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Software for image analysis endorsed further developments in the medical area that would accept state of the art reengineering processes to reproduce actual internal organs and structures of the human body. Previous research on FDM produced elements in the medicine field shown important discoveries on orthopedics. Preoperative planning shown to be suitable for additive manufacturing solutions that could help to improve the efficiency on procedures lowering potential risks after surgery. Accurate and well thought planning is necessary to choose the best way for the practice and deliver the best results. Tooling customization has shown to help into achieving this result. Bone-related surgeries require customized cutting guides for better accuracy. The following work aims to deliver the opportunity to use variations of Polylactic acid (PLA) based cutting guides in actual surgery practices by means of sustaining a regular heat-sterilization procedure without compromising its tailor-made characteristics. This would be possible by means of a proved, reliable procedure for obtaining the prototype from traditional CT scan images. As a result, HTPLA material composition and crystallization properties allowed to sustain a sterilization procedure in a way that does not compromise the reliability of the part, nor the safety of the procedure, so prototypes made with a similar process as the proposed one, can be used in actual surgery practices with safety.

This work is the outcome of a partnership between the Department of Industrial Engineering of the University of Bologna and the Rizzoli Orthopedic Institute of Bologna. The aim of this collaboration is using medical engineering tools during orthopedic surgeries. This article focuses on the design and construction of a custom-made surgical guide for cubitus varus. The guides are special aids that allow surgeons to perform operations smoothly, to achieve the planned result and to reduce the risk of inaccuracy. They are obtained with an additive manufacturing process that starts from a 3D digital model of the patient's bone obtained from CT scans and allow designing patient-specific templates using specific software as the Creo Parametric CAD. For the proper functioning of the guide the internal shape must correspond to the external profile of the patient's bone. In this way, the tool obtained fits exactly to the bone and it is possible to direct the cutting during surgery in a very specific direction as identified in the preoperative planning phase.

This work aims to present the application of mechanical modeling software in three dimensions in the medical field, analyzing the procedures used by the engineer to support the orthopedic surgeon in preoperative planning. The first step of the procedure involves CT examinations in patients selected for surgery: DICOM images are managed in post-processing to obtain multiplanar reconstructions of the bone lesion to be treated. The files are then optimized, made shareable and imported into CREO's work platform; this is part of a family of CAD software products for mechanical design, developed by PTC, and is the fundamental application dedicated to parametric modeling. The result will be a faithful representation of the anatomical part both before and after surgical procedure, screening all the intermediate phases. The doctor will assess different lines of action according to the results, than he will communicate them to the engineer who, consequently, will correct and regenerate the model. The method finds its power in the dialogue between engineer and doctor: In complex cases closer collaboration is needed while, for the evaluation of less demanding injuries, the exam could be assigned as a remote project which, once completed, is returned to the medical facility of competence.

Torsional deformities of the lower limb are common in children with cerebral palsy (CP)-determining gait problems. The mechanisms underlying transverse plane gait deviations arise from a combination of dynamic and static factors. The dynamic elements may be due to spasticity, contractures and muscle imbalances, while the static ones may result from excessive femoral anteversion, which decreases the efficiency of the hip abductors by reducing the muscular lever arms. A therapeutic approach has been identified in multi-level functional surgery for the lower limb. Treating the malalignments of the lower limb with femoral or tibial derotation provides optimal results, especially when supported by adequate biomechanical planning. This planning requires an integrated static-dynamic approach of morphological and functional evaluation, based on radiological measurements, physical examination and gait analysis. Instrumented gait analysis has been confirmed as essential in the evaluation and surgical decision making process for children affected by CP with transverse plane deformities. Computational simulations based on musculoskeletal models that integrate patient-specific CT morphological data into gait analysis can be used for the implementation of a surgical simulation system in pre-operative planning to test the possible effects of the different surgical treatment options on the torsional defects of the lower limbs. Recently, a computer-aided simulation process has been implemented in the preoperative planning of complex osteotomies for limb deformities in children. Three-dimensional (3D) digital models were generated from Computed Tomography (CT) scans, using free open-source software. The aim of this study is to integrate the patient-specific CT musculoskeletal model with morphological data and gait analysis data, with the personalized calculation of kinematic and kinetic parameters, which allow us to generate an “avatar” of the patient for a more in-depth evaluation of the gait abnormalities. The computational simulation platform proposed provides a realistic movable musculoskeletal model in a virtual environment, with the possibility of planning and monitoring the effects of virtual three-dimensional surgical corrections.

