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The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 1 | Pages 120 - 125
1 Jan 2004
Nilsson M Wang J Wielanek L Tanner KE Lidgren L

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models. A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth


Bone & Joint Research
Vol. 11, Issue 3 | Pages 162 - 170
14 Mar 2022
Samvelyan HJ Huesa C Cui L Farquharson C Staines KA

Aims

Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2-/-) display accelerated bone growth.

Methods

We examined vulnerability of Socs2-/- mice to OA following surgical induction of disease (destabilization of the medial meniscus (DMM)), and with ageing, by histology and micro-CT.


The Journal of Bone & Joint Surgery British Volume
Vol. 64-B, Issue 5 | Pages 607 - 611
1 Dec 1982
Macnicol M Catto A

Twenty-four patients treated for tibial shortening secondary to poliomyelitis were reviewed at least 20 years after operation. All subjects were active and only one expressed doubt about the value of tibial lengthening, considering the period of hospitalisation to have been a significant drawback. Approximately five centimetres were added to the length of the treated tibiae. Only one of the nine patients with lengthening of over five centimetres was able to walk at a rate of more than five kilometres per hour, compared with seven of the remaining 15 whose tibiae had been lengthened five centimetres or less


The Journal of Bone & Joint Surgery British Volume
Vol. 70-B, Issue 2 | Pages 315 - 318
1 Mar 1988
Garces G Santandreu M

The right sciatic nerve of 50 one-month-old male rats was cut under general anaesthesia. Groups of animals were sacrificed at intervals of up to 12 weeks after operation and the length of the femora, tibiae and first and fifth metatarsals were measured with a caliper accurate to 0.05 mm. From the first week, both metatarsals were between 3% and 5% shorter on the denervated side, but there was no further increase of the discrepancy. The femora were less than 1% longer in the denervated limb at the second and eighth week. No difference was found between the lengths of the tibiae. The various factors which could possibly be responsible for these findings are discussed


The Journal of Bone & Joint Surgery British Volume
Vol. 69-B, Issue 3 | Pages 429 - 432
1 May 1987
Middleton R Frost R

This paper describes the design, development and early surgical experience with a stereotactic device to allow closed retrieval and interchange of intramedullary rods in children with osteogenesis imperfecta. This relatively atraumatic procedure may allow more frequent rod interchange than with other techniques, lessening the likelihood of deformity and fracture in the unsupported skeleton when the bone has outgrown the intramedullary rod. The procedure was developed by design studies in vitro followed by intramedullary rodding of tibiae of New Zealand white rabbits. It has been used in children 12 times, in six tibiae and six femora: 11 rods have been successfully retrieved, with rod interchange in eight of these cases


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 6 | Pages 906 - 912
1 Aug 2003
Ding M Odgaard A Hvid I Hvid I

We obtained medial and lateral subchondral cancellous bone specimens from ten human postmortem proximal tibiae with early osteoarthritis (OA) and ten normal age- and gender-matched proximal tibiae. The specimens were scanned by micro-CT and the three-dimensional microstructural properties were quantified. Medial OA cancellous bone was significantly thicker and markedly plate-like, but lower in mechanical properties than normal bone. Similar microstructural changes were also observed for the lateral specimens from OA bone, although there had been no sign of cartilage damage. The increased trabecular thickness and density, but relatively decreased connectivity suggest a mechanism of bone remodelling in early OA as a process of filling trabecular cavities. This process leads to a progressive change of trabeculae from rod-like to plate-like, the opposite to that of normal ageing. The decreased mechanical properties of subchondral cancellous bone in OA, which are due to deterioration in architecture and density, indicate poor bone quality


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 6 | Pages 868 - 872
1 Jun 2005
Metcalfe AJ Saleh M Yang L

Biomechanical studies involving all-wire and hybrid types of circular frame have shown that oblique tibial fractures remain unstable when they are loaded. We have assessed a range of techniques for enhancing the fixation of these fractures. Eight models were constructed using Sawbones tibiae and standard Sheffield ring fixators, to which six additional fixation techniques were applied sequentially. The major component of displacement was shear along the obliquity of the fracture. This was the most sensitive to any change in the method of fixation. All additional fixation systems were found to reduce shear movement significantly, the most effective being push-pull wires and arched wires with a three-hole bend. Less effective systems included an additional half pin and arched wires with a shallower arc. Angled pins were more effective at reducing shear than transverse pins. The choice of additional fixation should be made after consideration of both the amount of stability required and the practicalities of applying the method to a particular fracture


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 3 | Pages 426 - 432
1 Mar 2005
Mueller CA Eingartner C Schreitmueller E Rupp S Goldhahn J Schuler F Weise K Pfister U Suedkamp NP

