Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study.

PURPOSE: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). METHODS: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). RESULTS: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. CONCLUSIONS: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

Diagnosis and treatment of Paget's disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS).

INTRODUCTION: Paget's disease of bone is a focal skeletal disorder causing bone deformities and impairing bone quality. Despite the prevalence of asymptomatic cases is increasing, the progression of the disease can lead to invalidating complications that compromise the quality of life. Doubts on clinical and therapeutic management aspects exist, although beneficial effects of antiresorptive drugs, particularly bisphosphonates are known. However, limited information is available from randomized controlled trials on the prevention of disease complications so that somewhat contrasting positions about treatment indications between expert panels from the main scientific societies of metabolic bone diseases exist. This task force, composed by expert representatives appointed by the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases and members of the Italian Association of Paget's disease of bone, felt the necessity for more specific and up to date indications for an early diagnosis and clinical management. METHODS: Through selected key questions, we propose evidence-based recommendations for the diagnosis and treatment of the disease. In the lack of good evidence to support clear recommendations, available information from the literature together with expert opinion of the panel was used to provide suggestions for the clinical practice. RESULTS AND CONCLUSION: Description of the evidence quality and support of the strength of the statements was provided on each of the selected key questions. The diagnosis of PDB should be mainly based on symptoms and the typical biochemical and radiological features. While treatment is mandatory to all the symptomatic cases at diagnosis, less evidence is available on treatment indications in asymptomatic as well as in previously treated patients in the presence of biochemical recurrence. However, given the safety and long-term efficacy of potent intravenous bisphosphonates such as zoledronate, a suggestion to treat most if not all cases at the time of diagnosis was released.

Taking care of inpatients with fragility hip fractures: the hip-padua osteosarcopenia (Hip-POS) fracture liaison service model.

PURPOSE: Osteoporotic fragility fractures (FF), particularly those affecting the hip, represent a major clinical and socio-economic concern. These fractures can lead to various adverse outcomes, which may be exacerbated by the presence of sarcopenia, especially among older and frail patients. Early identification of patients with FF is crucial for implementing effective diagnostic and therapeutic strategies to prevent subsequent fractures and their associated consequences. METHODS: The Hip-POS program, implemented at Azienda Ospedale-Università Padova, is a Fracture Liaison Service (FLS) program to evaluate patients aged > 50 years old admitted with fragility hip fractures, involving an interdisciplinary team. After the identification of patients with hip fractures in the Emergency Department, a comprehensive evaluation is conducted to identify risk factors for further fractures, and to assess the main domains of multidimensional geriatric assessment, including muscle status. Patients are then prescribed with anti-fracture therapy, finally undergoing periodic follow-up visits. RESULTS: During the first five months, a total of 250 patients were evaluated (70.4% women, median age 85 years). Following assessment by the Hip-POS team, compared to pre-hospitalization, the proportion of patients not receiving antifracture therapy decreased significantly from 60 to 21%. The prescription rates of vitamin D and calcium increased markedly from 29.6% to 81%. CONCLUSIONS: We introduced the Hip-POS program for the care of older adults with hip fractures. We aspire that our model will represent a promising approach to enhancing post-fracture care by addressing the multifactorial nature of osteoporosis and its consequences, bridging the gap in secondary fracture prevention, and improving patient outcomes.

Expert opinion on the management of patients with osteoporosis with anabolic drugs in Italy.

OBJECTIVE: Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79. METHODS: The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies. RESULTS: The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals. CONCLUSIONS: This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.

Burden of disease and clinical targets in adult patients with X-linked hypophosphatemia. A comprehensive review.