Background: total hip replacement (THR) is a rare surgical option in children and adolescents with disabling hip diseases. The aim of this study is to report results from a retrospective cohort of patients aged 18 years or less who underwent cementless Ceramic-on-Ceramic (CoC) THR at a single institution, investigating clinical and radiographic outcomes, survival rates, and reasons for revision of the implants. Materials and methods: we queried the Registry of Prosthetic Orthopedic Implants (RIPO) to identify all children and adolescents undergoing THR between 2000 and 2019 at a single Institution. Inclusion criteria were patients undergoing cementless CoC THR, aged less than 18 years at surgery, followed for at least 2 years. Sixty-eight patients (74 hips) matched all the inclusion criteria and were enrolled in the study. We assessed the clinical and radiographic outcomes, the rate of complications, the survival rate, and reasons for revision of the implants. Results: The mean follow-up was 6.6 ± 4.4 years (range 2–20). The most frequent reason for THR was post-traumatic or chemotherapy-induced avascular necrosis (38%). The overall survival rate of the cohort was 97.6% (95% CI: 84.9–99.7%) at 5 years of follow-up, 94.4% (95% CI: 79.8–98.6%) at 10 years and 15 years of follow-up. Two THR in two patients (2.7%) required revision. With the numbers available, Cox regression analysis could not detect any significant interaction between preoperative or intraoperative variables and implant survivorship (p-value 0.242 to 0.989).” The average HOOS was 85 ± 14.3 (range 30.6–100). Overall, 23 patients (48%) reported excellent HOOS scores (&gt, 90 points), 21 patients (44%) reported acceptable HOOS scores (60–90 points) while 4 patients (8%) reported poor outcomes (&lt, 60 points). Twenty-one patients (43%) were regularly involved into moderate- to high-intensity sport activities (UCLA ≥ 6). Conclusions: Cementless CoC THR is a successful procedure in children and teenagers, having demonstrated high implant survivorship and low rates of complications and failure. A meticulous preoperative planning and implant selection is mandatory, to avoid implant malposition, which is the main reason of failure and revision in these cases. Further studies are needed to assess the impact of the THR on the psychosocial wellbeing of teenagers, as well as risks and benefits and cost-effectiveness in comparison to the hip preserving surgical procedures.

Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We conducted a single-institution cross-sectional study. Patients were categorized according to IOR Classification, which identifies three patients' classes on the presence/absence of deformities and/or limitations. The present dataset was compared with our previously published data, to refine the classification. Nine hundred sixty-eight patients were included: 243 children (

Three-dimensional printed custom cutting guides (CCGs) are becoming more and more investigated in medical literature, as a patient-specific approach is often desired and very much needed in today’s surgical practice. Three-dimensional printing applications and computer-aided surgical simulations (CASS) allow for meticulous preoperatory planning and substantial reductions of operating time and risk of human error. However, several limitations seem to slow the large-scale adoption of 3D printed CCGs. CAD designing and 3D printing skills are inevitably needed to develop workflow and address the study, therefore, hospitals are pushed to include third-party collaboration, from highly specialized medical centers to industrial engineering companies, thus increasing the time and cost of labor. The aim of this study was to move towards the feasibility of an in-house, low-cost CCG 3D printing methodology for pediatric orthopedic (PO) surgery. The prototype of a femoral cutting guide was developed for its application at the IOR—Rizzoli Orthopedic Institute of Bologna. The element was printed with an entry-level 3D printer with a high-temperature PLA fiber, whose thermomechanical properties can withstand common steam heat sterilization without bending or losing the original geometry. This methodology allowed for extensive preoperatory planning that would likewise reduce the overall surgery time, whilst reducing the risks related to the intervention.

