In 2021 the bone grafting market was worth €2.72 billion globally. As allograft bone has a limited supply and risk of disease transmission, the demand for synthetic grafting substitutes (BGS) continues to grow while allograft bone grafts steadily decrease. Synthetic BGS are low in mechanical strength and bioactivity, inspiring the development of novel grafting materials, a traditionally laborious and expensive process. Here a novel BGS derived from sustainably grown coral was evaluated. Coral-derived scaffolds are a natural calcium carbonate bio-ceramic, which induces osteogenesis in bone marrow mesenchymal stem cells (MSCs), the cells responsible for maintaining bone homeostasis and orchestrating fracture repair. By 3D printing MSCs in coral-laden bioinks we utilise high throughput (HT) fabrication and evaluation of osteogenesis, overcoming the limitations of traditional screening methods.

MSC and coral-laden GelXA (CELLINK) bioinks were 3D printed in square bottom 96 well plates using a CELLINK BIO X printer with pneumatic adapter Samples were non-destructively monitored during the culture period, evaluating both the sample and the culture media for metabolism (PrestoBlue), cytotoxicity (lactose dehydrogenase (LDH)) and osteogenic differentiation (alkaline phosphatase (ALP)). Endpoint, destructive assays used included qRT-PCR and SEM imaging.

The inclusion of coral in the printed bioink was biocompatable with the MSCs, as reflected by maintained metabolism and low LDH release. The inclusion of coral induced osteogenic differentiation in the MSCs as seen by ALP secretion and increased RUNX2, collagen I and osteocalcin transcription.

Sustainably grown coral was successfully incorporated into bioinks, reproducibly 3D printed, non-destructively monitored throughout culture and induced osteogenic differentiation in MSCs. This HT fabrication and monitoring workflow offers a faster, less labour-intensive system for the translation of bone substitute materials to clinic.

Acknowledgements: This work was co-funded by Enterprise Ireland and Zoan Biomed through Innovation Partnership IP20221024.

Aims

There is ambiguity surrounding the degree of scaphoid union required to safely allow mobilization following scaphoid waist fracture. Premature mobilization could lead to refracture, but late mobilization may cause stiffness and delay return to normal function. This study aims to explore the risk of refracture at different stages of scaphoid waist fracture union in three common fracture patterns, using a novel finite element method.

Abstract

An increased prevalence of osteoarthritis (OA) in post-menopausal women has led to the suggestion that hormonal factors may play a role in the pathogenesis. This study aims to examine if undergoing a hysterectomy, both with retention and removal of ovaries, predisposes women to OA and secondly if the development is influenced by hormone replacement therapy (HRT).

Statistical shape modelling (SSM) is a method of image analysis allowing for detection of subtle shape variation described by landmark points. Through the generation of linearly independent modes of variation, each image can be described in terms of numerical scores. 149 radiographs from female participants of the Osteoarthritis Initiative (OAI) were examined to compare hip morphology in those who had undergone hysterectomies compared to controls.

No differences were observed in BMI, age, height or weight between groups. ANOVA and Games-Howell post-hoc analysis showed that modes 3 and 5 were statistically significant. Lower mode 3 scores were associated with hysterectomy (p=0.019), with narrowing of the femoral neck and increased acetabular coverage. Lower mode 5 scores were associated with hysterectomy and oophorectomy (p=0.049), displaying reduced coverage of the femoral head, superolateral migration of the femoral head and larger greater trochanter. No associations were observed between HRT use and OA.

The subtle morphologic features of hip OA present in only hysterectomised women suggests undergoing a hysterectomy may be a predisposing factor and a clinical consideration. The use of HRT was not observed to influence the development of OA and thus cannot be suggested as a protective measure.

To discover whether orthopaedic surgeons follow the BOA guidelines for secondary prevention of fragility fractures, a retrospective audit on neck of femur fractures treated in our hospital in October/November 2003 was carried out. There were 27 patients. Twenty-six patients (96%) had full blood count measured. LFT and bone-profile were measured in 18 patients (66%). Only nine patients (30%) had treatment for osteoporosis (calcium and vitamin D). Only one patient was referred for DEXA scan.

Steps were taken to create better awareness of the BOA guidelines among junior doctors and nurse practitioners. In patients above 80 years of age it was decided to use abbreviated mental score above 7 as a clinical criterion for DEXA referral. A hospital protocol based on BOA guidelines was made.

A re-audit was conducted during the period August-October 2004, with 37 patients. All of them had their full blood count and renal profile checked (100%). The bone-profile was measured in 28 (75.7%) and LFT in 34 (91.9%) patients. Twenty-four patients (65%) received treatment in the form of calcium + Vit D (20) and bisphosphonate (4). DEXA scan referral was not indicated in 14 patients as 4 of them were already on bisphosphonates and 10 patients had an abbreviated mental score of less than 7. Among the remaining 23 patients, nine (40%) were referred for DEXA scan. This improvement is statistically significant (p=0.03, chi square test).

