Showing papers by "Daniel Prieto-Alhambra published in 2015"
TL;DR: The number of THR/TKR operations in the UK up to 2035 is projected to be 95,877 and 118,666, higher for women than men and an exponential extrapolation of historical rates produces much higher estimates of THR and TKR counts in 2035.
365 citations
TL;DR: This study is the first to the authors' knowledge to demonstrate that reference point indentation is sensitive enough to reflect changes in cortical bone indentation after treatment with osteoporosis therapies in patients newly exposed to glucocorticoids.
Abstract: Glucocorticoids, widely used in inflammatory disorders, rapidly increase bone fragility and, therefore, fracture risk. However, common bone densitometry measurements are not sensitive enough to detect these changes. Moreover, densitometry only partially recognizes treatment-induced fracture reductions in osteoporosis. Here, we tested whether the reference point indentation technique could detect bone tissue property changes early after glucocorticoid treatment initiation. After initial laboratory and bone density measurements, patients were allocated into groups receiving calcium+vitamin D (Ca+D) supplements or anti-osteoporotic drugs (risedronate, denosumab, teriparatide). Reference point indentation was performed on the cortical bone layer of the tibia by a handheld device measuring bone material strength index (BMSi). Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA). Although Ca+D-treated patients exhibited substantial and significant deterioration, risedronate-treated patients exhibited no significant change, and both denosumab- and teriparatide-treated participants exhibited significantly improved BMSi 7 weeks after initial treatment compared with baseline; these trends remained stable for 20 weeks. In contrast, no densitometry changes were observed during this study period. In conclusion, our study is the first to our knowledge to demonstrate that reference point indentation is sensitive enough to reflect changes in cortical bone indentation after treatment with osteoporosis therapies in patients newly exposed to glucocorticoids. (c) 2015 American Society for Bone and Mineral Research.
74 citations
TL;DR: Patients with AS have a 5-fold higher risk of clinical spine fracture and a 35 % increased risk of non-vertebral fracture and this excess risk peaks early, in the first 2.5 years following AS diagnosis.
Abstract: 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.
64 citations
TL;DR: Newly diagnosed type 2 diabetes mellitus patients are at a 20 % increased risk of hip fracture even in early stages of disease, but no for all fractures.
Abstract: There is scarce data on the association between early stages of type 2 diabetes and fracture risk. We report a 20 % excess risk of hip fracture in the first years following disease onset compared to matched non-diabetic patients. Type 2 diabetes mellitus (T2DM) is a chronic disease that affects several target organs. Data on the association between T2DM and osteoporotic fractures is controversial. We estimated risk of hip fracture in newly diagnosed T2DM patients, compared to matched non-diabetic peers. We conducted a population-based parallel cohort study using data from the Sistema d’Informacio per al Desenvolupament de la Investigacio en Atencio Primaria (SIDIAP) database. Participants were all newly diagnosed T2DM patients registered in SIDIAP in 2006–2011 (T2DM cohort). Up to two diabetes-free controls were matched to each T2DM participant on age, gender, and primary care practice. Main outcome was incident hip fracture in 2006–2011, ascertained using the tenth edition of the International Classification of Diseases (ICD-10) codes. We used Fine and Gray survival modelling to estimate risk of hip fracture according to T2DM status, accounting for competing risk of death. Multivariate models were adjusted for body mass index, previous fracture, and use of oral corticosteroids. During the study period (median follow-up 2.63 years), 444/58,483 diabetic patients sustained a hip fracture (incidence rate 2.7/1,000 person-years) compared to 776/113,448 matched controls (2.4/1,000). This is equivalent to an unadjusted (age- and gender-matched) subhazard ratio (SHR) 1.11 [0.99–1.24], and adjusted SHR 1.20 [1.06–1.35]. The adjusted SHR for major osteoporotic and any osteoporotic fractures were 0.95 [0.89–1.01] and 0.97 [0.92–1.02]. Newly diagnosed T2DM patients are at a 20 % increased risk of hip fracture even in early stages of disease, but no for all fractures. More data is needed on the causes for an increased fracture risk in T2DM patients as well as on the predictors of osteoporotic fractures among these patients.
60 citations
TL;DR: It is shown in a population-based cohort study that GLP1-ra use is not associated with a decreased bone fracture risk compared to users of other anti-hyperglycemic drugs.
