Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants.

Originally, leptin was described as a product of adipocytes that acts on the hypothalamus to regulate appetite. However, subsequently, it has been shown that leptin receptors are distributed widely and that leptin has diverse functions, including promotion of hemopoietic and osteoblastic differentiation. It has been recognized for some time that both serum leptin and bone mass are correlated positively to body fat mass and, recently, we have shown a direct positive relationship between serum leptin and bone mass in nonobese women. We now report that leptin inhibits osteoclast generation in cultures of human peripheral blood mononuclear cells (PBMCs) and murine spleen cells incubated on bone in the presence of human macrophage colony-stimulating factor (hM-CSF) and human soluble receptor activator of NF-κB ligand (sRANKL). The half-maximal concentration inhibitory of leptin was approximately 20 nM in the presence of sRANKL at 40 ng/ml but decreased to approximately 2 nM when sRANKL was used at 5 ng/ml. The majority of the inhibitory effect occurred in the first week of the 3-week cultures. Inhibition did not occur when the PBMC cultures were washed vigorously to remove nonadherent cells or when purified CD14+ monocytes were used to generate osteoclasts, indicating an indirect or permissive effect via CD14− PBMC. Leptin increased osteoprotegerin (OPG) messenger RNA (mRNA) and protein expression in PBMC but not in CD14+ cells, suggesting that the inhibitory effect may be mediated by the RANKL/RANK/OPG system. Leptin may act locally to increase bone mass and may contribute to linkage of bone formation and resorption.

Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%–70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management.

Absorption-contrast x-ray imaging serves to visualize the variation in x-ray attenuation within the volume of a given sample, whereas phase contrast allows one to visualize variations in x-ray refractive index. The former imaging mechanism has been well known and widely utilized since the time of Röntgen’s Nobel prize winning work, whereas the latter mechanism—sought for, but not found, by Röntgen himself—has laid the foundation for a revolution in x-ray imaging which is the central topic of this review. We consider the physical imaging mechanisms underlying both absorption contrast and phase contrast, together with the associated inverse problem of how one may obtain quantitative two- or three-dimensional information regarding a sample, given one or more phase-contrast images of the same. Practical questions are considered, regarding optimized phase-contrast imaging geometries as a function of detector resolution, source size, x-ray spectrum, and dose. Experimental examples pertaining to biomedical applications are given, and prospects for the future outlined.

Summary: Purpose: Posttraumatic epilepsy (PTE) occurs in a proportion of traumatic brain injury (TBI) cases, significantly compounding the disability, and risk of injury and death for sufferers. To date, predictive biomarkers for PTE have not been identified. This study used the lateral fluid percussion injury (LFPI) rat model of TBI to investigate whether structural, functional, and behavioral changes post‐TBI relate to the later development of PTE.Methods: Adult male Wistar rats underwent LFPI or sham injury. Serial magnetic resonance (MR) and positron emission tomography (PET) imaging, and behavioral analyses were performed over 6 months postinjury. Rats were then implanted with recording electrodes and monitored for two consecutive weeks using video–electroencephalography (EEG) to assess for PTE. Of the LFPI rats, 52% (n = 12) displayed spontaneous recurring seizures and/or epileptic discharges on the video‐EEG recordings.Key Findings: MRI volumetric and signal analysis of changes in cortex, hippocampus, thalamus, and amygdala, ¹⁸F‐fluorodeoxyglucose (FDG)–PET analysis of metabolic function, and behavioral analysis of cognitive and emotional changes, at 1 week, and 1, 3, and 6 months post‐LFPI, all failed to identify significant differences on univariate analysis between the epileptic and nonepileptic groups. However, hippocampal surface shape analysis using large‐deformation high‐dimensional mapping identified significant changes in the ipsilateral hippocampus at 1 week postinjury relative to baseline that differed between rats that would go onto become epileptic versus those who did not. Furthermore, a multivariate logistic regression model that incorporated the 1 week, and 1 and 3 month ¹⁸F‐FDG PET parameters from the ipsilateral hippocampus was able to correctly predict the epileptic outcome in all of the LFPI cases. As such, these subtle changes in the ipsilateral hippocampus at acute phases after LFPI may be related to PTE and require further examination.Significance: These findings suggest that PTE may be independent of major structural, functional, and behavioral changes induced by TBI, and suggest that more subtle abnormalities are likely involved. However, there are limitations associated with studying acquired epilepsies in animal models that must be considered when interpreting these results, in particular the failure to detect differences between the groups may be related to the limitations of properly identifying/separating the epileptic and nonepileptic animals into the correct group.

Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (RANKL)–stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG–treated tumor-naïve mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence caused by 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.