ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Pathogenesis and etiology of calcium pyrophosphate crystal deposition (CPPD) disease

Pathogenesis and etiology of calcium pyrophosphate crystal deposition (CPPD) disease
Literature review current through: May 2024.
This topic last updated: Nov 02, 2023.

INTRODUCTION — Precipitation of crystals of calcium pyrophosphate (CPP) in connective tissues may be asymptomatic or may be associated with several forms of acute and chronic arthritis. These disorders comprise the spectrum of calcium pyrophosphate crystal deposition (CPPD) disease [1].

The pathogenesis and etiology of CPPD disease will be reviewed here. The clinical manifestations, diagnosis, and treatment of this disorder are discussed separately. (See "Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease" and "Treatment of calcium pyrophosphate crystal deposition (CPPD) disease".)

TERMINOLOGY — Calcium pyrophosphate (CPP) crystals were formerly abbreviated and commonly referred to as "CPPD," but the abbreviation "CPPD" now typically refers to "CPP crystal deposition." Chondrocalcinosis refers to radiographic calcification in hyaline cartilage and/or fibrocartilage. It is commonly present in patients with CPPD disease; however, it is neither absolutely specific for CPPD disease nor universal among affected patients. Acute CPP crystal arthritis replaces the term "pseudogout" [2]. Additional information on terminology is presented elsewhere. (See "Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease", section on 'Terminology'.)

PATHOGENESIS

CPP crystal formation and deposition — Calcium pyrophosphate (CPP) crystal formation is initiated in the pericellular matrix near midzone chondrocytes in both hyaline cartilage and fibrocartilage [3,4]. While the factors that control CPP crystal formation are not fully delineated, high extracellular pyrophosphate levels in cartilage are necessary for CPP crystal formation. Thus, much of the research on the pathophysiology of this disease has focused on pyrophosphate metabolism. High local levels of calcium and alterations in extracellular cartilage matrix also likely contribute to calcium pyrophosphate crystal deposition (CPPD) disease but are less well understood.

Chondrocytes and pyrophosphate — Pyrophosphate is constitutively generated by chondrocytes. It is a potent inhibitor of basic calcium phosphate mineralization and therefore prevents mineralization in normal cartilage matrix. Factors that increase pyrophosphate levels in cartilage contribute to CPPD.

Most pyrophosphate in cartilage is generated from extracellular adenosine triphosphate (ATP) [5]. Several observations indicate that overactivity of one or more of a group of nucleoside triphosphate pyrophosphohydrolase (NTPPPH) enzymes contribute to this process [6-8]. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is thought to be the most important of the enzymes responsible for NTPPPH activity in cartilage [9-11]. Deficiencies of ENPP1 cause ectopic calcification in mice, supporting a role for ENPP1 in pyrophosphate production and a role of pyrophosphate in inhibiting basic calcium phosphate mineral formation [12].

Alkaline phosphatase is another key enzyme regulating pyrophosphate levels that is responsible for degrading pyrophosphate. Reduced levels of alkaline phosphatase activity, such as those seen with hypophosphatasia, contribute to CPPD disease in affected individuals [13].

ANKH protein and pyrophosphate — The ANKH protein is also implicated in CPPD. Deficiencies in ank, the murine analog of the ANKH protein in humans, result in reduced extracellular pyrophosphate levels and extensive peripheral and axial skeleton ankylosis with basic calcium phosphate-containing material [14]. The ank gene (ANKH) product is a transmembrane protein, strongly expressed in chondrocytes, which serves either as an ATP transporter or, more likely, a regulator of a channel transporting extracellular ATP [5,15]. Thus, conditions that enhance ANKH activity could promote CPP crystal formation [16,17].

A role for ANKH is further supported by the observation that ANKH mutations have been observed in five kindreds with familial CPPD disease [18-21]. In addition, mutations/polymorphisms in or just upstream of the chromosome 5p locus of ANKH have also been identified in some individuals with idiopathic or sporadic CPPD disease [19,22]. Of interest, one such ANKH variant, a -4bp G→A polymorphism in the 5' untranslated promoter region of ANKH, correlates with radiographic chondrocalcinosis that is independent of age or the presence of osteoarthritis (OA), the two most common risk factors for chondrocalcinosis [23].

