Shaocheng Ma

Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties

Osteoporosis is characterised by trabecular bone loss resulting from increased osteoclast activation and unbalanced coupling between resorption and formation, which induces a thinning of trabeculae and trabecular perforations. Bisphosphonates are the frontline therapy for osteoporosis, which act by reducing bone remodelling, and are thought to prevent perforations and maintain microstructure. However, bisphosphonates may oversuppress remodelling resulting in accumulation of microcracks. This paper aims to investigate the effect of bisphosphonate treatment on microstructure and mechanical strength. Assessment of microdamage within the trabecular bone core was performed using synchrotron X-ray micro-CT linked to image analysis software. Bone from bisphosphonate-treated fracture patients exhibited fewer perforations but more numerous and larger microcracks than both fracture and non-fracture controls. Furthermore, bisphosphonate-treated bone demonstrated reduced tensile strength and Young’s Modulus. These findings suggest that bisphosphonate therapy is effective at reducing perforations but may also cause microcrack accumulation, leading to a loss of microstructural integrity and consequently, reduced mechanical strength.

Synchrotron Imaging Assessment of Bone Quality

Bone is a complex hierarchical structure, and its principal function is to resist mechanical forces and fracture. Bone strength depends not only on the quantity of bone tissue but also on the shape and hierarchical structure. The hierarchical levels are interrelated, especially the micro-architecture, collagen and mineral components; hence, analysis of their specific roles in bone strength and stiffness is difficult. Synchrotron imaging technologies including micro-CT and small/wide angle X-ray scattering/diffraction are becoming increasingly popular for studying bone because the images can resolve deformations in the micro-architecture and collagen–mineral matrix under in situ mechanical loading. Synchrotron cannot be directly applied in vivo due to the high radiation dose but will allow researchers to carry out systematic multifaceted studies of bone ex vivo. Identifying characteristics of aging and disease will underpin future efforts to generate novel devices and interventional therapies for assessing and promoting healthy aging. With our own research work as examples, this paper introduces how synchrotron imaging technology can be used with in situ testing in bone research.

Laparoscopic vs open hepatectomy for hepatocellular carcinoma in patients with cirrhosis: A meta-analysis of the long-term survival outcomes

BACKGROUND In patients with hepatocellular carcinoma (HCC) and cirrhosis, laparoscopic hepatectomy (LH) confers short-term benefits over open hepatectomy (OH) but the long-term outcomes of this procedure are unclear. This systematic review aims to compare the long-term survival outcomes of LH and OH for patients with HCC and underlying cirrhosis. METHODS EMBASE, MEDLINE and Scopus databases were searched from date of inception to 7th October 2016. Controlled clinical studies comparing LH to OH for HCC in cirrhotic patients, which reported long-term overall and disease-free survival were included. The studies were evaluated using the MOOSE guidelines and Newcastle-Ottawa Scale. Data were extracted and analysed using a fixed-effects model. RESULTS Five non-randomised, retrospective observational studies representing 888 patients were included. LH was associated with significantly lower tumour recurrence [OR: 0.65, 95% CI: 0.48, 0.89]. LH conferred greater overall survival at 1- [HR: 0.41, 95% CI: 0.25, 0.68], 3- [HR: 0.63, 95% CI: 0.46, 0.87] and 5-years [HR: 0.60, 95% CI: 0.45, 0.80]. With LH, there was higher disease-free survival at 1-year [HR: 0.71, 95% CI: 0.53, 0.96], but not at 3- [HR: 0.89, 95% CI: 0.70, 1.14]; and 5-years [HR: 0.85, 95% CI: 0.70, 1.04]. CONCLUSIONS Laparoscopic surgery is associated with comparable postoperative and survival outcomes in patients with HCC and underlying cirrhosis. With careful selection of patients, this approach is safe, feasible and advantageous.

Microindentation – a tool for measuring cortical bone stiffness?: A systematic review

Objectives Microindentation has the potential to measure the stiffness of an individual patient’s bone. Bone stiffness plays a crucial role in the press-fit stability of orthopaedic implants. Arming surgeons with accurate bone stiffness information may reduce surgical complications including periprosthetic fractures. The question addressed with this systematic review is whether microindentation can accurately measure cortical bone stiffness. Methods A systematic review of all English language articles using a keyword search was undertaken using Medline, Embase, PubMed, Scopus and Cochrane databases. Studies that only used nanoindentation, cancellous bone or animal tissue were excluded. Results A total of 1094 abstracts were retrieved and 32 papers were included in the analysis, 20 of which used reference point indentation, and 12 of which used traditional depth-sensing indentation. There are several factors that must be considered when using microindentation, such as tip size, depth and method of analysis. Only two studies validated microindentation against traditional mechanical testing techniques. Both studies used reference point indentation (RPI), with one showing that RPI parameters correlate well with mechanical testing, but the other suggested that they do not. Conclusion Microindentation has been used in various studies to assess bone stiffness, but only two studies with conflicting results compared microindentation with traditional mechanical testing techniques. Further research, including more studies comparing microindentation with other mechanical testing methods, is needed before microindentation can be used reliably to calculate cortical bone stiffness. Cite this article: M. Arnold, S. Zhao, S. Ma, F. Giuliani, U. Hansen, J. P. Cobb, R. L. Abel, O. Boughton. Microindentation – a tool for measuring cortical bone stiffness? A systematic review. Bone Joint Res 2017;6:542–549. DOI: 10.1302/2046-3758.69.BJR-2016-0317.R2.

