Assessment of Skeletal Fragility: Beyond Areal Bone Mineral Density

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Abstract

The advent of dual-energy X-ray absorptiometry (DXA) in the late 1980s revolutionized the estimation of bone mineral density (BMD) and led to the development of clear definitions of low BMD and osteoporosis. Three decades later, a number of limitations to this technique are highlighted in clinical practice, including its lower resolution and inability to differentiate the trabecular and cortical compartments of the skeleton, which can be important in several pathologic conditions such as diabetes mellitus and hyperparathyroidism. The work herein describes two different approaches to address these limitations.

Central quantitative computed tomography (QCT) is increasingly used in clinical trials and practice to assess bone mass or strength and to evaluate longitudinal changes in response to drug treatment. Using dual-energy (DE) QCT scans allows for assessment of bone marrow fat which can confound BMD measurements. Using this technology, 197 early postmenopausal women underwent spine and hip QCT scans at baseline and 3 years. The scans were analyzed as either single-energy (SE) or DE scans. SE scanning overestimated the 3-year rate of bone loss for trabecular bone at the spine; the deviation between SE and DE became progressively greater as the rate of bone loss increased. These findings demonstrate that SE QCT scans underestimate trabecular BMD and substantially overestimate rates of age-related bone loss due to ongoing conversion of red to yellow marrow. As such, using DE scanning technology permits the evaluation of changes in trabecular BMD independent of changes in marrow fat with aging and drugs that may alter marrow fat composition.

Trabecular bone score (TBS), on the other hand, estimates trabecular bone quality using the same lumbar spine images obtained for DXA assessment. Data obtained from TBS were used in 155 patients with monoclonal gammopathy with undetermined significance (MGUS), a cohort with high risk for fragility fractures. This group was matched 1:1 to a control group for sex, age, and BMI. Patients with MGUS had a significantly lower TBS and lower lumbar spine BMD compared to controls. Unlike control subjects, patients with MGUS tend to fracture despite normal BMD and intermediate or normal TBS values, highlighting the value of using this technology in disease-specific cohorts to allow for discrimination between trabecular and cortical changes and their relation to clinically relevant outcomes.

Cited Works (8)

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