Daniel Prieto-Alhambra

Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints

Objectives Data on the incidence of symptomatic osteoarthritis (OA) are scarce. We estimated incidence of clinical hip, knee and hand OA, and studied the effect of prevalent OA on joint-specific incident OA. Methods SIDIAP contains primary care records for>5 million people from Catalonia (Spain). Participants aged ≥40 years with an incident diagnosis of knee, hip or hand OA between 2006 and 2010 were identified using International Classification of Diseases (ICD)-10 codes. Incidence rates and female-to-male rate ratios (RRs) for each joint site were calculated. Age, gender and body mass index-adjusted HR for future joint-specific OA according to prevalent OA at other sites were estimated using Cox regression. Results 3 266 826 participants were studied for a median of 4.45 years. Knee and hip OA rates increased continuously with age, and female-to-male RRs were highest at age 70–75 years. In contrast, female hand OA risk peaked at age 60–64 years, and corresponding female-to-male RR was highest at age 50–55 years. Adjusted HR for prevalent knee OA on risk of hip OA was 1.35 (99% CI 1.28 to 1.43); prevalent hip OA on incident knee OA: HR 1.15 (1.08 to 1.23). Prevalent hand OA predicted incident knee and hip OA: HR 1.20 (1.14 to 1.26) and 1.23 (1.13 to 1.34), respectively. Conclusions The effect of age is greatest in the elderly for knee and hip OA, but around the menopause for hand OA. OA clusters within individuals, with higher risk of incident knee and hip disease from prevalent lower limb and hand OA.

HIV infection is strongly associated with hip fracture risk, independently of age, gender, and comorbidities: A population‐based cohort study

HIV infection and antiretroviral therapies have detrimental effects on bone metabolism, but data on their impact on fracture risk are controversial. We conducted a population‐based cohort study to explore the association between clinical diagnosis of HIV infection and hip and major osteoporotic fracture risk. Data were obtained from the SIDIAPQ database, which contains clinical information for >2 million patients in Catalonia, Spain (30% of the population). We screened the database to identify participants with a clinical diagnosis of HIV infection, and ascertained incident hip and osteoporotic major fractures in the population aged 40 years or older in 2007 to 2009. In addition, data on incident fractures involving hospital admission were obtained from the Hospital Admissions database. Cox regression models were used to estimate hazard ratios (HRs) for the HIV‐infected versus uninfected participants. Models were adjusted for age, sex, body mass index, smoking status, alcohol drinking, oral glucocorticoid use, and comorbid conditions (Charlson index). Among 1,118,156 eligible participants, we identified 2489 (0.22%) subjects with a diagnosis of HIV/AIDS. Age‐ and sex‐adjusted HR for HIV/AIDS were 6.2 (95% confidence interval [CI] 3.5–10.9; p < 0.001) and 2.7 (2.01–3.5; p < 0.001) for hip and major fractures, respectively; this remained significant after adjustment for all mentioned potential confounders: HR 4.7 (2.4–9.5; p < 0.001) and 1.8 (1.2–2.5; p = 0.002). After stratifying by age, the association between HIV infection and major fractures was attenuated for those aged <59 years (adjusted HR 1.35 [0.88–2.07], p = 0.17) but appeared stronger in older patients (adjusted HR 2.11 [1.05–4.22], p = 0.035). We report a strong association between HIV infection and hip fracture incidence, with an almost fivefold increased risk in the HIV infected, independent of sex, age, smoking, alcohol drinking, and comorbidities. Similarly, we demonstrate a 75% higher risk of all clinical fractures and a 60% increase in risk of non‐hip clinical fractures among patients with a diagnosis of HIV infection.

