Calcium-Containing Crystal-Associated Arthropathies in the Elderly Population

  • Elisabeth B. Matson
  • Anthony M. ReginatoEmail author


Crystal arthropathies commonly affect the elderly people and have been associated with the development of osteoarthritis. This chapter will detail the clinical features of and treatment for calcium pyrophosphate deposition disease and other forms of calcium-containing crystal-associated arthropathies.


Calcium pyrophosphate dihydrate Basic calcium phosphate Hydroxyapatite Calcium oxalate Steroid crystals Osteoarthritis Musculoskeletal ultrasound Aging 


  1. 1.
    Ellman MH, Brown NL, Levin B. Prevalence of knee chondrocalcinosis in hospital and clinic patients aged 50 or older. J Am Geriatr Soc. 1981;29:189–92.PubMedGoogle Scholar
  2. 2.
    Memin Y, Monville C, Ryckewaert A. Articular chondrocalcinosis after 80 years of age. Rev Rhum Mal Osteoartic. 1978;45: 77–82.PubMedGoogle Scholar
  3. 3.
    Wilkins E, Dieppe P, Maddison P, Evison G. Osteoarthritis and articular chondrocalcinosis in the elderly. Ann Rheum Dis. 1983;42:280–4.PubMedCrossRefGoogle Scholar
  4. 4.
    O’Duffy JD. Clinical studies of acute pseudogout attacks: comments on prevalence, predispositions, and treatment. Arthritis Rheum. 1976;19 Suppl 3:349–52.PubMedCrossRefGoogle Scholar
  5. 5.
    Richette P, Bardin T, Doherty M. An update on the epidemiology of calcium pyrophosphate dihydrate crystal deposition disease. Rheumatology (Oxford). 2009;48:711–5.CrossRefGoogle Scholar
  6. 6.
    Felson DT, Anderson JJ, Naimark A, Kannel W, Meenan F. The prevalence of chondrocalcinosis in the elderly and its association with knee osteoarthritis: the Framingham Study. J Rheumatol. 1989;16:1241–5.PubMedGoogle Scholar
  7. 7.
    Neame RL, Carr AJ, Muir K, Doherty M. UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte. Ann Rheum Dis. 2003;62:513–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Terkeltaub R. Diseases associated with articular deposition of calcium pyrophosphate dihydrate and basic calcium phosphate crystals. In: Harris ED, Budd RC, Firestein GS, Sergent JS, Ruddy S, Sledge CB, editors. Kelly’s textbook of rheumatology. 7th ed. Philadelphia: Elsevier & Launders; 2005. p. 1430.Google Scholar
  9. 9.
    Dieppe PA, Alexander GJ, Jones HE, Doherty M, Scott DG, Manhire A, et al. Pyrophosphate arthropathy: a clinical and radiological study of 105 cases. Ann Rheum Dis. 1982;41:371–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Ivorra J, Rosas J, Pascual E. Most calcium pyrophosphate crystals appear as non-birefringent. Ann Rheum Dis. 1999;58:582–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58:26–35.PubMedCrossRefGoogle Scholar
  12. 12.
    Bong D, Bennett R. Pseudogout mimicking systemic disease. JAMA. 1981;246:1438–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Pego-Reigosa J, Rodriguez-Rodriguez M, Hurtado-Hernandez Z, et al. Calcium pyrophosphate deposition disease mimicking polymyalgia rheumatica: a prospective followup study of predictive factors for this condition in patients presenting with polymyalgia symptoms. Arthritis Rheum. 2005;53:931–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Bouvet JP, le Parc JM, Michalski B, Benlahrache C, Auquier L. Acute neck pain due to calcifications surrounding the odontoid process: the crowned dens syndrome. Arthritis Rheum. 1985;28:1417–20.PubMedCrossRefGoogle Scholar
  15. 15.
    Salaffi F, Carotti M, Guglielmi G, Passarini G, Grassi W. The crowned dens syndrome as a cause of neck pain: clinical and computed tomography study in patients with calcium pyrophosphate dihydrate deposition disease. Clin Exp Rheumatol. 2008;26:1040–6.PubMedGoogle Scholar
  16. 16.
    Muthukumar N, Karuppaswamy U. Tumoral calcium pyrophosphate dihydrate deposition disease of the ligamentum flavum. Neurosurgery. 2003;53:103–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Armas JB, Couto AR, Bettencourt BF. Spondyloarthritis, diffuse idiopathic skeletal hyperostosis (DISH) and chondrocalcinosis. Adv Exp Med Biol. 2009;649:37–56.PubMedCrossRefGoogle Scholar
  18. 18.
    Jones AC, Chuck AJ, Arie EA, Green DJ, Doherty M. Diseases associated with calcium pyrophosphate deposition disease. Semin Arhritis Rheum. 1992;22:188–202.CrossRefGoogle Scholar
  19. 19.
