Background: Osteoarthritis (OA) is the most common degenerative joint disease and affects millions of people worldwide, particularly the elderly population. The pathophysiology of OA is complex and involves multiple factors. Methods: Several studies have emphasized the crucial role of inflammation in this process. The receptor activator of NF-κB ligand (RANKL), the receptor activator of NF-κB (RANK), and osteoprotegerin (OPG) trigger a signaling cascade that leads to the excessive production of RANKL in the serum. Conclusions: The aim of this narrative review is (i) to assess the role of the RANK/RANKL/OPG signaling pathway in the context of OA progression, focusing especially on the physiopathology and on all the mechanisms leading to the activation of the inflammatory cascade, and (ii) to evaluate all the potential therapeutic strategies currently available that restore balance to bone formation and resorption, reducing structural abnormalities and relieving pain in patients with OA.

Charcot Foot (CF), part of a broader condition known as Charcot Neuro-Osteoarthropathy (CNO), is characterized by neuropathic arthropathy with a progressive alteration of the foot. CNO is one of the most devastating complications in patients with diabetes mellitus and peripheral neuropathy but can also be caused by neurological or infectious diseases. The pathogenesis is multifactorial; many studies have demonstrated the central role of inflammation and the Receptor Activator of NF-κB ligand (RANKL)-Receptor Activator of NF-κB (RANK)-Osteoprotegerin (OPG) pathway in the acute phase of the disease, resulting in the serum overexpression of RANKL. This overexpression and activation of this signal lead to increased osteoclast activity and osteolysis, which is a prelude to bone destruction. The aim of this narrative review is to analyze this signaling pathway in bone remodeling, and in CF in particular, to highlight its clinical aspects and possible therapeutic implications of targeting drugs at different levels of the pathway. Drugs that act at different levels in this pathway are anti-RANKL monoclonal antibodies (Denosumab), bisphosphonates (BP), and calcitonin. The literature review showed encouraging data on treatment with Denosumab, although in a few studies and in small sample sizes. In contrast, BPs have been re-evaluated in recent years in relation to the high possibility of side effects, while calcitonin has shown little efficacy on CNO.

Background and Objectives: The treatment of end-stage ankle osteoarthritis (OA) and associated hindfoot deformities remains a major challenge for orthopedic surgeons. Numerous techniques and surgical approaches have been proposed for tibiotalar (TT) and tibiotalocalcaneal (TTC) arthrodesis, from arthroscopic to open, as well as numerous devices proposed for internal fixation (retrograde intramedullary nails, cannulated screws, and plating systems). The aim of this study was to retrospectively analyze the results, with at least 18 months of follow-up, with Silverback^TM TT/TTC Plating System Paragon28 in a group of 20 patients with severe OA and hindfoot deformities (mainly secondary post-traumatic OA). Materials and Methods: The demographic characteristics and past medical history of the patients were collected and analyzed to identify the cause of the pathology. The degree of OA and deformity were quantified based on foot and ankle weight-bearing radiography and CT examination. Pre- and post-operative clinical and functional scores (ROM, VAS, AOFAS, FFI, and SF-36) and radiographic parameters (anterior distal tibial angle, tibiotalar angle, coronal tibiotalar angle, and hindfoot alignment angle) were evaluated. Results: All of the patients showed clinical and radiographic fusion at an average of 14 weeks (range 12–48), with improvement in pain and functional scores, without major surgical complications and/or infections. Conclusions: Despite the limitations of our study, the results with this new plating system showed good results in terms of bone consolidation, post-operative complications, and improvement of pain and quality of life in patients with severe OA and deformities of the ankle and hindfoot.

Charcot Neuro-Osteoarthropathy (CNO) is a debilitating complication predominantly affecting individuals with diabetes and peripheral neuropathy. Radiological assessment plays a central role in the diagnosis, staging, and management of CNO. While plain radiographs remain the cornerstone of initial imaging, advanced modalities such as Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) have significantly enhanced diagnostic accuracy. Nuclear imaging, including bone scintigraphy, radiolabeled leukocyte scans, and FDG-PET/CT, offers additional diagnostic precision in complex cases, especially when differentiating CNO from infections or evaluating patients with metal implants. This review underscores the importance of a multimodal imaging approach suited to the clinical stage and specific diagnostic challenges of CNO. It highlights the critical need for standardized imaging protocols and integrated diagnostic algorithms that combine radiological, clinical, and laboratory findings. Advances in imaging biomarkers and novel techniques such as diffusion-weighted MRI hold promise for improving early detection and monitoring treatment efficacy. In conclusion, the effective management of CNO in diabetic foot patients requires a multidisciplinary approach that integrates advanced imaging technologies with clinical expertise. Timely and accurate diagnosis not only prevents debilitating complications but also facilitates the development of personalized therapeutic strategies, ultimately improving patient outcomes.

Background: Diabetic foot ulcers are a common complication of diabetes mellitus, often leading to progressive sensory deficits, impaired vascularization, and a predisposition to ulceration and gangrene. Untreated ulcers may cause recurrent infections that endanger a patient’s life. Amputation of part of the limb up to a well-vascularized level is one of the treatments employed for untreated ulcers. Objectives: Laboratory data were analyzed with the aim of identifying risk factors related to surgical amputation treatment of diabetic foot. We believe it is useful to identify risk factors that can be altered from a reversible condition in the clinical decision-making of treatment, thus manifesting themselves in a timely manner to provide the patient with an alternative to surgical amputation of the lower limb. Methods: Our retrospective study was conducted by the Department of Orthopedics and Traumatology at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome. We recruited 200 patients who underwent lower limb amputation for diabetic foot between 2017 and 2021 and had blood tests both 30 days and within 5 days before the first surgery. Results: This case–control study revealed a significant negative correlation between hemoglobin (Hb) levels and the occurrence of leg amputations. In contrast, C-reactive protein (CRP) levels, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) showed significant positive correlations with leg amputations. A 3-year follow-up of the cases also revealed a significative positive correlation between age, white blood cells (WBC) count, NLR, PLR, and death at 3 years. Conclusions: Our findings suggested that lower Hb levels and elevated CRP, NLR, and PLR levels in patients with diabetic foot disease may be associated with a higher risk of lower-limb amputation. Unexpectedly, this study also demonstrated that elderly age, WBC, CRP, NLR and PLR levels may be associated with a negative prognosis for these patients. These findings highlighted the importance of monitoring these laboratory values in diabetic patients to identify individuals at higher risk of leg amputations and implement appropriate interventions to prevent or minimize the occurrence of this severe complication.

Hereditary hemochromatosis (HH) is an autosomal recessive bleeding disorder characterized by tissue overload of iron. Clinical systemic manifestations in HH include liver disease, cardiomyopathy, skin pigmentation, diabetes mellitus, erectile dysfunction, hypothyroidism, and arthropathy. Arthropathy with joint pain is frequently reported at diagnosis and mainly involves the metacarpophalangeal and ankle joints, and more rarely, the hip and knee. Symptoms in ankle joints are in most cases non-specific, and they can range from pain and swelling of the ankle to deformities and joint destruction. Furthermore, the main radiological signs do not differ from those of primary osteoarthritis (OA). Limited data are available in the literature regarding treatment; surgery seems to be the gold standard for ankle arthropathy in HH. Pharmacological treatments used to maintain iron homeostasis can also be undertaken to prevent the arthropathy, but conclusive data are not yet available. This review aimed to assess the ankle arthropathy in the context of HH, including all its aspects: epidemiology, physiopathology, clinical and imaging presentation, and all the treatments available to the current state of knowledge.