Purpose of the study: The current approach for improving the performance of compact bone substitutes is to seed them with selected mesenchymatous stem cells amplified and differentiated to the osteoblastic line in vitro. We hypothesized that the preservation of all these elements in the bone marrow would be most effective for bone tissue formation. Material and methods: Subcutaneous and intramuscular implantation in C57BL/6 mice. We developed a new approach for bone tissue engineering based on an extemporaneous incorporation of total bone marrow into an injectable bone substitute (IBS2). IBS2 is a new polymerizable hydrogel associated with beads of calcium phosphate (BCP) which can be used to implant total bone marrow. A subcutaneous and intramuscular implantation model in mice was tested to analyze the feasibility of this type of graft. Total bone marrow cells from C57BL/6 male mice were seeded in IBS (10 million cells per 100 microliters). This implant was injected subcutaneously (dorsal position) and intramuscularly (left hind foot) in C57BL/6 female mice. TRAP activity was measured under optical microscopy on paraffin embedded HES stained slices at 4 and 8 weeks. Results and discussion: Incorporation of total bone marrow cells in injectable IBS2 produced implants which were rich in mesenchymatous cells, vessels, osteo-clasts, collagen fibers, and osteoid tissue. This demonstrated the great potential of this new approach. In addition, this method is simple and can be performed in the operative room without ex vivo culture. Comparison of this model of extemporaneous cell therapy with a graft of meschymatous cells amplified ex vivo is currently under way

Rarely, the extent of a malignant bone tumour may necessitate resection of the complete humerus to achieve adequate oncological clearance. We present our experience with reconstruction in such cases using a total humeral endoprosthesis (THER) in 20 patients (12 male and eight female) with a mean age of 22 years (6 to 59). We assessed the complications, the oncological and functional outcomes and implant survival. Surgery was performed between June 2001 and October 2009. The diagnosis included osteosarcoma in nine, Ewing’s sarcoma in eight and chondrosarcoma in three. One patient was lost to follow-up. The mean follow-up was 41 months (10 to 120) for all patients and 56 months (25 to 120) in survivors. There were five local recurrences (26.3%) and 11 patients were alive at time of last follow-up, with overall survival for all patients being 52% (95% confidence interval (CI) 23.8 to 74) at five years. The mean Musculoskeletal Tumor Society score for the survivors was 22 (73%; 16 to 23). The implant survival was 95% (95% CI 69.5 to 99.3) at five years.

The use of a THER in the treatment of malignant tumours of bone is oncologically safe; it gives consistent and predictable results with low rates of complication.

The purpose of this study is to enhance massive bone allografts osseointegration used to reconstruct large bone defects. These allografts show >50% complication rate requiring surgical revision in 20% cases. A new protocol for total bone decellularisation exploiting the vasculature can offer a reduction of postoperative complication by annihilating immune response and improving cellular colonization/ osseointegration. The nutrient artery of 18 porcine bones - humerus/femur/radius/ulna - was cannulated. The decellularization process involved immersion and sequential perfusion with specific solvents over a course of one week. Perfusion was realized by a peristaltic pump (mean flow rate: 6ml/min). The benefit of arterial perfusion was compared to a control group kept in immersion baths without perfusion. Bone samples were processed for histology (HE, Masson's trichrome and DAPI for cell detection), immunohistochemistry (IHC : Collagen IV/elastin for intraosseous vascular system evaluation, Swine Leukocyte Antigen – SLA for immunogenicity in addition to cellular clearance) and DNA quantification. Sterility and solvent residues in the graft were also evaluated with thioglycolate test and pH test respectively. Compared to native bones, no cells could be detected and residual DNA was <50ng/mg dry weight. Intramedullary spaces were completely cleaned. IHC showed the preservation of intracortical vasculature with channels bounded by Collagen IV and elastin within Haversian systems. IHC also showed a significant decrease in SLA signaling. All grafts were sterile at the last decellularization step and showed no solvent residue. The control group kept in immersion baths, paired with 6 perfused radii/ulnae, showed that the perfusion is mandatory to ensure complete decellularisation. Our results prove the effectiveness of a new concept of total bone decellularisation by perfusion. These promising results could lead to a new technique of Vascularized Composite Allograft transposable to pre-clinical and clinical models