High ANKH levels may also participate in sporadic CPPD disease. ANKH transcripts and ANKH protein levels are reported to be increased in surgical cartilage specimens from patients with sporadic CPPD when compared with control specimens from OA patients with no CPPD [24].

Other factors — Other factors have been implicated in CPP crystal formation, largely based upon in vitro studies. Cytokines and growth factors, such as transforming growth factor (TGF) beta, exert dramatic stimulatory effects on chondrocyte pyrophosphate production [25]. Small extracellular vesicles are elaborated by chondrocytes [10] and concentrate ENPP1 enzymes [11]. These vesicles generate CPP crystals in vitro when they are exposed to ATP and are hypothesized to act as foci of CPP crystal formation in the cartilage matrix. Extracellular matrix changes may also promote CPP crystal formation. For example, crosslinking of extracellular matrix proteins by transglutaminase enzymes [26] and increased levels of osteopontin [27] each increase CPP crystal formation in vitro.

Role of CPP crystals in disease — Definitive proof of a causal role of CPP crystals has not been fully established for the degenerative, noninflammatory manifestations of CPPD arthropathy. However, there is compelling evidence for a role of CPP crystals in acute and subacute joint inflammation. This is provided by the following observations:

There are striking similarities in the pathophysiologic mechanisms and clinical appearances of the monosodium urate crystal-induced gout flare and CPP crystal-induced arthritis [28]. Of particular note is the shared capacity of both crystal types to induce NACHT domain-, leucine-rich repeat-, and PYD-containing protein 3 (NLRP3)-dependent inflammasome assembly and activation in synovial mononuclear phagocytes and neutrophils. Activation of the NLRP3 inflammasome, in turn, activates latent caspase 1, resulting in interleukin 1 (IL-1) precursor processing and release of the proinflammatory cytokine IL-1-beta [29]. CPP crystals also induce neutrophil extracellular traps (NETs) that contribute to the inflammation seen in acute CPP crystal arthritis [30].

The biologic consequences of the interaction of CPP crystals with phagocytic cells (which include mitogenic activation and the release of proinflammatory cytokines) provide a potential basis for the more subacute inflammatory synovitis of CPPD arthropathy [28,31].

An etiologic or an amplifying role for CPP crystals in the destructive changes in OA appears highly likely. The degenerative arthritis accompanying CPPD disease frequently involves such joints as the metacarpophalangeal and wrist joints, which are commonly spared in classical OA [32], and chondrocalcinosis appears to be a primary determinant of the rate of radiographically determined joint deterioration in OA. Interestingly, CPP crystals may not be present early in the disease course of usual OA but appear to be secondarily associated with progression of the severity of the OA [33]. In a study of cadaveric knees from older adults (mean age of 78), the deposition of CPP crystals correlated with the degree and depth of cartilage degeneration [34].

CPP crystals also induce factors that promote osteoclastogenesis, providing an additional pathway for crystal-induced joint damage [35]. The observation that patients with OA and chondrocalcinosis in the knee have more pain than those with similar degrees of OA but without chondrocalcinosis also suggests a possible role of CPPD in OA pain [36].

Spontaneous resolution of acute attacks — Acute attacks of CPP crystal arthritis are typically self-limited. Although possible mechanisms for ameliorating inflammation due to CPP crystals have been suggested, a generally accepted explanation is lacking. Phagocytosis and dissolution of crystals may play a role, but observations in patients together with data from animal models indicate that inflammation can abate while crystals are still present in tissue or fluid.

