Calcium Hydroxyapatite Deposition Research Articles

Arthroscopic Decompression of Calcific Tendinitis of the Shoulder and Repair of Residual Rotator Cuff Defect

Background: Calcific tendinitis is a common source of shoulder pain and represents pathologic deposition of calcium hydroxyapatite within rotator cuff tendon tissue, most commonly the supraspinatus tendon. Indications: Arthroscopic decompression of calcific tendinitis with possible rotator cuff repair is indicated in patients with persistent, debilitating symptoms of pain and/or dysfunction who are recalcitrant to nonoperative treatments, including corticosteroid administration, ultrasound-guided needle barbotage, and/or extracorporeal shockwave therapy. Technique Description: With the patient in a beach chair position, a standard diagnostic shoulder arthroscopy is performed to evaluate for concomitant pathologies. Within the subacromial space, a thorough bursectomy is performed and the area of calcium deposition is localized with a spinal needle. A scalpel may be used to create a small incision through the rotator cuff tendon in line with its fibers to promote egress of calcific debris. Surrounding tissue and loose debris are removed with an arthroscopic shaver. Following decompression, the rotator cuff repair is inspected, and if a bursal-sided or full-thickness tear is identified, an arthroscopic repair is performed with a construct individualized to the specific tear pattern. Results: Surgical treatment conferred greater functional improvement and comparable pain reduction to nonoperative treatments in a systematic review comprised of 27 randomized trials. While the addition of a rotator cuff repair remains controversial, combined excision of calcific tendinitis with concomitant rotator cuff repair led to greater functional outcomes and pain reduction at 2-year minimum follow-up compared with isolated decompression. Conclusion: Calcific tendinitis within the shoulder may be treated successfully with arthroscopic decompression and subsequent repair of a residual rotator cuff defect, followed by a graduated physical rehabilitation program. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Calcinosis Cutis Complicated with Recurrent Tissue Infections in a Patient with Limited Cutaneous Systemic Sclerosis: A Case Report

Calcinosis related to systemic sclerosis is a debilitating vascular complication that negatively affects quality of life. It results from the deposition of calcium hydroxyapatite in soft tissues that occurs in the presence of normal calcium and phosphorus metabolism. Injuries can be painful and cause tissue inflammation, ulcers with infections, or deformities that cause functional disability. We present the case of a 29-year-old woman with a history of calcinosis cutis associated with systemic sclerosis, lesions complicated by soft tissue infections, leading to septic arthritis. During the approach, improvement was achieved with the use of intravenous antibiotics and a long oral regimen. As it is a disease without definitive treatment, we improve the patient's living conditions and prevent future infections with non-pharmacological therapeutic measures.

Differential diagnosis of T2 hypointense masses in musculoskeletal MRI.

Many soft tissue masses have an indeterminate appearance on MRI, often displaying varying degrees and extent of T2 hyperintensity. However, a subset of neoplasms and tumor-like lesions may exhibit prominent areas of T2 hypointensity relative to skeletal muscle. The hypointensity observed on T2-weighted MRI can be caused by a variety of substances, including evolving blood products, calcifications or other inorganic crystals, or fibrous tissue. Carefully evaluating the presence and pattern of T2 hypointensity in soft tissue masses and considering potential causes in their associated clinical contexts can help to narrow the differential diagnosis among neoplastic and non-neoplastic possibilities. These include endometriosis, aneurysmal bone cysts, tenosynovial giant cell tumor, arteriovenous malformation and pseudoaneurysm, calcium pyrophosphate and hydroxyapatite deposition diseases, tumoral calcinosis, gout, amyloidosis, hemangiomas with phleboliths, low-grade fibromyxoid sarcoma, ossifying fibromyxoid tumor, collagenous fibroma, desmoid-type fibromatosis, myxofibrosarcoma, peripheral nerve sheath tumors, dedifferentiated liposarcoma, and treated sarcoma.

Sonographic evaluation of the association between calcific tendinopathy and rotator cuff tear: a case-controlled comparison.

