CPPD

Definition

  • Calcium Pyrophosphate Dihydrate Deposition Disease
  • Chondrocalcinosis can refer to any calcium in cartilage

Classification

TypeNotes
Idiopathic chondrocalcinosisBy far the most common. Pseudorheumatoid arthritis with continuous attack, pseudo osteoarthritis with acute attacks, pseudo osteoarthritis without acute attacks, lanthanic (asymptomatic)
Hereditary
Secondary (“WHIP A DOG”)Wilson’s, haemochromatosis, hyperparathyroidism, hypothyroidism, hypophosphatasia, idiopathic, pseudogout, pernicious anaemia, acromegaly, diabetes, degenerate, ochronosis (alkaptonuria), gout

Pathology

CPPD, calcium pyrophosphate crystals
Calcium pyrophosphate crystals. Image by David Iberri, Wikimedia Commons, CC BY-SA 3.0.
  • Chondrocalcinosis is the finding of radioopaque crystals in hyaline cartilage & can be salts of
    • Calcium pyrophosphate dihydrate
    • Dicalcium phosphate hydrate
    • Hydroxyapatite
    • Calcium oxalate
  • May have acute or chronic presentation
    • Joints involved
      • Knee
      • Hip without symptoms often
      • Patellofemoral
      • Radiocarpal
      • Metacarpophalangeal

Investigations

CPPD, radiograph showing chondrocalcinosis
Radiograph showing chondrocalcinosis. Image by Taokinesis (Pixabay profile), Wikimedia Commons, CC0.

X-rays

  • Intraarticular crystals
  • Cartilage loss
  • Subchondral cysts
  • Structural collapse of the articular surface

Differential Diagnoses

  • Hyperparathyroidism
    • XR show subperiosteal erosions
    • Blood tests show hypercalcaemia & ↑ PTH
  • Haemochromatosis
    • Characteristic
      • Progressive degenerative arthritis of finger joints
    • XR shows calcification of multiple joints & discs
    • Serum iron & iron binding capacity are raised
  • Adult Onset Hypophosphatasia
    • Hereditary metabolic disturbance
    • Characterised by low levels of serum alkaline phosphatase
  • Ochronosis / Alkaptonuria
    • Inborn error of metabolism
    • Tyrosine pathway
    • Homogentisic acid oxidase is absent
      • Homogentisic acid accumulates
      • Homogentisic acid deposited as a dark brown pigment in
        • Connective tissue
        • Hyaline & Fibrocartilage
    • Presents in 4th decade
      • Pain & stiffness
      • In spine & larger joints
    • XR shows calcification of intervertebral discs
      • Progressing to obliteration of the disc space
      • And bony ankylosis
    • Excretion of homogentisic acid
      • Causes the urine to turn dark on standing

Epidemiology

  • M:F – 2:1
  • Usually patient > 50 years
  • Sometimes familial
  • Associated with
    • DM
    • Hypothyroidism
    • Gout
    • Hyperparathyroidism
    • Haemochromatosis
    • Pernicious Anaemia
    • Ochronosis

Pathology

  • CPPD crystals deposited in
    • Joint capsule
    • Articular cartilage
    • Fibrocartilage (Menisci)
  • Histologically
    • Crystals seen at margin of degenerate cartilage
    • Surrounding lacunae of chondrocytes

Pathogenesis

  • Pyrophosphate generated at chondrocyte surface in abnormal cartilage
    • By enzyme action
  • Combine with calcium to form crystals which “sit” in the cartilage
    • ? Alter biomechanical properties
  • Occasionally the crystals are released into the joint & arthritis results
    • Activation of vasoactive & chemotactic factors
    • Neutrophils attracted & phagocytose crystals
    • Release of lysosomal enzymes into joint fluid
  • Crystal release caused by
    • Sudden change in ionic Calcium & Pyrophosphate
    • Equilibrium in cartilage
    • Eg. after acute illness or surgery
    • Physical disruption of cartilage
      • Eg. due to trauma
    • Enzymatic degradation of matrix
      • Eg. in inflammatory arthritis

Chronic Chondrocalcinosis

  • Predisposes to development of secondary osteoarthritis
  • Crystals embedded in articular cartilage have desiccating effect

Clinical Features

  • 3 Different Conditions

Asymptomatic Chondrocalcinosis

  • Majority of cases
  • Common incidental finding is calcium of menisci

Pseudogout

  • Usually affects large joints
    • Knee > Shoulder > Wrist
    • Cf. Gout affects small joints
  • Usually monoarticular
  • Less pain than Gout
    • Rapid onset with peak in 24/24
    • Subsides in 1/52
  • May be provoked by
    • Trauma
    • Surgery
    • Illness

Chronic CPPD Arthropathy

  • Pseudo-Osteoarthritis
    • Usual features of Osteoarthritis
    • Polyarticular diseases like Osteoarthritis
      • Ie. Hips & knees
      • ? Due to CPPD in cartilage altering the biomechanics
    • In more unusual joints for Osteoarthritis
      • Eg. Ankles, shoulders, elbows
      • Key to differentiating from normal Osteoarthritis
  • Pseudo-Rheumatoid Arthritis
    • Acute synovitis & chronic arthritis
    • Rapidly progressive joint destruction

Investigations

  • Laboratory Tests
    • Synovial fluid
      • CPPD crystals seen extracellularly & in neutrophils
        • Rhomboidal
        • Weakly positive birefringent
    • Ie. Blue parallel to 1st order red filter & 135° to polarizer
    • WCC ~ 1000 x 10.6 /L
      • Especially neutrophils
  • Radiology
    • Calcium in articular cartilage
      • Fine linear densities
      • Parallel to subchondral bone
    • Calcium in fibrocartilage & connective tissue
      • More punctate densities
      • Common fibrocartilage with calcium deposits
        • Menisci
        • TFCC
        • Pubis
        • Annulus
    • Findings of Osteoarthritis usually present
    • Involves unusual sites such as
      • NWB Joints
      • PFJ
      • TNJ

Differential Diagnosis

Management

  • Symptomatic only
  • Crystals deposition can’t be prevented or reversed
  • Treatment consists of NSAID
  • May use intra-articular corticosteroids
  • Joint washout if severe

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.