Adhesion of components of extracellular fluid or plasma to crystals may decrease their inflammatory potential. As an example, addition of lipoproteins to CPP crystals reduces their ability to provoke neutrophil phagocytosis and cell lysis in vitro [37]. In an experimental model, the local low-density lipoprotein (LDL) concentration rose within hours after instillation of CPP crystals in association with decreasing inflammation [38]. IL-1-beta receptor antagonists and the formation of extensive NETs may also sequester inflammatory mediators and eventually quell the inflammatory response [39].

ETIOLOGY AND DISEASE ASSOCIATIONS — In most patients, calcium pyrophosphate crystal deposition (CPPD) disease is idiopathic, but joint trauma, familial chondrocalcinosis, and a variety of metabolic and endocrine disorders (table 1) are associated with or may cause the illness, especially among younger patients, who are less often affected by sporadic CPPD disease than older adults [40] (see "Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease", section on 'Post-diagnostic evaluation for associated diseases'):

Hemochromatosis – Hemochromatosis is clearly associated with the full spectrum of calcium pyrophosphate (CPP) crystal-related joint disease, including acute CPP crystal arthritis, chondrocalcinosis, and chronic inflammatory and degenerative arthritis, as was shown in a detailed literature review of reports of disorders with proposed associations with CPPD disease [40]. A subsequent larger study has also supported the validity of this association [41]. (See "Clinical manifestations and diagnosis of hereditary hemochromatosis" and "Arthritis and bone disease associated with hereditary hemochromatosis".)

Hyperparathyroidism – The association between hyperparathyroidism and CPPD disease has been described in multiple case reports and is now established in epidemiologic studies. In the United States veteran population, for example, hyperparathyroidism was strongly associated with CPPD disease with an odds ratio of 3.35 (95% CI 2.96-3.79) compared with age- and sex-matched controls [41]. (See "Primary hyperparathyroidism: Clinical manifestations" and "Primary hyperparathyroidism: Clinical manifestations", section on 'Rheumatologic conditions'.)

Flares of acute CPP crystal arthritis following parathyroidectomy for hyperparathyroidism have been observed [42]; these episodes may be related to abrupt reduction in serum calcium and magnesium levels during postoperative hypoparathyroidism (see "Hungry bone syndrome following parathyroidectomy in patients with end-stage kidney disease"). Such reduction may cause partial dissolution of crystals with subsequent release from the cartilage matrix into the joint fluid, allowing phagocytosis and the phlogistic response of inflammatory cells.

Gout – Gout is also clearly associated with CPPD disease. The coexistence of both monosodium urate and CPP crystals occurs in approximately 5 percent of patients with gout [43]. (See "Clinical manifestations and diagnosis of gout".)

Hypomagnesemia – Hypomagnesemia has been associated with CPPD disease [41,44]. Hypomagnesemia was a weak risk factor for CPPD disease in the United States veteran population study [41] but was strongly associated with CPPD disease in a study of patients with short bowel syndrome [44]. Gitelman syndrome, an inherited renal tubular disorder resulting in hypokalemia and hypomagnesemia, has also been associated with both chondrocalcinosis and acute CPP crystal arthritis [45,46]. (See "Hypomagnesemia: Causes of hypomagnesemia" and "Hypomagnesemia: Evaluation and treatment" and "Chronic complications of the short bowel syndrome in adults" and "Inherited hypokalemic salt-losing tubulopathies: Pathophysiology and overview of clinical manifestations".)

Hypophosphatasia – The association of hypophosphatasia with CPPD disease is largely based upon case reports, as the relative rarity of hypophosphatasia has precluded its inclusion in large studies [40]. (See "Epidemiology and etiology of osteomalacia", section on 'Hypophosphatasia'.)

Joint trauma – Joint trauma (including prior joint surgery) is a demonstrated risk factor for the development of subsequent CPPD disease. As a result, a history of trauma should be sought in younger patients in whom clinical or radiographic evidence of CPPD disease is found. This is particularly true of CPPD noted in the meniscus after meniscal tears [47,48].

Familial CPPD disease – Familial CPPD disease typically has an autosomal dominant inheritance. Clinical manifestations include more severe and widespread arthritis earlier in life than is commonly observed in the typical patient with CPPD disease [1]. (See "Pathogenesis of osteoarthritis", section on 'Aging'.)

