Taken together, our results reveal that accumulation of RhoA-expressing cells, mainly pro-inflammatory macrophages, are involved in the calcification paradox that occurs during disease progression in dKO mice, and that RhoA inhibition can restore the imbalanced mineralization (i.e. osteoporosis with co-incident ectopic bone formation in dystrophic muscle tissue) by limiting the accumulation of pro-inflammatory macrophages. Here, RHOA is linked to osteoporosis.