Mark L. Fuerst

Besides bone mineral density (BMD), other bone characteristics can be used to determine fracture risk, according to a 

.
	
	The results show low BMD is not the only cause of bone fragility, and the majority of older adults who sustain a fragility fracture do not meet the diagnostic criteria for osteoporosis.
	
	“Older women are at particularly high risk of fracture. In fact, the number of women who will experience a fragility fracture in any given year exceeds the number who will experience a first-time stroke, breast cancer, or myocardial infarction combined,” said co-lead author Mary L. Bouxsein, PhD, Director of the Center for Advanced Orthopedic Studies at Beth Israel Deaconess Medical Center, Boston, Massachusetts. “Improved methods to identify those in whom fractures are common but whom standard clinical testing does not identify as high risk would allow us to target treatment to this important group and ultimately reduce fracture burden.”

BMD assessed by dual-energy x-ray absorptiometry is the clinical standard for determining fracture risk. The majority of older adults who sustain a fracture, however, have T scores greater than −2.5. Therefore, they do not meet the clinical criteria for osteoporosis, the researchers noted. Importantly, bone fragility is due to low BMD and deterioration in bone structure.
	
	Bouxsein and colleagues assessed whether indices of high-resolution peripheral quantitative computed tomography (CT) were associated with fracture risk independently of femoral neck BMD and the Fracture Risk Assessment Tool (FRAX) score. They assessed 7254 participants, mean baseline age 69 years, in 8 cohorts from the US, France, Switzerland, Canada, and Sweden.
	
	Over a mean follow-up of 4.63 years, 8% of participants met the diagnostic criteria for osteoporosis, yet 11% of participants had incident fractures. Some 633 (86%) participants had femoral neck T scores greater than −2.5.

Those who experienced fracture were more likely to be older, female, have a lower BMI, use osteoporosis medications, and have a previous fracture. Participants who sustained fractures had worse bone measurements for nearly all parameters vs those who did not fracture.
	
	Several measures of bone density and structure at different sites on the bone, including the density of the compact bone tissue and the thickness of the spongy bone tissue at the wrist, were predictive of fracture. Other fractures risks included an increase in tibia cortical porosity and decrease in radius trabecular volumetric bone density. Failure load was the bone characteristic most strongly associated with risk of fracture.

The researchers concluded that high-resolution CT results and failure load improved prediction of fracture beyond femoral neck BMD or FRAX scores alone. “Results from this large international cohort of women and men suggest deficits in density and structure throughout the bone contribute to fracture risk independently of BMD and current risk assessment tools,” said lead author Lisa Samelson, PhD, an epidemiologist at Harvard Medical School, Boston, Massachusetts. “Further, assessment of these bone characteristics may be useful in those who would not otherwise be identified as being at high risk for fracture.”

Samelson EJ, Broe KE, Xu H, et al. Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study. Lancet Diabetes Endocrinol. 2019;7:34-43. 

Articles

Which additional bone traits, besides bone mineral density, can be used to determine fracture risk? Authors of a new study sought to find out.

Additional Bone Traits Beyond BMD Help Assess Fracture Risk

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Diabetes News Roundup: December 2018

Overtreating patients for hypothyroidism could raise their risk of atrial fibrillation (AF), and by association, their risk of stroke, according to a new study.

The results show elevated levels of the thyroid hormone free thyroxine even within the upper levels of normal reference ranges were associated with an increased risk of AF, which suggests the possible need to redefine the safest reference ranges in hypothyroidism treatment.

“We know patients with hypothyroidism have a higher risk of atrial fibrillation, but we didn’t consider increased risk within what’s considered the normal range of thyroid hormones. These findings show we might want to re-consider what we call normal,” said lead author Jeffrey L. Anderson, MD, Distinguished Clinical and Research Physician at the Intermountain Medical Center Heart Institute.
	Anderson presented the data at the American Heart Association Scientific Session conference in Chicago.

