Relationship between trabecular bone score, bone mineral density and vertebral fractures in patients with axial spondyloarthritis.

BACKGROUND: In patients with axial spondyloarthritis, vertebral fracture risk is elevated and not always correlated with bone mineral density (BMD). Trabecular bone score (TBS) may offer some advantages in the assessment of vertebral fracture risk in these patients. The primary objective of this study was to compare TBS and BMD between axial spondyloarthritis patients depending on their vertebral fracture status. Secondary objectives were to estimate the prevalence of morphometric vertebral fractures, and to explore factors associated with fracture, as well as the interference of syndesmophytes on BMD and TBS. METHODS: A cross-sectional study was conducted. Data were collected on demographic and clinical characteristics, lab results, imaging findings and treatment. Statistical analysis was performed using SPSS v.13 statistical software. RESULTS: Eighty-four patients (60 men and 24 women; mean age of 59 years) were included. Nearly half (47.6%) of them had lumbar syndesmophytes. The rate of morphometric fracture was 11.9%. TBS showed a higher area under the curve (0.89) than total hip, femoral neck and lumbar BMD (0.80, 0.78, and 0.70 respectively) for classifying patients regarding their fracture status. Nonetheless, the differences did not reach statistical significance. Syndesmophytes affected lumbar spine BMD (p < 0.001), but not hip BMD or TBS. Fractures were associated with TBS, total hip BMD, erythrocyte sedimentation rate and C-reactive protein levels. CONCLUSIONS: We identified decreased TBS and total hip BMD, as well as increased erythrocyte sedimentation rate and C-reactive protein levels as factors associated with morphometric vertebral fractures. Unlike lumbar spine BMD, TBS is not affected by the presence of syndesmophytes.

Apremilast in refractory orogenital ulcers and other manifestations of Behçet's disease. A national multicentre study of 51 cases in clinical practice.

OBJECTIVES: The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behçet's disease (BD). METHODS: National multicentre open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. RESULTS: We included 51 patients (35 women/16 men; mean age 44.7±13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-α-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behçet (n=1). After a mean follow-up of 8.5±6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. CONCLUSIONS: APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

Risk factors for the development of chronic back pain after percutaneous vertebroplasty versus conservative treatment.

In a recent randomized controlled trial comparing vertebroplasty (VP) versus conservative treatment (CT) in patients with symptomatic vertebral fractures (VF), we observed the development of chronic back pain (CBP) in nearly one-quarter of patients. The aim of this study was to identify the risk factors related to the development of severe CBP in these subjects. We evaluated risk factors including visual analog scale (VAS) at baseline and during the 1-year follow-up, age, gender, symptom onset time, number, type and severity of VF at baseline, number of vertebral bodies treated, incident VF, and antiosteoporotic treatment, among others. CBP was considered in patients with VAS ≥ 7 at 12 months. 91/125 patients completed the 12-months follow-up. CBP was observed in 23% of VP-treated patients versus 23% receiving CT. Patients developing CBP after VP showed a longer symptom onset time (82% ≥ 4 months in VP vs. 40% in CT, P = 0.03). On univariate analysis, female gender (OR 1.52; 95% CI 1.47-1.57, P < 0.0001), multiple acute VF (OR 1.79; 95% CI 1.71-1.87, P < 0.0001), VAS ≥ 7 two months after treatment (OR 11.04; 95% CI 6.71-18.17, P < 0.0001), and type of antiosteoporotic drug (teriparatide) (OR 0.12; 95% CI 0.03-0.60, P = 0.0236) were risk factors of CBP development in both groups. In the multivariate analysis, the main risk factors were baseline and post-treatment VAS ≥ 7, longer symptom onset time, and type of antiosteoporotic treatment. In conclusion, 23% of patients with symptomatic osteoporotic VF developed severe CBP independently of the type of treatment. Symptom onset time before VP and persistence of severe CBP after treatment were the main factors related to CBP with teriparatide treatment decreasing the risk of this complication.