X-linked hypophosphataemia (XLH) is a lifelong condition. Despite the mounting clinical evidence highlighting the long-term multi-organ sequelae of chronic phosphate wasting and consequent hypophosphatemia over the lifetime and the morbidities associated with adult age, XLH is still perceived as a paediatric disease. INTRODUCTION: Children who have XLH need to transition from paediatric to adult healthcare as young adults. While there is general agreement that all affected children should be treated (if the administration and tolerability of therapy can be adequately monitored), there is a lack of consensus regarding therapy in adults. METHODS: To provide guidance in both diagnosis and treatment of adult XLH patients and promote better provision of care for this potentially underserved group of patients, we review the available clinical evidence and discuss the current challenges underlying the transition from childhood to adulthood care to develop appropriate management and follow-up patterns in adult XLH patients. RESULTS AND CONCLUSIONS: Such a multi-systemic lifelong disease would demand that the multidisciplinary approach, successfully experienced in children, could be transitioned to adulthood care with an integration of specialized sub-disciplines to efficiently control musculoskeletal symptoms while optimizing patients' QoL. Overall, it would be desirable that transition to adulthood care could be a responsibility shared by the paediatric and adult XLH teams. Pharmacological management should require an adequate balance between the benefits derived from the treatment itself with complicated and long-term monitoring and the potential risks, as they may differ across age strata.

Vitamin D and disease severity in coronavirus disease 19 (COVID-19).

The role of 25-OH-vitamin D in the assessment of coronavirus disease 19 (COVID-19) has not been investigated. We sought to investigate the prevalence of 25-OH-vitamin D deficiency among COVID-19 patients, and to determine the associations between 25-OH-vitamin D status and the severity of the disease. We have conducted a retrospective observational study of COVID-19 patients admitted to the University of Verona Hospital Trust. Demographic, clinical and biochemical parameters were collected at hospital admission, and serum 25-OH-vitamin D levels were measured. The following outcomes were assessed: arterial partial oxygen pressure (PaO2); C-reactive protein (CRP); length of hospitalization; requirement of oxygen therapy; non-invasive ventilation (NIV); mechanical ventilation; and death. Among 61 patients enrolled, 72.1% was 25-OH-vitamin D deficient (<20 ng/mL) and 57.4% had 25-OHvitamin D <15 ng/mL. Patients with arterial PaO2 <60 mmHg had significantly lower mean 25-OH-vitamin D levels compared to patients with PaO2 ≥60 mmHg (13.3 ng/mL vs 20.4 ng/mL respectively, p=0.03). Vitamin D deficiency was associated with 3-fold higher risk of having arterial pO2 <60 mmHg. 25-OH-vitamin D deficiency was associated with increased CRP and dyspnea. 25-OH-vitamin D deficiency was associated with more severe systemic inflammatory response and respiratory failure in COVID-19 patients.

Effects of PCSK9 inhibitors on LDL cholesterol, cardiovascular morbidity and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality. METHODS AND RESULTS: A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12 weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4 weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2 years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09]). CONCLUSIONS: PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE. REGISTRATION NUMBER: PROSPERO-CRD42018087640.

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

Glucagon-like peptide-1 receptor agonists and atrial fibrillation: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The pharmacological stimulation of GLP-1 receptors is associated with an increase in heart rate. A pooled analysis of patient-level data from phase III trials with albiglutide revealed a significant increase in the risk of atrial fibrillation. Aim of the present meta-analysis is to summarize all available evidence on the effects of individual GLP-1 receptor agonists (RA), and of the whole class, on the incidence of atrial fibrillation. METHODS: A Medline search for GLP-1 RA (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥12 weeks, enrolling patients with type 2 diabetes and comparing a GLP-1 RA with placebo or any other non-GLP-1 RA drug. RESULTS: Of the 113 trials fulfilling the inclusion criteria, 19 did not report information on atrial fibrillation, whereas 63 reported zero events in all treatment groups. In the remaining trials (enrolling 17,966 and 15,305 patients in GLP-1 RA and comparator arms, respectively, 55.3% women, with a mean age of 57.0 ± 3.8 years), treatment with GLP-1 RA was not associated with a significant increase in the incidence of atrial fibrillation [Mantel-Haenszel OR (95% CI) 0.87 (0.71-1.05), p = 0.15]. CONCLUSIONS: In conclusion, available data suggest that GLP-1 RA is not associated with atrial fibrillation, with the only possible exception of albiglutide. Newly onset atrial fibrillation deserves to be investigated as an event of special interest in future trials with GLP-1 RA.

