Aneurysmal bone cyst (ABC) of the spine is a locally aggressive benign lesion which can be treated by en bloc resection with wide margin to reduce the risk of local recurrence. To avoid morbidity associated with surgery, selective arterial embolization (SAE) can be considered the first-line treatment for ABCs of the spine. We previously introduced the use of autologous bone marrow concentrate (BMC) injection therapy to stimulate bone healing and regeneration in ABC of the spine. In this prospective study we described the clinical and radiological outcomes of percutaneous injection of autologous BMC in a series of patients affected by ABCs of the spine. Fourteen patients (6 male, 8 female) were treated between June 2014 and December 2019 with BMC injection for ABC of the spine. The mean age was 17.85 years. The mean follow up was 37.4 months (range 12–60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits. Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48±2.36 HU to 161.71±23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up. The results of this study reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE is contraindicated or ineffective. The initial size of the cyst and its localization does not influence the efficacy of the treatment. However, data suggest that BMC injection could be indicated as treatment of choice for spinal ABC in young adolescent women

Introduction and Objective. Aneurysmal bone cyst (ABC) of the spine is a locally aggressive benign lesion which can be treated by en bloc resection with wide margin to reduce the risk of local recurrence. To avoid morbidity associated with surgery, selective arterial embolization (SAE) can be considered the first-line treatment for ABCs of the spine. Other emerging treatments for ABCs include bisphosphonates, percutaneous doxycycline, sclerotherapy and Denosumab. In addition, we previously introduced the use of autologous bone marrow concentrate (BMC) injection therapy to stimulate bone healing and regeneration in ABC of the spine. One of the potential advantages of such a method is that surgical treatments are not necessary, thus allowing for both a minimally invasive approach and the treatment of poorly accessible lesions. In this prospective study we described the clinical and radiological outcomes of percutaneous injection of autologous BMC in a series of patients affected by ABCs of the spine and followed for at least one year. Materials and Methods. Fourteen patients (6 male, 8 female) were treated between June 2014 to December 2019 with BMC injection for ABC of the spine. The mean age was 17.85 years. The mean follow up was 37.4 months (range 12– 60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits. Results. Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48±2.36 HU to 161.71±23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up. We also observed that five out of six female patients (83.3%) were less than sixteen years old and four of these (66.7%) were managed with a single dose of BMC injection, while a higher percentage of male patients (6/8, 75%) were more than sixteen years old and more than one injection was administered to them. Conclusions. The results of this study reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE is contraindicated or ineffective. The initial size of the cyst and its localization does not influence the efficacy of the treatment. However, BMC injection could be indicated as treatment of choice for spinal ABC in young adolescent women

The nature of the Aneurysmal Bone Cyst (ABC) is still controversial among benign tumor, often identifiable in the “aggressive” form (Enneking stage 3) or pseudotumoral lesion. It is well known instead the very high risk of intraoperative bleeding, indicating a strongly unfavorable relationship between the surgical morbidity and the nature of the disease. Recently, excellent results have been obtained in the treatment of ABC by repeated arterial embolizations (SAE), without any surgery, while initial experiences with administration of denosumab and doxycycline are still under study. This study presents the results of our initial experience in the treatment of vertebral ABC through the use of concentrated autologous mesenchymal stem cells (MSCs). Two teenagers aged 15 years, male, and 14 years, female, came to our attention both with diagnosis of ABC in C2 vertebra which was histologically confirmed. They were both neurologically intact, the girl complained of neck pain. The arteriography showed in both cases close relationships between the pathological ABC vascularization and the vertebral and cervical ascending arteries, making treatment by selective arterial embolization unsuitable. After discussion with the parents of patients, we jointly decided to undertake the treatment by direct injection of MSCs preceded, in the same operative session, by harvesting from the iliac crest of 60 cc of bone marrow (by needle aspiration) and its separation with the use of concentration system Res-Q ™ 60 BMC. In the second case the treatment was repeated two times at distance of 4 months. The clinical and radiological follow-up is to of 30 months from the first treatment in both cases. In the first case the presence of newly formed bone within the ABC appeared as a clear sign of recovery just a month after the first treatment and increased gradually, until the cyst appeared completely ossified one year after the treatment, with associated disappearance of the pain. In the second case an initial sclerotic peripheral margin appeared after the second treatment and later ossification progressed, concurrently with the disappearance of the pain. Treatment with selective serial arterial embolization is considered effective in the treatment of ABC even if not without risks, mainly related to the frequent and repeated exposure to ionizing radiation. Furthermore, in a certain percentage of cases the procedure is not technically executable, especially for the presence of arteries afferent to the medullar vascularization. Inconsistent results were obtained with other procedures: the injection of calcitonin, steroid, alcoholic solutions, or the use of sclerosing substances. Radiation therapy, though very effective, it is not considered the first choice. Recently, promising results have been achieved by the injection of mononuclear cells derived from bone marrow in the treatment of Aneurysmal Bone Cyst. Based on the early results obtained in the two cases described, the injection of MSCs can be considered a valid alternative in the treatment of vertebral ABCs untreatable by embolization