Base de datos SIDIAP, la historia clínica informatizada de Atención Primaria como fuente de información para la investigación epidemiológica

a Institut Universitari d’Investigació en Atenció Primària (IDIAP) Jordi Gol, Barcelona, España b Universitat Autònoma de Barcelona, Bellaterra, Barcelona, España c Institut Català de la Salut, Barcelona, España d Facultad de Medicina, Universitat de Girona, Girona, España e Institut d’Investigació Biomèdica de Girona (IdIBGi), Girona, España f Unitat de Recerca en Fisiopatologia Òssia i Articular (URFOA), Institut Municipal d’Investigació Mèdica (IMIM)-Hospital del Mar), Barcelona, España

Future projections of total hip and knee arthroplasty in the UK: results from the UK Clinical Practice Research Datalink

OBJECTIVE To estimate the future rate of primary total hip (THR) or knee (TKR) replacement in the UK to 2035 allowing for changes in population demographics and obesity. DESIGN Using age/gender/body mass index (BMI)-specific incidence rates from a population-based cohort study of 50,000 THR and 45,609 TKR patients from the UK Clinical Practice Research Datalink (CPRD) between 1991 and 2010, we projected future numbers of THR and TKR using two models: a static, estimated rate from 2010 applied to population growth forecasts to 2035, and a log-linear rate extrapolation over the same period. Both scenarios used population forecast data from the UK Office for National Statistics (ONS). RESULTS Assuming rates of THR and TKR for 2010, and given projected population changes in age, gender and BMI, the number of THRs and TKRs performed in the UK in 2035 is estimated to be, respectively: 95,877 and 118,666. By comparison, an exponential extrapolation of historical rates using a log-linear model produces much higher estimates of THR and TKR counts in 2035 at 439,097 and 1,219,362 respectively. Projected counts were higher for women than men. Assuming a changing (rather than fixed) future BMI distribution increases TKRs by 2035 but not THRs. CONCLUSIONS Using historical rates and population forecasts we have projected the number of THR/TKR operations in the UK up to 2035. This study will inform policymakers requiring estimates of future demand for surgery. Incorporating future forecasts for BMI into projections of joint replacement may be more relevant for TKR rather than THR.

Association between bisphosphonate use and implant survival after primary total arthroplasty of the knee or hip: population based retrospective cohort study.

Objectives To test whether bisphosphonate use is related to improved implant survival after total arthroplasty of the knee or hip. Design Population based retrospective cohort study. Setting Primary care data from the United Kingdom. Participants All patients undergoing primary total arthroplasty of the knee (n=18 726) or hip (n=23 269) in 1986-2006 within the United Kingdom’s General Practice Research Database. We excluded patients with a history of hip fracture before surgery or rheumatoid arthritis, and individuals younger than 40 years at surgery. Intervention Bisphosphonate users were classified as patients with at least six prescriptions of bisphosphonates or at least six months of prescribed bisphosphonate treatment with more than 80% adherence before revision surgery. Outcome measures Revision arthroplasties occurring after surgery, identified by READ and OXMIS codes. Parametric survival models were used to determine effects on implant survival with propensity score adjustment to account for confounding by indication. Results Of 41 995 patients undergoing primary hip or knee arthroplasty, we identified 1912 bisphosphonate users, who had a lower rate of revision at five years than non-users (0.93% (95% confidence interval 0.52% to 1.68%) v 1.96% (1.80% to 2.14%)). Implant survival was significantly longer in bisphosphonate users than in non-users in propensity adjusted models (hazard ratio 0.54 (0.29 to 0.99); P=0.047) and had an almost twofold increase in time to revision after hip or knee arthroplasty (time ratio 1.96 (1.01 to 3.82)). Assuming 2% failure over five years, we estimated that the number to treat to avoid one revision was 107 for oral bisphosphonates. Conclusions In patients undergoing lower limb arthroplasty, bisphosphonate use was associated with an almost twofold increase in implant survival time. These findings require replication and testing in experimental studies for confirmation.

HIV infection and its association with an excess risk of clinical fractures: a nationwide case-control study.

Background:Different studies have reported an association between HIV infection, antiretroviral therapies, and impaired bone metabolism, but data on their impact on fracture risk are scarce. We studied the association between a clinical diagnosis of HIV infection and fracture risk. Methods:We conducted a case–control study using data from the Danish National Health Service registries, including 124,655 fracture cases and 373,962 age- and gender-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Results:A total of 50 (0.40/1000) patients in the fracture group and 52 (0.14/1000) controls had an HIV diagnosis. The risk of any fracture was thus significantly increased among HIV-infected patients (age- and gender-matched OR = 2.89, 95% CI: 1.99 to 4.18). Similarly, significant increases in the risk of hip (OR = 8.99, 95% CI: 1.39 to 58.0), forearm (OR = 3.50, 95% CI: 1.26 to 9.72), and spine fractures (OR = 9.00, 95% CI: 1.39 to 58.1) were observed. Conclusions:HIV infection is associated with an almost 3-fold increase in fracture risk compared with that of age- and gender-matched uninfected patients. HIV patients are also at an almost 9-fold higher risk of hip fracture.

