There are multiple methods for assessing bone health, commonly used tools include: bone imaging, biochemical markers and histomorphometry.

DXA is considered by the World Health Organisation as the “gold standard” to diagnose osteoporosis and is the most widely used assessment technique for determining treatment effectiveness; although in some countries, peripheral quantitative computed tomography (p-QCT) is available as a research tool (Frotzler et al. 2008) Areal BMD (g/cm²) is quantified non-invasively with imaging technologies such as dual energy X-ray absorptiometry (DXA) and previously with dual energy photon absorptiometry (DPA). DXA measures areal BMD [aBMD= bone mineral content (BMC)(g)/area (cm²)]; whereas p-QCT measures volumetric BMD [vBMD = BMC(g)/volume (cm³)]. 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. 2009). 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).

Volumetric BMD (g/cm³) is assessed using peripheral quantitative computed tomography (pQCT). Peripheral QCT is a relatively safe and precise technique to differentiate cortical bone from trabecular bone, assess bone geometry and volumetric density. The imaging resolution has continued to improve and a high resolution (HR) pQCT now exists (80 micrometers) to give detailed information on peripheral bone microstructure.

Increases in aBMD or vBMD are presumed to be a suitable surrogate outcome for fracture risk reduction when assessing the effectiveness of SLOP therapy. Whereby, “optimal therapy” would be defined as increases in knee region BMD above the fracture threshold in the absence of low-trauma fracture.

Biochemical markers of bone turnover can be used as an adjunct to DXA in the assessment of bone health among patients with SCI. Serum and urine markers provide useful insight into bone metabolism at specific time points after injury and are an effective tool for monitoring response to therapy. The current therapeutic utility of bone turnover markers is limited by day-to-day, diurnal, inter-individual, and inter-assay variability. For urine markers, results need to be corrected for creatinine (Reiter et al. 2007).

The bone formation markers include bone-specific alkaline phosphatase (BALP), osteocalcin (OC N-terminal propeptide of type I collagen (PINP), and C-terminal propeptide of type I collagen (PICP).

Markers of bone resorption include urinary free and total pyridinoline (Pyr) and deoxypyridinoline (DPD) crosslinks, type 1 collagen C-telopeptide (CTX), and N-telopeptide (NTX). Pyr and DPD are molecules that provide stability to collagen and, along with CTX and NTX, are released when collagen is degraded during bone resorption (Brown et al. 2009).

For a bone marker to be useful in assessing the rate of bone turnover and/or monitoring therapy effectiveness, the difference in the rate of bone turnover before and after SCI, as well as the early period versus the late period after SCI, needs to be discernable.

Alignment of the choice of biomarkers across future bone health studies may allow for cross-study comparison or future meta-analyses.

Histomorphometry are measurements from bone biopsies to provide an in-depth understanding of bone. There are two types of bone histomorphometry, dynamic and static. Dynamic histomorphometry involves using substances such as tetracycline to measure tissue growth. Static histomorphometry involves determining the size and types of cells; measurements include length, area or cell counts. Although bone histomorphometry is considered an important tool, it is not always feasible because it requires surgically obtaining bone specimens from consenting participants.