Neuropsychiatric adverse reactions in patients treated with denosumab: two case reports and a review of data from the FDA Adverse Event Reporting System (FAERS).

Denosumab is a human monoclonal antibody indicated for patients with osteoporosis and a high risk of fractures. It targets RANKL, the receptor activator of NF-κB (RANK) ligand, blocking RANKL-RANK interaction and leading to rapid osteoclast-mediated bone resorption inhibition. But RANK is widely expressed in neurons, microglia, and astrocytes. RANKL/RANK/NF-κB system can play an important role in the neuroinflammatory response, depressive behavior, memory impairments, and neurotrophism. We present two well-documented case reports of recurrent neuropsychiatric manifestations in patients treated with denosumab and a descriptive review of similar cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2012 and 2022. Only those reported by healthcare professionals, coding denosumab as the only suspected drug, were retained. An 81-year-old woman with pre-existing mild cognitive impairment suffered two acute confusional episodes and another 81-year-old woman with depression in remission suffered two depressive recurrences with anxiety and psychomotor inhibition, in both cases following sequential administrations of denosumab without underlying calcium/phosphate imbalance. Scores on Naranjo Adverse Drug Reaction Probability Scale were 6 and 7, respectively, suggesting a probable causal relationship. Of the 91,151 cases with denosumab exposure reported to FAERS, 5.7% were related to psychiatric/neurological disorders and 23.8% of these corresponded to cognitive impairment, depressive/mood disturbances, or psychomotor retardation. Denosumab may cause transient but severe neuropsychiatric symptoms by several mechanisms involving RANKL blockade and subsequent immuno-inflammatory changes, at least in subjects with pre-existing neurobiological vulnerability. We recommend caution and careful monitoring of these patients following denosumab administrations.

Predictive factors of the neuropathic pain in patients with carpal tunnel syndrome and its impact on patient activity.

AIM: To determine the predictive factors of the neuropathic pain in patients with carpal tunnel syndrome (CTS), and the impact of such neuropathic pain on patient's activity. METHODS: Douleur Neuropathique 4 questionnaire, Short Form-Brief Pain Inventory test and Boston Carpal Tunnel Syndrome Questionnaire were completed and results were stratified according neuropathic pain and work activity of the patients. RESULTS: 69 of 90 patients with CTS had neuropathic pain (76.7%). Increasing by one the scores of numbness/tingling, pain intensity and neurologic affectation of the electromyogram meant increasing 3.3-, 2.7- and 4.4-times the risk of neuropathic pain, respectively. CONCLUSION: These results will be useful for a better neuropathic pain evaluation in patients with CTS, allowing the appropriate treatment.

Validación al castellano de la escala Boston Carpal Tunnel Questionnaire / Spanish validation of the Boston Carpal Tunnel Questionnaire

Introducción y objetivo: Describir el proceso de adaptación cultural y validación al español del cuestionario Boston Carpal Tunnel Questionnaire (BCTQ) de intensidad de los síntomas, capacidad funcional y calidad de vida en pacientes con síndrome del túnel carpiano, e informar de sus propiedades psicométricas. Material y métodos: Un panel de 3 expertos supervisó el proceso de adaptación. Tras la traducción, revisión y retrotraducción del instrumento se obtuvo un cuestionario en español que fue administrado a 2 muestras de pacientes: una muestra piloto de 20 pacientes para valorar la comprensibilidad y una de 90 pacientes para comprobar la validez estructural (análisis factorial y fiabilidad), la validez de constructo y la sensibilidad al cambio. Se realizó medición retest a 21 pacientes. Se realizó seguimiento a 40 pacientes. Resultados: El cuestionario fue bien entendido por todos los participantes. Tres ítems presentaron efecto suelo. La fiabilidad fue muy buena, consistencia interna: αS = 0,91 y αF = 0,87; estabilidad temporal test-retest: rS = 0,939 y rF = 0,986. Se comprobó que ambas subescalas del cuestionario se ajustaban a una dimensión general. Las subescalas correlacionaron con las medidas del dinamómetro (rS = 0,77 y rF = 0,75) y mostraron relación con la discriminación anormal entre 2 puntos, la atrofia muscular y el nivel de afectación según electromiografía. Las puntuaciones correlacionaron adecuadamente con cuestionarios ya validados: Douleur Neuropatique 4 questions y Cuestionario Breve de Dolor. El BCTQ demostró ser sensible a los cambio clínicos, con tamaños del efecto grandes (dS = −3,3 y dF = −1,9). Conclusiones: La versión en castellano del BCTQ ha demostrado tener buenas propiedades psicométricas, lo que garantiza su uso en el ámbito clínico (AU)

