articular CPPD deposits were observed in 15 patients (25%): 10 on the X-rays, eight in the SF and three in both examinations. Age at diagnosis of OA and incidence of obesity were similar in both groups. There was a trend (P = 0.21) towards men developing intra-articular CPPD crystal deposits more frequently than women. OA in only one knee joint was significantly more frequent in the group with CPPD (P<0.01). Of those with CPPD deposits 40% required surgery at the end of the observation period, compared to 27.2% of those without deposits (P = 0.27). The waiting period before knee surgery was shorter in the OA + CPPD group but the difference was not statistically significant. In conclusion, local CPPD crystal deposition was observed in 25% of cases during the evolution of knee OA. No predictive factors were found. OA of the knee could, per se, favour the development of CPPD deposits. The occurrence of intra-articular CPPD deposits seemed to be related to a more rapid and severe evolution of OA of the knee.

Selective inhibition of protein kinase C, mitogen-activated protein kinase, and neutrophil activation in response to calcium pyrophosphate dihydrate crystals, formyl-methionyl-leucyl-phenylalanine, and phorbol ester by O-(chloroacetyl-carbamoyl) fumagillol (AGM-1470; TNP-470)

The effect of O-(chloroacetyl-carbamoyl) fumagillol (AGM-1470; TNP-470) was investigated on protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activation in neutrophils stimulated by plasma-opsonized crystals of calcium pyrophosphate dihydrate (triclinic) [CPPD(T)], formyl-Met-Leu-Phe (fMLP), and phorbol 12-myristate 13-acetate (PMA). Neutrophil respiratory burst responses also were determined in AGM-1470-pretreated cells stimulated with the same agonists, using chemiluminescence and superoxide anion generation assays. AGM-1470 (5 μM) effectively inhibited PKC activation in cells treated with CPPD(T) crystals (50 mg/mL, 2 min) and fMLP (1 μM, 1 min), but had no effect on PMA-treated cells (0.5 μM, 5 min). AGM-1470 blocked MAPK activity completely and reduced neutrophil activation induced by fMLP and PMA but not by CPPD(T). The degree of inhibition of the respiratory burst plateaued at approximately 46 ± 9 and 54 ± 3% in fMLP- and PMA-treated cells, respectively. These data indicate that activation of neutrophil respiratory burst activity may be mediated through the MAPK pathway. AGM-1470 pretreatment did not inhibit CPPD(T) crystal- or fMLP-stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity. These findings, coupled with further observations that the PI 3-kinase inhibitor wortmannin (10 nM) inhibited fMLP- and CPPD(T) crystal-induced but not PMA-induced chemiluminescence, indicate that at least two distinct signaling pathways (mediated by PI 3-kinase or MAPK) lead to neutrophil respiratory burst responses. PKC may also be required in the MAPK-stimulated pathway. We propose that the inhibitory effect of AGM-1470 on the neutrophil respiratory burst may be due to its ability to inhibit PKC and MAPK activation.

Molecular modeling of inhibition of crystals of calcium pyrophosphate dihydrate by phosphocitrate

Crystalline calcium pyrophosphate dihydrate crystals occur frequently in degenerative joints diseases, causing acute attacks of pseudogout. These crystals appear in cartilage and can engender enzymatic damage to cartilage matrix. Currently no reliable method exists to prevent calcium pyrophosphate dihydrate deposition. In this study we investigate the role that phosphocitrate, a naturally occurring compound, may play in preventing calcium phosphate precipitation in cells or cellular compartments. Based on the experimental evidence that phosphocitrate blocks ATP-induced CPPD crystal growth in both articular cartilage vesicles and cartilage explants, we use molecular modeling to analyze how the inhibitory activity of phosphocitrate results from the stereospecific interaction between phosphocitrate and the specific faces of calcium pyrophosphate dihydrate crystal. Our molecular modeling binding studies indicate that phosphocitrate ion is able to bind to (010), (011), (100), (001), (01−1), and (1−10) faces of CPPD crystal with the strongest binding energies obtained for the high calcium density planes (010) and (011). We propose that the binding of phosphocitrate to specific faces of CPPD induces morphological changes that may lead to diminished crystal growth or its total cessation.

Nitric oxide: A modulator of human neutrophil oxigenating activity

The effect of O-(chloroacetyl-carbamoyl) fumagillol (AGM-1470; TNP-470) was investigated on protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activation in neutrophils stimulated by plasma-opsonized crystals of calcium pyrophosphate dihydrate (triclinic) [CPPD(T)], formyl-Met-Leu-Phe (fMLP), and phorbol 12-myristate 13-acetate (PMA). Neutrophil respiratory burst responses also were determined in AGM-1470-pretreated cells stimulated with the same agonists, using chemiluminescence and superoxide anion generation assays. AGM-1470 (5 μM) effectively inhibited PKC activation in cells treated with CPPD(T) crystals (50 mg/mL, 2 min) and fMLP (1 μM, 1 min), but had no effect on PMA-treated cells (0.5 μM, 5 min). AGM-1470 blocked MAPK activity completely and reduced neutrophil activation induced by fMLP and PMA but not by CPPD(T). The degree of inhibition of the respiratory burst plateaued at approximately 46 ± 9 and 54 ± 3% in fMLP- and PMA-treated cells, respectively. These data indicate that activation of neutrophil respiratory burst activity may be mediated through the MAPK pathway. AGM-1470 pretreatment did not inhibit CPPD(T) crystal- or fMLP-stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity. These findings, coupled with further observations that the PI 3-kinase inhibitor wortmannin (10 nM) inhibited fMLP- and CPPD(T) crystal-induced but not PMA-induced chemiluminescence, indicate that at least two distinct signaling pathways (mediated by PI 3-kinase or MAPK) lead to neutrophil respiratory burst responses. PKC may also be required in the MAPK-stimulated pathway. We propose that the inhibitory effect of AGM-1470 on the neutrophil respiratory burst may be due to its ability to inhibit PKC and MAPK activation.

