Abstract. Objectives. Osteoporosis of the pelvis and femur is diagnosed in a high proportion of lower-limb amputees which carries an increased fracture risk and subsequently serious implications on mobility, physical dependency and morbidity. Through the development of biofidelic musculoskeletal and finite element (FE) models, we aim to determine the effect of lower-limb amputation on long-term bone remodelling in the hip and to understand the potential underpinning mechanisms for bone degradation in the younger amputee population. Methods. Our models are patient specific and anatomically accurate. Geometries are derived from MRI-scans of one bilateral, above-knee, amputee and one body-matched control subject. Musculoskeletal modelling enables comparison of muscle and joint reaction-forces throughout gait. This provides the loading scenario implemented in FE. FE modelling demonstrates the effect of loading on the amputated limb via a prosthetic socket by comparing bone mechanical stimulation in amputee and control cases. Results. Musculoskeletal modelling shows that the bilateral amputee has 25% higher peak hip-reaction force than controls but a 54% lower peak knee-reaction force. Compensation for missing muscles and joints cause large-scale changes to the muscle loading patterns of the residual limb. FE analysis shows a 32% reduction in bone stimulation within the proximal femur and an 81% reduction in the distal femoral shaft when compared to the healthy control. A shielding effect from weight-bearing through a prosthetic socket was observed that may offset any increases in joint and muscle loading at the amputated hip. Conclusions. Bone loss in the young amputee population could be driven by unloading osteopenia where altered joint and muscle loads cause altered mechanical stimulus in the femur. Over many cycles of remodelling, a net bone loss occurs. Importantly, this suggests that the issue is preventable, or even reversible, with the implementation of targeted loading regimes or changes to the design of the prosthetic socket. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Anatomically, bone consists of building blocks called osteons, which in turn comprise a central canal that contains nerves and blood vessels. This indicates that bone is a highly innervated and vascularized tissue. The function of vascularization in bone (development) is well-established: providing oxygen and nutrients that are necessary for the formation, maintenance, and healing. As a result, in the field of bone tissue engineering many research efforts take vascularization into account, focusing on engineering vascularized bone. In contrast, while bone anatomy indicates that the role of innervation in bone is equally important, the role of innervation in bone tissue engineering has often been disregarded. For many years, the role of innervation in bone was mostly clear in physiology, where innervation of a skeleton is responsible for sensing pain and other sensory stimuli. Unraveling its role on a cellular level is far more complex, yet more recent research efforts have unveiled that innervation has an influence on osteoblast and osteoclast activity. Such innervation activities have an important role in the regulation of bone homeostasis, stimulating bone formation and inhibiting resorption. Furthermore, due to their anatomical proximity, skeletal nerves and blood vessels interact and influence each other, which is also demonstrated by pathways cross-over and joint responses to stimuli. Besides those closely connected sytems, the immune system plays also a pivotal role in bone regeneration. Certain cytokines are important to attract osteogenic cells and (partially) inhibit bone resorption. Several leukocytes also play a role in the bone regeneration process. Overall, bone interacts with several systems. Aberrations in those systems affect the bone and are important to understand in the context of bone regeneration. This crosstalk has become more evident and is taken more into consideration. This leads to more complex tissue regeneration, but may recapitulate better physiological situations

Introduction and Objective. Osteoarthritis of the knee joint is common in old age population in every part of world. Pain is the major source of disability in patients with osteoarthritis of the knee joint. Subchondral bone marrow is richly innervated with nociceptive pain fibers and may be a source of pain in patients with symptomatic degenerative joint disease. Current therapy for managing bone marrow oedema is core decompression (CD), combining core decompression and injection of hydroxyapatite cement or autologus chondrocyte supplementtion. But all of this work has been done in femoral head and authors documented good result with minimal complication. There are various studies in literature suggesting treatment to repair BME by restoring support and relieving abnormal stresses with accepted internal fixation and bone stimulating surgical techniques in relieving knee OA pain. In this study, we present efficacy of knee arthroscopy with adjunctive core decompression and supplementation with structural scaffold to improve self-rated visual analog scale (VAS) pain scores, rate of conversion to arthroplasty, and patient satisfaction levels. Materials and Methods. The study included patients aged between 40 and 75 years old, with pain in the knee for at least six months, associated with high-signal MRI lesion on T2 sequences, on the tibia or femur. Trephine was used as the bone decompression instrument. Trephine has a diameter of 8–10 mm and operation with trephine requires that a cortical incision window be made prior to decompression treatment, thus necessitating strict disinfection. This procedure was done under spinal anesthesia. After diagnostic arthroscopy, decompression was done under C –ARM in desired area on MRI. After decompression, defect was filled with Poly ester urea's scaffold impregnated with BMAC. Results. Patients were assessed using the visual analog pain scale and the KOOS score, one week before surgery and one, three, six, 12, and 24 weeks after the procedure. MRI images were analyzed Lesions were mapped and measured in the axial, coronal, and sagittal views to plan the injection site and the trajectory of the cannula used for the procedure. Radiographs using anteroposterior, profile, and Rosenberg views of the knee and lower limb were performed to classify the lesion according to the Kellgren-Lawrence classification and to assess lower limb alignment. Evaluation using the KOOS showed a mean total score in the preoperative period of 38.44 points and of 60.7, 59.08, 56.92, 64.40, and 71.36 points at one, three, six, 12, and 24 weeks after surgery, respectively. In the VAS assessment, mean was 7.8 points preoperatively and 2.8, 2.6, 2.5, 1.3, and 0.5 points in the same periods. Conclusions. Hence it can be Concluded that this new innovative technique has provided significant improvements in the parameters of pain and functional capacity in the short-term assessment

