Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

The February 2024 Spine Roundup³⁶⁰ looks at: Surgeon assessment of bone – any good?; Robotics reduces radiation exposure in some spinal surgery; Interbody fusion cage versus anterior lumbar interbody fusion with posterior instrumentation; Is robotic-assisted pedicle screw placement an answer to the learning curve?; Acute non-traumatic spinal subarachnoid haematomas: a report of five cases and a systematic review of the literature; Is L4-L5 lateral interbody fusion safe and effective?

Aims

The aim of this study was to determine both the incidence of, and the reoperation rate for, postoperative periprosthetic femoral fracture (POPFF) after total hip arthroplasty (THA) with either a collared cementless (CC) femoral component or a cemented polished taper-slip (PTS) femoral component.

The December 2023 Oncology Roundup³⁶⁰ looks at: A single osteotomy technique for frozen autograft; Complications, function, and survival of tumour-devitalized autografts used in patients with limb-sparing surgery; Is liquid nitrogen recycled bone and vascular fibula the biological reconstruction of choice?; Solitary pulmonary metastases at first recurrence of osteosarcoma; Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?; Open versus core needle biopsy in lower-limb sarcoma – current practice patterns and patient outcomes; Natural history of intraosseous low-grade chondroid lesions of the proximal humerus; Local treatment modalities and event-free survival in patients with localized Ewing’s sarcoma; Awaiting biopsy results in solitary pathological proximal femoral fractures.

Aims

The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Aims

This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

Aims

This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.

Aims

Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism.

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Aims. To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. Methods. 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology. Results. iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111). Conclusion. iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res 2022;11(5):260–269

Aims

The role of N,N-dimethylformamide (DMF) in diabetes-induced osteoporosis (DM-OS) progression remains unclear. Here, we aimed to explore the effect of DMF on DM-OS development.

Aims

Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning.

Aims

Anchorage of pedicle screw rod instrumentation in the elderly spine with poor bone quality remains challenging. Our study aims to evaluate how the screw bone anchorage is affected by screw design, bone quality, loading conditions, and cementing techniques.

Aims. Type 2 diabetes mellitus (T2DM) impairs bone strength and is a significant risk factor for hip fracture, yet currently there is no reliable tool to assess this risk. Most risk stratification methods rely on bone mineral density, which is not impaired by diabetes, rendering current tests ineffective. CT-based finite element analysis (CTFEA) calculates the mechanical response of bone to load and uses the yield strain, which is reduced in T2DM patients, to measure bone strength. The purpose of this feasibility study was to examine whether CTFEA could be used to assess the hip fracture risk for T2DM patients. Methods. A retrospective cohort study was undertaken using autonomous CTFEA performed on existing abdominal or pelvic CT data comparing two groups of T2DM patients: a study group of 27 patients who had sustained a hip fracture within the year following the CT scan and a control group of 24 patients who did not have a hip fracture within one year. The main outcome of the CTFEA is a novel measure of hip bone strength termed the Hip Strength Score (HSS). Results. The HSS was significantly lower in the study group (1.76 (SD 0.46)) than in the control group (2.31 (SD 0.74); p = 0.002). A multivariate model showed the odds of having a hip fracture were 17 times greater in patients who had an HSS ≤ 2.2. The CTFEA has a sensitivity of 89%, a specificity of 76%, and an area under the curve of 0.90. Conclusion. This preliminary study demonstrates the feasibility of using a CTFEA-based bone strength parameter to assess hip fracture risk in a population of T2DM patients. Cite this article: Bone Joint J 2021;103-B(9):1497–1504

Aims

The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data.

Cite this article: Bone Joint Res 2020;9(11):798–807.

Aims

The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated. Cite this article: Bone Joint Res 2020;9(8):524–530

Aims

Cementless acetabular components rely on press-fit fixation for initial stability. In certain cases, initial stability is more difficult to obtain (such as during revision). No current study evaluates how a surgeon’s impaction technique (mallet mass, mallet velocity, and number of strikes) may affect component fixation. This study seeks to answer the following research questions: 1) how does impaction technique affect a) bone strain generation and deterioration (and hence implant stability) and b) seating in different density bones?; and 2) can an impaction technique be recommended to minimize risk of implant loosening while ensuring seating of the acetabular component?

