Selective Dissolution of Calcium Pyrophosphate Dihydrate Crystals Using a Pyrophosphate Specific Receptor.

Pseudo-gout is caused by the deposition of highly insoluble calcium pyrophosphate dihydrate (CPPD) crystals in the joints of sufferers. This leads to inflammation and ultimately joint damage. The insolubility of CPPD is driven by the strong attraction of di-cationic calcium ions with tetra-anionic pyrophosphate ions. One of the challenges of dissolving CPPD is that a related mineral, hydroxy apatite (HA) is present in larger amounts in the form of bone and also contains strongly interacting calcium and phosphate ions. Our aim in this work was to selectively dissolve CPPD in preference to HA. To accomplish this, we used a known receptor for pyrophosphate that contains two complexed zinc ions that are ideally spaced to interact with the tetra-anion of pyrophosphate. We hypothesized that such a molecule could act as a preorganized tetra-cation that would be able to outcompete the two calcium ions present in the crystal lattice of CPPD. We demonstrate both visually and through analysis of released phosphorous that this molecule is able to preferentially dissolve CPPD over the closely related HA and thus can form the basis for a possible approach for the treatment of pseudo-gout.

An objective diagnosis of gout and calcium pyrophosphate deposition disease with machine learning of Raman spectra acquired in a point-of-care setting.

OBJECTIVE: Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department. METHODS: We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centra. We analyzed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or else. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine. RESULTS: The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI 92.3-98.3), while the accuracy for classification of MSU with using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI 87.9-95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI 82.7-92.2). The model was able to discriminate between pathologic crystals, artifacts, and other particles such as microplastics. CONCLUSION: We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner.

Acute calcium pyrophosphate crystal arthritis is associated with an increased rate of hip and knee joint surgery.

OBJECTIVE: Acute calcium pyrophosphate (CPP) crystal arthritis is a distinct manifestation of calcium pyrophosphate crystal deposition (CPPD). No studies have specifically examined whether acute CPP crystal arthritis is associated with progressive structural joint damage. The objective of this retrospective cohort study was to evaluate the relative rate of hip and knee joint arthroplasties as an estimate of structural joint damage accrual, in a population of patients with acute CPP crystal arthritis. METHODS: Data were collected from Waikato District Health Board (WDHB) to identify an acute CPP crystal arthritis cohort with clinical episodes highly characteristic of acute CPP crystal arthritis. Data on hip and knee joint arthroplasties were collected from the New Zealand Orthopaedic Association's Joint Registry. The rate of arthroplasties in the cohort was compared with the age-ethnicity-matched New Zealand population. Additional analysis was performed for age, obesity (BMI) and ethnicity. RESULTS: The acute CPP crystal arthritis cohort included 99 patients; 63 were male and the median age was 77 years (interquartile range, 71-82). The obesity rate was 36% with a median BMI of 28.4 kg/m2 (interquartile range, 25.8-32.2), comparable to the New Zealand population. The standardized surgical rate ratio in the cohort vs the age-ethnicity-matched New Zealand population was 2.54 (95% CI: 1.39, 4.27). CONCLUSION: Our study identified a considerable increase in the rate of hip and knee joint arthroplasties in patients with episodes of acute CPP crystal arthritis. This suggests CPP crystal arthritis may be a chronic condition, leading to progressive joint damage.

Calcium Pyrophosphate Crystal Formation and Deposition: Where Do we Stand and What Does the Future hold?

PURPOSE OF THE REVIEW: Although calcium pyrophosphate deposition (CPPD) has been known since the 1960s, our understanding of its pathogenesis remains rudimentary. This review aims to illustrate the known mechanisms underlying calcium pyrophosphate (CPP) crystal formation and deposition and explore future directions in research. By examining various perspectives, from basic research to clinical and imaging assessments, as well as new emerging methodologies, we can establish a starting point for a deeper understanding of CPPD pathogenesis. RECENT FINDINGS: Recent years have seen significant advances in CPPD research, particularly in the clinical field with the development of the 2023 ACR/EULAR classification criteria for CPPD disease, and in imaging with the introduction of the OMERACT ultrasonographic definitions and scoring system. However, progress in basic research has been slower. New laboratory approaches, such as Raman spectroscopy and omics sciences, offer promising insights that may help piece together the puzzle of CPPD. CPPD is a common yet understudied condition. As the population ages and CPPD becomes more prevalent, there is an urgent need to better understand the disease and the mechanisms involved in crystal formation and deposition, in order to improve diagnosis and therapeutic approaches.

