October 18, 2020

Calcium Hydroxyapatite Deposition Disease

Calcium hydroxyapatite deposition disease, also known as CHDD, is commonly known as calcific tendinitis. There have also been other names associated with the same disease including calcium apatite deposition disease (CADD), Hydroxyapatite deposition disease (HADD). It is also sometimes confused with pseudogout, which is calcium pyrophosphate deposition disease (CPDD). CHDD is a fairly common phenomenon and most cases are associated with the shoulder and rotator cuff. The two most commonly involved rotator cuff muscles are the supraspinatus and infraspinatus. The hip is the second most common and the spine is the third most common area. Other reports have shown localization the the triceps, common extensor and flexor tendons, hand, wrist, and patellar tendon, among others. It occurs more frequently in women and mostly between the ages of 30-60, although there have been cases in almost all ages [1].
Basic calcium phosphate crystals encompass several types of crystals, including carbonate apatite, octacalcium phosphate and whitlockite crystals. Crystals can deposit in tendons, bursa, muscles or periarticular structures. More recent studies have shown the calcium that deposits of calcific tendinitis is carbonate apatite, as opposed to studies from 1976 and 1990 that described hydroxyapatite [2-5]. The exact etiology is unknown. Some authors have speculated it is due to tendon degeneration, while others describe a cell-mediated process [6-7]. The natural progression has been described in 4 stages: precalcific, formative, resorptive and postcalcific. In the precalcific phase, collagen fibers of the tendon undergo metaplasia into fibrocartilage tissue. During the formative phase, chondrocytes begin to develop within the areas of fibrocartilage formation with eventual formation of calcified apatite crystals [8]. The resorptive phase is described as the most inflammatory, although most individuals go through the resorptive stage with mild or no symptoms. At a more cellular level, lymphocytes, leukocytes, and giant cells forming calcium granulomas characterize the inflammatory resorptive phase. Calcium crystal deposition is asymptomatic roughly 2 of 3 individuals and found incidentally in many cases [8]. Most cases involve a single site, but bilateral calcific tendinosis involving the shoulder has been shown in up to 23 percent of cases [9-10]. One study showed an association between estrogen and thyroid hormone disorders and the development of calcific tendinitis, which may account for at least a portion of the female predilection [11]. An association has also been found between adult onset diabetes and calcific tendinitis [12].
Basic calcium phosphate crystals encompass several types of crystals, including carbonate apatite, octacalcium phosphate and whitlockite crystals. Crystals can deposit in tendons, bursa, muscles or periarticular structures. More recent studies have shown the calcium that deposits of calcific tendinitis is carbonate apatite, as opposed to studies from 1976 and 1990 that described hydroxyapatite [2-5]. The exact etiology is unknown. Some authors have speculated it is due to tendon degeneration, while others describe a cell-mediated process [6-7]. The natural progression has been described in 4 stages: precalcific, formative, resorptive and postcalcific. In the precalcific phase, collagen fibers of the tendon undergo metaplasia into fibrocartilage tissue. During the formative phase, chondrocytes begin to develop within the areas of fibrocartilage formation with eventual formation of calcified apatite crystals [8]. The resorptive phase is described as the most inflammatory, although most individuals go through the resorptive stage with mild or no symptoms. At a more cellular level, lymphocytes, leukocytes, and giant cells forming calcium granulomas characterize the inflammatory resorptive phase. Calcium crystal deposition is asymptomatic roughly 2 of 3 individuals and found incidentally in many cases [8]. Most cases involve a single site, but bilateral calcific tendinosis involving the shoulder has been shown in up to 23 percent of cases [9-10]. One study showed an association between estrogen and thyroid hormone disorders and the development of calcific tendinitis, which may account for at least a portion of the female predilection [11]. An association has also been found between adult onset diabetes and calcific tendinitis [12].