Introduction and Objective. Management of gap non-union of the tibia, the major weight bearing bone of the leg remains controversial. The different internal fixation techniques are often weighed down by relatively high complication rates that include fractures which fail to heal (non-union). Minimally invasive techniques with ring fixators and bone transport (distraction osteogenesis) have come into picture as an alternative allowing alignment and stabilization, avoiding a graduated approach. This study was focused on fractures that result in a gap non-union of > 6 cm. Ilizarov technique was employed for management of such non-unions in this case series. The Ilizarov apparatus consists of rings, rods and kirschner wires that encloses the limb as a cylinder and uses kirschner wires to create tension allowing early weight bearing and stimulating bone growth. Ilizarov technique works on the principle of distraction osteogenesis, that is, pulling apart of bone to stimulate new bone growth. Usually, 4–5 rings are used in the setup depending on fracture site and pattern for stable fixation. In this study, we demonstrate effective bone transport and formation of gap non-union more than 6 cm in 10 patients using only 3 rings construct Ilizarov apparatus. Materials and Methods. This case study was conducted at Dr. D. Y. Patil Medical Hospital, Navi Mumbai, Maharashtra, India. The study involved 10 patients with a non-union or gap > 6 cm after tibial fracture. 3 rings were used in the setup for the treatment of all the patients. Wires were passed percutaneously through the bone using a drill and the projecting ends of the wires were attached to the metal rings and tensioned to increase stability. The outcome of the study was measured using the Oxford Knee scoring system, Functional Mobility Scale, the American Foot and Ankle Score and Visual Analog Scale. Further, follow up of patients was done upto 2 years. Results. All the patients demonstrated good fixation as was assessed clinically and radiologically. 9 patients had a clinical score of > 65 which implied fair to excellent clinical rating. The patients showed good range of motion and were highly satisfied with the treatment as measured by different scoring parameters. Conclusions. In this case study, we demonstrate that the Ilizarov technique using 3 rings is equally effective in treating non-unions > 6 cm as when using 4–5 rings. Obtaining good clinical outcome and low complication rate in all 10 patients shows that this modified technique can be employed for patients with such difficulties in the future

The goal of surgery for osteochondral lesions is to regenerate the damaged cartilage with ideally hyaline cartilage. The current gold standard treatment is bone marrow stimulation (BMS) by microfracture. In reality however BMS typically results in the generation of fibrocartilage. Orthobiologics including bone marrow aspirate, platelet rich plasma and hyaluronic acid products have been shown to promote cartilage healing and potentially increase the formation of hyaline cartilage in treated lesions. However the role of these products, the timing of their administration and frequency of application are still not clearly defined and their routine use is still not recommended. These issues and future directions for research and future clinical application will be discussed