Abstract. Background. Benign osteolytic lesions of bone represent a diverse group of pathological and clinical entities. The aim of this study is to highlight the importance of intraoperative endoscopic assessment of intramedullary osteolytic lesions in view of the rate of complications during the postoperative follow up period. Methods. 69 patients (median age 27 years) with benign osteolytic lesion had been prospectively followed up from December 2017 to December 2018 in a university hospital in Cairo, Egypt and in a level-1 trauma center in United Kingdom. All patients had been treated by curettage with the aid of endoscopy through a standard incision and 2 portals. Histological analysis was confirmed from intraoperative samples analysis. All patients had received bone allografts from different donor sites (iliac crest, fibula, olecranon, etc). None of them received chemo or radiotherapy. Results. Most of lesions were enchondroma (n=29), followed by Aneurysmal bone cyst (ABC) (n=16), Fibrodysplasia (n=13), Chondromyxoid fibroma (n=3), simple bone cyst (n= 3), non-ossifying fibroma (n= 3), giant cell tumour (n= 1) and chondromyxoid fibroma (n = 1). Site of lesion varied from metacarpals (n = 29), femur (n= 1), lower leg (n= 31), and upper limb (n=18). Complications happened only in 9 cases (pathological fractures (n=2), infection (n= 1), recurrence (n=3, all aneurysmal bone cyst), residual pain (n= 3, all in tibia). None of cases developed malignant transformation. Conclusion. Endoscopy is recommended in management of benign osteolytic bone lesions; as it aids in better visualization of the hidden lesions that are missed even after doing apparently satisfactory blind curettage. From our study the recurrence rate is 2% compared to the known 12–18% recurrence rate in the blind technique from literature

Abstract. Background. Schwannomas are slow-growing, benign tumours normally originating from the Schwann cells of the nerve sheath. Intraosseous schwannoma accounts for 0.175% of primary bone tumours and extremely rare especially outside the axial skeleton. Monoclonal gammopathy has been associated with soft tissue schwannomas but never with the intraosseous variety. Presenting problem. A 55-year-old woman with a background of monoclonal gammopathy of undetermined significance (MGUS) presented with a 2-year history of right thigh pain. CT scan showed a well defined, lytic lesion with a thin peripheral rim of sclerosis in the midshaft of the femur. MRI displayed a hyperintense, well marginated and homogenous lesion. Definitive diagnosis was made based on the classical histopathological appearance of schwannoma. Clinical management. We managed our patient with local curettage and prophylactic cephalomedullary nailing on the basis of a high mirel score. Discussion. Intraosseous schwannomas are poorly understood but most commonly reported in middle-aged women. Radiologically, their differential diagnosis includes malignant bone tumours, solitary bone cysts, aneurysmal bone cysts and giant cell tumours. As a result, they are usually diagnosed incidentally on histology. Although malignant transformation is possible in soft tissue schwannomas, all intraosseous schwannomas reported to date have been benign. This case demonstrates the importance of suspecting intraosseous schwannoma as a differential diagnosis for lytic bone lesions to avoid the overtreatment of patients. We also highlight monoclonal gammopathy of undetermined significance as a potential risk factor for a poorly understood disease and make recommendations about the appropriate management of these lesions. 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

