title: Effects of hormonal conditions and drugs on both muscle and bone strength can be assessed in a single rat test.
abstract: Strength of both muscles and bone are important for fracture prevention in osteoporotic individuals. Therefore, drugs that are preclinically tested in animals for preventing or treating osteoporosis, and reducing fracture risk, should not only be checked for their effects on bone strength, but also for those on muscle strength. We developed a rat model to measure both in the same animal, using a single test. The model is based on an in vivo, ventral three-point bending test of the lower leg (Nordsletten L. and Ekeland A. J Orthop Res 11:299-304; 1993). This model was developed to test the contribution of triceps surae muscle contraction to the strength of the tibia. We hypothesized that this same test can be applied to determine bone and muscle strength independently, in an absolute sense. To investigate this possibility, the muscle contribution to bone stresses was estimated from mechanical analyses, based on direct assessment of muscle strength in a separate test. Sixteen mature female Wistar rats were used, half of which were ovariectomized. After 12 weeks, the rats were tested in vivo in three-point bending of the right lower leg during muscle contraction, and then the isolated triceps surae muscle strength in the left lower leg was measured separately, in another model. The rats were then killed, and the left nude shafts were tested mechanically in three-point bending in vitro to determine structural strength of the bone alone. Ultimate external bending moments of the in vivo and in vitro tests, maximal muscle force, and geometrical parameters formed the basis for the analysis. While contracting, the triceps surae loads the tibia in axial compression and bending. We found that the axial compressive stress on the bone due to muscle contraction was less than 2.5% of the bending stress this produced. This indicates that muscle contribution to lower leg strength is due almost entirely to the bending moment it produces, counteracting the external moment put on the leg by the testing device. Thus, the difference between the in vivo (lower leg) and in vitro (nude tibia) failure bending moments is approximately equal to the maximal muscle bending moment. This information can be applied to test the effects of hormonal conditions and drugs on both muscle and bone strength independently, in a single rat test, using the aforementioned procedure.
authors.affiliation: Institute for Surgical Research and Center of Orthopaedics, National Hospital, Oslo, Norway. t.s.kaastad@ioks.uio.no
authors.forename: T S
authors.initials: TS
authors.lastname: Kaastad
authors.forename: R
authors.initials: R
authors.lastname: Huiskes
authors.forename: O
authors.initials: O
authors.lastname: ReikerAs
authors.forename: L
authors.initials: L
authors.lastname: Nordsletten
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D010024:Osteoporosis / Q000503:physiopathology; D010052:Ovariectomy; D010525:Peripheral Nerves / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013977:Tibia / Q000502:physiology*; D013978:Tibial Fractures / Q000503:physiopathology*; D015430:Weight Gain; D016474:Weight-Bearing
chemical_list: D012739:Gonadal Steroid Hormones