[Gout, beyond the joint: How should we treat it?] / La gota, más allá de la articulación: ¿cómo debemos tratarla?

Gout is a disease caused by the chronic deposition of monosodium urate crystals. Its clinical presentation as an acute, self-limiting arthritis and the belief that it is a banal, self-inflicted disease have led to its poor management. Despite advances in the knowledge of the disease and the simplicity of its management, no more than 30% of patients are well treated. In Spain, the prevalence of gout is 2.5% and its incidence is increasing. In the following article we will review the pathogenesis of gout and hyperuricaemia, highlighting the greater weight of genetics and renal function over diet. We will look at the consequences of crystal deposition. Gout, in addition to its joint presentation and renal involvement, has been shown to be an independent cardiovascular risk factor. Hypouricemic therapy is the most important treatment, as it is the one that dissolves the crystals and cures the disease. This requires the sustained achievement of uricemia levels below 6mg/dl. We will also review preventive and flares treatment, as well as the role of patient education in terms of both lifestyle and dietary habits and adherence to pharmacological treatment.

The treatment gap after major osteoporotic fractures in Denmark 2005-2014: a combined analysis including both prescription-based and hospital-administered anti-osteoporosis medications.

This study demonstrates a substantial and persistent anti-osteoporosis treatment gap in men and women ≥50 years old who sustained major osteoporotic fracture(s) between 2005 and 2014 in Denmark. This was not substantially reduced by including hospital-administered anti-osteoporosis treatments. Strengthened post-fracture organization of care and secondary fracture prevention is highly needed. INTRODUCTION: The purpose of this study was to evaluate the Danish anti-osteoporosis treatment gap from 2005 to 2014 in patients sustaining a major osteoporotic fracture (MOF), and to assess the impact of including hospital-administered anti-osteoporosis medications (AOM) on the treatment gap among these patients. METHODS: In this retrospective, registry-based study, we included men and women aged 50 years or older and living in Denmark, who sustained at least one MOF between 2005 and 2014. We applied a repeated cross-sectional design to generate cohorts of patients sustaining a first MOF, hip, vertebral, humerus, or forearm fracture, respectively, within each calendar year. We evaluated the treatment gap as the proportion of patients within each cohort not receiving treatment with AOM within 1 year of the fracture. Hospital-administered AOM was identified by SKS code. RESULTS: The treatment gap among MOF patients decreased from 85% in 2005 to 79% in 2014. The gap was smaller among hip and vertebral fracture patients as compared to humerus and forearm fracture patients, and it was smaller in women than in men. The use of hospital-administered AOM was relatively uncommon, with a maximum of 0.9% of MOF patients initiating hospital-administered AOM (in 2012). We observed substantial variations in this proportion between fracture types and gender. Hospital-administered AOM was most commonly used among vertebral fracture patients. CONCLUSION: A significant treatment gap among patients sustaining a major osteoporotic fracture was present throughout our analysis, and including hospital-administered AOM did not significantly improve the treatment gap assessment. Improved secondary fracture prevention is urgently needed.

Secular trends in the initiation of therapy in secondary fracture prevention in Europe: a multi-national cohort study including data from Denmark, Catalonia, and the United Kingdom.

