Aims. Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture. Methods. The WHiTE 8 Copal Or Palacos Antibiotic Loaded bone cement trial (WHiTE 8 COPAL) is a multicentre, multi-surgeon, parallel, two-arm, randomized clinical trial. The pragmatic study will be embedded in the World Hip Trauma Evaluation (WHiTE) (ISRCTN 63982700). Participants, including those that lack capacity, will be allocated on a 1:1 basis stratified by recruitment centre to either a low dose single antibiotic-loaded bone cement or a high dose dual antibiotic-loaded bone cement. The primary analysis will compare the differences in deep SSI rate as defined by the Centers for Disease Control and Prevention within 90 days of surgery via medical record review and patient self-reported questionnaires. Secondary outcomes include UK Core Outcome Set for hip fractures, complications, rate of antibiotic prescription, resistance patterns of deep SSI, and resource use (more specifically, cost-effectiveness) up to four months post-randomization. A minimum of 4,920 patients will be recruited to obtain 90% power to detect an absolute difference of 1.5% in the rate of deep SSI at 90 days for the expected 3% deep SSI rate in the control group. Conclusion. The results of this trial will provide evidence regarding clinical and cost-effectiveness between low dose single and high dose dual antibiotic-loaded bone cement, which will inform policy and practice guidelines such as the National Institute for Health and Care Excellence guidance on management of hip fractures. Cite this article: Bone Jt Open 2021;2(2):72–78

We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures. A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks. In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect. Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing

Aims

To evaluate whether an ultra-low-dose CT protocol can diagnose selected limb fractures as well as conventional CT (C-CT).

Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722

Objectives. This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. Methods. Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay. Results. The concentration of cytokine released from PRP varied over time and was influenced by various activation protocols. Ca-only activation had a significant effect on the DS PRPs (where the VEGF, FGF, and IL-1 concentrations were sustained) while Ca/thrombin activation had effects on both SS and DS PRPs (where the PDGF and VEGF concentrations were sustained and the TGF and FGF concentrations were short). The IL-1 content showed a significant increase with Ca-only or Ca/thrombin activation while these activations did not increase the MMP-9 concentration. Conclusion. The SS and DS methods differed in their effect on cytokine release, and this effect varied among the cytokines analysed. In addition, low dose of thrombin/calcium activation increased the overall cytokine release of the PRP preparations over seven days, relative to that with a calcium-only supplement or non-activation. Cite this article: Professor J. H. Oh. Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. Bone Joint Res 2016;5:37–45. doi: 10.1302/2046-3758.52.2000540

Aims. A fracture of the hip is the most common serious orthopaedic injury, and surgical site infection (SSI) is one of the most significant complications, resulting in increased mortality, prolonged hospital stay and often the need for further surgery. Our aim was to determine whether high dose dual antibiotic impregnated bone cement decreases the rate of infection. Patients and Methods. A quasi-randomised study of 848 patients with an intracapsular fracture of the hip was conducted in one large teaching hospital on two sites. All were treated with a hemiarthroplasty. A total of 448 patients received low dose single-antibiotic impregnated cement (control group) and 400 patients received high dose dual-antibiotic impregnated cement (intervention group). The primary outcome measure was deep SSI at one year after surgery. Results. The rate of deep SSI was 3.5% in the control group and 1.1% in the intervention group (p = 0.041; logistic regression adjusting for age and gender). The overall rate of non-infective surgical complications did not differ between the two groups (unadjusted chi-squared test; p > 0.999). Conclusion. The use of high dose dual-antibiotic impregnated cement in these patients significantly reduces the rate of SSI compared with standard low dose single antibiotic loaded bone cement. Cite this article: Bone Joint J 2016;98-B:1534–1541