The association between fracture site and obesity in men: a population-based cohort study.

A site‐dependent association between obesity and fracture has been reported in postmenopausal women. In this study we investigated the relationship between body mass index (BMI) and fracture at different skeletal sites in older men (≥65 years). We carried out a population‐based cohort study using data from the Sistema d‘Informació per al Desenvolupament de l‘Investigació en Atenció Primària (SIDIAPQ) database. SIDIAPQ contains the primary care and hospital admission computerized medical records of >1300 general practitioners (GPs) in Catalonia (Northeast Spain), with information on a representative 30% of the population (>2 million people). In 2007, 186,171 men ≥65 years were eligible, of whom 139,419 (74.9%) had an available BMI measurement. For this analysis men were categorized as underweight/normal (BMI < 25 kg/m2, n = 26,298), overweight (25 ≤ BMI < 30 kg/m2, n = 70,851), and obese (BMI ≥ 30 kg/m2, n = 42,270). Incident fractures in the period 2007 to 2009 were ascertained using International Classification of Diseases, 10th edition (ICD‐10) codes. A statistically significant reduction in clinical spine and hip fractures was observed in obese (relative risk [RR], 0.65; 95% confidence interval [CI], 0.53–0.80 and RR, 0.63; 95% CI, 0.54–0.74, respectively), and overweight men (RR, 0.77; 95% CI, 0.64–0.92 and RR, 0.63; 95% CI 0.55–0.72, respectively) when compared with underweight/normal men. Additionally, obese men had significantly fewer wrist/forearm (RR, 0.77; 95% CI, 0.61–0.97) and pelvic (RR, 0.44; 95% CI, 0.28–0.70) fractures than underweight/normal men. Conversely, multiple rib fractures were more frequent in overweight (RR, 3.42; 95% CI, 1.03–11.37) and obese (RR, 3.96; 95% CI, 1.16–13.52) men. In this population‐based cohort of older men, obesity was associated with a reduced risk of clinical spine, hip, pelvis, and wrist/forearm fracture and increased risk of multiple rib fractures when compared to normal or underweight men. Further work is needed to identify the mechanisms underlying these associations.

Validez del Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP) en el estudio de enfermedades vasculares: estudio EMMA

INTRODUCTION AND OBJECTIVES Information in primary care databases can be useful in research, but the validity of these data needs to be evaluated. We sought to analyze the validity of the data used in the EMMA study based on data from the Information System for the Development of Research in Primary Care. METHODS We compared the prevalence of cardiovascular risk factors observed in EMMA-hypertension, diabetes, hypercholesterolemia (and its treatments), obesity, and smoking-with equivalent data from the Registre Gironí del Cor (REGICOR), a population-based study that uses standardized methodology, in 2000. We also compared the incidence rates of vascular diseases and its association with these risk factors in a 5-year follow-up. RESULTS We analyzed data from 34 823 participants included in EMMA and 2540 REGICOR2000 study participants aged 35 to 74. The prevalence of risk factors did not differ significantly between the 2 studies, except for the prevalence of former smokers in men, which was higher in REGICOR2000 (24.7% [95% confidence interval, 23.9%-25.5%] vs 30.1% [95% confidence interval, 27.1%-33.1%]), and the proportion of patients with lipid-lowering and antihypertensive therapy, which was higher in EMMA (46.9% vs 32.7% and 8.7% vs 6.3%, respectively). There were no differences between the 2 studies when comparing the incidence of vascular diseases (2.1% in both studies in men and 1.18% [95% confidence interval, 0.7%-1.7%] in REGICOR2000 vs 0.75% [95% confidence interval, 0.64%-0.87%] in EMMA in women) and its association with risk factors. CONCLUSIONS The prevalence of cardiovascular risk factors and their association with the incidence of vascular disease observed in the EMMA study are consistent with those observed in an epidemiological population-based study with a standardized methodology.

