La fibrogenesis imperfecta ossium (FIO) è un disordine osteosclerotico raro e progressivo, coinvolgente l’intero scheletro, ad esito fatale, che colpisce gli adulti nelle decadi centrali della vita. Osservata per la prima volta nel 1938, venne successivamente descritta nel 1950 su base isto-patologica ma ricevette il suo acronimo solo nel 1966 e, da allora, ne sono stati descritti 29 casi. Sino dai primi due pazienti, emersero fratture spontanee e osteoide immaturo, che sostituiva il tessuto osseo a partire dall’endostio corticale sino al midollo rosso, in assenza di mineralizzazione come in corso di osteomalacia ma presenza di fibrille argirofile/aureofile, irregolari e prive di birifrangenza tipica del collagene. Data l’incertezza sull’eziopatogenesi, la malattia è stata trattata con differenti molecole ad azione osteoanabolica quali vitamina D, fluoruro di sodio, testosterone e GH ricombinante, ad oggi considerato il più promettente, mentre risultati trascurabili sono stati raggiunti con farmaci antiriassorbitivi (calcitonina, bisfosfonati). Risposte a glucocorticoidi e agenti alchilanti suggeriscono la presenza di una componente osteoimmunomodulatoria, rendendo la FIO un modello naturale per indagare il ruolo delle differenti fasi del rimodellamento osseo nel raggiungimento di una massa minerale efficiente e il tipo di terapie necessarie a questo obiettivo.

Abstract Purpose The optimal surgical approach for total ankle arthroplasty (TAA) remains debated. The anterior and lateral transfibular approaches differ in surgical exposure and may influence complication patterns. This systematic review and meta‐analysis aimed to compare revision rates, overall complication rates and specific complication profiles between anterior and lateral approaches in TAA. Methods A PRISMA‐compliant systematic review of PubMed, Embase and Scopus databases was performed. Studies reporting complications following primary TAA performed through either approach were included if they met predefined methodological quality criteria (QualSyst score ≥ 75%). Complication rates were compared using Fisher's exact test, and correlations between complication rates and patient or surgical factors were explored. Results Fifty‐one studies were included, comprising 7959 TAA procedures (7225 anterior and 734 lateral). Revision rates were higher in the anterior approach group (7.5% vs. 1.9%, p < 0.001), as were rates of malleolar fractures (1.7% vs. 0.3%, p = 0.001) and aseptic loosening (2.8% vs. 0.14%, p < 0.001). Deep infections were reported more frequently in lateral approach cohorts (3.1% vs. 0.57%, p < 0.001), although this finding was influenced by outlier studies. Wound complications and polyethylene‐related complications were comparable between approaches. No association was observed between complication rates and patient age, body mass index or surgical time. Conclusion Anterior and lateral approaches in TAA appear to be associated with different complication patterns rather than clear differences in overall safety. Both approaches remain valid surgical options, but awareness of their distinct complication profiles may help guide intraoperative precautions and post‐operative surveillance. However, heterogeneity in implant design, follow‐up duration and study methodology limits definitive conclusions regarding the superiority of one approach. Level of Evidence Level I, systematic review/meta‐analysis.

PURPOSE:Osteochondral lesions of the talus are a frequent cause of ankle pain and functional limitation, particularly in physically active patients. The purpose of this prospective study was to assess patient-reported outcomes, return to sport and work and safety after second-generation patient-specific focal talar resurfacing in patients with symptomatic talar osteochondral lesions. METHODS:Between October 2021 and July 2023, 40 patients were screened and 20 underwent implantation of a customized focal talar resurfacing implant. Outcomes were collected preoperatively and at 3, 6, 12 and 24 months using the Foot and Ankle Outcome Score (FAOS), visual analogue scale pain at rest and during activity and the EuroQol 5-dimension 5-level questionnaire. Time to return to sport and work and adverse events (complications, reoperations and treatment failures) were recorded. Changes over time were assessed with repeated-measures analysis of variance. Best-case and worst-case sensitivity analyses explored the impact of incomplete 24-month follow-up on treatment-failure estimates. RESULTS:Seventeen patients completed the 24-month follow-up. The mean FAOS total increased from 58.6 ± 16.6 preoperatively to 97.3 ± 4.9 at 24 months. Pain improved from 4.3 ± 2.7 to 0.0 ± 0.0 at rest and from 6.8 ± 1.7 to 0.1 ± 0.3 during activity. Seventeen of 20 patients returned to sport at a mean of 5.1 ± 3.2 months, and mean time to return to work was 4.2 ± 3.0 months. Three complications occurred, including one treatment failure requiring revision surgery. The observed treatment-failure rate was 1/20 (5%). CONCLUSIONS:Patient-specific talar resurfacing was associated with sustained improvements in pain, function and quality of life at 24 months, with high rates of return to sport and work. Larger studies with longer follow-up are needed to confirm durability and refine patient selection. LEVEL OF EVIDENCE:Level II.

