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].
Case Question
A 54 year old hairdresser comes to your office complaining of right shoulder pain over the past 3 months that seems to be much worse at night. Some pain does occur with abduction of her arm while using scissors. She has already been to her primary care provider and minimally improved with NSAIDs. You order a plain x-ray that shows an ill-defined and fluffy deposit along the supraspinatus. You diagnose her with calcium hydroxyapatite deposition disease. According to this description, which phase of this disease is most likely?
A. Precalcific
B. Formative
C. Crystalization
D. Postcalcific
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].
Figure 1. Calcific tendinitis of the supraspinatus in the acute phase, showing a more “fluffy apperance”. (adopted from [42])
Figure 2. Calcific tendinitis of the shoulder with a more discrete, 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].
Figure 3. 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].
Figure 4. Rotator cuff barbotage and calcific return. Acoutic shadowing is present (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.
CASE CONCLUSION
Answer B. 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. 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.
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. 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.
K. Uhthoff, K. Sarkar, and J. A. Maynard, “Calcifying tendinitis. A new concept of its pathogenesis,” Clinical Orthopaedics and Related Research, vol. 118, pp. 164–168, 1976.
REFERENCES
1. Louwerens,J.K., I. N. Sierevelt, R. P. van Hove, M. P. J. van den Bekerom, and A. van Noort, “Prevalence of calcific deposits within the rotator cuff tendons in adults with and without subacromial pain syndrome: clinical and radiologic analysis of 1219 patients,” Journal of Shoulder and Elbow Surgery, vol. 24, no. 10, pp. 1588–1593, 2015.
2. Dieppe, P. Crocker, E. C. Huskisson, and D. A. Willoughby, “Apatite deposition disease. a new arthropathy,” The Lancet, vol. 307, no. 7954, pp. 266–269, 1976.
3. J. Gartner and B. Simons, “Analysis of calcific deposits in calcifying tendinitis,” Clinical Orthopaedics and Related Research, no. 254, pp. 111–120, 1990
4. J. Hamada, W. Ono, K. Tamai, K. Saotome, and T. Hoshino, “Analysis of calcium deposits in calcific periarthritis,” Journal of Rheumatology, vol. 28, no. 4, pp. 809–813, 2001.
5. J. Hamada, K. Tamai, W. Ono, and K. Saotome, “Does the nature of deposited basic calcium phosphate crystals determine clinical course in calcific periarthritis of the shoulder?” Journal of Rheumatology, vol. 33, no. 2, pp. 326–332, 2006.
6. H. K. Uhthoff, K. Sarkar, and J. A. Maynard, “Calcifying tendinitis. A new concept of its pathogenesis,” Clinical Orthopaedics and Related Research, vol. 118, pp. 164–168, 1976.
7. R. K. Lippmann, “Observations concerning the calcific cuff deposit,” Clinical Orthopaedics, vol. 20, pp. 49–60, 1961.
8. H. K. Uhthoff and J. W. Loebr, “Calcific tendinopathy of the rotator cuff: pathogenesis, diagnosis, and management,” Journal of the American Academy of Orthopaedic Surgeons, vol. 5, no. 4, pp. 183–191, 1997.
9. N. S. Cho, B. G. Lee, and Y. G. Rhee, “Radiologic course of the calcific deposits in calcific tendinitis of the shoulder: does the initial radiologic aspect affect the final results?” Journal of Shoulder and Elbow Surgery, vol. 19, no. 2, pp. 267–272, 2010.
10. G. R. Ebenbichler, C. B. Erdogmus, K. L. Resch et al., “Ultrasound therapy for calcific tendinitis of the shoulder,” New England Journal of Medicine, vol. 340, no. 20, pp. 1533–1538, 1999.
11. P. Harvie, T. C. B. Pollard, and A. J. Carr, “Calcific tendinitis: natural history and association with endocrine disorders,” Journal of Shoulder and Elbow Surgery, vol. 16, no. 2, pp. 169–173, 2007.
12. M. E. Mavrikakis, S. Drimis, D. A. Kontoyannis, A. Rasidakis, E. S. Moulopoulou, and S. Kontoyannis, “Calcific shoulder periarthritis (tendinitis) in adult onset diabetes mellitus: a controlled study,” Annals of the Rheumatic Diseases, vol. 48, no. 3, pp. 211–214, 1989.
