Quantitative heel ultrasound as a predictor for osteoporosis

Bone mineral density (BMD), measured by dual energy x-ray absorptiometry (DEXA), is the best predictor of fracture risk and is currently considered the "gold standard" for diagnosing osteoporosis. Although prospective studies have shown that quantitative ultrasound (QUS) predicts future fracture risk independently of BMD,^1,2 most women with abnormal results will proceed to formal BMD measurement to assess the need for therapeutic intervention; women with normal QUS results may be reassured they do not need BMD measurement. It is unclear how many women have unnecessary further investigations or are falsely reassured. When used in this way, QUS has diagnostic value only if it can accurately predict BMD categories as determined by DEXA.

Our aim was to examine the role of QUS in predicting BMD diagnostic categories. We determined conventional sensitivity and specificity, as well as likelihood ratios (LRs). These have the advantage of allowing test results to be assessed for several diagnostic categories rather than only at a single cut-off between "normal" and "abnormal".³

The study was conducted in the Rheumatology Department of the Royal North Shore Hospital, Sydney, NSW (a tertiary care hospital), in 1997 and 1998. It was approved by the hospital's Human Research Ethics Committee.  

QUS of the left calcaneus was performed on the same day using a CUBA Mark II ultrasound instrument (McCue Ultrasonics, London, UK). The two most commonly used QUS parameters were measured: broadband ultrasound attenuation (BUA), which is thought to reflect bone mass and architecture, and velocity of sound (VOS), which reflects mass and elasticity of bone.⁴ 

Subjects were classified as having osteoporosis if at least one of the three BMD measurements (lumbar spine, neck of left femur or total left hip) indicated osteoporosis, and as having osteopenia if at least one measurement indicated osteopenia but none indicated osteoporosis.

BUA and VOS results were combined as a cQUS category: this was defined as normal if both results were normal, as osteopenic if either indicated osteopenia but neither indicated osteoporosis, and as osteoporotic if either indicated osteoporosis. Some QUS scanners calculate a stiffness parameter (unrelated to mechanical stiffness) from a linear combination of normalised BUA and VOS values. We calculated stiffness in an analogous manner,⁶ and categorised it as normal, osteopenic or osteoporotic based on T scores in the same way as other QUS values.

We calculated the sensitivity and specificity of QUS parameters in predicting BMD-defined osteoporosis and osteopenia. We also calculated the likelihood ratio (LR) for each QUS result (sensitivity/1 - specificity), defined as the ratio of the probability of the particular QUS result (normal, osteopenic or osteoporotic) in women with BMD-defined osteoporosis or osteopenia to the probability of the same result in women with normal BMD.⁷

As there is no consensus on what QUS cut-off values should be used to diagnose osteoporosis, the statistical analyses were repeated using a range of QUS T-score cut-off values for osteoporosis between -2.5 and -1.0.

QUS results are compared with BMD results in Box 1. The percentage of women with values in the osteoporotic range varied between QUS parameters (1% for BUA, 17% for VOS and the combined BUA-VOS category, and 14% for stiffness).

Normal QUS result: A BUA, VOS, cQUS or stiffness result in the normal range had a low LR (0-0.2) (ie, a normal result significantly lowered the odds or probability of the woman's having BMD-defined osteoporosis).

Osteoporotic QUS result: A BUA result in the osteoporotic range had an LR approaching infinity and so was highly predictive of BMD-defined osteoporosis. In contrast, a VOS, cQUS or stiffness result in the osteoporotic range had a much lower LR (4.0-5.2), increasing the odds of BMD-defined osteoporosis, but to a lesser extent than a BUA result in the osteoporotic range.

Osteopenic QUS result: QUS results in the osteopenic range were less predictive, as LR ranged from 1.0 to 2.4. Between 37% and 50% of subjects (depending on the QUS parameter) had results in this range (Box 1).

LRs for predicting low BMD (ie, osteoporosis or osteopenia; BMD T score < -1) are also shown in Box 2, and followed a similar pattern to LRs for predicting BMD-defined osteoporosis.

