Short-term intermittent administration of parathyroid hormone facilitates osteogenesis by different mechanisms in cancellous and cortical bone

• We analyzed the effects of hPTH(1–34) injection into rats at early phase.
• hPTH(1–34) injection increased the osterix-positive cells in bone marrow.
• hPTH(1–34) injection decreased sclerostin-positive cells in cortical bone.
• hPTH(1–34) exerts different effects in cancellous and cortical bone.

Intermittent administration of human parathyroid hormone (1–34)[hPTH(1–34)] induces anabolic action on the bones. To understand the mechanism underlying the early phase of hPTH(1–34)-induced anabolic action, we investigated the expression profiles of osterix and sclerostin after short-term intermittent administration of hPTH(1–34) using immunohistochemistry in adult rats. In the cancellous bone, hPTH(1–34) administration greatly increased the number of osterix-positive cells in the bone marrow on day 1, but the cells gradually decreased on days 3 and 5. Injections of hPTH(1–34) induced no significant changes in the number of sclerostin-positive osteocytes in the cancellous bone. In the cortical bone, intermittent administration of hPTH(1–34) significantly reduced the number of sclerostin-positive osteocytes. The serum sclerostin level was downregulated and the osteocalcin level was upregulated on day 5 after intermittent administration of hPTH(1–34). Intermittent hPTH(1–34) injections increased osteoblast surface, osteoid thickness, and osteoid surface in cancellous bone, but not in cortical bone. This study suggested that the increase in osterix-positive osteoprogenitors in cancellous bone and the decrease in sclerostin-positive osteocytes in cortical bone play important roles in anabolic action on osteogenesis induced by short-term administration of hPTH(1–34).