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The Journal of Bone & Joint Surgery British Volume
Vol. 46-B, Issue 1 | Pages 110 - 140
1 Feb 1964
Burwell RG

1. Previous immunological studies have shown that homografts of fresh marrow-free iliac bone are only weakly, if at all, antigenic. 2. In view of this finding an attempt was made to produce a foreign bone graft capable of forming new bone as readily as an iliac autograft by the following method. Living cells of high osteogenic potential and of autologous type were introduced into the graft by combining homologous fresh marrow-free iliac bone with the animal's own red marrow to form a fresh composite homograft-autograft of cancellous bone. 3. Such fresh composite homograft-autografts were inserted into a muscular site in Wistar rats and removed for microscopical examination at intervals of one to seven days and at two, six and twelve weeks after transplantation. 4. It is found that bone and marrow together as a fresh composite homograft-autograft form considerably more new bone than do either of the components of the graft transplanted separately. Homografts of fresh marrow-free iliac bone form, in general, a small amount of early phase and late phase new bone. Autografts of red marrow transplanted alone to a muscular site formed new bone in thirteen to thirty experiments (43 per cent). 5. The stimulus to osteogenesis, and the cellular source of osteoblasts, in marrow autografts is discussed in the light of present knowledge. The concept is suggested that after its transplantation there develops in marrow an inductive system leading to osteoblastic differentiation and bone formation. It is proposed that the necrosis of a portion of a marrow graft liberates osteogenic substances which are taken up by primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of the marrow which are induced, thereby, to differentiate as osteoblasts. 6. The cellular source of osteoblasts in a fresh composite homograft-autograft of cancellous bone is discussed. It is deduced that the new bone is derived mainly from the contained marrow of the graft, by mechanisms similar to those leading to osteoblastic differentiation in transplanted autografts of marrow. 7. The stimulus to the greater formation of new bone by fresh composite autograft-homografts than by autografts of marrow transplanted alone is discussed. Two explanations are suggested: 1) a more extensive necrosis of marrow in a composite homograft-autograft than in marrow transplanted alone; and 2) an inductive effect of bone upon marrow. 8. The new bone formed by autografts of fresh marrow-containing iliac bone, it is concluded, is derived not only from osteoblasts on the surfaces of the grafted bone but also from primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of its marrow. 9. Mechanisms which may play a role in the histogenesis of woven bone are discussed. 10. The significance of the relation of bone and marrow is considered briefly in the light of knowledge concerning the venous patterns of bone and marrow


Bone & Joint Research
Vol. 8, Issue 7 | Pages 304 - 312
1 Jul 2019
Nicholson JA Tsang STJ MacGillivray TJ Perks F Simpson AHRW

Objectives

The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management.

Methods

A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”.


Objectives

Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation.

Methods

MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone.


Bone & Joint Research
Vol. 8, Issue 10 | Pages 469 - 471
1 Oct 2019
Evans CH


Bone & Joint Research
Vol. 8, Issue 9 | Pages 414 - 424
2 Sep 2019
Schmalzl J Plumhoff P Gilbert F Gohlke F Konrads C Brunner U Jakob F Ebert R Steinert AF

Objectives

The long head of the biceps (LHB) is often resected in shoulder surgery and could therefore serve as a cell source for tissue engineering approaches in the shoulder. However, whether it represents a suitable cell source for regenerative approaches, both in the inflamed and non-inflamed states, remains unclear. In the present study, inflamed and native human LHBs were comparatively characterized for features of regeneration.

Methods

In total, 22 resected LHB tendons were classified into inflamed samples (n = 11) and non-inflamed samples (n = 11). Proliferation potential and specific marker gene expression of primary LHB-derived cell cultures were analyzed. Multipotentiality, including osteogenic, adipogenic, chondrogenic, and tenogenic differentiation potential of both groups were compared under respective lineage-specific culture conditions.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 139 - 147
1 Feb 2018
Takahara S Lee SY Iwakura T Oe K Fukui T Okumachi E Waki T Arakura M Sakai Y Nishida K Kuroda R Niikura T

Objectives

Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM.

Methods

Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint.


Objectives

Activation of the leptin pathway is closely correlated with human knee cartilage degeneration. However, the role of the long form of the leptin receptor (Ob-Rb) in cartilage degeneration needs further study. The aim of this study was to determine the effect of increasing the expression of Ob-Rb on chondrocytes using a lentiviral vector containing Ob-Rb.

Methods

The medial and lateral cartilage samples of the tibial plateau from 12 osteoarthritis (OA) patients were collected. Ob-Rb messenger RNA (mRNA) was detected in these samples. The Ob-Rb-overexpressing chondrocytes and controls were treated with different doses of leptin for two days. The activation of the p53/p21 pathway and the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells were evaluated. The mammalian target of rapamycin (mTOR) signalling pathway and autophagy were detected after the chondrocytes were treated with a high dose of leptin.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 173 - 178
1 Feb 2018
Peng X Wu X Zhang J Zhang G Li G Pan X

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment.

Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1.


