Glycemic Improvement and Active Charcot Neuroarthropathy: Osteocalcin as a Candidate Biomarker of Transient Skeletal...

Active Charcot neuroarthropathy (CN) remains difficult to predict. This hypothesis-generating article proposes a deliberately restricted, testable model in which a clinically meaningful fall in HbA1c may temporally coincide with active CN in a subset of people with diabetes, established neuropathy, and a vulnerable foot. The signal is based on a sequence of observations-an initial case report, a 44-case retrospective series, and the EPiChar study-and therefore is supportive of association and biological plausibility, but not causation. Within this framework, osteocalcin should presently be regarded mainly as a candidate biomarker of a transient skeletal activation state rather than a proven pathogenic mediator. This article should therefore be read as a suggestion for prospective testing and not as confirmation of an osteocalcin-mediated pathway. We propose that this systemic signal may intersect with established local drivers-neuropathy, repetitive microtrauma, inflammation, and RANKL/OPG imbalance-and can be tested prospectively with serial bone turnover markers, neuropathy phenotyping, kidney function, and modifiable exposure data during treatment intensification.

Active Charcot neuroarthropathy remains difficult to predict, and its timing is not fully explained by neuropathy and mechanical stress alone. We asked whether a clinically meaningful HbA1c fall may temporally coincide with active Charcot neuroarthropathy and whether osteocalcin could mark transient skeletal vulnerability. Available observations support association and biological plausibility, not causation, and do not prove that osteocalcin is a pathogenic mediator. Prospective monitoring studies are warranted, but current evidence does not justify delaying evidence-based glycemic optimization.