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. This evidence concerns the gene PTHLH and pachyonychia congenita.