Spinal surgery deals with the treatment of different pathological conditions of the spine such as tumors, deformities, degenerative disease, infections and traumas. Research in the field of vertebral surgery can be divided into two main areas: 1) research lines transversal to the different branches; 2) specific research lines for the different branches. The transversal lines of research are represented by strategies for the reduction of complications, by the development of minimally invasive surgical techniques, by the development of surgical navigation systems and by the development of increasingly reliable systems for the control of intra-operative monitoring. Instead, specific lines of research are developed within the different branches. In the field of oncological pathology, the current research concerns the development of in vitro models for the study of metastases and research for the study of targeted treatment methods such as electrochemotherapy and mesenchymal stem cells for the treatment of aneurysmal bone cysts. Research in the field of spinal deformities is focused on the development of increasingly minimally invasive methods and systems which, combined with appropriate pharmacological treatments, help reduce trauma, stress and post-operative pain. Scaffolds based on blood clots are also being developed to promote vertebral fusion, a fundamental requirement for improving the outcome of vertebral arthrodesis performed for the treatment of degenerative disc disease. To improve the management and the medical and surgical treatment of vertebral infections, research has focused on the definition of multidisciplinary strategies aimed at identifying the best possible treatment path. Thus, flow-charts have been created which allow to manage the patient suffering from vertebral infection. In addition, dedicated silver-coated surgical instrumentation and bone substitutes have been developed that simultaneously guarantee mechanical stability and reduce the risk of further local infection. In the field of vertebral traumatology, the most recent research studies have focused on the development of methods for the biostimulation of the bone growth in order to obtain, when possible, healing without surgery. Methods have also been developed that allow the minimally invasive percutaneous treatment of fractures by means of vertebral augmentation with PMMA, or more recently with the use of silicone which from a biomechanical point of view has an elastic modulus more similar to that of bone. It is clear that scientific research has changed clinical practice both in terms of medical and surgical management of patients with spinal pathologies. The results obtained stimulate the basic research to achieve even more. For this reason, new lines of research have been undertaken which, in the oncology field, aim at developing increasingly specific therapies against target receptors. Research efforts are also being multiplied to achieve regeneration of the degenerated intervertebral disc and to develop implants with characteristics increasingly similar to those of bone in order to improve mechanical stability and durability over time. Photodynamic therapies are being developed for the treatment of infections in order to reduce the use of antibiotic therapies. Finally, innovative lines of research are being launched to treat and regenerate damaged nerve structures with the goal, still far from today, of making patients with spinal cord injuries to walk

