Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt antagonist that inhibits bone formation. We hypothesized that inhibiting sclerostin would prevent development of bone disease and increase resistance to fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1-eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was associated with a decrease in fracture resistance in the vertebrae. Treatment with anti-sclerostin antibody increased osteoblast numbers and bone formation rate but did not inhibit bone resorption or reduce tumor burden. Treatment with anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic bone lesions, and increased fracture resistance. Treatment with anti-sclerostin antibody and zoledronic acid combined increased bone mass and fracture resistance when compared with treatment with zoledronic acid alone. This study defines a therapeutic strategy superior to the current standard of care that will reduce fractures for patients with MM

BackgroundAnkle-foot orthoses (AFO) are prescribed to manage difficulty walking due to foot drop, bony foot deformities and poor balance. Traditional AFOs are handmade using thermoplastic vacuum forming which provides limited design options, is labour-intensive and associated with long wait times. 3D printing has the potential to transform AFO production and health service delivery. The aim of this systematic review was to determine the feasibility of designing, manufacturing and delivering customised 3D printed AFOs by evaluating the biomechanical outcomes, mechanical properties and fit of 3D printed compared to traditionally manufactured AFOs.MethodElectronic databases were searched from January 1985 to June 2018 according to terms related to 3D printing and AFOs. Studies of any design from healthy or pathological populations of any age were eligible for inclusion. Studies must have investigated the effect of customised 3D printed AFOs using any 3D printing technique on outcomes related to walking ability, biomechanical function, mechanical properties, patient comfort, pain and disability. Any other orthotic type or AFOs without a 3D printed calf and foot section were excluded. The quality of evidence was assessed using the GRADE process.ResultsEleven studies met the eligibility criteria evaluating 3D printed AFOs in healthy adults, and adults and children with unilateral foot drop from a variety of conditions. 3D printing was used to replicate traditional AFOs and develop novel designs to optimise the stiffness properties or reduce the weight and improve the ease of use of the AFO. 3D printed custom AFOs were found to be comparable to traditional custom AFOs and prefabricated AFOs in terms of temporal-spatial parameters. The mechanical stiffness and energy dissipation of 3D printed AFOs were found to be similar to prefabricated carbon-fibre AFOs. However, the sample sizes were small (n = 1 to 8) and study quality was generally low.ConclusionThe biomechanical effects and mechanical properties of 3D printed AFOs were comparable to traditionally manufactured AFOs. Developing novel AFO designs using 3D printing has many potential benefits including stiffness and weight optimisation to improve biomechanical function and comfort.Electronic supplementary materialThe online version of this article (10.1186/s13047-019-0321-6) contains supplementary material, which is available to authorized users.

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissuespecific lesions associated with local double-inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1. We used a Cre-expressing adenovirus (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts, and in vivo in the fracture callus of Nf1 flox/flox and Nf1 flox/À mice.

Biodegradable polymers are appealing material for the manufacturing of surgical implants as such implants break down in vivo, negating the need for a subsequent operation for removal. Many biocompatible polymers produce acidic breakdown products that can lead to localized inflammation and osteolysis. This study assesses the feasibility of fabricating implants out of poly(propylene carbonate) (PPC)-starch that degrades into CO and water. The basic compression modulus of PPC-starch (1:1 w/w) is 34 MPa; however, the addition of glycerol (1% w/w) and water as plasticizers doubles this value and enhances the surface wettability. The bioactivity and stiffness of PPC-starch blends is increased by the addition of bioglass microparticles (10% w/w) as shown by in vitro osteoblast differentiation assay and mechanical testing. MicroCT analysis confirms that the bioglass microparticles are evenly distributed throughout biomaterial. PPC-starch-bioglass was tested in vivo in two animal models. A murine subcutaneous pellet degradation assay demonstrates that the PPC-starch-bioglass blend's volume fraction loss is 46% after 6 months postsurgery, while it is 27% for poly(lactic acid). In a rat knee implantation model, PPC-starch-bioglass screws inserted into the distal femur show osseointegration with no localized adverse effects after 3 and 12 weeks. These data support the further development of PPC-starch-bioglass as a medical biomaterial.