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Macrophage Colony Stimulating Factor Produces Increased Trabecular Bone Density and Turnover, Characteristic of an Anabolic Agent.  S.E. Riffle, Y.Y. Yuan, T.A. Bateman. Department of Bioengineering, Clemson University, Clemson, South Carolina.

Skeletal unloading in microgravity is known to cause significant bone loss, which may put astronauts at greater risk for fracture. Prospective countermeasures generally fall into two categories: anabolic and antiresorptive. Anabolic agents increase bone mass by activating osteoblasts, while more common antiresorptives inhibit osteoclasts. In order to identify novel anabolics, a study was performed using high doses of macrophage colony stimulating factor (M-CSF), an important regulatory cytokine in osteoclastogenesis. The purpose of this study was to determine if high dose M-CSF would cause an increase in bone mass, through coupled activation of osteoblasts. The study involved daily subcutaneous injections of M-CSF (5mg/kg) to 12 female mice (C57BL/6J) and inert phosphate buffered saline (PBS) to another 12 mice. All mice were sacrificed on Day 21, with hind limbs, spleen and serum collected. MicroCT of the tibia was used to assess trabecular and cortical bone parameters. Mechanical testing, quantitative histomorphometry, and mineral content analyses were performed. ELISA was used to quantify levels of bone formation and resorption markers. Mice receiving M-CSF had a 55% greater gain in body mass throughout the study compared to PBS. High doses of M-CSF led to an increase in bone turnover, evident by the 57% greater TRAP-5b and 44% greater osteocalcin levels versus PBS. M-CSF resulted in greater trabecular bone volume, connectivity density, and trabecular number, along with lower trabecular separation and mineral content compared to PBS. M-CSF increased bone turnover and BFR throughout the bone remodeling process. These findings may aid in the development of successful anabolic treatment options in the future, allowing osteoporotic patients and astronauts with bone loss to regain a more normal bone density.

(Supported by grants from NSBRI (NASA NCC 9-58), BioServe (NASA NCC 8-242), and S.C. Life Undergraduate Research Program.)