Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. RESULTS: Serum 25(OH) vitamin D levels were lower in MS patients than in controls (p = 0.009). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (p = 0.88). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (p = 0.05). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (p = 0.65). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (p = 0.03). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 (p = 0.63). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. CONCLUSION: Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.

The -675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus, its clinical manifestations, and comorbidities in Mexican-Mestizo population.

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the -675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The -675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81-3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62-4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31-2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84-3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the -675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.

Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.

Diseño de oligonucleótidos sonda para la detección de virus de interés en biodefensa / Oligonucleotide probes design for the detection of interesting in biodefense viruses

ANTECEDENTES: Los virus causan enfermedades en el hombre como la gripe, la rabia, la fiebre amarilla o la fiebre hemorrágica. Además, presentan características como alta variabilidad genética, virulencia y fácil transmisión y producción con infraestructuras mínimas, lo que les convierte en un problema de salud pública y de bioseguridad. Por todo ello, desarrollar sistemas de biodetección precisos y versátiles es un reto ante el cual, la tecnología de micromatrices de ADN, se presenta como un sistema de ideal. OBJETIVOS: Diseño de oligonucleótidos sonda para la detección de especies pertenecientes a nueve familias de virus de interés en biodefensa. Material y MÉTODOS: Se seleccionaron familias de virus de interés en biodefensa, se buscaron los genomas completos de los virus de referencia de cada una de ellas en las bases de datos (GenBank) y se identificaron fragmentos de 60 nucleótidos que cumplieran determinados condicionantes estructurales, evaluándose con BLASTN su capacidad de hibridación cruzada. RESULTADOS: Se obtuvieron los genomas de referencia de virus pertenecientes a nueve familias. Se diseñaron un total de 54 nucleótidos sonda, seis de ellos correspondientes al virus de la gripe A tipo H1N1 y se clasificaron las secuencias según su índice de identidad, permitiendo predecir la capacidad diagnóstica de las sondas diseñadas. CONCLUSIONES: Se han encontrado secuencias suficientes para identificar nueve familias de virus, de interés en la biodefensa, mediante la tecnología de hibridación de micromatrices de ADN

BACKGROUND: Viruses cause human diseases such as influenza, rage, yellow fever and hemorrhagic fever. In addition, they have characteristics such as high genetic variability, virulence and easy transmission and production with minimum level of infrastructure, which make them not only a public health but also a biosecurity problem. Therefore, the development of accurate and versatile biodetection systems is a challenge in which DNA microarray technology is released as an ideal system. OBJECTIVES: Probe design for virus detection by microarray technology. MATERIALS AND METHODS: Virus families with interest in biodefense were selected and the complete genomes of the reference viruses were searched in the databases (GenBank). Fragments of 60 nucleotides with some specific physical characteristics were identified. Finally, cross-hybridization capacity was also evaluated with BLASTN software. RESULTS: Viral genomes from nine families were obtained. A total of 54 probe nucleotides were designed, six of them corresponding to influenza A type H1N1 virus and the sequences were classified according to their identity index, allowing to predict the diagnostic capacity of the designed probes. CONCLUSION: It has been found enough sequences to identify nine virus families with interest in biodefense by means of the DNA microarray technology

Optimización del proceso de inmovilización de anticuerpos en inmunobiosensores / Optimization of the antibody immobilization process in immunobiosensors

Antecedentes: La detección rápida y específica de agresivos biológicos es fundamental en diversos campos como control ambiental, diagnóstico clínico, industria alimentaria, seguridad y defensa. La especificidad de la unión antígeno-anticuerpo es empleada en multitud de biosensores, como equipos de identificación de agentes de guerra biológicos, pero el cómo se una ese anticuerpo en la superficie del biosensor, en términos de densidad, orientación, y estabilidad determinará la capacidad diagnóstica del dispositivo. Objetivo: Desarrollo de procesos de inmovilización de anticuerpos en superficies planares que permitan una unión antígeno-anticuerpo eficiente, para su posterior uso en dispositivos inmunológicos de sensado. Material y Métodos: Se ensayaron tres métodos de inmovilización del anticuerpo-fluoresceína sobre una membrana Zprobe: adsorción pasiva, unión covalente con glutaraldehído (0,5 %) y unión orientada con proteína mediadora A/G (5 y 10 µg). Se seleccionó albúmina sérica bovina-ficoeritrina como simulante de toxina proteica. Resultados: El porcentaje de retención del anticuerpo inmovilizado durante el proceso de inmunocaptura fue similar en los métodos ensayados. La densidad del anticuerpo inmovilizado fue mayor en la inmovilización con glutaraldehído y menor con proteína A/G. Sin embargo, respecto a la eficiencia de la inmunocaptura del antígeno, la inmovilización del anticuerpo con glutaraldehído fue la menos eficiente frente a la inmovilización con proteínas A/G, que resultó ser la más eficaz. Conclusiones: La utilización de glutaraldehído en la inmovilización del anticuerpo, aunque incrementa la densidad de unión del mismo sobre una membrana Zprobe, interfiere en el proceso de inmunodetección antigénica, mientras que el uso de la proteína mediadora A/G permiten un sistema de inmunocaptura más eficiente, con una menor densidad de anticuerpo inmovilizado