Depending on your practice or the patient’s course, you may have plain radiographs of the shoulder to review. Many times this will greatly aid with the diagnosis and it is important to get external rotation views if CHDD is suspected. Plain radiographs can distinguish calcifications from mature ossifications, which will show a distinct cortical and/or trabecular bone pattern. Calcifications of plain radiographs are described as fluffy, ill-defined (Figure 1), and inhomogeneous or as discrete, homogeneous, and well defined (Figure 2) [6,19]. The ill-defined lesions are thought to be more associated with the acutely symptomatic phase of calcific tendinitis, while the well defined calcifications tend to be present in patients that are asymptomatic or have chronic pain [6,19].
CPPD calcium hydroxyapatite deposition disease calcific tendonitis shoulder xray
FIGURE 1. CALCIFIC TENDINITIS OF THE SUPRASPINATUS IN THE ACUTE PHASE, SHOWING A MORE “FLUFFY” APPEARANCE. ADOPTED FROM [42].
CPPD calcium hydroxyapatite deposition disease calcific tendonitis shoulder xray
FIGURE 2. CALCIFIC TENDINITIS OF THE SHOULDER WITH A MORE DISCRETE AND WELL DEFINED CALCIFICATION CORRELATING WITH THE POST-CALCIFIC STAGE. ADOPTED FROM [42].
Computed tomography (CT) is superior to conventional radiography for detecting calcifications and is particularly useful for identifying osseous erosions or migration of calcium into nearby structures. CT may provide additional information to distinguish calcification from ossification based on Hounsfield unit (HU) values, with calcifications typically demonstrating lower HU values of 100–400, as compared to 700 and over 1500 for trabecular and cortical bone, respectively [20]. Additionally, HADD can have a characteristic “comet tail” appearance on CT, which results from the longitudinal orientation of calcified deposits along tendons such that they seem to taper away from a site of bone involvement [20].
Depending on your practice and availability, ultrasonography (US) is also useful in the evaluation of CHDD. One large study with 951 patients showed a sensitivity of 87 percent with ultrasound, compared with 93 percent on plain radiographs [21]. Lesions generally appear hyperechoic with or without acoustic shadowing. Depending on the experience of the sonographer, he or she may be able to distinguish between the acute phase with an ill-defined, non arc-shaped, hyperechoic foci with less shadowing. The post-calcific stage is more likely well-defined, arc-shaped and hyperechoic [8]. There have also been reports of symptomatic, resorptive CHDD showing vascularity on color Doppler images [22-23].
CPPD calcium hydroxyapatite deposition disease of hip xray
CALCIFIC TENDINITIS OF THE HIP. ADOPTED FROM [41].
MRI, magnetic resonance imaging, can also be used as an imaging modality for CHDD. The calcifications are hypointense on all pulse sequences, which can lead to false positives and inability to fully characterize calcifications [24-25]. It can be helpful in determining the presence of inflammation associated with the acute resorptive phase and can also exclude other etiologies. It can also detect migration patterns, bursal fluid, soft tissue edema or marrow edema if close to bone. These images should always be correlated with plain radiographs or CT images [26].
MRI, magnetic resonance imaging, can also be used as an imaging modality for CHDD. The calcifications are hypointense on all pulse sequences, which can lead to false positives and inability to fully characterize calcifications [24-25]. It can be helpful in determining the presence of inflammation associated with the acute resorptive phase and can also exclude other etiologies. It can also detect migration patterns, bursal fluid, soft tissue edema or marrow edema if close to bone. These images should always be correlated with plain radiographs or CT images [26].
There is no consensus for standard treatment for CHDD. Most providers will attempt conservative management and most calcifications will decrease in size or pain will resolve within three months. Roughly seventy percent will improve with conservative measures in one year [27]. Treatment options include oral anti-inflammatory medications, corticosteroid injections and physical therapy. Physical therapy should focus on correction of upper body posture and restoration of scapulothoracic and glenohumeral strength and function, and it should not cause undue pain. One prospective study reported a success rate of 73 percent in 420 patients after three months, while another reports a 72 percent success rate in the same time frame.