A medial collateral ligament (MCL) rupture is an uncommon yet significant complication following total knee arthroplasty (TKA), potentially resulting in instability and accelerated prosthetic wear, particularly after medial-pivot total knee arthroplasty (MP-TKA). Complete ruptures are typically managed with direct repair, ligament reconstruction, or revision to a more constrained prosthetic implant. The primary objective is to restore knee stability while maintaining implant durability. We report the case of a 72-year-old woman with sarcopenic obesity who sustained an MCL rupture following MP-TKA performed for valgus knee osteoarthritis. The patient was successfully treated with revision to a more constrained prosthesis. MP-TKA relies on medial compartment congruency and soft-tissue integrity, particularly that of the MCL, to ensure joint stability and restore normal knee kinematics. This case highlights the management of MCL failure after MP-TKA in a patient with sarcopenic obesity. Revision to a constrained prosthesis may represent the most appropriate treatment option.

BACKGROUND:Total ankle replacement can be performed through a direct anterior approach or a lateral transfibular approach, but comparative evidence on perioperative burden and reoperation patterns remains limited. PURPOSE:To compare reoperation burden and perioperative outcomes between the direct anterior and lateral transfibular approaches for primary total ankle replacement. STUDY DESIGN:Retrospective cohort study. METHODS:Consecutive primary total ankle replacements performed at a single center between January 2016 and December 2021 were reviewed. Outcomes included reoperations, intraoperative and postoperative complications, operative time, length of hospital stay, and adjunctive procedures. Analyses were exploratory. RESULTS:The cohort included 188 patients (120 anterior, 68 lateral). Length of hospital stay was 3.56 ± 1.49 days after anterior procedures and 3.67 ± 1.35 days after lateral procedures (p = 0.67). Overall complication rates were 31.67% and 30.88%, respectively. Operative time was longer in the lateral group (139.00 ± 34.17 minutes) than in the anterior group (115.00 ± 26.70 minutes). Reoperations per patient were higher and more heterogeneous in the lateral group (0.730) than in the anterior group (0.096). Adjunctive procedures were common; Achilles tendon lengthening was more frequent in anterior procedures (61.67% vs 47.06%, p = 0.025). CONCLUSIONS:In this cohort, the two approaches showed similar early length of stay and overall complication rates. The lateral transfibular approach required longer operative time and showed a more heterogeneous reoperation burden, potentially influenced by case complexity and adjunctive procedures.

La reazione colorimetrica di Porter-Silber del 1950 per la misurazione nelle urine dei 17-idrossi-corticosteroidi è una pietra miliare nella diagnosi di ipercortisolismo. Sino dal XVII secolo i tumori “soprarenali” erano associati a virilismo e obesità, ma solo nel 1932 fu coniato l’eponimo di sindrome di Cushing per l’associazione tra “adenoma basofilo dell’adenoipofisi” e habitus pletoricus con adiposità androide e tronculare-sovraclaveare, facies lunaris, striae rubrae, ipertricosi, miopatia, atrofia cutis, acrocianosi, amenorrea, perdita di libido/impotenza, rarefazione ossea radiografica, leucocitosi neutrofila, linfo-/eosinopenia, ipernatremia/ipokaliemia, iperglicemia/glicosuria e ipertensione arteriosa. Cushing, però, riteneva che questo quadro clinico dipendesse da disfunzione gonadotropa, neuropofisaria e/o diencefalica (c.d. sindrome polighiandolare). Tuttavia, per la prima volta nel 1933, Julius Bauer associò quella sintomatologia obiettiva allo stimolo adenoipofisario della corteccia surrenalica (c.d. iperadrenalismo), un’ipotesi confermata da Fuller Albright nel 1942–43. Ciò condusse Bauer, nel 1950, a coniare la distinzione tra morbo e sindrome di Cushing, tutt’oggi accettata rispetto all’eponimo storico di sindrome di Cushing-Bauer, che corrisponde all’ipercortisolismo endogeno.