The study of CAD (computer aided design) modeling, design and manufacturing techniques has undergone a rapid growth over the past decades. In medicine, this development mainly concerned the dental and maxillofacial sectors. Significant progress has also been made in orthopedics with pre-operative CAD simulations, printing of bone models and production of patient-specific instruments. However, the traditional procedure that formulates the surgical plan based exclusively on two-dimensional images and interventions performed without the aid of specific instruments for the patient and is currently the most used surgical technique. The production of custom-made tools for the patient, in fact, is often expensive and its use is limited to a few hospitals. The purpose of this study is to show an innovative and cost-effective procedure aimed at prototyping a custom-made surgical guide for address the cubitus varus deformity on a pediatric patient. The cutting guides were obtained through an additive manufacturing process that starts from the 3D digital model of the patient’s bone and allows to design specific models using Creo Parametric. The result is a tool that adheres perfectly to the patient’s bone and guides the surgeon during the osteotomy procedure. The low cost of the methodology described makes it worth noticing by any health institution.

This work aims to present an in-house low-cost computer-aided simulation (CASS) process that was recently implemented in the preoperative planning of complex osteotomies for limb deformities in children. Five patients admitted to the Unit of Paediatric Orthopaedics and Traumatology from April 2018 to December 2019, for correcting congenital or post-traumatic limb deformities were included in the study. Three-dimensional (3D) digital models were generated from Computed Tomography (CT) scans, using free open-source software, and the surgery was planned and simulated starting from the 3D digital model. 3D printed sterilizable models were fabricated using a low-cost 3D printer, and animations of the operation were generated with the aim to accurately explain the operation to parents. All procedures were successfully planned using our CASS method and the 3D printed models were used during the operation, improving the understanding of the severely abnormal bony anatomy. The surgery was precisely reproduced according to CASS and the deformities were successfully corrected in four cases, while in one case, the intraoperative intentional undersizing of the bone osteotomy produced an incomplete correction of a congenital forearm deformity. Our study describes the application of a safe, effective, user-friendly, and low-cost CASS process in paediatric orthopaedics (PO) surgery. We are convinced that our study will stimulate the widespread adoption of this technological innovation in routine clinical practice for the treatment of rare congenital and post-traumatic limb deformities during childhood.

Purpose: The aim of the present study was to translate, cross-culturally adapt, and assess the psychometric properties of the Pedi-IKDC and Pedi-FABS scores in the Italian paediatric population with various knee pathologies. Methods: In accordance with the Paediatric Anterior Cruciate Ligament Monitoring Initiative (PAMI) research protocol, the original English versions of the questionnaires were translated into Italian. All patients aged 8–16 and scheduled for knee surgery were considered eligible in the study. An open-source platform was implemented to collect responses to the surveys which included general patient information, the questionnaires Pedi-IKDC, and Pedi-FABS. Two surveys were sent under stable clinical conditions before surgery (Q1 and Q2); a third survey was sent 3–4months after surgery (Q3). The following properties were calculated: reliability, internal consistency, criterion validity, responsiveness, and floor/ceiling effects. Results: Eighty-nine patients completed Q1, 81 patients completed Q2, and 49 patients completed Q3. Both questionnaires demonstrated acceptable properties. Pedi-IKDC: standard error of measurement (SEM) = 4.4, smallest detectable change (SDC) = 12.3, interclass correlation coefficient (ICC) = 0.96, Cronbach alpha (α) = 0.92, moderate-to-low correlation to Pedi-FABS, effect size (ES) = 0.79, standardized response mean (SRM) = 0.86, floor = 0%, ceiling = 22%. Pedi-FABS: SEM = 2.1, SDC = 5.8, ICC = 0.94, Cronback alpha (α) = 0.93, moderate-to-low correlation to Pedi-IKDK, ES = 0.60, SRM = 0.51, floor = 19%, ceiling = 0%. Conclusions: The Italian version of Pedi-IKDC and Pedi-FABS is valuable tools for patient assessment, by demonstrating good psychometric properties. In clinical setting, these questionnaires can be used to properly evaluate outcomes in Italian pediatric patients with knee pathologies. Level of evidence: II.

