Objectives

After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP).

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.

Aims

Femoral impaction bone grafting was first developed in 1987 using morselised cancellous bone graft impacted into the femoral canal in combination with a cemented, tapered, polished stem. We describe the evolution of this technique and instrumentation since that time.

The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):6–9.

Objectives

This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols.

The December 2014 Foot & Ankle Roundup360 looks at: Charcot feet, biomarkers and diabetes; weight bearing following Achilles tendon rupture; endobuttons and mal-reduced diastasis; evidence for stem cell therapies in osteochondral lesions of the talus; syndesmosis fixation in SER ankle fractures; and self-reporting for foot and ankle outcomes.

Nanotechnology is the study, production and controlled manipulation of materials with a grain size < 100 nm. At this level, the laws of classical mechanics fall away and those of quantum mechanics take over, resulting in unique behaviour of matter in terms of melting point, conductivity and reactivity. Additionally, and likely more significant, as grain size decreases, the ratio of surface area to volume drastically increases, allowing for greater interaction between implants and the surrounding cellular environment. This favourable increase in surface area plays an important role in mesenchymal cell differentiation and ultimately bone–implant interactions.

Basic science and translational research have revealed important potential applications for nanotechnology in orthopaedic surgery, particularly with regard to improving the interaction between implants and host bone. Nanophase materials more closely match the architecture of native trabecular bone, thereby greatly improving the osseo-integration of orthopaedic implants. Nanophase-coated prostheses can also reduce bacterial adhesion more than conventionally surfaced prostheses. Nanophase selenium has shown great promise when used for tumour reconstructions, as has nanophase silver in the management of traumatic wounds. Nanophase silver may significantly improve healing of peripheral nerve injuries, and nanophase gold has powerful anti-inflammatory effects on tendon inflammation.

Considerable advances must be made in our understanding of the potential health risks of production, implantation and wear patterns of nanophase devices before they are approved for clinical use. Their potential, however, is considerable, and is likely to benefit us all in the future.

Cite this article: Bone Joint J 2014; 96-B: 569–73.

Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-β, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches.

The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.

The treatment of osteochondral lesions is of great interest to orthopaedic surgeons because most lesions do not heal spontaneously. We present the short-term clinical outcome and MRI findings of a cell-free scaffold used for the treatment of these lesions in the knee. A total of 38 patients were prospectively evaluated clinically for two years following treatment with an osteochondral nanostructured biomimetic scaffold. There were 23 men and 15 women; the mean age of the patients was 30.5 years (15 to 64). Clinical outcome was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and a Visual Analgue scale for pain. MRI data were analysed based on the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system at three, 12 and 24 months post-operatively. There was a continuous significant clinical improvement after surgery. In two patients, the scaffold treatment failed (5.3%) There was a statistically significant improvement in the MOCART precentage scores. The repair tissue filled most of the defect sufficiently. We found subchondral laminar changes in all patients. Intralesional osteophytes were found in two patients (5.3%). We conclude that this one-step scaffold-based technique can be used for osteochondral repair. The surgical technique is straightforward, and the clinical results are promising. The MRI aspects of the repair tissue continue to evolve during the first two years after surgery. However, the subchondral laminar and bone changes are a concern.

Cite this article: Bone Joint J 2015; 97-B:318–23.

Conventional cemented acetabular components are reported to have a high rate of failure when implanted into previously irradiated bone. We recommend the use of a cemented reconstruction with the addition of an acetabular reinforcement cross to improve fixation.

We reviewed a cohort of 45 patients (49 hips) who had undergone irradiation of the pelvis and a cemented total hip arthroplasty (THA) with an acetabular reinforcement cross. All hips had received a minimum dose of 30 Gray (Gy) to treat a primary nearby tumour or metastasis. The median dose of radiation was 50 Gy (Q1 to Q3: 45 to 60; mean: 49.57, 32 to 72).

The mean follow-up after THA was 51 months (17 to 137). The cumulative probability of revision of the acetabular component for a mechanical reason was 0% (0 to 0%) at 24 months, 2.9% (0.2 to 13.3%) at 60 months and 2.9% (0.2% to 13.3%) at 120 months, respectively. One hip was revised for mechanical failure and three for infection.

Cemented acetabular components with a reinforcement cross provide good medium-term fixation after pelvic irradiation. These patients are at a higher risk of developing infection of their THA.

Cite this article: Bone Joint J 2015;97-B:177–84.

