Identifying novel biomarkers of pathological sarcopenia could facilitate diagnosis and treatment among the elderly. However “researchers need to ensure that emerging biomarkers undergo a thorough analytical validation by laboratory specialists before they are used in prospective clinical studies,” said Dr. Etienne Cavalier from The University of Liège, in Liege, Belgium, at the recent WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases held in Milan, Italy.

To illustrate the importance of this directive, Cavalier and colleagues performed a laboratory analysis of six established biomarkers for sarcopenia: myostatin, procollagen III N-terminal propeptide (PIIINP), activin A, irisin, osteoglycin, and transmembrane protein 19 (Tmem-19). Only myostatin and activin A were validated for use in prospective clinical studies.

Tmem-19 and osteoglycin were excluded from further study when it became clear that it was not possible to establish calibration curves for these markers. Irisin was excluded because of its high reproducibility coefficient of variation (20-45 percent vs approximately 10 percent for PIIINP, activin A, and myostatin).

Stability experiments revealed that although all three of the remaining markers were stable for 1 day at 4°C, only activin A and myostatin remained stable in both ethylenediaminetetraacetic acid (EDTA)-plasma and serum after 1 and 3 months at -20°C and -80°C.

Renal clearance of activin A, myostatin, and PIIINP was assessed in 10 patients with chronic kidney disease, and significant accumulation of both activin A and PIIINP was observed relative to the normal population.

The reference ranges for myostatin and activin A were established in 60 healthy men and 58 to 60 non-menopausal women with a mean age of 36.2±9.7 years and 30.1±5.5 years, respectively. The reference range for myostatin was 845 (437–1,312) to 6,067 (5,524–6,552) pg/mL for men or 600 (268–1,027) to 4,438 (4,026–4,837) pg/mL for women. The reference range for activin A was 177 (132–210) to 622 (580–661) pg/mL (men) or 98 (49–147) to 480 (430–525) pg/mL (women).

“Always perform a stability study [short- and long-term] in EDTA-plasma and serum before starting to collect relevant clinical samples for blood banks,” concluded Cavalier.