Joint distraction for knee osteoarthritis: protocol for a systematic review and meta-analysis

BackgroundOsteoarthritis is a degenerative joint disease that is highly prevalent worldwide. Knee osteoarthritis is the most common form of osteoarthritis and is a major cause of pain and disability. However, there remains a lack of treatments available that have demonstrated effectiveness in stopping or reversing the degenerative process. Joint distraction has emerged as a viable alternative in the treatment of knee osteoarthritis to delay the need for knee arthroplasty.MethodsAn electronic search will be conducted on MEDLINE, EMBASE, Web of Science, CINAHL, Cochrane and EBSCO databases. Clinical studies investigating joint distraction for knee osteoarthritis, which reported clinical or structural outcomes including ∆WOMAC index, ∆VAS pain score and ∆joint space width will be included. Risk of bias will be assessed using the Newcastle-Ottawa Scale for observational studies and Cochrane Collaboration tool for randomised controlled trials. Quality of studies will be assessed using the modified Coleman methodology score.DiscussionThis systematic review will summarise the short- and long-term clinical and structural outcomes following joint distraction for knee osteoarthritis. The findings from this review will establish the quality of currently available evidence, which will determine the need for further studies to establish the true effect size of this procedure.Systematic review registrationPROSPERO CRD42018087032

Measuring bone stiffness using spherical indentation

Objectives Bone material properties are a major determinant of bone health in older age, both in terms of fracture risk and implant fixation, in orthopaedics and dentistry. Bone is an anisotropic and hierarchical material so its measured material properties depend upon the scale of metric used. The scale used should reflect the clinical problem, whether it is fracture risk, a whole bone problem, or implant stability, at the millimetre-scale. Indentation, an engineering technique involving pressing a hard-tipped material into another material with a known force, may be able to assess bone stiffness at the millimetre-scale (the apparent elastic modulus). We aimed to investigate whether spherical-tip indentation could reliably measure the apparent elastic modulus of human cortical bone. Materials and methods Cortical bone samples were retrieved from the femoral necks of nineteen patients undergoing total hip replacement surgery (10 females, 9 males, mean age: 69 years). The samples underwent indentation using a 1.5 mm diameter, ruby, spherical indenter tip, with sixty indentations per patient sample, across six locations on the bone surfaces, with ten repeated indentations at each of the six locations. The samples then underwent mechanical compression testing. The repeatability of indentation measurements of elastic modulus was assessed using the co-efficient of repeatability and the correlation between the bone elastic modulus measured by indentation and compression testing was analysed by least-squares regression. Results In total, 1140 indentations in total were performed. Indentation was found to be repeatable for indentations performed at the same locations on the bone samples with a mean co-efficient of repeatability of 0.4 GigaPascals (GPa), confidence interval (C.I): 0.33–0.42 GPa. There was variation in the indentation modulus results between different locations on the bone samples (mean co-efficient of repeatability: 3.1 GPa, C.I: 2.2–3.90 GPa). No clear correlation was observed between indentation and compression values of bone elastic modulus (r = 0.33, p = 0.17). The mean apparent elastic modulus obtained by spherical indentation was 9.9 GPa, the standard deviation for each indent cycle was 0.11 GPa, and the standard deviation between locations on the same sample was 1.01 GPa. The mean compression apparent elastic modulus was 4.42 GPa, standard deviation 1.02 GPa. Discussion Spherical-tip indentation was found to be a repeatable test for measuring the elastic modulus of human cortical bone, demonstrated by a low co-efficient of repeatability in this study. It could not, however, reliably predict cortical bone elastic modulus determined by platens compression testing in this study. This may be due to indentation only probing mechanical properties at the micro-scale while platens compression testing assesses millimetre length-scale properties. Improvements to the testing technique, including the use of a larger diameter spherical indenter tip, may improve the measurement of bone stiffness at the millimetre scale and should be investigated further.

Standardizing compression testing for measuring the stiffness of human bone

Objectives The ability to determine human bone stiffness is of clinical relevance in many fields, including bone quality assessment and orthopaedic prosthesis design. Stiffness can be measured using compression testing, an experimental technique commonly used to test bone specimens in vitro. This systematic review aims to determine how best to perform compression testing of human bone. Methods A keyword search of all English language articles up until December 2017 of compression testing of bone was undertaken in Medline, Embase, PubMed, and Scopus databases. Studies using bulk tissue, animal tissue, whole bone, or testing techniques other than compression testing were excluded. Results A total of 4712 abstracts were retrieved, with 177 papers included in the analysis; 20 studies directly analyzed the compression testing technique to improve the accuracy of testing. Several influencing factors should be considered when testing bone samples in compression. These include the method of data analysis, specimen storage, specimen preparation, testing configuration, and loading protocol. Conclusion Compression testing is a widely used technique for measuring the stiffness of bone but there is a great deal of inter-study variation in experimental techniques across the literature. Based on best evidence from the literature, suggestions for bone compression testing are made in this review, although further studies are needed to establish standardized bone testing techniques in order to increase the comparability and reliability of bone stiffness studies. Cite this article: S. Zhao, M. Arnold, S. Ma, R. L. Abel, J. P. Cobb, U. Hansen, O. Boughton. Standardizing compression testing for measuring the stiffness of human bone. Bone Joint Res 2018;7:524–538. DOI: 10.1302/2046-3758.78.BJR-2018-0025.R1.