Levothyroxine dose and risk of fractures in older adults: nested case-control study.
Ontology highlight
ABSTRACT: Objective
To quantify the effect of levothyroxine dose on risk of fractures in older adults.Design
Nested case-control study.Setting
Population based health databases, Ontario, Canada.Participants
Adults aged 70 or more prescribed levothyroxine between 1 April 2002 and 31 March 2007 and followed for fractures until 31 March 2008. Cases were cohort members admitted to hospital for any fracture, matched with up to five controls from within the cohort who had not yet had a fracture.Main outcome measure
Primary outcome was fracture (wrist or forearm, shoulder or upper arm, thoracic spine, lumbar spine and pelvis, hip or femur, or lower leg or ankle) in relation to levothyroxine use (current, recent past, remote). Risk among current users was compared between those prescribed high, medium, and low cumulative levothyroxine doses in the year before fracture.Results
Of 213,511 prevalent levothyroxine users identified, 22,236 (10.4%) experienced a fracture over a mean 3.8 years of follow-up, 18,108 (88%) of whom were women. Compared with remote levothyroxine use, current use was associated with a significantly higher risk of fracture (adjusted odds ratio 1.88, 95% confidence interval 1.71 to 2.05), despite adjustment for numerous risk factors. Among current users, high and medium cumulative doses (>0.093 mg/day and 0.044-0.093 mg/day) were associated with a significantly increased risk of fracture compared with low cumulative doses (<0.044 mg/day): 3.45 (3.27 to 3.65) and 2.62 (2.50 to 2.76), respectively.Conclusion
Among adults aged 70 or more, current levothyroxine treatment was associated with a significantly increased risk of fracture, with a strong dose-response relation. Ongoing monitoring of levothyroxine dose is important to avoid overtreatment in this population.
SUBMITTER: Turner MR
PROVIDER: S-EPMC3084377 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundHigher levels of ceramides have been linked to several chronic diseases; also there is emerging cross-sectional evidence that ceramides are associated with lower physical functioning. This research assessed for the first time the prospective relationship between ceramide species and impaired lower-extremity function (ILEF) in older adults.MethodsCase-control study with 43 cases of ILEF and 86 age- and sex-matched controls, which was nested in the Seniors-ENRICA cohort of community-dwelling older adults. Incident ILEF from 2015 to 2017 was ascertained with the Short Physical Performance Battery. In 2015, 27 ceramide species were measured in plasma by liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were used to assess the longitudinal relationship between ceramides concentration and incidence of ILEF.ResultsAfter adjusting for education level, body mass index, alcohol and total energy intake, physical activity, and presence of chronic conditions, some ceramide species were related to 2-year incidence of ILEF. Specifically, the odds ratios of ILEF per 1-SD increase in ceramide concentration were: 1.66 [95% CI = (1.03, 2.68)] for ceramide C14:0, 1.61 (1.00, 2.59) for ceramide C16:0, and 1.64 (1.03, 2.60) for ceramide C16:1 (n-7). In the case of ceramides C16:0 and C16:1 (n-7), a stronger relationship was found in those with a higher body mass index; systolic blood pressure could also mediate the relationship between ceramide C16:1 (n-7) and ILEF (p for interaction = .03).ConclusionsHigher plasma levels of ceramides C14:0, C16:0, and C16:1 (n-7) are associated with higher risk of ILEF, and might serve as risk markers for functional decline in older adults.