Hip fractures are associated with poor outcomes and high mortality rates of 30%. The current gold standard to measure bone fragility is a Dual-Energy X-ray Absorptiometry (DEXA) scan measuring bone mineral density. Yet DEXA under-diagnoses bone fragility by 50% (1). To combat the burden of bone fragility, this experimental study combined ultrasound (US) with a sophisticated computational algorithm, namely full wave inversion (FWI), to evaluate femoral bone structure. The aims were to assess the association of bone structure between the proximal femoral diaphysis and femoral neck; secondly to evaluate whether transverse ultrasound could assess bone structure of the proximal femoral diaphysis. Bone structure of 19 ex vivo human femora was assessed by micro-CT analysis (mean age 88.11 years, male:female 13:6)(Nikon HMXST 225). Using ImageJ/BoneJ, three 10.2mm subsections of proximal diaphysis and femoral neck underwent analysis: the total bone volume fraction, cortical parameters (bone volume fraction, porosity, thickness) and trabecular parameters (porosity, thickness, spacing and connectivity). A unique US prototype was developed to analyse fifteen femoral diaphyseal subsections using two P4-1 transducers with a novel tomography sequence (Verasonics, Matlab ver R2019a, FWI TRUST protocol). Comparative quantitative analysis of US and Micro-CT measurements was assessed (Graphpad Prism 8.3.1). Micro-CT analysis of the proximal femoral diaphysis demonstrated low correlation to the femoral neck (Pearson r −0.54 to 0.55). US was able to capture cortical structure, though a wide limit of agreement seen when compared to micro-CT analysis (Bland-Altman range 36–59% difference). This novel US technique was able to capture cortical bone structure. Improvements in methodology and technology are required to improve the analysis of trabecular bone and overall accuracy. Further evaluation of US and FWI is required to develop the technique and determine its role in clinical practice

The August 2024 Oncology Roundup³⁶⁰ looks at: What factors are associated with osteoarthritis after cementation for benign aggressive bone tumour of the knee joint: a systematic review and meta-analysis; Recycled bone grafts treated with extracorporeal irradiation or liquid nitrogen freezing after malignant tumour resection; Intercalary resection of the tibia for primary bone tumours: are vascularized fibula autografts with or without allografts a durable reconstruction?; 3D-printed modular prostheses for the reconstruction of intercalary bone defects after joint-sparing limb salvage surgery for femoral diaphyseal tumours; Factors influencing the outcome of patients with primary Ewing’s sarcoma of the sacrum; The significance of surveillance imaging in children with Ewing’s sarcoma and osteosarcoma; Resection margin and soft-tissue sarcomas of the extremities treated with limb-sparing surgery and postoperative radiotherapy.