To compare the incidence of rotator cuff (RC) tears on shoulder ultrasounds of patients with RC calcific tendinopathy (CaT) to that of a control group without CaT. In this retrospective case-control study, 50 shoulder ultrasounds of patients with CaT were compared independently by 2 musculoskeletal radiologists to 50 patients from a control group without CaT to catalog the number and type of RC tears. RC tears in the CaT group were further characterized based on location, into tears in the specific tendon(s) containing calcium versus all tendon tears. RC tears were diagnosed in 38% (19/50) of the control group (16 full-thickness) as compared to 22% (11/50) with CaT (6 full-thickness). The fewer full-thickness tears in the CaT group (12%, 6 of 50) compared to that in the control group (32%, 16 of 50) was statistically significant (P = 0.016, odds ratio 0.29). Only 7 of the 11 tears in the CaT group were in a calcium-containing tendon (3 full-thickness). The fewer calcium-containing tendon tears compared to tears in the control group was also statistically significant (P = 0.006, odds ratio 0.27). Furthermore, the fewer full-thickness calcium-containing tendon tears (6%, 3/50) compared to full-thickness tears in the control group (32%, 16/50) were yet more statistically significant (P = 0.001, odds ratio 0.14). In patients with shoulder pain and CaT, we observed a decreased number of RC tears and especially calcium-containing tendon tears, as compared to similar demographic patients with shoulder pain but without CaT. Key Points • Patients with rotator cuff calcific tendinopathy have few rotator cuff tears, especially full-thickness tears, compared to a control group without calcific tendinopathy. • The tendons containing the calcium hydroxyapatite deposition were the least likely to have a rotator cuff tear. • Future studies could evaluate if calcium hydroxyapatite deposition provides a protective mechanism against rotator cuff tears. • Musculoskeletal ultrasound is more sensitive than MRI in the evaluation of rotator cuff calcific tendinopathy.

Therapeutics Development for Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders: Update 2020.

Pseudoxanthoma elasticum (PXE), the prototype of heritable ectopic mineralization disorders, manifests with deposition of calcium hydroxyapatite crystals in the skin, eyes and arterial blood vessels. This autosomal recessive disorder, due to mutations in ABCC6, is usually diagnosed around the second decade of life. In the spectrum of heritable ectopic mineralization disorders are also generalized arterial calcification of infancy (GACI), with extremely severe arterial calcification diagnosed by prenatal ultrasound or perinatally, and arterial calcification due to CD73 deficiency (ACDC) manifesting with arterial and juxta-articular mineralization in the elderly; the latter disorders are caused by mutations in ENPP1 and NT5E, respectively. The unifying pathomechanistic feature in these three conditions is reduced plasma levels of inorganic pyrophosphate (PPi), a powerful endogenous inhibitor of ectopic mineralization. Several on-going attempts to develop treatments for these conditions, either with the goal to normalize PPi plasma levels or by means of preventing calcium hydroxyapatite deposition independent of PPi, are in advanced preclinical levels or in early clinical trials. This overview summarizes the prospects of treatment development for ectopic mineralization disorders, with PXE, GACI and ACDC as the target diseases, from the 2020 vantage point.

Acute longus colli tendinitis and otolaryngology

IntroductionAcute longus colli tendinitis is caused by calcium hydroxyapatite deposition in the tendon of the longus colli muscle with subsequent inflammation. The calcifications are commonly located at the superior oblique portion at the level of the C1–C2 vertebrae. The typical clinical presentation consists of acute neck pain, odynophagia, and painful limitation of neck range of motion. ObjectivesWe will describe this disease with three that cases presented to our institution and compare the findings on imaging studies. MethodsWe retrospectively reviewed the clinical data, radiological features, and laboratory reports of three patients diagnosed with acute longus colli tendinitis. Computed tomography and plain radiographs were reviewed and compared by a single radiologist. A contemporary review of the literature was conducted using PubMed (Medline), Embase, and Cochrane library databases. ResultsComputed tomography showed greater sensitivity for the detection of the pathognomonic calcification than plain radiographs and facilitated the exclusion of other more severe conditions by following a systematic interpretation composed of five key elements. Plain radiographs showed non-specific signs of prevertebral soft tissue swelling and a decreased cervical lordotic curve. However, no calcification was identified on plain radiographs. The literature review revealed 153 articles containing 372 cases. Surgical or invasive procedures were mentioned in 13.7% of publications and were performed in 28 patients. ConclusionAcute longus colli tendinitis can mimic the clinical presentation of more severe conditions that the otolaryngologist may be required to evaluate, such as infectious, traumatic, and neoplastic diseases. Knowledge of this entity, with its pathognomonic imaging findings, can prevent misdirected medical therapy and unnecessary invasive procedures.

