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Background In contrast to cigarettes, electronic cigarette use (E-cigarettes) has grown substantially over the last decade. This is due to their promotion as both a safer alternative to cigarettes and as an aide to stop smoking. Critically, upon E-cigarette use, the user may be exposed to high doses of nicotine in addition to other compounds including flavouring chemicals, metal particulates and carbonyl compounds, particularly in highly vascularised tissues such as bone. However, there has been limited investigation into the impact of E-cigarette usage on bone physiology, particularly over extended time periods and there are no clinical recommendations regarding E-cigarette usage in relation to orthopaedic surgery. This literature review draws together data from studies that have investigated the impact of E-cigarette vapour and its major constituents on bone, detailing the models utilised and the relevant mechanistic and functional results. Main body Currently there is a lack of studies both in vivo and in vitro that have utilised E-cigarette vapour, necessary to account for changes in chemical composition of E-cigarette liquids upon vaping. There is however evidence that human bone and bone cells express nicotine receptors and exposure of both osteoblasts and osteoclasts to nicotine, in high concentrations may reduce their viability and impair function. Similarly, it appears that aldehydes and flavouring chemicals may also negatively impact osteoblast viability and their ability to form bone. However, such functional findings are predominantly the result of studies utilising bone cell lines such as MG-63 or Saos-2 cells, with limited use of human osteoblasts or osteoclasts. Additionally, there is limited consideration for a possible impact on mesenchymal stem cells, which can also play an import role in bone repair. Conclusion Understanding the function and mechanism of action of the various components of E-cigarette vapour in mediating human bone cell function, in addition to long term studies to determine the potential harm of chronic E-cigarette use on human bone will be important to inform users of potential risks, particularly regarding bone healing following orthopaedic surgery and injury.

Objective The aim was to identify the cost-effectiveness of minimally invasive sacroiliac joint fusion (MI SIJF) surgery with titanium triangular implants for patients with sacroiliac joint (SIJ) pain who have failed conservative management, compared to non-surgical management (NSM) from a National Health Service (NHS) England perspective. Methods Over a time horizon of 5 years, a cohort state transition model compared the costs and outcomes of treating patients with MI SIJF to those of traditional NSM treatment pathways. The NSM arm included two treatments: grouped physical therapy and corticosteroid injections (PTSI) or radiofrequency ablation (RFA). Three different strategies were considered: (1) a stepped pathway, (2) patients split between PTSI and RFA, and (3) RFA only. The outcome measure was incremental cost-effectiveness ratio (ICER), reported in 2018 British pounds per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were used to test the robustness of the model results. Results Patients undergoing MI SIJF accrued total procedure-related and pain-management costs of £8358, while NSM treatment strategy 1 had total costs of £6880. The MI SIJF cohort had 2.98 QALYs compared to strategy 1 with 2.30 QALYs. This resulted in an ICER for MI SIJF versus strategy 1 of £2164/QALY gained. Strategy 2 of the NSM arm had lower costs than strategy 1 (£6564) and 2.26 QALYs, and this resulted in an ICER of £2468/QALY gained for MI SIJF. Strategy 3 of the NSM arm had lower costs than strategy 1 (£6580), and this resulted in 2.28 QALYs and an ICER of £2518/QALY gained for MI SIJF. Probabilistic sensitivity analysis shows that at a threshold of £20,000/QALY gained, MI SIJF has a probability of being cost-effective versus NSM strategies of 96%, 97%, and 91% for strategies 1, 2, and 3, respectively. Conclusion MI SIJF appears to be cost-effective over a 5-year time horizon when compared to traditional NSM pathways in an NHS context. Electronic supplementary material The online version of this article (10.1007/s41669-020-00236-5) contains supplementary material, which is available to authorized users.

Study Design An observational descriptive study based on a single cohort of patients. Objective To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in adolescent idiopathic scoliosis (AIS) patients. Summary of Background Data Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathology of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex compared with outside the curve in AIS patients. Methods Facet spinal tissue was collected perioperatively from three sites, the concave and convex side at the curve apex and from outside the curve (noncurve) from three AIS female patients aged 13–16 years. Spinal tissue was analyzed by micro–computed tomography to determine bone mineral density (BMD) and trabecular structure. Primary osteoblasts were cultured from concave, convex, and noncurve facet bone chips. The phenotype of osteoblasts was determined by assessment of cellular proliferation, cellular metabolism (alkaline phosphatase and Seahorse Analyzer), bone nodule mineralization (Alizarin red assay), and the mRNA expression of Wnt signaling genes (quantitative reverse transcriptase polymerase chain reaction). Results Convex facet tissue exhibited greater BMD and trabecular thickness, compared with concave facet tissue. Osteoblasts at the convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralized bone nodules, compared with concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts, compared with noncurve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts, compared with either concave or noncurve. Conclusions Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in AIS patients. Level of Evidence Level IV, Prognostic.