13. J. R. Singh and K. Yip, “Gluteus maximus calcific tendonosis: a rare cause of sciatic pain,” American Journal of Physical Medicine and Rehabilitation, vol. 94, no. 2, pp. 165–167, 2015.
14. S. A. Garayoa, L. M. Romero-Muñoz, and J. Pons-Villanueva, “Acute compartment syndrome of the forearm caused by calcific tendinitis of the distal biceps,” Musculoskeletal Surgery, vol. 94, no. 3, pp. 137–139, 2010.
15. S. Yasen, “Acute calcific tendinitis of the flexor carpi ulnaris causing acute compressive neuropathy of the ulnar nerve: a case report,” Journal of Orthopaedic Surgery, vol. 20, no. 3, pp. 414–416, 2012.
16. D. Ring, A. R. Vaccaro, G. Scuderi, M. N. Pathria, and S. R. Garfin, “Acute calcific retropharyngeal tendinitis. Clinical presentation and pathological characterization,” The Journal of Bone & Joint Surgery—American Volume, vol. 76, no. 11, pp. 1636–1642, 1994.
17. N. C. Paik, “Acute calcific tendinitis of the gluteus medius: an uncommon source for back, buttock, and thigh pain,” Seminars in Arthritis and Rheumatism, vol. 43, no. 6, pp. 824–829, 2014.
18. T. Chung, R. Rebello, and E. E. Gooden, “Retropharyngeal calcific tendinitis: case report and review of literature,” Emergency Radiology, vol. 11, no. 6, pp. 375–380, 2005.
19. A. F. DePalma and J. S. Kruper, “Long-term study of shoulder joints afflicted with and treated for calcific tendinitis,” Clinical Orthopaedics, vol. 20, pp. 61–72, 1961.
20. Freire, V., Moser, T.P. & Lepage-Saucier, M. Radiological identification and analysis of soft tissue musculoskeletal calcifications. Insights Imaging 9, 477–492 (2018).
21. Farin PU, Jaroma H. Sonographic findings of rotator cuff calcifications. J Ultrasound Med. 1995;14(1):7-14. doi:10.7863/jum.1995.14.1.7
22. G. Merolla, S. Singh, P. Paladini, G. Porcellini, Calcific tendinitis of the rotator cuff: state of the art in diagnosis and treatment, J. Orthop. Traumatol. Off. J. Ital. Soc. Orthop. Traumatol. 17 (March (1)) (2016) 7–14.
23. B. Le Goff, J.-M. Berthelot, P. Guillot, J. Glémarec, Y. Maugars, Assessment of calcific tendonitis of rotator cuff by ultrasonography: comparison between symptomatic and asymptomatic shoulders, Joint Bone Spine 77 (May (3)) (2010) 258–263.
24. G.F. Bachmann, C. Melzer, C.M. Heinrichs, B. Möhring, M.B. Rominger, Diagnosis of rotator cuff lesions: comparison of US and MRI on 38 joint specimens, Eur. Radiol. 7 (March (2)) (1997) 192–197.
25. M. Maier, A. Stäbler, C. Schmitz, A. Lienemann, S. Köhler, H.R. Dürr, M. Pfahler, H.J. Refior, On the impact of calcified deposits within the rotator cuff tendons in shoulders of patients with shoulder pain and dysfunction, Arch. Orthop. Trauma Surg. 121 (July (7)) (2001) 371–378
26. ] B.P.G. Pereira, E.Y. Chang, D.L. Resnick, M.N. Pathria, Intramuscular migration of calcium hydroxyapatite crystal deposits involving the rotator cuff tendons of the shoulder: report of 11 patients, Skeletal Radiol. 45 (January (1)) (2016) 97–103.