    Zhang Y, Brown MA. Genetic studies of chondrocalcinosis. Curr Opin Rheumatol. 2005;17:330–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Gerster JC, Lagier R, Boivin G. Olecranon bursitis related to calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum. 1982;25:989–96.PubMedCrossRefGoogle Scholar
  21. 21.
    Gerster JC, Lagier R, Boivin G, Schneider C. Carpal tunnel syndrome in chondrocalcinosis of the wrist. Clinical and histologic study. Arthritis Rheum. 1980;23:926–31.PubMedCrossRefGoogle Scholar
  22. 22.
    Gerster JC, Lagier R, Boivin G. Achilles tendinitis associated with chondrocalcinosis. J Rheumatol. 1980;7:82–8.PubMedGoogle Scholar
  23. 23.
    Derfus BA, Kurian JB, Butler JJ, et al. The high prevalence of pathologic calcium crystals in pre-operative knees. J Rheumatol. 2002;29:570–4.PubMedGoogle Scholar
  24. 24.
    Nalbant S, Martinez JA, Kitumnuaypong T, Clayburne G, Sieck M, Schumacher Jr HR. Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies. Osteoarthritis Cartilage. 2003;11:50–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Viriyavejkul P, Wilairatana V, Tanavalee A, Jaovisidha K. Comparison of characteristics of patients with and without calcium pyrophosphate dihydrate crystal deposition disease who underwent total knee replacement surgery for osteoarthritis. Osteoarthritis Cartilage. 2007;15:232–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Neame RL, Carr AJ, Muir K, Doherty M. Relative risk of knee chondrocalcinosis in siblings of index cases with pyrophosphate arthropathy. Ann Rheum Dis. 2003;62:513–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Nagaosa Y, Lanyon P, Doherty M. Characterisation of size and direction of osteophyte in knee osteoarthritis: a radiographic study. Ann Rheum Dis. 2002;61:319–24.PubMedCrossRefGoogle Scholar
  28. 28.
    Neogi T, Nevitt M, Niu J, LaValley MP, Hunter DJ, Terkeltaub R, et al. Lack of association between chondrocalcinosis and increased risk of cartilage loss in knees with osteoarthritis: results of two prospective longitudinal magnetic resonance imaging studies. Arthritis Rheum. 2006;54:1822–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Sokoloff L, Varma AA. Chondrocalcinosis in surgically resected joints. Arthritis Rheum. 1988;31:750–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Muehleman C, Li J, Aigner T, et al. Association between crystals and cartilage degeneration in the ankle. J Rheumatol. 2008;35:1108–17.PubMedGoogle Scholar
  31. 31.
    Molloy ES, McCarthy GM. Calcium crystal deposition diseases: update on pathogenesis and manifestations. Rheum Dis Clin North Am. 2006;32:383–400.PubMedCrossRefGoogle Scholar
  32. 32.
    Rosenthal AK. Calcium crystal deposition and osteoarthritis. Rheum Dis Clin North Am. 2006;32:401–12.PubMedCrossRefGoogle Scholar
  33. 33.
    Wendling D, Tisserand G, Griffond V, Saccomani C, Toussirot E. Acute pseudogout after pamidronate infusion. Clin Rheumatol. 2008;27:1205–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Young-Min S, Herbert L, Dick M, Fordham J. Weekly alendronate-induced acute pseudogout. Rheumatology. 2005;44:131–2.PubMedCrossRefGoogle Scholar
  35. 35.
    Gallacher S, Boyle I, Capell H. Pseudogout associated with use of cyclical etidronate therapy. Scot Med J. 1991;36:49.PubMedGoogle Scholar
  36. 36.
    Malnick SD, Ariel-Ronen S, Evron E, Sthoeger ZM. Acute pseudogout as a complication of pamidronate. Ann Pharmacother. 1997;31:499–500.PubMedGoogle Scholar
  37. 37.
    Luzar MJ, Altawil B. Pseudogout following intraarticular injection of sodium hyaluronate. Arthritis Rheum. 1998;41:939–40.PubMedCrossRefGoogle Scholar
  38. 38.
    Disla E, Infante R, Fahmy A, Karten I, Cuppari GG. Recurrent acute calcium pyrophosphate dihydrate arthritis following intraarticular hyaluronate injection. Arthritis Rheum. 1999;42:1302–3.PubMedCrossRefGoogle Scholar
  39. 39.
    Geelhoed GW, Kelly TR. Pseudogout as a clue and complication in primary hyperparathyroidism. Surgery. 1989;106:1036–41.PubMedGoogle Scholar
  40. 40.
    Rubin MR, Silverberg SJ. Rheumatic manifestations of primary hyperparathyroidism and parathyroid hormone therapy. Curr Rheumatol Rep. 2002;4:179–85.PubMedCrossRefGoogle Scholar
  41. 41.