Study Design Retrospective observational study of a continuous series of 28 children. Purpose To determine the mechanical failure rate in our cohort of children treated with magnetically controlled growth rods (MCGRs). Overview of Literature Previous studies report a MCGR mechanical failure rate of 0%–75%. Methods All patients with MCGR implantation between 2012 and 2015 were examined and followed up for a minimum of 2 years. A retrospective evaluation of contemporaneously documented clinical findings was conducted, and radiographs were retrospectively examined for mechanical failure. The external remote controller (ERC)-specified length achieved in the clinic was compared to the length measured on subsequent radiographs. Results Fourteen mechanical failures were identified in 28 children (50%) across a total of 52 rods (24 pairs and four single constructs). Mechanical failures were due to: failure to lengthen under general anesthesia (seven children), actuator pin fracture (four), rod fracture (one), foundation screw failure (one), and ran out of rod length (one). Of the 14 mechanical failures, six were treated with final fusion operations (reflecting limited further growth potential), and eight patients were treated with the intention for further lengthening. We therefore consider these eight patients to represent the true incidence of mechanical failure in our cohort (29%). The difference between the ERC length and radiographic length was found to be identical in 11% cases; 35% were overestimates, and 54% were underestimates. The median underestimate was 2.45 mm whereas the median overestimate was 3.1 mm per distraction episode. In total, 95% of all ERC distractions were within ±10 mm of the radiographic length achieved over a median of nine distraction episodes. Conclusions Our series is the most comprehensive MCGR series published to date, and we present a mechanical failure rate of 29%. Clinicians should be mindful of the discrepancies between ERC length and radiographic measurements of rod length; other modalities may be more helpful in this regard.

Adolescent idiopathic scoliosis (AIS) is now considered to be a multifactorial heterogeneous disease, with recent genomic studies supporting the role of intrinsic factors in contributing to the onset of disease pathology and curve progression. Understanding the key molecular signalling pathways by which these intrinsic factors mediate AIS pathology may facilitate the development of pharmacological therapeutics and the identification of predictive markers of progression. The heterogenic nature of AIS has implicated multiple tissue types in the disease pathophysiology, including spinal bone, intervertebral disc and paraspinal muscles. In this review, we highlight some of the mechanisms and intrinsic molecular regulators within these different tissue types and review the evidence for their involvement in AIS pathology.

To assess the reliability of the indicators for performing magnetic resonance imaging in patients with scoliosis and assess the incidence of neural axis anomalies in a population with scoliosis referred to a specialist centre.A retrospective review of magnetic resonance imaging (MRI) reports of all patients under the age of 18 who underwent a pre-operative MRI for investigation of their scoliosis between 2009 and 2014 at a single institution was performed.There were 851 patients who underwent an MRI scan of their whole spine with a mean age of 14.08 years. There were 211 males and 640 females. One hundred and fourteen neural axis abnormalities (NAA) were identified. The presence of a left sided thoracic curve, a double thoracic curve, being male nor being diagnosed before the age of 10 were found to be statistically significant for the presence of a NAA. Furthermore, 2.34% of patients were also found to have an incidental finding (IF) of an extraspinal abnormality.From our series, the reported indications for performing an MRI scan in the presence of scoliosis are not reliable for the presence of an underlying NAA. We have demonstrated that there is a number of intra and extra dural anomalies found on MRI without clinical symptoms and signs. This acts as normative information for this group.Scoliosis; magnetic resonance imaging (MRI); neural axis abnormalities (NAA); adolescent idiopathic scoliosis (AIS).

