In Reply to the Letter to the Editor: Involvement of Irisin in Age-Related Osteoporosis and Its Inhibitory Effect on the Senescent Marker p21 in Osteoblasts

We appreciate the thoughtful letter from Professor Naharciregarding our recently published article showing that iri-sin correlates positively with bone mineral density (BMD) in acohort of older adult patients and downregulates the senescentmarker p21 in osteoblasts.(1)We thank him for the interest in ourrecent work and welcome the opportunity to respond to hiscomments. As noted by Naharci, several chronic diseases couldhave inuenced the levels of circulating irisin measured in ourcohort of older adult patients. In agreement with this premise,in our study, we enrolled patients by excluding all subjects withat least one chronic disease. Because our primary outcome wasto investigate possible links between circulating irisin, FNDC5expression in skeletal muscle, and BMD, the main exclusion cri-teria were taking anti-osteoporosis therapy and physical impair-ments affecting the performance of daily activities. However,subjects were also excluded if they had renal failure with glomer-ular ltration rate <30 mL/min, diastolic blood pressure>90 mmHg, systolic blood pressure >140 mmHg, any impair-ment of glucose metabolism such as diabetes or pre-diabetes,glucocorticoid use within the past 2 years, and thyroid, parathy-roid, and liver diseases.