| S-EPMC8489419 | biostudies-literature
Project description:This study examined the associations between the occurrence of osteoporotic fractures in detailed sites and combined physical activity (PA) and sunshine duration (SD). Data from the Korean National Health Insurance Service-National Health Screening Cohort for 7-year periods and from the Korea Meteorological Administration were used. Osteoporotic fractures (n = 12,103), including vertebral fractures, hip fractures, and distal radius fractures, and matched controls (n = 24,206) were selected in 1:2 ratios by age, sex, income, and region of residence. PA was classified as moderate- to high-intensity PA (High PA) and low-intensity PA (Low PA). SD was classified as Short SD (<6.1 h) and Long SD (≥6.1 h). Conditional logistic regression was used to calculate the odds ratios (ORs) with 95%-confidence intervals (CIs) of the combined PA and SD groups for the occurrence of each osteoporotic fracture. Compared to 'Low PA + Short SD', the adjusted ORs (95% CIs) for vertebral fracture in 'High PA + Short SD' and 'High PA + Long SD' were 0.83 (0.76-0.91) and 0.84 (0.77-0.92), respectively. Hip/distal radius fractures were not associated with the combined PA and SD group. We suggest that a higher intensity of PA is inversely associated with the risk of vertebral fracture.
| S-EPMC8878966 | biostudies-literature
Project description:ObjectiveWe aimed to investigate the association between statin use and the risk of major osteoporotic fractures in patients with metabolic syndrome (MetS).MethodsA nested case-control study was performed in patients with MetS (≥50 years) who had no history of osteoporotic fracture using the Korean National Health Insurance Service-Health Screening Cohort. This study included 17,041 patients diagnosed with new-onset osteoporotic fractures and controls matched in a 1:1 ratio by age, sex, body mass index, cohort entry date, and follow-up duration. Conditional logistic regression analysis was used to evaluate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsDuring a 4-year follow-up period, the risk of major osteoporotic fractures was significantly reduced by 9% (OR, 0.91; 95% CI, 0.85-0.97) in statin users compared with that in non-users. Among subtypes of major osteoporotic fracture, a risk reduction with statin therapy was significant for vertebral fracture (OR, 0.86; 95% CI, 0.79-0.94) but not for non-vertebral fracture (OR, 0.97; 95% CI, 0.88-1.06). Longer duration (OR, 0.97; 95% CI, 0.96-0.99, per 1-year increase) and higher cumulative dose (OR, 0.97; 95% CI, 0.95-0.99, per 365 defined daily doses) of statins were negatively associated with the risk of major osteoporotic fracture.ConclusionThis study supports the hypothesis that statin therapy has a beneficial effect on major osteoporotic fractures, especially vertebral fractures, in patients with MetS.
| S-EPMC8473960 | biostudies-literature
Project description:Levothyroxine is a synthetic T(4) hormone commonly used to treat thyroid disease. Increased incidence of mostly autoimmune thyroid disease has been associated with breast and other malignancies, and thyroid hormone levels might also be associated with risk of colorectal cancer (CRC). In this population-based matched case-control study (2566 pairs) of CRC in northern Israel, use of levothyroxine for at least 5 years was assessed using structured interviews and validated by prescription records. The analysis included use of statins, aspirin, and hormone replacement therapy; CRC family history; physical activity; vegetable consumption; ethnicity; age; and sex. All statistical tests were two-sided. The use of levothyroxine was associated with a statistically significantly reduced relative risk of CRC (odds ratio = 0.59, 95% confidence interval = 0.43 to 0.82, P = .001). This association remained statistically significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of CRC, ethnic group, and level of vegetable consumption (odds ratio = 0.60, 95% confidence interval = 0.44 to 0.81, P = .001). No statistically significant interactions were seen between use of levothyroxine and aspirin, statins, or hormone replacement therapy.