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

Bone tissue engineering constructs (BTEC) combining natural resorbable osteoconductive scaffolds and mesenchymal stem cells (MSCs) have given promising results to repair critical size bone defect. Yet, results remain inconsistent. Adjonction of an osteoinductive factor to these BTEC, such as rh-BMP-2, to improve bone healing, seems to be a relevant strategy. However, currently supraphysiological dose of this protein are used and can lead to adverse effects such as inflammation, ectopic bone and/or bone cyst formation. Interestingly, in a preliminary study conducted in ectopic site in a murine model, a synergistic effect on bone formation was observed only when a low dose of rh-BMP-2 was associated with MSCs-seeded coral scaffolds but not with a high dose. The objective of the study was then to evaluate a BTEC combining coral scaffold, MSCs and a low dose of rh-BMP-2 in a large animal model of clinical relevance. Sixteen sheep were used for this study. MSCs were isolated from an aspirate of bone marrow harvested from the iliac crest of each sheep receiving BTEC with MSCs, cultivated and seeded on Acroporacoral scaffolds one week before implantation. Rh-BMP-2, used at two different doses (low dose: 68μg/defect and high dose: 680μg/defect), was diluted and absorbed on Acroporacoral scaffold one day before implantation. Metatarsal segmental bone defects (25 mm) were made in the left metatarsal bone of the sheep, stabilized by plate fixation, and filled with Acroporacoral scaffolds loaded with either (i) MSCs and a low dose of rh-BMP-2 (Group 1;n=6), (ii) a low dose of rh-BMP-2 (Group 2;n=5), (iii) a high dose of rh-BMP-2 (Group 3;n=5). Standard radiographs were taken after each surgery and each month until sheep sacrifice, 4 months postoperatively. Bone healing and scaffold resorption were assessed by micro-computed-tomography (μCT) and histomorphometry. Results were compared to a historical control group in which coral scaffolds were loaded with MSCs. Bone volumes (BV) evaluated by μCT and bone surfaces (BS) evaluated by histomorphometry did not differ between groups (BV: 1914±870, 1737±841, 1894±1028 and 1835±1342 mm. 3. ; BS: 25,41±14,25, 19,85±8,31, 25,54±16,98 and 26,08±22,52 %; groups 1, 2, 3 and control respectively); however, an higher bone union was observed in group 1 compared to the others (3, 1, 2 and 2 sheep with bone union in groups 1, 2, 3 and control respectively). No histological abnormalities were observed in any group. Coral resorption was almost complete in all specimens. No significant difference in coral volumes and coral surfaces was observed between groups. A trend towards a higher variability in coral resorption was noted in group 1 compared to the others. There seems to be a benefit to associate low dose of rh-BMP-2 with MSCs-seeded coral scaffolds as this strategy allowed an increase of bone unions in our model. Yet, results remain inconsistent. Although, defective coupling between scaffold resorption and bone formation impaired bone healing in some animals, adjunction of rh-BMP-2 (even at low dose) to CSMs loaded construct is a promising strategy for bone tissue engineering

The CCI mobile bearing ankle implant used at our orthopedic department 2010–2013, was abandoned due to failures and findings of bone loss at revision. The aim of this study was to a) Determine our true revision rate, b) Investigate accuracy of measuring prevalence, size and location of periprosthetic bone cysts through X-ray and CT and c) Relate these findings to implant alignment and patient reported outcome measurements (PROMs). 51 primary surgeries were performed, prior to this study 8 had been revised. Out of 43 un-revised patients, 36 were enrolled and underwent evaluation with metal artefact reduction CT-scans and conventional X-ray. They filled out 3 PROMs; SEFAS, SF-12, EQ-5D. Cyst volume larger than 0.1 ml was measured using VITREA volume tools for CT-scans and calculation of spherical volume for X-rays; using AP- and lateral projections. Location of lesions was recorded, according to their position relative to the implant. Medial-/lateral- and anterior-/posterior tilt of the implant parts was measured using IMPAX built in measuring tools, applied to AP- and lateral X-ray projection. The relation between lesions location and alignment of components was analyzed by logistic regression. Bias and ICC estimation between CT and X-ray was analyzed by mixed effect model. Log transformation was used to fit the normal distribution assumption. PROMs association to osteolytic volume was analyzed by linear- and logistic regression. P-values of 0.05 were considered statistically significant. Finding large osteolytic lesions caused 4 additional patients to undergo revision and 7 are being monitored due to high risk of failure. Of the original 51 implants 14 have been revised. 8 cases because of osteolytic lesions and aseptic loosening (true revisions w. exchange of components or bone transplants), 3 periprosthetic fractures (2 non-traumatic fractures) and 3 cases of exostosis. The 3- and 5 year revision rate was 14% and 16% for true revisions and 17% and 27% overall. Cystic lesions were found in 81% of participants. Total cyst-volume was on average 13% larger on X-ray, however this difference was not significant (p = 0.55), with intraclass correlation being 0.66. Total cystic volume was not significantly related to PROM-scores (P 0.16–0.5). Location of cysts showed association with alignment of components (P 0.02–0.08). Mean tibia component anterior tilt was 89 degrees (SD 4). Mean medial tilt was 91 degrees (SD 3) for the tibial and 90 degrees (SD 4) for the talar component. The implant investigated performs below standard, compared to public registries. 1, 2. that report overall 5 year revision rates at 5 – 6.5%. We obtained larger measurements from X-rays than CT, unlike previous studies comparing these modalities. Cysts were common and large. Correlation between lesion location and alignment of implant, with valgus and anterior tilt of components causing more lesions in adjacent zones, may suggest a link between implant failure and alignment of components