Current situation of osteogenesis imperfecta in Spain: results from a Delphi study.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare disease characterized by low bone mass and bone fragility, associated with an increased risk of fractures, and skeletal and extra-skeletal symptoms that results in an impairment of health-related quality of life of OI patients. Since published studies on OI in Spain are limited, this study aimed to determine the epidemiology, assessed the disease burden, management and unmet needs of OI patients in Spain. Thirty-four experts in the management of patients with osteogenesis imperfecta completed two rounds of online consultation and reported real-life experience and data from Spanish hospitals. Delphi study questionnaires were based on literature review. A working group of nationally recognized clinical experts supported the development of the study questionnaires and the final validation of results. RESULTS: The estimated prevalence of patients diagnosed with OI in Spain is 0.56:10,000 inhabitants (95%CI: 0.54-0.59), which represents that, approximately, 2,669 OI patients are currently managed in Spanish hospitals. It is estimated that approximately 269 new patients would be diagnosed with OI each year in Spain, representing an estimated incidence of 0.06 (95%CI: 0.05-0.06) per 10,000 inhabitants per year. Clinical management of OI in Spain is performed by a range of medical specialists; however, multidisciplinary care is not fully implemented. The absence of an approved curative treatment or a treatment to reduce the clinical features of the disease remains the main unmet need. CONCLUSIONS: This study provides a snapshot of the current situation of patients with OI in Spain reported by clinical experts. The results provide an estimation of the epidemiology of the disease, and complement the available evidence on disease burden, clinical management, and unmet needs of these patients in Spain.

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.

Persistence and Use of Ixekizumab in Patients with Psoriatic Arthritis in Real-World Practice in Spain. The PRO-STIP Study.

INTRODUCTION: Ixekizumab (IXE) is an IgG4-type monoclonal antibody targeting IL-17A indicated alone or in combination with methotrexate, for the treatment of active psoriatic arthritis (PsA) in adult patients with insufficient response or with intolerance to one or more disease-modifying anti-rheumatic drug (DMARD) therapy. The PRO-STIP study aimed to describe persistence, patient characteristics, treatment patterns, and effectiveness in patients with PsA receiving IXE in a real-world clinical setting in Spain. METHODS: This was an observational, multicentric, retrospective, longitudinal study in adult PsA patients who started IXE between January 2019 and December 2020, with at least 24 weeks of follow-up. A descriptive analysis of patient characteristics and treatment patterns was performed. The primary objective, treatment persistence, was estimated by Kaplan-Meier survival curve. Effectiveness was evaluated by Disease Activity in Psoriatic Arthritis (DAPSA) scores at baseline and at 12 and 24 weeks. RESULTS: Eighty-nine patients met the selection criteria (55.1% women and mean age 51.5 years). The median time from PsA diagnosis to starting IXE was 7.7 years (IQR 3.4-14.6). Prior to IXE, 95.5% patients had been treated with at least one biologic or targeted synthetic DMARD (b/tsDMARD). The observed persistence rates were 95.5%, 84.3% and 68.5% at 24, 48, and 104 weeks, respectively. The median persistence was not reached in the study period (mean persistence, 86.9 [95% CI 80.6-93.2] weeks). Twenty-eight (31.5%) patients discontinued IXE, 19 patients (21.3%) due to loss of effectiveness and two patients (2.2%) due to adverse events. In patients receiving treatment and with available effectiveness assessment (n = 24), DAPSA decreased significantly from baseline 23.7 (95% CI 19.5-27.9) to 14.8 (95% CI 10.5-19.2) at 12 weeks (p = 0.005) and 14.3 (95% CI 11.1-17.4) at 24 weeks (p = 0.004). CONCLUSIONS: PsA patients treated with IXE in a real-world setting show high treatment persistence through 104 weeks and improvements in disease activity after treatment initiation. This suggests that IXE could be an effective treatment for patients with PsA. RETROSPECTIVELY REGISTERED: Date of registration: 25th May 2021.

High incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis. A case-control study.

