A new letter reply, in press this week at Clinical Infectious Diseases (18 April 2026), from our long-time friends and colleagues Eric Senneville and Benjamin Lipsky — two of the most thoughtful voices in diabetic foot infection — is worth a careful read. It is their (likely final) rejoinder in an ongoing conversation sparked by the Lagrand et al. trial comparing ulcer-bed biopsy to percutaneous bone biopsy for guiding antibiotic therapy in diabetic foot osteomyelitis (DFO).
The title says it all: Absence of evidence or evidence of absence?
The setup
Lagrand and colleagues reported that medically treated DFO patients did similarly well whether antibiotics were chosen based on ulcer-bed biopsy or on percutaneous bone biopsy. For many readers, the headline was that we might finally be free to skip the needle. Senneville and Lipsky are not so sure — and the reasons are worth sitting with.
Three points worth chewing on
1. The remission rates were surprisingly low. Lagrand’s 12-month remission was 31–39%, compared with roughly 65% in the Tone et al. RCT on antibiotic duration. The authors attribute this largely to a strict remission definition, but Senneville and Lipsky point out that comorbidity burden and antibiotic regimens may also be at play. When your event rate is that high, it gets harder — not easier — to demonstrate that one diagnostic strategy outperforms another.
2. Roughly 40% of bone cultures came back negative. This is the piece I find most interesting. A negative bone culture is not a null result; it is a signal — of sampling error, of low bacterial burden, or of the fact that this bone may not actually have active osteomyelitis. In real-world practice, a negative bone culture is powerful information: it often shortens antibiotics and avoids toxicity. If the trial defaulted those patients to ulcer culture-directed therapy, the comparison may have been blunted before it began.
3. The trial was powered to detect a 30% absolute difference. That is a big delta. Smaller differences — 10%, 15% — could be clinically meaningful and still slip under the statistical radar. Senneville and Lipsky make the epistemic point cleanly: what we have here is absence of evidence of superiority, not evidence of equivalence. They are different things, and we should not quietly swap one for the other.
The nuance they land on
Importantly, the authors are not arguing for bone biopsy in every case. Their conclusion is measured and, I think, the right one for where the field sits today: ulcer-bed biopsy is probably fine for many patients with DFO, but bone biopsy retains a role when there is diagnostic uncertainty, when first-line therapy has failed, or when precise antibiotic selection really matters — think resistant organisms, prosthetic hardware, or patients who cannot afford another round of empiric guessing.
They also flag what most of us are watching for: the VA INTREPID rifampin RCT, which could reframe how we think about adjunctive therapy in DFO regardless of which biopsy you choose.
Why this matters beyond the foot
The implications extend well past our corner of medicine. Chronic osteomyelitis in general — vertebral, post-traumatic, hardware-associated — leans heavily on bone sampling for microbiologic guidance. If we are going to walk back that practice, we should do it deliberately, with eyes open, and on the basis of more than one trial. This letter is a useful reminder that a single well-run study, however elegant, rarely rewrites a century of pathology in one pass.
Bottom line: read the letter. It is short, generous, and a model of how to disagree well in the literature. Senneville EM, Lipsky BA. Clinical Infectious Diseases, DOI: 10.1093/cid/ciag266 (in press, 18 April 2026).
#DFO #osteomyelitis #diabeticfoot #DFU #DFI #boneBiopsy #antibioticStewardship #IDSA #IWGDF #limbpreservation #evidenceBasedMedicine #ClinInfectDis #ALPS #SALSA
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