BackgroundTotal ankle arthroplasty (TAA) is increasingly used as an alternative to arthrodesis for end-stage ankle arthritis. The extent to which implant bearing type and design evolution influence outcomes and survival remains debated.MethodsA systematic review and meta-analysis was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD420251073944). PubMed, Embase, and Scopus were searched for English-language studies (2004-2025) reporting anterior-approach TAA with specified implant generation (I-IV) and bearing type (fixed [FB] vs mobile [MB]). Studies with a QualSyst score ≥ 75% were included. Primary outcomes were American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS), range of motion (ROM), complications, and revisions.ResultsForty-two studies comprising 4,271 implants were analyzed (FB: 1,546; MB: 2,725). Functional improvements were mainly driven by implant generation rather than bearing type. ΔAOFAS increased from 33.7 ± 22.3 in Gen II to 44.5 ± 28.3 in Gen IV (P < .001). ΔVAS varied across generations (Gen II 5.8 ± 2.1; Gen III 4.6 ± 2.8; Gen IV 5.46 ± 1.60; all P < .001 vs baseline). MB implants showed lower pre- and postoperative AOFAS scores but comparable ΔAOFAS to FB designs (36.4 vs 37.5; P = .358). MB systems provided greater pain relief (ΔVAS 5.62 vs 4.60; P < .001) but had higher revision rates (12.0% vs 6.2%; P < .001). FB implants achieved superior postoperative ROM gains in plantarflexion (+6.0° vs -2.9°; P < .001) and dorsiflexion (+2.71° vs +0.75°; P < .001). Excluding Gen I, complication rates decreased from 32.6% in Gen II to 18.8% in Gen III and 10.3% in Gen IV (all P < .01); revision rates declined from 16.5% (Gen II) and 9.6% (Gen III) to 0.5% (Gen IV) (P < .01).ConclusionsImplant generation is the primary determinant of outcomes, complications, and survival in anterior-approach TAA. Bearing type played a secondary role: MB devices provided greater pain relief, whereas FB systems achieved superior ROM recovery and lower revision risk. Fourth-generation implants yielded the most reliable results. Further prospective studies with standardized functional and kinematic assessments are warranted.Level of Clinical Evidence:Level I-Systematic Review/Meta-Analysis.

Nonunion of the second metatarsal presents a significant clinical challenge, often leading to pain, functional impairment, and deformity. Various treatment strategies have been described in the literature, tailored to the patient’s specific characteristics. To provide a comprehensive overview of the available therapeutic options, a literature review was conducted. In this context, this article aims to present an innovative and personalized surgical technique for patients with nonunion and an altered metatarsal formula following a proximal shaft fracture of the second metatarsal. This technique enables the simultaneous consolidation of the nonunion and restoration of metatarsal alignment, with favorable clinical, functional, and radiological outcomes observed over a three-year follow-up period.

Purpose:Treatment strategies for osteochondral defects (OCDs) of the ankle have substantially increased over the last decade. The development of a small metallic implant to fill the defect has led to the second-generation patient-specific metal implant (Episealer Talus® Implant) designed based on computed tomography and magnetic resonance imaging images. Methods:There is a pool of patients falling into the so-called 'treatment gap', a grey zone composed of active patients with symptomatic OCDs in the context of an otherwise healthy joint, or patients with a failed primary treatment. To minimize the risk of perioperative complications, there are a series of tips and tricks that can be considered. Results:Correct execution of the operative approach, proper positioning of the guides, posterior capsule and deep deltoid ligament release and the use of Hintermann spreader allow a perfect visualization of the OCDs minimizing the risk of iatrogenic lesions. Correct execution of the medial malleolus osteotomy, release of soft tissue, proper triplanar alignment of the custom-made guide, its strong stabilization during the reaming and the use of vigorous washes minimizes the potential damage on healthy cartilage. Correct sinking of the implant is crucial; the goal is to place the Episealer Talus at least 0.5 mm below the cartilage surface. Filling a large subchondral cyst with the cancellous bone can be useful to provide better stability of the implant. Conclusion:Episealer Talus for talar OCDs possibly represents an additional tool for surgeons and patients. It is important to avoid mistakes during implant placement. Levels of Evidence:Level V, expert opinion.

