Pathophysiology of osteolytic/osteoblastic metastatic bone disease in PC posits that metastatic tumor cells release humoral factors (osteoclast precursors, such as parathyroid hormone-related protein, interleukin-6) that stimulate osteoclastic recruitment and differentiation, while PC cells concomitantly produce soluble paracrine factors (TGF beta, IGF, bone morphogenetic protein), causing excessive osteoblast activation. The gene discussed is IGF1; the disease is pachyonychia congenita.