Search

Importance: The benefit of thyroid hormone therapy for subclinical hypothyroidism is uncertain. New evidence from recent large randomized clinical trials warrants an update of previous meta-analyses.Objective: To conduct a meta-analysis of the association of thyroid hormone therapy with quality of life and thyroid-related symptoms in adults with subclinical hypothyroidism.Data Sources: PubMed, EMBASE, ClinicalTrials.gov, Web of Science, Cochrane Library, CENTRAL, Emcare, and Academic Search Premier from inception until July 4, 2018.Study Selection: Randomized clinical trials that compared thyroid hormone therapy with placebo or no therapy in nonpregnant adults with subclinical hypothyroidism were eligible. Two reviewers independently evaluated eligibility based on titles and abstracts of all retrieved studies. Studies not excluded in this first step were independently assessed for inclusion after full-text evaluation by 2 reviewers.Data Extraction and Synthesis: Two independent reviewers extracted data, assessed risk of bias (Cochrane risk-of-bias tool), and evaluated the quality of evidence (GRADE tool). For synthesis, differences in clinical scores were transformed (eg, quality of life) into standardized mean differences (SMDs; positive values indicate benefit of thyroid hormone therapy; 0.2, 0.5, and 0.8 correspond to small, moderate, and large effects, respectively). Random-effects models for meta-analyses were applied.Main Outcomes and Measures: General quality of life and thyroid-related symptoms after a minimum follow-up of 3 months.Results: Overall, 21 of 3088 initially identified publications met the inclusion criteria, with 2192 adults randomized. After treatment (range, 3-18 months), thyroid hormone therapy was associated with lowering the mean thyrotropin value into the normal reference range compared with placebo (range, 0.5-3.7 mIU/L vs 4.6 to 14.7 mIU/L) but was not associated with benefit regarding general quality of life (n = 796; SMD, -0.11; 95% CI, -0.25 to 0.03; I2=66.7%) or thyroid-related symptoms (n = 858; SMD, 0.01; 95% CI, -0.12 to 0.14; I2=0.0%). Overall, risk of bias was low and the quality of evidence assessed with the GRADE tool was judged moderate to high.Conclusions and Relevance: Among nonpregnant adults with subclinical hypothyroidism, the use of thyroid hormone therapy was not associated with improvements in general quality of life or thyroid-related symptoms. These findings do not support the routine use of thyroid hormone therapy in adults with subclinical hypothyroidism. [ABSTRACT FROM AUTHOR]

importance Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. objective To assess the association of subclinical thyroid dysfunction with hip. nonspine. spine, or any fractures. DATA sources and STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26.2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. data extraction Individual participant data were obtained from 13 prospective cohorts in the United States. Europe. Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mlU/L). subclinical hyperthyroidism (TSH <0.45 mlU/L). and subclinical hypothyroidism (TSH ≥4.50-19.99 mlU/L) with normal thyroxine concentrations. main OUTCOME AND MEASURES The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS Among 70 298 participants. 4092 (5.8%) had subdinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762 401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%: 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%: 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% Cl. 1.13-1.64; 146 events in 2082 participants vs 2534 in 56 471); for any fracture. HR was 1.28 (95% Cl. 1.06-1.53; 121 events in 888 participants vs 2203 in 25 901); for nonspine fracture. HR was 1.16 (95% Cl. 0.95-1.41; 107 events in 946 participants vs 1745 in 21722); and for spine fracture. HR was 1.51 (95% Cl. 0.93-2.45; 17 events in 732 participants vs 255 in 20 328). Lower TSH was associated with higher fracture rates; for TSH of less than 0.10 mlU/L. HR was 1.61 for hip fracture (95% Cl, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% Cl. 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% Cl. 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% Cl. 1.88-6.78,8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% Cl, 1.19-1.93) for hip fracture. 1.42 (95% Cl. 1.16-1.74) for any fracture, and 1.74 (95% Cl. 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. conclusions and relevance Subdinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mlU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures. [ABSTRACT FROM AUTHOR]

The article provides information on a study which determined whether baseline electrocardiographic (ECG) abnormalities or development of new and persistent ECG abnormalities are associated with increased coronary heart disease (CHD) events. The population-based study enrolled 2,192 white and African American older adults aged 70 to 79 years from health, Aging and Body Composition Study without known cardiovascular disease (CVD). The study then assessed incident CHD events among participants without preexisting CVD at baseline.

The article discusses a study of the association of the bone mineral density (BMD) and Fracture Risk Algorithm (FRAX) score with hip and non-spine fracture risk in older adults with type-2 diabetes mellitus (DM) in the U.S. The researchers used data from the observational studies namely, Study of Osteoporotic Fractures, the Osteoporotic Fractures in Men Study, and the Health, Aging, and Body Composition study, which have adjudicated fracture outcomes. They found that both femoral neck BMD score and FRAX score are both associated with hip and nonspine fracture in older women and men with DM.

The article focuses on a study which examined the risks of coronary heart disease (CHD) and total mortality among adults with subclinical hypothyroidism. The study included 55,287 adults in the U.S., Europe, Australia, Brazil and Japan, who were followed up from 1972 to 2007. Of the total study participants, 3,450 developed subclinical hypothyroidism, while 51,837 had euthyroidism. Study authors found that increased thyroid-stimulating hormone (TSH) concentration increased the risk of CHD and CHD-related mortality. They concluded that patients with subclinical hypothyroidism have higher risk of CHD.