This paper presents the application of a low-cost 3D printing technology in pre-operative planning and intra-operative decision-making. Starting from Computed Tomography (CT) scans, we were able to reconstruct a 3D model of the area of interest with a very simple and rapid workflow, using open-source software and an entry level 3D printer. The use of High Temperature Poly-Lactic Acid (HTPLA) by ProtoPasta allowed fabricating sterilizable models, which could be used within the surgical field. We believe that our method is an appealing alternative to high-end commercial products, being superior for cost and speed of production. It could be advantageous especially for small and less affluent hospitals that could produce customized sterilizable tools with little investment and high versatility.

Our purpose is to develop the preoperative diagnosis stage for orthopedic surgical treatments using additive manufacturing technology. Our methods involve fast implementations of an additive manufactured bone model, converted from CAT data, through appropriate software use. Then, additive manufacturing of the formed surfaces through special 3D-printers. With the structural model redesigned and printed in three dimensions, the surgeon is able to look at the printed bone and he can handle it because the model perfectly reproduces the real one upon which he will operate. We found that additive manufacturing models can precisely characterize the anatomical structures of fractures or lesions. The studied practice helps the surgeon to provide a complete preoperative valuation and a correct surgery, with minimized duration and risks. This structural model is also an effective device for communication between doctor and patient.

This experimental study defines the usage of a computer-aided surgical simulation process that is effective, safe, user-friendly, and low-cost, that achieves a detailed and realistic representation of the anatomical region of interest. The chosen tools for this purpose are state-of-the-art Computer Aided Design (CAD) software for mechanical design, and are the fundamental application dedicated to parametric modeling. These tools support different work environments, each one is for a specific type of modeling, and they allow the simulation of surgery. The result will be a faithful representation of the anatomical part both before and after the surgical procedure, screening all the intermediate phases. The doctor will assess different lines of action according to the results, then he will communicate them to the engineer who, consequently, will correct the antisymmetric issue and regenerate the model. Exact measurements of the mutual positions of the various components, skeletal and synthetic, can be achieved; all the osteosynthesis tools, necessary for the surgeon, can be included in the project according to different types of fracture to perfectly match the morphology of the bone to be treated. The method has been tested on seven clinical cases of different complexity and nature and the results of the simulations have been found to be of great effectiveness in the phase of diagnosis and of preoperative planning for the doctors and surgeons; therefore, allowing a lower risk medical operation with a better outcome. This work delivers experimental results in line with theoretical research findings in detail; moreover, full experimental and/or methodical details are provided, so that outcomes could be obtained.

Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3β inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore “late” effects on terminal differentiation or “early” mitochondrial effects, respectively. GSK3β inhibition significantly enhanced mitochondrial oxidative stress and damage and endochondral ossification based on increased nuclear translocation of Runx-2 and β-catenin, calcium deposition, cell death and enhanced remodelling of the extracellular matrix as demonstrated by the increased collagenolytic activity of supernatants, despite unmodified (MMP-1) or even reduced (MMP-13) collagenase gene/protein expression. Molecular dissection of the underlying mechanisms showed that GSK3β inhibition achieved with pharmacological/silencing strategies impacted on the control of collagenolytic activity, via both decreased inhibition (reduced TIMP-3) and increased activation (increased MMP-10 and MMP-14). To conclude, the inhibition of GSK3β enhances terminal differentiation via concerted effects on ECM and therefore its activity represents a tool to keep articular cartilage homeostasis.

