The most reliable predictor of future fracture risk is a previous fracture of any kind. The etiology of this increased fracture risk is not fully known, but it is possible that fracture initiates systemic bone loss, leading to greater fracture risk at all skeletal sites. In this study, we investigated systemic bone loss and recovery after femoral fracture in young (3-month-old) and middle-aged (12-month-old) mice. Transverse femur fractures were created using a controlled impact, and whole-body bone mineral density (BMD), trabecular and cortical microstructure, bone mechanical properties, bone formation and resorption rates, mouse voluntary movement, and systemic inflammation were quantified at multiple time points post-fracture. We found that fracture led to decreased whole-body BMD in both young and middle-aged mice 2 weeks post-fracture; this bone loss was recovered by 6 weeks in young but not middle-aged mice. Similarly, trabecular bone volume fraction (BV/TV) of the L5 vertebral body was significantly reduced in fractured mice relative to control mice 2 weeks post-fracture (-11% for young mice, -18% for middle-aged mice); no significant differences were observed 6 weeks post-fracture. At 3 days post-fracture, we observed significant increases in serum levels of interleukin-6 and significant decreases in voluntary movement in fractured mice compared with control mice, with considerably greater changes in middle-aged mice than in young mice. At this time point, we also observed increased osteoclast number on L5 vertebral body trabecular bone of fractured mice compared with control mice. These data show that systemic bone loss occurs after fracture in both young and middle-aged mice, and recovery from this bone loss may vary with age. This systemic response could contribute to increased future fracture risk after fracture; these data may inform clinical treatment of fractures with respect to improving long-term skeletal health. © 2018 American Society for Bone and Mineral Research.

The most reliable predictor of future fracture risk is a previous fracture of any kind. The etiology of this increased fracture risk is not fully known, but it is possible that fracture initiates systemic bone loss leading to greater fracture risk at all skeletal sites. In this study we investigated systemic bone loss and recovery following femoral fracture in young (3 month old) and middleaged (12 month old) mice. Transverse femur fractures were created using a controlled impact, and whole-body bone mineral density (BMD), trabecular and cortical microstructure, bone mechanical properties, bone formation and resorption rates, mouse voluntary movement, and systemic inflammation were quantified at multiple time points post-fracture. We found that fracture led to decreased whole-body BMD in both young and middle-aged mice 2 weeks postfracture; this bone loss was recovered by 6 weeks in young, but not middle-aged mice. Similarly, trabecular bone volume fraction (BV/TV) of the L5 vertebral body was significantly reduced in fractured mice relative to control mice 2 weeks post-fracture (-11% for young mice, -18% for middle-aged mice); this bone loss was fully recovered by 6 weeks post-fracture in young mice.At 3 days post-fracture we observed significant increases in serum levels of interleukin-6 and significant decreases in voluntary movement in fractured mice compared to control mice, with considerably greater changes in middle-aged mice than in young mice. At this time point we also observed increased osteoclast number on L5 vertebral body trabecular bone of fractured mice compared to control mice. These data show that systemic bone loss occurs after fracture in both young and middle-aged mice, and recovery from this bone loss may vary with age. This systemic response could contribute to increased future fracture risk following fracture, and these data may inform clinical treatment of fractures with respect to improving long-term skeletal health.

OBJECTIVE To evaluate short- and long-term outcomes for dogs undergoing anal sacculectomy for massive (> 5 cm) apocrine gland anal sac adenocarcinoma (AGASACA). ANIMALS 28 client-owned dogs with massive AGASACA. PROCEDURES A retrospective multi-institutional study was performed. Pre-, intra-, and post-operative data was collected, and variables were statistically analyzed for associations with progression-free interval (PFI) and overall survival (OS). RESULTS At the time of anal sacculectomy, 19 (68%) dogs underwent concurrent iliosacral lymph node extirpation, including 17 of 18 (94%) dogs with suspected nodal metastasis preoperatively. Five (18%) dogs experienced grade 2 intraoperative complications. Ten (36%) dogs experienced postoperative complications, including 1 grade 3 and 1 grade 4 complication. No dogs had permanent fecal incontinence, tenesmus, or anal stenosis. Nineteen dogs received adjuvant chemotherapy, radiation, or both. Local recurrence occurred in 37% of dogs. Dogs with lymph node metastasis at surgery were more likely than dogs without metastasis to develop new/progressive lymph node metastasis (10/17 [59%] vs 0/10 [0%]; P = .003) and distant metastasis (7/17 [41%] vs 0/10 [0%]; P = .026). Median PFI was 204 days (95% CI, 145 to 392). Median OS was 671 days (95% CI, 225 to upper limit not reached). Nodal metastasis at the time of surgery was associated with shorter PFI (P = .017) but not OS (P = .26). Adjuvant therapy was not associated with outcome. CLINICAL RELEVANCE Dogs with massive AGASACA experienced prolonged survival following anal sacculectomy despite a high incidence of local recurrence and metastasis. Lymph node metastasis at the time of surgery was a negative prognostic indicator for PFI but not OS.