Beyond BMD: Measures of Bone Microstructure Predict Fracture Risk

Key deficits in bone microarchitecture of trabecular and cortical bone structure, as measured by high-resolution peripheral quantitative computed tomography (CT), can predict risk of fracture in older men and women even when standard measures of bone mineral density (BMD) are in the normal range, according to new research.

Standard measures of areal BMD (aBMD) are assessed by dual-energy X-ray absorptiometry (DXA), but low BMD is not the only cause of bone fragility, and most older adults who sustain a fragility fracture do not meet the diagnostic criteria for osteoporosis, explain Elizabeth Samelson, PhD, of the Institute for Aging Research at Hebrew SeniorLife and Harvard Medical School, in Boston, Massachusetts, and colleagues, in their article published online November 28 in the Lancet Diabetes and Endocrinology.

"As most of our study participants with fractures had femoral neck aBMD T-scores in the osteopenic or normal range, our results indicate that assessment of bone microstructure might be useful in people who would not otherwise be identified as being at risk of fracture," they say.

"Therefore, while femoral neck aBMD and Fracture Risk Assessment Tool (FRAX) score remain the clinical standards for risk stratification, assessment of additional bone traits might improve prediction of fracture risk," they add.

Accurate Fracture Predictors

Annual costs associated with fragility fractures exceed US$19 billion in the United States and €36 billion in Europe, the researchers explain in their article. "Given the predicted growth in the number of older adults, the number of fractures and associated costs are projected to increase by two to four times worldwide in the next few decades," they state.

But because most older adults who suffer a fragility fracture do not meet the diagnostic criteria for osteoporosis, physicians currently lack validated means of assessing fracture risk in these patients.

Improved methods to identify people at the highest risk of fracture would allow for the treatment of patients who would probably have the greatest benefit-to-risk profiles and might ultimately reduce fracture burden.

High-resolution peripheral quantitative CT (HR-pQCT) shows cortical and trabecular bone density and microarchitecture at peripheral skeletal sites with minimum radiation exposure and can differentiate between individuals with and without a history of fracture, often independently of DXA BMD, they explain.

In the largest prospective study of its kind, Samelson and colleagues evaluated data on 7254 older adults with a mean baseline age of 69 years from the Bone Microarchitecture International Consortium, including cohorts in the United States, France, Switzerland, Canada, and Sweden.

With a mean follow-up of 4.6 years, 11% (765) of participants sustained incident fractures.

Among those with fractures, as many as 86% (633) had femoral neck T-scores greater than –2.5, and therefore did not meet the criteria of "osteoporosis."

After multivariate adjustment for factors including age, sex, cohort, height, and weight, peripheral skeleton failure load (the stress under which bone begins to fracture), assessed using HR-pQCT (XtremeCT, Scanco Medical), showed the strongest association with fracture, with a hazard ratio (HR) of 2.40 per 1 standard deviation (SD) decrease for the tibia and HR 2.13 per 1 SD decrease for the radius.

Whereas the associations between HR-pQCT measures and incident fractures were reduced after further adjustment for femoral neck aBMD or FRAX score, they remained significant for most bone parameters.

The most accurate set of fracture predictors included cortical volumetric density, trabecular number, and trabecular thickness at the radius, and those variables plus cortical area at the tibia, which is consistent with previous studies, the authors note.

No strong associations were observed between cortical porosity and incident fracture, however, which is contrary to some previous cross-sectional studies, they add.

"This discrepancy could be due to differences in fracture outcomes: previous studies used forearm or hip fracture, whereas we assessed any fracture and major osteoporotic fracture," they note.

Look Beyond BMD When Possible

Previous studies have shown similar associations with fracture; however, the research has been limited largely to case-control studies with few incident fractures and a lack of cohorts combining men and women.

These latest results support efforts to look beyond BMD in assessing fracture risk when possible, stress Samelson and colleagues.

"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", Samelson added in a press statement from her institution.

"Although HR-pQCT is not widely available, our findings suggest that expansion of the clinical use of this technique and the development of alternative technologies to assess cortical and trabecular bone structure and strength could be beneficial."

"We have provided the groundwork to develop new models for fracture prediction, thereby improving risk stratification and reducing the public health burden of osteoporosis," they conclude.

The study was supported by the National Institutes of Health.

Lancet Diabetes Endocrinol. Published online November 28, 2018. Abstract

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