Aims. Tantalum (Ta) trabecular metal components are increasingly used to reconstruct major bone defects in revision arthroplasty surgery. It is known that some metals such as silver have antibacterial properties. Recent reports have raised the question regarding whether Ta components are protective against infection in revision surgery. This laboratory study aimed to establish whether Ta has intrinsic antibacterial properties against planktonic bacteria, or the ability to inhibit biofilm formation. Materials and Methods. Equal-sized pieces of Ta and titanium (Ti) acetabular components were sterilised and incubated with a low dose inoculum of either Staphylococcus (S.) aureus or S. epidermidis for 24 hours. After serial dilution, colony forming units (cfu) were quantified on Mueller-Hinton agar plates. In order to establish whether biofilms formed to a greater extent on one material than the other, these Ta and Ti pieces were then washed twice, sonicated and washed again to remove loosely adhered planktonic bacteria. They were then re-incubated for 24 hours prior to quantifying the number of cfu. All experiments were performed in triplicate. Results. More than 1x10. 8. cfu/ml were observed in both the Ta and Ti experiments. After washing and sonication, more than 2x10. 7. cfu/ml were observed for both Ta and Ti groups. The results were the same for both S. aureus and S. epidermidis. Conclusion. Compared with Ti controls, Ta did not demonstrate any intrinsic antibacterial activity or ability to inhibit biofilm formation. Hence, intrinsic antimicrobial properties of Ta do not account for the previously observed reduction in the frequency of subsequent infections when Ta was used in revision procedures. . Cite this article: Bone Joint J 2017;99-B:1153–6

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

Curettage and packing with polymethylmethacrylate cement is a routine treatment for giant-cell tumour (GCT) of bone. We performed an in vitro evaluation of the cytotoxic effect of a combination of cement and methotrexate, doxorubicin and cisplatin on primary cell cultures of stromal GCT cells obtained from five patients. Cement cylinders containing four different concentrations of each drug were prepared, and the effect of the eluted drugs was examined at three different time intervals. We found that the cytotoxic effect of eluted drugs depended on their concentration and the time interval, with even the lowest dose of each drug demonstrating an acceptable rate of cytotoxicity. Even in low doses, cytotoxic drugs mixed with polymethylmethacrylate cement could therefore be considered as effective local adjuvant treatment for GCTs

Cite this article: Bone Joint Res 2023;12(3):199–201.

Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.

Cite this article: Bone Joint J 2023;105-B(7):729–734.

Aims

Leg length discrepancy (LLD) is a common pre- and postoperative issue in total hip arthroplasty (THA) patients. The conventional technique for measuring LLD has historically been on a non-weightbearing anteroposterior pelvic radiograph; however, this does not capture many potential sources of LLD. The aim of this study was to determine if long-limb EOS radiology can provide a more reproducible and holistic measurement of LLD.

Aims

Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Aims

There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

Aims

The volume of ambulatory total hip arthroplasty (THA) procedures is increasing due to the emphasis on value-based care. The purpose of the study is to identify the causes for failed same-day discharge (SDD) and perioperative factors leading to failed SDD.

Aims

Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

Aims

Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored after rifampicin (RMP) therapy.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

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

Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model.

Aims

A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing.

Aims

To benchmark the radiation dose to patients during the course of treatment for a spinal deformity.

Aims

Poly(methyl methacrylate) (PMMA)-based bone cements are the industry standard in orthopaedics. PMMA cement has inherent disadvantages, which has led to the development and evaluation of a novel silorane-based biomaterial (SBB) for use as an orthopaedic cement. In this study we test both elution and mechanical properties of both PMMA and SBB, with and without antibiotic loading.

Aims

Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model.

Aims

Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents.

Aims

To investigate the effect of polyethylene manufacturing characteristics and irradiation dose on the survival of cemented and reverse hybrid total hip arthroplasties (THAs).

Aims

LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling.

Aims

Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs).

Aims

Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process.

Aims

The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential.

Aims

To describe the incidence of adverse clinical outcomes related to COVID-19 infection following corticosteroid injections (CSI) during the COVID-19 pandemic. To describe the incidence of positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing, positive SARS-COV2 IgG antibody testing or positive imaging findings following CSI at our institution during the COVID-19 pandemic.

Aims

Recent studies have suggested that corticosteroid injections into the knee may harm the joint resulting in cartilage loss and possibly accelerating the progression of osteoarthritis (OA). The aim of this study was to assess whether patients with, or at risk of developing, symptomatic osteoarthritis of the knee who receive intra-articular corticosteroid injections have an increased risk of requiring arthroplasty.

Aims

Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.

Objectives

The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics.

Objectives

The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics.

