D Prieto-Alhambra

Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

Aromatase inhibitor (AI)-associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. We wished to establish the optimal concentration of 25(OH)D that prevents or minimizes arthralgia. We used a prospective cohort of 290 women starting AI in whom baseline vitamin D was measured. All received daily vitamin D3 (800xa0IU) with calcium. Women with baseline 25(OH)D concentration <30xa0ng/ml also received 16,000xa0IU of D3 orally every 2 weeks. The primary outcome was incident or worsening joint pain derived from baseline and 3-month visual analogic scale (VAS) for joint pain. Regression models were used to analyse the association between vitamin D concentrations at 3xa0months and pain adjusting for age, BMI, season when the sample was drawn, aromatase inhibitor (exemestane vs. letrozole/anastrozole), prior tamoxifen therapy, baseline NTX, and previous fracture. 90% of women had a 25(OH)D <30xa0ng/ml at baseline. After supplementation (daily 800xa0IU and additional 16,000xa0IU every 2 weeks), 50% of them still failed to reach adequate concentrations at 3 months. In the whole cohort, there was an increase in joint pain (mean 1.16 points SD 2.66; Pxa0<xa00.001) and the increase was significantly (Pxa0=xa00.02) attenuated in those that reached concentrations of 25(OH)D of ≥40xa0ng/ml, with a lower risk of incident arthralgia (OR 0.12xa0**xa0[0.03 to 0.40]). A target concentration of 40xa0ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.

IMPACT OF HIP FRACTURE ON HOSPITAL CARE COSTS: A POPULATION BASED STUDY

SummaryUsing a large cohort of hip fracture patients, we estimated hospital costs to be £14,163 and £2139 in the first and second year following fracture, respectively. Second hip and non-hip fractures were major cost drivers. There is a strong economic incentive to identify cost-effective approaches for hip fracture prevention.IntroductionThe purpose of this study was to estimate hospital costs of hip fracture up to 2xa0years post-fracture and compare costs before and after the index fracture.MethodsA cohort of patients aged over 60xa0years admitted with a hip fracture in a UK region between 2003 and 2013 were identified from hospital records and followed until death or administrative censoring. All hospital records were valued using 2012/2013 unit costs, and non-parametric censoring methods were used to adjust for censoring when estimating average annual costs. A generalised linear model examined the main predictors of hospital costs.ResultsA cohort ofxa033,152 patients with a hip fracture was identified (mean age 83 years (SD 8.2). The mean censor-adjusted 1- and 2-year hospital costs after index hip fracture were £14,163 (95xa0% confidence interval (CI) £14,008 to £14,317) and £16,302 (95xa0% CI £16,097 to £16,515), respectively. Index admission accounted for 61xa0% (£8613; 95xa0% CI £8565 to £8661) of total 1-year hospital costs which were £10,964 higher compared to the year pre-event (pu2009<u20090.001). The main predictors of 1-year hospital costs were second hip fracture, other non-hip fragility fractures requiring hospitalisation and hip fracture-related complications. Total UK annual hospital costs associated with incident hip fractures were estimated at £1.1 billion.ConclusionsHospital costs following hip fracture are high and mostly occur in the first year after the index hip fracture. Experiencing a second hip fracture after the index fracture accounted for much of the increase in costs. There is a strong economic incentive to prioritise research funds towards identifying the best approaches to prevent both index and subsequent hip fractures.

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 dInformació per al Desenvolupament de lInvestigació 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 (nu2009=u200932,346) 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; pu2009<u20090.001) and nonvertebral (HR 1.19; 95% CI, 1.02 to 1.39; pu2009=u20090.03) 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.

Burden of pelvis fracture: a population-based study of incidence, hospitalisation and mortality.

SummaryThe objective of this study was to describe the incidence and consequences of pelvic fractures in a community cohort. The incidence of pelvic fractures increases with age with a protective effect of higher body mass index. Almost 60% of those with a pelvic fracture required an inpatient stay, with a median of 9 days. There was a higher 3-year mortality in those admitted (17%) vs. those not admitted (6.3%). Given the substantial health burden, further work is required to identify the optimal post-fracture therapeutic strategy to improve outcomes.IntroductionThe burden of pelvis fractures is projected to increase, but there is a paucity of community-based studies describing rates, mortality and future fracture risk. We therefore estimated the age, gender and BMI-specific incidence of pelvis fracture in Catalonia (North-East Spain), and assessed hospital stay and mortality following fracture.MethodsThe SIDIAPQ database contains validated clinical information from computerised medical records of a representative sample of 30% of the population of Catalonia. We conducted a retrospective cohort study including all subjects aged ≥40 in SIDIAPQ and linked to the regional Hospital Admissions Database from 2007 to 2009. Pelvis fractures were ascertained using ICD-10 codes. Incidence and mortality rates were calculated.ResultsA total of 1,118,173 patients (582,820 women) were observed for 3xa0years and 1,356 had a pelvic fracture. The rate for pelvic fracture was 4.35/10,000 person-years (pyar) [95% CI 4.13–4.59] (men—2.73 [2.48–3.01]; women—5.82 [5.46–6.20]). This increased with age, peaking in those over 90xa0years: 29.41 [25.74–33.59]. Higher BMI was protective (HR 0.75 per SD BMI; [0.69–0.82]). Moreover, 59.1% of fractured patients were hospitalised with a median (IQR) stay of 9 (5–16) days, and after the 3-year follow-up 13.9% died (mortality rate 10.7/100 pyar [9.3–12.3]) with higher rates in those hospitalised (17.0%).ConclusionsPelvic fractures are associated with high rates of hospitalisation and mortality. Given this, further work is required to identify the optimal post-fracture therapeutic strategy to improve outcomes in this elderly patient group.