Calcium Pyrophosphate Crystal Deposition: Insights to Risks Factors and Associated Conditions.

PURPOSE OF THE REVIEW: This review provides an overview of medical conditions and risk factors associated with CPPD. RECENT FINDINGS: Recent studies have indicated that CPPD patients may have a higher risk for systemic conditions such as cardiovascular diseases. Calcium pyrophosphate deposition disease (CPPD) is a common crystal arthropathy that primarily affects older adults, and, in most cases, the aetiology is idiopathic. Age is the most remarkable risk factor and due to the aging population, the prevalence of this condition is expected to increase. Strong evidence supports an association between CPPD and several metabolic and endocrine conditions, including hemochromatosis, hyperparathyroidism, hypomagnesemia, and hypophosphatasia. Additionally, there is growing evidence of an increased risk for cardiovascular diseases among CPPD patients, alongside potential links to rheumatic disorders, gender, medications, and joint trauma. Further research is needed to explore the underlying mechanisms linking CPPD to associated conditions and to develop targeted therapies with the aim of improving patient outcomes.

Diagnosis of calcium pyrophosphate crystal deposition disease by ultrasonography: how many and which sites should be scanned?

OBJECTIVE: To develop the optimal US scanning protocol for the diagnosis of CPPD disease. METHODS: In this cross-sectional study, consecutive patients with a crystal-proven diagnosis of CPPD disease, and age-, sex-matched disease controls and with a negative synovial fluid analysis were prospectively enrolled in two Italian Institutions. Four rheumatologists, blinded to patients' clinical details, performed US examinations using a standardised scanning protocol including 20 joints (shoulders, elbows, wrists, metacarpophalangeal joints from 2nd to 5th fingers, hips, knees, ankles). CPPD was identified as presence/absence, according to the OMERACT definitions. Reduced US scanning protocols were developed by selecting the most informative joints to be imaged by US using the LASSO technique. Patients were randomly divided into training and validation sets. Their diagnostic accuracy was tested comparing the area under the ROC curves. RESULTS: 204 participants were enrolled: 102 with CPPD disease and 102 disease controls [age (mean±standard deviation) 71.3 ± 12.0 vs 71.1 ± 13.5 years, female: 62.8% vs 57.8%].The median number of joints with US evidence of CPPD was 5 (IQR: 4-7) and 0 (IQR: 0-1) in patients with CPPD disease and controls, respectively (p< 0 01).The detection of CPPD in ≥ 2 joints using a reduced scanning protocol (bilateral assessment of knees, wrists, and hips) showed a sensitivity of 96.7% (95%CI: 82.8-99.9) and a specificity of 100 (95%CI: 88.8-100.0) for the diagnosis of CPPD disease and had good feasibility [(mean±standard deviation) 12.5 ± 5.3 min]. CONCLUSION: Bilateral US assessment of knees, wrists, and hips had excellent accuracy and good feasibility for the diagnosis of CPPD disease.

In patients with acute mono/oligoarthritis, a targeted ultrasound scanning protocol shows great accuracy for the diagnosis of gout and CPPD.

