A Review of the Methods and Associated Mathematical Models Used in the Measurement of Fat-Free Mass

Fat-free mass (FFM) represents the lean component of the body devoid of fat. It has been shown to be a useful predictor of drug dose requirements, particularly in obesity where the excess fat mass does not contribute to drug clearance. However, measuring FFM involves complex and/or expensive experimental methodologies that preclude their use in routine clinical practice. Thus, models to predict FFM from readily measurable variables, such as body weight and height, have been developed and are used in both population pharmacokinetic modelling and clinical practice. In this review, methods used to measure FFM are explained and compared in terms of their assumptions, precision, and limitations. These methods are broadly classified into six different principles: densitometry, hydrometry, bioimpedance, whole-body counting, dual energy X-ray absorptiometry, and medical imaging. They vary in their processes and key biological assumptions that are often not applicable in certain populations (e.g. children, elderly, and certain disease states). This review provides a summary of the various methods of FFM measurement and estimation, and links these methods to a scientific framework to help clinicians and researchers understand the usefulness and potential limitations of these methods.