Antecedent: A quick and specific detection of biological warfare agent is the keystone in several fields like environmental control, clinic diagnostic, food industry, security and defence. The specificity of antigen-antibody binding is used in a multitude of biosensors like biological warfare-agent detection equipment. However, how the antibody is attached to the biosensor surface, in terms of density, orientation and stability, will determine the diagnosis capability of the device. Aim: the development of antibodies immobilization proceedings in planar surface for an efficient antigen-antibody reaction to be used in immunological sensing devices. Material and Methods: three immobilization methods of fluorescein labelled antibody were assayed on Zprobe membrane: passive adsorption, covalent bond by glutaraldehyde, well-oriented immobilization by the intermediate protein A/G. Bovine serum albumin labelled with R-phycoerytrin was selected as toxin surrogate. 0,5 % glutaraldehyde and A/G chimeric protein (5 and 10 µg) were used as immobilization reactive. Results: immobilized antibody retention during the immunocapture process was similar between all the assayed immobilization methods. The immobilized antibody density by glutaraldehyde was higher than that by protein A/G. However, with regard to the antigenic immune-capture efficiency antibody immobilization by glutaraldehyde was the less efficient than immobilization by protein A/G. Conclusions: Antibody immobilization by glutaraldehyde, in spite of increasing the retained antibody density on the Zprobe membrane, interferes in the antigenic immunodetection whereas the intermediate protein A/G improves it, allowing a very efficient immunocapture system with less antibody density

Simulacro de Actuación de las Unidades Operativas NRBQ / Training exercise of CBN Operating Units

Antecedentes: Ante la creciente amenaza terrorista, la mayoría de los países han creado Unidades Operativas especializadas en la lucha contra armas de destrucción masiva (ADM). Uno de los puntos críticos en un incidente bioterrorista es la detección e identificación precoz de estos agentes, para lo cual es imprescindible realizar una adecuada toma de muestras, conservación, transporte y custodia de las mismas hasta el laboratorio de referencia. Objetivo: Valorar el entrenamiento de las Unidades de toma de muestras NBQ mediante la realización de simulacros. Lugar de realización: Área de Defensa Biológica del Instituto Nacional de Técnica Aeroespacial «Esteban Terradas» (INTA). Diseño: Se presenta la preparación y desarrollo de un ejercicio de entrenamiento de los Equipos de Reconocimiento (RECO) y de Muestreo e Identificación de Agentes Biológicos, Químicos y Radiológicos (SIBCRA en inglés) del Regimiento de la Defensa NBQ Valencia I (RGTO DNBQ Valencia I). Resultados: Se obtienen muestras NBQ y se evalúa la eficacia de la operativa de la toma de muestras, transmisión de los datos y coordinación general del ejercicio (AU)

Antecedents: Due to the merging terrorist threat, most of the countries have created specialized operating units to fight weapons of mass destruction. One of the critical points in a bioterrorist incident is the early detection and identification of these agents. In this sense, it is essential to perform appropriate procedures for sampling, storage, transportation and custody of them until the reference laboratory. Objective: to train the different NBC Units by means of simulacrums. Place of performance: Biological Defense Area of the National Institute of Aerospace Technique "Esteban Terradas" (INTA). Design: This paper shows the preparation and development of a training exercise of Reconnaissance teams (RECO) and Sampling and Identification of Biological, Chemical and Radiological Agents teams (SIBCRA) from NBC Defense Regiment Valencia I. Results: NBQ samples are obtained and the efficiency of the operations, sampling, data transmission and general coordination of the exercise is evaluated (AU)