OBJECTIVES: To determine an US scanning protocol with the best accuracy for the diagnosis of gout and CPPD in patients with acute mono/oligo-arthritis of unknown origin. METHODS: Patients with acute mono/oligo-arthritis in whom a joint aspiration at the most clinically involved joint (target joint) was requested were consecutively enrolled. US was performed in each patient before the arthrocentesis. The accuracy of different US findings and scanning protocols for the diagnosis of gout and CPPD was calculated. RESULTS: A total of 161 subjects were included (32 gout patients, 30 CPPD patients and 99 disease-controls). US findings had a high specificity for gout (0.92-0.96) and CPPD (0.90-0.97), while the sensitivity ranged from 0.73 to 0.85 in gout (double contour sign and tophi, respectively) and from 0.60 to 0.90 in CPPD (hyaline and fibrocartilage deposits, respectively). The US assessment of two joints bilaterally (gout: knees, MTP1 joints; CPPD: knees, wrists) plus the target joint had an excellent diagnostic sensitivity (gout: 0.91, CPPD: 0.93) and specificity (gout: 0.91, CPPD: 0.89). This targeted US scanning protocol yielded to higher diagnostic accuracy compared with the US evaluation of the target joint [gout area under the curve (AUC) 0.91 vs 0.84, P = 0.03; CPPD AUC 0.93 vs 0.84, P = 0.04] unless the target joint was the knee or the MTP1 joint in gout and the knee or the wrist in CPPD. CONCLUSIONS: A targeted US scanning protocol of two joints bilaterally plus the target joint showed an excellent accuracy (>90%) for the diagnosis of crystal arthritis in patients with acute mono/oligoarthritis.

An Update on the Diagnosis and Management of Calcium Crystal Disease.

PURPOSE OF REVIEW: This article aims to review the challenges to diagnosis and management of calcium crystal deposition diseases and evaluate the literature published over the past 3 years. RECENT FINDINGS: The awaited development of classification criteria is an essential step in the progression of calcium crystal deposition disease clinical research. There have been recent improvements in the accuracy of imaging for the diagnosis of crystal deposition diseases with published definitions of characteristic features. Factors associated with acute flares of disease have been identified and an association with increased cardiovascular risk has been demonstrated. Targeted treatment options for calcium crystal diseases remain elusive. However, there have been advances in understanding the molecular mechanisms of disease revealing potential targets for future drug development. Calcium-crystal deposition diseases are increasing in incidence and prevalence as populations age and continue to associate with a high burden of disability. Despite this, calcium crystal deposition disease remains under-studied with a paucity of evidence-based treatment guidelines.

Ultrasound findings of calcium pyrophosphate deposition disease at metacarpophalangeal joints.

OBJECTIVE: To explore the spectrum of articular and peri-articular ultrasound (US) findings at metacarpophalangeal (MCP) joints in calcium pyrophosphate (CPP) deposition disease (CPPD). METHODS: Consecutive CPPD patients (chronic CPP crystal inflammatory arthritis or OA with CPPD), and age- and sex-matched controls with RA were prospectively enrolled. Patients underwent bilateral US examination of MCP joints. CPP deposits, synovial inflammation, osteophytes, cartilage damage and bone erosions were recorded. RESULTS: Sixty CPPD patients (33, 55.0% with OA with CPPD and 27, 45.0% with chronic CPP crystal inflammatory arthritis) and 40 RA patients were enrolled. CPP deposits were detected in 24 (40.0%) CPPD patients and in 3 (7.5%) RA patients (P <0.01). In CPPD patients, different types of CPP deposits were identified at MCP joints: 17 (28.3%) patients had dorsal capsuloligamentous deposits, 14 (23.3%) intra-cartilaginous deposits, 13 (21.7%) lateral capsuloligamentous deposits, 12 (20.0%) intra-articular deposits, eight (13.3%) double contour sign and five (8.3%) flexor digitorum tendons' deposits. CPPD patients with chronic CPP crystal inflammatory arthritis showed more US findings indicating synovial inflammation and CPP deposits than those with OA with CPPD. Conversely, a higher prevalence of US features indicating structural damage was noted in this latter phenotype. CPP deposits and bone erosions were the US findings with the highest value for diagnosing chronic CPP crystal inflammatory arthritis and RA, respectively. CONCLUSION: This study provides pictorial evidence of the broad spectrum of US findings indicating CPP deposits at MCP joints in CPPD. Furthermore, we reported different US patterns in different CPPD phenotypes.

Calcium pyrophosphate deposition (CPPD) in a liver transplant patient: are hypomagnesemia, tacrolimus or both guilty? A case-based literature review.

