J Cachexia Sarcopenia Muscle (2012) 3:181–190 8 Clinical outcome measures of sarcopenia Ultimately, the goal of clinical trials for sarcopenia treat- ments will require the evaluation of clinical benefit. In fact, clinical measures can also be considered as biomarkers as they reflect the impact of the pathological process of sarco- penia on the patient's health. The assessment of measures of muscle strength (e.g., hand grip), muscle power (e.g., leg extension power), and physical performance [e.g., Short Physical Performance Battery [4] and gait speed tests] com- prise important indices of the individual's physical function. In addition, functional outcome measures will need to be developed in order to help understand the impact of any treatment-related quantitative gains in performance on the person's daily life. 9 Recommendations 9.1 Adoption of comprehensive operative definitions The lack of a unique operative definition of sarcopenia and the numerous methodological issues could potentially hin- der efforts to study sarcopenia and to develop effective treatments. Such difficulties should not hamper the process of exploring this syndrome which severely affects the health status of millions of older persons. The current ambiguities can be easily overcome by adopting flexible and compre- hensive approaches in the design of studies, for example, by avoiding reliance on a single parameter or technique to evaluate age-related skeletal muscle decline. The adoption of a variety of assessment approaches in combination is agreeable. Although this might lead to the risk of conflicting results (and increase the need of resources), it will serve to (1) capture different domains of the sarcopenia syndrome, (2) provide useful insights about the pathophysiological process underlying this phenomenon, and (3) facilitate the development and use of the findings in future and more definitive studies. In this context, it is noteworthy the lack of studies simultaneously testing different techniques mea- suring skeletal muscle (e.g., MRI, CT, DXA, etc.) in rela- tionship with clinically meaningful outcomes. Such studies might greatly help in the standardization of instruments and in the adoption of an univocal direction in the study of sarcopenia. 9.2 MRI and CT scan to be equally considered as “gold standard” imaging techniques It is now clear that, to be adequately assessed, the sarcopenia phenomenon cannot merely rely on the evaluation of the contractile part of skeletal muscle. The close relationship between lean mass and adipose tissue in determining age- 187 related decline of skeletal muscle is evident [38, 76, 77]. Therefore, techniques allowing the simultaneous evaluation of fat and muscle should be preferred. DXA, CT, and MRI are the most important assessment instruments. CT and MRI should be considered the “gold standard” techniques. The balance of pros and cons for both CT and MRI does not allow a clear indication on which of the two should be preferred. Resources, instrument availability, and need of details will represent the factors guiding the investigator's preference for one over the other. On the other hand, DXA should not be discarded and still represents the instrument more likely to promote the “clinical relevance” of sarcope- nia. For its characteristics, DXA may be an extremely inter- esting methodology to be used for preliminary screening. Moreover, its use in combination with either CT or MRI will help drive the research in the field towards more clinical aspects. While imaging and other biomarkers will be valu- able tools for initial proof of concept studies, assessment tools for evaluating the effect of treatments on outcomes reflecting clinical benefit will be required to support eventual pivotal studies. 9.3 Adequate length of study To evaluate the efficacy of a specific intervention on sarco- penia, it is necessary that the follow-up will be sufficiently long to allow the hypothesized modifications of biomarkers. Surely, not all biomarkers will be similarly influenced by the intervention. Such variations will depend on multiple fac- tors, including the population characteristics, the type and strength of the tested intervention, and the sensibility of the biomarker to changes. However, 6 months have been gen- erally indicated as the minimum timeframe to expect changes in imaging parameters. 9.4 Sarcopenia is a “work in progress” The study of sarcopenia is still in its infancy, but we have clearly acknowledged the great potential benefits arising from the understanding and treatment of this condition at both person and population levels. Taking together the uncertainties of exploring a novel field with the exponential acceleration of scientific progress, it is currently difficult to provide long-lasting statements, recommendations, and guidelines. It is likely that what seems reasonable today will be confounded by several studies in the near future. For this reason, extreme caution is needed to avoid jeopardizing the future development of research in the field. It is important to consider the study of sarcopenia as a “work in progress,” always amenable to changes and redirections. After all, the first phase II trials in this syndrome are just starting, and this is the appropriate time to raise doubts and pose questions. With time, a stronger foundation for sarcopenia