This paper demonstrates a large post-fracture anti-osteoporosis treatment gap in the period 2005 to 2015. The gap was stable in Denmark at around 88-90%, increased in Catalonia from 80 to 88%, and started to increase in the UK towards the end of our study. Improved post-fracture care is needed. INTRODUCTION: Patients experiencing a fragility fracture are at high risk of subsequent fractures, particularly within the first 2 years after the fracture. Previous studies have demonstrated that only a small proportion of fracture patients initiate therapy with an anti-osteoporotic medication (AOM), despite the proven fracture risk reduction of such therapies. The aim of this paper is to evaluate the changes in this post-fracture treatment gap across three different countries from 2005 to 2015. METHODS: This analysis, which is part of a multinational cohort study, included men and women, aged 50 years or older, sustaining a first incident fragility fracture. Using routinely collected patient data from three administrative health databases covering Catalonia, Denmark, and the United Kingdom, we estimated the treatment gap as the proportion of patients not treated with AOM within 1 year of their first incident fracture. RESULTS: A total of 648,369 fracture patients were included. Mean age 70.2-78.9 years; 22.2-31.7% were men. In Denmark, the treatment gap was stable at approximately 88-90% throughout the 2005 to 2015 time period. In Catalonia, the treatment gap increased from 80 to 88%. In the UK, an initially decreasing treatment gap-though never smaller than 63%-was replaced by an increasing gap towards the end of our study. The gap was more pronounced in men than in women. CONCLUSION: Despite repeated calls for improved secondary fracture prevention, an unacceptably large treatment gap remains, with time trends indicating that the problem may be getting worse in recent years.

The association between type 2 diabetes mellitus, hip fracture, and post-hip fracture mortality: a multi-state cohort analysis.

Type 2 diabetes mellitus (T2DM) is associated with an excess risk of fractures and overall mortality. This study compared hip fracture and post-hip fracture mortality in T2DM and non-diabetic subjects. The salient findings are that subjects in T2DM are at higher risk of dying after suffering a hip fracture. INTRODUCTION: Previous research suggests that individuals with T2DM are at an excess risk of both fractures and overall mortality, but their combined effect is unknown. Using multi-state cohort analyses, we estimate the association between T2DM and the transition to hip fracture, post-hip fracture mortality, and hip fracture-free all-cause death. METHODS: Population-based cohort from Catalonia, Spain, including all individuals aged 65 to 80 years with a recorded diagnosis of T2DM on 1 January 2006; and non-T2DM matched (up to 2:1) by year of birth, gender, and primary care practice. RESULTS: A total of 44,802 T2DM and 81,233 matched controls (53% women, mean age 72 years old) were followed for a median of 8 years: 23,818 died without fracturing and 3317 broke a hip, of whom 838 subsequently died. Adjusted HRs for hip fracture-free mortality were 1.32 (95% CI 1.28 to 1.37) for men and 1.72 (95% CI 1.65 to 1.79) for women. HRs for hip fracture were 1.24 (95% CI 1.08 to 1.43) and 1.48 (95% CI 1.36 to 1.60), whilst HRs for post-hip fracture mortality were 1.28 (95% CI 1.02 to 1.60) and 1.57 (95% CI 1.31 to 1.88) in men and women, respectively. CONCLUSION: T2DM individuals are at increased risk of hip fracture, post-hip fracture mortality, and hip fracture-free death. After adjustment, T2DM men were at a 28% higher risk of dying after suffering a hip fracture and women had 57% excess risk of post-hip fracture mortality.

El papel del calcio y la vitamina D en la prevención y tratamiento de la osteoporosis / No disponible

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El papel de la determinación de un marcador de resorción, el telopéptido carboxiterminal del colágeno I, en la valoración del cumplimiento terapéutico en pacientes tratadas con bifosfonatos orales / The determining role of a resorption marker,carboxyterminal telopeptide of collagen I,in assessing therapeutic compliance inpatients treated with oral bisphosphonates