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

SummaryThere is scarce data on the association between early stages of type 2 diabetes and fracture risk. We report a 20xa0% excess risk of hip fracture in the first years following disease onset compared to matched non-diabetic patients.IntroductionType 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.MethodsWe 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.ResultsDuring the study period (median follow-up 2.63xa0years), 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].ConclusionsNewly diagnosed T2DM patients are at a 20xa0% 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.

The effect of body mass index on the risk of post-operative complications during the 6 months following total hip replacement or total knee replacement surgery

OBJECTIVEnTo assess the effect of obesity on 6-month post-operative complications following total knee (TKR) or hip (THR) replacement.nnnDESIGNnData for patients undergoing first THR or TKR between 1995 and 2011 was taken from the Clinical Practice Research Datalink. Logistic regression was used to assess whether body mass index (BMI) was associated with 6-month post-operative complications [deep vein thrombosis or pulmonary embolism (DVT/PE), myocardial infarction (MI), stroke, respiratory infection, anaemia, wound infection, urinary tract infection or death] after controlling for the effects of age, gender, smoking, drinking, socio-economic status (SES), co-morbidities and medications.nnnRESULTSn31,817 THR patients and 32,485 TKR patients were identified for inclusion. Increasing BMI was associated with a significantly higher risk of wound infections, from 1.6% to 3.5% in THR patients (adjusted P < 0.01), and from 3% to 4.1% (adjusted P < 0.05) in TKR patients. DVT/PE risk also increased with obesity from 2.2% to 3.3% (adjusted P < 0.01) in THR patients and from 2.0% to 3.3% (adjusted P < 0.01) in TKR patients. Obesity was not associated with increased risk of other complications.nnnCONCLUSIONnWhilst an increased risk of wound infection and DVT/PE was observed amongst obese patients, absolute risks remain low and no such association was observed for MI, stroke and mortality. However this is a selected cohort (eligible for surgery according to judgement of NHS GPs and surgeons) and as such these results do not advocate surgery be given without consideration of BMI, but indicate that universal denial of surgery based on BMI is unwarranted.

The impact of common co-morbidities (as measured using the Charlson index) on hip fracture risk in elderly men: a population-based cohort study.

SummaryWe used a large population-based health care database to determine the impact of common co-morbidities on hip fracture risk amongst elderly men. We demonstrated that diabetes, chronic obstructive pulmonary disease, renal failure, HIV infection, dementia, and cerebrovascular disease are independent predictors of hip fracture, as is a Charlson score of ≥3.IntroductionRisk factors for hip fractures in men are still unclear. We aimed to identify common co-morbidities (amongst those in the Charlson index) that confer an increased risk of hip fracture amongst elderly men.MethodsWe conducted a population-based cohort study using data from the SIDIAPQ database. SIDIAPQ contains primary care and hospital inpatient records of a representative 30xa0% of the population of Catalonia, Spain (>2 million people). All men aged ≥65xa0years registered on 1 January 2007 were followed up until 31 December 2009. Both exposure (co-morbidities in the Charlson index) and outcome (incident hip fractures) were ascertained using ICD codes. Poisson regression models were fitted to estimate the effect of (1) each individual co-morbidity and (2) the composite Charlson index score, on hip fracture risk, after adjustment for age, body mass index, smoking, alcohol drinking, and use of oral glucocorticoids.ResultsWe observed 186,171 men for a median (inter-quartile range) of 2.99 (2.37–2.99) years. In this time, 1,718 (0.92xa0%) participants had a hip fracture. The following co-morbidities were independently associated with hip fractures: diabetes mellitus, chronic obstructive pulmonary disease (COPD), renal failure, HIV infection, dementia, and cerebrovascular disease. A Charlson score of ≥3 conferred an increased hip fracture risk.ConclusionCommon co-morbidities including diabetes, COPD, cerebrovascular disease, renal failure, and HIV infection are independently associated with an increased risk of hip fracture in elderly men. A Charlson score of 3 or more is associated with a 50xa0% higher risk of hip fracture in this population.

