Letter to the Editor: Severe Rebound-Associated Vertebral Fractures After Denosumab Discontinuation Free

We read the paper by Lamy et al. (1) with great interest. Several points need further clarification.

First, it is somewhat surprising that despite carefully documenting such a large number of vertebral fractures (VFs) over such a short period, no images were presented for the benefit of the readers. Also, no images were presented in the authors' very recent report on the first three of the nine patients from this report, either (2). Interestingly, another case report and a letter to the editor, published in the same issue of that journal, did include images (3, 4).

Second, the vertebral biopsy image is largely uninformative. Instead, a simple unlabeled needle biopsy from the ilium during the vertebroplasty procedure would have provided the most necessary architectural information.

Third, elevation in markers is predictable, considering the timing of the measurement (i.e., shortly after fractures and/or during the healing period) (5).

Fourth, to infer solely on the basis of serum markers that bone remodeling after discontinuation of denosumab increased to such an extent as to cause rapid (and presumably severe) microarchitectural deterioration that resulted in cascading VFs defies biological plausibility, which is a requirement for such unusual observations (6).

Finally, the risk of fractures was high for the majority of patients prior to the initiation of treatment because of the very low bone mineral density, regardless of the Fracture Risk Assessment Tool estimate.

Before concluding that rebound increase in bone remodeling caused these cascading VFs, documentation of the evidence by transiliac bone biopsy, preferably following in vivo tetracycline labeling, is necessary to directly assess the status of bone structure and remodeling.

Abbreviations:

 
• VF

  vertebral fracture.

Acknowledgments

Disclosure Summary: The authors have nothing to disclose.

References

Author notes