Objectives. Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain. Methods. We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells. Results. We showed that both N- and C-terminal PTHrP peptides at 100 nM decreased reactive oxygen species production and forkhead box protein O activation following hydrogen peroxide (H. 2. O. 2. )-induced oxidation, which was related to decreased lipid oxidative damage and caspase-3 activation in these cells. This was associated with their ability to restore the deleterious effects of H. 2. O. 2. on cell growth and alkaline phosphatase activity, as well as on the expression of various osteoblast differentiation genes. The addition of Rp-cyclic 3′,5′-hydrogen phosphorothioate adenosine triethylammonium salt (a cyclic 3',5'-adenosine monophosphate antagonist) and calphostin C (a protein kinase C inhibitor), or a PTH type 1 receptor antagonist, abrogated the effects of N-terminal PTHrP, whereas protein phosphatase 1 (an Src kinase activity inhibitor), SU1498 (a vascular endothelial growth factor receptor 2 inhibitor), or an anti osteostatin antiserum, inhibited the effects of C-terminal PTHrP. Conclusion. These findings indicate that the antioxidant properties of PTHrP act through its N- and C-terminal domains and provide novel insights into the osteogenic action of PTHrP. Cite this article: S. Portal-Núñez, J. A. Ardura, D. Lozano, I. Martínez de Toda, M. De la Fuente, G. Herrero-Beaumont, R. Largo, P. Esbrit. Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains. Bone Joint Res 2018;7:58–68. DOI: 10.1302/2046-3758.71.BJR-2016-0242.R2

Aims

The aim of this study was to assess whether it is possible to predict the mortality, and the extent and time of neurological recovery from the time of the onset of symptoms and MRI grade, in patients with the cerebral fat embolism syndrome (CFES). This has not previously been investigated.

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The outcome following the development of neurological complications after corrective surgery for scoliosis varies from full recovery to a permanent deficit. This study aimed to assess the prognosis and recovery of major neurological deficits in these patients, and to determine the risk factors for non-recovery, at a minimum follow-up of two years.

Aims. Several studies have reported the safety and efficacy of subcapital re-alignment for patients with slipped capital femoral epiphysis (SCFE) using surgical dislocation of the hip and an extended retinacular flap. Instability of the hip and dislocation as a consequence of this surgery has only recently gained attention. We discuss this problem with some illustrative cases. Materials and Methods. We explored the literature on the possible pathophysiological causes and surgical steps associated with the risk of post-operative instability and articular damage. In addition, we describe supplementary steps that could be used to avoid these problems. Results. The causes of instability may be divided into three main groups: the first includes causes directly related to SCFE (acetabular labral damage, severe abrasion of the acetabular cartilage, flattening of the acetabular roof and a bell-shaped deformity of the epiphysis); the second, causes not related to the SCFE (acetabular orientation and poor quality of the soft tissues); the third, causes directly related to the surgery (capsulotomy, division of the ligamentum teres, shortening of the femoral neck, pelvi-trochanteric impingement, previous proximal femoral osteotomy and post-operative positioning of the leg). Conclusion. We present examples drawn from our clinical practice, as well as possible ways of reducing the risks of these complications, and of correcting them if they happen. Cite this article: Bone Joint J 2017;99-B:16–21

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.

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The aim of this study was to investigate whether wear and backside deformation of polyethylene (PE) tibial inserts may influence the cement cover of tibial trays of explanted total knee arthroplasties (TKAs).

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The primary aim of this study was to determine the rates of return to work (RTW) and sport (RTS) following a humeral shaft fracture. The secondary aim was to identify factors independently associated with failure to RTW or RTS.

Aims. The intra-articular administration of tranexamic acid (TXA) has been shown to be effective in reducing blood loss in unicompartmental knee arthroplasty and anterior cruciate reconstruction. The effects on human articular cartilage, however, remains unknown. Our aim, in this study, was to investigate any detrimental effect of TXA on chondrocytes, and to establish if there was a safe dose for its use in clinical practice. The hypothesis was that TXA would cause a dose-dependent damage to human articular cartilage. . Materials and Methods. The cellular morphology, adhesion, metabolic activity, and viability of human chondrocytes when increasing the concentration (0 mg/ml to 40 mg/ml) and length of exposure to TXA (0 to 12 hours) were analyzed in a 2D model. This was then repeated, excluding cellular adhesion, in a 3D model and confirmed in viable samples of articular cartilage. Results. Increasing concentrations above 20 mg/ml resulted in atypical morphology, reduced cellular adhesion and metabolic activity associated with increased chondrocyte death. However, the cell matrix was not affected by the concentration of TXA or the length of exposure, and offered cellular protection for concentrations below 20 mg/ml. Conclusion. These results show that when in vitro chondrocytes are exposed to higher concentrations of TXA, such as that expected following recommended intra-articular administration, cytotoxicity is observed. This effect is dose-dependent, such that a tissue concentration of 10 mg/ml to 20 mg/ml could be expected to be safe. Cite this article: Bone Joint J 2018;100-B:404–12

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Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations.