Identification of Differentially Expressed Genes Associated with Extracellular Matrix Degradation and Inflammatory Regulation in Calcific Tendinopathy Using RNA Sequencing.

Calcific tendinopathy (CT), developed due to calcium hydroxyapatite deposition in the rotator cuff tendon, mostly affects women in their 40s and 50s and causes severe shoulder pain. However, the molecular basis of its pathogenesis and appropriate treatment methods are largely unknown. In this study, we identified 202 differentially expressed genes (DEGs) between calcific and adjacent normal tendon tissues of rotator cuff using RNA sequencing-based transcriptome analysis. The DEGs were highly enriched in extracellular matrix (ECM) degradation and inflammation-related processes. Further, matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 13 (MMP13), two of the enzymes associated with ECM degradation, were found to be highly upregulated 25.85- and 19.40-fold, respectively, in the calcific tendon tissues compared to the adjacent normal tendon tissues. Histopathological analyses indicated collagen degradation and macrophage infiltration at the sites of calcific deposit in the rotator cuff tendon. Our study acts as a foundation that may help in better understanding of the pathogenesis associated with CT, and thus in better management of the disease.

Arthroscopic Treatment of an Unusual Intramuscular Calcium Hydroxyapatite Crystal Deposit on the Rotator Cuff

Hydroxyapatite crystal deposition disease and its pathophysiology are poorly understood; however, it is known that calcific tendinitis is the most common condition related to this deposition in the upper limb. Movement of the crystals toward the myotendinous junction is rare; to the best of our knowledge, only 19 cases have been described in the literature, one of which was a case of intramuscular deposition without migration. The purpose of this technical note is to describe the technical details of the arthroscopic treatment of intramuscular calcium hydroxyapatite deposits without intratendinous migration.

Calcium hydroxyapatite deposition disease: Imaging features and presentations mimicking other pathologies

ObjectiveCalcium hydroxyapatite depositional disease (HADD) is usually asymptomatic and self-limiting; however, when there is an associated inflammatory process or HADD occurs in an unusual location, it may mimic trauma, infection, or neoplasm. The purpose of this article is to review the imaging features of HADD and how to distinguish it from more worrisome entities that can have similar appearances. ConclusionAn understanding of the presentations of HADD is important to allow early and confident diagnosis. In particular, familiarity with presentations that resemble more ominous pathologies is essential to avoid costly and time-consuming workup or intervention.

Band keratopathy in children previously treated with diode laser for type 1 retinopathy of prematurity

Band keratopathy is a corneal degeneration caused by chronic inflammation, systemic abnormalities, or, rarely, a primary biallelic SLC4A4 mutation leading to calcium hydroxyapatite deposition in Bowman's layer. We report a series of 16 eyes of 10 children with a remote history of diode laser treated retinopathy of prematurity who developed late-onset band keratopathy without evidence of other prior risk factors. The majority of patients developed band keratopathy bilaterally. Five eyes had visually significant central band keratopathy that required treatment with disodium ethylenediaminetetracetic acid (EDTA) chelation or phototherapeutic keratectomy. Band keratopathy may be an underreported late ophthalmic complication of diode-laser treated retinopathy of prematurity.

Label-free quantitative proteomics identifies Smarca4 is involved in vascular calcification

Vascular calcification (VC) is a pathological process characterized by abnormal deposition of calcium phosphate, hydroxyapatite and other mineral substances in the vascular wall. Hyperphosphorus is an important risk factor associated with VC in the general population and patients with chronic kidney disease (CKD). However, there is still a lack of early biomarkers for hyperphosphorus induced VC. We established a calcific rat aorta vascular smooth muscle cells (RASMCs) model by stimulating with β-glycerophosphate. Then we performed label-free quantitative proteomics combined with liquid chromatograph–mass spectrometer/mass spectrometer (LC-2D-MS/MS）analysis and bioinformatics analysis to find the potential biomarkers for VC. In the current study, we identified 113 significantly proteins. Fifty six of these proteins were significantly up-regulated and the other 57 proteins were significantly decreased in calcific RASMCs, compared to that of normal control cells (fold-change (fc)>1.2, p < .05). Bioinformatics analysis indicated that these significant proteins mainly involved in the placenta blood vessel development and liver regeneration. Their molecule function was cell adhesion molecule binding. Among them, Smarca4 is significantly up-regulated in calcific RASMCs with fc = 2.72 and p = .01. In addition, we also established VC rat model. Real-time quantitative PCR analysis confirmed that the expression of Smarca4 was significantly increased in the aorta of calcified rat. Consistent with the up-regulation of Smarca4, the expression of VC associated microRNA such as miR-133b and miR-155 was also increased. Consequently, our study demonstrates that Smarca4 is involved in hyperphosphorus-induced VC. This finding may contribute to the early diagnosis and prevention of VC.