Calcium pyrophosphate deposition (CPPD) can be induced by a persistent hypomagnesemia. Tacrolimus is an immunosuppressive treatment especially used in organ transplant, potentially inducer of hypomagnesemia by renal loss. A 53-year-old man, liver transplant 10 months earlier, developed an acute peripheral oligoarthritis of wrist, hip and elbow with fever, associated with acute low back pain. Synovial fluid was sterile, and revealed calcium pyrophosphate crystals. Spinal imaging showed inflammatory changes. Magnesium blood level was low at 0.51 mmol/l, with high fractional excretion in favor of renal loss. Tacrolimus was changed for everolimus, proton pump inhibitor was stopped, and magnesium oral supplementation was started. After 8 months follow-up and slow prednisone tapering, he did not relapse pain. Persistent hypomagnesemia is a rare secondary cause of CPPD. In this entity, drug liability should be investigated such as tacrolimus in organ transplant patient.

The role of Interleukin-1 receptor antagonist as a treatment option in calcium pyrophosphate crystal deposition disease.

Calcium Pyrophosphate Crystal Deposition (CPPD) disease is characterized by the deposition of calcium pyrophosphate crystals in the cartilage. In most cases, it can manifest as a subclinical condition named chondrocalcinosis, often revealed by joint x-ray examination. In other cases, deposition can cause flares of arthritis, known as acute CPP crystal arthritis. In the last few years, many pathogenic pathways have been discovered. Interleukin-1 (IL-1) plays a key role in the pathogenesis of CPPD disease, both as a mediator of inflammatory response to crystals and as a promoter of damage to articular cartilage. In this review, we investigated the role of IL-1R inhibitor, such as Anakinra, as an alternative to the various therapeutic strategies for CPPD disease, especially among patients resistant to traditional treatment with NSAIDs, corticosteroids and colchicine.

Rare presentation of intradural calcium pyrophosphate dihydrate crystal deposition.

Calcium pyrophosphate dihydrate crystal deposition (CPPD), also known as pseudogout, can have spinal manifestations in roughly one quarter of patients. We present a rare, intradural manifestation of CPPD requiring surgical intervention, with a review of pertinent differential diagnoses on imaging. A 48-year-old male presented with urinary retention, and was found to have an intradural lesion with peripheral enhancement on gadolinium T1-weighted magnetic resonance imaging. Due to the patient's progressive neurological deterioration, he was taken for a minimally invasive approach for resection of the lesion. Histopathological analysis revealed crystal deposits with rhomboidal birefringence consistent with CPPD. The imaging features of this lesion were atypical for any of the traditional intradural extramedullary lesions. Typically seen extradurally, recognizing CPPD as a potential culprit for intradural compression is helpful to recognize for providers.

A Phage Display-Identified Short Peptide Capable of Hydrolyzing Calcium Pyrophosphate Crystals-The Etiological Factor of Chondrocalcinosis.

Chondrocalcinosis is a metabolic disease caused by the presence of calcium pyrophosphate dihydrate crystals in the synovial fluid. The goal of our endeavor was to find out whether short peptides could be used as a dissolving factor for such crystals. In order to identify peptides able to dissolve crystals of calcium pyrophosphate, we screened through a random library of peptides using a phage display. The first screening was designed to select phages able to bind the acidic part of alendronic acid (pyrophosphate analog). The second was a catalytic assay in the presence of crystals. The best-performing peptides were subsequently chemically synthesized and rechecked for catalytic properties. One peptide, named R25, turned out to possess some hydrolytic activity toward crystals. Its catalysis is Mg2+-dependent and also works against soluble species of pyrophosphate.

Utility of Ultrasound and Dual Energy CT in Crystal Disease Diagnosis and Management.

PURPOSE OF REVIEW: The objective of this review is to critically discuss the latest evidence on the use of ultrasound and dual energy computed tomography (DECT) for the assessment of microcrystalline arthritis. RECENT FINDINGS: Both techniques have been included in the classification and diagnostic criteria for gout, while only ultrasound appears in the diagnostic recommendations for CPPD. Regarding the management of the diseases, there is encouraging evidence for the use of both techniques for the follow-up of gout patients, while very few or null data are available for CPPD. Ultrasound has been adequately validated for the diagnosis of CPPD, while some issues have still to be clarified regarding gout. DECT has also demonstrated to be accurate for gout diagnosis, but very few data are available regarding CPPD. Future research should aim to improve the reliability of both techniques and to create scoring systems for a more accurate follow-up of patients.