The researchers surveyed the electronic medical records of 174 914 patients, mean age 63.8 years, treated at Intermountain Healthcare facilities whose free thyroxine levels were recorded and who were not on thyroid replacement medication. They took what is considered a normal range of free thyroxine levels, divided it into four quartiles, and looked at those patients’ records for a current or future diagnosis of AF.

After a mean follow-up of 6.3 years, they found 7.4% of the patients had free thyroxine levels below the normal reference range, 88.4% had levels in the normal range, and 4.2% had levels above the normal range. After adjustment, the relative risk of prevalent AF was 40% higher for patients in the highest quartile of free thyroxine levels vs patients in the lowest quartile, which translated into a 16% increase in newly developing AF during follow up.

After adjustment, the relative risk of prevalent AF was 40% higher for patients in the highest quartile of free thyroxine levels vs patients in the lowest quartile, which translated into a 16% increase in newly developing AF during follow up.

This suggests, said Anderson, that the optimal healthy range of free thyroxine should be reconsidered and redefined. “Thyroid hormones are associated with losing weight and having more energy, which may lead to people being treated at the high end of the normal range,” he said. “Are we harming people by putting them at a higher risk of atrial fibrillation, and therefore stroke?”

The study also found that free thyroxine should be measured, along with thyroid-stimulating hormone, which is more commonly tested for in patients with irregular thyroid hormone levels, but was not helpful within the normal range in refining risk.

The link between free thyroxine levels and AF was recently recognized in the 

, a population-based cohort study first started in 1990. The new study replicates the results in a much larger population and establishes the link between free thyroxine levels and AF among patients treated in the United States.

“The next step for researchers is to conduct a randomized trial to see if targeting a lower versus a higher upper range of free thyroxine in patients receiving thyroid hormone replacement therapy leads to a lower risk of atrial fibrillation and stroke along with other possible heart-related issues, like atherosclerosis,” said Anderson.

: Anderson JL, et al. Poster Sa1208. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.

A new study found that elevated free thyroxine within the upper range of normal may increase risk of AF; is may be time to redefine what is "safe" when treating hypothyroidism.

Overtreating Hypothyroid Could Raises Risk of Atrial Fibrillation  

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The prevalence of coeliac disease in osteoporosis patients is similar to that of the general population, according to a 

This finding argues against routinely screening osteoporosis patients for coeliac disease, contrary with current guideline recommendations.

Guidelines published by the British National Institute for Health and Care Excellence in 2015 on the management of coeliac disease recommend assessment of bone mineral density (BMD) at the time of annual physical examination, using the World Health Organization fracture risk assessment tool before considering the need for a dual-energy X-ray absorptiometry (DXA) scan. There is controversy around the validity of fracture risk assessment tools vs DXA in this specific population.

A recent meta-analysis reported that coeliac disease patients are at a 30% increased risk of any fracture and at a 69% increased risk of hip fracture. Another recent meta-analysis found that coeliac disease patients had an increased risk of osteoporosis, and so did a large screening study.

“These studies did not, however, examine the risk of coeliac disease in patients first diagnosed with osteoporosis. Such information is crucial for clinicians as this will guide whether they should screen individuals with osteoporosis for coeliac disease,” stated researchers led by Monika Laszkowska, MD, of the Columbia University College of Physicians and Surgeons in New York, New York. They note that the reported prevalence of coeliac disease in those with osteoporosis has varied between 0% and 33%.

Laszkowska and colleagues conducted a systematic review of articles published in PubMed, Medline, or EMBASE through May 2017 to identify studies looking at prevalence of coeliac disease in patients with osteoporosis. They identified 8 relevant studies, comprising data from 3188 individuals with osteoporosis. Of these, 59 individuals (1.9%) had coeliac disease.

A weighted pooled analysis demonstrated biopsy-confirmed coeliac disease in 1.6% of those with osteoporosis. The heterogeneity was moderate and influenced by the underlying coeliac disease prevalence in the general population. After adding 4 studies, including 814 patients with coeliac disease defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%).

“Importantly, the prevalence of coeliac disease did not change when we included studies based on positive coeliac disease serology – the absolute proportion went from 1.9% to 2.6% but the pooled weighted prevalence remained at 1.6%,” wrote the researchers.