Background. Autologous Chondrocyte Implantation (ACI) is a procedure which is gaining acceptance for the treatment of cartilage defects in the knee with good results and a long term durable outcome. Its use in other joints has been limited, mainly to the ankle. We aimed to assess the outcome of ACI in the treatment of chondral and osteochondral defects in the hip. Methods. Fifteen patients underwent ACI for chondral or osteochondral defects in the femoral head with a follow up of upto 8 years (mean of 2 years) in our institution with a mean age of 37 years at the time of operation. Pre-operatively hip function was assessed by using the Harris Hip Score and MRI. Post-operatively these were repeated at 1 year and hip scores repeated annually. Failure was defined as a second ACI to the operated lesion or a conversion to a hip resurfacing or replacement. Results. The mean pre-op Harris Hip Score (HHS) was 55 which increased to 63 at 1 year and 70 at the latest follow up. Patients who underwent ACI for cartilage defects secondary to trauma (four) were better with a mean HHS of 69 at a mean follow up of 3.5 years. Six patients underwent THR at a mean of 32 months and were classed as failures. Five patients had evidence of avascular necrosis (AVN) of the femoral head post operatively of which four AVN pre-op. Conclusion. These early results suggest that ACI could be a viable option for the treatment of isolated chondral defects in the hip. The presence of AVN or bone cysts pre-op may be a predictor of failure

Bony tumours of the foot account for approximately 3% of all osseous tumours. However, literature regarding os calcis tumours comprises individual case reports, short case series or literature reviews, with the last large case series in 1973. We retrospectively reviewed the medical notes and imaging for all patients with calcaneal tumours recorded in the Scottish Bone Tumour Registry since the 1940's. Demographics, presentation, investigation, histology, management and outcome were reviewed. 38 calcaneal tumours were identified. Male to female ratio 2:1, mean age at presentation 30 with heel pain and swelling, average length of symptoms 9 months. 4 cases present with pathological fracture. 24 tumours benign including 6 unicameral bone cysts, 3 chondroblastoma, 3 PVNS with calcaneal erosion, and a wide variety of individual lesions. 13 malignant tumours comprising 6 osteosarcoma, 5 chondrosarcoma and 2 Ewings sarcoma. 1 metastatic carcinoma. Tumours of the calcaneus frequently are delayed in diagnosis due to their rarity and lack of clinician familiarity. They are more common in men and have a 1 in 3 risk of malignancy, covering a wide variety of lesions. Outcome is dependent on early diagnosis, timely surgery and most importantly neo-adjuvant chemotherapy. Diagnosis is often made on plain radiograph but MRI is the gold standard. We present the largest case series of calcaneal tumours, from our experience with the Scottish Bone Tumour Registry. Despite their rarity clinicians should maintain a high index of suspicion as accurate and timely diagnosis is important to management and outcome