Objetivo: Se estima que al año entre el 50-60% de los pacientes tratados con fármacos para la osteoporosis son incumplidores. Disponemos de diferentes métodos indirectos de valoración del cumplimiento. Nuestro objetivo es testar una única determinación del telopéptido carboxiterminal del colágeno tipo I (CTX) para valorar el cumplimiento en pacientes tratadas con bifosfonatos, de forma aislada o junto al cuestionario de Morinsky-Green. Material y método: Estudio de validación diagnóstica realizado en 10 centros de Cataluña. Mediante muestreo consecutivo se seleccionaron mujeres postmenopáusicas con osteoporosis y tratadas con un mismo fármaco antirresortivo en el último año; se excluyeron aquellas tratadas con un fármaco diferente a bifosfonato, con deterioro cognitivo, enfermedad terminal, o insuficiencia renal avanzada, o fractura en el año previo. Se recogieron datos sobre el diagnóstico de osteoporosis y tipo de tratamiento. Se solicitó analítica con determinación del CTX. Como gold-standard se utilizó la tasa de posesión de medicación (Medication Possession Ratio, MPR). Mediante metodología de la curva ROC se estableció el punto de corte teórico del CTX. Se calculó la sensibilidad, la especificidad y los valores predictivos positivos para estimar el cumplimiento terapéutico. Resultados: Se incluyeron 100 pacientes, de las cuales más de la mitad recibían alendronato. Según la MPR, un 70% eran cumplidoras. El valor medio del CTX fue de 0,193±0,146 ng/ml, siendo inferior en las pacientes cumplidoras. Se estableció como punto de corte para valorar el cumplimiento un valor de 0,196 ng/ml. La valoración conjunta del CTX junto al cuestionario de Morinsky-Green presentó mayor capacidad discriminativa. Conclusiones: La realización de una única determinación del CTX (<0,196 ng/ml) junto al cuestionario de Morinsky-Green permite valorar mejor el cumplimiento terapéutico en pacientes tratadas con bifosfonatos

Objective:It is estimated that in one year between 50‐60% of patients treated with osteoporosis drugs are non‐com‐pliant. There are different indirect methods of assessing compliance. Our objective is to test a single determination ofthe carboxyterminal telopeptide of type I collagen (CTX) to assess compliance in patients treated with bisphosphonates,either on its own or together with the Morinsky‐Green questionnaire.Material and method:A diagnostic assessment study was carried out in 10 centers in Catalonia. Through consecutivesampling, postmenopausal women with osteoporosis were selected and treated with the same antiresorptive drug inthe last year. Those treated with a drug other than bisphosphonate, with cognitive impairment, terminal illness, advancedrenal failure or fracture in the previous year, were excluded. Data were collected on the diagnosis of osteoporosis andtype of treatment. Analysis was requested with CTX determination. As a gold standard, the medication possession rate(MPR) was used. Using the ROC curve methodology, the theoretical CTX cut‐off point was established. Sensitivity, spe‐cificity and positive predictive values were calculated to estimate therapeutic compliance.Results:100 patients were included, of which more than half were being treated with alendronate. According to theMPR, 70% were compliant. The mean CTX value was 0.193±0.146 ng/ml. It was lower in the compliant patients. A valueof 0.196 ng/ml was established as a cut‐off point to assess compliance. The joint assessment of the CTX together withthe Morinsky‐Green questionnaire showed greater discriminatory capacity.Conclusions:Carrying out a single determination of CTX (<0.196 ng/ml) along with the Morinsky‐Green questionnaireallows us to more accurately assess the therapeutic compliance in patients treated with bisphosphonates

Real-world antidiabetic drug use and fracture risk in 12,277 patients with type 2 diabetes mellitus: a nested case-control study.

We conducted a nested case-control study to study the association between antidiabetic treatments (alone or in combination) use and fracture risk among incident type 2 Diabetes mellitus patients. We found an increased risk of bone fracture with insulin therapy compared to metformin monotherapy. INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions. METHODS: A case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5 million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10 years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6 months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator). RESULTS: Data on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications. CONCLUSIONS: Insulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part of T2DM treatment.

Osteoporosis y Atención Primaria. Como valorar el riesgo de fractura. Utilización de las escalas de riesgo / Osteoporosis and Primary Care. How toassess the risk of fracture. Use of risk scales

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Uso de fármacos para la osteoporosis en pacientes con diabetes mellitus tipo 2: estudio de cohortes de base poblacional / Use of drugs for osteoporosis treatment in patients with type 2 diabetes mellitus: population-based cohort study