| S-EPMC2857798 | biostudies-literature
Project description:PurposeUnderstanding how the convergence between chronic and complex diseases-such as cancer-and emerging conditions of older adults-such as frailty-takes place would help in halting the path that leads to disability in this age group. The objective of this manuscript is to describe the association between a past medical history of cancer and frailty in Mexican older adults.MethodsThis is a nested in cohort case-control study of the Mexican Health and Aging Study. Frailty was categorized by developing a 55-item frailty index that was also used to define cases in two ways: incident frailty (incident >0.25 frailty index score) and worsening frailty (negative residuals from a regression between 2001 and 2012 frailty index scores). Exposition was defined as self-report of cancer between 2001 and 2012. Older adults with a cancer history were further divided into recently diagnosed (<10 years) and remotely diagnosed (>10 years from the initial diagnosis). Odds ratios were estimated by fitting a logistic regression adjusted for confounding variables.ResultsOut of a total of 8022 older adults with a mean age of 70.6 years, the prevalence of a past medical history of cancer was 3.6 % (n = 288). Among these participants, 45.1 % had been diagnosed with cancer more than 10 years previously. A higher risk of incident frailty compared to controls [odds ratio (OR) 1.53 (95 % confidence interval (CI) 1.04-2.26, p = 0.03); adjusted model OR 1.74 (95 % CI 1.15-2.61, p = 0.008)] was found in the group with a recent cancer diagnosis. Also, an inverse association between a remote cancer diagnosis and worsening frailty was found [OR = 0.56 (95 % CI 0.39-0.8), p = 0.002; adjusted model OR 0.61 (95 % CI 0.38-0.99, p = 0.046)].ConclusionsCancer is associated with a higher frailty index, with a potential relevant role of the time that has elapsed since the cancer diagnosis.Implications for cancer survivorsCancer survivors may be more likely to develop frailty or worsening of the health status at an older age. This relationship seems especially evident among individuals with a recent oncological diagnosis. Health professionals in charge of older adult care should be aware of this association in order to improve outcomes of older adults who survived cancer.
| S-EPMC4966647 | biostudies-literature
Project description:We investigated the association between thiazide use and the risk of low-energy fractures among community dwellers with Alzheimer's disease. Longer use was associated with a decreased risk of low-energy fractures. This study extends the previous knowledge of reduced fracture risk of thiazides to persons with Alzheimer's disease.IntroductionTo investigate the association between thiazide use and the risk of low-energy fractures (LEF), and hip fracture among community dwellers with Alzheimer's disease (AD). No prior study has evaluated the effect of thiazides on LEF risk of AD patients.MethodsLEF cases were identified from the MEDALZ study, including all community-dwelling persons diagnosed with AD in Finland 2005-2011. During the follow-up from AD diagnoses until the end of 2015, cases with LEF (N = 10,416) and hip fracture (N = 5578) were identified. LEF cases were matched with up to three controls without LEF, according to time since AD diagnosis, age and gender. Thiazide use identified from the Prescription register data was modeled with PRE2DUP method. Current use was defined in 0-30 days' time window before the fracture/matching date, and duration of current use was assessed. The association between thiazide exposure and LEFs was assessed with conditional logistic regression.ResultsCurrent thiazide use was observed in 10.5% of LEF cases and 12.5% of controls. Current thiazide use was associated with a decreased risk of LEF (adjusted OR [aOR] 0.83, 95% CI 0.77-0.88). In terms of the duration of use, no association was observed with short-term use (< 1 year or 1-3 years), while longer use (> 3 years) was associated with a reduced risk of LEF (aOR 0.77, 95% CI 0.71-0.83) and hip fracture (aOR 0.68, 95% CI 0.60-0.78).ConclusionsOur study extends the previous knowledge of reduced fracture risk of thiazides to persons with AD, a population with significantly increased background risk of fractures.
