Denosumab is an FDA-approved drug for osteoporosis. It works by binding RANKL, thus inhibiting osteoclastic activity. Denosumab has also been shown to have a favorable impact on tumor response in relatively small, short-term studies among patients with giant-cell tumor of bone (GCTB).
In the March 21, 2018 issue of The Journal, Errani et al. report on a longer-term follow up (minimum 24 months, median 85.6 months) in two cohorts of patients with GCTB who were treated with joint-preserving curettage: those treated with curettage plus denosumab and those treated with curettage alone. The study found that denosumab administration was significantly associated with unfavorable outcomes in patients treated with curettage. Specifically, the local GCTB recurrence rate was nearly 4 times higher (60% vs 16%) in patients treated with denosumab plus curettage, compared to those treated with curettage alone.
Recent in vitro studies have shown that denosumab only slows giant-cell multiplication to some degree. The authors point out that patients treated with denosumab in this cohort study had more severe GCTB disease, which would seem to further confirm that cellular proliferation of giant cells is ineffectively slowed by this RANKL-binding drug. What’s most important about the Errani et al. study is that it’s the first one to look at the longer-term outcomes of denosumab usage before and after curettage for GCTB.
The authors emphasize that while their study shows a strong and independent association between denosumab administration and a high level of local recurrence, “causation could not be evaluated.” Still, at a time when clinicians, payers, and patients are critically evaluating every facet of treatment, it seems difficult to recommend the use of denosumab in addition to curettage for GCTB. The data in this study should encourage the musculoskeletal oncology community to continue to investigate other adjunctive treatments to be used with curettage for this disease process.
Marc Swiontkowski, MD
In the February 15, 2017 issue of The Journal, Aneja et al. utilize a large administrative database to examine the critical question of venous thromboembolism (VTE) risk as it relates to managing patients with metastatic femoral lesions. The authors found that prophylactic intramedullary (IM) nailing clearly resulted in a higher risk of both pulmonary embolism and deep-vein thrombosis, relative to IM nailing after a pathologic fracture. Conversely, the study found that patients managed with fixation after a pathological fracture had greater need for blood transfusions, higher rates of postoperative urinary tract infections, and a decreased likelihood of being discharged to home.
The VTE findings make complete clinical sense, because when we ream an intact bone, the highly pressurized medullary canal forces coagulation factors into the peripheral circulation. When we ream after a fracture, the pressures are much lower, and neither the coagulation factors nor components of the metastatic lesion are forced into the peripheral circulation as efficiently, although some may partially escape through the fracture site.
One might conclude that we should never consider prophylactic fixation in the case of metastatic disease in long bones, but that would not be a patient-centric position to hold. In my opinion, the decision about whether to prophylactically internally fix an impending pathologic fracture should be based on patient symptoms and consultations with the patient’s oncologist and radiation therapist.
If all of the findings from Aneja et al. are considered, and if the patient’s symptoms are functionally limiting after initiation of appropriate radiation and chemotherapy, prophylactic fixation should be performed, along with vigilantly managed VTE-prevention measures. This study is ideally suited to inform these discussions for optimum patient care.
Marc Swiontkowski, MD
It is not often that readers of scholarly journals have a “Wow!” moment, a chance to be unexpectedly delighted by a new discovery.1 In the September 14, 2016 edition of JBJS Case Connector, Zhang et al. provide readers of the JBJS family of journals the first of what we hope will be many such moments: the ability to link to and navigate a digital, whole-slide image (WSI) of an entire microscope slide.
Illustrating the histology of tumors and the tissue-level details in basic science studies has long been a challenge. Until recently, readers were usually subjected to the few fields of view that the author chose to photograph. The more senior among you may remember with nostalgia attempting to make sense of fuzzy, black-and-white, circular, histology images viewed as if seen through an antique monocular microscope (Fig. 1). The advent of color printing (often at the author’s extra expense) and eventually digital photographs improved somewhat the quality of each image, but readers were still required to accept that the author had selected fields of view that were truly representative of the subject matter.
In their case report titled “Morphological Transformation of Giant-Cell Tumor of Bone After Treatment with Denosumab,” Zhang et al. include two links to whole-slide images. In the first, readers can link from a conventional digital photograph of a core needle biopsy to the whole-slide image of the giant cell tumor. The authors also include several conventional photographs of the tumor after resection, along with a link to the corresponding scanned microscope slide.
The use of a viewing algorithm similar to that used by Google Earth allows readers to navigate and zoom in on not just the few isolated fields of view selected by the authors, but the hundreds to thousands of additional fields contained in the original microscope slide of this complicated tumor. While it’s very helpful for illustrating tumor histology, we anticipate that WSI technology will be even more valuable when applied to basic science studies of fracture healing or cartilage, nerve, and tendon repair—as well as many other possible applications.
Thomas Bauer, MD
JBJS Case Connector Co-Editor
- Glassy EF, Rebooting the Pathology Journal. Learning in the Age of Digital Pathology. Archiv Pathol Lab Med 2014;138:728-729.