Aims

Many biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots.

Aims

Accurate estimations of the risk of fracture due to metastatic bone disease in the femur is essential in order to avoid both under-treatment and over-treatment of patients with an impending pathological fracture. The purpose of the current retrospective in vivo study was to use CT-based finite element analyses (CTFEA) to identify a clear quantitative differentiating factor between patients who are at imminent risk of fracturing their femur and those who are not, and to identify the exact location of maximal weakness where the fracture is most likely to occur.

Aims

To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA.

Objectives

Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures.

Objectives

In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians.

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

Objectives. Advanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality. Methods. An in vitro model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence. Results. Treatment with AG and PM showed a significant decrease in AGE content versus control groups, as well as a significant decrease in the change in indentation distance, a reliable parameter for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05). Conclusions. The data suggest that AG and PM prevent AGE formation and subsequent biomechanical degradation in vitro. Modulation of AGEs may help to identify novel therapeutic targets to mitigate bone quality deterioration, especially deterioration due to ageing and in AGE-susceptible populations (e.g. diabetics). Cite this article: O. Abar, S. Dharmar, S. Y. Tang. The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone. Bone Joint Res 2018;7:105–110. DOI: 10.1302/2046-3758.71.BJR-2017-0135.R1

Aims

Hydroxyapatite coatings for uncemented fixation in total knee arthroplasty can theoretically provide a long-lasting biological interface with the host bone. The objective of this study was to test this hypothesis with propriety hydroxyapatite, peri-apatite, coated tibial components using component migration measured with radiostereometric analysis over two years as an indicator of long-term fixation.

Objectives. Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Methods. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results. BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm. 2. vs 6.55/cm. 2. vs 5.25/cm. 2. ). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusion. BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP-induced microcrack accumulation may be significant. Cite this article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R. Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density. Bone Joint Res 2017;6:602–609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1

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.

Objectives

Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.

Objectives

Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs.

Objectives

This investigation sought to advance the work published in our prior biomechanical study (Journal of Orthopaedic Research, 2016). We specifically sought to determine whether there are additional easy-to-measure parameters on plain radiographs of the proximal humerus that correlate more strongly with ultimate fracture load, and whether a parameter resembling the Dorr strength/quality characterisation of proximal femurs can be applied to humeri.

Objectives

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.

Objectives

Up to 40% of unicompartmental knee arthroplasty (UKA) revisions are performed for unexplained pain which may be caused by elevated proximal tibial bone strain. This study investigates the effect of tibial component metal backing and polyethylene thickness on bone strain in a cemented fixed-bearing medial UKA using a finite element model (FEM) validated experimentally by digital image correlation (DIC) and acoustic emission (AE).

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.

Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.

Objectives

The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity.

Aims

We aimed to assess the influence of ethnicity on the incidence of heterotopic ossification (HO) after total hip arthroplasty (THA).

There is an increased risk of fracture following osteoplasty of the femoral neck for cam-type femoroacetabular impingement (FAI). Resection of up to 30% of the anterolateral head–neck junction has previously been considered to be safe, however, iatrogenic fractures have been reported with resections within these limits. We re-evaluated the amount of safe resection at the anterolateral femoral head–neck junction using a biomechanically consistent model.

In total, 28 composite bones were studied in four groups: control, 10% resection, 20% resection and 30% resection. An axial load was applied to the adducted and flexed femur. Peak load, deflection at time of fracture and energy to fracture were assessed using comparison groups.

There was a marked difference in the mean peak load to fracture between the control group and the 10% resection group (p < 0.001). The control group also tolerated significantly more deflection before failure (p < 0.04). The mean peak load (p = 0.172), deflection (p = 0.547), and energy to fracture (p = 0.306) did not differ significantly between the 10%, 20%, and 30% resection groups.

Any resection of the anterolateral quadrant of the femoral head–neck junction for FAI significantly reduces the load-bearing capacity of the proximal femur. After initial resection of cortical bone, there is no further relevant loss of stability regardless of the amount of trabecular bone resected.