Damage to the dorsomedial branch of the medial dorsal cutaneous nerve is not uncommon in surgery of the hallux. The resultant morbidity can be disabling. In the light of the senior author’s operative observation of a sentinel vein, we undertook a cadaver study to investigate the anatomical relationships of the dorsomedial branch of the medial dorsal cutaneous nerve. This established that in 14 of 16 cadaver great toes exposed via a modified medial incision, there is an easily identified vein which runs transversely superficial and proximal to the nerve. In a prospective clinical study of 171 operations on the great toe using this approach, we confirmed this anatomical relationship in 142 procedures (83%), with no complaint of numbness or pain in the scar at follow-up. We attribute this to careful identification of the ‘sentinel’ vein and the subjacent sensory nerve, which had been successfully protected from damage. We recommend this technique when operating on the great toe.

Aims. The aim of this study was to examine the real time in vivo kinematics of the hip in patients with cam-type femoroacetabular impingement (FAI). Patients and Methods. A total of 50 patients (83 hips) underwent 4D dynamic CT scanning of the hip, producing real time osseous models of the pelvis and femur being moved through flexion, adduction, and internal rotation. The location and size of the cam deformity and its relationship to the angle of flexion of the hip and pelvic tilt, and the position of impingement were recorded. Results. In these patients with cam-type FAI, there was significant correlation between the alpha angle and flexion to the point of impingement (mean 41.36°; 14.32° to 57.95°) (R = -0.5815 and p = < 0.001). Patients with a large cam deformity (alpha angle > 78°) had significantly less flexion to the point of impingement (mean 36.30°; 14.32° to 55.18°) than patients with a small cam deformity (alpha angle 60° to 78°) (mean 45.34°; 27.25° to 57.95°) (p = < 0.001). Conclusion. This study has shown that cam-type impingement can occur early in flexion (40°), particularly in patients with large anterior deformities. These patients risk chondrolabral damage during routine activities such as walking, and going up stairs. These findings offer important insights into the cause of the symptoms, the mechanisms of screening and the forms of treatment available for these patients. Cite this article: Bone Joint J 2017;99-B(4 Supple B):41–8

Controversy continues to surround the management of patients with an open fracture of the lower limb and an associated vascular injury (Gustilo type IIIC). This study reports our 15-year experience with these fractures and their outcome in 18 patients (15 male and three female). Their mean age was 30.7 years (8 to 54) and mean Mangled Extremity Severity Score (MESS) at presentation was 6.9 (3 to 10). A total of 15 lower limbs were salvaged and three underwent amputation (two immediate and one delayed). Four patients underwent stabilisation of the fracture by external fixation and 12 with an internal device. A total of 11 patients had damage to multiple arteries and eight had a vein graft. Wound cover was achieved with a pedicled flap in three and a free flap in six. Seven patients developed a wound infection and four developed nonunion requiring further surgery. At a mean follow-up of five years (4.1 to 6.6) the mean visual analogue scale for pain was 64 (10 to 90). Depression and anxiety were common. Activities were limited mainly because of pain, and the MESS was a valid predictor of the functional outcome. Distal tibial fractures had an increased rate of nonunion when associated with posterior tibial artery damage, and seven patients (39%) were not able to return to their previous occupation

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Endoprosthetic reconstruction with a distal femoral arthroplasty (DFA) can be used to treat distal femoral bone loss from oncological and non-oncological causes. This study reports the short-term implant survivorship, complications, and risk factors for patients who underwent DFA for non-neoplastic indications.

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The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA).

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There is evidence that morbidly obese patients have more intra- and postoperative complications and poorer outcomes when undergoing total hip arthroplasty (THA) with the direct anterior approach (DAA). The aim of this study was to determine the efficacy of DAA for THA, and compare the complications and outcomes of morbidly obese patients with nonobese patients.

The subject of central nervous system damage includes a wide variety of problems, from the slow selective ‘picking off’ of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system

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Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem.