Evaluation of topographical and chemical modified TiAl6V4 implant surfaces in a weight-bearing intramedullary femur model in rabbit.

For cementless total joint replacement implants, the biological response to physicochemical surface characteristics is crucial for their success that depends on fixation by newly formed bone. In this study, the surface of TiAl6V4 (Tilastan®) implants was modified by (a) corundum blasting, (b) corundum blasting followed by electrochemical calcium phosphate (CaP) deposition, and (c) titanium plasma spraying followed by electrochemical CaP deposition. All modifications resulted in a surface roughness suitable to enhance primary implant stabilization and to favor osteoblast adhesion and function; the thin, biomimetic CaP coating is characterized by fast resorbability and served as chemical cue to stimulate osteogenesis. After implantation in a full weight-bearing rabbit intramedullary distal femur model, osseointegration was investigated after 3, 6, and 12 weeks. For all modifications, new bone formation, occurring from the endosteum of the femoral cortical bone, was observed in direct contact to the implant surface after 3 weeks. At the later time points, maturation of the woven bone into lamellar bone with clearly defined osteons was visible; the remodeling process was accelerated by the CaP coating. The ingrowth of newly formed bone into the pores of the titanium plasma sprayed surfaces indicates a strong interlock and finally implant fixation. Our findings indicate a positive impact of the tested surface modifications on osseointegration.

Conventional Primary Central Chondrosarcoma of the Pelvis: Prognostic Factors and Outcome of Surgical Treatment in 162 Patients.

BACKGROUND: Studies focusing on the oncological outcome after treatment of conventional primary central chondrosarcoma of pelvic bone are lacking. We conducted this retrospective study at 5 referral centers to gain insight in the outcome of treatment for this tumor type and to identify risk factors for impaired oncological outcome. METHODS: One hundred and sixty-two consecutive patients (118 male patients [73%]) who underwent resection of a conventional primary central chondrosarcoma of pelvic bone from 1985 to 2013 were evaluated. The median age was 51 years (range, 15 to 78 years). The median follow-up was 12.6 years (95% confidence interval [CI], 8.4 to 16.9 years). There were 30 grade-I lesions (19%), 93 grade-II lesions (57%), and 39 grade-III lesions (24%). RESULTS: Sixty-two patients (38%) experienced local recurrence: 9 grade-I lesions (30%), 31 grade-II lesions (33%), and 22 grade-III lesions (56%). Forty-eight patients (30%) developed metastases. The risk of disease-related death was 3% for grade-I tumors (1 of 30; this patient had a grade-II recurrence and died of metastases), 33% (31 of 93) for grade-II tumors, and 54% (21 of 39) for grade-III tumors. Identified risk factors for impaired disease-specific survival were tumor grade (grade II: hazard ratio [HR], 20.18; p = 0.003; and grade III: HR, 58.94; p < 0.001), resection margins (marginal: HR, 3.21; p = 0.001; and intralesional: HR, 3.56; p < 0.001), and maximal tumor size (HR, 1.08 per cm; p = 0.026). Deep infection (19% [n = 31]) was the predominant complication. CONCLUSIONS: This study offers a standard for survival rates for conventional primary central chondrosarcoma of the pelvis. The survival for grade-I tumors was excellent. Wide resection margins were associated with a significant survival advantage for higher-grade tumors. Because of the inability to reliably distinguish low-grade and high-grade tumors preoperatively, we conclude that any central pelvic chondrosarcoma should be treated with aggressive primary resection with the aim of obtaining wide resection margins. There may be aggressive biologic features in some tumors for which a surgical procedure alone may not be adequate to improve outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus results in increased risk of fracture and delayed fracture healing. ZDF fa/fa rats are an established model of type 2 diabetes mellitus with low bone mass and delayed bone healing. We tested whether a sclerostin-neutralizing antibody (Scl-AbVI) would reverse the skeletal deficits of diabetic ZDF rats. Femoral defects of 3 mm were created in 11-week-old diabetic ZDF fa/fa and nondiabetic ZDF +/+ rats and stabilized by an internal plate. Saline or 25 mg/kg Scl-AbVI was administered subcutaneously (s.c.) twice weekly for 12 weeks (n = 9-10/group). Bone mass and strength were assessed using pQCT, micro-computed tomography (µCT), and biomechanical testing. Bone histomorphometry was used to assess bone formation, and the filling of the bone defect was analyzed by µCT. Diabetic rats displayed lower spinal and femoral bone mass compared to nondiabetic rats, and Scl-AbVI treatment significantly enhanced bone mass of the femur and the spine of diabetic rats (p < 0.0001). Scl-AbVI also reversed the deficit in bone strength in the diabetic rats, with 65% and 89% increases in maximum load at the femoral shaft and neck, respectively (p < 0.0001). The lower bone mass in diabetic rats was associated with a 65% decrease in vertebral bone formation rate, which Scl-AbVI increased by sixfold, consistent with a pronounced anabolic effect. Nondiabetic rats filled 57% of the femoral defect, whereas diabetic rats filled only 21% (p < 0.05). Scl-AbVI treatment increased defect regeneration by 47% and 74%, respectively (p < 0.05). Sclerostin antibody treatment reverses the adverse effects of type 2 diabetes mellitus on bone mass and strength, and improves bone defect regeneration in rats.

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.