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Reyes C.,Institute Universitari dInvestigacio en Atencio Primaria Jordi Gol | Hitz M.,Copenhagen University | Prieto-Alhambra D.,Institute Universitari dInvestigacio en Atencio Primaria Jordi Gol | Prieto-Alhambra D.,Parc Of Salut Mar And Institute Salud Carlos Iii | And 2 more authors.
Journal of Cellular Biochemistry | Year: 2016

Bisphosphonates are the mainstay of osteoporosis treatment but also play a fundamental role in treating other bone diseases such as Osteogenesis Imperfecta, Pagets' disease, and in the prevention of adverse skeletal effects in certain cancers such as prostate cancer or multiple myeloma. In the last decades, the refinement of bisphosphonates and an increase in the number of new bisphosphonates commercialized has altered the clinical management of these diseases. Despite differences between randomized controlled trials and observational studies, overall all bisphosphonates licensed have proven to reduce the risk of fracture through the inhibition of bone resorption. Other beneficial effects include pain reduction in bone metastasis and potentially a decrease in mortality. However, the chronic nature of most of these disorders implies long-term treatments, which can be associated with long-term adverse effects. Some of the adverse effects identified include an increased risk of atypical femur fractures, osteonecrosis of the jaw, gastrointestinal side effects, or atrial fibrillation. The harm/benefit thinking and the constant update regarding these medications are vital in the day-to-day decision-making in clinical practices. The aims of this review are to compile the basic characteristics of these drugs and outline the most important benefits and side effects and provide a clinical context as well as a research agenda to fill the gaps in our knowledge. © 2015 Wiley Periodicals, Inc.

Reyes C.,Biomedical Research Institute Sant Pau | Reyes C.,Autonomous University of Barcelona | Garcia-Gil M.,Autonomous University of Barcelona | Garcia-Gil M.,Idiap Research Institute | And 18 more authors.
Bone | Year: 2015

To determine the association between socioeconomic deprivation (SES) and hip fracture risk. Methods: Retrospective cohort study using a population-based database (primary care records) of over 5 million people. Eligibility: all living subjects registered during the period 2009-2012 and resident in an urban area. Measures: a validated SES composite index (proportion of unemployed, temporary workers, manual workers, low educational attainment and low educational attainment among youngsters) estimated for each area based on census data. Outcome: incident hip fracture rates as coded in medical records using ICD-10 codes. Statistics: zero-inflated Poisson models fitted to study the association between SES quintiles and hip fracture risk, adjusted for age, sex, obesity, smoking and alcohol consumption. Results: Compared to the most deprived, wealthy areas had a higher hip fracture incidence (age- and sex-adjusted incidence 38.57 (37.14-40.00) compared to 34.33 (32.90-35.76) per 10,000 person-years). Similarly, most deprived areas had a crude and age- and sex-adjusted lower risk of hip fracture, RR of 0.71 (0.65-0.78) and RR of 0.90 (0.85-0.95), respectively, compared to wealthiest areas. The association was attenuated and no longer significant after adjustment for obesity: RR 0.96 (0.90-1.01). Further adjustment for smoking and high alcohol consumption did not make a difference. Conclusion: Wealthiest areas have an almost 30% increased risk of hip fracture compared to the most deprived. Differences in age-sex composition and a higher prevalence of obesity in deprived areas could explain this higher risk. © 2014 Elsevier Inc.

