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Osteoporosis and periodontal disease are two diseases that affect millions of people worldwide. The common element is represented by bone loss. Periodontal disease consists of a set of inflammatory and/or degenerative changes concerning the periodontium, that evolve in the first phase with the loss of the connection between the superficial periodontium and the tooth, and subsequently with the damage of the profound periodontium. Recent studies in the literature show that osteoporosis, by lowering systemic bone mineral density and alveolar bone, can create a favorable framework for the progression of the periodontal impairment. This paper aims to present the main epigenetic changes related to micro-RNA from the two pathologies, focusing on the common elements that they share.