    Ames PR, Rainey MG. Consecutive pseudogout attacks after repetitive granulocyte colony-stimulating factor administration for neutropenia. Mod Rheumatol. 2007;17:445–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Sandor V, Hassan R. Kohn E Exacerbation of pseudogout by granulocyte colony-stimulating factor. Ann Intern Med. 1998;129:424–5.Google Scholar
  43. 43.
    Pasquetti P, Selvi E, Righeschi K, Fabbroni M, De Stefano R, Frati E, et al. Joint lavage and pseudogout. Ann Rheum Dis. 2004;63:1529–30.PubMedCrossRefGoogle Scholar
  44. 44.
    Doherty M, Watt I, Dieppe PA. Localised chondrocalcinosis in post-meniscectomy knees. Lancet. 1982;1:1207–10.PubMedCrossRefGoogle Scholar
  45. 45.
    Grassi W, Meenagh G, Pascual E, Filippucci E. “Crystal clear”-sonographic assessment of gout and calcium pyrophosphate deposition disease. Semin Arthritis Rheum. 2006;36:197–202.PubMedCrossRefGoogle Scholar
  46. 46.
    Dalbeth N, McQueen FM. Use of imaging to evaluate gout and other crystal deposition disorders. Curr Opin Rheumatol. 2009;21:124–31.PubMedCrossRefGoogle Scholar
  47. 47.
    Kean WF, Rainsford KD, Kean IR. Management of chronic musculoskeletal pain in the elderly: opinions in oral medication use. Inflammopharmacology. 2008;16:53–75.PubMedCrossRefGoogle Scholar
  48. 48.
    Doherty M, Dieppe PA. Double blind, placebo controlled trial of magnesium carbonate in chronic pyrophosphate arthropathy. Ann Rheum Dis. 1983;42(Suppl):106.CrossRefGoogle Scholar
  49. 49.
    Zhang Y, Terkeltaub R, Nevitt M, Xu L, Neogi T, Aliabadi P, et al. Lower prevalence of chondrocalcinosis in Chinese subjects in Beijing than in white subjects in the United States: the Beijing Osteoarthritis Study. Arthritis Rheum. 2006;54:3508–12.PubMedCrossRefGoogle Scholar
  50. 50.
    Rosenthal AK, Ryan LM. Probenecid inhibits transforming growth factor-beta 1 induced pyrophosphate elaboration by chondrocytes. J Rheumatol. 1994;21:896–900.PubMedGoogle Scholar
  51. 51.
    Alvarellos A, Spilberg I. Colchicine prophylaxis in pseudogout. J Rheumatol. 1986;13:804–5.PubMedGoogle Scholar
  52. 52.
    Rothschild B, Yakaobov LE. Prospective 6-month double blind trial of hydroxychloroquine treatment of CPPD. Compr Ther. 1997;23:327–30.PubMedGoogle Scholar
  53. 53.
    Chollet-Janin A, Finckh A, Dudler J, Guerne PA. Methotrexate as an alternative therapy for chronic calcium pyrophosphate deposition disease: an exploratory analysis. Arthritis Rheum. 2007;56:688–92.PubMedCrossRefGoogle Scholar
  54. 54.
    McGonagle D, Tan AL, Madden J, Emery P, McDermott MF. Successful treatment of resistant pseudogout with anakinra. Arthritis Rheum. 2008;58:631–3.PubMedCrossRefGoogle Scholar
  55. 55.
    Carroll GJ, Stuart RA, Armstrong JA, Breidahl PD, Laing BA. Hydroxyapatite crystals are a frequent finding in osteoarthritic synovial fluid, but not related to increased concentrations of keratin sulfate or interleukin 1. J Rheumatol. 1991;18:861–6.PubMedGoogle Scholar
  56. 56.
    Paul H, Reginato AJ, Schumacher HR. Alizarin red S staining as a screening test to detect calcium compounds in synovial fluid. Arthritis Rheum. 1983;26:191–200.PubMedCrossRefGoogle Scholar
  57. 57.
    Reginato AM, Olsen BR. Genetics and experimental models of crystal-induced arthritis. Lessons learned from mice and men: is it crystal clear? Curr Opin Rheumatol. 2007;19:134–45.PubMedCrossRefGoogle Scholar
  58. 58.
    Moss DW, Eaton RH, Smith JK, Whitby LG. Association of inorganic-pyrophosphatase activity with human alkaline-phosphatase preparations. Biochem J. 1967;102:53–7.PubMedGoogle Scholar
  59. 59.
    Terkeltaub R, Rosenbach M, Fong F, Goding J. Causal link between nucleotide pyrophosphohydrolase overactivity and increased intracellular inorganic pyrophosphate generation demonstrated by transfection of cultured fibroblasts and osteoblasts with plasma cell membrane glycoprotein-1. Relevance to calcium pyrophosphate dihydrate deposition disease. Arthritis Rheum. 1994;37: 934–41.PubMedCrossRefGoogle Scholar
  60. 60.