Introduction. Hand tumors are usually rare and there is not much literature about series of cases. We have studied a series of 110 cases. Hand tumors do consists of both benign and malignant cases. Methods. We studied series of 110 cases at Karnataka Institute of Medical Sciences, Hubli and Mysore Medical College & Research Institute, Mysore. We retrospectively reviewed the records of 110 patients who underwent double ray amputations at our center over few years: few had amputations of the fourth and fifth rays and others amputation of the second and third rays. Mean age at surgery was 34 years (range, 10–45 years), and minimum follow up was 64 months (mean, 98 months; range, 64–136 months). Some patients had high-grade soft tissue sarcomas of the hand, synovial sarcomas, malignant peripheral nerve sheath tumors, and undifferentiated sarcoma. No patients had detectable metastases at surgery. Results. All patients were completely disease-free at latest follow up. One patient was alive with lung metastases detected 32 months after surgery. No patients developed local tumor recurrence. Functional assessment showed a mean Musculoskeletal Tumor Society score of 24 (range, 19–28) and mean grip strength 24% of the contra lateral side (range, 17%–35%). Conclusions. The majority of osseous tumors of the hand are benign. The surgeon who evaluates and treats osseous tumors of the hand has to be familiar with limb anatomy, tumor biology, various presentations of the tumors and the range of treatment possibilities and their limitations. Lesions in the hand more often present earlier in their course than those at other sites, just because they are more likely to superficial and easily noticed. Ganglion cyst is the most frequently encountered comprising 50–70% of benign tumors of hand. Enchondroma was the next common benign bone tumour followed by osteoid osteoma, osteoblastoma, aneurismal bone cyst, giant cell tumor, epidermoid cyst, and osteochondroma. Although malignant neoplasms in the hand that arise from tissues other than the skin are very rare, the hand may be the site of distant breast, lung, kidney, esophagus, or colon adenocarcinoma metastases, most of which have a predilection for the distal phalanges. Malignant tumours of the hand are rare, although there remain many instances in which marginal excisions are performed for unsuspected malignant hand lesions. Suboptimal biopsy incisions and inadvertent contamination during these excisions may result in larger resections or amputations being necessary to ensure complete removal of the tumour with negative margins

Osteoarthritis (OA) affects bone cartilage and underlying bone. Mechanically, the underlying bone provides support to the healthy growth of the overlying cartilage. However, with the progress of OA, bone losses and cysts occur in the bone and these would alter the biomechanical behaviour of the joint, and further leading to bone remodelling adversely affect the overlying cartilage. Human femoral head and femoral condyle were collected during hip or knee replacement operation due to the end stage of osteoarthritis (age 50–70), and the cartilage patches were graded and marked. A volunteer patient, with minor cartilage injury in his left knee while the right knee is intact, was used as control. Peripheral quantitative computed tomography (pQCT) was used to scan the bone and to determine the volumetric bone mineral density (vBMD) distribution. The examination of retrieved tissue explants from osteoarthritic patients revealed that patches of cartilage were worn away from the articular surface, and patches of intact cartilage were left. The cysts, ranging from 1 to 10mm were existed in all osteoarthritic bones, and were located close to cartilage defects in the weight-bearing regions, and closely associated with the grade of cartilage defect as measured by pQCT. The bone mineral density (vBMD) distribution demonstrated that the bones around cysts had much higher vBMD than the trabecular bone away from the cysts. Compared to the subchondral bone under thicker cartilage, subchondral bone within cartilage defect has higher vBMD. This may result from the mechanical stimulation as a result of bone-bone direct contact with less protection of cartilage in cartilage defect regions. This study showed an association between cartilage defect and subchondral bone mineral density distribution. Cysts were observed in all osteoarthritic samples and they are located close to cartilage defects in the weight-bearing regions. Cartilage defect altered the loading pattern of the joints, this leading to the bone remodelling and resultant bone structural changes as compared to the normal bone tissues. This work was financially supported by The ARUK Proof of Concept Award (grant no: 21160)

Objectives

The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01).