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Bone & Joint Research
Vol. 10, Issue 11 | Pages 714 - 722
1 Nov 2021
Qi W Feng X Zhang T Wu H Fang C Leung F

Aims

To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model.

Methods

A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 8 | Pages 1050 - 1054
1 Aug 2005
Shetty AA Slack R Tindall A James KD Rand C

We describe the survival of 134 consecutive JRI Furlong hydroxyapatite-coated uncemented total hip replacements. The mean follow-up was for 14.2 years (13 to 15). Patients were assessed clinically, using the Merle d’Aubigné and Postel score. Radiographs were evaluated using Gruen zones for the stem and DeLee and Charnley zones for the cup. Signs of subsidence, radiolucent lines, endosteal bone formation (spot welds) and pedestal formation were used to assess fixation and stability of the stem according to Engh’s criteria. Cup angle, migration and radiolucency were used to assess loosening of the cup. The criteria for failure were revision, or impending revision because of pain or loosening. Survival analysis was performed using a life table and the Kaplan-Meier curve. The mean total Merle d’Aubigné and Postel score was 7.4 pre-operatively and 15.9 at follow-up. During the study period 22 patients died and six were lost to follow-up. None of the cups was revised. One stem was revised for a periprosthetic fracture following a fall but none was revised for loosening, giving a 99% survival at 13 years. Our findings suggest that the long-term results of these hydroxyapatite-coated prostheses are more than satisfactory


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 2 | Pages 298 - 303
1 Feb 2010
Toom A Suutre S Märtson A Haviko T Selstam G Arend A

We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically. Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (. sd. 4.5) versus 12.7% (. sd. 2.9, p < 0.019), respectively. Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification


The Journal of Bone & Joint Surgery British Volume
Vol. 73-B, Issue 3 | Pages 501 - 505
1 May 1991
Kirkeby O

Revascularisation of syngeneic and allogeneic intramuscular bone grafts have been studied using radioactive microspheres to measure the ingrowth of blood vessels. New bone formation and resorption were measured by 85strontium uptake and by graft weight reduction. Revascularisation, and mineralisation rate were significantly higher in syngeneic grafts than in allogeneic grafts at two, three and six weeks after implantation. The syngeneic grafts lost weight faster indicating that the allogeneic grafts resorbed more slowly. The ingrowth of new vessels is impaired in allogeneic bone, and this probably inhibits the rate of bone formation and resorption of the grafts


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 3 | Pages 416 - 420
1 Mar 2005
Bobyn JD Hacking SA Krygier JJ Harvey EJ Little DG Tanzer M

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone


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.


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1604 - 1610
1 Oct 2021
Takaoka Y Goto K Tamura J Okuzu Y Kawai T Kuroda Y Orita K Matsuda S

Aims

We aimed to evaluate the long-term outcome of highly cross-linked polyethylene (HXLPE) cemented acetabular components and assess whether any radiolucent lines (RLLs) which arose were progressive.

Methods

We retrospectively reviewed 170 patients who underwent 187 total hip arthroplasties at two hospitals with a minimum follow-up of ten years. All interventions were performed using the same combination of HXLPE cemented acetabular components with femoral stems made of titanium alloy. Kaplan-Meier survival analysis was performed for the primary endpoint of acetabular component revision surgery for any reason and secondary endpoint of the appearance of RLLs. RLLs that had appeared once were observed over time. We statistically assessed potential relationships between RLLs and a number of factors, including the technique of femoral head autografting and the Japanese Orthopaedic Association score.


The Journal of Bone & Joint Surgery British Volume
Vol. 57-B, Issue 1 | Pages 36 - 45
1 Feb 1975
Chalmers J Gray DH Rush J

Using bone decalcilied with 0.6 N hydrochloric acid as an inducing agent, the inductive capacity of different soft tissue sites was investigated. Muscle and fascia regularly permitted the induction of bone, while spleen, liver and kidney suppressed bone induction. Bone formation could be induced in these organs if living autologous fascia was implanted together with the inducing agent; while bone formation was inhibited when living autologous spleen tissue was implanted with the inducing agent to normally favourable sites. The administration of systemic heparin and the diphosphonate ethane-1-hydroxyl, 1-diphosphonic acid (EHDP) suppressed bone induction. It is suggested that for bone induction to occur in soft tissues, three conditions must be present: 1) an inducing agent; 2) an osteogenic precursor cell; and 3) an environment which is permissive to osteogenesis. The presence of osteogenic inhibitors in spleen, liver and kidney is postulated


The Journal of Bone & Joint Surgery British Volume
Vol. 44-B, Issue 3 | Pages 675 - 687
1 Aug 1962
Burger M Sherman BS Sobel AE