Aims

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

Local and systemic concentrations of cobalt (Co) and chromium (Cr) ions may be elevated in patients with accelerated tribo-corrosion at prosthesis bearing surfaces and modular taper junctions. Previous studies by us and others have shown that exposure to these metals negatively affect the viability and function of osteoblasts and osteoclasts in vitro, with implications for bone health. More recently, we have observed an increase in total bone mineral density and reduced bone turnover (TRAP5b and osteocalcin) in patients with well-functioning metal-on-metal hip resurfacing (MOMHR). Here, we provide data to support the hypothesis that osteoclast differentiation and function is altered in this patient population, and that this effect is transferrable through their serum. Patients with well-functioning MOMHR (n=18) at median follow-up of 8 years were individually matched for gender, age and time-since-surgery to a low-exposure group consisting of patients with metal-on-polyethylene total hip arthroplasty (THA). The median circulating concentrations of Co and Cr for the MOMHR group were 2.53µg/L and 2.5µg/L respectively, compared to 0.02µg/L and 0.03µg/L for the THA group. Monocyte fraction of peripheral blood was isolated from these patients, seeded onto dentine wafers and differentiated into osteoclasts using media supplemented with RANKL and M-CSF (osteoclastogenic media, OM). Cultures were monitored for the onset of resorption, following which they were treated with OM, autologous serum or serum from the other individual within the matched MOMHR - THA pair, all supplemented with RANKL and M-CSF. At the end of the culture, cells were TRAP stained and quantified for total osteoclast number, number of resorbing osteoclasts and percentage resorption using the CellD Software Package (Olympus, Southend-on-Sea, U.K.). For cells differentiated in osteoclastogenic media, the resorbing ability of osteoclasts derived from MOMHR patients was reduced by 30% (P=0.046) compared to THA. Correlation analyses showed that chronic exposure to Co and Cr trends towards negative association with resorption ability of these osteoclasts (r = −0.3, P=0.06). Furthermore, the resorbing ability of osteoclasts generated from MOMHR patients and differentiated in autologous serum was reduced 33% (p < 0 .0001), whilst matched THA serum caused a smaller reduction of 14% (p < 0 .01). When cells derived from THA patients were differentiated in autologous serum, the resorbing ability of osteoclasts was similarly reduced by 35% (p < 0 .0001), whilst the matched MOMHR serum also caused a reduction of 21% (p < 0 .0001). Reduced osteoclastogenic response of precursor cells from patients with higher circulating Co and Cr suggests an inherent change in their potential to differentiate into functional osteoclasts. The data also suggests that functional response of mature osteoclasts generated from patient precursor cells are dependent on the prior systemic metal concentrations and the presence of higher circulating CoCr in patients with MOMHR. These effects are modest, but may explain the subtle increase in systemic bone mineral density and decreased bone turnover observed in patients after 8 years exposure compared to age, sex, and exposure-time matched patients who received a conventional THA

Aims

The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD).

Aims

Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.

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

Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

Aims

To compare changes in gait kinematics and walking speed 24 months after conventional (C-MLS) and minimally invasive (MI-MLS) multilevel surgery for children with diplegic cerebral palsy (CP).

Aims

We aimed to address the question on whether there is a place for shoulder stabilization surgery in patients who had voluntary posterior instability starting in childhood and adolescence, and later becoming involuntary and uncontrollable.

Aims

Vitamin E-infused highly crosslinked polyethylene (VEPE) has been introduced into total hip arthroplasty (THA) with the aim of further improving the wear characteristics of moderately and highly crosslinked polyethylenes (ModXLPE and HXLPE). There are few studies analyzing the outcomes of vitamin E-infused components in cemented arthroplasty, though early acetabular component migration has been reported. The aim of this study was to measure five-year polyethylene wear and acetabular component stability of a cemented VEPE acetabular component compared with a ModXLPE cemented acetabular component.

Aims

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

We have previously observed an increase in total bone mineral density and reduced bone turnover (TRAP5b and osteocalcin) in patients with well-functioning metal-on-metal hip resurfacing (MOMHR). Here, we provide data to support the hypothesis that osteoclast differentiation and function is altered in this patient population, and that this effect is transferrable through their serum. Patients with well-functioning MOMHR (cases, n=18) at a median follow-up of 8 years were individually matched for gender, age and time-since-surgery to a low-exposure group consisting of patients with THA (controls, n=18). The monocyte fraction of patient peripheral blood was isolated and differentiated into osteoclasts on dentine wafers using RANKL and M-CSF supplemented media (osteoclastogenic media, OM). Cultures were monitored for the onset of resorption, at which point the cells were treated with OM, autologous serum or serum from matched MOMHR/THA donors, all supplemented with RANKL and M-CSF. At the end of the culture, cells were TRAP-stained and quantified using CellD Software Package, Olympus. When cells were differentiated in standard osteoclastogenic media, the resorbing ability of osteoclasts derived from MOMHR patients was reduced 22%(p<0.0079) compared to THA. The resorbing ability of osteoclasts generated from MOMHR patients and differentiated in autologous serum was reduced 33%(p<0.0001), whilst matched THA serum caused a smaller reduction of 14%(p<0.01). When cells derived from THA patients were differentiated in autologous serum, the resorbing ability of osteoclasts was similarly reduced by 35%(p<0.0001), whilst the matched MOMHR serum also caused a reduction of 21%(p<0.0001). This data suggests that prior exposure to higher circulating Co and Cr in patients with MOMHR reduces osteoclastogenesis, and that the detrimental effect on the functionality of mature osteoclasts is transferable through the serum. This has implications for systemic bone health of patients with MOMHR or modular taper junctions