Introduction and Objective: To describe the process of cultural adaptation and validation of the Boston Carpal Tunnel Questionnaire (BCTQ) measuring symptom intensity, functional status and quality of life in carpal tunnel syndrome patients and to report the psychometric properties of this version. Material and methods: A 3 expert panel supervised the adaptation process. After translation, review and back-translation of the original instrument, a new Spanish version was obtained, which was administered to 2 patient samples: a pilot sample of 20 patients for assessing comprehension, and a 90 patient sample for assessing structural validity (factor analysis and reliability), construct validity and sensitivity to change. A re-test measurement was carried out in 21 patients. Follow-up was accomplished in 40 patients. Results: The questionnaire was well accepted by all participants. Celling effect was observed for 3 items. Reliability was very good, internal consistency: αS = 0.91 y αF = 0.87; test-retest stability: rS = 0.939 and rF = 0.986. Both subscales fitted to a general dimension. Subscales correlated with dynamometer measurements (rS = 0.77 and rF = 0.75) and showed to be related to abnormal 2-point discrimination, muscle atrophy and electromyography deterioration level. Scores properly correlated with other validated instruments: Douleur Neuropatique 4 questions and Brief Pain Inventory. BCTQ demonstrated to be sensitive to clinical changes, with large effect sizes (dS = −3.3 and dF = −1.9). Conclusions: The Spanish version of the BCTQ shows good psychometric properties warranting its use in clinical settings (AU)

[Spanish validation of the Boston Carpal Tunnel Questionnaire]. / Validación al castellano de la escala Boston Carpal Tunnel Questionnaire.

INTRODUCTION AND OBJECTIVE: To describe the process of cultural adaptation and validation of the Boston Carpal Tunnel Questionnaire (BCTQ) measuring symptom intensity, functional status and quality of life in carpal tunnel syndrome patients and to report the psychometric properties of this version. MATERIAL AND METHODS: A 3 expert panel supervised the adaptation process. After translation, review and back-translation of the original instrument, a new Spanish version was obtained, which was administered to 2 patient samples: a pilot sample of 20 patients for assessing comprehension, and a 90 patient sample for assessing structural validity (factor analysis and reliability), construct validity and sensitivity to change. A re-test measurement was carried out in 21 patients. Follow-up was accomplished in 40 patients. RESULTS: The questionnaire was well accepted by all participants. Celling effect was observed for 3 items. Reliability was very good, internal consistency: αS=0.91 y αF=0.87; test-retest stability: rS=0.939 and rF=0.986. Both subscales fitted to a general dimension. Subscales correlated with dynamometer measurements (rS=0.77 and rF=0.75) and showed to be related to abnormal 2-point discrimination, muscle atrophy and electromyography deterioration level. Scores properly correlated with other validated instruments: Douleur Neuropatique 4 questions and Brief Pain Inventory. BCTQ demonstrated to be sensitive to clinical changes, with large effect sizes (dS=-3.3 and dF=-1.9). CONCLUSIONS: The Spanish version of the BCTQ shows good psychometric properties warranting its use in clinical settings.

High Prevalence of Neuropathic Pain Features in Patients with Knee Osteoarthritis: A Cross-Sectional Study.

OBJECTIVE: The present epidemiological research evaluated the prevalence of neuropathic pain characteristics in patients with painful knee osteoarthritis (OA) and the plausibility that such neuropathic features were specific of OA. METHODS: Outpatients with chronic pain associated with knee OA who attended orthopedic surgery or rehabilitation clinics were systematically screened for neuropathic pain with the Douleur Neuropathique in 4 questions (DN4) questionnaire. Data from medical files and those obtained during a single structured clinical interview were correlated with the DN4 scores. Information on potential confounders of neuropathic-like qualities of knee pain was collected to evaluate as much as possible only the symptoms attributable to OA. RESULTS: Of 2,776 patients recruited, 2,167 patients provided valid data from 2,992 knees. The DN4 was scored positively (≥ 4) in 1,125 patients (51.9%) and 1,459 knees (48.8%). When patients with potential confounders were excluded, the respective prevalences were 33.3% and 29.4%. Patients who scored positively in the DN4 had more severe pain, greater structural damage, and more potential confounders of neuropathic pain. Three potential confounders conveyed much of the variability explained by regression analyses. However, latent class analyses revealed that the concourse of other factors is required to explain the neuropathic pain qualities. CONCLUSIONS: A relevant proportion of patients with chronic pain associated with knee OA featured neuropathic pain qualities that were not explained by other conditions. The present research has provided reasonable epidemiological grounds to attempt their definite diagnosis and classification.

