BACKGROUND: Circulating osteoprogenitor (COP) cells are considered as a surrogate of stem cell population. Lamin A, a protein of the inner nuclear membrane, plays a pivotal role in stem cell differentiation. Lamin A deficiency is associated with osteosarcopenia in vivo (Tong et al, Mech Ageing Dev. 2011). We therefore hypothesized that quantification of lamin A in COP cells could be used as a robust biomarker for musculoskeletal diseases. METHODS: Random sample of community-dwelling individuals enrolled in the Nepean Osteoporosis and Frailty (NOF) Study (mean age 82.8; N = 77; 70% female; 27 fit, 23 pre-frail and 27 frail). COP cells were identified by flow cytometry using selective gating for CD45+/OCN+. Lamin A was quantified in COP cells using percentage of lamin A+ COP cells and Mean Fluorescence Intensity (MFI) for lamin A. Logistic regression models estimated the relationship between the percentage of lamin A-expressing COP cells and prevalent disability and frailty. RESULTS: Low lamin A expression in COP cells was associated with disability as indicated by low scores in the Barthel (activities of daily living) and OARS (instrumental activities of daily living) scales (p<0.004, p<0.01 respectively). In addition, low MFI values were associated with a significantly higher score in the frailty index (Rockwood) (p<0.03). Moreover, lower percentage of COP cells expressing lamin A was associated with two fold greater odds of being frail than being fit (odds ratio (OR) = 2.06, 95% confidence interval (CI) = 0.98-4.3). CONCLUSION: In this study we demonstrated the feasibility of a new non-invasive diagnostic method to quantify of lamin A expression in COP cells. Low levels of lamin A expression in COP cells were associated with disability and frailty. Although longitudinal validation studies are still required, this diagnostic method has a high potential to become a robust biomarker for musculoskeletal disease.