Background and Objectives: The surgical approach for Haglund’s triad remains a topic of ongoing debate. This study presents pioneering data on Achilles tendon reattachment using the SpeedBridge technique following partial detachment, retrocalcaneal bursa excision, and Haglund prominence resection in patients with Haglund’s triad. Materials and Methods: A retrospective analysis was conducted on patients operated on between March 2019 and March 2022, encompassing demographic data and preoperative and 6-month and 12-month postoperative assessments of the VAS (Visual Analog Scale), AOFAS (American Orthopedic Foot & Ankle Society) score, and SF-36. Results: Nine patients (three females and six males) with a mean age of 53.8 years underwent surgery, with a mean follow-up of 34 months. The results indicated a significant improvement (p < 0.0001) in the VAS, AOFAS, and SF-36 at the 12-month follow-up. Conclusions: Taking into account the limitations of the study, including its retrospective design and the small sample size, the use of SpeedBridge for Achilles tendon reattachment, alongside the aforementioned procedures, demonstrated promising outcomes. These findings warrant further investigation in future randomized studies with larger sample sizes to confirm their efficacy.

La malnutrizione, intesa come nutrizione deficitaria e/o inappropriata, ha svolto storicamente un ruolo chiave per diagnosi cliniche relative al dismetabolismo glicolipidico, quale elemento necessario e sufficiente per un ragionamento diagnostico parsimonioso. Caso emblematico è la diagnosi di diabete mellito da malnutrizione, un disordine glicolipidico noto dagli inizi del XX secolo, divenuto attuale in Italia in relazione all’immigrazione dai paesi dove era stato originariamente identificato (Africa, Asia). Caratterizzato a metà del 1900 come diabete J (da Jamaica), si presentava come una forma “ibrida” tra diabete mellito Tipo 1 e 2 in un fenotipo sottopeso giovane che, di recente, sappiamo avere similitudini con quello normopeso metabolicamente insano. Questo diabete conduce di rado alla chetosi, richiede dosaggi insulinici elevati, non si associa a steatosi epatica, mantiene una riserva insulinica, potrebbe rispondere favorevolmente a nutrizione iperproteica e terapia combinata con insulina e ipoglicemizzanti orali e, quest’anno, è stato classificato dalla International Diabetes Federation come diabete mellito Tipo 5.

INTRODUCTION:Many different operative procedures have been described to treat hallux valgus, but many of them are inappropriate for active, skeletally immature patients. This retrospective evaluation aimed to show the efficacy of SERI (Simple, Effective, Rapid, Inexpensive) technique in young patients affected by mild to moderate hallux valgus deformity at a mid-term to long-term follow-up. METHODS:All patients were clinically and radiographically evaluated, independently by 2 researchers, by American Orthopaedic Foot and Ankle Society (AOFAS) Hallux-Metatarsophalangeal-Interphalangeal score and radiographic examination. RESULTS:Twenty-nine feet, undergone SERI procedure, have been reviewed at a mean follow-up of 5 years. The mean AOFAS score was significantly improved from 59.7 preoperatively to a mean value of 90.7 at last follow-up. Mean correction degrees have been recorded for both angles (hallux valgus angle [HVA] -13.7° and intermetatarsal angle [IMA] -6.7°). CONCLUSIONS:The SERI technique represents a powerful surgical procedure for the treatment of painful, mild to moderate, juvenile hallux valgus. Recurrence and complication rate make this surgical approach effective, repeatable, and safe. LEVEL OF EVIDENCE:Level IV, Retrospective case series.

Purpose:The purpose of this systematic review was to compare clinical outcomes and complication rates between inlay and onlay patellofemoral arthroplasty (PFA) for isolated patellofemoral osteoarthritis (PFOA). A secondary objective was to evaluate implant-specific performance among various prosthetic designs. Methods:A comprehensive literature search was conducted using PubMed/MEDLINE, EMBASE and the Cochrane Database to identify studies published between January 1980 and 20 January 2025. Studies were included if they reported functional outcomes and complication rates for inlay or onlay PFA with a mean follow-up of 5 years. The majority of included studies were Level III or IV observational studies; therefore, the strength of the evidence is limited and conclusions should be interpreted with caution. Results:Seventy-six studies met the inclusion criteria, encompassing 4484 patients and 5084 implants. Onlay prostheses were associated with significantly higher rates of good to excellent outcomes (88% vs. 76%, p < 0.001), lower complication rates (7% vs. 19%, p < 0.001), and lower revision rates (4% vs. 8% TKA conversions, p = 0.02) compared to inlay implants. Among onlay designs, the Avon (Stryker) and Gender Solutions (Zimmer) prostheses showed the best results, with 90% and 87% success rates, respectively. The Lubinus (Link) inlay prosthesis demonstrated the poorest performance, with high complication and revision rates. Patellar maltracking was more frequent in the inlay group (4% vs. 1%), though not statistically significant. Infection and aseptic loosening rates were negligible in both groups. Conclusion:Onlay PFA appears to offer clinical advantages over inlay designs in the treatment of isolated PFOA, with trends toward superior functional outcomes, lower complication and revision rates, and more consistent performance across models. However, these results should be interpreted in light of the predominance of non-randomized studies and the heterogeneity of the available literature. The findings support the preferential use of onlay implants, particularly the Avon and Gender Solutions designs. Implant selection should be guided by evidence-based performance and patient-specific anatomical considerations. Level of Evidence:Level IV.

