Recommendations for High-resolution Peripheral Quantitative Computed Tomography Assessment of Bone Density, Microarchitecture, and Strength in Pediatric Populations.

PURPOSE OF REVIEW: The purpose of this review is to summarize current approaches and provide recommendations for imaging bone in pediatric populations using high-resolution peripheral quantitative computed tomography (HR-pQCT). RECENT FINDINGS: Imaging the growing skeleton is challenging and HR-pQCT protocols are not standardized across centers. Adopting a single-imaging protocol for all studies is unrealistic; thus, we present three established protocols for HR-pQCT imaging in children and adolescents and share advantages and disadvantages of each. Limiting protocol variation will enhance the uniformity of results and increase our ability to compare study results between different research groups. We outline special cases along with tips and tricks for acquiring and processing scans to minimize motion artifacts and account for growing bone. The recommendations in this review are intended to help researchers perform HR-pQCT imaging in pediatric populations and extend our collective knowledge of bone structure, architecture, and strength during the growing years.

Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model.

Despite evidence that deregulated Notch signalling is a master regulator of multiple myeloma (MM) pathogenesis, its contribution to myeloma bone disease remains to be resolved. Notch promotes survival of human MM cells and triggers human osteoclast activity in vitro. Here, we show that inhibition of Notch through the γ-secretase inhibitor XII (GSI XII) induces apoptosis of murine MOPC315.BM myeloma cells with high Notch activity. GSI XII impairs murine osteoclast differentiation of receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 cells in vitro. In the murine MOPC315.BM myeloma model GSI XII has potent anti-MM activity and reduces osteolytic lesions as evidenced by diminished myeloma-specific monoclonal immunoglobulin (Ig)-A serum levels and quantitative assessment of bone structure changes via high-resolution microcomputed tomography scans. Thus, we suggest that Notch inhibition through GSI XII controls myeloma bone disease mainly by targeting Notch in MM cells and possibly in osteoclasts in their microenvironment. We conclude that Notch inhibition is a valid therapeutic strategy in MM.

Examining the influence of short-term implantation on oxidative degradation in retrieved highly crosslinked polyethylene tibial components.

Concerns remain regarding the oxidative resistance of highly crosslinked polyethylene (PE). The study investigated the in vivo performance of Durasul highly crosslinked PE by comparing the oxidation index, density, and percent crystallinity in the weightbearing and nonweightbearing region of retrieved components with unused time zero tibial components. Retrieved and unused Sulene conventional PE tibial components were examined for comparison and the effects of shelf age, in vivo duration, and ex vivo duration were also investigated. The oxidation index was not significantly different between unused time zero and retrieved Durasul PE components. Regression analysis data supported these findings in that neither shelf age, in vivo duration, nor ex vivo duration was a significant predictor of oxidation index in the retrieved Durasul PE components. In contrast, the retrieved conventional PE components had significantly greater oxidation index, density, and percent crystallinity compared with unused time zero PE components. Regression data suggested that in vivo and ex vivo duration, but not shelf aging, influenced the changes observed in the conventional PE components. These data also showed that in vivo loading did not significantly affect the oxidation index, density, or percent crystallinity in either the retrieved Durasul or conventional PE tibial components. This investigation demonstrates that changes in oxidation index, density, and percent crystallinity of retrieved Durasul PE components after short-term in vivo durations are likely not a clinical concern. These data should be used as a benchmark to compare with future studies examining the long-term oxidative resistance of Durasul highly crosslinked PE tibial components.

Surface damage analysis of retrieved highly crosslinked polyethylene tibial components after short-term implantation.

The use of highly crosslinked polyethylene (PE) in the knee remains controversial, because of reduced fatigue fracture properties of the material. The current study investigated postmelt surface damage as well as potential contributors to this damage in retrieved highly crosslinked PE tibial components, after short-term in vivo durations. Retrieved conventional PE tibial components were examined for comparison, as well as unused time zero highly crosslinked and conventional PE tibial components for inherent manufacturing surface characterization. Predominant surface damage modes on highly crosslinked PE components were machine mark loss and abrasion, while conventional PE components primarily had machine mark loss, abrasion, and delamination. In vivo duration, PE thickness, and conformity of the design were significant predictors of surface damage on retrieved conventional PE components. Donor weight and the conformity of the design were significant predictors of surface damage on retrieved highly crosslinked PE components. This retrieval data on highly crosslinked PE tibial components suggest that in vivo wear occurred, observed as postmelt surface damage. The highly crosslinked Durasul material examined in this retrieval study appeared to outperform the conventional PE components made from 4150 resin, ram-extruded and gamma-sterilized in air, but not the conventional components made from 1020 resin, compression molding and gamma sterilization in nitrogen. Early retrieval data of highly crosslinked PE tibial components are important to serve as a benchmark to be compared with future longer-term retrieval studies investigating whether surface damage translates to clinically relevant particulate wear debris generation and PE clinical performance.

