Hydroxyapatite Crystal Deposition Disease (HADD)

Hydroxyapatite is the major component and an essential ingredient of normal bone and teeth. It is hydroxyapatite that makes up bone minerals and the matrix of teeth.

Hydroxyapatite crystal deposition disease (HADD) is a condition characterized by the accumulation of hydroxyapatite crystals in the soft tissues surrounding joints, leading to inflammation, tenderness, and pain. Hydroxyapatite is a mineral found in normal bone and teeth, and it’s essential for their structure. However, when these crystals build up in and around joints, they can cause significant discomfort.

Hydroxyapatite crystal deposition disease is one of several types of crystal-induced arthropathies, a category that also includes conditions like gout (uric acid crystals) and pseudogout (calcium pyrophosphate dihydrate crystals). Not all patients with HADD will experience symptoms, and the condition can sometimes be mistaken for other issues like infectious arthritis, cellulitis, or gout. Therefore, a proper diagnosis is crucial for effective treatment

Epidemiology:

• HADD is usually a uniarticular condition, meaning it affects one joint at a time.
• It strikes women more frequently than men, with the average age of onset around 45 years.
• The disease often occurs in the glenohumeral joint (shoulder), particularly affecting the supraspinatus tendon. However, HADD can also affect other joints such as the hips, knees, wrists, and elbows.

Hydroxyapatite molecules can group together (crystallize) to form microscopic clumps, called hydroxyapatite crystals.

Tiny crystals of hydroxyapatite sometimes form in or around joints and can cause inflammation of joints and tissues around the joints, such as tendons and ligaments. They have been described particularly as a cause of rotator cuff inflammation of the shoulder.

The inflammation caused by hydroxyapatite crystals has been referred to as hydroxyapatite crystal disease or hydroxyapatite deposition disease (HADD).

While not fully understood, the cause of hydroxyapatite crystal disease is believed to be the accumulation of small calcium phosphate crystals in the joint tissue.

Several factors contribute to hydroxyapatite crystal deposition disease, including metabolic and genetic components. Key factors include:

• Diabetes: It is a substantial risk factor, most likely due to persistent low-grade inflammation and oxidative stress caused by the condition.
• Thyroid and estrogen metabolism disorders: These metabolic disorders can cause abnormal calcium metabolism, which contributes to hydroxyapatite crystal formation.
• Genetic factors: The HLA-A1 genotype is linked to an increased risk of hydroxyapatite crystal disease.

Additionally, these crystals may accumulate due to other factors, such as:

• Age
• Joint trauma or injury
• Underlying medical conditions (such as osteoarthritis, hyperparathyroidism, and hypophosphatemia)
• Other factors (such as obesity, a diet high in purines, and excessive alcohol consumption)

No. These conditions are similar in that they are all caused by the inflammation that results from the body's reaction to crystals. However, hydroxyapatite crystals are distinctly different from the crystals of pseudogout or gout. While hydroxyapatite crystals can sometimes also be found in the company of the calcium pyrophosphate crystals characteristic of pseudogout, these are quite different types of crystals.

Hydroxyapatite crystal deposition disease (HADD) is the buildup of hydroxyapatite crystals in soft tissues such as tendons, ligaments, and bursae. This can result in disorders such as calcific tendinitis or bursitis, which are marked by discomfort, swelling, and reduced movement. It typically affects the shoulder; however, it can also occur in other places.

Gout is caused by the deposition of monosodium urate crystals in the joints. The big toe is the most common joint, however other joints can also be affected. Gout causes sudden, severe pain, redness, edema, and warmth in the affected joint; it is also known as acute inflammatory arthritis. Elevated serum uric acid levels are usually associated with gout.

Pseudogout, commonly known as calcium pyrophosphate deposition disease (CPPD), is characterized by the deposition of calcium pyrophosphate dihydrate crystals in the joints. Commonly afflicted areas are the knees and wrists. Pseudogout has the same clinical appearance as gout, including joint pain, edema, and stiffness. When shown on imaging, it is commonly referred to as "chondrocalcinosis."

Key differences between hydroxyapatite crystal deposition disease, gout, and pseudogout:

Each condition requires a unique diagnosis and therapeutic approach based on the type of crystals involved and the affected anatomical areas.

Hydroxyapatite crystal disease (HACD) symptoms vary depending on the location of crystal buildup and the severity.

Common symptoms of HACD may include:

• Pain
• Swelling
• Limited range of motion
• Stiffness
• Popping or clicking sounds
• Weakness

Sometimes, hydroxyapatite crystals can be seen clumped in the fluid of a joint that has developed arthritis. The crystals are usually so small as to be invisible under a regular microscope and thus require a special (electron) microscope for identification.

