ObjectiveLocal antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model.MethodsSixty-four, male Sprague-Dawley rats were inoculated with 10 μl of 1.5 x 108 CFU/ml of Staphylococcus aureus in a surgically drilled defect in the right proximal tibia. Infected animals were randomly allocated into prevention and treatment groups with 32 rats each. In the prevention group, the defect was filled with a plug containing either PMMA or CaP/CaS immediately after the inoculation. In the treatment group, the infected defects were irrigated, debrided, and filled with either a PMMA or CaP/CaS plug. Both CaP/CaS and PMMA were impregnated with 10% weight of vancomycin. Rats were sacrificed 6 weeks after cement insertion. Infection was detected by bacterial culture and histological analysis. Bone formation in the defect was assessed with micro-computed tomography and histology.ResultsNo bacteria were detected in any group. Both the prevention and treatment groups using CaP/CaS had significantly more bone volume fraction, bone area, and cartilage area than the PMMA groups.ConclusionsWhen loaded with 10% of vancomycin, CaP/CaS and PMMA have the same efficacy for treatment and prevention of osteomyelitis. CaP/CaS enhances bone defect healing through improved bone remodeling in our osteomyelitis rat model.

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.

With the ageing population, musculoskeletal conditions are becoming more inherent. Delayed union is defined as a slower than normal fracture healing response, with no healing after 4 to 6 months; however, the union is anticipated given sufficient time. In the context of delayed/non-union, fragility fractures in osteoporotic populations carry significant patient morbidity and socioeconomic costs. Multiple mechanisms hinder fracture healing in osteoporotic patients, imbalanced bone remodelling leads to impaired bone microarchitecture due to reduced osteoblast number and activity and as such, callus formation is diminished. Since stem cells can self-renew and differentiate into various tissue lineages, they are becoming very popular in tissue regeneration in musculoskeletal conditions. In this review, we discuss the role of stem cells in physiological fracture healing and their potential therapeutic use following a fracture. We explore the potential of stem cells, the release of chemokines and cytokines to reduce fracture risk in osteoporosis.

Increasingly, the rat femoral fracture model is being used for preclinical investigations of fracture healing, however, the effect of gap size and its influence on mechanobiology is not well understood. We aimed to evaluate the influence of osteotomy gap on osteotomy healing between the previously published extremes of guaranteed union (0.5 mm) and non-union (3 mm) using this model.A femoral osteotomy in 12–14 week old female Wistar rats was stabilised with a micro fixator (titanium blocks, carbon fiber bars) with an osteotomy gap of 1.0 mm (n = 5), 1.5 mm (n = 7), 2.0 mm (n = 6). After five weeks, the left femur was retrieved. The osteotomy gap was scanned using X-ray microtomography and then histologically evaluated. The radiographic union rate (complete mineralised bone bridging across the osteotomy) was three times higher for the 1.0 mm than the 2.0 mm gap. The 1.0 mm gap had the largest callus (0.069μm3) and bone volume (0.035μm3). Callus and bone volume were approximately 50% smaller within the 2.0 mm gap.Using cadaveric rat femurs stabilised with the external fixator, day 0 mechanical assessment of construct stiffness was calculated on materials testing machine displacement vs load output. The construct stiffness for the 1.0, 1.5 and 2.0 mm gaps was 32.6 ± 5.4, 32.5 ± 2.4, and 32.4 ± 8.3 N/mm (p = 0.779). Interfragmentary strain (IFS) was calculated using the change in osteotomy gap displacement as measured using microstrain miniature differential reluctance transducer spanning the osteotomy gap. Increasing the gap size significantly reduced the IFS (p = 0.013). The mean ‘day 0’ IFS for the 1.0, 1.5 and 2.0 mm gaps were 11.2 ± 1.3, 8.4 ± 1.5 and 6.1 ± 1.2% respectively.A 1.5 mm gap resulted in a delayed fracture healing by 5 weeks and may represent a useful test environment for fracture healing therapy. Increasing gap size did not affect construct stiffness, but did reduce the ‘day 0’ IFS, with a doubling of non-union and halving of bone volume measured between 1.0 and 2.0 mm gaps.