Summary Statement. Treatment of non-union is a highly demanding field with respect to bone healing. BMP 7 is a useful, wide-ranged tool in treating non-union of the foot and benign bone tumors. It represents a low-risk procedure with a high level of reliability. Introduction. Treatment of non-union is a highly demanding field with respect to bone healing. Treatment of tibial fracture non-union with the bone morphogenetic protein 7 (BMP-7) has been successfully reported. BMP 7 is a recombinant human protein produced in ovary cells of the Chinese hamster. It is responsible for the differentiation of mesenchymal stem cells from the periost, muscle and sponious bone and stimulates bone formation. It is the aim of our study to investigate the use of BMP 7 for other locations than the tibia, such as the foot and benign bone tumors. We strive for union or revision in each medical case. Patients & Methods. At our clinic we applied BMP-7 to 13 patients (9 patients with non-union, 4 patients with benign bone cysts). 9 patients with non-union of the foot (4 forefoot, 1 midfoot, 3 hindfoot, 1 tibia) were surgically treated by resection, stabilisation, and application of BMP 7. The study included 5 men and 4 women at an average age of 58,4 years (range 33 – 80), 13 previous surgeries had been carried out. The period of follow up was on average 16.3 months (5 – 40 months). The indication for using BMP-7 instead of autologous bone graft was poor local blood supply, poor local soft tissue because of previous interventions and risk factors like smoking and diabetes. Following an indicated open biopsy, the 4 cases of benign bone tumors (1 juvenile bone cyst of the talus, 1 osteofibrose dysplasia of the proximal tibia and 2 juvenile bone cysts of the proximal humerus) were all treated with resection, followed by an application of BMP-7 and external or internal fixation. In addition two received bone grafting and two received cortisone. The average age of the tumor group was 16,75 years (11–24 years, 2 male, 2 female). Results. At follow-up all patients were satisfied with respect to pain and function, no operative complications had occurred and bone fusion had finished in 7 patients after 3 months. One ankle joint had a fibrous fusion but was free of pain. One arthrodesis of the first metatarsophalangeal joint was turned into a resection arthroplasty, today the patient is free of pain and uses a normal shoe. Both bone cysts have the radiological evidence of rehabilitation. At one humeruscyst we removed the TENS-nails without complications. We had no complications like heterotopic ossification, local erythema or pressure sensitivity. Discussion/Conclusion. These results show that BMP 7 is a useful, wide-ranged tool in treating non-union of the foot and benign bone tumors. It represents a low-risk procedure with a high level of reliability

Aim of the study was to evaluate if abrasion-arthroplasty (AAP) and abrasion-chondroplasty (ACP) leads to a release of mesenchymal stem cell (MSC) like cells from the bone marrow to the joint cavity where they probably differentiate into a chondrogenic phenotype. Introduction. Cartilage demage is a sever problem in our aging society. About 5 million people only in Germany are affected. Osteoathritis is a degeneration of cartilage caused by aging or traumata 50 % of the people over 40 have signs of osteoarthritis. But the ability of self-regeneration of cartilage is strongly limited. There are different approaches to therapy osteoathritic lesions. Arthroscopic treatment of OA includes bone marrow stimulation technique such as abrasion arthroplasty (AAP) and microfracturing (MF). Beside the support of chondrocyte progenitor cells the environment is also important for the commitment to chondrocytes. Therefore insulin-like growth factor-1 (IGF-1) and transforming growth factor beta-1 (TGF-β1) are important factors during the regeneration process. In the present study we characterised the heamarthrosis and the released cells after AAP and its ability to differentiate into the chondrocyte lineage. Material and Methods. Postoperative haemarthrosis was taken 5, 22 or 44 hours after surgery. 7.5 mg Dexamethasone (Corticosteroid) was administered into the knee joint to prevent postoperative inflammation. Mononuclear cells were isolated from haemarthrosis from the drainage bottle by ficoll density gradient centrifugation. The isolated cells were characterised using fluorescence-activated cell-sorting (FACS) analysis for characteristic markers of MSC such as CD 44, 73, 90, 105. After expanding cells were cultured in a pellet culture. After 3 weeks, histochemistry and immunohistochemistry against Sox9, collagen II and proteoglycan were performed. The release of IGF1, BMP4 and BMP7 was analysed in haemarthrosis serum by ELISA and Luminex technology. Results. The isolated cells after AAP are positive for the mesenchymal stem cell marker CD105, CD90, CD73, CD 44 and negative for the marker of hematopoetic stem cells CD 34. Isolated cells after ACP couldn't be expanded for further characterizations. The staining of the 3D-culture revealed a positive signal for the chondrogen transcription factor Sox9 and the expression of extracellular markerproteins like collagen type II and proteoglycan. Both surgery techniques, AAP and ACP provides a chondrogenic environment. We were able to detect IGF-1, TGFß, BMP4 and BMP7 in the haemarthrosis. Discussion. The benefit of abrasion arthroplasty surgery and microfracturing is controversial discussed because they do not consistently result in hyaline cartilage. But the opening of the bone marrow allows the release of monocytic cells which have the potential to differentiate into a chondrogenic phenotype. In 3D-culture these cells express Sox9 and a collagen proteoglycan rich matrix. The haemarthrosis provides also a cartilage-stimulating environment. We could detect IGF1, TGFβ, BMP4 and 7 which could enhance the commitment concerning differentiation of MSCs to a chondrogenic lineage concerning the production of cartilage specific extracellular matrix. Taken together our study provides the evidence for a therapeutic benefit of opening bone marrow in order to generate neocartilage after AAP

