What would most commonly cause bone pain and enlargement in the context of Paget's disease?

In Paget's disease of bone, the primary etiology involves osteoclast dysfunction. This condition is characterized by disorganized bone remodeling, where there is an initial increase in osteoclastic activity followed by a compensatory increase in osteoblastic activity. However, the osteoclasts do not function properly in Paget's disease, leading to excessive bone resorption followed by chaotic formation of new bone by osteoblasts.

The result of this pathological process is the formation of enlarged, structurally abnormal bones that are weaker and can cause pain due to the metabolic activity and the mechanical stress placed upon them. Patients often experience pain due to the excessive bone turnover and the local effects of enlarged and deformed bones—for example, due to microfractures or nerve compression. Thus, osteoclast dysfunction is central to the development of bone pain and enlargement in Paget's disease.

Other conditions like infection, neoplasm, or isolated osteoblast dysfunction can lead to bone pain or changes, but they do not encompass the specific imbalance of bone remodeling seen in Paget's disease. This unique interplay of osteoclastic and osteoblastic activity in Paget’s disease distinctly points to osteoclast dysfunction as the primary cause of the symptoms observed.