OBJECTIVES: To estimate the incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis (RA) and analyze risk factors for fracture. METHODS: Incidence of clinical fragility fractures in 330 postmenopausal women with RA was compared to that of a control population of 660 age-matched postmenopausal Spanish women. Clinical fractures during the previous five years were recorded. We analyzed associations with risk factors for fracture in both populations and with disease-related variables in RA patients. RESULTS: Median age of RA patients was 64 years; median RA duration was eight years. Sixty-nine percent were in remission or on low activity. Eighty-five percent had received glucocorticoids (GCs); 85 %, methotrexate; and 40 %, ≥1 biologic DMARD. Fifty-four patients and 47 controls had ≥1 major osteoporotic fracture (MOF). Incidence of MOFs was 3.55 per 100 patient-year in patients and 0.72 in controls (HR: 2.6). Risk factors for MOFs in RA patients were age, previous fracture, parental hip fracture, years since menopause, BMD, erosions, disease activity and disability, and cumulative dose of GCs. Previous fracture in RA patients was a strong risk for MOFs (HR: 10.37). CONCLUSION: Of every 100 postmenopausal Spanish women with RA, 3-4 have a MOF per year. This is more than double that of the general population. A previous fracture poses a high risk for a new fracture. Other classic risk factors for fracture, RA disease activity and disability, and the cumulative dose of GCs are associated with fracture development.

Effects of bilirubin and sera from jaundiced patients on osteoblasts: contribution to the development of osteoporosis in liver diseases.

UNLABELLED: Low bone formation is considered to be the main feature in osteoporosis associated with cholestatic and end-stage liver diseases, although the consequences of retained substances in chronic cholestasis on bone cells have scarcely been studied. Therefore, we analyzed the effects of bilirubin and serum from jaundiced patients on viability, differentiation, mineralization, and gene expression in the cells involved in bone formation. The experiments were performed in human primary osteoblasts and SAOS-2 human osteosarcoma cells. Unconjugated bilirubin or serum from jaundiced patients resulted in a dose-dependent decrease in osteoblast viability. Concentrations of bilirubin or jaundiced serum without effects on cell survival significantly diminished osteoblast differentiation. Mineralization was significantly reduced by exposure to 50 µM bilirubin at all time points (from -32% to -55%) and jaundiced sera resulted in a significant decrease on cell mineralization as well. Furthermore, bilirubin down-regulated RUNX2 (runt-related transcription factor 2) gene expression, a basic osteogenic factor involved in osteoblast differentiation, and serum from jaundiced patients significantly up-regulated the RANKL/OPG (receptor activator of nuclear factor-κB ligand/osteoprotegerin) gene expression ratio, a system closely involved in osteoblast-induced osteoclastogenesis. CONCLUSION: Besides decreased cell viability, unconjugated bilirubin and serum from jaundiced patients led to defective consequences on osteoblasts. Moreover, jaundiced serum up-regulates the system involved in osteoblast-induced osteoclastogenesis. These results support the deleterious consequences of increased bilirubin in advanced chronic cholestasis and in end-stage liver diseases, resulting in disturbed bone formation related to osteoblast dysfunction.

Psoriasis induced by biological therapy.

OBJECTIVE: To describe a multicentre case series of new onset or worsening of psoriasis in patients treated with biological drugs. MATERIAL AND METHODS: Descriptive study. We reviewed the clinical history of patients with chronic inflammatory disease (CID) treated with biological drugs, who developed new onset or worsening of psoriasis during the follow-up period. RESULTS: Twenty-six cases of paradoxical psoriasis (PP) were recorded. Ninety-three percent of the patients were treated with anti-TNFα and adalimumab was responsible for 50% of the cases. Only 5 patients had a personal history of psoriasis. The biological drug was discontinued in 13 patients. Lesion recurrence was more frequent when another anti-TNFα was reintroduced. CONCLUSIONS: The PP is a reversible adverse effect that can be observed in patients exposed to biological drugs, mainly anti-TNFα.

Osteogenesis imperfecta. Report of 15 Cases. / Osteogénesis imperfecta. Descripción de 15 casos.

Osteogenesis imperfecta (OI) is an inherited connective tissue disease. The disease has been linked to mutations in one of the type I collagen genes. The diagnosis is based on clinical and radiologic findings. The management of OI in adults is not well-established and includes physical rehabilitation, surgical procedures, the use of antiresorptive therapy and anabolic agents. The aim of the present work was to analyze the clinical and analytical characteristics of these patients in adulthood, as well as to evaluate the different treatments administered. We reviewed the cases of OI diagnosed in our center over the last 12 years (2005-2017). We describe 15 adult patients with OI.