Association between low C-peptide and fragility fractures in postmenopausal women without diabetes.

PURPOSE: C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women. METHODS: A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients' fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement. RESULTS: Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6, SE = 4.17, p < 0.001, CI 0.001-0.002; B = -24.8, SE = 5.23, p < 0.001, CI 0001-0.002; respectively). CONCLUSIONS: This study confirms an inverse association between serum C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.

Nephrolithiasis, bone mineral density, osteoporosis, and fractures: a systematic review and comparative meta-analysis.

Our meta-analysis demonstrates that people with nephrolithiasis have decreased bone mineral density, an increased odds of osteoporosis, and potentially an elevated risk of fractures. INTRODUCTION: People with nephrolithiasis might be at risk of reduced bone mineral density (BMD) and fractures, but the data is equivocal. We conducted a meta-analysis to investigate if patients with nephrolithiasis have worse bone health outcomes (BMD), osteoporosis, and fractures versus healthy controls (HCs). METHODS: Two investigators searched major databases for articles reporting BMD (expressed as g/cm2 or a T- or Z-score), osteoporosis or fractures in a sample of people with nephrolithiasis, and HCs. Standardized mean differences (SMDs), 95 % confidence intervals (CIs) were calculated for BMD parameters; in addition odds (ORs) for case-control and adjusted hazard ratios (HRs) in longitudinal studies for categorical variables were calculated. RESULTS: From 1816 initial hits, 28 studies were included. A meta-analysis of case-control studies including 1595 patients with nephrolithiasis (mean age 41.1 years) versus 3402 HCs (mean age 40.2 years) was conducted. Patients with nephrolithiasis showed significant lower T-scores values for the spine (seven studies; SMD = -0.69; 95 % CI = -0.86 to -0.52; I 2 = 0 %), total hip (seven studies; SMD = -0.82; 95 % CI = -1.11 to -0.52; I 2 = 72 %), and femoral neck (six studies; SMD = -0.67; 95 % CI = --1.00 to -0.34; I 2 = 69 %). A meta-analysis of the case-controlled studies suggests that people with nephrolithiasis are at increased risk of fractures (OR = 1.15, 95 % CI = 1.12-1.17, p < 0.0001, studies = 4), while the risk of fractures in two longitudinal studies demonstrated trend level significance (HR = 1.31, 95 % CI = 0.95-1.62). People with nephrolithiasis were four times more likely to have osteoporosis than HCs (OR = 4.12, p < 0.0001). CONCLUSIONS: Nephrolithiasis is associated with lower BMD, an increased risk of osteoporosis, and possibly, fractures. Future screening/preventative interventions targeting bone health might be indicated.

Guidelines for the diagnosis, prevention and management of osteoporosis.

Osteoporosis poses a significant public health issue. National Societies have developed Guidelines for the diagnosis and treatment of this disorder with an effort of adapting specific tools for risk assessment on the peculiar characteristics of a given population. The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has recently revised the previously published Guidelines on the diagnosis, riskassessment, prevention and management of primary and secondary osteoporosis. The guidelines were first drafted by a working group and then approved by the board of SIOMMMS. Subsequently they received also the endorsement of other major Scientific Societies that deal with bone metabolic disease. These recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on leading experts' experience and opinion, and on good clinical practice. The osteoporosis prevention should be based on the elimination of specific risk factors. The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk, and this is the case only when the risk of fracture is rather high as measured with variables susceptible to pharmacological effect. DeFRA (FRAX® derived fracture risk assessment) is recognized as a useful tool for easily estimate the long-term fracture risk. Several secondary forms of osteoporosis require a specific diagnostic and therapeutic management.

Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes.