The diagnosis of HADD typically involves a combination of clinical evaluation, imaging studies, and sometimes laboratory tests.

Imaging studies

X-rays:

• Often the first imaging test used, X-rays show characteristic calcific deposits in tendons or tissues surrounding the joints. Plain radiographs may show calcifications of varying size and shape in the tendons, bursae, and joint capsule.
• Calcifications appear radiopaque (dense) on radiographs, especially as the disease progresses and deposits merge into larger clusters.

Ultrasound:

• Useful for detecting and characterizing calcific deposits, it can also guide aspiration or therapeutic interventions.

MRI:

• May be used if the diagnosis is uncertain or if there is a need to evaluate for other soft tissue abnormalities. MRI scans show signal changes consistent with inflammation around the deposits. Hydroxyapatite crystals appear as deposits along the bursal surface of the supraspinatus tendon

Laboratory tests

• These are generally not specific for HADD. Inflammatory markers in the blood, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), may be elevated if there is significant inflammation.

Joint fluid analysis

• Hydroxyapatite crystals are usually too small to be visible under a regular microscope and require electron microscopy for identification. Alizarin red S staining can be used as a screening test to detect calcium compounds in synovial fluid.

HADD is primarily diagnosed through a combination of clinical assessment and imaging studies, with X-rays and ultrasound being the most commonly used modalities. MRI can be helpful in complex cases. Laboratory tests may aid in ruling out other conditions but are not specific for HADD. Accurate diagnosis is essential for appropriate management, which may include conservative measures, physical therapy, and in some cases, interventional procedures.

Hydroxyapatite deposition disease (HADD), also known as calcium apatite deposition disease (CADD), typically progresses through four stages:

Precalcific stage: Not visible on standard imaging techniques

• This is the initial phase where changes occur in the cells of the tendons, predisposing them to calcification.
• Tenocytes (tendon cells) are transformed into chondrocyte-like cells, which are capable of producing a cartilaginous matrix.
• There is increased cellular activity within the tendon or periarticular tissue, leading to matrix production that sets the groundwork for calcification.
• There are often no symptoms during this stage, and the changes are usually not detectable with standard imaging techniques.

Calcific stage: This stage is divided into two phases: formative and resting.

• Formative phase: Hydroxyapatite crystals begin to accumulate within the previously formed cartilaginous matrix. Calcifications appear round to oval with sharp borders.
• Resting phase: The deposit becomes more stable and is often well-delineated. Calcifications remain stable in size and shape.
• There may be pain, swelling, and decreased range of motion as the calcific deposits grow and exert pressure on surrounding structures.
• The deposition of hydroxyapatite crystals within the matrix leads to a palpable mass and visible changes on x-ray. Inflammation and irritation of adjacent tissues can occur due to the physical presence of the deposits.

Resorptive stage: This is considered the most painful stage.

• This stage is characterized by the body's inflammatory response to the calcific deposit, leading to partial or complete resorption of the crystals.
• Macrophages and other inflammatory cells infiltrate the area, breaking down the hydroxyapatite crystals. This process can be intensely painful and is associated with a robust inflammatory reaction.
• The calcifications begin to break down and liquefy, which can lead to leakage out of the tendon. This leakage causes acute inflammation and pain.
• The resorptive phase is characterized by ill-defined calcifications with a "comet tail-like" appearance on imaging. It is during this stage that people are most likely to seek medical attention due to significant joint pain, swelling, and decreased mobility.

Postcalcific stage: The final stage or healing stage

• The area previously occupied by the calcific deposit undergoes healing and remodeling.
• Pain and inflammation typically subside. There may be residual discomfort or stiffness, but many patients experience a significant reduction in symptoms.
• The tissue where the deposit was located is remodeled, often leaving behind a fibrocartilaginous scar. The tendon or affected tissue may return to near-normal function, although some structural abnormalities may persist.

It’s important to note that not everyone with the condition experiences symptoms, and the severity can vary greatly from person to person. Diagnosis is typically made through physical examination, imaging, and ruling out other conditions.

How do you treat hydroxyapatite? The treatment of the inflammation caused by hydroxyapatite crystals includes rest, cold application, and medications to reduce inflammation. Cortisone-related medications injected into inflamed tissues can also sometimes help decrease inflammation and thereby relieve pain.

Treatment options for hydroxyapatite crystal deposition disease aim to alleviate pain, reduce inflammation, and improve function.

Conservative approach

Rest and activity modification:

• Initial management often includes rest and modifying activities that exacerbate symptoms to prevent further irritation of the affected area.
• Reducing mechanical stress on the involved tendons helps decrease inflammation and pain.

Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs):

• Oral NSAIDs, such as ibuprofen or naproxen, are commonly used to manage pain and inflammation for short-term relief during acute flare-ups. They help reduce symptoms but do not treat the underlying cause.

Ice therapy and heat therapy:

• Applying ice packs to the affected area can help reduce inflammation and numb pain. For acute symptoms, ice should be applied for 15-20 minutes several times a day.
• Applying heat to the affected area can help relieve pain and stiffness. Heat increases blood flow and relaxes muscles.
• Ice therapy and heat therapy can be used alternatively throughout the day

Physical therapy:

• A physical therapist can provide exercises to improve range of motion, strengthen the affected muscles, and reduce stiffness. Therapy may include stretching, strengthening exercises, and modalities such as ultrasound therapy to break up calcifications. Physical therapy exercises and techniques can help maintain joint mobility and strength.

Corticosteroid injections:

• Local injection of corticosteroids can provide significant pain relief by reducing inflammation. They are often used for severe or persistent cases.
• However, these injections are generally limited to avoid potential side effects such as tendon weakening.

Extracorporeal shock wave therapy (ESWT):

• ESWT involves the application of shock waves to the affected area to break down calcium deposits. The shock waves promote reabsorption of calcium deposits and stimulate healing. Multiple sessions are often required for optimal results.

Interventional treatments

Ultrasound-guided needling and lavage:

• A minimally invasive procedure where needles are used under ultrasound guidance to break up and aspirate calcium deposits. This technique helps remove calcium crystals and reduce symptoms. For calcifications larger than 1 cm, ultrasound-guided washings can be used to aspirate and irrigate the deposits.

Ultrasound ablation

• High-intensity focused ultrasound can be used to break up calcifications. The heat from the ultrasound causes the deposits to dissolve.

Surgery

Reserved for cases that do not respond to conservative treatments and are associated with significant pain or functional impairment.

• Arthroscopic surgery: A minimally invasive surgery to remove calcium deposits.
• Open surgery: A more invasive option when arthroscopic surgery is not feasible.
• Recovery: Postoperative rehabilitation is crucial for recovery and restoring function.

Pain management:

• In addition to NSAIDs and corticosteroids, other pain management strategies such as acetaminophen or opioid analgesics (for short-term use) may be employed. These medications provide additional pain relief when necessary.

Alternative and complementary therapies:

• Acupuncture: Some patients find relief through acupuncture, which may help reduce pain and inflammation.
• Dietary Supplements: Supplements such as glucosamine and chondroitin may be considered, though evidence for their efficacy is limited.

Education and self-management:

• Educating patients about the nature of HADD, potential triggers, and self-management strategies is important for long-term management. Providing information on proper ergonomics, posture, and lifestyle modifications can empower patients to manage their condition effectively.

The choice of treatment depends on the severity of symptoms, the location and size of the calcium deposits, and the patient's overall health and preferences. It's essential to tailor the treatment plan to the individual patient's needs, and often a combination of therapies is used to achieve the best outcome. Regular follow-up with health care providers is crucial to monitor progress and adjust the treatment plan as necessary.

While this disease can be painful and debilitating, it often resolves on its own over time. The symptoms can improve within a few weeks, although pain and functional impairment may persist if the hydroxyapatite deposits are not reabsorbed. If left untreated, hydroxyapatite crystals can potentially cause joint destruction. 

Factors influencing resolution:

• The size and location of the deposits play a significant role in the disease's course. Smaller deposits are more likely to be resorbed spontaneously, while larger or more deeply embedded deposits might persist.
• Individual variability in the body's response to the crystals also affects the resolution. Some people may experience faster and more complete resolution, while others may have lingering issues.

Most calcifications will decrease in size, or pain will resolve within three months, and roughly 70% of cases will improve with conservative measures within one year. While hydroxyapatite deposition disease can resolve on its own, the timeline and recovery can vary from person to person. In some cases, HADD may recur or become chronic. If you suspect you have HADD or are experiencing symptoms, it’s best to consult with a health care professional for a proper diagnosis and treatment plan.

• What is calcium hydroxyapatite deposition? Calcium hydroxyapatite deposition, also known as hydroxyapatite crystal deposition disease (HADD), refers to the accumulation of hydroxyapatite crystals in tissues, commonly occurring in joints, tendons, and periarticular structures. This can lead to conditions such as calcific tendinitis, causing pain and inflammation.
• What is hydroxyapatite deposition CPPD? Hydroxyapatite deposition CPPD (calcium pyrophosphate deposition disease) involves the accumulation of hydroxyapatite crystals in joint cartilage, leading to joint pain and inflammation. It is often associated with other conditions such as osteoarthritis and can be diagnosed through imaging and crystal analysis of joint fluid.