Based on our findings we recommend any patients who undergo anterolateral femoral head–neck junction osteoplasty should be advised to modify their post-operative routine until cortical remodelling occurs to minimise the subsequent fracture risk.

Cite this article: Bone Joint J 2015;97-B:1214–19.

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities.

Cite this article: Bone Joint Res 2015;4:105–116

Objectives

There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed.

This paper investigates whether cortical comminution and intra-articular involvement can predict displacement in distal radius fractures by using a classification that includes volar comminution as a separate parameter.

A prospective multicentre study involving non-operative treatment of distal radius fractures in 387 patients aged between 15 and 74 years (398 fractures) was conducted. The presence of cortical comminution and intra-articular involvement according to the Buttazzoni classification is described. Minimally displaced fractures were treated with immobilisation in a cast while displaced fractures underwent closed reduction with subsequent immobilisation. Radiographs were obtained after reduction, at 10 to 14 days and after union. The outcome measure was re-displacement or union.

In fractures with volar comminution (Buttazzoni type 4), 96% (53 of 55) displaced. In intra-articular fractures without volar comminution (Buttazzoni 3), 72% (84 of 117) displaced. In extra-articular fractures with isolated dorsal comminution (Buttazzoni 2), 73% (106 of 145) displaced while in non-comminuted fractures (Buttazzoni 1), 16 % (13 of 81 ) displaced.

A total of 32% (53 of 165) of initially minimally displaced fractures later displaced. All of the initially displaced volarly comminuted fractures re-displaced. Displacement occurred in 31% (63 of 205) of fractures that were still in good alignment after 10 to 14 days.

Regression analysis showed that volar and dorsal comminution predicted later displacement, while intra-articular involvement did not predict displacement. Volar comminution was the strongest predictor of displacement.

Cite this article: Bone Joint J 2014;96-B:978–83.

In 1999, we developed a technique for biological reconstruction after excision of a bone tumour, which involved using autografts of the bone containing the tumour treated with liquid nitrogen. We have previously reported the use of this technique in 28 patients at a mean follow up of 27 months (10 to 54).

In this study, we included 72 patients who underwent reconstruction using this technique. A total of 33 patients died and three were lost to follow-up, at a mean of 23 months (2 to 56) post-operatively, leaving 36 patients available for a assessment at a mean of 101 months 16 to 163) post-operatively. The methods of reconstruction included an osteo-articular graft in 16, an intercalary in 13 and, a composite graft with prosthesis in seven.

Post-operative function was excellent in 26 patients (72.2%), good in seven (19.4%), and fair in three (8.3%) according to the functional evaluation system of Enneking. No recurrent tumour occurred within the grafts. The autografts survived in 29 patients (80.6%), and the rates of survival at five and ten years were 86.1% and 80.6 %, respectively. Seven of 16 osteo-articular grafts (44%) failed because of fracture or infection, but all the composite and intercalary grafts survived.

The long-term outcomes of frozen autografting, particularly using composite and intercalary grafts, are satisfactory and thus represent a good method of treatment for patients with a sarcoma of bone or soft tissue.

Cite this article: Bone Joint J 2014;96-B:555–61.

We analysed the effects of commonly used medications on human osteoblastic cell activity in vitro, specifically proliferation and tissue mineralisation. A list of medications was retrieved from the records of patients aged > 65 years filed in the database of the largest health maintenance organisation in our country (> two million members). Proliferation and mineralisation assays were performed on the following drugs: rosuvastatin (statin), metformin (antidiabetic), metoprolol (β-blocker), citalopram (selective serotonin reuptake inhibitor [SSRI]), and omeprazole (proton pump inhibitor (PPI)). All tested drugs significantly stimulated DNA synthesis to varying degrees, with rosuvastatin 5 µg/ml being the most effective among them (mean 225% (sd 20)), compared with metformin 10 µg/ml (185% (sd 10)), metoprolol 0.25 µg/ml (190% (sd 20)), citalopram 0.05 µg/ml (150% (sd 10)) and omeprazole 0.001 µg/ml (145% (sd 5)). Metformin and metoprolol (to a small extent) and rosuvastatin (to a much higher extent) inhibited cell mineralisation (85% (sd 5)). Our results indicate the need to evaluate the medications prescribed to patients in terms of their potential action on osteoblasts. Appropriate evaluation and prophylactic treatment (when necessary) might lower the incidence and costs associated with potential medication-induced osteoporosis.