Heritable Ectopic Mineralization Disorders: Pathomechanisms and PotentialTreatment.

Pseudoxanthoma elasticum (PXE), a prototype of heritable ectopic mineralization disorders, is an autosomal recessive disease characterized by deposition of calcium hydroxyapatite in the skin, eyes, and cardiovascular system, with protean manifestations (Li etal., 2016; Li and Uitto, 2013; Neldner, 1988). The classic form of PXE is late-onset and slow-progressing, and the major clinical problems relate to loss of vision and development of cardiovascular complications (Neldner, 1988). The classic form of PXE is caused by loss-of-function mutations in the ABCC6 gene encoding ATP-binding cassette subfamily C, member 6 (ABCC6), a putative transmembrane efflux transporter protein expressed primarily in the liver and kidneys. The metabolic hypothesis concerning PXE postulates that the absence of functional ABCC6 activity, primarily in the liver, results in deficiency of circulating factor(s) that is physiologically required to prevent ectopic mineralization under normal calcium and phosphate homeostasis (Li etal., 2016) (Figure1). However, the factor(s) transported by ABCC6 from the intracellular milieu to the extracellular space have not been identified.

501 Plasma PPi is the major, but not exclusive, cause of ectopic mineralization in pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE), a prototype of heritable ectopic mineralization disorders, affects the skin, eyes and the arterial blood vessels. PXE is caused by inactivating mutations in the ABCC6 gene and the disease is characterized by calcium hydroxyapatite deposition on connective tissues. It was recently discovered that absence of ABCC6-mediated ATP release from the liver and consequently reduced plasma PPi levels underlie PXE. In this study, we examined whether elevated circulating levels of PPi, a powerful mineralization inhibitor, is the sole mechanism by which ABCC6 counteracts ectopic mineralization in PXE. Abcc6-/- mice, a model of PXE, were crossed with transgenic mice with ubiquitous expression of human ENPP1, an ectonucleotidase which generates PPi from ATP. We generated Abcc6-/-mice either wild type or hemizygous for human ENPP1. The Enpp1asj mice, a model for generalized arterial calcification of infancy caused by ENPP1 mutations, were also crossed with human ENPP1 transgenic mice to compensate for the loss of the endogenous mouse protein. Plasma levels of PPi and the degree of mineralization of connective tissue capsule of vibrissae, a reliable biomarker of the mineralization process in these mice, were determined. Overexpression of human ENPP1 in Enpp1asj mice normalized plasma PPi levels to that of wild type mice, and consequently, completely prevented mineralization. In contrast, significantly reduced mineralization was noted in Abcc6-/- mice with overexpression of human ENPP1, however, with small mineralization foci still evident despite increased plasma PPi levels. These results suggest that PPi is the major mediator of connective tissue mineralization in PXE, but there is a second, as-yet unknown, alternative mechanism other than PPi by which ABCC6 prevents ectopic mineralization under physiologic conditions.

Neck Pain and Acute Dysphagia

The acute tendinitis of the longus colli muscle is an unusual diagnosis in the cases of acute dysphagia with cervical pain. Is a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the prevertebral space and can cause pharyngeal swelling with impaired swallow. It is absolutely critical to make the differential diagnosis with deep cervical infections in order to avoid invasive treatments.

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells.

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO43− symmetric stretch vibrations at 959 cm−1 assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue–implant-interfaces or disease diagnosis.

A Case of Bilateral Acute Calcific Tendinitis of the Gluteus Medius, Treated by Ultrasound-guided Needle Lavage and Corticosteroid Injection.

Calcium hydroxyapatite deposition disease is a common pathology, most frequently located in the rotator cuff tendons of the shoulder, for which different therapeutic approaches are used. Ultrasound guided needle lavage and injection of anesthetic/corticosteroid is a well-known and extensively described treatment for calcific tendinits of the rotator cuff. We present a case of bilateral calcific tendinitis of the gluteus medius tendon, both sides successfully treated using ultrasound guided needle lavage of the deposits and injection of an anesthetic and corticosteroid. We propose to not only use this approach for rotator cuff tendons, but also for calcific tendinitis at other locations.