The re-audit shows that, although there is an improvement in the situation, we are still below the standards of secondary prevention of fragility fractures with 60% of femoral fragility fracture patients not being referred for DEXA scan. A pathway lead by a fracture liaison nurse dedicated to osteoporotic fracture patients should improve the situation.

Introduction: Primary cilia are found on virtually every mammalian cell; however, functions of primary cilia have not been extensively studied in chondrocytes. Interestingly, defects in the primary cilium result in skeletal defects such as polydactyly in Bardet-Biedl Syndrome (Bbs), a ciliary disorder that also results in obesity and retinopathy.

Wild-type mice and mutant mice of the ciliary proteins Bbs1, Bbs2, and Bbs6 were evaluated for histological and biochemical differences in chondrocytes from articular cartilage. The aim was to examine cartilage abnormalities related to ciliary defects in Bbs mutant mice.

Methods: Using immunofluorescence microscopy, chondrocytic cilia were visualized from load-bearing joints. Knee joints were then embedded in paraffin, stained, and serially sectioned. Articular cartilage was analyzed microscopically to evaluate histological differences between wild-type and mutant mice. Separately, chondrocytes were expanded in cell culture and implanted in solid agarose plugs that were sectioned over two weeks to quantify differences between mouse strains.

Results: Significant differences in ciliary morphology were not identified between mouse strains. However, histological analysis revealed that Bbs mutant mice had significantly lower articular joint thickness (p< .05) and lower proteogly-can content saturation (p< .05) than wild-type. Moreover, there were significant cell distribution differences between mouse strains (p< .05), indicating that mutant cartilage had changes consistent with early osteoarthritis. In cell culture, the fraction of ciliated cells in Bbs mutant cultures was significantly lower than in wild-type cultures (p< .05).

Discussion/Conclusion: These data indicate that Bbs gene function plays a role in normal cartilage maintenance and suggest that the chondrocytic primary cilium contributes significantly to articular cartilage biochemistry.

Distal radioulnar joint surgery has been dominated by different types of partial or complete ulnar head excision. This remains a reasonable option in rheumatoid surgery. However, in the long run, this can create a number of problems. We have used Herbert modular prosthesis to tackle these very difficult situations. This prosthesis comprises of a press fit stem in three sizes and a ceramic head, also available in three sizes.

In Wrightington hospital upper limb unit 61 patients underwent Herbert ulnar head replacement. Fifty-eight were clinically and radiologically reviewed.

Between December 1998 and December 2002 21 male and 27 female patients were operated. The mean age was 49.8 years with a range of 28–72 years. Twenty two left, eighteen right and two bilateral replacements were performed. The mean follow-up was 20.02 months with a range of 3–60 months.

All patients were reviewed by an independent observer using range of motion, grip strength and satisfaction as outcome.

Primary diagnoses included failed Darrach, Bower, Sauve Kapandji and traumatic ulnar head excision. Forty-five patients were satisfied with the outcome. Pain score showed a mean improvement of 4 with a range of 0–10. The grip strength compared to normal side was decreased in 50% of the patients. The range of motion compared to normal side improved by a mean of 10 degrees (range 3–20) in supination and 13 (range 4–23) in pronation.

Radiological review showed new bone (8) and notch formation (9). Stress shielding of 0–19mm was observed in distal ulna with revision or emergency stem.

Complication occurred in eight patients instability (4), RSD (1), implant failure (1) and two others. Twelve patients required further surgery. No loosening was observed at revision.

Conclusion: This is a suitable revision and primary replacement but no long term following is required.

Introduction: The emergence of multidrug resistant Gram negative bacilli susceptible to hardly any beta lactam compound has led to infections close to a therapeutic dead end. In such circumstances, Imipenem-cilastatin (I-C) is often the only remaining therapeutic option. We report our experience with the prolonged administration of high-doses of I-C in the treatment of osteoarticular infections with bacteria resistant to other beta-lactam agents (or 4^l generation cephalosporins in 14 cases).

Materials and methods: Our retrospective study over 7 years included 29 patients with septic arthritis (n=3) continuous osteitis (n=6), septic non-union(n=12) and prosthetic joint infections (n=8). Treatment included an extensive surgical debridement and post-operative combination antibiotherapy with intravenous I-C and aminoside (54%) and/or fluoroquinolones (46%) and/or fosfomycin (29%). Associated microorganisms requiring yet additional antimicrobial agents were associated in 17 (59%) cases. I-C was maintained for an average of 46 days (extremes 21–90), at an average dose of 3,8g/day (extremes 2–6). The bacteria warranting I-C were cephalosporinase hyperproducing Enterobacter cloacae (38%), extended spectrum beta-lactamases producing enterobacteria (31%), Pseudomonas aeruginosa (21%) and/or Acinetobacter baumanii (21%).