Cite this article: Bone Joint J 2013;95-B:1575–80.

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing.

A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague–Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology.

The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm^-2 (sd 7.63) vs 24.65 Nmm^-2 (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007).

Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Cite this article: Bone Joint J 2013;95-B:1263–8.

The lateral compartment is predominantly affected in approximately 10% of patients with osteoarthritis of the knee. The anatomy, kinematics and loading during movement differ considerably between medial and lateral compartments of the knee. This in the main explains the relative protection of the lateral compartment compared with the medial compartment in the development of osteoarthritis. The aetiology of lateral compartment osteoarthritis can be idiopathic, usually affecting the femur, or secondary to trauma commonly affecting the tibia. Surgical management of lateral compartment osteoarthritis can include osteotomy, unicompartmental knee replacement and total knee replacement. This review discusses the biomechanics, pathogenesis and development of lateral compartment osteoarthritis and its management.

Cite this article: Bone Joint J 2013;95-B:436–44.

Osteoporosis is common and the health and financial cost of fragility fractures is considerable. The burden of cardiovascular disease has been reduced dramatically by identifying and targeting those most at risk. A similar approach is potentially possible in the context of fragility fractures. The World Health Organization created and endorsed the use of FRAX, a fracture risk assessment tool, which uses selected risk factors to calculate a quantitative, patient-specific, ten-year risk of sustaining a fragility fracture. Treatment can thus be based on this as well as on measured bone mineral density. It may also be used to determine at-risk individuals, who should undergo bone densitometry. FRAX has been incorporated into the national osteoporosis guidelines of countries in the Americas, Europe, the Far East and Australasia. The United Kingdom National Institute for Health and Clinical Excellence also advocates its use in their guidance on the assessment of the risk of fragility fracture, and it may become an important tool to combat the health challenges posed by fragility fractures.

Previously, we showed that case-specific non-linear finite element (FE) models are better at predicting the load to failure of metastatic femora than experienced clinicians. In this study we improved our FE modelling and increased the number of femora and characteristics of the lesions. We retested the robustness of the FE predictions and assessed why clinicians have difficulty in estimating the load to failure of metastatic femora. A total of 20 femora with and without artificial metastases were mechanically loaded until failure. These experiments were simulated using case-specific FE models. Six clinicians ranked the femora on load to failure and reported their ranking strategies. The experimental load to failure for intact and metastatic femora was well predicted by the FE models (R² = 0.90 and R² = 0.93, respectively). Ranking metastatic femora on load to failure was well performed by the FE models (τ = 0.87), but not by the clinicians (0.11 < τ < 0.42). Both the FE models and the clinicians allowed for the characteristics of the lesions, but only the FE models incorporated the initial bone strength, which is essential for accurately predicting the risk of fracture. Accurate prediction of the risk of fracture should be made possible for clinicians by further developing FE models.

Stems improve the mechanical stability of tibial components in total knee replacement (TKR), but come at a cost of stress shielding along their length. Their advantages include resistance to shear, reduced tibial lift-off and increased stability by reducing micromotion. Longer stems may have disadvantages including stress shielding along the length of the stem with associated reduction in bone density and a theoretical risk of subsidence and loosening, peri-prosthetic fracture and end-of-stem pain. These features make long stems unattractive in the primary TKR setting, but often desirable in revision surgery with bone loss and instability. In the revision scenario, stems are beneficial in order to convey structural stability to the construct and protect the reconstruction of bony defects. Cemented and uncemented long stemmed implants have different roles depending on the nature of the bone loss involved.

This review discusses the biomechanics of the design of tibial components and stems to inform the selection of the component and the technique of implantation.

