Disuse-induced loss of bone mineral density and bone strength is attenuated by post-lactational bone gain in NMRI mice

Lactation in mice is associated with a substantial bone loss, which almost completely recovers within four weeks after weaning. The post-lactational recovery mechanism is considered one of the most potent physiological bone anabolic responses in adult life. The aim of the study was to investigate whether the post-lactational bone anabolic response could attenuate or prevent a disuse bone loss induced by botulinum toxin (BTX) in mice. Eighty-one 10-week-old female NMRI mice were divided into the following groups: Pregnant, Lactation, Recovery + Vehicle, Recovery + BTX, No Lactation, No Lactation + Vehicle, No Lactation + BTX, and Virgin Control. The mice lactated for 12 days before weaning followed by 21 days of recovery. On the last day of lactation, disuse was induced by injecting 2 IU of BTX per 100 g body weight into the right hind limb. Mechanical testing, μCT, and dynamic bone histomorphometry were performed on the right femur. Lactation induced a loss of aBMD and of vBMD, Tb.Th, and MS/BS at the distal femoral metaphysis, Ct.Th and bone strength at the femoral mid-diaphysis, and femoral neck bone strength compared to pregnant mice. This bone loss was partly or fully reversed after 21 days of recovery from lactation. In non-lactating mice, BTX resulted in a loss of aBMD and of vBMD, BV/TV, Tb.Th, MS/BS, and BFR/BS at the distal femoral metaphysis, Ct.Th at the femoral mid-diaphysis, and femoral neck bone strength compared to ambulating non-lactating mice. The post-lactational response attenuated the BTX-induced loss of aBMD, Tb.Th, Ct.Th, trabecular MS/BS and BFR/BS, and femoral neck bone strength indicating that the recovery after lactation had reduced the negative effects of BTX on these parameters. In contrast, it was unable to counteract the loss of BV/TV and vBMD at the distal femoral metaphysis. In conclusion, the post-lactational response attenuated disuse-induced decrease of femoral aBMD, femoral neck bone strength, trabecular and cortical thickness, and trabecular MS/BS, BFR/BS, while it could not counteract the disuse-induced loss of BV/TV and vBMD.