1. A study has been made of the repair of bony defects in the calvaria of albino rats. 2. An accelerated rate of bone repair was observed in experimental defects into which chondroitin sulphate-treated demineralised bone was implanted. 3. Acid-soluble collagen reconstituted with chondroitin sulphate was also more effective as an implant than was acid-soluble collagen reconstituted with sodium chloride. 4. It is concluded from these studies that chondroitin sulphate treatment accelerated the rate of new bone formation induced by demineralised bone, by reconstituted acid-soluble collagen, and to a lesser extent by Gelfoam. It was also found that demineralised bone and fresh homogenous bone promoted bone repair, but that chondroitin sulphate-treated demineralised bone promoted the most rapid rate of bone repair among the substances tested. 5. The possible role of chondroitin sulphate in bone formation is discussed


Bone & Joint Research
Vol. 10, Issue 1 | Pages 41 - 50
1 Jan 2021
Wong RMY Choy VMH Li J Li TK Chim YN Li MCM Cheng JCY Leung K Chow SK Cheung WH

Aims

Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.

Methods

A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture.


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 522 - 529
1 Mar 2021
Nichol T Callaghan J Townsend R Stockley I Hatton PV Le Maitre C Smith TJ Akid R

Aims

The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses.

Methods

Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods.


Bone & Joint Research
Vol. 10, Issue 1 | Pages 51 - 59
1 Jan 2021
Li J Ho WTP Liu C Chow SK Ip M Yu J Wong HS Cheung W Sung JJY Wong RMY

Aims

The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

Methods

Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted.


The Journal of Bone & Joint Surgery British Volume
Vol. 45-B, Issue 3 | Pages 582 - 596
1 Aug 1963
Vanderhoeft PJ Kelly PJ Janes JM Peterson LFA

Puppies in the second half of their growing period have been observed for one and a half to four and a half months after creation of a superficial femoral arteriovenous fistula on the right side. From measurements of the whole bone and from microradiographic and tetracycline-fluorophore studies of the diaphysial bone, it is believed that the following statistically significant phenomena may be attributed to the influence of the arteriovenous fistula. 1. All bones distal to the fistula are influenced in their growth. The tibia and metatarsals become heavier and larger, but retain normal shape. Although stimulation of longitudinal growth is small, it is significant for the tibiae and nearly significant for the femora in these short-term experiments. 2. The histological structure of the bones remains normal but quantitative changes are induced. The compact bone is more porous because of an increased number of osteones. Haversian turnover itself is affected in that the individual formation time of osteones tends to become longer, especially in the metatarsals. 3. Periosteal new bone formation is immediately stimulated, producing a flare of new bone. This accounts for the increase in diaphysial weight in the tibia but not in the metatarsals, where the same effect results from decreased resorption of old bone. 4. Endosteal new bone formation is depressed, especially in the metatarsals, resulting in an enlarged medullary cavity


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 5 | Pages 760 - 766
1 Jul 2001
Suzuki H Takahashi K Yamagata M Shimizu S Moriya H Yamazaki M

We have examined the process of fusion of the intertransverse processes and bone graft in the rabbit by in situ hybridisation and evaluated the spatial and temporal expression of genes encoding pro-α1 (I) collagen (COL1A1), pro-α1 (II) collagen (COL2A1) and pro-α1 (X) collagen (COL10A1). Beginning at two weeks after operation, osteogenesis and chondrogenesis occurred around the transverse process and the grafted bone at the central portion of the area of the fusion mass. Osteoblasts and osteocytes at the newly-formed woven bone expressed COL1A1. At the cartilage, most chondrocytes expressed COL2A1 and some hypertrophic chondrocytes COL10A1. In some regions, co-expression of COL1A1 and COL2A1 was observed. At four weeks, such expressions for COL1A1, COL2A1 and COL10A1 became prominent at the area of the fusion mass. From four to six weeks, bone remodelling progressed from the area of the transverse processes towards the central zone. Osteoblasts lining the trabeculae expressed a strong signal for COL1A1. At the central portion of the area of the fusion mass, endochondral ossification progressed and chondrocytes expressed COL2A1 and COL10A1. Our findings show that the fusion process begins with the synthesis of collagens around the transverse processes and around the grafted bone independently. Various spatial and temporal osteogenic and chondrogenic responses, including intramembranous, endochondral and transchondroid bone formation, progress after bone grafting at the intertransverse processes. Bone formation through cartilage may play an important role in posterolateral spinal fusion


The Journal of Bone & Joint Surgery British Volume
Vol. 50-B, Issue 4 | Pages 844 - 851
1 Nov 1968
Olerud S Danckwardt-Lillieström G