Raman spectroscopic sensing of carbonate intercalation in breast microcalcifications at stereotactic biopsy.

Microcalcifications are an early mammographic sign of breast cancer and frequent target for stereotactic biopsy. Despite their indisputable value, microcalcifications, particularly of the type II variety that are comprised of calcium hydroxyapatite deposits, remain one of the least understood disease markers. Here we employed Raman spectroscopy to elucidate the relationship between pathogenicity of breast lesions in fresh biopsy cores and composition of type II microcalcifications. Using a chemometric model of chemical-morphological constituents, acquired Raman spectra were translated to characterize chemical makeup of the lesions. We find that increase in carbonate intercalation in the hydroxyapatite lattice can be reliably employed to differentiate benign from malignant lesions, with algorithms based only on carbonate and cytoplasmic protein content exhibiting excellent negative predictive value (93–98%). Our findings highlight the importance of calcium carbonate, an underrated constituent of microcalcifications, as a spectroscopic marker in breast pathology evaluation and pave the way for improved biopsy guidance.

Aragonite coating solutions (ACS) based on artificial seawater

Aragonite (CaCO3, calcium carbonate) is an abundant biomaterial of marine life. It is the dominant inorganic phase of coral reefs, mollusc bivalve shells and the stalactites or stalagmites of geological sediments. Inorganic and initially precipitate-free aragonite coating solutions (ACS) of pH 7.4 were developed in this study to deposit monolayers of aragonite spherules or ooids on biomaterial (e.g., UHMWPE, ultrahigh molecular weight polyethylene) surfaces soaked in ACS at 30°C. The ACS solutions of this study have been developed for the surface engineering of synthetic biomaterials. The abiotic ACS solutions, enriched with calcium and bicarbonate ions at different concentrations, essentially mimicked the artificial seawater composition and started to deposit aragonite after a long (4h) incubation period at the tropical sea surface temperature of 30°C. While numerous techniques for the solution deposition of calcium hydroxyapatite (Ca10(PO4)6(OH)2), of low thermodynamic solubility, on synthetic biomaterials have been demonstrated, procedures related to the solution-based surface deposition of high solubility aragonite remained uncommon. Monolayers of aragonite ooids deposited at 30°C on UHMWPE substrates soaked in organic-free ACS solutions were found to possess nano-structures similar to the mortar-and-brick-type botryoids observed in biogenic marine shells. Samples were characterized using SEM, XRD, FTIR, ICP-AES and contact angle goniometry.

Deposition of calcium hydroxyapatite on negatively charged polyphosphazene surfaces

ABSTRACTA number of polyphosphazenes with negatively charged β‐alanine (β‐Ala) and γ‐amino butyric acid (GABA) side groups were synthesized and studied for their ability to initiate the growth of hydroxyapatite (HAp) during exposure to simulated body fluid (SBF). All the polymers were hydrolytically sensitive, with the final hydrolysis rate dependent on the specific active side groups (GABA &gt; β‐Ala). These systems also underwent extensive mineralization, with calcium phosphate deposited across their entire surface during exposure to SBF (up to 115 wt % gain after 4 weeks). This degree of deposition is a major advance over previously reported polyphosphazene systems, which underwent a maximum of 27 wt % gain after immersion in SBF for 4 weeks. The extent of mineralization over the surface was monitored using environmental scanning electron microscopy (ESEM) coupled with energy dispersive X‐ray spectroscopy (EDS). In addition, X‐ray diffraction (XRD) was used to determine the identity of the mineralized material. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41741.

The presentation, assessment, pathogenesis, and treatment of calcinosis in juvenile dermatomyositis.

Calcinosis is one of the hallmark sequelae of juvenile dermatomyositis (JDM), and despite recent progress in the therapy of JDM, dystrophic calcification still occurs in approximately one third of patients. This review discusses our current, albeit limited, understanding of risk factors for the development of calcinosis in JDM, as well as approaches to assessment, and current views on its pathogenesis. Anecdotal approaches to treating calcinosis associated with JDM, including both anti-inflammatory therapies and agents aimed at inhibiting the deposition of calcium hydroxyapatite, are reviewed. An improved understanding of the pathogenesis of calcinosis, the establishment of standardized measurement tools to assess calcinosis, and randomized controlled trials employing more sensitive outcome measures are needed to develop efficacious therapies for this often disabling complication.