Background: Femoral neck fractures are rare but serious injuries in children and adolescents, often resulting from high-energy trauma and prone to complications like avascular necrosis (AVN) and nonunion. Even rarer is the development of slipped capital femoral epiphysis (SCFE) following femoral neck fracture, which presents unique diagnostic and treatment challenges. SCFE can destabilize the femoral head, with severe cases requiring complex surgical interventions. Case presentation: This report details a case of a 15-year-old male with autism spectrum disorder (ASD) who developed severe SCFE one month after treatment for a Delbet type III femoral neck fracture. The condition was managed with an Imhäuser intertrochanteric osteotomy (ITO), in situ fixation (ISF), and osteochondroplasty (OChP), supported by virtual surgical planning (VSP) and 3D-printed patient-specific instruments (PSIs) for precise correction and fixation. Discussion: The surgery was completed without complications. Six months after the operation, the patient exhibited a pain-free, mobile hip with radiographic evidence of fracture healing and no signs of AVN. Functional outcomes were favorable despite rehabilitation challenges due to ASD. Conclusions: The Imhäuser ITO, combined with ISF and OChP, effectively addressed severe SCFE after femoral neck fracture, minimizing AVN risk. VSP and PSIs enhanced surgical accuracy and efficiency, demonstrating their value in treating rare and complex pediatric orthopedic conditions.

Level 3 - Retrospective cohort study, Case-control study, Meta-analysis of Level 3 studies Degenerative arthropathy of the tibio-tarsal joint is a condition that afflicts about 1% of the world's population, with consequences in terms of impact on the quality of life of the patients. In recent decades, ankle prosthetic replacement has seen an important spread with increasingly promising results. Among the most frequent complications described in the short to medium term of primary ankle prosthesis we find the formation of periarticular heterotopic ossifications. However, the clinical impact of these findings remains highly debated in the literature, and the need for prophylactic treatments is controversial, due to the paucity of scientific evidence in the literature. 105 treated total ankle prosthetic replacement patients at a minimum radiological follow-up of 12 months were included in the study, the patients were retrospectively analysed by dividing them into two subgroups, 43 patients treated of ankle prosthesis with lateral access and 62 patients treated with anterior access. Patients were evaluated radiographically by assessing the presence, location, and severity of periarticular heterotopic ossifications according to modified Brooker's classification; and they were evaluated clinically by NRS and FAAM score and rate of re-interventions due to the presence of heterotopic ossifications. Individual and procedural risk factors has been taken into consideration. 84 patients (80%) developed radiographic findings of HO. A surgical intervention was required because of HO in 19 of these 84 patients which is 23 %. Intervention for HO would be considered only in those patients who had HO. The AA group consisted of 62 patients, forty-five (73% of 62) developed HO and 10 of these 45 patients had sufficient symptoms which was treated with arthrolysis. The LA group consisted of 43 patients, thirty-nine (91%) developed HO and 9 of these 39 patients had sufficient symptoms which was treated with arthrolysis. LA group had a higher prevalence of HO than the AA group (91% vs 73%). There is a direct correlation between clinical scores and degree of HO (FAAM and Pain Score). Prosthesis with LA more frequently develop HO than AA. In addition, young patients, delayed ankle mobilization and weightbearing can be accounted as risk factors in the development of HOs; conversely smoking, BMI, duration of surgery and post-traumatic arthritis were not found to have a significant impact. Demographics characteristics and mean score results at the end of follow-up