Results: Early outcome was favorable in 24 patients (82%). Two patients relapsed with the bacteria requiring I-C. Three failed to negate succion fluid cultures : one was discharged with no change in his condition, one agreed to a leg amputation and the third died of candidemic septic shock in SICU with drainage fluid still bactériologie ally positive. Repeated secondary colonization and systemic infection with yeasts led to a monitoring of yeast load. Per os amphotencin B and immediate treatment of urinary colonization prevented further systemic dissemination of candical infections. No other tolerance incidents were noted. Acquired resistance occurred only once in a P. aeruginosa isolate while Imipenem-cilastatin was chosen to cover an ESBL producing Escherichia coli. Secondary treatment with ceftazidime was then successful in eradicating P. aeruginosa.

Conclusion: I-C has been widely used for the treatment of mixed flora infections as a wide spectrum antibiotic.

We report good tolerance of high posology long term administration in documented osteoarticular indications if yeast colonization is properly monitored, and eradication rates are comparable to those reported in infections with susceptible bacteria.

Purpose: Although hamstring retraction is a frequent complication of spastic hypertoniq, very few series have been reported in adults. The purpose of this study was to evaluate results of therapeutic modalities proposed: distal hamstring tenotomy and use of an external fixator in case of permanent knee flexion.

Material and methods: This retrospective series included 37 cerebral palsy patients, 59 with permanent knee flexion. Mean flexion was 69° (20–130°). Mean motion was 61° (10–100°). Deformation of the supra and infra joints was present in 82%. There were 22 patients with bilateral permanent knee flexion. Simple tenotomy of the sartorius, the semitendinous and the gracilis with lengthenings of the semimembranous and biceps. Disinsertion of the gastrocnemius and section of posterior aponeurosis were associated as needed. Postoperative immobilization was achieved with a Zimmer cast in case of moderate flexion and with an external femorotibial fixator in case of major deformation. Postoperative rehabilitation exercises performed several times daily were initiated in all patients.

Results: At mean follow-up of 641 days, residual flexion was 6° (0–40°) and mean joint motion was 111°. All knees were stable. Three dehiscent wounds required surgical repair. The function objective, established pre-operatively, was achieved or exceeded.

Discussion: When postoperative immobilization is necessary, external fixation limits cutaneous risks and facilitates rehabilitation. It appears to be better than successive cases. Unlike other authors, we did not find section of the posterior cruciate ligament to be necessary.

Conclusion: Distal hamstring tenotomy associated with postoperative immobilization with an external fixator is a reliable and effective technique for the treatment of permanent knee flexion in cerebral palsy adults.

Transient osteoporosis of the hip is a rare condition of unknown aetiology affecting middle aged men with no risk factors and women in their third trimester of pregnancy. The condition invariably resolves spontaneously, however, due to its rarity and initially normal plain radiographs, the syndrome is often not appreciated early in its development, and particularly represents a diagnostic problem of differentiation from osteonecrosis.

We present a case of unilateral transient osteoporosis of the hip in a 52 year old male and a case of bilateral hip involvement in a 32 year old female in her 35th week of pregnancy. Both cases include the initial and follow-up plain radiographs, MRI and DEXA scan findings, through to symptomatic resolution.

We present a literature review of the disease and analyse the current evidence on aetiology, the problems in diagnosis and the current treatment modalities.

Chondrocyte sensitivity to strain depends on signal transduction pathways which include integrin-dependent increases in intracellular calcium. Human articular chondrocytes were cultured as monolayers in silicone dishes. After loading the cells with the calcium-fluorescent dye Fluo-3/AM the dishes were mounted in a 4-point bending apparatus and then fixed to a laser scanning confocal microscope. Biaxial substrate strain (15 000e) was applied to the silicone dish via a hand operated cam rotated at ~60 RPM (1 Hz) for 10 or for 50 cycles. Changes in intracellular calcium in single cells were determined by measuring the mean pixel values in the basal and stimulated images taken at different time points. The data reported for 50 cycle treatments represent 49 single cells of six independent cell isolations. The data for 10 cycle strain treatment are from a single experimental setup.

Increases in intracellular calcium were consistently observed in chondrocytes exposed to 15 000me for 50 cycles in a range from 1.3- to 4.0-fold with an average of 2.3-fold (SD=0.79). Few cells responded before 30 minutes but most of the responses occurred 30–60 minutes after strain. Consistent intracellular Ca++-increases were also seen after 10 strain cycles, however responses were detected within 5 minutes post-strain. The relative increase (2.7-fold ± 1.7) was similar in magnitude to 50 cycle responses.

Intracellular Ca++-fluxes in chondrocytes and other cells occur by at least two different mechanisms: through stretch-activated channels in the plasma membrane permit immediate Ca++-influx during strain application or by Ca++-efflux from intracellular compartments stimulated by slower acting second messengers. Our results suggest that the early response to 10 strain cycles is due to Ca++-influx via membrane channels while the later response to 50 cycles is due to Ca++-efflux from intracellular compartments, probably mediated by cytokines released in response to an initial Ca++-influx from the medium.