UNLABELLED: In this population-based, cross-sectional study in Italian postmenopausal females not affected by diabetes, we showed a link between serum C-peptide and lumbar bone mineral density, suggesting that C-peptide exerts an insulin-independent effect on bone mass. INTRODUCTION: It is well known that type 1 (T1) diabetes, characterized by insulin and C-peptide deficiency, is associated with a low lumbar bone mineral density and an increased risk for fracture. While a role for insulin in the pathogenesis of osteoporosis has been demonstrated, the association between C-peptide and the bone mineral density has not been investigated. We conducted a study in a cohort of 84 postmenopausal women without diabetes to clarify the association between serum C-peptide and the lumbar bone mineral density. METHODS: Participants underwent a bone mineral density evaluation by DXA and biochemical analysis including the C-peptide assay. RESULTS: rteen percent of the population had osteoporosis and 38% had osteopenia. With ANOVA test, we showed that women with the lowest C-peptide concentration had lower lumbar mineral density in comparison to those in all other C-peptide concentration group (p = 0.02 among groups after adjustment). The univariate and multivariate analysis showed that C-peptide was positively associated with both lumbar T-score and Z-score besides other well-known factors like age (with T-score p < 0.001; beta = -0.38) and BMI (with T-score p = 0.009; beta = 0.34), while insulin was not correlated with the lumbar bone mineral density. The area under the receiver operating characteristic (ROC) curve for C-peptide to predict the absence of lumbar osteoporosis was 0.74 (SE = 0.073; p = 0.013). CONCLUSIONS: These results suggest that C-peptide may exert an insulin- and BMI-independent effect on lumbar bone mineral density and that further large-scale studies are needed in order to clarify its role in bone mineralization especially in subjects without diabetes.

PATHOLOGIC AND IMPENDING FRACTURES: BIOLOGICAL AND CLINICAL ASPECTS.

Bone metastases from carcinomas are epidemiologically rising because of the increased survival rate of oncologic patients, related to several factors such as improvement of primary and secondary screening, advancement of medical research and technology and the better understanding of mechanisms underlying bone metastases origination from primary tumor. Skeletal Related Events (SREs) can seriously affect quality of life in patients with metastatic disease. These events include the necessity of radiotherapy or bone surgery, malignant hypercalcemia, pathologic fractures and spinal cord compression. Among the SREs, pathologic fractures are the most disabling events and represent an emergency in these delicate patients. A pathologic fracture is defined as a fracture that occurs at the level of a pre-existing bone lesion (that is often a tumor), spontaneously or as the result of low-energy trauma (1). The pre-existence of the metastatic lesion in the bone, its evaluation and the assessment of progression can make these complications predictable and preventable. Pathologic fractures imply several severe consequences, including patient immobilization (in the case of fractures involving the lower limbs), loss of autonomy, anaemia, need of blood transfusion, discontinuation of medical therapies or radiotherapy and protracted hospitalization. Secondary effects of prolonged immobilization and loss of autonomy further lengthen this list of complications in patients who are already significantly limited in their activities. In the present paper, the authors present a review on the main aspects involved in bone metastastic disease: biology, quality of life, economic impact and survival.

Behaviour of dental pulp stem cells on different types of innovative mesoporous and nanoporous silicon scaffolds with different functionalizations of the surfaces.

Dental pulp stem cells (DPSCs) are stem cells found in the dental pulp. The ability of DPSCs to differentiate towards odontoblastic and osteoblastic phenotype was reported first in the literature, then in the following years, numerous studies on odontogenesis were carried out, starting from mesenchymal stem cells isolated from tissues of dental and oral origin. The aim of this research was to evaluate the behaviour of DPSCs grown on silicon nanoporous and mesoporous matrices and differentiated towards the osteogenic phenotype, but also to investigate the use of DPSCs in pilot studies focused on the biological compatibility of innovative dental biomaterials. Twenty-eight silicon samples were created with standardized procedures. These scaffolds were divided into samples made of silicon bulk, nanoporous silicon, mesoporous silicon, nanoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS) and methanol (MeOH), nanoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS)/toluene, mesoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS) and methanol (MeOH) andmesoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS)/toluene. DPSC proliferation on the tested silicon scaffolds was analyzed at 3 and 5 days. The assay showed that DPSCs proliferated better on mesoporous scaffolds functionalized with APTMS/toluene compared to a silicon one. These results show that the functionalization of silicon scaffold with APTMS/toluene supports the growth of DPSCs and could be used for future applications in tissue engineering.

