Where’s the break? Critique of radiographic vertebral fracture diagnostic methods

Vertebrall fractures are the most common osteoporotic fractures and are associated with the highest risk of subsequent incident fractures [1]. The majority of vertebral fractures do not come to medical attention and thus remain undiagnosed [2]. In most osteoporosis guidelines [3, 4], vertebral fracture, unrelated to trauma and on its own, represents an intervention threshold for pharmacological treatment and may need no further risk assessment, including bone mineral density (BMD) measurement. Furthermore, the Endocrine Society has recently published a clinical practice guideline related to therapy of osteoporosis in menopausal women who are a year or more past their final menstruation, [5] in which they recommended treatment with bone-forming agents in these women with osteoporosis at very high risk of fracture, such as those with severe (Grade 3) or multiple vertebral fractures. Anabolic therapy has recently proven to be superior to antiresorptives for incident vertebral fracture prevention in randomized, controlled clinical trial data of teriparatide versus risedronate [6].

Although vertebral fractures are common and important in osteoporosis diagnosis and management, the definition of osteoporotic vertebral fracture remains controversial [7‐10]. Our purpose is to clear confusion for clinicians.

In 2000, 21.5% of men and 23.5% of women in a population-based national cohort of 6433 persons aged ≥ 50 years showed a Grade 1 or higher vertebral fracture (VF) or deformity that were systematically assessed by lateral vertebral radiography [11]. This prevalence was based on technologist triage followed by determination of 20–25% anterior wedging or three standard deviations (3 SD) greater height deviation than unaffected vertebrae at the same anatomical level in the same cohort [12]. On spine radiographs, the method identified the anterior, posterior, and middle vertebral heights of the superior and inferior endplates and compared the morphometry with the same, unaffected vertebral body in the population, as had Eastell in Rochester data [13]. Further refinements of the morphometric approach to vertebral fractures were developed by the late Professor Harry Genant at the University of California, San Francisco [14] who further clarified vertebral deformities by grades of height loss—Grade 1 loss of 20–25%, Grade 2 of 26–40%, and Grade 3 of > 40% [14] that remain in common use. Although this now-classical text also mentions “endplate deformities and buckling of cortices” and “loss of vertical continuity of vertebral morphology” (page 1145), the persuasive powers of its diagram of changed vertebral shapes has since taken precedence [14].

However, not every vertebral deformity represents an osteoporotic vertebral fracture.

Cross-sectional Canadian Multicentre Osteoporosis Study (CaMos) data on vertebral deformities or VF from randomly sampled women (2/3) and men (1/3) around nine urban centers from coast to coast across Canada, published in 2000, were similar to results previously documented in large USA, British, and European cohorts [12]. (Note that these radiographic VF, no matter how evaluated, are distinct from clinical VF in which a person has focal, usually acute, back pain and an investigating spine radiograph shows evidence of fracture.)

At about the same time, one of us (JCP), an academic working in the Vancouver, Canada, osteoporosis clinic was referred a healthy 60-year old Chinese man for osteoporosis evaluation and treatment because his CaMos spine radiographs had been interpreted as revealing a Grade 1 “vertebral fracture” at T-8. He was healthy, of normal weight and height, and his bone mineral density (BMD) was normal. He had no family history of fragility fracture, no clinical risk factors, no major trauma, and no previous fracture. (Note that this was pre-FRAX but we estimate his major osteoporotic fracture risk would have been less than 3%.) Should this man be prescribed an osteoporosis therapy (etidronate, the bisphosphonate then available in Canada)? Said another way: Did this healthy fellow with a Grade 1 vertebral deformity have osteoporosis that required treatment?

The diagnosis of “vertebral fracture” is controversial. It is often remarked that there is no “gold standard” for diagnosis of osteoporotic vertebral fracture [15]. Two primary assessment methods currently compete: the morphometric method of Genant (called Genant Semiquantitative analysis, GSQ) [14] that relies on assessment of vertebral height, and the morphologic (or “structural”) method which depends on informed recognition of breaks in superior and inferior endplates as proposed by the Sheffield group (called Algorithm-Based Qualitative, ABQ) [16], and modified by Lentle et. al. to also include cortical breaks (mABQ) [7]. Others have questioned “short anterior height” vertebrae as part of systemic osteoporosis [17].

Figure 1 illustrates the fundamental issue in radiographic vertebral fracture/deformity diagnosis. It shows that vertebrae may have the same shape and dimensions as normal (called Grade 0), yet have morphologic vertebral endplate or anterior cortical breaks. In addition, an intact vertebra may have a shortened anterior height and be considered a Grade 1 morphometric “vertebral fracture” but have little relationship with what we know of clinical osteoporosis. Previous cross-sectional data have examined the frequency of morphometric versus morphologic fractures and shown that Grade 1 morphometric “VF” are a lot more prevalent than are morphologic VF [7, 8].

To decide which of the two competing methods (barring a gold standard) is the more specific and accurate for radiographic vertebral fracture (VF) assessment (morphometric versus morphologic), we need to answer several questions:

Using recently published, population-based data, primarily from the CaMos and the Rotterdam Study research, we seek to answer these key questions.