Characteristics of Early Paget's Disease in SQSTM1 Mutation Carriers: Baseline Analysis of the ZiPP Study Cohort.

Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Ankylosing spondylitis is associated with an increased risk of vertebral and nonvertebral clinical fractures: a population-based cohort study.

The objective of this work was to study the associations between ankylosing spondylitis (AS) and clinical vertebral and nonvertebral fractures. Data from a large population-based public health database in Spain, Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP), were used in this parallel cohort study. All participants registered in SIDIAP on January 1, 2006, were screened to identify those with a diagnosis of AS. Five age-matched, gender-matched, and general practice surgery-matched controls were selected for each patient with AS. All participants were followed until December 31, 2011, transfer out date, or death date. Fractures during this time were classified as vertebral or nonvertebral. Adjustment was made for potential confounders (tobacco smoking, alcohol consumption, body mass index, and use of oral steroids). Of 4,920,353 eligible patients in SIDIAP, 6474 AS patients with matched controls (n = 32,346) were available. A higher proportion of patients with AS versus controls had clinical vertebral (0.86% versus 0.41%) and nonvertebral (3.4% versus 2.7%) fractures. Adjusted Cox regression models showed an increased risk of clinical vertebral (hazard ratio [HR] 1.93; 95% confidence interval [CI], 1.39 to 2.68; p < 0.001) and nonvertebral (HR 1.19; 95% CI, 1.02 to 1.39; p = 0.03) fractures among patients with AS. However, the observed increased risks were apparent only in those not on regular nonsteroidal anti-inflammatory drugs (NSAIDs). There were no interactions with inflammatory bowel disease, psoriasis, or previous back pain. Patients with AS are at increased risk of vertebral and nonvertebral clinical fractures, independently of various risk factors. Regular use of NSAIDs appears to eliminate the excess fracture risk related to AS, but the mechanisms involved are unknown.

Efficacy of a multidisciplinary treatment program in patients with severe fibromyalgia.

The purpose of this study was to evaluate the efficacy of a multidisciplinary treatment program in patients severely affected by fibromyalgia. Thirty-four fibromyalgia patients were randomly divided into two groups. The control group: 17 women who continued their medical treatment and participated in four educational sessions and the experimental group that included 17 patients who besides the former medical treatment also underwent a weekly 1-h session program for 8 weeks including massage therapy, ischemic pressure on the 18 tender points, aerobic exercise and thermal therapy. At the beginning of the program, there were no significant differences between the two groups in any of the parameters. At the end of treatment, there was a significant improvement in the experimental group in the following items: vitality, social functioning, grip strength and the 6-min walk test. At 1 month after the end of treatment, the experimental group showed significant differences in overall health perception, social functioning, grip strength and the 6-min walk test. At that time, considering the threshold for clinical efficacy set at an improvement of 30% or above for the analyzed variables, 25% of the patients met the requirement for improvement of the following: number of symptoms: Visual Analogic Scale for fatigue, Fibromyalgia Impact Questionnaire and Beck Anxiety Inventory. In conclusion, patients with severe manifestations of fibromyalgia can obtain improvement with a short-term, low-cost and simple-delivery multidisciplinary program. However, additional studies including higher numbers of patients are needed to confirm the beneficial effect of this treatment program.