Osteoporosis is a systemic metabolic disease defined by a decreased bone mineral density, microarchitectural deterioration, and an increased incidence of fragility fractures that may lead to morbidity and mortality. Boron may stimulate new bone formation and regeneration, when combined with nano-hydroxyapatite. We questioned whether injecting boron-containing nano-hydroxyapatite composites with hyaluronan increased the bone mineral density and new bone formation in osteoporotic rabbit femurs. The regenerative effects of injectable boron-containing nano-hydroxyapatite composites from 6 to 12 weeks, which may prevent osteoporotic femoral fractures, were assessed. Boron-containing (10 mu g/ml) nano-hydroxyapatite composites were injected into the intramedullary femoral cavity with hyaluronan. These significantly increased the histomorphometric new bone surface to the total bone surface ratio at 6 and 9 weeks. The micro-tomographic bone volume to the total volume ratio and bone mineral density in osteoporotic rabbit femurs increased when compared to the hyaluronan (p = 0.004, p = 0.004, p = 0.004, p = 0.01, respectively) and the sham-control (p = 0.01, p = 0.004, p = 0.01, p = 0.037, respectively) groups. The boron-containing group had a higher bone mineralization and new bone formation compared to the nano-hydroxyapatite group, although the difference was not statistically significant. These findings reveal that intramedullary injection of boron-containing nano-hydroxyapatite with hyaluronan increases new bone formation and mineralization in ovariectomized rabbit femurs. Boron-containing nano-hydroxyapatite composites are promising tissue engineering biomaterials that may have regenerative potential in preventing primary and/or secondary femoral fractures in osteoporosis patients.