Failures in bipolar fresh osteochondral allograft for the treatment of end-stage knee osteoarthritis.

PURPOSE: Bipolar fresh osteochondral allografts (BFOA) recently became a fascinating option for articular cartilage replacement, in particular in those young patients non-suitable for traditional replacement because of age. While the use of osteochondral allografts for the treatment of focal osteochondral lesions in the knee is well established, their use in the treatment of end-stage arthritis is far more controversial. The purpose of this paper is to describe our experience in a series of seven patients who underwent a resurfacing of both tibio-femoral and patello-femoral joints by BFOA. METHODS: From 2005 to 2007, seven patients (mean age 35.2 ± 6.3 years) underwent BFOA for end-stage arthritis of the knee. Patients were evaluated clinically, radiographically and by CT scan preoperatively and at established intervals up to the final follow-up. RESULTS: No intra-operative complications occurred. Nevertheless, joint laxity and aseptic effusion, along with a progressive chondrolysis, lead to early BFOA failure in six patients, which were revised by total knee arthroplasty at 19.5 ± 3.9 months follow-up. Only one patient, who received the allograft to convert a knee arthrodesis, gained a satisfactory result at the last follow-up control. CONCLUSIONS: BFOA in the knee joint still remains an inapplicable option in the treatment of post-traumatic end-stage arthritis of the young patient, due to the high rate of failure. Further studies are necessary in order to investigate the causes of failure and improve the applicability of this method. Still, after extensive counselling with the patient, BFOA may represent a salvage procedure aimed to revise scarcely tolerated knee arthrodesis. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

Tibial component alignment and risk of loosening in unicompartmental knee arthroplasty: a radiographic and radiostereometric study.

PURPOSE: Unicompartmental knee arthroplasty (UKA) has shown a higher rate of revision compared with total knee arthroplasty. The success of UKA depends on prosthesis component alignment, fixation and soft tissue integrity. The tibial cut is the crucial surgical step. The hypothesis of the present study is that tibial component malalignment is correlated with its risk of loosening in UKA. METHODS: This study was performed in twenty-three patients undergoing primary cemented unicompartmental knee arthroplasties. Translations and rotations of the tibial component and the maximum total point motion (MTPM) were measured using radiostereometric analysis at 3, 6, 12 and 24 months. Standard radiological evaluations were also performed immediately before and after surgery. Varus/valgus and posterior slope of the tibial component and tibial-femoral axes were correlated with radiostereometric micro-motion. A survival analysis was also performed at an average of 5.9 years by contacting patients by phone. RESULTS: Varus alignment of the tibial component was significantly correlated with MTPM, anterior tibial sinking, varus rotation and anterior and medial translations from radiostereometry. The posterior slope of the tibial component was correlated with external rotation. The survival rate at an average of 5.9 years was 89%. The two patients who underwent revision presented a tibial component varus angle of 10° for both. CONCLUSIONS: There is correlation between varus orientation of the tibial component and MTPM from radiostereometry in unicompartmental knee arthroplasties. Particularly, a misalignment in varus larger than 5° could lead to risk of loosening the tibial component. LEVEL OF EVIDENCE: Prognostic studies-retrospective study, Level II.

Tibio-femoral and patello-femoral joint kinematics during navigated total knee arthroplasty with patellar resurfacing.

