CD169+ macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair.

Osteal macrophages (osteomacs) contribute to bone homeostasis and regeneration. To further distinguish their functions from osteoclasts, which share many markers and growth factor requirements, we developed a rapid, enzyme-free osteomac enrichment protocol that permitted characterization of minimally manipulated osteomacs by flow cytometry. Osteomacs differ from osteoclasts in expression of Siglec1 (CD169). This distinction was confirmed using the CD169-diphtheria toxin (DT) receptor (DTR) knock-in model. DT treatment of naïve CD169-DTR mice resulted in selective and striking loss of osteomacs, whilst osteoclasts and trabecular bone area were unaffected. Consistent with a previously-reported trophic interaction, osteomac loss was accompanied by a concomitant and proportionately striking reduction in osteoblasts. The impact of CD169+ macrophage depletion was assessed in two models of bone injury that heal via either intramembranous (tibial injury) or endochondral (internally-plated femoral fracture model) ossification. In both models, CD169+ macrophage, including osteomac depletion compromised bone repair. Importantly, DT treatment in CD169-DTR mice did not affect osteoclast frequency in either model. In the femoral fracture model, the magnitude of callus formation correlated with the number of F4/80+ macrophages that persisted within the callus. Overall these observations provide compelling support that CD169+ osteomacs, independent of osteoclasts, provide vital pro-anabolic support to osteoblasts during both bone homeostasis and repair.

Systematic Review of En Bloc Resection in the Management of Ewing's Sarcoma of the Mobile Spine with Respect to Local Control and Disease-Free Survival.

There is no consensus on the optimal method of local control in Ewing's sarcoma (ES) of the mobile spine. Recent reports have suggested that en bloc resection may improve local control and survival. The authors therefore performed a systematic review to answer the following questions: (1) What is the outcome of en bloc resection for ES of the mobile spine with respect to local control and disease-free survival (DFS)? (2) How should residual ES of the mobile spine be treated?Inclusion criteria were articles published between the years 1960 and 2014 in English that contained more than five patients. This yielded 204 articles, from which 4 were selected for detailed analysis. The literature was graded for quality, summarized, and presented to a group of spinal oncology experts with consensus recommendations made.All 4 studies were retrospective case series graded as very low quality evidence. Local control strategies included radiotherapy (RT) alone, surgery and RT, or surgery alone. There was no standardized outcome reported across studies with respect to the type of surgical procedure, margins, and outcomes of interest such as local recurrence (LR) and DFS. When the en bloc procedures were pooled together, 2 of the 21 patients with available LR data developed LR (9.5%), and 5 of the 7 patients with available DFS data were disease free at a mean of 76 months. The remaining 2 died at 10 and 29 months, respectively. No studies were identified detailing the treatment of residual ES of the mobile spine.There is no consensus on the optimal method of local control for spinal ES or the treatment of residual disease. A weak recommendation supports that when the en bloc resection is technically possible, in combination with RT, this appears to provide superior local control than RT alone, or incomplete excision and RT. The effect on survival is indeterminate.