This prospective multicentre study was undertaken to determine whether the timing of the post-operative administration of bisphosphonate affects fracture healing and the rate of complication following an intertrochanteric fracture. Between August 2008 and December 2009, 90 patients with an intertrochanteric fracture who underwent internal fixation were randomised to three groups according to the timing of the commencement of risedronate treatment after surgery: Group A (from one week after surgery), Group B (from one month after surgery), and Group C (from three months after surgery). The radiological time to fracture healing was assessed as the primary endpoint, and the incidence of complications, including excessive displacement or any complication requiring revision surgery, as the secondary endpoint. The mean time to fracture healing post-operatively in groups A, B and C was 10.7 weeks (sd 4.4), 12.9 weeks (sd 6.2) and 12.3 weeks (sd 7.1), respectively (p = 0.420). At 24 weeks after surgery, all fractures had united, except six that had a loss of fixation. Functional outcomes at one year after surgery according to the Koval classification (p = 0.948) and the incidence of complications (p = 0.386) were similar in the three groups.

This study demonstrates that the timing of the post-operative administration of bisphosphonates does not appear to affect the rate of healing of an intertrochanteric fracture or the incidence of complications.

The June 2012 Research Roundup³⁶⁰ looks at: platelet-rich plasma; ageing, bone and mesenchymal stem cells; cytokines and the herniated intervertebral disc; ulcerative colitis, Crohn’s disease and anti-inflammatories; the effect of NSAIDs on bone healing; osteoporosis of the fractured hip; herbal medicine and recovery after acute muscle injury; and ultrasound and the time to fracture union.

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.

In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study.

The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.

Extensive limb lengthening may be indicated in achondroplastic patients who wish to achieve a height within the normal range for their population. However, increasing the magnitude of lengthening is associated with further complications particularly adjacent joint stiffness and fractures. We studied the relationship between the magnitude of femoral lengthening and callus pattern, adjacent joint stiffness and fracture of the regenerate bone in 40 femoral lengthenings in 20 achondroplastic patients. They were divided into two groups; group A had lengthening of less than 50% and group B of more than 50% of their initial femoral length. The patterns of radiological callus formation were classified according to shape, type and features. The incidence of callus features, knee stiffness and regenerate bone fracture were analysed in the two groups. Group B was associated with an increased incidence of concave, lateral and central callus shapes, adjacent joint and stiffness and fracture. Statistically, the incidence of stiffness in adjacent joints and regenerate bone fracture was significantly associated with the magnitude of lengthening.

We suggest that careful radiological assessment of the patterns of callus formation is a useful method for the evaluation and monitoring of regenerate bone.

Failure of fixation is a common problem in the treatment of osteoporotic fractures around the hip. The reinforcement of bone stock or of fixation of the implant may be a solution. Our study assesses the existing evidence for the use of bone substitutes in the management of these fractures in osteoporotic patients. Relevant publications were retrieved through Medline research and further scrutinised. Of 411 studies identified, 22 met the inclusion criteria, comprising 12 experimental and ten clinical reports. The clinical studies were evaluated with regard to their level of evidence. Only four were prospective and randomised.

Polymethylmethacrylate and calcium-phosphate cements increased the primary stability of the implant-bone construct in all experimental and clinical studies, although there was considerable variation in the design of the studies. In randomised, controlled studies, augmentation of intracapsular fractures of the neck of the femur with calcium-phosphate cement was associated with poor long-term results. There was a lack of data on the long-term outcome for trochanteric fractures. Because there were only a few, randomised, controlled studies, there is currently poor evidence for the use of bone cement in the treatment of fractures of the hip.

We review the treatment of pelvic Ewing’s sarcoma by the implantation of extracorporeally-irradiated (ECI) autografts and compare the outcome with that of other reported methods.

We treated 13 patients with ECI autografts between 1994 and 2004. There were seven males and six females with a median age of 15.7 years (interquartile range (IQR) 12.2 to 21.7). At a median follow-up of five years (IQR 1.8 to 7.4), the disease-free survival was 69% overall, and 75% if one patient with local recurrence after initial treatment elsewhere was excluded. Four patients died from distant metastases at a mean of 17 months (13 to 23). There were three complications which required operative intervention; one was a deep infection which required removal of the graft. The functional results gave a mean Musculoskeletal Tumor Society score of 85% (60% to 97%), a mean Toronto extremity salvage score of 86% (69% to 100%) and a mean Harris hip score of 92 (67 to 100).