An increased rate of falling leads to a rise in fracture risk in postmenopausal women with self-reported osteoarthritis: a prospective multinational cohort study (GLOW)

Objectives Patients with osteoarthritis have increased bone mass but no decrease in fractures. The association between self-reported osteoarthritis and incident falls and fractures was studied in postmenopausal women. Methods The Global Longitudinal Study of Osteoporosis in Women is a prospective multinational cohort of 60 393 non-institutionalised women aged ≥55 years who had visited primary care practices within the previous 2 years. Questionnaires were mailed at yearly intervals. Patients were classified as having osteoarthritis if they answered yes to the question, ‘Has a doctor or other health provider ever said that you had osteoarthritis or degenerative joint disease?’, and this was validated against primary care records in a subsample. Information on incident falls, fractures and covariates was self-reported. Cox and Poisson models were used for incident fractures and number of falls, respectively, to compute hazard ratios (HRs) and rate ratios (RRs) for baseline osteoarthritis status. Results Of 51 386 women followed for a median of 2.9 years (interquartile range 2.1–3.0), 20 409 (40%) reported osteoarthritis. The adjusted HR for osteoarthritis predicting fracture was 1.21 (95% CI 1.13 to 1.30; p<0.0001) and the adjusted RR for falls was 1.24 (95% CI 1.22 to 1.26; p<0.0001). However, the association between osteoarthritis and fracture was not significant after adjustment for incident falls (HR 1.06 (95% CI 0.98 to 1.15; p=0.13)). Conclusions Postmenopausal women with self-reported osteoarthritis have a 20% increased risk of fracture and experience 25% more falls than those without osteoarthritis. These data suggest that increased falls are the causal pathway of the association between osteoarthritis and fractures.

Mortality rates at 10 years after metal-on-metal hip resurfacing compared with total hip replacement in England: retrospective cohort analysis of hospital episode statistics.

Objectives To compare 10 year mortality rates among patients undergoing metal-on-metal hip resurfacing and total hip replacement in England. Design Retrospective cohort study. Setting English hospital episode statistics database linked to mortality records from the Office for National Statistics. Population All adults who underwent primary elective hip replacement for osteoarthritis from April 1999 to March 2012. The exposure of interest was prosthesis type: cemented total hip replacement, uncemented total hip replacement, and metal-on-metal hip resurfacing. Confounding variables included age, sex, Charlson comorbidity index, rurality, area deprivation, surgical volume, and year of operation. Main outcome measures All cause mortality. Propensity score matching was used to minimise confounding by indication. Kaplan-Meier plots estimated the probability of survival up to 10 years after surgery. Multilevel Cox regression modelling, stratified on matched sets, described the association between prosthesis type and time to death, accounting for variation across hospital trusts. Results 7437 patients undergoing metal-on-metal hip resurfacing were matched to 22 311 undergoing cemented total hip replacement; 8101 patients undergoing metal-on-metal hip resurfacing were matched to 24 303 undergoing uncemented total hip replacement. 10 year rates of cumulative mortality were 271 (3.6%) for metal-on-metal hip resurfacing versus 1363 (6.1%) for cemented total hip replacement, and 239 (3.0%) for metal-on-metal hip resurfacing versus 999 (4.1%) for uncemented total hip replacement. Patients undergoing metal-on-metal hip resurfacing had an increased survival probability (hazard ratio 0.51 (95% confidence interval 0.45 to 0.59) for cemented hip replacement; 0.55 (0.47 to 0.65) for uncemented hip replacement). There was no evidence for an interaction with age or sex. Conclusions Patients with hip osteoarthritis undergoing metal-on-metal hip resurfacing have reduced mortality in the long term compared with those undergoing cemented or uncemented total hip replacement. This difference persisted after extensive adjustment for confounding factors available in our data. The study results can be applied to matched populations, which exclude patients who are very old and have had complex total hip replacements. Although residual confounding is possible, the observed effect size is large. These findings require validation in external cohorts and randomised clinical trials.