Strains applied to bone can stimulate its development and adaptation. High strains and rates of strain are thought to be osteogenic, but the specific dose response relationship is not known. In vivo human strain measurements have been performed in the tibia to try to identify optimal bone strengthening exercises for this bone, but no measurements have been performed in the distal radial metaphysis, the most frequent site of osteoporotic fractures. Using a strain gauged bone staple, in vivo dorsal metaphyseal radial strains and rates of strain were measured in ten female patients during activities of daily living, standard exercises and falls on extended hands. Push-ups and falling resulted in the largest compression strains (median 1345 to 3146 με, equivalent to a 0.1345% to 0.3146% length change) and falling exercises in the largest strain rates (18 582 to 45 954 με/s). On the basis of their high strain and/or strain rates these or variations of these exercises may be appropriate for distal radial metaphyseal bone strengthening

Near infrared light between the wavelengths of 700 and 950 nanometers has a relatively low absorption in tissue, and light of these wavelengths is able to penetrate several centimetres into tissue. Absorption of light is primarily due to hemoglobin. The absorption spectra for oxy-hemoglobin and deoxy-hemoglobin are different, and therefore comparison of light absorption at different wavelengths allows an assessment of the relative concentrations of these two chromophores. Light penetrates bone as well as soft-tissue, and near infrared spectroscopy (NIRS) is potentially a relatively simple, low-cost technique for assessing perfusion in bone. However, although absorption of light is low, scattering is high, and the spatial resolution of the measurement is poor. Application of the technique to the study of bone perfusion requires consideration of the potential confounding absorption arising from adjacent tissues that may have higher perfusion. A clinical problem of interest in our institute is that of vascular changes occurring in bone of patients with spinal cord injury (SCI), and the relationship of these changes to bone density changes. We have, therefore, concentrated on developing NIRS for measurement of the proximal tibia, which is a common site for fractures in these patients. In order to develop a probe for the measurement of bone, experiments were performed with phantoms containing infrared absorbing dyes. Numerical simulations were also performed using the Monte Carlo technique. One of the most important design considerations is the distance between the optode delivering light to the skin, and the collecting optode which detects light. It was found that a separation of 20 mm between the light source and detector was an optimum compromise for minimizing contributions from overlying skin and surrounding muscle, while still being able to detect light efficiently enough to measure dynamic changes in chromophore concentration. We have now started to apply this technique clinically. Relative changes of oxy- and deoxy-hemoglobin concentration have been measured in response to a range of interventions. Comparison has been made of the effect of different interventions designed to modify perfusion of bone (neuro-muscular stimulation of the calf, intermittent pneumatic compression, low amplitude high frequency vibration, and venous tourniquet). We are studying vascular reactivity in chronic SCI patients and controls and we have also started to investigate the effect of daily neuro-muscular stimulation in acute SCI patients. Preliminary results of these clinical studies will be presented

The intermittent administration of parathyroid hormone (PTH) increases the formation of bone by stimulating osteoblastic activity. Our study evaluates the possibility that intermittent treatment with PTH (1-34) may also enhance the implant-bone fixation of stainless-steel screws. Twenty-eight rats received one screw in either one (n = 8) or in both (n = 20) proximal tibiae. We administered either PTH (1-34) in a dosage of 60 μg/kg/day (n = 14) or vehicle (n = 14) over a period of four weeks. At the end of this time, the degree of fixation was assessed by measuring the removal torque on one screw in each rat (n = 28) and the pull-out strength on the contralateral screw (n = 20). PTH increased the mean removal torque from 1.1 to 3.5 Ncm (p = 0.001) and the mean pull-out strength from 66 to 145 N (p = 0.002). No significant differences in body-weight or ash weight of the femora were seen. Histological examination showed that both groups had areas of soft tissue at the implant-bone interface, but these appeared less in the PTH group. These results indicate that intermittent treatment with PTH may enhance the early fixation of orthopaedic implants

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

We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling.

Bone marrow mesenchymal stromal cells were aspirated from immature male green fluorescent protein transgenic rats and cultured in a monolayer. Four weeks after the creation of the osteochondral defect, the rats were divided into three groups of 18: the control group, treated with an intra-articular injection of phosphate-buffered saline only; the drilling group, treated with an intra-articular injection of phosphate-buffered saline with a bone marrow-stimulating procedure; and the bone marrow mesenchymal stromal cells group, treated with an intra-articular injection of bone marrow mesenchymal stromal cells plus a bone marrow-stimulating procedure. The rats were then killed at 4, 8 and 12 weeks after treatment and examined.

The histological scores were significantly better in the bone marrow mesenchymal stromal cells group than in the control and drilling groups at all time points (p < 0.05). The fluorescence of the green fluorescent protein-positive cells could be observed in specimens four weeks after treatment.