Cancellous allograft bone chips are commonly used in the reconstruction of defects in bone after removal of benign tumours. We investigated the MRI features of grafted bone chips and their change over time, and compared them with those with recurrent tumour. We retrospectively reviewed 66 post-operative MRIs from 34 patients who had undergone curettage and grafting with cancellous bone chips to fill the defect after excision of a tumour. All grafts showed consistent features at least six months after grafting: homogeneous intermediate or low signal intensities with or without scattered hyperintense foci (speckled hyperintensities) on T1 images; high signal intensities with scattered hypointense foci (speckled hypointensities) on T2 images, and peripheral rim enhancement with or without central heterogeneous enhancements on enhanced images. Incorporation of the graft occurred from the periphery to the centre, and was completed within three years. Recurrent lesions consistently showed the same signal intensities as those of pre-operative MRIs of the primary lesions. There were four misdiagnoses, three of which were chondroid tumours.

We identified typical MRI features and clarified the incorporation process of grafted cancellous allograft bone chips. The most important characteristics of recurrent tumours were that they showed the same signal intensities as the primary tumours. It might sometimes be difficult to differentiate grafted cancellous allograft bone chips from a recurrent chondroid tumour.

Cite this article: Bone Joint J 2015;97-B:121–8.

This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology.

Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing.

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses.

Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure.

In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Cite this article: Bone Joint J 2014;96-B:291–8.

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.

Injury to the anterior cruciate ligament (ACL) is one of the most devastating and frequent injuries of the knee. Surgical reconstruction is the current standard of care for treatment of ACL injuries in active patients. The widespread adoption of ACL reconstruction over primary repair was based on early perception of the limited healing capacity of the ACL. Although the majority of ACL reconstruction surgeries successfully restore gross joint stability, post-traumatic osteoarthritis is commonplace following these injuries, even with ACL reconstruction. The development of new techniques to limit the long-term clinical sequelae associated with ACL reconstruction has been the main focus of research over the past decades. The improved knowledge of healing, along with recent advances in tissue engineering and regenerative medicine, has resulted in the discovery of novel biologically augmented ACL-repair techniques that have satisfactory outcomes in preclinical studies. This instructional review provides a summary of the latest advances made in ACL repair.

Cite this article: Bone Joint Res 2014;3:20–31.

For over a decade, bisphosphonate administration has evolved and become the cornerstone of the prevention and treatment of fragility fractures. Millions of post-menopausal women have relied on, and continue to depend on, the long-acting, bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In return, we have seen the number of fragility fractures decrease, along with associated costs and emotional benefits. However, with any drug, there are often concerns with side effects and complications, and this unique drug class is seeing one such complication in atypical subtrochanteric femoral fracture, counterproductive to that which it was designed to prevent. This has created concern over long-term bisphosphonate administration and its potential link to these atypical fractures. There is controversial evidence surrounding such a definitive link, and no protocol for managing these fractures.

This review offers the latest information regarding this rare but increasingly controversial adverse effect and its potential connection to one of the most successful forms of treatment that is available for the management of fragility fractures.

The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically.

Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets.

Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures.

Resurfacing arthroplasty of the hip is being used increasingly as an alternative to total hip replacement, especially for young active patients. There is concern about necrosis of the femoral head after resurfacing which can result in fracture and loosening. Most systems use a cemented femoral component, with the potential for thermal necrosis of the cancellous bone of the reamed femoral head. We used thermal probes to record temperatures close to the cement-bone interface during resurfacing arthroplasty.

The maximum temperature recorded at the cement-bone interface in four cases was approximately 68°C which was higher than that reported to kill osteocytes. A modified surgical technique using insertion of a suction cannula into the lesser trochanter, generous pulsed lavage and early reduction of the joint significantly reduced the maximum recorded cancellous bone temperature to approximately 36°C in five cases (p = 0.014).

We recommend the modified technique since it significantly reduces temperatures at the cement-bone interface.

We reviewed 59 bone graft substitutes marketed by 17 companies currently available for implantation in the United Kingdom, with the aim of assessing the peer-reviewed literature to facilitate informed decision-making regarding their use in clinical practice. After critical analysis of the literature, only 22 products (37%) had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita), Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question the need for so many different products, especially with limited published clinical evidence for their efficacy, and conclude that there is a considerable need for further prospective randomised trials to facilitate informed decision-making with regard to the use of current and future bone graft substitutes in clinical practice.

Cite this article: Bone Joint J 2013;95-B:583–97.