1. The healing of the radius and tibia in dogs after compression plating of osteotomies made by a Gigli saw was studied. 2. The methods used were indian ink microangiography and terramycin labelling. The Spalteholz technique and azane colouring were used. 3. Revascularisaton of the fracture region took place both from newly formed vessels in the Haversian systems and from periosteal and endosteal vessels. 4. The fracture gap was filled at an early stage by a vascular network. Under stable conditions direct angiogenic bone formation took place around this network. 5. Rebuilding of the cortical bone in the fracture region occurred by osteoclastic activity. Groups of osteoclasts made cavities in the necrotic bone and were immediately followed by loops of vessels; behind and around the loop new bone was formed. Another form of bone absorption consisted of bundles of vessels which eroded necrotic cortical bone without new bone formation. 6. The new bone was initially oriented along the fracture gap but, by conversion into secondary osteones, it became progressively oriented longitudinally in the direction of the original bone. 7. Under stable conditions some periosteal and endosteal callus formation occurred though it was of slight importance. It regressed very soon and was seldom seen in the radiographs


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 8 | Pages 1108 - 1114
1 Nov 2004
Wick M Lester DK

The Alloclassic and Endoplus femoral stems have the same grit-blasted surface and are hot forged from the same titanium alloy. Only the external form of the implants differs slightly. It was our aim to examine the differences in radiographic bone response between the Alloclassic (second generation) and the Endoplus (third generation) femoral stems. We compared 79 prostheses in 70 matched patients studied over a minimum of two years. Radiolucent lines, adaptive bone remodelling, subsidence, heterotopic bone formation and lysis were recorded in the Gruen zones. Radiolucencies were mainly found in zones 1 and 7 but to a greater extent in the Endoplus than in the Alloclassic group (p < 0.001 in zone 1, p < 0.05 in zone 7). We found lucent lines in three or more Gruen zones in seven patients all of whom were in the Endoplus group (p < 0.05). Zones 2 and 6 had a significantly higher rate of lucencies in the Endoplus group (p < 0.001). We encountered a combination of proximal lucent lines in zones 1 and 7 with distal hypertrophy of the cortical bone in zones 2, 3, 5 and 6 in eight patients, all from the Endoplus group (p < 0.05). In other patients bone atrophy (stress shielding) in zones 2 and 6 was seen more frequently in the Endoplus than in the Alloclassic group (p < 0.001). In neither group was there radiological evidence of osteolysis. Heterotopic bone formation and subsidence occurred with similar frequency in both groups. Our study shows that a small change in the form of the femoral implant can result in statistically significant radiological changes in bone remodelling. Whether this will result in clinical compromise is unknown. However, it seems likely that the Endoplus femoral stem will perform differently from the Alloclassic


Bone & Joint Research
Vol. 10, Issue 4 | Pages 237 - 249
1 Apr 2021
Chen X Chen W Aung ZM Han W Zhang Y Chai G

Aims

LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling.

Methods

The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 7 | Pages 984 - 988
1 Jul 2007
Omi H Kusumi T Kijima H Toh S

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 μg/kg; mid, 7.5 μg/kg and high 75 μg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction. After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm. 3. over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae. The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis


Bone & Joint Research
Vol. 10, Issue 3 | Pages 218 - 225
1 Mar 2021
Wiesli MG Kaiser J Gautier E Wick P Maniura-Weber K Rottmar M Wahl P

Aims

In orthopaedic and trauma surgery, implant-associated infections are increasingly treated with local application of antibiotics, which allows a high local drug concentration to be reached without eliciting systematic adverse effects. While ceftriaxone is a widely used antibiotic agent that has been shown to be effective against musculoskeletal infections, high local concentrations may harm the surrounding tissue. This study investigates the acute and subacute cytotoxicity of increasing ceftriaxone concentrations as well as their influence on the osteogenic differentiation of human bone progenitor cells.

Methods

Human preosteoblasts were cultured in presence of different concentrations of ceftriaxone for up to 28 days and potential cytotoxic effects, cell death, metabolic activity, cell proliferation, and osteogenic differentiation were studied.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 388 - 400
8 Jul 2021
Dall’Ava L Hothi H Henckel J Di Laura A Tirabosco R Eskelinen A Skinner J Hart A

Aims

The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants.

Methods

We compared two groups, one made via 3D-printing (n = 7) and the other using conventional techniques (n = 7). We collected implant details, type of surgery and removal technique, patient demographics, and clinical history. Bone integration was assessed by macroscopic visual analysis, followed by sectioning to allow undecalcified histology on eight sections (~200 µm) for each implant. The outcome measures considered were area of bone attachment (%), extent of bone ingrowth (%), bone-implant contact (%), and depth of ingrowth (%), and these were quantified using a line-intercept method.