Myeloradiculopathy Secondary to Pseudogout in the Cervical Ligamentum Flavum: Case Report

Abstract A case of cervical myeloradiculopathy secondary to deposits of calcium pyrophosphate dihydrate (Ca2P2O7 2H2O) (CPPD) crystals in the degenerating ligamentum flavum, with marked granulomatous inflammation, is presented. This uncommon clinical presentation of pseudogout (CPPD deposition disease) was confirmed after surgical removal of a compressive cervical ligamentum flavum. The diagnosis of CPPD crystal deposition was determined by polarized light microscopy and energy-dispersive x-ray microanalysis in frozen sections of the biopsy specimen. A review of seven previously reported cases along with the present case failed to reveal trauma as a causative factor.

Crystal Identification in Human Synovial Fluids: Methods and Interpretation

Gout is largely solved, both from diagnostic and therapeutic standpoints. Acute gout is easily suppressed and joint destruction can be prevented and at least reversed by lowering the serum uric acid level with relatively safe and very effective drugs. But the arthritides associated with the calcium-containing crystals remain untreatable by other than symptomatic or surgical means. If we had a method or a drug to remove CPPD or BCP crystal deposits from joints, would it make any difference in the severity of the arthritis? Which of the paradigms shown in Figure 5 holds for these crystals? If joint damage directly follows crystal deposition as in gout, then crystal removal should prove prophylactic. The unusual pattern of joint degeneration associated with polyarticular CPPD crystal deposition and the initial appearance of CPPD crystals in radiographically normal cartilage favors this idea. But radiologic chondrocalcinosis appearing in knees subjected years before to meniscectomy but not in the contralateral knees suggests that crystal deposition, in these cases at least, is secondary to trauma or surgery. If degeneration of cartilage precedes crystal deposition, as it probably does in the case of BCP crystals, then crystal removal may not be particularly helpful. Dieppe and his colleagues proposed that the calcium crystals provide a positive feedback (amplification) loop. This represents the minimalistic view of their importance. The biologic consequences of the calcium crystal deposition diseases are now being explored at the molecular level. Much more data are needed before more than speculative answers to the questions posed here can be formulated. Calcium crystal deposition is more common in older persons. The degenerative and destructive arthropathies associated with them will predictably become increasingly common as our population ages.

Inorganic Pyrophosphate Metabolism in Arthritis

Once thought of as a biosynthetic waste product, over the last 2 decades PPi has become understood as an entity with a variety of biologic roles (see Table 1). Documented roles include participation in intracellular Ca++ traffic, mediation of nucleotide and iron transport, storage of molecules in cellular granules, modification of enzyme function, and modulation of mineralization. Much has been established regarding plasma, urine, and synovial fluid levels (see Fig. 1) and urinary excretion in health and disease. Derangements in intracellular PPi content of skin fibroblasts have been noted in patients with CPPD deposition arthropathy (see Table 2). Mechanisms by which elevated PPi concentration develops in synovial fluid from joints with CPPD deposition and related arthropathies have come under scrutiny. The chondrocyte is now recognized as the probable cellular source of intra-articular extracellular PPi (see Figs. 3 and 4). Special attention has been focused on two basic pathways by which chondrocytes could generate extracellular PPi (see Fig. 2). In the first mechanism, chondrocytes demonstrate a set of ectoenzymes which could work in concert to directly produce extracellular PPi. The second pathway involves the major reactions by which PPi is formed within the cell and how intracellular PPi thus formed could be transported into the extracellular space. Much future research is needed regarding these two pathways and their relative importance in the pathogenesis of CPPD crystal deposition and related arthropathies.

急速にこ関節破壊をきたしたＣｈｏｎｄｒｏｃａｌｃｉｎｏｓｉｓの１例

A case (73-year-old female) of chondrocalcinosis with destructive coxarthrosis was reported. The case had complained of slight pain in her left knee and severe pain in her hip for several months.X-ray findings of the left hip showed severe destructive changes of the femoral head and of the acetabulum with subluxation, and those of the left knee showed calcification of the meniscus. Laboratory data of the blood and urine were normal, but microscopic study on the joint fluid of the hip and of the knee revealed CPPD crystals through the compensated polarized light.Total hip replacement was carried out for the hip. Histological findings of the femoral head were almost the same as those of ordinary coxarthrosis. However, histological findings of the synovium showed many CPPD crystal depositions on the surface.