Mutations that cause familial CPPD disease cluster in two loci, CCAL1 on 8q and CCAL2 on 5p. The TNFRSF11B gene, which codes for osteoprotegerin [49], represents the 8q cluster of mutations that comprise CCAL1 [50]. Initial studies suggest that bone may be the target tissue in patients with this mutation, but further work is needed to define the mechanisms through which osteoprotegerin contributes to CPPD disease [50,51]. The 5p cluster is thought to be related to a mutant form of the human homolog of the ank gene (ANKH) on 5p, which encodes a transmembrane protein that is clearly involved in pyrophosphate regulation [18-21]. (See 'ANKH protein and pyrophosphate' above.)

Patients with ANKH mutations often demonstrate chondrocalcinosis prior to joint degeneration, while patients with osteoprotegerin mutations have simultaneous onset of CPPD disease and severe joint degeneration [50]. The frequency of these associations is unknown.

Other associated disorders and precipitating factors – Other conditions that may be associated with CPPD disease include:

X-linked hypophosphatemic rickets and familial hypocalciuric hypercalcemia – X-linked hypophosphatemic rickets and familial hypocalciuric hypercalcemia are probably associated with CPPD disease, but the relationship is less clearly demonstrable in these very rare disorders. (See "Hereditary hypophosphatemic rickets and tumor-induced osteomalacia" and "Disorders of the calcium-sensing receptor: Familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia".)

Osteopenia – An increased frequency of osteopenia has been demonstrated in patients with CPPD disease in the United Kingdom [52], and subsequently this was also noted in the United States veteran study [41].

Acromegaly, Wilson disease, and ochronosis – Patients with chondrocalcinosis or CPPD disease in association with acromegaly, Wilson disease, and ochronosis have been reported [40], but it has been challenging to confirm these associations in population-based studies due to the rarity of these conditions. (See "Rheumatologic manifestations of acromegaly" and "Wilson disease: Clinical manifestations, diagnosis, and natural history" and "Disorders of tyrosine metabolism", section on 'Alkaptonuria'.)

Bisphosphonate administration – Administration of oral bisphosphonates may precipitate attacks of acute CPP crystal arthritis. This was shown in a study from England that found a small increased risk of acute CPP crystal arthritis in patients who had recently received bisphosphonates (incidence rate ratio [IRR] 1.33, 95% CI 1.05-1.69) [53].

Other drug associations – Some [54,55], but not all [41], studies have suggested a potential association between diuretics and CPPD. In addition, use of proton pump inhibitors and H2 blockers may be more frequent among patients with CPPD disease than in age-matched controls [55,56]. While hypomagnesemia is often invoked as a potential mechanism for all of these drugs, these findings remain inconsistent and warrant further investigation.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Calcium pyrophosphate deposition disease (The Basics)")

Beyond the Basics topics (see "Patient education: Calcium pyrophosphate crystal deposition (CPPD) disease (Beyond the Basics)")

SUMMARY

Calcium pyrophosphate (CPP) crystal formation and deposition – Calcium pyrophosphate (CPP) crystal formation is initiated in cartilage located near the surface of chondrocytes. The disorder is generally thought to be associated with excessive cartilage pyrophosphate production, leading to local CPP supersaturation and CPP crystal formation or deposition, although aberrations in both mineral and organic phase metabolism are probably variably involved in calcium pyrophosphate crystal deposition (CPPD) disease. (See 'Pathogenesis' above.)

Role of CPP crystals in disease – There is compelling evidence for a role of the CPP crystal in acute and subacute joint inflammation, although a definitive causal role of CPPD disease in all of the clinical manifestations with which deposition is associated, particularly the noninflammatory changes, has not been established. The typically self-limited nature of acute attacks of CPP crystal arthritis is not well understood. (See 'Role of CPP crystals in disease' above and 'Spontaneous resolution of acute attacks' above.)