We conclude that ECI grafting is a suitable form of treatment for localised and resectable pelvic Ewing’s sarcoma.

We matched 78 patients with a loose cemented Charnley Elite Plus total hip replacement (THR) by age, gender, race, prosthesis and time from surgery with 49 patients with a well-fixed stable hip replacement, to determine if poor bone quality predisposes to loosening. Clinical, radiological, biomechanical and bone mineral density indicators of bone quality were assessed.

Patients with loose replacements had more pain, were more likely to have presented with atrophic arthritis and to have a history of fragility fracture, narrower femoral cortices and lower peri-prosthetic or lumbar spine bone mineral density (all t-test, p < 0.01). They also tended to be smokers (chi-squared test, p = 0.08). Vitamin-D deficiency was common, but not significantly different between the two groups (t-test, p = 0.31)

In this series of cemented hip replacements performed between 1994 and 1998, aseptic loosening was associated with poor bone quality. Patients with a THR should be screened for osteoporosis and have regular radiological surveillance.

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 μg/kg; mid, 7.5 μg/kg and high 75 μg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction.

After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm³ over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae.

The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis.

We investigated several factors which affect the stability of cortical screws in osteoporotic bone using 18 femora from cadavers of women aged between 45 and 96 years (mean 76). We performed bone densitometry to measure the bone mineral density of the cortical and cancellous bone of the shaft and head of the femur, respectively. The thickness and overall bone mass of the cortical layer of the shaft of the femur were measured using a microCT scanner. The force required to pull-out a 3.5 mm titanium cortical bone screw was determined after standardised insertion into specimens of the cortex of the femoral shaft.

A significant correlation was found between the pull-out strength and the overall bone mass of the cortical layer (r² = 0.867, p < 0.01) and also between its thickness (r² = 0.826, p < 0.01) and bone mineral density (r² = 0.861, p < 0.01). There was no statistically significant correlation between the age of the donor and the pull-out force (p = 0.246), the cortical thickness (p = 0.199), the bone mineral density (p = 0.697) or the level of osteoporosis (p = 0.378).

We conclude that the overall bone mass, the thickness and the bone mineral density of the cortical layer, are the main factors which affect the stability of a screw in human female osteoporotic cortical bone.

Despite advances in the prevention and treatment of osteoporotic fractures, their prevalence continues to increase. Their operative treatment remains a challenge for the surgeon, often with unpredictable outcomes. This review highlights the current aspects of management of these fractures and focuses on advances in implant design and surgical technique.

We describe a method of reconstruction using tumour-bearing autograft treated by liquid nitrogen in 28 patients. The operative technique consisted of en bloc excision of the tumour, removal of soft tissue, curettage of the tumour, drilling and preparation for internal fixation or prosthetic replacement before incubation for 20 minutes in liquid nitrogen, thawing at room temperature for 15 minutes, thawing in distilled water for ten minutes, and internal fixation with an intramedullary nail, plate or composite use of prosthetic replacement. Bone graft or cement was used to augment bone strength when necessary. The limb function was rated as excellent in 20 patients (71.4%), good in three (10.7%), fair in three (10.7%), and poor in two (7.1%). At the final follow-up six patients had died at a mean of 19.8 months after the operation, while 21 remained free from disease with a mean follow-up of 28.1 months (10 to 54). One patient is alive with disease. Bony union was seen at a mean of 6.7 months after the operation in 26 patients. Complications were encountered in seven patients, including three deep infections, two fractures, and two local recurrences. All were managed successfully. Our results suggest that this is a simple and effective method of biological reconstruction