| S-EPMC6614156 | biostudies-literature
Project description:To evaluate the association between bisphosphonate use and the risk of atypical femoral fractures among women aged 65 or older.Nested case-control study.General practice research database in Spain.Use of oral bisphosphonates before the occurrence of atypical fractures among cases or the corresponding index date among controls. Bisphosphonate use was categorised as ever versus never users. Ever users were divided according to the total time since first prescription.Cases were defined as women aged 65 years or older with a first diagnosis of subtrochanteric or diaphyseal fracture, recorded in the BIFAP database between 1 January 2005 and 31 December 2008, and with at least 1 year of follow-up before the index date. For each case, five age-matched and calendar-year-matched controls without a history of hip or atypical fracture were randomly selected from the database.OR of atypical femoral fracture by bisphosphonate use was determined using conditional logistic regression. Models were adjusted for comorbidities and use of other medications.The analysis included 44 cases and 220 matched controls (mean age, 82 years). Ever use of bisphosphonates was more frequent in cases than controls (29.6% vs 10.5%). In multivariate analyses, OR (95% CI) of atypical femoral fracture was 4.30 (1.55 to 11.9) in ever versus never users of bisphosphonates. The risk increased with long-term use, with an OR of 9.46 (2.17 to 41.3) comparing those using bisphosphonates over 3 years versus no users (p for trend=0.01).Bisphosphonate use was associated with an increased risk of subtrochanteric or diaphyseal fractures in elderly women in a low fracture risk population, with a higher risk among long-term bisphosphonate users.
| S-EPMC3563115 | biostudies-literature
Project description:BackgroundDespite the rising number of older adults with medical encounters for opioid misuse, dependence, and poisoning, little is known about patterns of prescription opioid dose and their association with risk for opioid-related adverse events (ORAEs) in older patients. The study aims to compare trajectories of prescribed opioid doses in 6 months preceding an incident ORAE for cases and a matched control group of older patients with chronic noncancer pain (CNCP).Methods and findingsWe conducted a nested case-control study within a cohort of older (≥65 years) patients diagnosed with CNCP who were new users of prescription opioids, assembled using a 5% national random sample of Medicare beneficiaries from 2011 to 2018. From the cohort with a mean follow-up of 2.3 years, we identified 3,103 incident ORAE cases with ≥1 opioid prescription in 6 months preceding the event, and 3,103 controls matched on sex, age, and time since opioid initiation. Key exposure was trajectories of prescribed opioid morphine milligram equivalent (MME) daily dosage over 6 months before the incident ORAE or matched controls. Among the cases and controls, 2,192 (70.6%) were women, and the mean (SD) age was 77.1 (7.1) years. Four prescribed opioid trajectories before the incident ORAE diagnosis or matched date emerged: gradual dose discontinuation (from ≤3 to 0 daily MME, 1,456 [23.5%]), gradual dose increase (from 0 to >3 daily MME, 1,878 [30.3%]), consistent low dose (between 3 and 5 daily MME, 1,510 [24.3%]), and consistent moderate dose (>20 daily MME, 1,362 [22.0%]). Few older patients (<5%) were prescribed a mean daily dose of ≥90 daily MME during 6 months before diagnosis or matched date. Patients with gradual dose discontinuation versus those with a consistent low dose, moderate dose, and increase dose were more likely to be younger (65 to 74 years), Midwest US residents, and receiving no low-income subsidy. Compared to patients with gradual dose discontinuation, those with gradual dose increase (adjusted odds ratio [aOR] = 3.4; 95% confidence interval (CI) 2.8 to 4.0; P < 0.001), consistent low dose (aOR = 3.8; 95% CI 3.2 to 4.6; P < 0.001), and consistent moderate dose (aOR = 8.5; 95% CI 6.8 to 10.7; P < 0.001) had a higher risk of ORAE, after adjustment for covariates. Our main findings remained robust in the sensitivity analysis using a cohort study with inverse probability of treatment weighting analyses. Major limitations include the limited generalizability of the study findings and lack of information on illicit opioid use, which prevents understanding the clinical dose threshold level that increases the risk of ORAE in older adults.ConclusionsIn this sample of older patients who are Medicare beneficiaries, 4 prescription opioid dose trajectories were identified, with most prescribed doses below 90 daily MME within 6 months before ORAE or matched date. An increased risk for ORAE was observed among older patients with a gradual increase in dose or among those with a consistent low-to-moderate dose of prescribed opioids when compared to patients with opioid dose discontinuation. Whether older patients are susceptible to low opioid doses warrants further investigations.