    Ho AM, Johnson MD, Kingsley DM. Role of the mouse ank gene in control of tissue calcification and arthritis. Science. 2000;289:265–70.PubMedCrossRefGoogle Scholar
  61. 61.
    Derfus BA, Kurtin SM, Camacho NP, Kurup I, Ryan LM. Comparison of matrix vesicles derived from normal and osteoarthritic human articular cartilage. Connect Tissue Res. 1996;35: 337–42.PubMedCrossRefGoogle Scholar
  62. 62.
    Ryan LM, Wortmann RL, Karas Jr B. Cartilage nucleoside triphosphate (NTP) pyrophosphohydrolase. I. Identification as an ecto-enzyme. Arthritis Rheum. 1984;27:404–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Okawa A, Nakamura I, Goto S, Moriya H, Nakamura Y, Ikegawa S. Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nat Genet. 1998;19:271–3.PubMedCrossRefGoogle Scholar
  64. 64.
    Williams CJ, Zhang Y, Timms A, Bonavita G, Caeiro F, Broxholme J, et al. Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane ­protein ANKH. Am J Hum Genet. 2002;71:985–91.PubMedCrossRefGoogle Scholar
  65. 65.
    Pendleton A, Johnson MD, Hughes A, Gurley KA, Ho AM, Doherty M, et al. Mutations in ANKH cause chondrocalcinosis. Am J Hum Genet. 2002;71:933–40.PubMedCrossRefGoogle Scholar
  66. 66.
    Williams CJ, Pendleton A, Bonavita G, Reginato AJ, Hughes AE, Peariso S, et al. Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum. 2003;48:2627–31.PubMedCrossRefGoogle Scholar
  67. 67.
    Zhang Y, Johnson K, Russell RG, Wordsworth BP, Carr AJ, Terkeltaub RA, 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;52:1110–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Church LD, Cook GP, McDermott MF. Primer: inflammasomes and interleukin 1beta in inflammatory disorders. Nat Clin Pract Rheumatol. 2008;4:34–42.PubMedCrossRefGoogle Scholar
  69. 69.
    Liu-Bryan R, Pritzker K, Firestein GS, Terkeltaub R. TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation. J Immunol. 2005;174:5016–23.PubMedGoogle Scholar
  70. 70.
    Liu-Bryan R, Scott P, Sydlaske A, Rose DM, Terkeltaub R. Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2005;52:2936–46.PubMedCrossRefGoogle Scholar
  71. 71.
    Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237–41.PubMedCrossRefGoogle Scholar
  72. 72.
    Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest. 2006;116:2262–71.PubMedCrossRefGoogle Scholar
  73. 73.
    McGonagle D, Tan AL, Shankaranarayana S, Madden J, Emery P, McDermott MF. Management of treatment resistant inflammation of acute on chronic tophaceous gout with anakinra. Ann Rheum Dis. 2007;66:1683–4.PubMedCrossRefGoogle Scholar
  74. 74.
    Hoffman GS, Schumacher HR, Paul H, et al. Calcium oxalate microcrystalline associated arthritis in end stage renal disease. Ann Intern Med. 1982;97:36–42.PubMedGoogle Scholar
  75. 75.
    Reginato AJ, Kurnik BRC. Calcium oxalate and other crystals associated with kidney diseases and arthritis. Semin Arthritis Rheum. 1989;18:198–224.PubMedCrossRefGoogle Scholar
  76. 76.
    Maldonado M, Prasad V, Reginato A. Oxalate crystal deposition disease. Curr Rheumatol Rep. 2002;4:257–64.PubMedCrossRefGoogle Scholar
  77. 77.
    Reginato A, Falasca G, Usmani Q. Do we really need to pay attention to the less common crystals? Review about the clinical significance of rare crystals found in synovial fluid in articular tissues. Curr Opin Rheumatol. 1999;11:446–52.PubMedCrossRefGoogle Scholar
  78. 78.
    Kaplan P, Resnick D, Murphey M. Destructive non-infectious spondyloarthropathy in hemodialysis patients. Musculoskelet Radiol. 1987;162:241–4.Google Scholar
  79. 79.
    Reginato AJ, Ferreiro Seoane JL, Barbazan Alvarez C, et al. Arthropathy and cutaneous calcinosis in hemodialysis oxalosis. Arthritis Rheum. 1986;29:1387–95.PubMedCrossRefGoogle Scholar
  80. 80.
    Cole BJ, Schumacher HR. Injectable corticosteroids in modern practice. J Am Acad Orthop Surg. 2005;13:37–46.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Rhode Island HospitalUniversity Medicine FoundationRIUSA

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