This paper presents a a novel alghorithm of diagnosis and treatment of rigid flatfoot due to tarsal coalition. It introduces a workflow based on 3D printed models, that ensures more efficiency, not only by reducing costs and time, but also by improving procedures in the preoperative clinical phase. Since this paper concerns the development of a new methodology that integrates both engineering and medical fields, it highlights symmetry. An economic comparison is made between the traditional method and the innovative one, the results demonstrate a reduction in costs with the latter. The current, traditional method faces critical issues in diagnosing the pathologies of a limb (such as the foot) and taking decisions for further treatment of the same limb. The proposed alternative methodology thus uses new technologies that are part of the traditional workflow, only replacing the most obsolete ones. In fact, it is increasingly becoming necessary to introduce new technologies in orthopedics, as in other areas of medicine, to offer improved healthcare services for patients. Similar clinical treatments can be performed using the aforementioned technologies, offering greater effectiveness, more simplicity of approach, shorter times, and lower costs. An important technology that fits into this proposed methodology is 3D printing.

Materials used for total knee arthroplasty (TKA), may elicit an immune response whose role in the outcome of the arthroplasty is still unclear. The aim of this study was to evaluate the frequency of sensitization in patients who had undergone TKA, and the clinical impact of this event on the outcome of the implant. Ninety-four subjects were recruited, including 20 patients who had not yet undergone arthroplasty, 27 individuals who had a well-functioning TKA, and 47 patients with loosening of TKA components. Sensitization was detected by using patch testing including haptens representative of cobalt-based alloys (CoCrMo), titanium-based alloys (TiAlV), and bone cements. The frequency of positive skin reactions to metals increased significantly after TKA, either stable or loosened (No Implant 20%; Stable TKA 48.1%, p = 0.05; Loosened TKA 59.6%, p = 0.001, respectively). We found a higher frequency of positive patch testing to vanadium in patients who had a Stable TKA with at least one TiAlV component (39.1%, p = 0.01). The medical history for metal allergy seems to be a risk factor, because the TKA failure was fourfold more likely in patients who had symptoms of metal hypersensitivity before TKA. The prognostic value was supported by survival analysis, because in these individuals the outcome of the implant was negatively influenced (the logrank test Chi square 5.1, p = 0.02). This study confirms that in patients with a TKA the frequency of positive patch testing is higher than in the normal population, although no predictive value is attributable to the sensitization because patch testing was not able to discriminate between stable and loose implants. On the contrary, the presence of symptoms of metal allergy before implantation should be taken into account as a potential risk factor for TKA failure.

Sarcopenia, the progressive loss of muscle mass and strength, is a phenomenon characterizing human aging whose etiology is still not clear. While there is increasing evidence for the influence of inter-muscular adipose tissue infiltration in the development of sarcopenia, much less is known about a possible role for intra-muscular triglycerides (IMTG). IMTG accumulate in form of lipid droplets decorated by proteins such as Perilipins (Plins). In skeletal muscle the most abundant are Plin2 and Plin5. In this study we compared the expression of these two Plins in Vastus lateralis muscle samples of subjects of different age, both healthy donors (HD) and patients with limited lower limb mobility (LLMI). These latter are characterized by a condition of chronic physical inactivity. Plin2 expression resulted higher in old age for both HD and LLMI patients, while Plin5 slightly decreased only in LLMI patients. Moreover, in these patients, only Plin2 was associated with the decrease of muscle strength and the expression of factors related to muscle atrophy (MuRF1, Atrogin and p53). An increase in Plin2 and a concomitant decrease of Plin5 was also observed when we considered animal model of disuse-induced muscle atrophy. As a whole, these data indicate that Plin2 and Plin5 have a different expression pattern during muscle aging and inactivity, and only Plin2 appears to be associated with functional alterations of the muscle.