We aimed to highlight the relationship between age and the architectural properties of trabecular bone, to outline the patterns in which the variations in these properties take place, and to investigate the influence of the architecture on the mechanical properties of trabecular bone in growing animals. We studied 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. They were serially sectioned and their architectural properties were determined. Similar cubes were obtained from the identical anatomical position of the contralateral tibia and their compressive mechanical properties measured. The values obtained from the skeletally immature and mature individuals were compared. Multiple regression analyses were performed between the architectural and the mechanical properties. The bone volume fraction, the mean trabecular volume, the architectural and the mechanical anisotropy, the elastic modulus, the bone strength, the energy absorption to failure, and the elastic energy correlated positively with increasing age whereas the connectivity density, the bone surface density, the ultimate strain, the absorption of viscoelastic energy and the relative loss of energy correlated inversely. The values of all variables were significantly different in the skeletally mature and immature groups. We determined the patterns in which the variations took place. The bone volume fraction of the trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the mean trabecular volume and the bone surface density, it explained 81% of the variations in the compressive elastic modulus of specimens obtained from the contralateral tibiae

Our aim was to determine the relationship between age and the mechanical and physical properties of trabecular bone, to describe the patterns in which the variations in these properties take place, and to investigate the influence of the physical properties on the mechanical characteristics of trabecular bone during growth. We used 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. We performed non-destructive compression tests of the specimens in three orthogonal directions and compression tests to failure in the axial direction. The physical properties of the specimens were also determined. The data were correlated with age and compared in skeletally immature and mature animals. Multiple regression analyses were performed between the mechanical and the physical properties. Age correlated positively with elastic modulus, bone strength, energy absorption to failure, elastic energy, mechanical anisotropy ratio, tissue density, apparent density, apparent ash density, and bone mineral content, and inversely with ultimate strain, viscoelastic energy absorption, relative energy loss, the collagen content of bone and the percentage porosity. The values of all variables were significantly different in the skeletally mature and immature groups. The apparent density of trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the content of bone muscle and bone collagen, the apparent density could explain 84% of the variation in the elastic modulus, whereas only a small portion of the variation in ultimate strain could be explained by the variation in apparent density

Cancer-induced bone diseases are often associated with increased bone resorption and pathological fractures. In recent years, osteoprotective agents such as bisphosphonates have been studied extensively and have been shown to inhibit cancer-related bone resorption in experimental and clinical studies. The third-generation bisphosphonate, ibandronate (BM 21.0955), is a potent compound for controlling tumour osteolysis and hypercalcaemia in rats bearing Walker 256 carcinosarcoma. We have studied the effect of ibandronate given as an interventional treatment on bone strength and bone loss after the onset of tumour growth in bone. Our results suggest that it is capable of preserving bone quality in rats bearing Walker 256 carcinosarcoma cells. Since other bisphosphonates have produced comparable results in man after their success in the Walker 256 animal models our findings suggest that ibandronate may be a powerful treatment for maintaining skeletal integrity in patients with metastatic bone disease

There have been conflicting reports on the effects of gamma irradiation on the material properties of cortical allograft bone. To investigate changes which result from the method of preparation, test samples must be produced with similar mechanical properties to minimise variations other than those resulting from treatment. We describe a new method for the comparative measurement of bone strength using standard bone samples. We used 233 samples from six cadavers to study the effects of irradiation at a standard dose (28 kGy) alone and combined with deep freezing. We also investigated the effects of varying the dose from 6.8 to 60 kGy (n = 132). None of the treatments had any effect on the elastic behaviour of the samples, but there was a reduction in strength to 64% of control values (p < 0.01) after irradiation with 28 kGy. There was also a dose-dependent reduction in strength and in the ability of the samples to absorb work before failure. We suggest that irradiation may cause an alteration in the bone matrix of allograft bone, but provided it is used in situations in which loading is within its elastic region, then failure should not occur

We compared, under laboratory conditions, the resistance to cutting out of the AO dynamic hip screw and the Pugh sliding nail. The mean load at cut out, adjusted for bone strength, was 70% greater for the Pugh sliding nail. The reasons for this difference are discussed