Aims

Idiopathic scoliosis is the most common spinal deformity in adolescents and children. The aetiology of the disease remains unknown. Previous studies have shown a lower bone mineral density in individuals with idiopathic scoliosis, which may contribute to the causation. The aim of the present study was to compare bone health in adolescents with idiopathic scoliosis with controls.

There is good scientific rationale to support the use of growth factors to promote musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich plasma (PRP) and other blood-derived products has yet to be proven. Characterization and reporting of PRP preparation protocols utilized in clinical trials for the treatment of musculoskeletal disease is highly inconsistent, and the majority of studies do not provide sufficient information to allow the protocols to be reproduced. Furthermore, the reporting of blood-derived products in orthopaedics is limited by the multiple PRP classification systems available, which makes comparison of results between studies challenging. Several attempts have been made to characterize and classify PRP; however, no consensus has been reached, and there is lack of a comprehensive and validated classification. In this annotation, we outline existing systems used to classify preparations of PRP, highlighting their advantages and limitations. There remains a need for standardized universal nomenclature to describe biological therapies, as well as a comprehensive and reproducible classification system for autologous blood-derived products.

Cite this article: Bone Joint J 2019;101-B:891–896.

Objectives

Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol.

Aims

The aims of this study were to compare the efficacy of two agents, aspirin and warfarin, for the prevention of venous thromboembolism (VTE) after simultaneous bilateral total knee arthroplasty (SBTKA), and to elucidate the risk of VTE conferred by this procedure compared with unilateral TKA (UTKA).

Aims

The aim of this study was to quantify the risk of developing cancer from the exposure to radiation associated with surgery to correct limb deformities in children.

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences.

Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a ‘milder’ agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents.

The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use.

There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE.

Cite this article: Bone Joint J 2017;99-B:1420–30.

Aims

In 2013, we introduced a specialized, centralized, and interdisciplinary team in our institution that applied a standardized diagnostic and treatment algorithm for the management of prosthetic joint infections (PJIs). The hypothesis for this study was that the outcome of treatment would be improved using this approach.

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

Aims

Dupuytren’s contracture is a benign, myoproliferative condition affecting the palmar fascia that results in progressive contractures of the fingers. Despite increased knowledge of the cellular and connective tissue changes involved, neither a cure nor an optimum form of treatment exists. The aim of this systematic review was to summarize the best available evidence on the management of this condition.

Aims

Delayed diagnosis is a well-known complication of a Monteggia fracture-dislocation. If left untreated, the dislocated radial head later becomes symptomatic. The purposes of this study were firstly, to evaluate the clinical and radiological results of open reduction of the radial head and secondly, to identify the factors that may affect the outcome of this procedure.

Objectives

The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation in vitro and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model.

Objectives

As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing.

Aims

To investigate the bone penetration of intravenous antibiotic prophylaxis with flucloxacillin and gentamicin during hip and knee arthroplasty, and their efficacy against Staphylococcus (S.) aureus and S. epidermidis.

Aims

The pelvis rotates in the sagittal plane during daily activities. These rotations have a direct effect on the functional orientation of the acetabulum. The aim of this study was to quantify changes in pelvic tilt between different functional positions.

Aims

Our aim was to prepare a systematic review and meta-analysis to compare the outcomes of cemented and cementless hemiarthroplasty of the hip, in elderly patients with a fracture of the femoral neck, to investigate the mortality, complications, length of stay in hospital, blood loss, operating time and functional results.

Aims

Accurate placement of the acetabular component during total hip arthroplasty (THA) is an important factor in the success of the procedure. However, the reported accuracy varies greatly and is dependent upon whether free hand or navigated techniques are used. The aim of this study was to assess the accuracy of an instrument system that incorporates 3D printed, patient-specific guides designed to optimise the placement of the acetabular component.

Aims

The primary aim of this study was to analyse the position of the acetabular and femoral components in total hip arthroplasty undertaken using an anterior surgical approach.