Psoriasis Induced by Biological Therapy. / Psoriasis inducida por terapia biológica.

OBJECTIVE: To describe a multicentre case series of new onset or worsening of psoriasis in patients treated with biological drugs. MATERIAL AND METHODS: Descriptive study. We reviewed the clinical history of patients with chronic inflammatory disease (CID) treated with biological drugs, who developed new onset or worsening of psoriasis during the follow-up period. RESULTS: Twenty-six cases of paradoxical psoriasis (PP) were recorded. Ninety-three percent of the patients were treated with anti-TNFα and adalimumab was responsible for 50% of the cases. Only 5 patients had a personal history of psoriasis. The biological drug was discontinued in 13 patients. Lesion recurrence was more frequent when another anti-TNFα was reintroduced. CONCLUSIONS: The PP is a reversible adverse effect that can be observed in patients exposed to biological drugs, mainly anti-TNFα.

[Whipple's disease. Analysis of 6 cases]. / Enfermedad de Whipple. Estudio de 6 casos.

BACKGROUND AND OBJECTIVE: Whipple's disease (WD) is an infrequent multisystemic process, with a bacterial etiology and with a marked variability in relation to its clinical manifestations. The diagnosis is established by histopathologic study or by polymerase chain reaction (PCR) test. Our objective was to analyze the clinical characteristics and evolution of these patients. PATIENTS AND METHOD: We have reviewed the patients diagnosed with WD in our hospital during the last 20 years (1987-2007). RESULTS: We describe 6 patients with WD (5 men and one woman), with a mean age of 47 years. Most patients presented articular symptoms (n = 5), in 3 cases with intermittent rheumatism. The mean period of time previous to diagnosis was 59 months. All patients developed a chronic diarrheic syndrome, constitutional syndrome and polyadenopathies at the time of diagnosis. Laboratory studies showed increased erythrocyte sedimentation rate and C-reactive protein values, ferropenic microcytic anemia and low serum levels of cholesterol. The clinical diagnosis was confirmed by pathologic study in 5 patients, and by means of PCR study of spleen tissue in one patient. All patients were treated with cotrimoxazole for 2 years, with resolution of the symptoms. After a mean follow-up of 98 months, no recurrence of the symptoms has been observed in any case. CONCLUSIONS: Articular symptoms in the form of intermittent rheumatism are the most common form of presentation of WD. Diarrheic and constitutional syndrome, which are observed later in all patients, as well as the presence of adenopathies, oblige us to discard this process.

[Effectiveness of vertebroplasty in painful chronic osteoporotic vertebral fractures. A report of 5 patients]. / Eficacia de la vertebroplastia en fracturas vertebrales crónicas sintomáticas debidas a osteoporosis. Estudio de 5 pacientes.

BACKGROUND AND OBJECTIVE: Percutaneous vertebroplasty (PVP) has been successfully used in the treatment of pain related to osteoporotic vertebral fractures refractory to medical therapy, especially in the treatment of acute factures. However, the effectiveness of this therapeutic approach in the treatment of painful chronic vertebral fractures is less clear. PATIENTS AND METHODS: In this report we evaluate the short and long-term effectiveness in pain relief of PVP in a group of 5 patients with pain related to chronic osteoporotic vertebral fractures without bone marrow edema (BME) on magnetic resonance imaging (MRI). All patients were followed during one year, assessing analgesic use, pain evolution (on a 10-point visual analog scale [VAS]), new vertebral fractures and other clinical complications. Seven procedures were performed in the 5 patients. RESULTS: All patients reported substantial improvement in back pain 2 weeks after the procedure, with a mean decrease of 53% in the VAS. However, one year after PVP most patients (4 out 5) worsened, achieving similar VAS scores to those obtained at baseline. No additional vertebral fractures or other clinical complications were observed. CONCLUSION: The present cases suggest that the long-term effectiveness of PVP in the treatment of painful chronic vertebral fractures without BME on MRI is scarce.