27. Wölk T, Wittenberg RH. Kalzifizierendes Subakromialsyndrom–Klinische und sonographische Ergebnisse unter nicht-operativer Therapie [Calcifying subacromial syndrome–clinical and ultrasound outcome of non-surgical therapy]. Z Orthop Ihre Grenzgeb. 1997;135(5):451-457. doi:10.1055/s-2008-1039415
28. Ogon P, Suedkamp NP, Jaeger M, Izadpanah K, Koestler W, Maier D. Prognostic factors in nonoperative therapy for chronic symptomatic calcific tendinitis of the shoulder. Arthritis Rheum. 2009;60(10):2978-2984. doi:10.1002/art.24845
29. Cho NS, Lee BG, Rhee YG. Radiologic course of the calcific deposits in calcific tendinitis of the shoulder: does the initial radiologic aspect affect the final results?. J Shoulder Elbow Surg. 2010;19(2):267-272.
30. de Witte PB, Kolk A, Overes F, Nelissen RG, Reijnierse M. Rotator cuff calcific tendinitis: Ultrasound-guided needling and lavage versus subacromial corticosteroids: Five-year outcomes of a randomized controlled trial. Am J Sports Med. 2017;45:3305–14.
31. Raja A, Craig EV, Braman JP. Rotator cuff tendon calcific tendinitis treatment algorithm for primary care musculoskeletal physicians. J Family Med Prim Care. 2019;8(5):1647-1652. doi:10.4103/jfmpc.jfmpc_110_19
32. Pasquotti G, Faccinetto A, Marchioro U, Todisco M, Baldo V, Cocchio S, et al. US-guided percutaneous treatment and physical therapy in rotator cuff calcific tendinopathy of the shoulder: Outcome at 3 and 12 months. Eur Radiol. 2016;26:2819–27.
33. L. Gerdesmeyer, S. Wagenpfeil, M. Haake, M. Maier, M. Loew, K. Wortler, et al. Extracorporeal shock wave therapy for the treatment of chronic calcifying tendonitis of the rotator cuff: a randomized controlled trial. JAMA, 290 (2003), pp. 2573-2580
34. C.J. Hsu, D.Y. Wang, K.F. Tseng, Y.C. Fong, H.C. Hsu, Y.F. Jim./ Extracorporeal shock wave therapy for calcifying tendinitis of the shoulder. J Shoulder Elbow Surg, 17 (2008), pp. 55-59
35. Huisstede, Bionka MA, et al. “Evidence for effectiveness of Extracorporal Shock-Wave Therapy (ESWT) to treat calcific and non-calcific rotator cuff tendinosis–a systematic review.” Manual therapy 16.5 (2011): 419-433.
36. Gatt, Daniel L., and Charalambos P. Charalambous. “Ultrasound-guided barbotage for calcific tendonitis of the shoulder: a systematic review including 908 patients.” Arthroscopy: The Journal of Arthroscopic & Related Surgery 30.9 (2014): 1166-1172.
37. Arirachakaran A, Boonard M, Yamaphai S, Prommahachai A, Kesprayura S, Kongtharvonskul J. Extracorporeal shock wave therapy, ultrasound-guided percutaneous lavage, corticosteroid injection and combined treatment for the treatment of rotator cuff calcific tendinopathy: a network meta-analysis of RCTs. Eur J Orthop Surg Traumatol. 2017;27(3):381-390. doi:10.1007/s00590-016-1839-y
38. Hurt G, Baker CL., Jr Calcific tendinitis of the shoulder. Orthop Clin North Am. 2003;34(4):567–575. [PubMed] [Google Scholar]
39. Seil R, Litzenburger H, Kohn D, Rupp S. Arthroscopic treatment of chronically painful calcifying tendinitis of the supraspinatus tendon. Arthroscopy. 2006;22(5):521–527.
40. Sansone V, Maiorano E, Galluzzo A, Pascale V. Calcific tendinopathy of the shoulder: clinical perspectives into the mechanisms, pathogenesis, and treatment. Orthop Res Rev. 2018;10:63-72. Published 2018 Oct 3. doi:10.2147/ORR.S138225
41. Hongsmatip P, Cheng KY, Kim C, Lawrence DA, Rivera R, Smitaman E. Calcium hydroxyapatite deposition disease: Imaging features and presentations mimicking other pathologies. Eur J Radiol. 2019;120:108653.
42. Beckmann NM. Calcium Apatite Deposition Disease: Diagnosis and Treatment. Radiol Res Pract. 2016;2016:4801474.
