Clinical Studies

Bone mineral density is

used to

diagnose osteoporosis

Measuring BMD has been shown to be the most reliable method to quantify risk of an osteoporotic fracture and osteoporosis is defined as having a BMD below a certain threshold. The most commonly used BMD measurement method is DXA (Dual energy X-ray Absorptiometry) of the central skeleton (hip and spine). While DXA is the gold standard and most frequently used diagnostic tool, it has been shown in practice to not be convenient for use in preventive care of osteoporosis.

OneScreen can predict common osteoporotic fractures

The most important aspect of a screening test for osteoporosis is the ability to predict common osteoporotic fractures of the wrist, hip and vertebrae. The use of BMD measured by DXR (DXR- BMD) to predict fractures has been investigated in a number of clinical studies. Using central DXA as reference, DXR has been shown to identify patients with osteoporosis of the hip and spine (Dhainaut, 2010; Vasireddy, 2010) and to predict hip fractures (Wilczek, 2013), wrist fractures (Bouxsein, 2002; Black, 2001) and vertebral fractures (Bouxsein, 2002; Bach- Mortensen, 2006; Vasireddy, 2010).

OneScreen has been tested in several clinical trials

The magnitude of the increased risk due to reduced BMD is often quantified as a risk increase per T-score decrease in BMD. For a DXA measurement of the hip, this value is around 2.6 (Marshall, 1996),meaning that the risk of a woman with a T-score of -2.5 suffering a hip fracture is 11 times higher than a woman with T-score 0. In this respect, DXR compares well with hip DXA, with a similar risk increase of 2.5 per T-score decrease in BMD (Wilczek, 2013) corresponding to a tenfold increase in fracture risk. Furthermore, a receiver operating characteristics (ROC) curve analysis showed that DXR-BMDhad an area under the curve (AUC) of 0.89 for women and 0.84 for men (Wilczek, 2013). This corresponds to a woman who suffers a hip fracture have a 89 % chance of being identified by DXR.

This data is supported by earlier work from which show that DXR is equal to peripheral and central DXA in the prediction of fractures of the wrist and spine (Bouxsein, 2002; Bach- Mortensen, 2006).Overall the general performance of DXR-BMD in predicting fractures appears equal to central DXA and superior to other peripheral methods as quantitative ultrasound (QUS) (Boonen, 2005.

Osteoporosis detection with OneScreen

DXA in used in the diagnosis of osteoporosis therefore any other method to determine BMD will be compared to DXA in detecting osteoporosis. If we compare DXR-BMD and DXA the correlation varies from bone site to bone site. Specifically the correlation (r) is 0.9 for a wrist measurement and 0.6-0.7 for a hip measurement (Rosholm, 2001; Black, 2001; Bouxsein, 2002 Dhainaut, 2010).

However, more important than correlation is how well a DXR result can predict a clinical classification done by DXA. Data from a UK study presented by Dr. Vasireddy show that DXR- BMD has 90% sensitivity towards osteoporosis of the hip. Furthermore, ROC analyses show an AUC of 0.78. This means that 90 % of those that have osteoporosis at the hip can be detected using DXR-BMD and a woman with osteoporosis have a 78 % chance of being detected with DXR. This data is supported by Dhainaut et al., which also compared DXR with hip DXA in determining which patients could be given the diagnosis osteoporosis or be said not to have osteoporosis they also found 90 % sensitivity (Dhainaut, 2010). They also confirmed the ROC analysis from Vasireddy and found an AUCof 0.82 towards osteoporosis. In the same study, they report that a DXR T-score of -2.7 had a positive predictor value (PPV) of 75% for osteoporosis and a negative predictor value (NPV) of 96%. Whichmeans that 75 % of patients with low DXR- BMD will be confirmed to have osteoporosis and that 96 %of patients that do not have low DXR- BMD will not have osteoporosis. Taken together, these studiessuggest that OneScreen can be an effective selection tool for DXA.

The automated analysis gives OneScreen good precision

Furthermore, DXR has been found to have excellent short- and long-term precision (Dhainaut, 2011; Hoff, 2009) with a coefficient of variation < 0.3% (Sectra, data on file). This precision enables small changes in DXR-BMD over time to be detected. The ability to follow anti- resorptive treatment was investigated by Haigh et al. This study was conducted on osteoporotic women from the vertebralosteoporosis trial (VOT) (McCloskey, 2001). The study concludes that DXR-BMD has similar properties and performance as DXA-BMD when it comes detecting changes in BMD that arise during anti-resorptive treatment and that these changes can be followed over time (Haigh, 2002).

References

Bach-Mortensen P, Hyldstrup L, Appleyard M, et al. Digital x-ray radiogrammetry identifies women at risk of osteoporotic fracture: results from a prospective study. Calcif Tissue Int. 2006;79(1):1-6.

Black DM, Palermo L, Sorensen T, et al. A normative reference database study for Pronosco X-posure System. J Clin Densitom. 2001;4(1):5-12.

Boonen S, Nijs J, Borghs H, et al. Identifying postmenopausal women with osteoporosis by calcaneal ultrasound, metacarpal digital X-ray radiogrammetry and phalangeal radiographic absorptiometry: a comparative study. Osteoporos Int. 2005;16(1):93-100.

Bouxsein ML, Palermo L, Yeung C, et al. Digital X-ray radiogrammetry predicts hip, wrist and vertebral fracture risk in elderly women: a prospective analysis from the study of osteoporotic fractures. Osteoporos Int. 2002;13(5):358- 365.

Dhainaut A, Rohde GE, Syversen U, et al. The ability of hand digital X-ray radiogrammetry to identify middle-aged and elderly women with reduced bone density, as assessed by femoral neck dual-energy X-ray absorptiometry. J Clin Densitom. 2010;13(4):418-425.

Dhainaut A, Hoff M, Kalvesten J, et al. Long-term in-vitro precision of direct digital X-ray radiogrammetry. Skeletal Radiol. 2011;40(12):1575-1579.

FDA. http://www.accessdata.fda.gov/cdrh_docs/pdf2/k021527.pdf. 2002 Fredrik Borgström. http://www.quantifyresearch.com/. 2013

Haigh C, Reaney L, Adams J, et al. Radiogrammetry Indices are Sensitive to Clodronate Treatment In Women With Osteoporosis. J Bone Miner Res. 2002;17(Sup 1):S231

Hoff M, Dhainaut A, Kvien TK, et al. Short-time in vitro and in vivo precision of direct digital X-ray radiogrammetry. J Clin Densitom. 2009;12(1):17-21.

Kanis JA, McCloskey EV, Johansson H, et al. A reference standard for the description of osteoporosis. Bone. 2008;42(3):467-475.

Kanis JA, McCloskey EV, Johansson H, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013;24(1):23-5

McCloskey E, Selby P, de Takats D et al. Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis. Bone. 2001;28(3):310-5.

Rosholm A, Hyldstrup L, Backsgaard L, et al. Estimation of bone mineral density by digital X-ray radiogrammetry: theoretical background and clinical testing. Osteoporos Int. 2001;12(11):961-969.

Wilczek M, Kälvesten J, Algulin J, et al. Digital X-ray radiogrammetry of hand or wrist radiographs can predict hip fracture risk– a study in 5,420 women and 2,837 men. Eur Radiol. 2013;23(5):1383–1391Vasireddy S. Metacarpal Radiographic Indices in the assessment of bone strength and fracture risk. Thesis. University of Sheffield. 2