Características dermatoscópicas del triquilemoma facial / Dermoscopic Features of Facial Trichilemmoma

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Protocolo para la identificación rápida y sensible de ricina en muestras ambientales ante una alerta biológica / Protocol for rapid and sensitive identification of ricin in environmental samples during a biological alert

Introducción: La ricina es una toxina muy potente que ha adquirido importancia por su potencial uso como arma biológica, fundamentalmente en forma pulverulenta. El desarrollo de métodos que permitan una detección rápida y temprana tras la exposición a la toxina permitiría reducir las tasas de morbilidad y mortalidad asociadas. Ante una alerta/amenaza biológica con una muestra sospechosa de contener ricina, la Red de Laboratorios de Alerta Biológica (RELAB), infraestructura de naturaleza científico-técnica creada mediante la Orden PRE/305/2009, autoriza el envío de la muestra al Instituto Nacional de Técnica Aerospacial (INTA), uno de los laboratorios de referencia que integran esta Red. Objetivos: Desarrollo de un protocolo para la detección de ricina basado en una doble detección, un ensayo inmunológico y un análisis proteico, para aumentar la fiabilidad del diagnóstico además de acortar sensiblemente el tiempo de respuesta del laboratorio. Material y Métodos: El diagnóstico inmunológico con anticuerpos in house combinados en un ELISA tipo Sandwich. El diagnóstico proteico mediante la técnica SDS-PAGE (electroforesis en gel de poliacrilamida con dodecilsulfato sódico) para determinar el tamaño y la estructura de las distintas proteínas de la muestra. Resultados: La optimización del marcado de los anticuerpos de detección, así como la preparación y almacenamiento de placas previamente tapizadas/bloqueadas permite conseguir un ensayo muy sensible (<1 ng/mL) en un tiempo inferior a cuatro horas. Conclusión: La realización de ambos ensayos en paralelo permite disponer de un método diagnóstico robusto, sensible y rápido (AU)

Introduction: Ricin is a powerful toxin wich has gained importance due to its potential use as biological weapon, essentially in powder form. The development of methods that promote a rapid detection after the toxin exposure will allow us to reduce its associated rates of both mobility and mortality. In the face of biological threat with samples suspected of containing ricin, the Biological-Alert-Laboratory-Network (RELAB), which is a scientific-technical infrastructure created by the Order of the Ministry of the Presidency PRE/305/2009, authorizes the shipment of this type of samples to the National Institute of Aerospace Technique (INTA), one of the Reference Laboratory belonging to this Network. Aim: Development of one protocol to detect ricin based on both an immunological assay and a protein analysis focused to reduce noticeably the response time of the laboratory. Material and Methods: The Immunological diagnosis of ricin uses in house antibodies combined in an ELISA sandwich. Protein diagnosis through the SDS-PAGE technique defines the size and structure of different proteins contained in the sample. Results: The optimization of detection antibody labelling and the development of precoated-and-preblocked stored plates has allowed us to achieve a very sensitive assay (<1 ng/mL) less than four hours. Conclusion: Carrying out both assays in paralell enables us to have a hardy, sensitive and rapid method to identify ricin (AU)

Polymorphism rs2073618 of the TNFRSF11B (OPG) Gene and Bone Mineral Density in Mexican Women with Rheumatoid Arthritis.

Osteoporosis (OP) is highly prevalent in rheumatoid arthritis (RA) and is influenced by genetic factors. Single-nucleotide polymorphism (SNP) rs2073618 in the TNFRSF11B osteoprotegerin (OPG) gene has been related to postmenopausal OP although, to date, no information has been described concerning whether this polymorphism is implied in abnormalities of bone mineral density (BMD) in RA. We evaluated, in a case-control study performed in Mexican-Mestizo women with RA, whether SNP rs2073618 in the TNFRSF11B gene is associated with a decrease in BMD. RA patients were classified as follows: (1) low BMD and (2) normal BMD. All patients were genotyped for the rs2073618 polymorphism by PCR-RFLP. The frequency of low BMD was 74.4%. Higher age was observed in RA with low BMD versus normal BMD (62 and 54 years, resp.; p < 0.001). Worse functioning and lower BMI were observed in RA with low BMD (p = 0.003 and p = 0.002, resp.). We found similar genotype frequencies in RA with low BMD versus RA with normal BMD (GG genotype 71% versus 64.4%, GC 26% versus 33%, and CC 3% versus 2.2%, resp.; p = 0.6). We concluded that in Mexican-Mestizo female patients with RA, the rs2073618 polymorphism of the TNRFS11B gene is not associated with low BMD.