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.

Summary Statement. The modulation of both quantity and quality of peri-implant bone with either PTH or loading may be viable options to improve implant fixation and patient outcomes. A strong bone-implant interface is essential for successful joint replacement surgery. This study investigated the differences in bone surrounding and within a porous titanium implant after single or combined treatment with two anabolic bone therapies: intermittent parathyroid hormone (teriparatide) and mechanical loading. Porous titanium implants were inserted bilaterally on the distal lateral femurs of rabbits. The right implant was loaded daily (1 MPa, 50 cycles/day) while the left implant was not. Rabbits received daily PTH injections (20 ug/kg) or saline vehicle. Periprosthetic cancellous bone 0.5, 1.0, and 2.0 mm below the implant surface, bone at the 0.25 mm bone-implant interface and total bone within each implant were examined using tissue-level analyses (quantitative backscattered electron microscopy), cellular analyses (immunohistochemistry staining of osteoblasts with procollagen-1 and TRAP staining of osteoclasts), and shear testing (implant-bone interface). Statistical significance was determined using GEE models (p<0.05). For tissue located 0.5 mm below the implant, significant increases in bone area per total area (BA/TA) were observed with PTH treatment (56%) and with loading (27%). Further, an 18% increase in mineralization density with PTH treatment and a 20% increase in mineralization density with loading was found. Loading effects were not present beyond the 0.5 mm periprosthetic region, but PTH significantly increased BA/TA 2.0 mm below and mineralization density 1.0 mm below the implant. Tissue-level changes were supported by increases in osteoblast activity 0.5 mm below the implant with PTH (79%) and loading (34%), as well as by minimal osteoclast changes. At the 0.25 mm implant-bone interface PTH and loading increased BA/TA (16% and 23%, respectively), but only loading increased mineralization density (7%). Further, total integrated bone area was increased 35% with PTH. Both PTH and loading enhanced the mechanical integrity of the implant-bone; shear strength increased 34% and 60%, respectively. Although combined treatment was not synergistic, both PTH and loading individually enhanced the amount and mineralization density of bone at the implant interface and immediately below the interface, thereby increasing the mechanical strength of the metal-bone interface. This research suggests that modulation of both quantity and quality of peri-implant bone may be viable options to improve implant fixation and patient outcomes