One of the aims of this work was to find criteria by which the quality of bone as a supporting tissue might be judged. This inevitably involves discussion and, if possible, assessment, of the relative importance of the inorganic and organic material of the bone. It is relatively easy to measure the mineral content, and for that reason it has always received more than its due share of attention. In the present experiment the composition of the ash of all bones was remarkably constant, with a Ca/P ratio of 2. Furthermore, X-ray crystallography showed that the structure of the inorganic material was the same in all cases. The great difficulty of measuring variations in the quality of the organic material which is, of course, protein in nature makes it impossible to say how much it influences bone strength. Since at least 40 per cent. of the bone is collagen, either a quantitative or a qualitative alteration might alter bone strength. X-ray crystallography revealed no qualitative differences in the collagen material of bones of the three groups; so that for the present it would seem safer to assume that alterations in the physical properties of the bones are due to variations in the relative proportions of organic and inorganic constituents (Dawson 1946, Bell et al. 1947). These experiments show that the three diets produce highly significant differences in the percentage of ash, in S. B. , and in E. It is possible that some variations in the percentage of ash are due to variations in the absolute collagen (weight of collagen in unit volume of bone substance); but the range of variation in the percentage of ash leaves no reasonable doubt that differences in percentage ash between the diet groups are due essentially to differences in absolute ash. Presumably the collagen contributes something to the strength of the bone; but the indications are that it plays a minor part and that the relative weakness and flexibility of rachitic bones is due to decrease in the absolute ash content. Within any one diet group, the relation between percentage ash and the other two variables, S. B. and E, is masked by other sources of variation such as those associated with the many measurements involved; and thus the correlation between percentage ash and S. B. , and also between percentage ash and E, is not significant. At first sight, the scatter diagrams (Figs. 5 and 6) appear to indicate a correlation between ash and S. B. , and between ash and E. Closer inspection shows, however, that the apparent trend is due largely to differences between the means of the diet groups, and that the points within any one group show no such obvious trend. Figure 7 shows that the position with regard to correlation between S. B. and E is very different. Here there is an obvious trend within each diet group; the amount of scatter is very much less. Calculation shows that, even when the differences between the means of diet groups is excluded, there is still a significant correlation between S. B. and E. The question of the correlation between the three variables is discussed more fully in the addendum to this paper. Although the "goodness" of a bone is usually judged by its breaking stress, the experimental findings recorded above suggest that it may be assessed equally well on the basis of elastic properties as shown by Young's modulus. Normal bones, group S in these experiments, were elastic up to 79 per cent. of their breaking stress (Table II): the poorer bones of groups R and N were, however, only a little inferior in this respect. In some cases there was no apparent deviation of the load-deflexion curve from a straight line until the bone was about to break. Such a curve was published in the first paper of this series (Bell, Cuthbertson and Orr 1941), but in the light of further experience this curve is scarcely typical. The terminal falling over of the curve is illustrated in Figure 4 and is much more marked in the bones of group R. While stress at the upper limit of elasticity varies over a wide range in the three groups (Table II and Fig. 4), the strain at this point is remarkably constant at about 1·5 per cent. This same percentage displacement must occur between the molecules of the bone material at the elastic limit—and it may be that, up to this amount of molecular displacement, the deformation is reversible; but that beyond it, plastic changes occur. We have no evidence as to whether the limiting displacement concerns mineral or protein constituents of the bone, or both. We have already commented on the remarkable strength of bone material (Bell et al., 1941). The breaking stress of normal rat bone is about the same as that of cast iron, and about half that of mild steel. Young's modulus, however, is only one-tenth that of cast iron and one-twentieth that of steel. Thus bone, despite its lightness (specific gravity about 2·5 as compared with 7·9 for iron), is remarkably strong and at the same time more flexible than might be expected. Presumably the biological advantage is that greater flexibility helps to absorb sudden impacts. It is unusual in metallic substances to find the elastic modulus proportional to the strength; this is more characteristic of materials like concrete and timber. Another remarkable property of bone is that it remains elastic up to three-quarters of the breaking stress. Most metals show considerable ductility before reaching their breaking point. While Young's modulus is of interest, both on its own account and as an index of the quality of the bone, its close association with breaking stress suggests that it might be used to predict the maximum load which a bone can carry safely. Since E, unlike S. B. , can be measured without damage, useful information might be gained by measuring the elasticity of living human bones