Abstract: Glucagon-like Peptide-1 receptor agonists (GLP1-ra) are a relatively new class of anti-hyperglycemic drugs which may positively affect bone metabolism and thereby decrease (osteoporotic) bone fracture risk. Data on the effect of GLP1-ra on fracture risk are scarce and limited to clinical trial data only. The aim of this study was to investigate, in a population-based cohort, the association between the use of GLP1-ra and bone fracture risk. We conducted a population-based cohort study, with the use of data from the Clinical Practice Research Datalink (CPRD) database (2007–2012). The study population (N = 216,816) consisted of all individuals with type 2 diabetes patients with at least one prescription for a non-insulin anti-diabetic drug and were over 18 years of age. Cox proportional hazards models were used to estimate the hazard ratio of fracture in GLP1-ra users versus never-GLP1-ra users. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and the use of other drugs. There was no decreased risk of fracture with current use of GLP1-ra compared to never-GLP1-ra use (adjusted HR 0.99, 95 % CI 0.82–1.19). Osteoporotic fracture risk was also not decreased by current GLP1-ra use (adjusted HR 0.97; 95 % CI 0.72–1.32). In addition, stratification according to cumulative dose did not show a decreased bone fracture risk with increasing cumulative GLP1-ra dose. We showed in a population-based cohort study that GLP1-ra use is not associated with a decreased bone fracture risk compared to users of other anti-hyperglycemic drugs. Future research is needed to elucidate the potential working mechanisms of GLP1-ra on bone.
58 citations
TL;DR: Deprived areas have higher rates OA (hand, hip, knee) and their increased prevalence of obesity accounts for a 50% of the excess risk of knee OA observed, which could help public health interventions to reduce the prevalence of Obesity.
56 citations
TL;DR: HRT use is associated with an almost 40% reduction in revision rates after a TKA/THA, and preoperative HRT appeared unrelated to implant survival.
Abstract: Objectives Osteolysis and subsequent prosthesis loosening is the most common cause for revision following total knee arthroplasty (TKA) or total hip arthroplasty (THA). Hormone replacement therapy (HRT) could reduce osteolysis through its antiresorptive effects. We studied whether HRT use is associated with reduced revision rates in a community-based cohort of women undergoing TKA or THA for osteoarthritis. Methods Female participants in the General Practice Research Database undergoing a primary TKA or THA from 1986 to 2006 were included. We excluded patients aged Results We matched 2700 HRT users to 8100 non-users, observed for a median (IQR) of 3.3 (1.5–6.1) years after TKA/THA. HR for HRT ≥6 months was 0.62 (95% CI 0.41 to 0.94), whereas HR for ≥12 months was 0.48 (0.29 to 0.78). Higher adherence and therapy duration were associated with further reductions in revision rates. Preoperative HRT appeared unrelated to implant survival. Conclusions HRT use is associated with an almost 40% reduction in revision rates after a TKA/THA. These findings require replication in external cohorts and experimental studies.
35 citations
TL;DR: Drug combinations are common in the treatment of OA patients, who are thus exposed to potential drug interactions, with unknown impacts on their health, including the increasing use of opioids and COX-2 inhibitors.
Abstract: Objective. Patients with OA use different drugs in their search for relief. We aimed to study the prevalence of use and combinations of different medications for OA in a population-based cohort of OA patients in Catalonia, Spain, while characterizing users of each of the drugs available, with a particular focus on cardiovascular risk factors. Methods. Data were obtained from the Sistema d‘Informacio per al Desenvolupament de l‘Investigacio en Atencio Primaria (SIDIAP) database, which includes electronic medical records and pharmacy invoice data for >5 million people from Catalonia. Study participants were those with a clinical diagnosis of OA in 2006–10. Drugs studied included oral and topical NSAIDs, analgesics (paracetamol, metamizole), opioids (tramadol, fentanyl), cyclooxygenase 2 (COX-2) inhibitors and symptomatic slow-acting drugs in OA. Drug utilization was described using medication possession ratios (MPRs), equivalent to the proportion of days covered with the drug of interest. The annual incidence of new users in the first year after OA diagnosis from 2006 to 2010 was estimated for all studied drugs among newly diagnosed OA patients using Poisson regression. Results. We identified 238 536 study participants. The most common regimen of treatment consisted of at least three drugs (53.9% of patients). The drugs most frequently used regularly (MPR ?50%) were chondroitin (21.2%), glucosamine (15.8%) and oral NSAIDs (14.4%). The incidence of the use of opioids, COX-2 inhibitors and chondroitin increased over the 5 year period, whereas all others decreased. Conclusion. Drug combinations are common in the treatment of OA patients, who are thus exposed to potential drug interactions, with unknown impacts on their health. The increasing use of opioids and COX-2 inhibitors is noteworthy because of the potential impact on safety and costs.
34 citations
TL;DR: Both death and hip fracture rates are increased (by 83% and 16%, respectively) in CKD patients, but the association between CKD and hip fractures is attenuated when an excess of mortality is taken into account.
31 citations
TL;DR: The wealthiest areas have an almost 30% increased risk of hip fracture compared to the most deprived areas, and differences in age-sex composition and a higher prevalence of obesity in deprived areas could explain this higher risk.
