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.
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