We describe our technique and rationale using hybrid fixation for primary total hip arthroplasty (THA) at the Hospital for Special Surgery. Modern uncemented acetabular components have few screw holes, or no holes, polished inner surfaces, improved locking mechanisms, and maximised thickness and shell-liner conformity. Uncemented sockets can be combined with highly cross-linked polyethylene liners, which have demonstrated very low wear and osteolysis rates after ten to 15 years of implantation. The results of cement fixation with a smooth or polished surface finished stem have been excellent, virtually eliminating complications seen with cementless fixation like peri-operative femoral fractures and thigh pain. Although mid-term results of modern cementless stems are encouraging, the long-term data do not show reduced revision rates for cementless stems compared with cemented smooth stems. In this paper we review the conduct of a hybrid THA, with emphasis on pre-operative planning, surgical technique, hypotensive epidural anaesthesia, and intra-operative physiology.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):54–9.

Objectives

Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis.

Total knee arthroplasty (TKA) is a major orthopaedic intervention. The length of a patient's stay has been progressively reduced with the introduction of enhanced recovery protocols: day-case surgery has become the ultimate challenge.

This narrative review shows the potential limitations of day-case TKA. These constraints may be social, linked to patient’s comorbidities, or due to surgery-related adverse events (e.g. pain, post-operative nausea and vomiting, etc.).

Using patient stratification, tailored surgical techniques and multimodal opioid-sparing analgesia, day-case TKA might be achievable in a limited group of patients. The younger, male patient without comorbidities and with an excellent social network around him might be a candidate.

Demographic changes, effective recovery programmes and less invasive surgical techniques such as unicondylar knee arthroplasty, may increase the size of the group of potential day-case patients.

The cost reduction achieved by day-case TKA needs to be balanced against any increase in morbidity and mortality and the cost of advanced follow-up at a distance with new technology. These factors need to be evaluated before adopting this ultimate ‘fast-track’ approach.

Cite this article: Bone Joint J 2015;97-B(10 Suppl A):40–4.

The August 2015 Research Roundup360 looks at: Lightbulbs, bleeding and procedure durations; Infection and rheumatoid agents; Infection rates and ‘bundles of care’ revisited; ACI: new application for a proven technology?; Hydrogel coating given the thumbs up; Hydroxyapatite as a smart coating?

Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA.

In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism.

The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications.

This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA.

Cite this article: Bone Joint J 2015;97-B:905–10.

Objectives

Computed tomography (CT) plays an important role in evaluating wear and periacetabular osteolysis (PAO) in total hip replacements. One concern with CT is the high radiation exposure since standard pelvic CT provides approximately 3.5 millisieverts (mSv) of radiation exposure, whereas a planar radiographic examination with three projections totals approximately 0.5 mSv. The objective of this study was to evaluate the lowest acceptable radiation dose for dual-energy CT (DECT) images when measuring wear and periacetabular osteolysis in uncemented metal components.

Only limited data are available regarding the infiltration of local anaesthetic for total hip arthroplasty (THA), and no studies were performed for THA using the anterior approach.

In this prospective, randomised placebo-controlled study we investigated the effect of both standard and reverse infiltration of local anaesthetic in combination with the anterior approach for THA. The primary endpoint was the mean numeric rating score for pain four hours post-operatively. In addition, we recorded the length of hospital stay, the operating time, the destination of the patient at discharge, the use of pain medication, the occurrence of side effects and pain scores at various times post-operatively.

Between November 2012 and January 2014, 75 patients were included in the study. They were randomised into three groups: standard infiltration of local anaesthetic, reversed infiltration of local anaesthetic, and placebo. There was no difference in mean numeric rating score for pain four hours post-operatively (p = 0.87). There were significantly more side effects at one and eight hours post-operatively in the placebo group (p = 0.02; p = 0.03), but this did not influence the mobilisation of the patients. There were no differences in all other outcomes between the groups.

We found no clinically relevant effect when the infiltration of local anaesthetic with ropivacaine and epinephrine was used in a multimodal pain protocol for THA using the anterior approach.

Cite this article: Bone Joint J 2015; 97-B:734–40.

The October 2014 Shoulder & Elbow Roundup³⁶⁰ looks at: PRP is not effective in tennis elbow; eccentric physiotherapy effective in subacromial pain; dexamethasone in shoulder surgery; arthroscopic remplissage for engaging Hill-Sach’s lesions; a consistent approach to subacromial impingement; delay in fixation of proximal humeral fractures detrimental to outcomes.

