Objective: I.m. injections with Botox (BTX) leads to a paralysis of the muscles, resulting in a rapid loss of muscle and bone mass (disuse osteoporosis). Adipocytes and osteoblasts derive from the same mesenchymal stem cell, and commitment to one linage represses commitment to the other. Furthermore, the existence of a close communication between bone cells and endothelial cells is widely accepted.
The purpose of the study was to quantify the changes in adiposity and vasculature in disuse osteopenic rats with and without treatment with the bisphosphonate zoledronate (Zln).
Materials and methods: Sixty female Wistar rats were randomized into five groups. One group served as baseline, while two groups were injected with BTX in the right hind-limb and two groups with saline. Zln was given to one BTX and one saline group. After 6 weeks the animals were sacrificed. Subsequently, the distal femora were μCT scanned, and the proximal femoral bone strength was determined with mechanical testing. Finally, a histological quantification of the bone marrow adiposity and vascularity was performed on the proximal tibial and distal femoral metaphyses. All procedures were approved by the Danish Animal Experiments Inspectorate.
Results: BTX resulted in lower BV/TV (−32.2%, P<0.01) and bone strength (−17.1%, P<0.05), and higher bone marrow adiposity in the tibia (247%, P<0.05) and femur (1511%, P<0.05). Zln prevented loss of BV/TV (67.2%, P<0.001) and bone strength (20.5%, P<0.05) and significantly attenuated (−64.4%, P<0.05) the BTX-induced increase in adiposity. Furthermore, the vascularity of the tibia was significantly higher (43.5%, P<0.01) in the BTX-Zln group compared to the BTX group.
Conclusion: BTX-induced disuse osteopenia resulted in a significant increase in bone marrow adiposity, whereas it did not affect the vasculature. The BTX-induced increase in adiposity was significantly reduced by treatment with Zln. No antiangiogenic effect of Zln on the bone marrow was found.
17 - 20 May 2014
European Calcified Tissue Society