Bone has long been known to be responsive to mechanical loading. For at least 25 years it has been known that osteocytes sense mechanical load, and because of their response to mechanical loading, osteocytes are believed to be the mechanosensory cell. The Wnt/β-catenin signaling pathway has been shown to be crucial in bone development. Mutations in LRP5 and SOST, which cause high bone mass, have increased interest in the Wnt pathway as a potential target for osteoporosis therapy and have helped link Wnt/β-catenin signaling to bone’s response to mechanical loading. Because of its specificity to osteocytes, the Wnt inhibitor sclerostin is a target for anabolic bone therapies. The response of bone to mechanical loading is critically regulated by osteocytes secreting sclerostin, which binds to Lrp5.

To treat periprosthetic fractures, bicortical screw placement should be attempted to maximize load to failure and torsional/sagittal bending stiffness.

Early loosening and implant migration are two problems that lead to failures in cementless (press-fit) femoral knee components of total knee replacements. To begin to address these early failures, this study determined the anterior-posterior mechanical properties from four locations in the human distal femur. Thirty-three cylindrical specimens were removed perpendicular to the press-fit surface after the surgical cuts on 10 human cadaveric femurs (age 71.5+/-14.2 years) had been made. Compression testing was performed that utilized methods to reduce the effects of end-artifacts. The bone mineral apparent density (BMAD), apparent modulus of elasticity, yield and ultimate stress, and yield and ultimate strain were measured for 28 cylindrical specimens. The apparent modulus, yield and ultimate stress, and yield and ultimate strain each significantly differed (p<0.05) in the superior and inferior locations. Linear and power law relationships between superior and inferior mechanical properties and BMAD were determined. The inferior apparent modulus and stresses were higher than those in the superior locations. These results show that the press-fit fixation characteristics of the femoral knee component differ on the anterior shield and posterior condyles. This information will be useful in the assignment of mechanical properties in finite element models for further investigations of femoral knee components. The property-density relations also have applications for implant design and preoperative assessment of bone strength using clinically available tools.

The failure of an osseous fracture to heal (development of a non-union) is a common and debilitating clinical problem. Mice lacking the tumor suppressor Pten in osteoblasts have dramatic and progressive increases in bone volume and density throughout life. Since fracture healing is a recapitulation of bone development, we investigated the process of fracture healing in mice lacking Pten in osteoblasts (Ocn-cretg/+;Ptenflox/flox). Mid-diaphyseal femoral fractures induced in wild-type and Ocn-cretg/+;Ptenflox/flox mice were studied via micro-computed tomography (µCT) scans, biomechanical testing, histological and histomorphometric analysis, and protein expression analysis. Ocn-cretg/+;Ptenflox/flox mice had significantly stiffer and stronger intact bones relative to controls in all cohorts. They also had significantly stiffer healing bones at day 28 post-fracture (PF) and significantly stronger healing bones at days 14, 21, and 28 PF. At day 7 PF, the proximal and distal ends of the Pten mutant calluses were more ossified. By day 28 PF, Pten mutants had larger and more mineralized calluses. Pten mutants had improved intramembranous bone formation during healing originating from the periosteum. They also had improved endochondral bone formation later in the healing process, after mature osteoblasts are present in the callus. Our results indicate that the inhibition of Pten can improve fracture healing and that the local or short-term use of commercially available Pten-inhibiting agents may have clinical application for enhancing fracture healing.