The treatment of fractures of the proximal tibia is complex and makes great demands on the implants used. Our study aimed to identify what levels of primary stability could be achieved with various forms of osteosynthesis in the treatment of diaphyseal fractures of the proximal tibia. Pairs of human tibiae were investigated. An unstable fracture was simulated by creating a defect at the metaphyseal-diaphyseal junction. Six implants were tested in a uniaxial testing device (Instron) using the quasi-static and displacement-controlled modes and the force-displacement curve was recorded. The movements of each fragment and of the implant were recorded video-optically (MacReflex, Qualysis). Axial deviations were evaluated at 300 N. The results show that the nailing systems tolerated the highest forces. The lowest axial deviations in varus and valgus were also found for the nailing systems; the highest axial deviations were recorded for the buttress plate and the less invasive stabilising system (LISS). In terms of rotational displacement the LISS was better than the buttress plate. In summary, it was found that higher loads were better tolerated by centrally placed load carriers than by eccentrically placed ones. In the case of the latter, it appears advantageous to use additive procedures for medial buttressing in the early phase


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 4 | Pages 588 - 592
1 May 2001
Wimhurst JA Brooks RA Rushton N

We used a rat model in vivo to study the effects of particulate bone cements at the bone-implant interface. A ceramic pin was implanted into the tibiae of 48 rats. Three types of particle of clinically relevant size were produced from one bone-cement base without radio-opacifier, with zirconium dioxide (ZrO. 2. ) and with barium sulphate (BaSO. 4. ). The rats were randomly assigned to four groups to receive one of the three bone cements or normal saline with 2% v/v Sprague-Dawley serum as the control. A total of 10. 9. particles was injected into the knee at 8, 10 and 12 weeks after the original surgery. The animals were killed at 14 weeks and the tibiae processed for histomorphometry. The area of fibrous tissue and the gap between the implant and bone were measured using image analysis. All three types of particle were associated with a larger area of bone resorption than the control. Only in the case of the BaSO. 4. -containing cement did this reach statistical significance (p = 0.01). Particles of bone cement appear to promote osteolysis at the bone-implant interface and this effect is most marked when BaSO. 4. is used as the radiopaque agent


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 135 - 144
1 Jul 2021
Kuyl E Shu F Sosa BR Lopez JD Qin D Pannellini T Ivashkiv LB Greenblatt MB Bostrom MPG Yang X

Aims

Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

Methods

Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 484 - 493
13 Jul 2022
Hayer S Niederreiter B Kalkgruber M Wanic K Maißner J Smolen JS Aletaha D Blüml S Redlich K

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

Methods

Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 7 | Pages 1017 - 1022
1 Jul 2010
Kelley SP Bache CE Graham HK Donnan LT

We report the outcome of 28 patients with spina bifida who between 1989 and 2006 underwent 43 lower extremity deformity corrections using the Ilizarov technique. The indications were a flexion deformity of the knee in 13 limbs, tibial rotational deformity in 11 and foot deformity in 19. The mean age at operation was 12.3 years (5.2 to 20.6). Patients had a mean of 1.6 previous operations (0 to 5) on the affected limb. The mean duration of treatment with a frame was 9.4 weeks (3 to 26) and the mean follow-up was 4.4 years (1 to 9). There were 12 problems (27.9%), five obstacles (11.6%) and 13 complications (30.2%) in the 43 procedures. Further operations were needed in seven patients. Three knees had significant recurrence of deformity. Two tibiae required further surgery for recurrence. All feet were plantigrade and braceable. We conclude that the Ilizarov technique offers a refreshing approach to the complex lower-limb deformity in spina bifida


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 1 | Pages 14 - 17
1 Jan 1996
Wang HM Crank S Oliver G Galasko CSB

Previous studies have shown that the activity of the cytostatic drug methotrexate (MTX) embedded in acrylic cement is not affected by thermal changes in the cement. MTX is slowly released from the cement for several months and remains biologically active throughout this period. Our aim was to determine whether MTX embedded in cement would control the local growth of a tumour. In 15 rabbits we injected 0.1 ml of VX. 2. tumour suspension into the proximal tibia. At 3, 5, 7, 10 and 14 days three animals were killed and the tibiae removed and examined histologically. With increasing growth of the VX. 2. carcinoma there was increased bone destruction and a rise in the numbers of osteoclasts, but after 14 days the numbers of osteoclasts had decreased. We then injected VX. 2. into the tibiae of another 45 rabbits. After 5 days most of the tumour was curetted out and the defect filled with cement containing either 0 g, 0.1 g, 0.5 g, 1.0 g or 2.0 g MTX/40 g cement. The rabbits were divided into three groups and killed at 3, 7 or 10 days after implantation of cement. The number of osteoclasts and the amount of bone destruction were measured in each tibia. In all three groups bone destruction and osteoclast proliferation were markedly decreased with higher doses of MTX, but bone destruction was not eliminated. Our findings show that in the higher doses used, which were not toxic to the animal, MTX-embedded cement may be of value in minimising the amount of tumour-induced osteolysis and may be a useful adjunct in the surgical management of pathological fractures


Bone & Joint Research
Vol. 11, Issue 6 | Pages 362 - 370
9 Jun 2022
Zhou J He Z Cui J Liao X Cao H Shibata Y Miyazaki T Zhang J

Aims

Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA.

