Bone imaging is typically used to assess BMD, morphology, or microstructure. Imaging modalities that are used for bone health assessment include dual-energy X-ray absorptiometry (DXA), dual-energy photon absorptiometry (DPA), and standard and high-resolution peripheral quantitative computed tomography (pQCT, HR-pQCT). Nevertheless, the availability of pQCT scanners is mainly limited to research institutions in part due to the incompatibility of pQCT data with DXA-derived T-scores, lack of normative studies, and specific treatment thresholds (Engelke et al. 2008, Adams et al. 2014, Zysset et al. 2015). There are more than 50,000 whole-body DXA, approximately 800 pQCT (XCT 2000 and 3000) and just 50 HR-pQCT (XtremeCT and XtremeCT II) scanners used in clinical practice/research worldwide (Shepherd et al. 2014; personal communication with Stratec Medizintechnik GmbH and Scanco Medical).
Bone mineral density assessment by DXA imaging is considered by the World Health Organization as the “gold standard” to diagnose osteoporosis and is the most widely used assessment technique for determining treatment effectiveness. DXA is a non-invasive, relatively safe modality for measuring areal BMD (aBMD), which is defined as BMC per unit area in g/cm2. DPA is an older technology for measuring aBMD that is sometimes reported in studies conducted before the 1990s.
Increases in areal BMD (aBMD) are presumed to be a suitable surrogate outcome for fracture risk reduction when assessing the effectiveness of SLOP therapy. “Optimal therapeutic outcome” would be defined as an increase in knee region BMD above the fracture threshold in the absence of fragility fracture.
There are several established methods for measuring BMD at the knee (Garland et al. 1993; Moreno et al. 2001; Eser et al. 2004; Morse et al. 2009b). Regardless of the methodology chosen, assessment of knee region BMD is crucial as it best predicts knee region fracture risk after SCI (Eser et al. 2005; Garland et al. 2005; Lala et al. 2013). Figure 2 displays a sample of a lumbar spine DXA image with vertebral delineation.
Figure 2. Lumbar spine DXA image with vertebral delineation. Source: https://www.hologic.com/hologic-products/breast-skeletal/horizon-dxa-system#resources
Peripheral QCT is another non-invasive, relatively safe imaging modality that can be used to diagnose osteoporosis. Whereas DXA measures areal BMD, pQCT measures volumetric BMD (vBMD), which is defined as bone mineral content (BMC) per unit volume in g/cm3. vBMD stands alongside aBMD as a surrogate outcome for fracture risk reduction. In addition to assessing volumetric bone density, pQCT can also differentiate cortical bone from trabecular bone and quantify architecture. However, pQCT is available as a clinical diagnostic tool in only a few countries.
High-resolution pQCT (HR-pQCT) improves upon the resolution of standard pQCT imaging and is now available with as fine as 42µm resolution. This imaging modality gives detailed information on the microarchitecture of peripheral bone but is not widely available outside of research applications in North America and is not recommended for cross-sectional studies at this time.
The current official positions of the International Society for Clinical Densitometry (ISCD) (Engelke et al. 2008, Kanis et al. 2015, Adams et al. 2014, Zysset et al. 2015), does not yet recommend routine use of pQCT for diagnosis of osteoporosis, fracture risk prediction or monitoring treatment effectiveness. This position is in part due to the incompatibility of pQCT data with DXA derived T-scores, inconsistency in measurement sites and bone analysis, lack of normative studies, and specific treatment thresholds (Engelke et al. 2008, Adams et al. 2014, Zysset et al. 2015). An example of a pQCT image can be seen in Figure 3.
Figure 3. Example of pQCT data. Upper panel represents the tibial epiphysis (predominantly trabecular bone; red colour tones). Lower panel represents the tibial diaphysis (predominantly cortical bone; white colour tones).