Purpose: The study was conducted to evaluate the effect of salmon calcitonin (sCT) on fracture healing in normal and hypogonadal male rats. Material and Method: Fifty six male Wistar rats, aged 3 months, were undertaken hemiosteotomy of the distal femur shaft, of standard length and width. Half of the animals had been orchiectomised at the age of 2 months. The animals were divided in 8 groups, 7 rats each, as follow: A, a (normal, no sCT), B, b (normal+Sct), C,c(orchiectomised) and D,d (orchiectomised+Sct). Salmon calcitonin was administered immediately after the hemiosteotomy in a dose of 5IU/day subcutaneously. Groups A, a, C and c were given placebo. The animals of the groups a b, c, and d were killed at 2 weeks, while the animals of the groups A, B, C, and D were killed at 4 weeks. After the euthanasia, total bone density and cortical bone density of the callus was estimated by peripheral quantitative computed tomography (pQCT). Histological and histomorfometric parameters of the callus were estimated as well. Results: The mean cortical bone density was 1221.93±13.82 (g/cm. 3. ±SE) for the group a, 1281.3±13.57 for b, 1221.41±18.24 for c, 1245±17.12 for d, 1173.45±34.14 for A, 1298.9±11 for B, 1280.78±13.68 for C, and 1279.4U19.2 for D. The mean total bone density was 843.95±13.69 (g/cm. 3. ±SE) for the group a, 859.84±26.46 for b, 892.27±25.3 fore, 861.37±10.88 for d, 818.97±32.5 for A, 926.39±19.6 for B, 888.31±24.19 for C, and 912.75±28.13 for D. Values of cortical bone density in group b and B were significantly greater than a and A, respectively (b> a, p=0.01 and B> A, p=0.002). Total bone density of the callus was statistically greater in group B than A (B> A, p=0.01). According to the histological and histomorphometric results, sCT increased the amount of cartilage (p=0.014) and the amount of woven bone (p=0.015) in group b compared to a, while osteoblasts number showed no difference between the two groups. Comparing groups c and d, sCT increased the amount of cartilage (p=0.036) and the amount of woven bone (p=0.0014) in group d compared to c, while decreased osteoblasts number in group d (p=0.03). In four weeks the amount of cartilage is significant greater in group D versus C (p=0.006), as well as the amount of woven bone (p=0.0004). The size of the callus is significant greater in group D compared to C as well (p=0.052). Conclusion: It appears that salmon calcitonin administration improves significantly the parameters of callus bone density in normal rats and increases the amount of cartilaginous callus and woven bone both in normal and orchiectomised rats

Objective. In this study, we aim to compare total bone amount extracted in total knee arthroplasty in implant design and the bone amount extracted through intercondylar femoral notch cut. Material and Method. In this study, we implemented 10 implants on a total of 50 sawbones from 5 different total knee arthroplasty implant brands namely Nex-Gen Legacy (Zimmer, Warsaw, IN, USA), Genesis 2 PS (Smith&Nephew, Memphis, TN, USA), Vanguard (Biomet Orthopedics Inc., Warsaw, IN, USA), Sigma PS (De Puy, Johnson&Johnson, Warsaw, IN, USA), Scorpio NRG PS (Stryker Co., Kalamazoo, USA). Equal or the closest sizes of each brand on anteroposterior plane were selected, and cuts were made following standard technique(see Fig 1 and 2). Extracted bone pieces were measured in terms of volume and length on three planes, and statistically analysed. The volume of all pieces available after each femoral incision was measured according to Archimedes’ principles. Furthermore, the volume of each intercondylar femoral notch pieces was measured separately from other pieces but with the same method. The measurement of intercondylar femoral notch pieces on 3 planes (medial-lateral, anterior-posterior, superior-inferior) was made using Kanon slide gauge (Ermak Ltd, Istanbul, TR). Femoral notch incision pieces were scanned with CAD/CAM technology using three-dimensional scanner 1 SeriesTM (Dental Wings Inc, Montreal, QC, Canada), and the measurements were confirmed with DWOS CAD 4.0.1 software (Dental Wings Inc, Montreal, QC, Canada)(see figure 3a-e). The volume of 10 intercondylar femoral notch pieces performed through the set of each brand was averaged, and considered as the incision volume of that particular brand. Results. The comparison made by excluding femoral notch cuts did not produce any statistically significant difference between the amounts of bone extracted. The least volumetric value measured in extracted intercondylar femoral notch cut was obtained using Vanguard (3,6±0,4 cm3). The gradually increasing volumes were obtained from Nex-Gen (3,7±0,5 cm3), Sigma (5,7±0,4 cm3), Genesis 2 (6,3±0,3 cm3) and Scorpio NRG (6,7±0,7 cm3), respectively. There was no statistical difference between Genesis 2 and Scorpio NRG, and between Nex-Gen and Vanguard. Conclusion. There are significant differences among implant designs in terms of preserving bone stock, and much of these differences stems from intercondylar femoral notch incision