Methods

Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 767 - 779
8 Dec 2021
Li Y Yang Y Wang M Zhang X Bai S Lu X Li Y Waldorff EI Zhang N Lee WY Li G

Aims

Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.

Methods

The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 200 - 209
1 Apr 2022
Liu YD Liu JF Liu B

Aims

The role of N,N-dimethylformamide (DMF) in diabetes-induced osteoporosis (DM-OS) progression remains unclear. Here, we aimed to explore the effect of DMF on DM-OS development.

Methods

Diabetic models of mice, RAW 264.7 cells, and bone marrow macrophages (BMMs) were established by streptozotocin stimulation, high glucose treatment, and receptor activator of nuclear factor-κB ligand (RANKL) treatment, respectively. The effects of DMF on DM-OS development in these models were examined by micro-CT analysis, haematoxylin and eosin (H&E) staining, osteoclast differentiation of RAW 264.7 cells and BMMs, H&E and tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA) of TRAP5b and c-terminal telopeptides of type 1 (CTX1) analyses, reactive oxygen species (ROS) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), Cell Counting Kit-8 (CCK-8) assay, and Western blot.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 1 | Pages 68 - 74
1 Jan 2012
Christel PS Akgun U Yasar T Karahan M Demirel B

The clinical diagnosis of a partial tear of the anterior cruciate ligament (ACL) is still subject to debate. Little is known about the contribution of each ACL bundle during the Lachman test. We investigated this using six fresh-frozen cadaveric lower limbs. Screws were placed in the femora and tibiae as fixed landmarks for digitisation of the bone positions. The femur was secured horizontally in a clamp. A metal hook was screwed to the tibial tubercle and used to apply a load of 150 N directed anteroposteriorly to the tibia to simulate the Lachman test. The knees then received constant axial compression and 3D knee kinematic data were collected by digitising the screw head positions in 30° flexion under each test condition. Measurements of tibial translation and rotation were made, first with the ACL intact, then after sequential cutting of the ACL bundles, and finally after complete division of the ACL. Two-way analysis of variance analysis was performed. During the Lachman test, in all knees and in all test conditions, lateral tibial translation exceeded that on the medial side. With an intact ACL, both anterior and lateral tibial landmarks translated significantly more than those on the medial side (p < 0.001). With sequential division of the ACL bundles, selective cutting of the posterolateral bundle (PLB) did not increase translation of any landmark compared with when the ACL remained intact. Cutting the anteromedial bundle (AMB) resulted in an increased anterior translation of all landmarks. Compared to the intact ACL, when the ACL was fully transected a significant increase in anterior translation of all landmarks occurred (p < 0.001). However, anterior tibial translation was almost identical after AMB or complete ACL division. We found that the AMB confers its most significant contribution to tibial translation during the Lachman test, whereas the PLB has a negligible effect on anterior translation. Section of the PLB had a greater effect on increasing the internal rotation of the tibia than the AMB. However, its contribution of a mean of 2.8° amplitude remains low. The clinical relevance of our investigation suggests that, based on anterior tibial translation only, one cannot distinguish between a full ACL and an isolated AMB tear. Isolated PLB tears cannot be detected solely by the Lachman test, as this bundle probably contributes more resistance to the pivot shift


Bone & Joint Research
Vol. 10, Issue 8 | Pages 514 - 525
2 Aug 2021
Chen C Kang L Chang L Cheng T Lin S Wu S Lin Y Chuang S Lee T Chang J Ho M

Aims

Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model.

Methods

Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies.


Bone & Joint Research
Vol. 4, Issue 5 | Pages 84 - 92
1 May 2015
Hamamura K Nishimura A Iino T Takigawa S Sudo A Yokota H

Objectives. Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92


Bone & Joint Open
Vol. 2, Issue 10 | Pages 825 - 833
8 Oct 2021
Dailey HL Schwarzenberg P Webb, III EB Boran SAM Guerin S Harty JA

Aims

The study objective was to prospectively assess clinical outcomes for a pilot cohort of tibial shaft fractures treated with a new tibial nailing system that produces controlled axial interfragmentary micromotion. The hypothesis was that axial micromotion enhances fracture healing compared to static interlocking.

Methods

Patients were treated in a single level I trauma centre over a 2.5-year period. Group allocation was not randomized; both the micromotion nail and standard-of-care static locking nails (control group) were commercially available and selected at the discretion of the treating surgeons. Injury risk levels were quantified using the Nonunion Risk Determination (NURD) score. Radiological healing was assessed until 24 weeks or clinical union. Low-dose CT scans were acquired at 12 weeks and virtual mechanical testing was performed to objectively assess structural bone healing.