Enfermedad de Rosai-Dorfman cutánea facial / Facial Cutaneous Rosai-Dorfman Disease

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Onicomicosis subungueal proximal en paciente tratado con inhibidores del factor de necrosis tumoral alfa / Proximal subungual onychomycosis in a patient treated with tumor necrosis factor alpha blockers

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Placa infiltrada en labio superior de paciente con mieloma múltiple / Indurated plaque on the upper lip of a patient with multiple myeloma

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Association between -174G/C and -572G/C interleukin 6 gene polymorphisms and severe radiographic damage to the hands of Mexican patients with rheumatoid arthritis: a preliminary report.

Several interleukin 6 gene (IL6) polymorphisms are implicated in susceptibility to rheumatoid arthritis (RA). It has not yet been established with certainty if these polymorphisms are associated with the severe radiographic damage observed in some RA patients, particularly those with the development of joint bone ankylosis (JBA). The objective of the present study was to evaluate the association between severe radiographic damage in hands and the -174G/C and -572G/C IL6 polymorphisms in Mexican Mestizo people with RA. Mestizo adults with RA and long disease duration (>5 years) were classified into two groups according to the radiographic damage in their hands: a) severe radiographic damage (JBA and/or joint bone subluxations) and b) mild or moderate radiographic damage. We compared the differences in genotype and allele frequencies of -174G/C and -572G/C IL6 polymorphisms (genotyped using polymerase chain reaction-restriction fragment length polymorphism) between these two groups. Our findings indicated that the -174G/C polymorphism of IL6 is associated with severe joint radiographic damage [maximum likelihood odds ratios (MLE_OR): 8.03; 95%CI 1.22-187.06; P = 0.03], whereas the -572G/C polymorphism of IL6 exhibited no such association (MLE_OR: 1.5; 95%CI 0.52-4.5; P = 0.44). Higher anti-cyclic citrullinated peptide antibody levels were associated with more severe joint radiographic damage (P = 0.04). We conclude that there is a relevant association between the -174G/C IL6 polymorphism and severe radiographic damage. Future studies in other populations are required to confirm our findings.

The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis.

Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (p < 0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07-1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05-2.3; p = 0.003), or CC (RR = 1.83; 95% CI = 1.07-3.14; p = 0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03-1.72; p = 0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF.

Association between bone turnover markers, clinical variables, spinal syndesmophytes and bone mineral density in Mexican patients with ankylosing spondylitis.

OBJECTIVES: To compare bone turnover marker (BTM) levels and bone mineral density (BMD) between patients with ankylosing spondylitis (AS) and healthy controls (HC) and to evaluate, in AS, the association between BTM levels and clinical variables, spinal syndesmophytes, and BMD using multivariate analysis. METHOD: Seventy-eight AS patients were compared with 58 HC matched by gender. Spinal syndesmophytes in AS and other characteristics were assessed. C-terminal telopeptide fragments of type I collagen (CTX), bone-specific alkaline phosphatase (BAP), osteocalcin (OC) serum levels, and BMD of the lumbar spine, femoral neck, and forearm were evaluated. RESULTS: AS males and females had lower BAP levels than their respective HC (p < 0.001 and p = 0.001). AS patients with bridging syndesmophytes had higher OC levels than AS patients either with non-bridging syndesmophytes (p = 0.001) or without spinal syndesmophytes (p < 0.001). OC and CTX levels correlated significantly with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). In the multivariate linear regression adjusted by age, gender, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BMD in the lumbar spine, and C-reactive protein (CRP), we observed an association between BAP levels and anti-tumour necrosis factor (anti-TNF) use (p = 0.05) whereas OC levels were associated with mSASSS (p < 0.001) and anti-TNF use (p = 0.05), and CTX levels were exclusively associated with mSASSS (p = 0.03). In the logistic regression analysis, only OC levels were associated with the presence of syndesmophytes in AS [odds ratio (OR) 2.42, 95% confidence interval (CI) 1.19-5.75]. CONCLUSIONS: We observed an increase in OC levels in AS patients with syndesmophytes. BTM levels were associated with the severity of spinal damage. Future longitudinal studies should evaluate whether these BTMs should be included as tools to determine the prognosis and progression of spinal damage.