The reparative reaction including angiogenesis and osteogenesis in human bone after an ischemic event remains unknown. To investigate the reparative reaction in human bone, the distribution of tartrate resistant acid phosphatase (TRAP)-positive cells and the expressions of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and CD31 were observed around the fracture site in 101 hips in 100 patients with femoral neck fracture. These 17 men and 83 women had a mean age of 80 years (range, 58–97 years). Of the hips, 17 were Garden stage 3, and 84 were Garden stage 4. The mean duration from fracture to surgery was 6.3 days (range, 1–14 days). Hematoxylin–eosin staining, TRAP staining, and immunohistochemistry using anti-HIF-1α, anti-VEGF anti-FGF-2, and anti-CD31 antibodies were performed for the coronal section of the retrieved whole femoral heads. TRAP-positive cells were detected near the trabecular bone around the fracture site in ten hips (10 %). HIF-1α expression was detected in 41 hips (41 %), mainly in the endothelial cells of the vessels. VEGF showed diffuse cytoplasmic staining of the mononuclear cells in the edematous area in 39 hips (39 %) while FGF-2 was detected in the cytoplasm of mononuclear cells in the bone marrow in 82 hips (82 %). CD31 was expressed in the bone marrow vessels in 35 hips (35 %). There were significant differences in HIF-1α expression relative to the duration between the fracture and the surgery, and in CD31 expression relative to Garden stage. HIF-1α expression was detected around the fracture site in the early period after fracture and CD31 expression was detected more frequently in Garden 3 hips while VEGF and FGF-2 expressions were detected regardless of Garden classification.
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The institution of one of the authors (NS) has received funding from a grant from the Japanese Investigation Committee under the auspices of the Ministry of Health and Welfare. We thank Mrs. Mari Shinkawa, Miss Yasuko Taniguchi, Miss Takako Shizuka, and Miss Mizuki Nakata for the technical support of sample preparation.
Conflict of interest
There is no conflict of interest in the present study.
Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
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Sakai, T., Iwana, D., Nakamura, N. et al. Histological characteristics of the human femoral head in patients with femoral neck fracture. Virchows Arch 461, 705–711 (2012). https://doi.org/10.1007/s00428-012-1331-y
- Femoral neck fracture
- Tartrate resistant acid phosphatase (TRAP)
- Hypoxia inducible factor-1α (HIF-1α)
- Vascular endothelial growth factor (VEGF)
- Fibroblast growth factor-2 (FGF-2)