Etiology and disease associations – Most cases of CPPD disease are idiopathic, but joint trauma, including prior joint surgery; familial CPPD disease; and a variety of metabolic and endocrine disorders, including hemochromatosis and hyperparathyroidism, are associated with or may cause the illness, particularly among younger patients (table 1). (See 'Etiology and disease associations' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Lawrence Ryan, MD, and Michael A Becker, MD, who contributed to an earlier version of this topic review.

  1. Rosenthal AK, Ryan LM. Calcium Pyrophosphate Deposition Disease. N Engl J Med 2016; 374:2575.
  2. Zhang W, Doherty M, Bardin T, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis 2011; 70:563.
  3. Masuda I, Ishikawa K, Usuku G. A histologic and immunohistochemical study of calcium pyrophosphate dihydrate crystal deposition disease. Clin Orthop Relat Res 1991; :272.
  4. Reginato AJ, Schumacher HR, Martinez VA. The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study. Arthritis Rheum 1974; 17:977.
  5. Rosenthal AK, Gohr CM, Mitton-Fitzgerald E, et al. The progressive ankylosis gene product ANK regulates extracellular ATP levels in primary articular chondrocytes. Arthritis Res Ther 2013; 15:R154.
  6. Rachow JW, Ryan LM. Adenosine triphosphate pyrophosphohydrolase and neutral inorganic pyrophosphatase in pathologic joint fluids. Elevated pyrophosphohydrolase in calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum 1985; 28:1283.
  7. Tenenbaum J, Muniz O, Schumacher HR, et al. Comparison of phosphohydrolase activities from articular cartilage in calcium pyrophosphate deposition disease and primary osteoarthritis. Arthritis Rheum 1981; 24:492.
  8. Ryan LM, Wortmann RL, Karas B, McCarty DJ Jr. Cartilage nucleoside triphosphate (NTP) pyrophosphohydrolase. I. Identification as an ecto-enzyme. Arthritis Rheum 1984; 27:404.
  9. Siegel SA, Hummel CF, Carty RP. The role of nucleoside triphosphate pyrophosphohydrolase in in vitro nucleoside triphosphate-dependent matrix vesicle calcification. J Biol Chem 1983; 258:8601.
  10. Derfus BA, Rachow JW, Mandel NS, et al. Articular cartilage vesicles generate calcium pyrophosphate dihydrate-like crystals in vitro. Arthritis Rheum 1992; 35:231.
  11. Johnson K, Pritzker K, Goding J, Terkeltaub R. The nucleoside triphosphate pyrophosphohydrolase isozyme PC-1 directly promotes cartilage calcification through chondrocyte apoptosis and increased calcium precipitation by mineralizing vesicles. J Rheumatol 2001; 28:2681.
  12. Okawa A, Nakamura I, Goto S, et al. Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nat Genet 1998; 19:271.
  13. Whyte MP, Murphy WA, Fallon MD. Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred. Am J Med 1982; 72:631.
  14. Ho AM, Johnson MD, Kingsley DM. Role of the mouse ank gene in control of tissue calcification and arthritis. Science 2000; 289:265.
  15. Szeri F, Lundkvist S, Donnelly S, et al. The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP. PLoS Genet 2020; 16:e1008884.
  16. Xu H, Zhang X, Wang H, et al. Continuous cyclic mechanical tension increases ank expression in endplate chondrocytes through the TGF-β1 and p38 pathway. Eur J Histochem 2013; 57:e28.
  17. Skubutyte R, Markova D, Freeman TA, et al. Hypoxia-inducible factor regulation of ANK expression in nucleus pulposus cells: possible implications in controlling dystrophic mineralization in the intervertebral disc. Arthritis Rheum 2010; 62:2707.