27 citations
TL;DR: It is demonstrated that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy.
Abstract: Aromatase inhibitors (AIs) are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AIs have an increased risk of bone loss and arthralgia compared with those treated with tamoxifen. In addition to the effects of AIs, the population of women with early breast cancer has a high prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency. In our experience 88% of patients had concentrations lower than 30 ng/ml. Vitamin D supplementation should be adapted to the baseline concentration. Another relevant finding in our research program was the close relationship between 25(OH)D levels and intensity of AI-related arthralgia (AIrA). A target concentration of 40 ng/ml 25(OH)D may prevent development of AIrA. We also demonstrate that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy. We recommend establishing an individualized protocol of bone-health surveillance based on baseline and evolutionary clinical variables.
TL;DR: The genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss.
Abstract: Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P<0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss.
TL;DR: Monthly risedronate, weekly alendronsate, and daily teriparatide are the drugs with the best persistence, whilst daily oral drugs have 40–60 % higher first-year discontinuation rates compared toweekly alendronate.
Abstract: Although a number of reports suggest very low persistence with oral bisphosphonates, there is limited data on persistence with other anti-osteoporosis medications We compare rates of early discontinuation (in the first year) with all available outpatient anti-osteoporosis drugs in Catalonia, Spain We conducted a population-based retrospective cohort study using data from the SIDIAP database SIDIAP contains computerized primary care records and pharmacy dispensing data for >80 % of the population of Catalonia (>5 million people) All SIDIAP participants starting an anti-osteoporosis drug between 1/1/2007 and 30/06/2011 (with 2 years wash-out) were included We modelled persistence as the time between first prescription and therapy discontinuation (refill gap of at least 6 months) using Fine and Gray survival models with competing risk for death We identified 127,722 patients who started any anti-osteoporosis drug in the study period The most commonly prescribed drug was weekly alendronate (N = 55,399) 1-Year persistence ranges from 40 % with monthly risedronate to 77 % with daily risedronate, and discontinuation was very common [from 495 % (monthly risedronate) to 844 % (daily risedronate)] as was also switching in the first year of therapy [from 28 % (weekly alendronate) to 10 % (daily alendronate)] Multivariable-adjusted models showed that only monthly risedronate had better one-year persistence than weekly alendronate and teriparatide equivalent, whilst all other therapies had worse persistence Early discontinuation with available anti-osteoporosis oral drugs is very common Monthly risedronate, weekly alendronate, and daily teriparatide are the drugs with the best persistence, whilst daily oral drugs have 40–60 % higher first-year discontinuation rates compared to weekly alendronate
04 Nov 2015
TL;DR: Socioeconomic deprivation, measured with the MEDEA index, was related with an increase in total mortality in urban areas of Catalonia, and in rural areas there was no association with mortality.
Abstract: Objective: To analyse the association between MEDEA (Mortality in small areas of Spain and socioeconomic and environmental inequalities) index and mortality in urban and rural areas of Catalonia. Methods: An ecological study based on the analysis of census section. The data source used for census section and variables to calculate the MEDEA index was the census (2001). Mortality data were obtained from System for the Development of Research in Primary Care (SIDIAP). The census sections were classified as rural or urban. The association between mortality and the socioeconomic index was analysed as categorical variable (quintiles). Poisson models were fitted to study the association between MEDEA index and mortality. Analysis was done with the STATA software, version 12. Results: In January 2009, a total of 4,526,071 adults (> 14 years old) were assigned to ICS (Institut Catala de la Salut ) primary healthcare centres. The identified population lived in 5,214 census sections out of a total of 5,222 existing areas, from which 4096 (78.5%) were urban. The association between MEDEA quintiles and mortality was significant for urban areas excluding Barcelona: excess mortality was 5% (IRR = 1.05 IC 95% 1.01-1.10), being higher in urban areas (IRR = 1.11 95% CI 1.08 to 1.15) and even higher in Barcelona (IRR = 1.24 95% CI 1.18 to 1.31). This association was not significant for rural areas (IRR = 0.95 CI 95% 0.88-1.02). Conclusions :Socioeconomic deprivation, measured with the MEDEA index, was related with an increase in total mortality in urban areas of Catalonia. In rural areas there was no association with mortality.
12 Oct 2015
08 Apr 2015
TL;DR: This trabajo ha sido financiado por the Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad (RETICEF) y las ayudas FIS PI10/01464 y PI13/00444.
Abstract: Este trabajo ha sido financiado por la Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad (RETICEF; RD12/0043/0022), y las ayudas FIS PI10/01464 y PI13/00444 (Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion). La Generalitat de Cataluna (DIUE 2014 SGR 775) y los fondos FEDER tambien han contribuido a su financiacion