Background In osteoarthritis (OA), an inflammatory environment is responsible for the imbalance between the anabolic and catabolic activity of chondrocytes and, thus, for articular cartilage derangement. This study was aimed at providing further insight into the impairment of the anabolic cytokine IL-4 and its receptors in human OA cartilage, as well as the potential ability of IL-4 to antagonize the catabolic phenotype induced by IL-1β. Methodology/Principal Findings The in vivo expression of IL-4 and IL-4 receptor subunits (IL-4R, IL-2Rγ, IL-13Rα1) was investigated on full thickness OA or normal knee cartilage. IL-4 expression was found to be significantly lower in OA, both in terms of the percentage of positive cells and the amount of signal per cell. IL-4 receptor type I and II were mostly expressed in mid-deep cartilage layers. No significant difference for each IL-4 receptor subunit was noted. IL-4 anti-inflammatory and anti-catabolic activity was assessed in vitro in the presence of IL-1β and/or IL-4 for 24 hours using differentiated high density primary OA chondrocyte also exhibiting the three IL-4 R subunits found in vivo. Chemokines, extracellular matrix degrading enzymes and their inhibitors were evaluated at mRNA (real time PCR) and protein (ELISA or western blot) levels. IL-4 did not affect IL-1β-induced mRNA expression of GRO-α/CXCL1, IL-8/CXCL8, ADAMTS-5, TIMP-1 or TIMP-3. Conversely, IL-4 significantly inhibited RANTES/CCL5, MIP-1α/CCL3, MIP-1β/CCL4, MMP-13 and ADAMTS-4. These results were confirmed at protein level for RANTES/CCL5 and MMP-13. Conclusions/Significance Our results indicate for the first time that OA cartilage has a significantly lower expression of IL-4. Furthermore, we found differences in the spectrum of biological effects of IL-4. The findings that IL-4 has the ability to hamper the IL-1β-induced release of both MMP-13 and CCL5/RANTES, both markers of OA chondrocytes, strongly indicates IL-4 as a pivotal anabolic cytokine in cartilage whose impairment impacts on OA pathogenesis.

International audience; Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL) muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength.

A new HPLC method for the determination of glucosamine (2-amino-2-deoxy-D-glucose) in human synovial fluid was developed and validated. Synovial fluid samples were analyzed after a simple protein precipitation step with trichloroacetic acid using a polymer-based amino column with a mobile phase composed of 10 mM ammonium acetate (pH 7.5)-acetonitrile (20:80, v/v) at 0.3 mL/min flow rate. D-[1-13C]glucosamine was used as internal standard. Selective detection was performed by tandem mass spectrometry with electrospray source, operating in positive ionization mode and in multiple reaction monitoring acquisition (m/z 180-->72 and 181-->73 for glucosamine and internal standard, respectively). The limit of quantification (injected volume=3 microL) was 0.02 ng, corresponding to 10 ng/mL in synovial fluid. Calibration curves obtained using matrix-matched calibration standards and internal standard at 600 ng/mL were linear up to 2000 ng/mL. Precision values (%R.S.D.) were < or = 14% in the entire analytical range. Accuracy (%bias) ranged from -11% to 10%. The recoveries measured at three concentration levels (50, 800, and 1500 ng/mL) were higher than 89%. The method was successfully applied to measure endogenous glucosamine levels in synovial fluid samples collected from patients with knee osteoarthritis and glucosamine levels after oral administration of glucosamine sulfate (DONA) at the dose of 1500 mg/day for 14 consecutive days (steady-state).

SummaryObjectiveWe investigated the synovial and plasma glucosamine concentrations in osteoarthritic patients following oral administration of crystalline glucosamine sulphate at the therapeutic dose of 1500mg once-a-day for 14 days.DesignTwelve osteoarthritic patients (six males and six females) received 14 consecutive once-daily oral administrations of crystalline glucosamine sulphate soluble powder (1500mg), in an open fashion. Plasma and synovial fluid were collected simultaneously from the same patient, at baseline and, at steady state (3h after the last dose). Glucosamine was determined in plasma and synovial fluid by liquid chromatography–tandem mass spectrometry.ResultsMedian endogenous glucosamine concentrations in plasma and synovial fluid were 52.0ng/ml (0.29μM) and 36.5ng/ml (0.21μM), respectively (P=0.001), and varied substantially among patients (41–121ng/ml and