Peripheral compartment as the initial access for hip arthroscopy in complex cases: technical note.

When performing arthroscopic procedures, the hip joint is divided into central and peripheral compartments. Currently, both compartments are evaluated in most of the procedures, but the procedures are usually started by accessing the central compartment. When a direct approach to the central compartment is significantly impeded, it is necessary to perform the initial arthroscopic approach to the hip from the peripheral compartment using either an intracapsular technique or an extracapsular technique. The technical pearls that might be required in these patients are discussed, and typical clinical cases are presented.

Treatment satisfaction after switching to another therapy in Spanish orthopaedic clinic outpatients with knee or hip osteoarthritis previously refractory to paracetamol.

BACKGROUND AND OBJECTIVE: Hip and knee osteoarthritis is highly prevalent in the elderly, and the incidence is estimated to increase in the coming decades. Prior to surgery, symptomatic treatment, starting with non-pharmacological therapies, should be prescribed. Paracetamol (acetaminophen) is the recommended first pharmacological treatment for osteoarthritis. If paracetamol is ineffective, non-steroidal anti-inflammatory drug (NSAID) treatment is indicated. The superiority of NSAIDs over paracetamol has been demonstrated in several studies. Furthermore, the assessment of patient satisfaction could be an adequate indicator of the quality of care given and is likely related to the evolution of the condition and the therapeutic regimen. The objective of this study was to assess the satisfaction of patients diagnosed with hip and/or knee osteoarthritis who had been previously treated with paracetamol and switched to NSAID treatment due to a lack of effectiveness by paracetamol. METHODS: An observational, prospective, multicentre and comparative study was conducted in 2009 among patients diagnosed with hip and knee OA who visited outpatient orthopaedic clinics. The evaluation of treatment effectiveness was carried out using a patient-based visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The satisfaction regarding change of treatment due to a lack of effectiveness and/or the presence of adverse effects was evaluated using the osteoARthritis Treatment Satisfaction (ARTS) questionnaire. RESULTS: A total of 2437 patients were evaluated (knee OA: 1438 [59%]; hip OA: 621 [25.5%]; knee and hip OA: 124 [5.1%]; and without OA location registered: 254 [10.4%]). The study findings showed an increase in patient satisfaction after abandoning the use of paracetamol to treat OA. Statistically significant increases in both overall satisfaction mean (from 57.7 [SD 13.5] to 71.3 [SD 12.0]) and in each of the four domains of the ARTS questionnaire were observed (p < 0.0001 in all cases). According to the WOMAC and a VAS, treatment effectiveness increased significantly after 3 months (p < 0.0001) and significant correlations with satisfaction were observed (r = -0.32 and r = -0.29, respectively; p < 0.0001). The mean (SD) change in global satisfaction in patients treated with NSAIDs was 14.9 (15.5) versus 7.2 (14.4) for patients treated with non-NSAIDs (p < 0.0001). Patients taking NSAID treatment showed substantially more improvement over those taking non-NSAID treatment. CONCLUSION: NSAIDs relieve pain due to OA in paracetamol-resistant patients and improve treatment effectiveness and patient satisfaction with treatment. Furthermore, paracetamol-refractory subjects under conventional medical treatment with NSAIDs experienced the drug as more effective and also tended to be more satisfied with treatment than those treated with non-NSAIDs.

Current considerations for the treatment of severe chronic pain: the potential for tapentadol.