Relationship between bone ingrowth, mineral apposition rate, and osteoblast activity.

To better understand skeletal attachment of porous coated total hip and knee implants over time, this study investigated the dynamics of osteoblast populations at the interface of porous coated implants in a weight-bearing ovine model. The relationship between cancellous bone ingrowth, mineral apposition rate (MAR), and osteoblast activity indicators such as osteoblast area, relative osteoblast number, osteoid width, and osteoid area (O.Ar.) were investigated. The data demonstrated that the percent O.Ar. was a marginally significant predictor of bone ingrowth and MAR over time, suggesting that the amount of osteoid present influenced bone ingrowth and MAR in the porous coated implants. The data also demonstrated that all osteoblast activity indicators were significantly greater in the porous coated region compared to the host bone region, while controlling for in situ time (p < 0.05). This may have been due to the trauma of implantation or the influence of the implant load on the bone tissue promoting a regional acceleratory phenomenon. The localized response suggests that specific therapies may be developed to affect the physiology of osteoblasts at the interface of implants, which may allow for improve skeletal attachment of biomaterials and clinical outcomes of cementless joint replacements.

Possible explanation for the white band artifact seen in clinically retrieved polyethylene tibial components.

Studies have focused attention on the appearance of a subsurface white band in clinically retrieved polyethylene components and the possible contribution of this phenomenon to early polyethylene delamination. Unconsolidated polyethylene particles and oxidation have been suggested as possible reasons for the appearance of the white band. Calcium stearate and other additives used in processing ultra-high molecular weight polyethylene may also contribute to formation of the white band. A quantitative investigation was conducted on 11 retrieved tibial components that exhibited a subsurface white band to determine whether the amount of calcium stearate particles and additives were greater in the white band region when compared with the mid-portion of the same section of polyethylene. Calcium stearate particles and other additives were quantified using backscattered electron imaging with correlated elemental analysis. The particles were identified based on morphology and elemental patterns similar to reference calcium stearate particles and known additives. Significantly more (p < 0. 0001) calcium stearate particles and additives were present in the white band region (4578 +/- 418 particles/mm(2); mean +/- standard error) than the mid-portion region (1250 +/- 147 particles/mm(2)) of the sectioned tibial inserts. The percent area occupied by calcium stearate particles and additives was five times higher (p < 0.0001) within the white band region (0.81 +/- 0.10%) than the mid-portion region (0.16 +/- 0.03%). The increased presence of calcium stearate and other additives in the white band region suggests that they may play a role in the formation of the white band. In future investigations it may be important to consider how calcium stearate and other additives in polyethylene resins affect white band formation and the possible contribution to crazing, early delamination, and osteolysis in total joint replacement.

Elemental and morphological identification of third-body particulate and calcium stearate inclusions in polyethylene components.

Third-body particulate such as human bone chips, hydroxyapatite, and bone cement are considered contributing factors in accelerated wear in total joint replacement. Particulate wear debris is now considered the major contributing factor in aseptic loosening of total joint replacements. The ability to distinguish between different third-body particulate is necessary to better understand wear mechanisms when conducting implant retrieval analysis. The objective of this investigation is to demonstrate that backscattered electron imaging with correlated energy dispersive X-ray analysis can accurately identify third-body particulate in retrieved polyethylene components. It is important that this technique can also distinguish between third-body particulate and normal inclusions in the polyethylene such as calcium stearate, based on the distinct morphology and elemental composition of each material. Therefore, the ability to distinguish third-body particulate from calcium stearate inclusions is essential in gaining a better understanding of the contributing factors associated with coating separation and accelerated wear observed in clinically retrieved polyethylene components.