Heterotopic periarticular ossifications (HO) are a frequent short to mid-term complication following Total Ankle Replacement (TAR). Historically two primary surgical approaches exist-Lateral Approach (LA) and Anterior Approach (AA)-each bound with different prosthetic designs. However, there is no consensus on the incidence, real clinical impact, or need for reintervention of HO between these approaches, nor on the necessity of prophylactic treatments. This retrospective, monocentric, comparative study (evidence level III) involved radiological classification of patients using the modified Brooker Classification System (mBCS) by two independent orthopedic surgeons. A total of 105 patients undergoing LA or AA TAR at the same center were included. Radiographic HO was observed in 84 patients (80 %). Of these, 19 (23 %) required surgical intervention due to symptomatic HO. In the AA group (62 patients, Vantage Exactech prosthesis), 45 (73 %) developed HO, with 10 having sufficient symptoms which were treated with arthrolysis. In the LA group (43 patients, Trabecular Metal Zimmer prosthesis), 39 (91 %) developed HO, with 9 requiring arthrolysis. HO was more prevalent in the LA group than in the AA group (91 % vs. 73 %). A direct correlation was found between clinical scores (FAAM and Pain Score) and HO severity. Prosthesis with LA more frequently develop HO than AA. In addition, young patients, delayed ankle mobilization and weightbearing can be accounted as risk factors in the development of HOs; conversely smoking, BMI, duration of surgery and post-traumatic arthritis were not found to have a significant impact.

Il cromosoma 2 umano si è formato all’incirca 1 milione di anni fa, dalla fusione telomerica dei due bracci corti degli autosomi omologhi presenti nelle grandi scimmie e nel progenitore comune ad esse e a Homo sapiens. Dando origine a una struttura bicentromerica, il cromosoma 2 manifesta instabilità alla segregazione/ricombinazione del DNA, da cui deriva aumento nel rischio mutazionale. Evidenze storiche di disordini osteometabolici e di massa adiposa derivati da queste mutazioni sono rintracciabili dal primo millennio a.C. al XXI secolo, suggerendo che questo cromosoma contribuisce alla stabilità evolutiva e individuale delle masse somatiche (free fat mass e fat mass) umane, insieme ad altri autosomi, come 15, 21 e 22, che producono sindromi genetiche dismetaboliche storicamente note. Complessivamente, nell’ultimo milione di anni circa gli intervalli di locus genico 2q31-37 e 2p13-25 avrebbero assicurato il mantenimento del programma evolutivo di sviluppo corporeo in Homo sapiens, confermando che sul cromosoma 2 risiede un controllo fondamentale per la speciazione dell’Uomo moderno.

BackgroundIn an era of precision and stratified medicine, homogeneity in population-based cohorts, stringent causative entry, and pattern analysis of datasets are key elements to investigate medical treatments. Adhering to these principles, we collected in vivo and in vitro data pointing to an insulin-sensitizing/insulin-mimetic effect of myo-inositol (MYO) relevant to cell regeneration in dentistry and oral surgery. Confirmation of this possibility was obtained by in silico analysis of the relation between in vivo and in vitro results (the so-called bed-to-benchside reverse translational approach).ResultsFourteen subjects over the 266 screened were young adult, normal weight, euglycemic, sedentary males having normal appetite, free diet, with a regular three-times-a-day eating schedule, standard dental hygiene, and negligible malocclusion/enamel defects. Occlusal caries were detected by fluorescence videoscanning, whereas body composition and energy balance were estimated with plicometry, predictive equations, and handgrip. Statistically significant correlations (Pearson r coefficient) were found between the number of occlusal caries and anthropometric indexes predicting insulin resistance (IR) in relation to the abdominal/visceral fat mass, fat-free mass, muscular strength, and energy expenditure adjusted to the fat and muscle stores. This indicated a role for IR in affecting dentin reparative processes. Consistently, in vitro administration of MYO to HUVEC and Swiss NIH3T3 cells in concentrations corresponding to those administered in vivo to reduce IR resulted in statistically significant cell replication (ANOVA/Turkey tests), suggesting that MYO has the potential to counteract inhibitory effects of IR on dental vascular and stromal cells turnover. Finally, in in silico experiments, quantitative evaluation (WOE and information value) of a bioinformatic Clinical Outcome Pathway confirmed that in vitro trophic effects of MYO could be transferred in vivo with high predictability, providing robust credence of its efficacy for oral health.ConclusionOur reverse bed-to-benchside data indicate that MYO might antagonize the detrimental effects of IR on tooth decay. This provides feasibility for clinical studies on MYO as a regenerative factor in dentistry and oral surgery, including dysmetabolic/aging conditions, bone reconstruction in oral destructive/necrotic disorders, dental implants, and for empowering the efficacy of a number of tissue engineering methodologies in dentistry and oral surgery.