Periodontitis and osteoporosis are prevalent inflammation-associated skeletal disorders that pose significant public health challenges to our aging population. Both periodontitis and osteoporosis are bone disorders closely associated with inflammation and aging. There has been consistent intrigue on whether a systemic skeletal disease such as osteoporosis will amplify the alveolar bone loss in periodontitis. A survey of the literature published in the past 25years indicates that systemic low bone mineral density (BMD) is associated with alveolar bone loss, while recent evidence also suggests a correlation between clinical attachment loss and other parameters of periodontitis. Inflammation and its influence on bone remodeling play critical roles in the pathogenesis of both osteoporosis and periodontitis and could serve as the central mechanistic link between these disorders. Enhanced cytokine production and elevated inflammatory response exacerbate osteoclastic bone resorption while inhibiting osteoblastic bone formation, resulting in a net bone loss. With aging, accumulation of oxidative stress and cellular senescence drive the progression of osteoporosis and exacerbation of periodontitis. Vitamin D deficiency and smoking are shared risk factors and may mediate the connection between osteoporosis and periodontitis, through increasing oxidative stress and impairing host response to inflammation. With the connection between systemic and localized bone loss in mind, routine dental exams and intraoral radiographs may serve as a low-cost screening tool for low systemic BMD and increased fracture risk. Conversely, patients with fracture risk beyond the intervention threshold are at greater risk for developing severe periodontitis and undergo tooth loss. Various Food and Drug Administration-approved therapies for osteoporosis have shown promising results for treating periodontitis. Understanding the molecular mechanisms underlying their connection sheds light on potential therapeutic strategies that may facilitate co-management of systemic and localized bone loss.