RESUMEN
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, Recoveryâ¯+â¯Vehicle, Recoveryâ¯+â¯BTX, No Lactation, No Lactationâ¯+â¯Vehicle, No Lactationâ¯+â¯BTX, and Virgin Control. The mice lactated for 12â¯days before weaning followed by 21â¯days of recovery. On the last day of lactation, disuse was induced by injecting 2â¯IU of BTX per 100â¯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 21â¯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.
Asunto(s)
Densidad Ósea , Enfermedades Óseas Metabólicas , Animales , Huesos , Femenino , Fémur , Lactancia , RatonesRESUMEN
Strontium ranelate (SrR) has both bone anabolic and anti-resorption properties and has therefore the potential to increase the healing of bone defects. The aim of the present study was to investigate the effect of systemic treatment with SrR during the healing of cortical bone defects in rats. In addition, the vertebral bodies were examined in order to elucidate the effect of short-term treatment with SrR on intact trabecular bone. Sixty 16-week-old female Wistar rats were randomized into four groups. A cylindrical defect was drilled through the anterior cortex of the mid-femoral diaphysis in both hind limbs. Two of the groups were treated with SrR (900 mg/kg b.w.) mixed into the food and two groups served as controls. The animals were euthanized after either 3 or 8 weeks of treatment. Healing of the defects was analyzed with µCT, mechanical testing, and stereology. Treatment with SrR resulted in increased thickness of the defects after 3 weeks of treatment, whereas no effect on bone volume fraction (BV/TV), mechanical properties (maximum strength and maximum stiffness), periosteal callus volume, or osteoclast-covered bone surfaces (Oc.S/BS) after either 3 or 8 weeks of treatment was found. Furthermore, SrR increased the bone material density (ρ) of the vertebral bodies, and tended to increase BV/TV after 8 weeks of treatment (p = 0.087). The mechanical properties of the vertebral bodies were not influenced by SrR treatment. In conclusion, 3 weeks of treatment with SrR increased the thickness of the healing mid-femoral cortical bone defects in rats, but did not influence BV/TV, mechanical properties, periosteal callus volume, or Oc.S/BS after either 3 or 8 weeks. Furthermore, SrR had no effect on the microstructure and mechanical properties of the vertebral bodies.