Two prospective observational studies reported success rates of 73 percent (306 of 420 patients) and 72 percent (66 of 87 patients), respectively, after a minimum of three months of conservative treatment [28-29]. Negative prognostic factors reported were bilateral involvement, deposits larger than 1500 mm, localization near anterior acromion and subacromial extension of the deposits [28]. Oftentimes patients in acute pain are treated with a subacromial corticosteroid injection. Studies have reported improvement in pain and VAS scores after both subacromial injection and ultrasound guided subacromial-subdeltoid injection with needling [30-31]. Palpation guided subacromial injections showed a decreasing effect and recurrence was common between 6 weeks and 6 months. The chance of subsequent treatment was shown to be higher in the palpation guided group when compared to the ultrasound guided injection group. Another 2015 study with 47 patients showed improvement of shoulder function with an ultrasound guided injection paired with physical therapy [32].
Another treatment option is extracorporeal shock wave therapy, or ESWT. ESWT uses acoustic waves to fragment calcific deposits. One high quality study by Gerdesmeyer et al. showed significant between-group differences in the treatment group on pain, the total Constant Score, and on calcific deposit size in 96 patients [33]. Another lower quality randomized showed similar results at 12 months in 47 patients [34]. It has also been shown in low quality studies that multiple sessions are greater than one session for decreasing calcification size and high-ESWT (max 0.45 mJ/mm2) is superior to low-ESWT (0.02–0.06 mJ/mm2) when comparing shoulder function for calcific rotator cuff tendinitis at 3 months [35].
Ultrasound-guided needle lavage or barbotage is a technique that involves using ultrasound to guide a large-bore needle into the calcium deposits to break them up, irrigate and lavage them out of the pathologic tension. A systematic review in 2014 analyzed rotator cuff barbotage for calcific tendinopathy of the shoulder in 908 patients and concluded that barbotage is a safe and effective treatment option. All studies were prospective or retrospective. Various shoulder function scores were used all showed significant improvement. In the studies that did not use a shoulder function score, good or excellent outcomes were reported in 92 percent (198 of 214 patients) [36]. A 13 percent re-treatment rate was reported with the main reason being continued pain. One percent went on to require surgery. The most commonly reported complication was bursitis. It is also worth noting that the preferred technique was the “two needle technique” as opposed to the “milking technique,” or single needle technique. A 2016 meta-analysis showed corticosteroids following barbotage can decrease pain. It also showed barbotage plus ESWT significantly improved CMS (Constant-Murley score), VAS (Visual Analog score) and decreased size of calcium deposit when compared to ESWT, while barbotage plus subacromial injection (SAI) significantly improved CMS and decreased size of calcium deposit when compared to SAI [37].
ultrasound barbotage of calcific tendonitis shoulder
FIGURE 4. ROTATOR CUFF BARBOTAGE AND CALCIFIC RETURN. ACOUSTIC SHADOWING IS PRESENT (ARROW). ADOPTED FROM [42].
Around 10 percent of cases are refractory to minimally invasive measures and may go on for shoulder arthroscopy. Many providers may recommend surgical treatment if symptoms persist more than 6 months despite treatment. There is debate on whether complete eradication of all calcifications is necessary for good outcomes. Most orthopedic surgeons will elect not to suture residual tendons (side to side versus suture anchor repair) unless there is a large defect [38]. There is a substantial agreement among orthopedic journals and studies about the opportunity of performing an acromioplasty only when there are signs of subacromial impingement with rough coracoacromial ligament borders or when the undersurface of the acromion is exposed [39,40].
In conclusion, calcium hydrpxyapatite deposition disease (CHDD) is well known in the orthopedic community and many names exist for the same process, including CADD and HADD. It affects the shoulder in the great majority of cases, but also affects the spine, hip, elbow and hand, with all of them being treated similarly. Plain radiographs paired with a thorough history and physical examination will help aid in the diagnosis. Around two thirds of cases can be treated nonoperatively and with non-invasive measures, but around ten percent may go on to require surgery. It has been shown that ultrasound-gudied barbotage and extracorporeal shock wave therapy are effective treatments for calcific tendinopathy and are low risk. Even though most of the therapies have shown benefit, the quality of evidence remains poor and more randomized controlled trials are necessary to validate their efficacy. There is even greater paucity of evidence in regards to calcific tendinopathy outside of the shoulder with mostly case reports.

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