Medicines

Background/Objectives: Kienböck disease (idiopathic avascular necrosis of the lunate) is treated almost exclusively surgically; its pharmacological evidence base comprises fewer than five primary publications and ~20 patient-level observations. Femoral-head, jaw, and knee osteonecrosis have decades of evidence, including randomised trials. We ask whether extra-carpal evidence can be translated to Kienböck disease and the wider Carpal Avascular Necrosis Family (lunate, scaphoid/Preiser, capitate, hamate, triquetrum). Methods: We conducted a narrative review reported per SANRA, searching PubMed, CrossRef, Google Scholar and three specialty registries from inception to 2026 across eleven drug classes and eleven skeletal sites. All references were independently verified against primary sources (PubMed/CrossRef). No Kienböck-specific randomised or controlled data exist; all conclusions therefore rest on indirect, extra-carpal evidence. Results: Three pathways (subchondral insufficiency fracture, microvascular ischaemia, hypercoagulability) predict drug-class plausibility differently by site. Iloprost is the candidate most consistently aligned across the translation axes, though no direct lunate data exist; teriparatide provides the only randomised evidence suggesting reversal of established osteonecrosis at any site (medication-related osteonecrosis of the jaw). The lunate sits within a coherent carpal AVN family sharing end-arterial supply, Lichtman-grade trajectories, and a near-identical evidence vacuum. Conclusions: A Four-Axis Translation Framework (mechanistic alignment, anatomic concordance, Lichtman-stage applicability, lunate-specific risk–benefit geometry) is proposed to evaluate which extra-carpal evidence is admissible at the lunate; with the carpal AVN family construct, these are the review’s two novel contributions.

Background: Olfactory dysfunction (OD) is a key symptom of chronic rhinosinusitis with nasal polyps (CRSwNP). Dupilumab improves clinical outcomes, including patient-reported olfactory function. This study aimed to analyze correlations between patient-reported olfactory improvement, quality of life, and endoscopic outcomes in patients treated with dupilumab. Methods: A real-life, single-center retrospective study included 35 patients with severe, uncontrolled CRSwNP treated with dupilumab. Patient-reported olfactory function was assessed using a visual analog scale (VAS-olfaction), quality of life with the Sinonasal Outcome Test-22 (SNOT-22), and polyp size with the Nasal Polyp Score (NPS) at baseline, 6 months, and 12 months. Changes from baseline were analyzed using the Wilcoxon signed-rank test, whereas correlations were evaluated using Spearman’s rank correlation coefficient. Results: Dupilumab was associated with significant improvements in patient-reported olfactory function, quality of life, and polyp size at 6 and 12 months. Improvements in VAS-olfaction correlated significantly with SNOT-22 at 6 months (p = 0.035) and 12 months (p = 0.024). In a sensitivity analysis excluding the smell/taste item from the SNOT-22, these correlations were attenuated and no longer reached statistical significance. No significant correlation was observed between patient-reported olfactory improvement and NPS. Conclusions: Patient-reported olfactory improvement correlated with quality of life but not with reductions in global polyp burden. These findings suggest that this improvement may not be fully explained by changes in polyp size alone.

Background: Memantine, an uncompetitive and voltage-dependent N-methyl-D-aspartate (NMDA) receptor antagonist, is clinically established for moderate-to-severe Alzheimer’s disease. Its pharmacodynamic profile, low-to-moderate affinity, rapid open-channel block, and strong voltage dependency allows selective inhibition of pathological NMDA overactivation while preserving physiological neurotransmission. Increasing evidence shows that these same mechanistic principles operate in the peripheral nervous system, where NMDA receptors contribute to excitotoxicity, oxidative stress, neuroinflammation, and maladaptive nociceptive signaling. Purpose: To synthesize emerging preclinical and clinical evidence demonstrating memantine’s modulatory and neuroprotective actions in peripheral neurons and glia and to outline implications for drug repurposing across neurology, pain medicine, oncology, supportive care, and ophthalmology. Methodology: A narrative integration of mechanistic studies, in vivo preclinical models, and heterogeneous clinical trials evaluating memantine’s effects on peripheral sensory neurons, autonomic neurons, Schwann cells, retinal ganglion cells, and neuromuscular junction physiology. Evidence was examined across conditions involving excitotoxicity, oxidative injury, mitochondrial dysfunction, apoptotic signaling, neuroinflammation, and neuropathic pain amplification. Results: Memantine consistently attenuates peripheral excitotoxic calcium influx, suppresses NOX-2–mediated ROS generation, stabilizes mitochondrial membrane potential, modulates Bax/Bcl-2 signaling, and reduces neuroinflammatory cytokine activity. It also inhibits dorsal horn wind-up selectively under neuropathic conditions. These convergent mechanisms yield protective effects across chemotherapy-induced peripheral neuropathy (CIPN), diabetic neuropathy, traumatic nerve injury, phantom limb pain, retinal ganglion cell excitotoxicity, and organophosphate-induced neuromuscular toxicity. Clinical evidence includes improved multimodal neuropathy outcomes in diabetic neuropathy when combined with gabapentin, reduced phantom limb pain prevalence and intensity at six months, and a five-fold reduction in post-mastectomy neuropathic pain with pre-emptive administration. Conclusions: Memantine should be conceptually reframed as a system-wide neuroprotective agent with substantial translational potential beyond the CNS. Priorities for future development include NR2B-selective peripheral NMDA antagonists, peripherally restricted formulations, single-cell transcriptomic mapping of peripheral NMDA receptor subtypes, and adequately powered PNS-specific randomized trials.