Modal Frequencies Associations with Musculoskeletal Components of Human Legs for Extracorporeal Bone Healing Assessment Based on a Vibration Analysis Approach

Reliable and quantitative assessments of bone quality and fracture healing prompt well-optimised patient healthcare management and earlier surgical intervention prior to complications of nonunion and malunion. This study presents a clinical investigation on modal frequencies associations with musculoskeletal components of human legs by using a prototype device based on a vibration analysis method. The findings indicated that the first out-of-plane and coupled modes in the frequency range from 60 to 110 Hz are associated with the femur length, suggesting these modes are suitable quantitative measures for bone evaluation. Furthermore, higher-order modes are shown to be associated with the muscle and fat mass of the leg. In addition, mathematical models are formulated via a stepwise regression approach to determine the modal frequencies using the measured leg components as variables. The optimal models of the first modes consist of only femur length as the independent variable and explain approximately 43% of the variation of the modal frequencies. The subsequent findings provide insights for further development on utilising vibration-based methods for practical bone and fracture healing monitoring.

Teriparatide in fracture healing: Case series and review of literature

Teriparatide (TPTD) (recombinant Parathyroid Hormone 1-34) is one of the pioneer osteo-anabolic agents approved for management of osteoporosis. Being an anabolic agent, it increases bone mineral density by inducing formation of new bone by the action on osteoblasts. As new bone formation is an important aspect of fracture healing as well, Teriparatide has long been a product of interest with respect to its effect on the process of fracture healing. Though fracture healing is not an approved indication for Teriparatide, there is quite a substantial amount of published data related to its effectiveness in fracture healing. With an intent to better understand the role of teriparatide in fracture, we share few case reports of successful fracture healing after giving Teriparatide and also review the published evidences of union taking place in difficult delayed union and non-union cases secondary to mechanical instability, inadequate fixation support or other reasons. This article thus, intended to summarize the accumulating preclinical and clinical evidence for role of TPTD in accelerating fracture healing in various conditions like conservative management of fractures, vertebral fractures, non-unions, delayed unions and atypical femoral fractures.

Microbial healing of nature-like rough sandstone fractures for rock weathering mitigation

Rock weathering fractures in nature are complex and fracture healing is an effective strategy for rock weathering mitigation. This study is a first attempt to apply microbially induced calcium carbonate precipitation (MICP) technology in the healing of nature-weathering-like rough fractures (NWLRF). Sandstone was studied as an example due to it is a wide-spread construction, sculpture and monuments material all over the world. In order to achieve a high healing efficiency, a repeated mixture injection strategy was proposed. Based on a series of laboratory MICP injection experiments on four types of NWLRF, we systematically explored the fundamental micro-healing mechanism and the influence of factors including fracture aperture, characteristics of branch fractures, and cementation solution concentration. Experimental results demonstrated that MICP healing with the repeated mixture injection strategy had the ability to efficiently heal the penetrated NWLRF well with length in centimeter-scale and aperture in millimeter-scale, but cannot heal the non-penetrated branch fractures under low injection pressure. The repeated mixture injection strategy furtherly achieved a high apparent fracture healing ratio and a significant reduction of transmissivity. The apparent fracture healing ratios of all main fractures were higher than 80% and the maximum was 99.1%. Fracture transmissivity was reduced by at least three orders of magnitude from about 1×10-4 m2/s to less than 1×10-7 m2/s, and the highest reduction reached to four orders. For the aspect of the effects, larger cementation solution concentration, finer aperture and the existing of penetrated branch fracture were beneficial to improve the healing effect. Moreover, the MICP healing mechanism with high fracture healing ratio and significant reduction of transmissivity on sandstone NWLRF was also analyzed. The research results have important theoretical significance and technical guidance value for the disaster prevention and mitigation of rock weathering.

A Novel Mouse Model to Study Fracture Healing of Tibia

Background Delayed union of most tibial fractures due to their special anatomical structures.So an effective animal model is very important to study the mechanism and method of fracture healing.However, due to the small tibia of mice, the operation is difficult, and the surgical model requires high surgical skills. The construction of the fixation model of intramedullary nail for this fracture has improved and simplified the traditional fixation model of intramedullary nail, which not only achieves the purpose of constructing the fracture model, but also makes it more simple and effective.Therefore, the aim of the current study was to develop a new mouse model to study fracture healing of tibia. Methods We chose a combination between an open osteotomy and intramedullary stabilization. The 22G needle was inserted into the fracture end in a closed manner by using an open approach for osteotomy at the middle and lower 1/3 level of the tibia.Fractured tibia were analyzed using microcomputed tomography and histology at days 7,14,21and 28after surgery. All animals displayed normal limb loading and a physio-logical gait pattern within the first three days after fracture. No animals were lost due to surgery or anesthesia. Results X-ray confirmed that the fracture types obtained by the fracture modeling method were transverse fractures. X-ray, Micro-CT, immunohistochemistry, histological staining and Real-time PCR showed that the fracture healing of mice was typical endochondral ossification, with high repeatability. Conclusion The mouse tibial fracture model established by intramedullary nailing is safe, rapid and simple. Its fracture healing is a typical intrachondral ossification with high repeatability, which can be better used for the study of molecular mechanism and clinical transformation of fracture healing and bone metabolism.

Exogenous PTH 1-34 Attenuates Impaired Fracture Healing in Endogenous PTH Deficiency Mice via Activating Indian Hedgehog Signaling Pathway and Accelerating Endochondral Ossification

Fracture healing is a complicated, long-term, and multistage repair process. Intermittent administration of parathyroid hormone (PTH) has been proven effective on intramembranous and endochondral bone formation during the fracture healing process, however, the mechanism is unclear. In this study, we investigated the role of exogenous PTH and endogenous PTH deficiency in bone fracture healing and explored the mechanism by using PTH knockout (PTH-/-) mice and ATDC5 cells. In a mouse femur fracture model, endogenous PTH deficiency could delay endochondral ossification whereas exogenous PTH promotes accumulation of endochondral bone, accelerates cartilaginous callus conversion to bony callus, enhances maturity of bony callus, and attenuates impaired fracture healing resulting from endogenous PTH deficiency. In fracture callus tissue, endogenous PTH deficiency could inhibit chondrocyte proliferation and differentiation whereas exogenous PTH could activate the IHH signaling pathway to accelerate endochondral ossification and rescue impaired fracture healing resulting from endogenous PTH deficiency. In vitro, exogenous PTH promotes cell proliferation by activating IHH signaling pathway on ATDC5 cells. In mechanistic studies, by using ChIP and luciferase reporter assays, we showed that PTH could phosphorylate CREB, and subsequently bind to the promoter of IHH, causing the activation of IHH gene expression. Therefore, results from this study support the concept that exogenous PTH 1-34 attenuates impaired fracture healing in endogenous PTH deficiency mice via activating the IHH pathway and accelerating endochondral ossification. Hence, the investigation of the mechanism underlying the effects of PTH treatment on fracture repair might guide the exploration of effective therapeutic targets for fracture.