Ankylosing spondylitis confers substantially increased risk of clinical spine fractures: A nationwide case-control study

SummaryAnkylosing 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 50xa0% 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.IntroductionAnkylosing 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.MethodsFrom 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.ResultsWe identified 139/124,655 (0.11xa0%) AS fracture cases, compared to 271/373,962 (0.07xa0%) AS controls. Unadjusted (age- and gender-matched) odds ratio (OR) were 1.54 [95xa0% confidence interval (95xa0%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 2.5xa0years following AS diagnosis: OR 2.69 [1.84–3.92] for any fracture.ConclusionsPatients with AS have a 5-fold higher risk of clinical spine fracture and a 35xa0% increased risk of non-vertebral fracture. This excess risk peaks early, in the first 2.5xa0years of AS disease. Patients should be assessed for fracture risk early after AS diagnosis.

Relationship between mortality and BMI after fracture: a population-based study of men and women aged ≥40 years.

Fractures in obese older individuals contribute significantly to the overall burden on primary health care, but data on their impact on mortality are lacking. We studied the association between obesity and mortality following hip and nonhip clinical fractures in a retrospective, population‐based cohort study. The Sistema dInformació pel Desenvolupament de la Investigació en Atenció Primària (SIDIAPQ) database contains primary care computerized medical records of a representative sample of >2.1 million people (35% of the population) in Catalonia (Spain), linked to hospital admissions data. We included in this analysis anyone aged 40 years and older suffering a hip or nonhip clinical fracture in 2007 to 2009 in the SIDIAPQ database. The main exposure was the most recent body mass index (BMI) measured before fracture, categorized as underweight (<18.5u2009kg/m2), normal (18.5 to <25u2009kg/m2), overweight (25 to <30u2009kg/m2), and obese (≥30u2009kg/m2). Furthermore, the study outcome was all‐cause mortality in 2007 to 2009 as provided to SIDIAPQ by the National Office of Statistics. Time to death after fracture was modeled using Cox regression. Multivariate models were adjusted for age, gender, smoking, alcohol intake, oral glucocorticoid use, and Charlson comorbidity index. Within the study period, 6988 and 29,372 subjects with a hip or nonhip clinical fracture were identified and followed for a median (interquartile range) of 1.17 (0.53–2.02) and 1.36 (0.65–2.15) years, respectively. Compared to subjects of normal weight, adjusted hazard ratios (HRs) for mortality in overweight and obese subjects were 0.74 (95% CI, 0.62–0.88; pu2009=u20090.001) and 0.74 (95% CI, 0.60–0.91; pu2009=u20090.004) after hip and 0.50 (95% CI, 0.32–0.77; pu2009=u20090.002), 0.56 (95% CI, 0.36–0.87; pu2009=u20090.010) after nonhip fracture. In conclusion, the highest mortality was observed in individuals with low BMI, but compared to subjects of normal weight, obese and overweight individuals survived longer following fracture. The latter observation is consistent with data reported in other chronic conditions, but the reasons for reduced mortality in obese and overweight subjects when compared to those of normal weight require further research.

Vitamin D threshold to prevent aromatase inhibitor-related bone loss: the B-ABLE prospective cohort study

Aromatase inhibitor (AI)-related bone loss is associated with increased fracture rates. Vitamin D might play a role in minimising this effect. We hypothesised that 25-hydroxy-vitamin D concentrations [25(OH)D] after 3xa0months supplementation might relate to bone loss after 1xa0year on AI therapy. We conducted a prospective cohort study from January 2006 to December 2011 of a consecutive sample of women initiating AI for early breast cancer who were ineligible for bisphosphonate therapy and stayed on treatment for 1xa0year (Nxa0=xa0232). Serum 25(OH)D was measured at baseline and 3xa0months, and lumbar spine (LS) bone mineral density at baseline and 1xa0year. Subjects were supplemented with daily calcium (1xa0g) and vitamin D3 (800xa0IU) and additional oral 16,000xa0IU every 2xa0weeks if baseline 25(OH)D was <30xa0ng/ml. Linear regression models were fitted to adjust for potential confounders. After 1xa0year on AI therapy, 232 participants experienced a significant 1.68xa0% [95xa0% CI 1.15–2.20xa0%] bone loss at LS (0.017xa0g/cm2 [0.012–0.024], Pxa0<xa00.0001). Higher 25(OH)D at 3xa0months protected against LS bone loss (−0.5xa0% per 10xa0ng/ml [95xa0% CI −0.7 to −0.3xa0%], adjusted Pxa0=xa00.0001), and those who reached levels ≥40xa0ng/ml had reduced bone loss by 1.70xa0% [95xa0% CI 0.4–3.0xa0%; adjusted Pxa0=xa00.005] compared to those with low 25(OH)D levels (<30xa0ng/ml). We conclude that improved vitamin D status using supplementation is associated with attenuation of AI-associated bone loss. For this population, the current Institute of Medicine target recommendation of 20xa0ng/ml might be too low to ensure good bone health.