Objetivo: Determinar si existen diferencias en la prevalencia del uso de fármacos para la osteoporosis entre pacientes diabéticos tipo 2 (DM2) y no diabéticos. Material y método: Estudio de cohortes retrospectivas con datos del Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP), que contiene información clínica anonimizada de más de 5 millones de pacientes de Cataluña. Se seleccionaron todos los pacientes de ≥50 años de edad con diagnóstico de DM2, que fueron apareados con dos sujetos sin diabetes. Se recogió información sobre variables descriptivas, fracturas prevalentes y el uso de fármacos para la osteoporosis agrupados en bifosfonatos (BF), suplementos calcio y vitamina D (CaD), y cualquier fármaco para la osteoporosis (FPO). Mediante regresión logística se calculó la asociación entre la presencia de DM2 y el uso de FPO, ajustando por variables confusoras. Resultados: Se identificaron 166.106 pacientes con DM2 y 332.212 no diabéticos. Los DM2 tenían mayor prevalencia de fractura que los no diabéticos (1,3% vs. 0,3%). El uso de BF en los pacientes con DM2 era del 6,6%, frente al 9,3% en los no diabéticos (p<0,001); de CaD, 9,7% vs. 12,3% (p<0,001); y de FPO, 7,6% vs. 10,7% (p<0,001). Tras ajustar por variables confusoras, los pacientes con DM2 presentaban menor probabilidad de ser tratados con BF (OR=0,67; IC95%: 0,64-0,68), con CaD (OR=0,71; IC95%: 0,70-0,73) o con FPO (OR=0,66; IC95%: 0,64-0,67) que los no diabéticos. Conclusiones: A pesar de presentar una mayor prevalencia de fracturas previas, los pacientes con DM2 tienen más del 30% de probabilidad de no recibir un FPO que los no diabéticos. Esto podría ser debido a una infravaloración del riesgo en estos pacientes (AU)

Objective: Ascertain whether there are differences in the prevalence of osteoporosis drugs in patients with type 2 diabetes (DM2) and non-diabetic patients. Material and methods: Retrospective cohort study with data from the Information System for the Development of Primary Care Research (SIDIAP), which contains anonymous clinical information from more than 5 million patients in Catalonia. All 50-year-old patients diagnosed with DM2, who were matched with two subjects without diabetes, were selected. Information on descriptive variables, prevalent fractures and the use of osteoporosis drugs grouped in bisphosphonates (BF), calcium and vitamin D supplements (CaD), and any osteoporosis drug (OD) were collected. Through logistic regression, the association between the presence of DM2 and the use of OD was calculated, adjusting for confounding variables. Results: A total of 166,106 patients with DM2 and 332,212 non-diabetics. The DM2 group presented a higher prevalence of fracture than did diabetics (1.3% vs 0.3%). The use of BF in patients with DM2 was 6.6%, compared to 9.3% in non-diabetics (p<0.001). Of CaD, 9.7% vs 12.3% (p<0.001) and OD, 7.6% vs 10.7% (p<0.001). After adjusting for variable confounders, the patients with DM2 presented a lower probability of being treated with BF (OR=0.67, 95% CI: 0.64-0.68), with CaD (OR=0.71, 95% CI: 0.70-0.73) or with OD (OR=0.66, 95% CI: 0.64-0.67) than non-diabetics. Conclusions: Despite having a higher prevalence of fractures in patients with DM2, they have more than 30% chance of not having received an OD than non-diabetic patients. This may be attributed to an underestimation of risk in these patients (AU)

Excess of all-cause mortality after a fracture in type 2 diabetic patients: a population-based cohort study.

Post-fracture mortality in type 2 diabetes mellitus (T2DM) patients has been poorly studied. We report an absolute and relative excess all-cause mortality following a fracture in these patients compared to non-diabetic patients. INTRODUCTION: T2DM and osteoporotic fractures are independently associated with a reduced lifespan, but it is unknown if T2DM confers an excess post-fracture mortality compared to non-diabetic fracture patients. We report post-fracture all-cause mortality according to T2DM status. METHODS: This is a population-based cohort study using data from the SIDIAP database. All ≥50 years old T2DM patients registered in SIDIAP in 2006-2013 and two diabetes-free controls matched on age, gender, and primary care center were selected. Study outcome was all-cause mortality following incident fractures. Participants were followed from date of any fracture (AF), hip fracture (HF), and clinical vertebral fracture (VF) until the earliest of death or censoring. Cox regression was used to calculate mortality according to T2DM status after adjustment for age, gender, body mass index, smoking, alcohol intake, and previous ischemic heart and cerebrovascular disease. RESULTS: We identified 166,106 T2DM patients and 332,212 non-diabetic, of which 11,066 and 21,564, respectively, sustained a fracture and were then included. Post-fracture mortality rates (1000 person-years) were (in T2DM vs non-diabetics) 62.7 vs 49.5 after AF, 130.7 vs 112.7 after HF, and 54.9 vs 46.2 after VF. Adjusted HR (95% CI) for post-AF, post-HF, and post-VF mortality was 1.30 (1.23-1.37), 1.28 (1.20-1.38), and 1.20 (1.06-1.35), respectively, for T2DM compared to non-diabetics. CONCLUSIONS: T2DM patients have a 30% increased post-fracture mortality compared to non-diabetics and a remarkable excess in absolute mortality risk. More research is needed on the causes underlying such excess risk, and on the effectiveness of measures to reduce post-fracture morbi-mortality in T2DM subjects.

One and two-year persistence with different anti-osteoporosis medications: a retrospective cohort study.

Adherence to anti-osteoporosis medications is poor. We carried out a cohort study using a real-world population database to estimate the persistence of anti-osteoporosis drugs. Unadjusted 2-year persistence ranged from 10.3 to 45.4%. Denosumab users had a 40% lower risk of discontinuation at 2 years compared to alendronate users. PURPOSE: The purpose of this study was to estimate real-world persistence amongst incident users of anti-osteoporosis medications. METHODS: This is a retrospective cohort using data from anonymised records and dispensation data ( www.sidiap.org ). Eligibility comprised the following: women aged ≥50, incident users of anti-osteoporosis medication (2012), with data available for at least 12 months prior to therapy initiation. Exclusions are other bone diseases/treatments and uncommon anti-osteoporosis drugs (N < 100). Follow-up was from first pharmacy dispensation until cessation, end of study, censoring or switching. Outcomes are 2- and 1-year persistence with a permissible gap of up to 90 days. Persistence with alendronate was compared to other bisphosphonates, strontium ranelate, selective oestrogen receptor modulators, teriparatide and denosumab. Cox models were used to estimate hazard ratios of therapy cessation according to drug used after adjustment for age, sex, BMI, smoking, alcohol drinking, Charlson co-morbidity index, previous fractures, use of anti-osteoporosis medication/s, oral corticosteroids and socio-economic status. RESULTS: A total of 19,253 women were included. Unadjusted 2-year persistence [95% CI] ranged from 10.3% [9.1-11.6%] (strontium ranelate) to 45.4% [43.1-47.8%] (denosumab). One-year persistence went from 35.8% [33.9%-37.7%] (strontium ranelate) to 65.8% [63.6%-68.0%] (denosumab). At the end of the first year and compared to alendronate users, both teriparatide and denosumab users had reduced cessation risk (adjusted HR 0.76, 95% CI 0.67-0.86 and 0.54, 95% CI 0.50-0.59 respectively) while at the end of the second year, only denosumab had a lower risk of discontinuation (adjusted HR 0.60, 95% CI 0.56-0.64). CONCLUSIONS: Unadjusted 2-year persistence is suboptimal. However, both teriparatide and denosumab users had better 1-year persistence and only denosumab had 2-year better persistence compared to alendronate users. Unmeasured confounding by indication might partially explain our findings.

Incident type 2 diabetes and hip fracture risk: a population-based matched cohort study.

SUMMARY: 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. INTRODUCTION: 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. METHODS: We conducted a population-based parallel cohort study using data from the Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (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. RESULTS: 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]. CONCLUSIONS: 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.