The soluble and membrane‐bound forms of CSF‐1 are synthesized by osteoblasts and stromal cells in the bone microenvironment. Transgenic mice, generated to selectively express sCSF‐1 in bone, showed increased cortical thickness in the femoral diaphysis caused by new bone formation along the endosteal surface. The ability of sCSF‐1 to enhance bone cell activity in vivo is potentially relevant for increasing cortical bone in a variety of disorders.

Introduction: The soluble form of colony‐stimulating factor‐1 (sCSF‐1) and the membrane‐bound form of CSF‐1 (mCSF‐1) have been shown to support osteoclastogenesis in vitro; however, the effect of each peptide on bone remodeling in vivo is unclear. To determine the effect of sCSF‐1, selectively expressed in bone, the skeletal phenotype of transgenic mice harboring the human sCSF‐1 cDNA under the control of the osteocalcin promoter was assessed.

Methods: At 5 and 14 weeks, mice were analyzed for CSF‐1 protein levels, weighed, and X‐rayed, and femurs were removed for peripheral quantitative computed tomography, histology, and histomorphometry.

Results: High levels of human sCSF‐1 were detected in bone extracts and, to a lesser extent, in plasma. Adult transgenic mice showed normal body weight and increased circulating monocytic cells. At 5 weeks, the femoral diaphysis was similar in CSF‐1T and wt/wt littermates. However, by 14 weeks, the femoral diaphysis in CSF‐1T mice showed increased cortical thickness and bone mineral density. In contrast to the diaphysis, the femoral metaphysis of CSF‐1T mice showed normal cancellous bone comparable with wt/wt littermates at each time point. Histological sections demonstrated increased woven bone along the endosteal surface of the diaphysis and intracortical remodeling. Fluorochrome‐labeling analysis confirmed endocortical bone formation in CSF‐1T, with a 3.1‐fold increase in the percentage of double‐labeled surfaces and a 3.6‐fold increase in the bone formation rate compared with wt/wt mice. Although remodeling resulted in a slightly porous cortex, sCSF‐1 preferentially stimulated endocortical bone formation, leading to increased cortical thickness.

Conclusions: These findings indicate that sCSF‐1 is a key determinant of bone cell activity in the corticoendosteal envelope.