ObjectivesThis study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis.MethodsMesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant.ResultsCD marker expression and proliferation of the MSCs from the three groups was not significantly different. The young MSCs demonstrated significantly increased differentiation into bone and fat and superior migration towards SDF-1. The migration of SDF-1 doubled with young rats compared with the adult rats (p = 0.023) and it was four times higher when compared with cells isolated from ovariectomized (OVX) osteopenic rats (p = 0.013).ConclusionYoung rat MSCs are significantly more responsive to osteogenic differentiation, and, contrary to other studies, also demonstrated increased adipogenic differentiation compared with cells from adult and ostopenic rats. Young-rat-derived cells also showed superior migration towards SDF-1 compared with MSCs from OVX and adult control rats.Cite this article: A. Sanghani-Kerai, L. Osagie-Clouard, G. Blunn, M. Coathup. The influence of age and osteoporosis on bone marrow stem cells from rats. Bone Joint Res 2018;7:289–297. DOI: 10.1302/2046-3758.74.BJR-2017-0302.R1.

Intraosseous cysts of the carpal bones are an infrequent cause of chronic wrist pain. The main body of work has investigated their occurrence in the proximal carpus, with limited incidence in the distal row. We review the current literature on the treatment of symptomatic carpal cysts following the report of a 17-year-old male with a 12-month history of progressive right wrist pain due to an intraosseous ganglion of the trapezoid. This review explores the pathology of carpal cysts, their varying presentation and current treatments.

Purpose Osteochondrodysplasias are characterised by aberrant cartilage and bone development; consequently, patients may be subject to premature hip degeneration. In this population hip arthroplasty outcomes are variable. This series reviews the use of custom femoral implants in total hip replacements for patients with severe skeletal dysplasia. Methods We reviewed 14 hips in nine patients with genetic dwarfism. Computed tomography (CT) scans of the pelvis and femurs were used to create custom titanium stems. Postoperative radiographs were reviewed for migration, osteolysis, fracture and restoration of leg length. Pre-and postoperative Harris hip scores (HHS) were compared, with a mean follow-up of 36.3 months. Mean age was 36.5 years (range 15-50 years) and mean height was 48 inches (range 42-55 inches). Three joints were classified as Crowe type I, two type II, three type III and six type IV. Results Three hips (21%) required revision: two for stem migration and one for acetabular osteolysis. Eleven hips (79%) were stable with signs of osseointegration. No fractures, nerve damage or dislocations occurred. Two stems required cement fixation, and no liners were constrained. Significant osteolysis was seen on three radiographs. All patients walked independently, and mean HHS improved from 45 (24-58) to 71 (47-89). All leg length discrepancies were restored to within 3 mm of equal. Conclusions This study reports good midterm outcomes in a variety of skeletal dysplasias, thus confirming the efficacy of custom femoral implants in the management of this patient group.

Background and purpose — Hip precautions limiting flexion, adduction, and internal rotation have been prescribed traditionally to minimize dislocation rates following THA. We assessed the prevalence of hip dislocation following posterior approach total hip arthroplasty without postoperative hip precautions. Methods — A systematic review of multiple medical databases was performed using the PRISMA guidelines and checklist. All clinical outcome studies that reported dislocation rates and postoperative instructions following posterior approach, primary surgery, published within the last 6 years, were included. Results — 6,900 patients were included from 7 Level I–IV studies, with 3,517 treated with and 3,383 without precautions. There was no statistically significant difference in the rates of dislocation between groups (2.2% in restricted group vs. 2.0% in unrestricted group). All but 1 study demonstrated no statistically significant differences in patient-reported outcome scores between restricted and unrestricted groups, including those pertaining to return to function, confidence, and pain. Interpretation — The review found no impact on dislocation rates following total hip arthroplasty performed through a posterior approach, regardless of the use of hip precautions. We also found no impact of the prescription of hip precautions on patient-reported outcome scores.