Vestergaard P.,Aarhus University Hospital | Prieto-Alhambra D.,Autonomous University of Barcelona | Prieto-Alhambra D.,Parc Of Salut Mar And Institute Salud Carlos Iii | Prieto-Alhambra D.,University of Oxford | And 3 more authors.
Osteoporosis International | Year: 2013

Antidepressants have been associated with fractures. In a case-control study, increasing age was associated with more fractures in users of selective serotonin reuptake inhibitors and tricyclic antidepressants, whereas for anxiolytics and sedatives, more fractures were seen among the younger users. Depression per se did not seem associated with fractures. Introduction: This study aims to study the effects of age and dose of selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) and anxiolytics/sedatives on fracture risk. Methods: The study was designed as a case-control study. From the Danish National Health Service, we identified 124,655 fracture cases and 373,962 age- and gender-matched controls. Crude odds ratios were estimated, and propensity score adjustment was used to minimise confounding by indication. Results: A higher risk of fractures was associated with an increasing dose of anxiolytics and sedatives; the highest excess risk was present in the age stratum below 40 years of age (p < 0.01), and thereafter, the excess risk of fractures declined with age. For SSRI, a growing excess risk of fractures was seen with both increasing dose and age. Regarding TCA, no particular trend with age was present. However, an increasing risk of fractures was associated with increasing TCA dose in the age group above 60 years. Finally, for other antidepressants, no particular trend with age or dose was observed. In our data, a hospital diagnosis of depression or manic depression was associated with fewer fractures. Conclusion: Caution should be shown upon prescription of SSRI to older subjects. A hospital diagnosis of depression or manic depression and thus potentially a more severe disease was not a risk factor for fractures. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.

Munoz-Ortego J.,Hospital Universitari Sagrat Cor | Vestergaard P.,University of Aalborg | Rubio J.B.,Parc de Salut Mar | Wordsworth P.,Botnar Research Center | And 11 more authors.
Journal of Bone and Mineral Research | Year: 2014

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'Informaciõ per al Desenvolupament de l'Investigaciõ en Atenciõ 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. © 2014 American Society for Bone and Mineral Research © 2014 American Society for Bone and Mineral Research.

Prieto-Alhambra D.,University of Oxford | Prieto-Alhambra D.,University of Southampton | Prieto-Alhambra D.,Parc Of Salut Mar And Institute Salud Carlos Iii | Prieto-Alhambra D.,Autonomous University of Barcelona | And 12 more authors.
Osteoporosis International | Year: 2014

Summary: Ankylosing spondylitis (AS) leads to osteopenia/osteoporosis and spine rigidity. We conducted a case-control study and found that AS-affected patients have a 5-fold and 50 % increased risk of clinical spine and all clinical fractures, respectively. Excess risk of both is highest in the first years and warrants an early bone health assessment after diagnosis.Introduction: Ankylosing spondylitis (AS) is related to spine rigidity and reduced bone mass, but data on its impact on fracture risk are scarce. We aimed to study the association between AS and clinical fractures using a case-control design.Methods: From the Danish Health Registries, we identified all subjects who sustained a fracture in the year 2000 (cases) and matched up to three controls by year of birth, gender and region. Clinically diagnosed AS was identified using International Classification of Diseases, 8th revision (ICD-8; 71249), and International Classification of Diseases, 10th revision (ICD-10; M45) codes. We also studied the impact of AS duration. Conditional logistic regression was used to estimate crude and adjusted odds ratios (ORs) for non-traumatic fractures (any site, clinical spine and non-vertebral) according to AS status and time since AS diagnosis. Multivariate models were adjusted for fracture history, socio-economic status, previous medical consultations, alcoholism and use of oral glucocorticoids.Results: We identified 139/124,655 (0.11 %) AS fracture cases, compared to 271/373,962 (0.07 %) AS controls. Unadjusted (age- and gender-matched) odds ratio (OR) were 1.54 [95 % confidence interval (95 %CI) 1.26–1.89] for any fracture, 5.42 [2.50–11.70] for spine and 1.39 [1.12–1.73] for non-vertebral fracture. The risk peaked in the first 2.5 years following AS diagnosis: OR 2.69 [1.84–3.92] for any fracture.Conclusions: Patients with AS have a 5-fold higher risk of clinical spine fracture and a 35 % increased risk of non-vertebral fracture. This excess risk peaks early, in the first 2.5 years of AS disease. Patients should be assessed for fracture risk early after AS diagnosis. © 2014, International Osteoporosis Foundation and National Osteoporosis Foundation.

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