Letters Section Editor: Stephen J. Lurie,
MD, PhD, Senior Editor.
To the Editor: Dr Schett and colleagues1 reported that a low level of the receptor activator
of nuclear factor κB ligand (RANKL) is an independent predictor of nontraumatic
fracture and that it may gain relevance for assessment of fracture risk. However,
the study has several weaknesses, and important information is missing.
First, the study is based on what appears to be an untested laboratory
method. Soluble RANKL levels in normal serum are extremely low, in the (sub)picomolar
range. According to Schett et al, RANKL was measured "by a commercial sandwich
enzyme-linked immunosorbent assay [ELISA] (Biomedica, Vienna, Austria) as
described [in their reference 12]." In contrast with Biomedica's OPG ELISA,
I have not been able to find any references to publications using this product
or showing validity and reliability on Biomedica's Web site, and it is not
mentioned in the article's reference 12, which describes immunoprecipitation
of murine RANKL. In addition, it is not clear in the "Laboratory Methods"
section whether each participant's serum was analyzed as a single sample,
in duplicate, or in triplicate. Although the levels are reported to be stable
over time, the correlation between 1990 (or 1995) and 2000 measurements is
not shown, and the regression line in Figure 2 in the article seems to be
based on the few individuals with RANKL concentrations greater than 2 pmol/L.
Melhus H. Soluble RANKL and Risk of Nontraumatic Fracture. JAMA. 2004;291(22):2703. doi:10.1001/jama.291.22.2703-a