  18. Williams CJ, Zhang Y, Timms A, et al. Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH. Am J Hum Genet 2002; 71:985.
  19. Pendleton A, Johnson MD, Hughes A, et al. Mutations in ANKH cause chondrocalcinosis. Am J Hum Genet 2002; 71:933.
  20. Hughes AE, McGibbon D, Woodward E, et al. Localisation of a gene for chondrocalcinosis to chromosome 5p. Hum Mol Genet 1995; 4:1225.
  21. Andrew LJ, Brancolini V, de la Pena LS, et al. Refinement of the chromosome 5p locus for familial calcium pyrophosphate dihydrate deposition disease. Am J Hum Genet 1999; 64:136.
  22. Zhang Y, Johnson K, Russell RG, et al. Association of sporadic chondrocalcinosis with a -4-basepair G-to-A transition in the 5'-untranslated region of ANKH that promotes enhanced expression of ANKH protein and excess generation of extracellular inorganic pyrophosphate. Arthritis Rheum 2005; 52:1110.
  23. Abhishek A, Doherty S, Maciewicz R, et al. The association between ANKH promoter polymorphism and chondrocalcinosis is independent of age and osteoarthritis: results of a case-control study. Arthritis Res Ther 2014; 16:R25.
  24. Uzuki M, Sawai T, Ryan LM, et al. Upregulation of ANK protein expression in joint tissue in calcium pyrophosphate dihydrate crystal deposition disease. J Rheumatol 2014; 41:65.
  25. Rosenthal AK, Cheung HS, Ryan LM. Transforming growth factor beta 1 stimulates inorganic pyrophosphate elaboration by porcine cartilage. Arthritis Rheum 1991; 34:904.
  26. Rosenthal AK, Derfus BA, Henry LA. Transglutaminase activity in aging articular chondrocytes and articular cartilage vesicles. Arthritis Rheum 1997; 40:966.
  27. Rosenthal AK, Gohr CM, Uzuki M, Masuda I. Osteopontin promotes pathologic mineralization in articular cartilage. Matrix Biol 2007; 26:96.
  28. Dalbeth N, Haskard DO. Pathophysiology of crystal-induced arthritis. In: Crystal-Induced Arthropathies: Gout, Pseudogout, and Apatite-Associated Syndromes, Wortmann RL, Schumacher HR Jr, Becker MA, Ryan LM (Eds), Taylor & Francis Group, 2006. p.239.
  29. Martinon F, Pétrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440:237.
  30. Pang L, Hayes CP, Buac K, et al. Pseudogout-associated inflammatory calcium pyrophosphate dihydrate microcrystals induce formation of neutrophil extracellular traps. J Immunol 2013; 190:6488.
  31. Cheung HS, Story MT, McCarty DJ. Mitogenic effects of hydroxyapatite and calcium pyrophosphate dihydrate crystals on cultured mammalian cells. Arthritis Rheum 1984; 27:668.
  32. Wilkins E, Dieppe P, Maddison P, Evison G. Osteoarthritis and articular chondrocalcinosis in the elderly. Ann Rheum Dis 1983; 42:280.
  33. Nalbant S, Martinez JA, Kitumnuaypong T, et al. Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies. Osteoarthritis Cartilage 2003; 11:50.
  34. Ryu K, Iriuchishima T, Oshida M, et al. The prevalence of and factors related to calcium pyrophosphate dihydrate crystal deposition in the knee joint. Osteoarthritis Cartilage 2014; 22:975.
  35. Chang CC, Tsai YH, Liu Y, et al. Calcium-containing crystals enhance receptor activator of nuclear factor κB ligand/macrophage colony-stimulating factor-mediated osteoclastogenesis via extracellular-signal-regulated kinase and p38 pathways. Rheumatology (Oxford) 2015; 54:1913.
  36. Han BK, Kim W, Niu J, et al. Association of Chondrocalcinosis in Knee Joints With Pain and Synovitis: Data From the Osteoarthritis Initiative. Arthritis Care Res (Hoboken) 2017; 69:1651.
