Joint pain and inflammation as well as joint degeneration can be caused by calcium pyrophosphate crystals (CPP crystals), which can deposit in a joint's cartilage. When these crystals are present in a joint it is called calcium pyrophosphate deposition (CPPD).
Experts are unsure what causes CPPD and the symptoms can vary widely. Patients with CPPD typically have one of the following:
- Osteoarthritis with CPPD. Research suggests that CPP crystals are up to three times more common in patients who have osteoarthritis than those who do not.1 Some experts believe that people who have osteoarthritis with calcium pyrophosphate deposition may experience more swelling and inflammation than people who have osteoarthritis without crystals.2,3
- Pseudogout. The crystals can trigger an immune system response that results in acute pain, swelling, and redness that lasts for a brief period of time, generally 5 to 14 days.4,5 This condition is known as acute calcium pyrophosphate crystal arthritis or, more simply, pseudogout. (The symptoms can mimic gout, which is caused by uric acid crystals, not CPP crystals.)
- Chronic CPP crystal inflammatory arthritis. The crystals can trigger an immune response that is less extreme than pseudogout, resulting in a milder, duller pain with some swelling and redness. This condition is sometimes misdiagnosed as osteoarthritis or rheumatoid arthritis and may be referred to as pseudo-osteoarthritis and pseudo-rheumatoid arthritis.
- No symptoms. Many people have calcium pyrophosphate crystals in their joints but do not experience any pain. In these cases, no treatment is needed.
Calcium pyrophosphate crystals cannot be removed from a joint. However, inflammation and swelling caused by the crystals can accelerate joint damage, so individuals who experience these symptoms should talk to their doctor and seek treatment.
Who Gets CPPD?
Estimates vary regarding how many people have calcium pyrophosphate crystal deposition, but researchers know for certain that risk increases dramatically with age. The European League Against Rheumatism says that, when controlling for other factors, the risk of calcium pyrophosphate crystal deposition doubles every 10 years for people between ages 45 and 85.6
One study found that 15% of people aged 65 to 74 had signs of calcium pyrophosphate crystal deposition, as did 40% of people aged 84 and older.7
In addition to aging, genetics also plays a role. Research suggests that a mutation in the ANKH gene, a gene that helps regulate metabolism, makes a person more prone to accumulating calcium pyrophosphate crystals at an earlier age compared to people without the genetic mutation.8,9
Lastly, underlying medical conditions have been associated with the development of CPPD, including excess iron storage disease (hemochromatosis), an overactive parathyroid gland (hyperparathyroidism), low magnesium levels, and most commonly, an underactive thyroid (hypothyroidism).
How Does CPPD Cause Symptoms?
Though experts have known about calcium pyrophosphate crystals for decades, research has yet to uncover how and why the crystals form in cartilage or why some people with CPPD experience symptoms and others do not. Many experts theorize the following steps occur:
- CPP crystals are produced within a joint's cartilage as the result of
- Faulty metabolism within the cartilage itself10
- A more general metabolic disorder that is not isolated to cartilage
- An endocrine disorder (your doctor should run basic blood tests if this condition is diagnosed).
- The CPP crystals accumulate in the cartilage and can be released when the cartilage is disturbed through normal wear-and-tear, an injury or trauma.
- The CPP crystals are released into the synovial joint fluid and can lodge in the surrounding soft joint tissue, including the joint's synovial lining as well as bursa, ligaments and tendons.
- The release of CPP crystals into the joint triggers an immune system response. The immune response may be acute, resulting in a flare of severe pain, swelling, redness, and warmth called pseudogout, or it may be more mild, causing dull pain and swelling that can be mistaken for osteoarthritis.
Calcium pyrophosphate deposition is the leading cause of the cartilage calcification, making the cartilage harder and less flexible.1 This calcification process is called chondrocalcinosis, and it may occur in a seemingly healthy joint or occur a joint that already shows signs of degeneration.
- For further reading: Understanding Joint Pain
- Zhang et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis.
- Ledingham J, Regan M, Jones A, Doherty M. Factors affecting radiographic progression of knee osteoarthritis.
- Rosenthal AK. Crystals, inflammation, and osteoarthritis.