This article reports on a study that examines the relationship between bone density and high-trauma fracture and between high-trauma fracture and subsequent fracture in older people. By and large the medical community believes that fractures caused by high-trauma are not osteoporotic. Fractures caused by low-trauma such as short falls are considered osteoporotic because they are related to low bone mineral density (BMD). The authors say these beliefs have consequences related to medical care and medical screening. The study found that high-trauma injuries were in fact associated to low BMD and subsequent fracture in older adults and as such they should be included as outcomes in osteoporosis trials and studies.

This article presents the results of a study to evaluate the cost-effectiveness of bone densitometry followed by 5 years of oral bisphosphonate therapy in older men to prevent fractures for those found to have osteoporosis compared with no intervention. The study used a Markov cost-utility model using Data Pro Healthcare software. Background mortality was estimated from 2003 U.S. vital statistics. The probabilities of each type of fracture were established as functions of age, presence of osteoporosis and other factors from data gathered by the Rochester Epidemiology Project. The study found lifetime costs gained for the densitometry and follow up treatment were less than $50,000 for men aged 65 and older with a prior fracture. The study concludes that the densitometry and bisphosphonate therapy may be cost-effective for men as young as 70.

Context: The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain. Objective: To compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years. Design and Setting: Randomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT). Participants: One thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment. Intervention: Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n=333), or placebo (n = 437) for 5 years (1998-2003). Main Outcome Measures: The primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence. Results: Compared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (-2. 4%; 95% confidence interval [Cl],-2. 9% to- 1. 8%; P<. 001) and spine (-3. 7%; 95% Cl,-4. 5% to -3. 0%; P<. 001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55. 6% (P<. 001)forC-telopeptideof type 1 collagen, 59. 5% (P <. 001) for serum N = propeptide of type 1 collagen, and 28. 1 % (P<. 001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1. 00; 95% Cl, 0. 76-1. 32) was not significantly different between those continuing (19%) and discontinuing (18. 9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5. 3% for placebo and 2. 4% for alendronate; RR, 0. 45; 95% Cl, 0. 24-0. 85) but no significant reduction in morphometric vertebral fractures (11. 3% for placebo and 9. 8% for alendronate; RR, 0. 86; 95% Cl, 0. 60-1. 22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens. Conclusions: Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years. [ABSTRACT FROM AUTHOR]

The article reports on a study which examined whether expending energy throughout the day affected mortality rates among older adults. Research findings indicated that energy expenditure was associated with lower risk of mortality in healthy older adults and that expending energy may influence survival.

Context: Physical activity has been related to reduced mortality, but it is not clear whether changes in physical activity affect mortality among older women. Objective: To examine the relationship of changes in physical activity and mortality among older women. Design, Setting, and Participants: Prospective cohort study conducted at 4 US research centers (Baltimore, Md; Portland, Ore; Minneapolis, Minn; and Monongahela Valley, Pa) among 9518 community-dwelling white women aged 65 years or older who were assessed at baseline (1986-1988), 7553 of whom were reassessed at a follow-up visit (1992-1994; median, 5.7 years later). Main Outcome Measures: Walking and other physical activities at baseline and follow-up; vital status, with cause of death confirmed by death certificates/discharge summaries, tracked for up to 12.5 years after baseline (up to 6.7 years after the follow-up visit). Results: Compared with continually sedentary women, those who increased physical activity levels between baseline and follow-up had lower mortality from all causes (hazard rate ratio [HRR], 0.52; 95% confidence interval [CI], 0.40-0.69), cardiovascular disease (HRR, 0.64; 95% CI, 0.42-0.97), and cancer (HRR, 0.49; 95% CI, 0.29-0.84), independent of age, smoking, body mass index, comorbid conditions, and baseline physical activity level. Associations between changes in physical activity and reduced mortality were similar in women with and without chronic diseases but tended to be weaker among women aged at least 75 years and among those with poor health status. Women who were physically active at both visits also had lower all-cause mortality (HRR, 0.68; 95% CI, 0.56-0.82) and cardiovascular mortality (HRR, 0.62; 95% CI, 0.44-0.88) than sedentary women. Conclusion: Increasing and maintaining physical activity levels could lengthen life for older women but appears to provide less benefit for women aged at least 75 years and those with poor health status. [ABSTRACT FROM AUTHOR]

This JAMA Insights Clinical Update reviews bone turnover markers measurable in blood and urine and summarizes evidence supporting their use to predict osteoporosis and osteoporotic fractures, assess treatment adherence and efficacy, and monitor bone loss after drug discontinuation. [ABSTRACT FROM AUTHOR]

Editorial. Comments on the observations that statin may prevent cardiovascular disease and fractures, and emphasizes that this has not been proven as fact. Background on the studies of statin; Details on the effects of bisphosphonates on bones; Comments on information not included in the studies; Cautions against prescriptions of statins to prevent fractures.

The author offers a response to a commentary on his study which summarized evidence supporting the use of bone turnover markers (BTMs), identify knowledge gaps, and describe how those gaps affect clinical use.

A letter to the editor is presented in response to the article "Subclinical hypothyroidism and the risk of coronary heart disease and mortality," by N. Rodondi and colleagues, along with the response of the authors.

A reply is presented by Drs. John T. Schousboe, Brent C. Taylor, Douglas C. Bauer and colleagues to a letter to the editor about their article "Cost-effectiveness of bone densitometry followed by treatment of osteoporosis in older men."