  37. Burt HM, Jackson JK, Rowell J. Calcium pyrophosphate and monosodium urate crystal interactions with neutrophils: effect of crystal size and lipoprotein binding to crystals. J Rheumatol 1989; 16:809.
  38. Kumagai Y, Watanabe W, Kobayashi A, et al. Inhibitory effect of low density lipoprotein on the inflammation-inducing activity of calcium pyrophosphate dihydrate crystals. J Rheumatol 2001; 28:2674.
  39. Schauer C, Janko C, Munoz LE, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med 2014; 20:511.
  40. Jones AC, Chuck AJ, Arie EA, et al. Diseases associated with calcium pyrophosphate deposition disease. Semin Arthritis Rheum 1992; 22:188.
  41. Kleiber Balderrama C, Rosenthal AK, Lans D, et al. Calcium Pyrophosphate Deposition Disease and Associated Medical Comorbidities: A National Cross-Sectional Study of US Veterans. Arthritis Care Res (Hoboken) 2017; 69:1400.
  42. Bilezikian JP, Connor TB, Aptekar R, et al. Pseudogout after parathyroidectomy. Lancet 1973; 1:445.
  43. Jaccard YB, Gerster JC, Calame L. Mixed monosodium urate and calcium pyrophosphate crystal-induced arthropathy. A review of seventeen cases. Rev Rhum Engl Ed 1996; 63:331.
  44. Richette P, Ayoub G, Bardin T, et al. Hypomagnesemia and chondrocalcinosis in short bowel syndrome. J Rheumatol 2005; 32:2434.
  45. Punzi L, Calò L, Schiavon F, et al. Chondrocalcinosis is a feature of Gitelman's variant of Bartter's syndrome. A new look at the hypomagnesemia associated with calcium pyrophosphate dihydrate crystal deposition disease. Rev Rhum Engl Ed 1998; 65:571.
  46. Cobeta-Garcia JC, Gascón A, Iglesias E, Estopiñán V. Chondrocalcinosis and Gitelman's syndrome. A new association? Ann Rheum Dis 1998; 57:748.
  47. Doherty M, Watt I, Dieppe PA. Localised chondrocalcinosis in post-meniscectomy knees. Lancet 1982; 1:1207.
  48. Lindén B, Nilsson BE. Chondrocalcinosis following osteochondritis dissecans in the femur condyles. Clin Orthop Relat Res 1978; :223.
  49. Ramos YF, Bos SD, van der Breggen R, et al. A gain of function mutation in TNFRSF11B encoding osteoprotegerin causes osteoarthritis with chondrocalcinosis. Ann Rheum Dis 2015; 74:1756.
  50. Williams CJ, Qazi U, Bernstein M, et al. Mutations in osteoprotegerin account for the CCAL1 locus in calcium pyrophosphate deposition disease. Osteoarthritis Cartilage 2018; 26:797.
  51. Mitton-Fitzgerald E, Gohr CM, Williams CJ, et al. Effects of the TNFRSF11B Mutation Associated With Calcium Pyrophosphate Deposition Disease in Osteoclastogenesis in a Murine Model. Arthritis Rheumatol 2021; 73:1543.
  52. Abhishek A, Doherty S, Maciewicz R, et al. Association between low cortical bone mineral density, soft-tissue calcification, vascular calcification and chondrocalcinosis: a case-control study. Ann Rheum Dis 2014; 73:1997.
  53. Roddy E, Muller S, Paskins Z, et al. Incident acute pseudogout and prior bisphosphonate use: Matched case-control study in the UK-Clinical Practice Research Datalink. Medicine (Baltimore) 2017; 96:e6177.
  54. Rho YH, Zhu Y, Zhang Y, et al. Risk factors for pseudogout in the general population. Rheumatology (Oxford) 2012; 51:2070.
  55. Felson DT, Rabasa G, Chen X, et al. The association of diuretics and proton pump inhibitors with chondrocalcinosis. ACR Open Rheumatol 2021; 3:390.
  56. Liew JW, Peloquin C, Tedeschi SK, et al. Proton-Pump Inhibitors and Risk of Calcium Pyrophosphate Deposition in a Population-Based Study. Arthritis Care Res (Hoboken) 2022; 74:2059.
Topic 1665 Version 28.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