Background: This study is a single centre retrospective review of prospectively collected data. The ‘law of diminishing returns’ describes the number of lengthening episodes that a traditional growth rod (TGR) can undergo before stiffness across the construct prevents further increases in overall length. It is unclear whether this will affect MCGR when used in the management of early onset scoliosis (EOS). Methods: A retrospective review of prospectively collected data on the experience of MCGR lengthening in a heterogenous cohort of children with EOS from a single centre. Results: There were 53 MCGRs in 28 patients with EOS with a number of different underlying diagnoses. The mean age of the cohort was 8 years 3 months (SD, 2 years 7 months). The mean follow-up period since primary rod implantation was 2 years 0 months (SD, 1 year 1 month). MCGR lengthening was performed on up to 12 occasions [median, 4; interquartile range (IQR), 4; range, 1–12]. There was no statistically significant difference in the amount of length achieved over then number of lengthening episodes (P=0.427). For those with at least 2 years follow up the median number of lengthening was 10 (IQR 2, range 9–12) and there was no statistically significant difference seen (P=0.438). Growth velocity of MCGRs against age was less than previously documented norms for the thoracic spine, but was maintained as age increased. Conclusions: The ‘law of diminishing returns’ does not affect serial lengthening of MCGR in the way that has been observed using TGR. It was also demonstrated that in the MCGR group growth velocity was maintained relative to that of the normal spine.

The present study investigates the effect of vancomycin and gentamicin antibiotics on primary human osteoblasts. Osteoblasts were incubated with vancomycin, gentamicin, or with povidone-iodine (PVI), at concentrations advocated for wound irrigation. Osteoblast proliferation, metabolic function, and bone mineralization were measured.The aim of the study was to model gentamicin and vancomycin wound irrigation in vitro and to examine the effect on osteoblast viability and cellular function in comparison to 0.35% PVI.Vancomycin, gentamicin, and dilute PVI are employed as wound irrigants in spinal surgery to reduce infection. We have, however, recently demonstrated that 0.35% PVI has a detrimental effect on osteoblast cellular function and bone mineralization. Studies to determine the effects of antibiotic wound irrigation solutions on osteoblasts and bone mineralization are therefore warranted.Primary human osteoblasts were exposed for 20 minutes to phosphate buffered saline (PBS) control, vancomycin (35 or 3.5 mmol/L), gentamicin (34 or 3.4 mmol/L), or 0.35% PVI for 3 minutes. Cellular proliferation was measured during 7 days by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Osteoblast metabolic function was determined using a Seahorse XFe24 Bioanalyzer. Mineralized bone nodules were quantified using Alizarin red.At concentrations advocated for wound irrigation, both gentamicin (3.4 mmol/L) and vancomycin (3.5 mmol/L) induced a transient 15% to 20% reduction in osteoblast proliferation, which returned to control values within 72 hours. This was in marked contrast to the effect of 0.35% PVI, which resulted in a sustained reduction in osteoblast proliferation of between 40% and 50% during 7 days. Neither gentamicin nor vancomycin at concentrations up to 10× clinical dose had any effect on osteoblast oxygen consumption rate, or significantly affected mineralized bone nodule formation.Vancomycin and gentamicin solutions, at concentrations advocated for intrawound application in spinal surgery, have a small but transient effect on osteoblast proliferation, and no effect on either osteoblast metabolic function or bone nodule mineralization.N/A.

STUDY DESIGN A study examining the clinical protocol of scoliosis wound irrigation, demonstrating povidone-iodine's (PVI) effect on human osteoblast cells. Primary and immortal cell line osteoblasts were treated with 0.35% PVI for 3 minutes, and analyzed for proliferation rate, oxidative capacity, and mineralization. OBJECTIVE To model spinal wound irrigation with dilute PVI in vitro, in order to investigate the effect of PVI on osteoblast proliferation, metabolism, and bone mineralization. SUMMARY OF BACKGROUND DATA Previously PVI irrigation has been proposed as a safe and effective practice to avoid bacterial growth after spinal surgery. However, recent evidence in multiple cell types suggests that PVI has a deleterious effect on cellular viability and cellular function. METHODS Primary and immortal human osteoblast cells were exposed to either phosphate buffered saline control or with 0.35% PVI for 3 minutes. Cellular proliferation was measured over the duration of 7 days by MTS assay. Oxygen consumption rate, extracellular acidification rate, and proton production rate were analyzed using a Seahorse XF24 Bioanalyzer. Protein expression of the electron transport chain subunits CII-SDHB, CIII-UQRCR2, and CV-ATP5A was measured via Western blotting. Mineralized bone nodules were stained with alizarin red. RESULTS Expressed as a percentage of normal osteoblast proliferation, osteoblasts exposed to 0.35% PVI exhibited a significant 24% decrease in proliferation after 24 hours. This was a sustained response, resulting in a 72% decline in cellular proliferation at 1 week. There was a significant reduction in oxygen consumption rate, extracellular acidification rate, and proton production rate (P