When QUS T-score cut-off values for osteoporosis were increased from -2.5 to -1.0, sensitivity increased, but at the expense of decreasing specificity and LR (data not shown). For example, a BUA cut-off of -1.0 gave 83% sensitivity, 69% specificity and LR, 2.6. Corresponding values for a VOS cut-off of -1.0 were 96%, 41% and 1.6.

In the light of our study, how can we interpret QUS results?

• If a BUA result is in the osteoporotic range (LR, Infinity), then BMD-defined osteoporosis is almost certain (predictive value, 100%). However, the low sensitivity of BUA (9%) means that many women with osteoporosis would be missed if BUA alone were used.
  
• If results are
normal for both BUA and VOS (cQUS normal; LR, 0), we can confidently rule out BMD-defined osteoporosis. If LR is 0, then, no matter what the pre-test probability of osteoporosis, the post-test probability will be < 5% (Box 3).

• All results in the osteopenic range, and VOS and stiffness results in the osteoporotic range, are less predictive of BMD category.

Therefore, if QUS were performed on a population similar to ours (14% prevalence of osteoporosis), then (from Box 1) 1% would have a BUA result in the osteoporotic range (likely to have osteoporosis) and 33% would have both BUA and VOS results in the normal range (osteoporosis could fairly confidently be ruled out, with a post-test probability < 5%). However, there would be a degree of uncertainty about the remaining 66%, who would then need a DEXA scan to identify those with osteoporosis.

Previous studies of QUS as a predictor of BMD have generally used conventional sensitivity and specificity analyses only, not LRs, and have not used the WHO BMD definitions. For example, two community-based cross-sectional studies on 700 postmenopausal¹⁰ and 1000 perimenopausal women,¹¹ respectively, found that there was a 40%-50% overlap in the number of women in the lowest quartile of both DEXA and QUS measurements. Two other studies found QUS parameters to have a sensitivity of 65%-70% for BMD in the lowest quartile.^6,12 Only one study other than ours has evaluated QUS in terms of WHO BMD definitions. It found BUA and VOS to have higher sensitivities, of 77% and 69%, respectively, for diagnosing osteoporosis in 100 women aged 60-69 years.¹³These higher sensitivities may have been due to use of higher BUA and VOS cut-off values. As expected, specificities were lower than in our study.

The ultrasound instrument used in this study, the McCue Cuba Mark II, is not identical to the Achilles ultrasound instrument (Lunar, Madison, Wis, USA) used in Australian pharmacies. Nevertheless, a comparison of the two machines found that BUA measurements on a Cuba Mark II instrument were highly correlated with "stiffness" measurements on a Lunar Achilles instrument (r = 0.906; 95% CI, 0.873-0.931).¹⁴ Another study compared measurements of 30 women between the Cuba Mark II used in our study and an Achilles, finding an r value of 0.8.¹⁵ Therefore, it is unlikely that the Achilles instrument would be a significantly better predictor of BMD than our Cuba Mark II.

There is no consensus on what cut-off values to use with QUS to diagnose osteoporosis. We found that changing the cut-off could achieve higher sensitivity, but only by accepting higher rates of false positives (lower specificity) and less discriminating LRs.

Although there is enough evidence to support the use of QUS as an independent predictor of fracture risk,^1,2 our study shows that QUS should not been seen as a substitute for BMD measurement. The results of our study suggest that, when women in the community are "screened" for osteoporosis using QUS, a few women will be confidently identified with BMD-defined osteoporosis. Another small group will be able to be reassured that they are unlikely to have osteoporosis. However, for the great majority, the presence or absence of osteoporosis will remain uncertain.

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Department of Nuclear Medicine, St Vincent's Hospital, Sydney, NSW.
Nick A Pocock, FRACP, MD, Senior Staff Specialist.

Reprints will not be available from the authors.
Correspondence: Dr V Naganathan, Department of Rheumatology, Royal North Shore Hospital, St Leonards, NSW 2065.
Email: vasinATmed.usyd.edu.au