Background: Knee osteoarthritis (KOA) in people with overweight or obesity is clinically heterogeneous, reflecting mechanical loading, synovial and systemic inflammation, metabolic dysfunction, structural severity, and pain-related factors. We evaluated multidomain outcomes after semaglutide initiation and characterized clinically relevant response patterns. Methods: This retrospective, self-controlled cohort included 93 adults treated in routine rheumatology care; 88 completed a six-month follow-up. There was no untreated concurrent comparator; within-patient changes and exposure–outcome associations were therefore interpreted as non-causal. Changes in pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function, anthropometry, inflammatory markers, glycated hemoglobin (HbA1c), lipids, dose exposure, and safety were evaluated. Joint multivariable models included percentage weight loss and maximum achieved dose. Exploratory K-means phenotyping integrated dose, weight loss, body mass index (BMI) decrease, visual analog scale (VAS) and WOMAC improvement, and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and HbA1c reductions, with candidate solutions and resampling stability examined. Results: At six months, mean weight decreased by 10.88 kg, VAS pain score by 2.47 points, WOMAC total by 22.50 points, CRP by 2.67 mg/L, ESR by 7.62 mm/h, and HbA1c by 0.51 percentage points (all p < 0.001). Weight loss remained independently associated with WOMAC improvement, while achieved dose retained positive adjusted associations with pain, function, inflammatory, and metabolic changes. Exploratory clustering identified five clinically interpretable patterns along a broader response-intensity gradient, including high-burden multidomain response, high-dose concordant response, dose-modified intermediate response, inflammation-preserved response despite moderate weight loss, and dose-limited graded response. These observational coefficients and clusters cannot distinguish treatment-related effects from residual confounding or co-interventions. Conclusions: Substantial within-patient improvements were observed, but the uncontrolled design precludes causal attribution. The exploratory patterns may be compatible with contributions from baseline disease burden, dose exposure, mechanical unloading, and residual inflammatory variation; they do not establish weight-independent pharmacologic effects or validated patient subtypes. Prospective controlled, multicenter validation is required.

Physical energy-based therapies are non-invasive adjunctive interventions that deliver mechanical, electromagnetic, light, or radiofrequency/thermal energy to tissues with the aim of reducing symptoms and improving tolerance of active rehabilitation. Osteoarthritis (OA) is a heterogeneous whole-joint disorder in which cartilage degeneration, subchondral bone remodeling, synovitis, peri-articular tissue dysfunction, neuromuscular impairment, and pain sensitization may interact to produce pain, stiffness, and activity restriction. As conservative therapy for OA, education, progressive therapeutic exercise, weight management when indicated, and self-management remain the core of care. Nevertheless, some patients cannot fully participate in exercise because of pain, fear of movement, load intolerance, comorbidity, or limited access to supervised rehabilitation. This narrative review synthesizes evidence published mainly between 2016 and 2026 for extracorporeal shock wave therapy (ESWT), photobiomodulation/low-level laser therapy (PBMT/LLLT), pulsed electromagnetic field therapy (PEMF), transfer energy capacitive and resistive/capacitive–resistive electric transfer (TECAR/CRET) therapy, body weight support and aquatic unloading strategies, and mechanosonic vibration therapies. The available literature suggests that ESWT and PBMT/LLLT may provide short- to mid-term pain and function benefits in selected patients with knee OA when parameters are aligned with evidence-supported dosing windows. PEMF and vibration therapies show promising but less consistent effects because protocols, devices, sham conditions, and populations vary. TECAR/CRET and unloading approaches are best interpreted as enabling tools that may reduce guarding, improve walking tolerance, or increase the quality of therapeutic exercise, rather than stand-alone disease-modifying treatments. Current national and society guidelines consistently prioritize exercise, education, and weight management; most of the modalities reviewed here are absent from guidelines or are supported only indirectly, which justifies cautious wording and individualized use. A practical application model is, therefore, time-limited and goal-oriented: identify the barrier to rehabilitation, select a modality with a plausible mechanism and published protocol, monitor pain and functional response, and discontinue the modality if it does not improve participation in active care.

Background and Objectives: Foot bone marrow edema of presumed algodystrophic or bone marrow edema syndrome-like origin is clinically difficult to classify, and the relationship between MRI extent, pain severity, and functional impairment remains insufficiently defined. This study aimed to describe MRI distribution patterns and short-term clinical changes in a small real-world cohort of patients with persistent NSAID-resistant foot pain and presumed algodystrophic/BMES-like bone marrow edema. Materials and Methods: This retrospective single-center observational cohort study included 19 consecutive patients with persistent foot pain; MRI-demonstrated bone marrow edema; inadequate response to NSAIDs; management with a multimodal protocol that included neridronate, vitamin D supplementation, and, in selected patients, adjunctive physiotherapy and magnetotherapy; and available 3-month follow-up. The protocol consisted of intramuscular neridronate 25 mg once daily for 16 consecutive days, resulting in a total cumulative dose of 400 mg, together with vitamin D supplementation. Eleven patients also underwent adjunctive physiotherapy and magnetotherapy. MRI findings were categorized by anatomical location group, multilocalization, and compartment involvement. Clinical outcomes included baseline and 3-month Visual Analog Scale scores, WOMAC scores, and descriptive changes in NSAID use. Nonparametric paired and exploratory subgroup analyses were performed. Results: Mean age was 51.3 ± 14.9 years, and 52.6% of patients were female. MRI showed predominant midfoot involvement, with the navicular and third cuneiform most frequently affected. Median VAS changed from 8.0 at baseline to 3.0 at 3 months, and median WOMAC changed from 80.0 to 41.0; because no control group was available, these paired changes should be interpreted descriptively. Daily NSAID use decreased from 78.9% at baseline to 0% at follow-up. These findings describe clinical improvement after a multimodal management approach but do not establish the independent treatment effect of neridronate. In exploratory analyses, only two patients had multi-compartment involvement; therefore, any apparent pain-severity signal in this subgroup was considered unstable and hypothesis-generating only. Edema location group and multilocalization were not statistically associated with VAS or WOMAC outcomes. Conclusions: In this small retrospective single-center case series, presumed algodystrophic/BMES-like foot bone marrow edema most commonly involved the midfoot, particularly the navicular and cuneiform region. Pain scores, WOMAC scores, and daily NSAID use decreased over 3 months after multimodal care. However, the uncontrolled design, small sample size, concomitant vitamin D supplementation, adjunctive physiotherapy or magnetotherapy in many patients, and self-limiting nature of BMES-like conditions prevent attribution of these changes to neridronate or to any single treatment component. The apparent relationship between multi-compartment edema and greater pain severity was based on only two patients and should be regarded only as a weak exploratory observation.