Bone & Joint Research
Vol. 8, Issue 8 | Pages 397 - 404
1 Aug 2019
Osagie-Clouard L Sanghani-Kerai A Coathup M Meeson R Briggs T Blunn G

Objectives

Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1).

Methods

Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34.


Objectives

Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo.

Methods

ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry.


Bone & Joint Research
Vol. 8, Issue 6 | Pages 255 - 265
1 Jun 2019
Hernigou J Schuind F

Objectives

The aim of this study was to review the impact of smoking tobacco on the musculoskeletal system, and on bone fractures in particular.

Methods

English-language publications of human and animal studies categorizing subjects into smokers and nonsmokers were sourced from MEDLINE, The Cochrane Library, and SCOPUS. This review specifically focused on the risk, surgical treatment, and prevention of fracture complications in smokers.


Bone & Joint 360
Vol. 8, Issue 2 | Pages 38 - 41
1 Apr 2019


Bone & Joint Research
Vol. 8, Issue 6 | Pages 232 - 245
1 Jun 2019
Lu C Zhang T Reisdorf RL Amadio PC An K Moran SL Gingery A Zhao C

Objectives

Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery.

Methods

A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs).


Bone & Joint Research
Vol. 7, Issue 10 | Pages 548 - 560
1 Oct 2018
Qayoom I Raina DB Širka A Tarasevičius Š Tägil M Kumar A Lidgren L

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.


The Bone & Joint Journal
Vol. 100-B, Issue 4 | Pages 507 - 515
1 Apr 2018
Nnadi C Thakar C Wilson-MacDonald J Milner P Rao A Mayers D Fairbank J Subramanian T

Aims

The primary aim of this study was to evaluate the performance and safety of magnetically controlled growth rods in the treatment of early onset scoliosis. Secondary aims were to evaluate the clinical outcome, the rate of further surgery, the rate of complications, and the durability of correction.

Patients and Methods

We undertook an observational prospective cohort study of children with early onset scoliosis, who were recruited over a one-year period and followed up for a minimum of two years. Magnetically controlled rods were introduced in a standardized manner with distractions performed three-monthly thereafter. Adverse events which were both related and unrelated to the device were recorded. Ten children, for whom relevant key data points (such as demographic information, growth parameters, Cobb angles, and functional outcomes) were available, were recruited and followed up over the period of the study. There were five boys and five girls. Their mean age was 6.2 years (2.5 to 10).


The Journal of Bone & Joint Surgery British Volume
Vol. 44-B, Issue 3 | Pages 453 - 463
1 Aug 1962
Casuccio C

Relating the results of our investigations to the knowledge hitherto acquired about the etiology of osteoporosis (which I have already referred to), I am inclined to interpret the pathogenesis of osteoporosis in the following way: 1) Primary osteoblastic deficiency: congenital (Lobstein); involutive (senile osteoporosis?); 2) Reduced osteoblastic activity from absence of trophic stimuli: (inactivity, ovarian agenesia, eunuchoidism, menopause); 3) Reduced osteoblastic activity from inhibitory stimuli: (cortisone, adrenocorticotrophic hormone (A.C.T.H.), stress, Cushing's disease, thyrotoxicosis); 4) Normal osteoblastic activity but insufficiency of constructive material: (malnutrition, disturbances of the digestive system, insufficiency of vitamin C, diabetes, thyrotoxicosis, cortisone, A.C.T.H., stress, Cushing's disease). Osteoporosis may therefore be the consequence either of a congenital osteoblastic deficiency, such as that found in cases of osteogenesis imperfecta, or of reduced osteoblastic activity due to absence of trophic stimuli such as mechanical stress and the sex hormones, or of reduced activity of the bone cells due to anti-anabolic substances which inhibit them, such as cortisone and its derivatives and the thyroid hormone in strong doses, or lastly of reduced availability of construction material due to its introduction in reduced quantities (starvation, dysfunction of the digestive system) or due to hindering of synthesis (deficiency of vitamin C, diabetes, cortisone and its derivatives) or due to an excessive degree of destruction (thyrotoxicosis). In the case of anti-anabolic hormones from the adrenal cortex, the mechanism may thus be twofold: inhibition of the osteoblasts and deprivation of the osteoblasts of glucoprotein material due to a general anomaly of metabolism. This may perhaps explain the most serious forms of bone atrophy which are usually observable in cases of hyperfunction of the adrenal cortex. Senile osteoporosis should, in my opinion, be included in the first of our groups because it cannot be said to be brought about by any of the causes usually cited for osteoporosis– such as deficiency of sex hormones, excess of hormones from the adrenal cortex, deficiency of calcium, etc.–and in all probability it will depend on a progressive involution of the osteoblasts brought about by old age. Senile involution is an expression of the descending phase of life's parabola and it involves all the organs and all the parenchymatous tissues in the human body, but it does not cause a parallel reduction of functions and activities on all of them equally. The skeletal system is one of the first to feel these reductions, because in old age life necessarily becomes less intense. Consequently in the economy of the ageing subject the generally reduced level of metabolism brings about a sort of selection in the nourishment of the different organs and systems, and sometimes almost a dismantling of some of these in an attempt to fall in with the new and reduced level of activities of some of the parenchymatous tissues, activities which may be incomplete or even transferred elsewhere. We believe that the moment which originally determines the beginning of senile osteoporosis coincides with the involutional process of cellular metabolism that strikes at all parenchymatous tissue during old age–striking, in the case of osteoporosis, hardest of all at the bony tissues. There is, indeed, no doubt that certain essential processes of cellular metabolism do alter with age, and that the reduction in the activity of the gonads does have considerable importance. In any case, just as adolescence and old age cannot be explained only in terms of gonadal activity, so the involution of the skeleton cannot be due merely to the involution of the gonads. How should one then interpret the well known benefit afforded by administration of sex hormones in cases of osteoporosis? Probably the action of oestrogens and androgens is, in this case, of a pharmacological nature, and comparable, for instance, to the action of digitalis on the cardiac muscle. It will be remembered how digitalis acts almost exclusively on myofibrils which have become inadequate, and has little or no effect on a normal myocardium. Similarly, the sex hormones would seem to exert a stimulating action on osteoblasts that are on the way to involution, while they exert little or no action on normal osteoblasts. In support of this we have the findings of Urist and other workers, who demonstrated that the administration of sex hormones produces calcium and nitrogen retention only in osteoporotics, while in non-osteoporotic subjects of the same age it produces no effect. On the other hand, the action of the sex hormones might act in cases of senile osteoporosis by returning the changed level of protein metabolism to normal. From the data in the literature and from the results of our own investigations, I conclude that osteoporosis in general, and senile osteoporosis in particular, are first and foremost the result of a disturbance in the metabolism of bone, and that the metabolic disturbance is closely and exclusively related to the degree of activity and the state of activity of the cells in the bone. Lastly, I believe that senile osteoporosis should not be considered an actual disease but rather as one limited aspect of the normal descending parabola which affects to a greater or less degree all the tissues of the body


