title: Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral densitometry may flaw osteopenic/osteoporotic interpretations and mislead assessment of antiresorptive therapy effectiveness.
abstract: New, anatomically realistic simulation studies based on a cadaveric lumbar vertebra and a broad range of soft tissue anthropometric representations have quantitatively delineated inaccuracies inherent in dual-energy X-ray absorptiometry (DXA) in vivo bone mineral density (BMD) methodology. It is found that systematic inaccuracies in DXA BMD measurements may readily exceed +/-20% at typical in vivo lumbar vertebral sites, especially for osteopenic/osteoporotic, postmenopausal, and elderly patients. These findings are quantitatively compared with extensive clinical evidence of strong, positive correlations between soft tissue anthropometrics and DXA in vivo BMD upon which prior significant bone biology interpretations and implications have been based. The agreement is found to be both qualitatively and quantitatively excellent. Moreover, recent extensive multicenter clinical studies have also exposed new facets of strong linkages between body mass/percent body fat/body mass index (BMI) and DXA-measured BMD that are particularly relevant to osteopenia/osteoporosis and remedial effectiveness of antiresorptive drug therapy. These seemingly disparate and unrelated diagnostic and prognostic aspects of clinically observed associations between soft tissue anthropometrics and measured vertebral BMD are, in this study, self-consistently shown to share the common origin of being manifestations of systematic inherent inaccuracies in DXA in vivo BMD methodology, without the need to invoke any underlying biologically causal mechanism(s). These inaccuracies arise principally from absorptiometric disparities between the intra- and extraosseous soft tissues within the DXA scan region of interest. The present evaluative comparisons are based exclusively on an incisive and diverse body of clinical data that appears difficult to dismiss or discount. Previous invocations of biologically causal mechanisms responsible for this broad range of observations linking body mass, percent body fat, and/or BMI to measured BMD now appear questionable. This doubtful status has also been extended in the present work to previously reported relationships between antiresorptive therapies and observed changes in DXA-derived BMD. These findings strongly indicate that critical and insightful reassessments of diagnostic/prognostic imputations underpinned by DXA in vivo BMD measurements are warranted. It is suggested that a good deal of what is known of bone fragility, bone densitometry, antiresorptive drug efficacy, and/or other therapeutic regimens, if based on patient-specific in vivo DXA methodology, may prove to be equivocal and tenuous.
authors.affiliation: School of Physics, University of Melbourne, Melbourne, Victoria 3010, Australia. h.bolotin@physics.unimelb.edu.au
authors.forename: H H
authors.initials: HH
authors.lastname: Bolotin
mesh_terms: D015502:Absorptiometry, Photon / Q000009:adverse effects*; D000273:Adipose Tissue / Q000166:cytology / Q000000981:diagnostic imaging; D000886:Anthropometry; D016477:Artifacts; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D001853:Bone Marrow / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D001862:Bone Resorption / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008954:Models, Biological; D010024:Osteoporosis / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016896:Treatment Outcome