Fluorescence Differentiation of ATP-related Multiple Enzymatic Activities in Synovial Fluid as a Marker of Calcium Pyrophosphate Deposition Disease using Kyoto Green.

Calcium pyrophosphate deposition disease (CPPD) is a crystal induced inflammation in joints, and causes severe pain in elderly people. The accumulation of pyrophosphate (PPi) in synovial fluid (SF) results from several enzymatic reactions, especially the highly activated e-NPPs, which catalyze the conversion of ATP to PPi. This study demonstrates the detection of relative catalytic activity of 3 enzymes-ecto-nucleotide pyrophosphatase/phosphodiesterases (e-NPPs), tissue nonspecific alkaline phosphatase (TNAP), and ecto-nucleoside triphosphate diphosphohydrolases (e-NTPDases)-using a single molecular sensor called Kyoto Green. Kyoto Green exhibits excellent performance in sensing the catalytic activity of the commercial representatives of the e-NPPs, TNAP, and e-NTPDases, which are ENPP1, PPase, and apyrase, respectively, in both single-enzyme and multi-enzyme assays. Analysis of SF enzymes in 19 SF samples from human and swine revealed moderate activity of e-NPPs, high activity of e-NTPDases, and low activity of TNAP. Our newly developed method for analysis of multiple enzymatic activities using Kyoto Green in biological SF will assist improvement in accuracy of the CPPD prognosis/diagnosis, which will minimize unnecessary medical procedures.

Identification of adenine-N9-(methoxy)ethyl-ß-bisphosphonate as NPP1 inhibitor attenuates NPPase activity in human osteoarthritic chondrocytes.

Overproduction of extracellular diphosphate due to hydrolysis of ATP by NPP1 leads to pathological calcium diphosphate (pyrophosphate) dihydrate deposition (CPPD) in cartilage, resulting in a degenerative joint disease that today lacks a cure. Here, we targeted the identification of novel NPP1 inhibitors as potential therapeutic agents for CPPD deposition disease. Specifically, we synthesized novel analogs of AMP (NPP1 reaction product) and ADP (NPP1 inhibitor). These derivatives incorporate several chemical modifications of the natural nucleotides including (1) a methylene group replacing the Pα,ß-bridging oxygen atom to provide metabolic resistance, (2) sulfonate group(s) replacing phosphonate(s) to improve binding to NPP1's catalytic zinc ions, (3) an acyclic nucleotide analog to allow flexible binding in the NPP1 catalytic site, and (4) a benzimidazole base replacing adenine. Among the investigated compounds, adenine-N9-(methoxy)ethyl-ß-bisphosphonate, 10, was identified as an NPP1 inhibitor (Ki 16.3 µM vs. the artificial substrate p-nitrophenyl thymidine-5'-monophosphate (p-Nph-5'-TMP), and 9.60 µM vs. the natural substrate, ATP). Compound 10 was selective for NPP1 vs. human NPP3, human CD39, and tissue non-specific alkaline phosphatase (TNAP), but also inhibited human CD73 (Ki 12.6 µM). Thus, 10 is a dual NPP1/CD73 inhibitor, which could not only be of interest for treating CPPD deposition disease and calcific aortic valve disease but may also be considered for the immunotherapy of cancer. Compound 10 proved to be a promising inhibitor, which almost completely reduces NPPase activity in human osteoarthritic chondrocytes at a concentration of 100 µM.

Issues in CPPD Nomenclature and Classification.

PURPOSE OF REVIEW: This paper covers confusion and challenges in the nomenclature of calcium pyrophosphate deposition disease. Clinicians, investigators, and patients are faced with a variety of terms that are used to describe CPPD and its phenotypes, and clarity is greatly needed to help advance research and patient care. Motivation for the upcoming development of CPPD classification criteria is reviewed. RECENT FINDINGS: EULAR proposed recommended terminology for CPPD in 2011. International Classification of Diseases (ICD-9 and ICD-10) billing codes identify definite or probable CPPD with variable accuracy depending on the clinical setting and comparator group. READ diagnostic codes have been employed to identify pseudogout in UK datasets but their accuracy has not been evaluated. CPPD classification criteria will provide a system for identifying a relatively homogenous group of patients to be included in clinical studies, enabling comparison of outcomes across studies. CPPD nomenclature remains challenging for clinicians, investigators, and patients. A lay-friendly definition of CPPD, using easily accessible terminology, would be welcome. CPPD classification criteria are a necessary step in moving forward CPPD clinical research and may involve a range of clinical, laboratory, and imaging modalities.