Various studies have shown that treatment with a gluten-free diet improved BMD in patients with coeliac disease. “Such studies suggest that treatment of coeliac disease is likely to decrease the excess fracture risk, and therefore a diagnosis of coeliac disease is probably beneficial to individuals with a history of fractures,” wrote the researchers.

The mechanism for osteoporosis in coeliac disease patients likely is multifactorial. “Individuals with coeliac disease often have a low bone density at diagnosis, even in the absence of other symptoms or manifestations of coeliac disease,” they wrote. The researchers suggest this may be due to malabsorption of vitamin D and calcium resulting in secondary hyperparathyroidism, as well as other factors, including chronic inflammation with increased cytokine levels that interfere with bone growth and autoimmune factors.

Contrary to current guideline recommendations, a new review argues against routine coeliac disease screening for osteoporosis patients. 

No Need to Routinely Screen Osteoporosis Patients for Celiac Disease

Thyroid hormone therapy for subclinical hypothyroidism is not associated with improved quality of life (QOL) or of thyroid-related symptoms, according to 

Journal of the American Medical Association.

Subclinical hypothyroidism is a common condition, affecting an estimated 13 million people in the US, and is more prevalent among women and older persons. It is often treated with thyroid hormones, especially when it occurs with symptoms typically attributed to hypothyroidism, such as tiredness, constipation, and unexplained weight gain. The benefits of treatment have remained uncertain.

“Relatively limited evidence exists from randomized clinical trials to guide therapy of subclinical hypothyroidism. Systematic reviews have been inconclusive and clinical practice guidelines have varied regarding recommendations for managing subclinical hypothyroidism,” stated the researchers, led by Martin Feller, MD, of the Bern University Hospital in Sweden.

The researchers conducted a meta-analysis of 21 randomized clinical trials including 2192 participants with subclinical hypothyroidism to investigate the association of thyroid hormone therapy with QOL and thyroid-related symptoms. Randomized clinical trials that compared thyroid hormone therapy with placebo or no therapy in non-pregnant adults with subclinical hypothyroidism were included in the analysis.

Study sizes ranged from 20 to 737 participants and the length of treatment ranged from 3 to 18 months. The mean ages of participants ranged from 32 to 74 years. The baseline mean thyrotropin values ranged from 4.4 to 12.8 mIU/L.

Overall, 21 of 3088 initially identified publications met the inclusion criteria. After treatment, thyroid hormone therapy was associated with lowering the mean thyrotropin value into the normal reference range compared with placebo, but was not associated with benefit regarding general QOL or thyroid-related symptoms.

"...[treatment] was associated with lowering the mean thyrotropin value into the normal reference range compared with placebo, but was not associated with benefit regarding general QOL or thyroid-related symptoms."



“Results of this review consistently demonstrated no association of thyroid replacement therapy with improved outcomes, including a relatively large number of diverse outcomes. Most outcomes, except cardiovascular events and mortality, had narrow confidence intervals. In addition, this meta-analysis focused on patient-centered outcomes such as QOL and fatigue, which are the most common symptoms that prompt therapy in general practice,” the researchers wrote.

Current guidelines are cautious with treatment recommendations but, “more than 90% of persons with subclinical hypothyroidism and a thyrotropin level of less than 10 mIU/L would actually qualify for treatment,” the researchers wrote. “However, results of this meta-analysis are not consistent with these guideline recommendations. In addition to absence of an association of thyroid hormone therapy with improved outcomes, thyroid hormone therapy is associated with adverse effects when overtreatment occurs.”

Mean thyrotropin values at baseline were <7.0 mIU/L in 11 of 21 included trials, and only 2 trials examined participants with a mean baseline thyrotropin level >10 mIU/L. “Therefore, the current findings may not be generalizable to people with subclinical hypothyroidism and a thyrotropin level higher than 10 mIU/L,” the researchers noted.

A new meta-analysis found no improvement in symptoms or in quality of life among more than 2000 participants treated for subclinical disease.