The main form of treatment of a chordoma of the mobile spine is total en bloc spondylectomy (TES), but the clinical results are not satisfactory. Stand-alone carbon ion radiotherapy (CIRT) for bone and soft-tissue sarcomas has recently been reported to have a high rate of local control with a low rate of local recurrence.

We report two patients who underwent TES after CIRT for treating a chordoma in the lumbar spine with good medium-term outcomes. At operation, there remained histological evidence of viable tumour cells in both cases. After the combination use of TES following CIRT, neither patient showed signs of recurrence at the follow-up examination. These two cases suggest that CIRT should be combined with total spondylectomy in the treatment of chordoma of the mobile spine.

Cite this article: Bone Joint J 2013;95-B:1392–5.

The outcome after total hip replacement has improved with the development of surgical techniques, better pain management and the introduction of enhanced recovery pathways. These pathways require a multidisciplinary team to manage pre-operative education, multimodal pain control and accelerated rehabilitation. The current economic climate and restricted budgets favour brief hospitalisation while minimising costs. This has put considerable pressure on hospitals to combine excellent results, early functional recovery and shorter admissions.

In this review we present an evidence-based summary of some common interventions and methods, including pre-operative patient education, pre-emptive analgesia, local infiltration analgesia, pre-operative nutrition, the use of pulsed electromagnetic fields, peri-operative rehabilitation, wound dressings, different surgical techniques, minimally invasive surgery and fast-track joint replacement units.

Cite this article: Bone Joint J 2013;95-B:1587–94.

Hip arthrodesis remains a viable surgical technique in well selected patients, typically the young manual labourer with isolated unilateral hip disease. Despite this, its popularity with patients and surgeons has decreased due to the evolution of hip replacement, and is seldom chosen by young adult patients today. The surgeon is more likely to encounter a patient who requests conversion to total hip replacement (THR). The most common indications are a painful pseudarthrosis, back pain, ipsilateral knee pain or contralateral hip pain. Occasionally the patient will request conversion because of difficulty with activities of daily living, body image and perceived cosmesis. The technique of conversion and a discussion of the results are presented.

Cite this article: Bone Joint J 2013;95-B, Supple A:114–19.

The April 2013 Research Roundup³⁶⁰ looks at: when the ‘residency cake’ is done; steroids, stem cells and tendons; what exactly is osteoarthritis; platelet-rich plasma; CRPS; d-Dimer for DVT; reducing bacterial adhesion; and fin or limb?

The June 2012 Knee Roundup³⁶⁰ looks at: ACI and mosaicplasty; ACI after microfracture; exercise therapy and the degenerate medial meniscal tear; intra-articular bupivacaine or ropivacaine at knee arthroscopy; lateral trochlear inclination and patellofemoral osteoarthritis; bone loss and ACL reconstruction; assessing stability using the contralateral knee; tranexamic acid and a useful review of knee replacement.

Objectives

To study the vascularity and bone metabolism of the femoral head/neck following hip resurfacing arthroplasty, and to use these results to compare the posterior and the trochanteric-flip approaches.

The incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is thought to be low following foot and ankle surgery, but the routine use of chemoprophylaxis remains controversial. This retrospective study assessed the incidence of symptomatic venous thromboembolic (VTE) complications following a consecutive series of 2654 patients undergoing elective foot and ankle surgery. A total of 1078 patients received 75 mg aspirin as routine thromboprophylaxis between 2003 and 2006 and 1576 patients received no form of chemical thromboprophylaxis between 2007 and 2010. The overall incidence of VTE was 0.42% (DVT, 0.27%; PE, 0.15%) with 27 patients lost to follow-up. If these were included to create a worst case scenario, the overall VTE rate was 1.43%. There was no apparent protective effect against VTE by using aspirin.

We conclude that the incidence of VTE following foot and ankle surgery is very low and routine use of chemoprophylaxis does not appear necessary for patients who are not in the high risk group for VTE.