PURPOSE: In total knee arthroplasty, surgical navigation systems provide tibio-femoral joint (TFJ) tracking for relevant bone preparation, disregarding the patello-femoral joint (PFJ). Therefore, the important intra-operative assessment of the effect of component positioning, including the patella, on the kinematics of these two joints is not available. The objective of this study is to explore in vivo whether accurate tracking of the patella can result in a more physiological TFJ and PFJ kinematics during surgery. METHODS: Ten patients underwent navigated knee replacement with patellar resurfacing. A secondary system was used to track patellar motion and PFJ kinematics using a special tracker. Patellar resection plane position and orientation were recorded using an instrumented probe. During all surgical steps, PFJ kinematics was measured in addition to TFJ kinematics. RESULTS: Abnormal PFJ motion patterns were observed pre-operatively at the impaired knee. Patellar resection plane orientation on sagittal and transverse planes of 3.9° ± 9.0° and 0.4° ± 4.1° was found. A good restoration of both TFJ and PFJ kinematics was observed in all replaced knees after resurfacing, in particular the rotations in the three anatomical planes and medio-lateral patellar translation. CONCLUSIONS: Patella tracking results in nearly physiological TFJ and PFJ kinematics in navigated knee arthroplasty with resurfacing. The intra-operative availability also of PFJ kinematics can support the positioning not only of the patellar component in case of resurfacing, but also of femoral and tibial components.

Platelet-rich plasma for foot and ankle pathologies: a systematic review.

BACKGROUND: The aim of this article is to review systematically all the literature available on the clinical application of PRP for the treatment of foot and ankle pathologies, to understand its potential and best indications for clinical use. METHODS: A systematic search of the PubMed database was performed. Research criteria were the following: (1) papers in the English language, (2) dealing with the clinical application of PRP for the treatment of orthopedic-related conditions affecting the foot and ankle district, (3) with I to IV level of evidence, and (4) reporting clinical results. RESULTS: A total of 17 studies fulfilled the inclusion criteria. Nine papers dealt with Achilles tendon management, 2 articles with plantar fasciitis, 3 papers with talar osteochondral lesions, 2 with PRP application in total ankle replacement, and 1 article with PRP in foot and ankle fusions. The overall evaluation of the results reported does not clearly demonstrate the potential of PRP treatment in any of the specific fields of application. CONCLUSIONS: Considering the literature currently available, no clear indications for using PRP in the foot and ankle district emerged. LEVEL OF EVIDENCE: Level IV, systematic review of Level I, II, III and IV studies.

Reliability of toxicokinetic modelling for PFAS exposure assessment in contaminated water in northern Italy.

Introduction: Long-term contamination of tap water and groundwater by perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been documented in the Veneto region of northern Italy. This study aimed to assess the exposure of individuals residing in the contaminated area and to test several toxicokinetic (TK) models of varying complexities to identify an efficient method for predicting perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) concentrations in human serum using observed data.The ultimate goal is to provide public health officials with guidance on selecting the appropriate TK model for specific contexts, a reliable and rapid tool to support human bio-monitoring (HBM) studies. Methods: Two simpler empirical TK models and a more complex multi-compartment physiologically based toxicokinetic (PBTK) model were compared with individual and aggregate data from an HBM study. In addition, the PBPK model was modified by adjusting input parameters and introducing new terms into the equations within the original model code. These modifications aimed to optimize the results compared to the original model, with some versions incorporating adjustments to account for the influence of menstruation in women. All models were evaluated to understand their strengths and weaknesses, providing guidance on the appropriate model to use according to specific scenarios. Results: The results obtained from the tested models were quite similar, with significant improvements observed only in the modified models. Simpler models also provided satisfactory results in scenarios involving low PFOS serum concentrations and recent exposure cessation. In many cases, predictions demonstrated high accuracy, particularly at the aggregate level and for women. Conclusions: These findings suggest that environmental protection agencies and health authorities may benefit from employing the tested models at the aggregate level as an initial step in HBM studies, rather than conducting more invasive and expensive screening campaigns.