Studies suggest that around 20% of adults in Europe experience chronic pain, which not only has a considerable impact on their quality of life but also imposes a substantial economic burden on society. More than one-third of these people feel that their pain is inadequately managed. A range of analgesic drugs is currently available, but recent guidelines recommend that NSAIDs and COX-2 inhibitors should be prescribed cautiously. Although the short-term efficacy of opioids is good, adverse events are common and doses are frequently limited by tolerability problems. There is a perceived need for improved pharmacological treatment options. Currently, many treatment decisions are based solely on pain intensity. However, chronic pain is multifactorial and this apaproach ignores the fact that different causative mechanisms may be involved. The presence of more than one causative mechanism means that chronic pain can seldom be controlled by a single agent. Therefore, combining drugs with different analgesic actions increases the probability of interrupting the pain signal, but is often associated with an increased risk of drug/drug interactions, low compliance and increased side effects. Tapentadol combines µ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule, with both mechanisms contributing to its analgesic effects. Preclinical testing has shown that µ-opioid agonism is primarily responsible for analgesia in acute pain, whereas noradrenaline reuptake inhibition is more important in chronic pain. In clinical trials in patients with chronic pain, the efficacy of tapentadol was similar to that of oxycodone, but it produced significantly fewer gastrointestinal side-effects and treatment discontinuations. Pain relief remained stable throughout a 1-year safety study. Thus, tapentadol could possibly overcome some of the limitations of currently available analgesics for the treatment of chronic pain.

Teriparatide (rh [1-34] PTH) improved osteointegration of a hemiarthroplasty with signs of aseptic loosening.

Incidences of osteoporosis and fragility fractures are constantly increasing, which are associated with increased morbidity and mortality. When these patients undergo surgery, a higher number of postoperative complications may be expected because of poor bone quality and delayed healing. As a result, poorer primary stability of the implant, initial loosening, and impaired fixation strength in different regions may be seen. In these patients, we can choose the most advanced implants, but it is necessary to stimulate bone biology to increase the stability of the implant. This article reports the result obtained in a patient diagnosed with osteoporosis with aseptic loosening of a hip hemiarthroplasty after treatment with teriparatide (rh [1-34] PTH). This drug is indicated for the treatment of osteoporosis in men and postmenopausal women with high fracture risk and glucocorticoid-induced osteoporosis, and is administered subcutaneously for 2 years. It has an anabolic effect through stimulation of the osteoblast population that increases trabecular connectivity, cortical thickness, and bone mineral content. In animal models, teriparatide improved implant fixation 2 to 4 weeks after administration, resulting in the thickening of bone trabeculae and increased bone mass in the peri-implant area. In this retrospective analysis of clinical data and radiographic and scintigraphic images, after 24 months of treatment, the patient experienced clinical improvement associated with the disappearance of radiographic signs of loosening and a decrease in pathological radiotracer uptake in the bone scan, which are signs of osteointegration after treatment with teriparatide.

Prescription patterns and appropriateness of NSAID therapy according to gastrointestinal risk and cardiovascular history in patients with diagnoses of osteoarthritis.

BACKGROUND: Prescription of non-steroidal anti-inflammatory drugs (NSAIDs) should be based on the assessment of both gastrointestinal (GI) and cardiovascular (CV) risk for the individual patient. We aimed to assess the GI/CV risk profile and the pharmacological management of patients with osteoarthritis (OA) in clinical practice. METHODS: We conducted a cross-sectional, multicentre, observational study of consecutive OA patients that visited 1,760 doctors throughout the Spanish National Health System (NHS) in a single day. The presence of GI risk factors, CV histories, hypertension and current pharmacological treatments was recorded. RESULTS: Of the 60,868 patients, 17,105 had a diagnosis of OA and were evaluable. The majority (93.4%) had more than one GI risk factor and 60.3% were defined to be at high-GI risk. Thirty-two percent had a history of CV events, 57.6% were treated with anti-hypertensive therapy and 22.6% had uncontrolled hypertension. One-fifth of patients were treated with non-NSAID therapies, whereas the remaining patients received NSAIDs. Non-selective NSAIDs (nsNSAID) plus proton pump inhibitor (PPI) or cyclooxigenase-2 (COX-2)-selective NSAIDs alone were more frequently prescribed in patients at increased GI risk. Patients with a positive CV history received nsNSAIDs or COX-2-selective NSAIDs in 41.3% and 31.7% of cases, respectively. When both the GI and CV histories were combined, 51% of the overall population was being prescribed drugs that were either not recommended or contraindicated. CONCLUSIONS: Over 90% of patients with OA are at increased GI and/or CV risk. In over half of these patients, the prescription of NSAIDs was not in accordance with current guidelines or recommendations made by regulatory agencies.