Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice

Abstract

Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX.

Introduction

Measurements of bone mineral density (BMD) are a central component of any provision that arises from the definition of osteoporosis, agreed internationally as: a progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture [1]. This definition captures the notion that low areal BMD (aBMD) is an important component of fracture risk, but that other bone abnormalities contribute to skeletal fragility. The conceptual description of osteoporosis thus centres both on the assessment of bone mass and quality, specifically bone microstructure. Until recently, there were no satisfactory clinical means to assess bone microstructure non-invasively, so that the operational diagnosis of osteoporosis is based on the measurement of aBMD. Osteoporosis is so-defined as a femoral neck aBMD 2.5 SD or more below the young adult female mean (T-score ≤ − 2.5) [2], [3]. The same T-score derived at other sites is widely used in clinical practice (e.g., lumbar spine, total hip, distal radius).

A consequence of this operational definition, which identifies the small proportion of the population at highest risk, is that the greater number of individuals above this threshold, although individually at lower risk, contributes the greater number of fractures to the total burden. Indeed, the majority of fragility fractures occur in patients who have an aBMD T-score > − 2.5. In other words, the detection rate for these fractures (sensitivity) is low [4], which is why widespread population-based screening is not generally recommended in women at menopause [2], [5]. Thus, factors other than bone mass influence bone strength and fracture risk, including microarchitectural deterioration of bone tissue, as given in the conceptual definition of osteoporosis. Additional skeletal and extra-skeletal factors, such as bone geometry, micro-damage, mineralization, bone turnover, age, and a large range of clinical risk factors, including family history, prior fracture and fall risk, contribute to the overall assessment of fracture risk [6], [7], [8], [9]. Several of these additional factors are captured by FRAX®. FRAX estimates the 10-year probability of hip and major osteoporotic fracture based on the individual's risk factor profile [4]. Apart from BMD, FRAX does not capture other skeletal determinants of bone strength that improve upon or are at least partly independent of aBMD [10]. Several such determinants are the subject of clinical research [11], [12], [13], [14], [15], [16], [17], [18] using novel imaging techniques, such as quantitative computed tomography (QCT) and high resolution (peripheral) QCT [19], [20], and minimally invasive approaches for probing bone material properties, notably microindentation techniques [21]. Although there is evidence of their predictive ability for fracture [22], [23], none of these modalities appears to reliably outperform aBMD in the prediction of the various types of osteoporotic fractures, and their general lack of availability and validation in the clinical setting means that an adjunctive role alongside DXA-measured aBMD is unlikely to be feasible in most settings in the near future. In contrast, trabecular bone score (TBS) is a novel imaging technique, based on standard DXA images, and appears to constitute an index of bone texture that provides skeletal information additional to the standard aBMD results [24].

TBS has emerged as a novel grey-level texture measurement that uses experimental variograms of 2D projection images, quantifying variation in grey-level texture from 1 pixel to the adjacent pixels. TBS is not a direct measurement of bone microarchitecture but it is related to 3D bone characteristics such as the trabecular number, the trabecular separation and the connectivity density [25], [26]. An elevated TBS appears to represent strong, fracture-resistant microarchitecture, whilst a low TBS reflects weak, fracture-prone microarchitecture. As such, there is evidence that TBS can differentiate between two 3-dimensional (3D) microarchitectures that exhibit the same bone density, but different trabecular characteristics. TBS is generally obtained by re-analysis of AP lumbar spine DXA images, which allows direct comparison with aBMD and application to existing datasets. This latter opportunity has led to a rapid rise in published research assessing its potential role in the assessment and management of osteoporosis.

Lumbar TBS, like aBMD, is an age dependent variable. Little change in TBS is observed between the ages of 30 and 45 years. Thereafter, a progressive decrease is observed with advancing age [27], which is more marked in women than in men. The percentage decrease with age is similar to that for lumbar spine aBMD, as is the short term reproducibility [25].

This paper reports the findings of a European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) Working Group, which first convened in September 2014 with the aim of comprehensively assessing the evidence supporting the use of TBS in clinical practice. More specifically, this report reviews the potential value of TBS as an independent adjunct to risk assessment using DXA aBMD and/or FRAX in settings such as post-menopausal and secondary osteoporosis, and its potential use in assessment of response to treatment.

A Medline search for publications with the terms trabecular bone score or TBS was undertaken in September 2014. Published articles in English and French were extracted. Papers in abstract form were not included except where the authors supplied a full copy of the submitted manuscript. A total of 479 papers were identified of which 67 manuscripts were considered relevant and the full publication reviewed. The search was subsequently updated in February 2015 and a total of 73 papers were reviewed.