Calcium-Containing Crystals and Osteoarthritis: an Unhealthy Alliance.

PURPOSE OF REVIEW: Osteoarthritis (OA) is the most common form of joint disease globally and is associated with significant morbidity and disability. Increasing evidence points to an important inflammatory component in the development and progression of OA. The precise pathways involved in OA inflammatory processes remain to be clarified. Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals can induce inflammation and arthritis and recent studies point to a potential pathogenic role in OA. In the light of this evidence, we explore the relationship and potential mechanistic pathways linking calcium-containing crystals and OA. RECENT FINDINGS: CPP crystals induce inflammation through the NLRP3 inflammasome while BCP crystals mediate both NLRP3 dependent and independent effects. BCP crystals have been demonstrated to induce key mitogenic and inflammatory pathways and contribute to cartilage degradation. Calcium-containing crystals induce key inflammatory pathways and may represent an attractive novel target in OA, a condition devoid of effective treatments.

Pseudogout among Patients Fulfilling a Billing Code Algorithm for Calcium Pyrophosphate Deposition Disease.

To test the performance of a billing claims-based calcium pyrophosphate deposition disease (CPPD) algorithm for identifying pseudogout. We applied a published CPPD algorithm at an academic institution and randomly selected 100 patients for electronic medical record review for 3 phenotypes: (1) definite/probable CPPD, (2) definite/probable pseudogout; (3) definite pseudogout. Clinical data were recorded and positive predictive value (PPV) (95% CI) for each phenotype was calculated. We then modified the published algorithm to require ≥ 1 of 4 relevant terms ("pseudogout", "calcium pyrophosphate crystals", "CPPD", or "chondrocalcinosis") through automated text searching in clinical notes, and re-calculated PPVs. To estimate the percentage of pseudogout patients not identified by the published algorithm, we reviewed a random sample of 50 patients with ≥ 1 of 4 relevant terms in clinical notes who did not fulfill the published algorithm. Among patients fulfilling the published algorithm, 68% had ≥ 1 of 3 phenotypes. The published algorithm had PPV 24.0% (95% CI 19.3-28.7%) for definite/probable pseudogout and 18.0% (95% CI 14.5-21.5%) for definite pseudogout. Requiring ≥ 1 of 4 relevant terms in clinical notes increased PPV to 33.3% (95% CI 26.8-39.8%) for definite/probable pseudogout and 24.6% (95% CI 19.8-29.4%) for definite pseudogout. Among patients not fulfilling the published algorithm, 16.0% had definite/probable pseudogout and 6.0% had definite pseudogout. A billing code-based CPPD algorithm had low PPV for identifying pseudogout. Adding text searching modestly enhanced the PPV, though it remained low. These findings highlight the need for improved approaches to identify pseudogout to facilitate epidemiologic studies.

Non-union rate of type II and III odontoid fractures in CPPD versus a control population.

OBJECTIVE: The objective was to determine if there is a significant difference between rates of non-union of type II and III odontoid fractures in patients with calcium pyrophosphate dihydrate deposition (CPPD) compared with a control population. MATERIALS AND METHODS: A 10-year retrospective picture archive and communications system review was performed of 31 CPPD patients and 31 control patients. Imaging studies were reviewed for radiographic or CT evidence of osseous union and complications. RESULTS: There was a significant difference in the rates of non-union between the two groups, with the non-union rate reaching 90.3% in the CPPD group and 32% in the control group. Comparing the degree of displacement and angulation of the two groups did not show a significant difference. CONCLUSION: The results indicate that odontoid fracture non-union rates are significantly higher in CPPD patients and should be taken into consideration when diagnosing odontoid fractures and deciding on appropriate treatment.