Bone & Joint Research
Vol. 7, Issue 1 | Pages 46 - 57
1 Jan 2018
Zhou J Zhou XG Wang JW Zhou H Dong J

Objective

In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits.

Methods

The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects.


The Bone & Joint Journal
Vol. 100-B, Issue 6 | Pages 755 - 760
1 Jun 2018
Lou T Hamushan M Li H Wang C Chai Y Han P

Aims

The aim of this study was to describe the technique of distraction osteogenesis followed by arthrodesis using internal fixation to manage complex conditions of the ankle, and to present the results of this technique.

Patients and Methods

Between 2008 and 2014, distraction osteogenesis followed by arthrodesis using internal fixation was performed in 12 patients with complex conditions of the ankle due to trauma or infection. There were eight men and four women: their mean age was 35 years (23 to 51) at the time of surgery. Bone healing and functional recovery were evaluated according to the criteria described by Paley. Function was assessed using the ankle-hindfoot scale of the American Orthopedic Foot and Ankle Society (AOFAS).


Bone & Joint Research
Vol. 7, Issue 5 | Pages 357 - 361
1 May 2018
Shin T Lim D Kim YS Kim SC Jo WL Lim YW

Objectives

Laser-engineered net shaping (LENS) of coated surfaces can overcome the limitations of conventional coating technologies. We compared the in vitro biological response with a titanium plasma spray (TPS)-coated titanium alloy (Ti6Al4V) surface with that of a Ti6Al4V surface coated with titanium using direct metal fabrication (DMF) with 3D printing technologies.

Methods

The in vitro ability of human osteoblasts to adhere to TPS-coated Ti6Al4V was compared with DMF-coating. Scanning electron microscopy (SEM) was used to assess the structure and morphology of the surfaces. Biological and morphological responses to human osteoblast cell lines were then examined by measuring cell proliferation, alkaline phosphatase activity, actin filaments, and RUNX2 gene expression.


Bone & Joint Research
Vol. 8, Issue 3 | Pages 107 - 117
1 Mar 2019
Lim ZXH Rai B Tan TC Ramruttun AK Hui JH Nurcombe V Teoh SH Cool SM

Objectives

Long bone defects often require surgical intervention for functional restoration. The ‘gold standard’ treatment is autologous bone graft (ABG), usually from the patient’s iliac crest. However, autograft is plagued by complications including limited supply, donor site morbidity, and the need for an additional surgery. Thus, alternative therapies are being actively investigated. Autologous bone marrow (BM) is considered as a candidate due to the presence of both endogenous reparative cells and growth factors. We aimed to compare the therapeutic potentials of autologous bone marrow aspirate (BMA) and ABG, which has not previously been done.

Methods

We compared the efficacy of coagulated autologous BMA and ABG for the repair of ulnar defects in New Zealand White rabbits. Segmental defects (14 mm) were filled with autologous clotted BM or morcellized autograft, and healing was assessed four and 12 weeks postoperatively. Harvested ulnas were subjected to radiological, micro-CT, histological, and mechanical analyses.