| S-EPMC8923459 | biostudies-literature
Project description:Corticosteroid (CS)-related infection risk in immune thrombocytopenia (ITP) is unknown. The aim of this study was to assess the adjusted CS risk function of severe infection in persistent or chronic primary ITP adults. We designed a nested case-control study in the FAITH cohort. This cohort is built through the French national health insurance database named SNIIRAM and includes all treated incident persistent or chronic primary ITP adults in France (ENCePP n°4574). Patients who entered the FAITH cohort between 2009 and 2012 were eligible (n = 1805). Cases were patients with infection as primary diagnosis code during hospitalization. Index date was the date of first hospitalization for infection. A 2:1 matching was performed on age and entry date in the cohort. Various CS exposure time-windows were defined: current user, exposure during the 1/3/6 months preceding index date and from the entry date. CS doses were converted in prednisone equivalent (PEQ). The cumulative CS doses were averaged in each time-window to obtain daily PEQ dosages. Each CS exposure definition was assessed using multivariate conditional regression models. During the study period, 161 cases (9 opportunistic) occurred. The model with the best goodness of fit was CS exposure during the month before the index date (OR: 2.48, 95% CI: 1.61-3.83). The dose-effect relation showed that the risk existed from averaged daily doses ≥5 mg PEQ (vs. <5 mg: 2.09, 95% CI: 1.17-3.71). The risk of infection was mainly supported by current or recent exposure to CS, even with low doses.
| S-EPMC4641733 | biostudies-literature
Project description:BackgroundIn general, hypothyroidism can be adequately treated with a consistent daily dose of levothyroxine. However, the need for levothyroxine dose adjustments is frequent in clinical practice. The extent to which levothyroxine dose adjustments increase the utilization of healthcare resources has not previously been described in the clinical literature.ObjectiveThe primary objective of our study was to measure the effect of levothyroxine dose adjustments in terms of their utilization of healthcare resources including direct and indirect costs. A secondary goal was to identify any differences in patient characteristics that may be responsible for levothyroxine dose adjustments.MethodsA retrospective medical chart review was conducted among patients of selected healthcare providers in the USA. Patients who were recently started on levothyroxine therapy (<6 months) were excluded to avoid situations that were more likely attributable to treatment initiation than inadequate therapeutic effect. Trained nurses extracted data from patient charts and electronic medical record systems for review. We analyzed the cost of resources consumed by the frequency of levothyroxine dose changes over 24 months: 0 dose changes (no dose adjustment group); one dose change, two dose changes, three or more dose changes (≥1 dose adjustment group).ResultsThe study included 454 patients. Overall estimated resource utilization was higher per patient in the ≥1 dose adjustment group (US$5824) vs. the no dose adjustment group (US$3166) during the 24-month study period. When direct and indirect costs were combined, overall costs of care were greatest in patients requiring three or more dose adjustments (US$8220/patient). Patients in this cohort incurred 2.5-fold greater total costs compared with patients requiring no dose adjustments (US$8220 vs. US$3166). Among the 58 patients in the group requiring three or more dose adjustments, mean direct medical costs were significantly higher than in the patients requiring no dose adjustments (US$6387 vs. US$2182). Patients with at least one dose adjustment experienced a 40.3% increase in lost productivity vs. patients who had no dose adjustments (US$1381 vs. US$984). Loss of productivity was highest among patients with three or more levothyroxine dose adjustments. Among this cohort, there was an 86.4% increase in lost productivity vs. patients who had no levothyroxine dose adjustments (US$1833 vs. US$984).ConclusionsPatients experiencing multiple levothyroxine dose adjustments were shown to consume more healthcare resources, resulting in higher costs than those who required no dose adjustments. Each care episode contributed to lost time and wages with total estimated lost productivity escalating with increasing levothyroxine dose adjustments over a 24-month period.
| S-EPMC5209418 | biostudies-literature