The use of passive stretching of the elbow after arthrolysis is controversial. We report the results of open arthrolysis in 81 patients. Prospectively collected outcome data with a minimum follow-up of one year were analysed. All patients had sustained an intra-articular fracture initially and all procedures were performed by the same surgeon under continuous brachial plexus block anaesthesia and with continuous passive movement (CPM) used post-operatively for two to three days. CPM was used to maintain the movement achieved during surgery and passive stretching was not used at any time. A senior physiotherapist assessed all the patients at regular intervals. The mean range of movement (ROM) improved from 69° to 109° and the function and pain of the upper limb improved from 32 to 16 and from 20 to 10, as assessed by the Disabilities of the Arm Shoulder and Hand score and a visual analogue scale, respectively. The greatest improvement was obtained in the stiffest elbows: nine patients with a pre-operative ROM < 30° achieved a mean post-operative ROM of 92° (55° to 125°). This study demonstrates that in patients with a stiff elbow after injury, good results may be obtained after open elbow arthrolysis without using passive stretching during rehabilitation.

A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement.

At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating.

These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.

We studied the effects of hyperbaric oxygen (HBO) and zoledronic acid (ZA) on posterior lumbar fusion using a validated animal model. A total of 40 New Zealand white rabbits underwent posterior lumbar fusion at L5–6 with autogenous iliac bone grafting. They were divided randomly into four groups as follows: group 1, control; group 2, HBO (2.4 atm for two hours daily); group 3, local ZA (20 μg of ZA mixed with bone graft); and group 4, combined HBO and local ZA. All the animals were killed six weeks after surgery and the fusion segments were subjected to radiological analysis, manual palpation, biomechanical testing and histological examination.

Five rabbits died within two weeks of operation. Thus, 35 rabbits (eight in group 1 and nine in groups 2, 3 and 4) completed the study. The rates of fusion in groups 3 and 4 (p = 0.015) were higher than in group 1 (p < 0.001) in terms of radiological analysis and in group 4 was higher than in group 1 with regard to manual palpation (p = 0.015). We found a statistically significant difference in the biomechanical analysis between groups 1 and 4 (p = 0.024). Histological examination also showed a statistically significant difference between groups 1 and 4 (p = 0.036).

Our results suggest that local ZA combined with HBO may improve the success rate in posterior lumbar spinal fusion.

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors.

Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes.

There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism.

The major advantage of hip resurfacing is the decreased amount of bone resection compared with a standard total hip replacement. Fracture of the femoral neck is the most common early complication and poor bone quality is a major risk factor. We undertook a prospective consecutive case control study examining the effect of bone mineral density changes in patients undergoing hip resurfacing surgery. A total of 423 patients were recruited with a mean age of 54 years (24 to 87). Recruitment for this study was dependent on pre-operative bilateral femoral bone mineral density results not being osteoporotic. The operated and non-operated hips were assessed. Bone mineral density studies were repeated over a two-year period. The results showed no significant deterioration in the bone mineral density in the superolateral region in the femoral neck, during that period.

These findings were in the presence of a markedly increased level of physical activity, as measured by the short-form 36 health survey physical function score.

We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial fluid and whole blood taken from a group of 92 patients with failed current-generation metal-on-metal hip replacements. We applied acid oxidative digestion to our trace metal analysis protocol, which found significantly higher levels of metal ion concentrations in blood and synovial fluid than a non-digestive method. Patients were subcategorised by mode of failure as either ‘unexplained pain’ or ‘defined causes’. Using this classification, chromium and cobalt ion levels were present over a wider range in synovial fluid and not as strongly correlated with blood ion levels as previously reported. There was no significant difference between metal ion concentrations and manufacturer of the implant, nor femoral head size below or above 50 mm. There was a moderately positive correlation between metal ion levels and acetabular component inclination angle as measured on three-dimensional CT imaging.

Our results suggest that acid digestion of samples of synovial fluid samples is necessary to determine metal ion concentrations accurately so that meaningful comparisons can be made between studies.

We investigated the effect of mitomycin-C on the reduction of the formation of peritendinous fibrous adhesions after tendon repair. In 20 Wistar albino rats the tendo Achillis was cut and repaired using a modified Kessler technique. The rats were divided into two equal groups. In group 1, an injection of mitomycin-C was placed between the tendon and skin of the right leg. In group 2, an identical volume of sterile normal saline was injected on the left side in a similar fashion. All the rats received mitomycin-C or saline for four weeks starting from the day of operation. The animals were killed after 30 days. The formation of peritendinous fibrous tissue, the inflammatory reaction and tendon healing were evaluated. The tensile strength of the repaired tendons was measured biomechanically. Microscopic evidence of the formation of adhesions and inflammation was less in group 1. There was no significant difference in the tensile load required to rupture the repaired tendons in the two groups.

Mitomycin-C may therefore provide a simple and inexpensive means of preventing of post-operative adhesions.

This study examined the role of vitamin D as a factor accounting for fatty degeneration and muscle function in the rotator cuff. There were 366 patients with disorders of the shoulder. A total of 228 patients had a full-thickness tear (group 1) and 138 patients had no tear (group 2). All underwent magnetic resonance arthrography and an isokinetic muscle performance test. The serum concentrations of vitamin D (25(OH)D₃) were measured.

In general, a lower serum level of vitamin D was related to higher fatty degeneration in the muscles of the cuff. Spearman’s correlation coefficients were 0.173 (p = 0.001), −0.181 (p = 0.001), and −0.117 (p = 0.026) for supraspinatus, infraspinatus and subscapularis, respectively. In group 1, multivariate linear regression analysis revealed that the serum level of vitamin D was an independent variable for fatty degeneration of the supraspinatus and infraspinatus.

The serum vitamin D level has a significant negative correlation with the fatty degeneration of the cuff muscle and a positive correlation with isokinetic muscle torque.

Severe acute respiratory syndrome (SARS) is a newly described infectious disease caused by the SARS coronavirus which attacks the immune system and pulmonary epithelium. It is treated with regular high doses of corticosteroids. Our aim was to determine the relationship between the dosage of steroids and the number and distribution of osteonecrotic lesions in patients treated with steroids during the SARS epidemic in Beijing, China in 2003.

We identified 114 patients for inclusion in the study. Of these, 43 with osteonecrosis received a significantly higher cumulative and peak methylprednisolone-equivalent dose than 71 patients with no osteonecrosis identified by MRI. We confirmed that the number of osteonecrotic lesions was directly related to the dosage of steroids and that a very high dose, a peak dose of more than 200 mg or a cumulative methylprednisolone-equivalent dose of more than 4000 mg, is a significant risk factor for multifocal osteonecrosis with both epiphyseal and diaphyseal lesions. Patients with diaphyseal osteonecrosis received a significantly higher cumulative methylprednisolone-equivalent dose than those with epiphyseal osteonecrosis. Multifocal osteonecrosis should be suspected if a patient is diagnosed with osteonecrosis in the shaft of a long bone.

We carried out a prospective study over a period of 12 months to measure the exposure to radiation of the hands of a dedicated foot and ankle surgeon. A thermoluminescent dosimeter ring (TLD) was used to measure the cumulative dose of radiation. Fluoroscopy was used in operations on the foot and ankle. The total screening time was 3028 s, with a mean time per procedure of 37.4 s (0.6 to 197). This correlated positively with the number of procedures performed (r = 0.92, p < 0.001), and with the dose of radiation in both the left (r = 0.85, p = 0.0005) and right TLDs (r = 0.59, p = 0.419). There was no significant difference in the dose of radiation between the two hands (t-test, p = 0.62). The total dose to the right TLD over the 12 months was 2.4 millisieverts.

This is a simple and convenient method for evaluating the exposure of a single surgeon to radiation. The radiation detected was well below the annual dose limit set by the International Commission on Radiological Protection.

We present a retrospective study of 25 patients treated by open arthrolysis of the elbow for post-traumatic stiffness. The mean follow-up was for 7.8 years (5 to 10.8). The range of movement of the elbow, pain scores and functional outcomes were recorded pre- and postoperatively. An improvement in the mean range of movement from 55° (0° to 95°) to 105° (55° to 135°) was obtained in our patients at one year. This improvement was maintained over the mean follow-up period of 7.8 years (5 to 10.8). Improvement in pain, function and patient satisfaction was recorded in 23 of the 25 patients at final follow-up.

On the basis of this study, we believe that the results of open arthrolysis for post-traumatic stiffness of the elbow are durable over the medium term.

We report a case of fatal haemorrhage following a low-energy fracture of the pubic ramus in an 85-year-old woman.

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.