[Three-dimensional architecture of intraosseous vascular anatomy of the hamate: a micro-computed tomography study].

OBJECTIVE: To obtain three-dimensional intraosseous artery of the hamate and to provide the vascular anatomy basis of hamate fracture fixation. METHODS: PbO (lead monoxide, Sinopharm Chemical Reagent Beijing Co. Ltd) was ground into particles less than 40 µm and suspended in turpentine oil (Chemical Reagent Beijing Co. Ltd) at ratios of 1 g : 1.5 mL, 1 g : 1 mL and 1 g : 0.5 mL. Three specimens were investigated. Brachial arteries were cannulated and perfused with lead-based contrast agent. Hamates were harvested and scanned using micro-computed tomography (microCT). The acquisition protocols were as follows: CT scan setup: total rotation [Degrees], 360; rotation steps, 360; X-ray detector setup: transaxial, 2048; axial, 2048; exposure time, 1 500 ms, Binning, 1; system magnification: high-med. X-ray tube setup: 80 kV, 500 mA current. The down-sampling factor used in the reconstruction was 2. The effective voxel size of the final image was 27.30 µm. The three-dimensional model of the hamate was generated and the distribution and pattern of vessels were evaluated. RESULTS: There were abundant extraosseous vessels around the hamate. They were mainly running in the tendons and ligaments around the hamate. Four vascular zones were identified on the hamate surface. They were on the palmar platform of the hamate body, on the dorsal side, on the ulnar side and on the tip of hamulus, namely. There were anastomoses among 4 vascular zones. We did not observe any vessels penetrating through the articular cartilage. The extraosseous vessels of the vascular zones gave a number of intraosseous branches into the hamate. The hamate body received intraosseous blood supply from the dorsal, palmar and ulnar while the hamulus from the palmar, ulnar and hamulus tip. There were some intraosseous branches anastomosing with each other. CONCLUSION: The extraosseous and intraosseous vessels of the hamate were more than what used to be considered. The hamate body and hamulus received blood supply from multiple directions and arteries anastomosed extensively both outside and inside the hamate, making it possible that the intraosseous perfusion survived after fracture. It is likely that the nonunion after the hamate fracture is not caused by the vascular damage but the malalignment of the fragments.

Intraosseous Injection of Simvastatin in Poloxamer 407 Hydrogel Improves Pedicle-Screw Fixation in Ovariectomized Minipigs.

BACKGROUND: Osteoporosis leads to poor osseointegration and reduces implant stability. Statins have been found to stimulate bone formation, but the bioavailability from oral administration is low. Local application may be more effective at augmenting bone formation and enhancing implant stability. This study was performed to evaluate the efficacy of an intraosseous injection of simvastatin in thermosensitive poloxamer 407 hydrogel to enhance pedicle-screw fixation in calcium-restricted ovariectomized minipigs. METHODS: Nine mature female Guangxi Bama minipigs underwent bilateral ovariectomy and were fed a calcium-restricted diet for 18 months. Simvastatin (0, 0.5, or 1 mg) in thermosensitive poloxamer 407 hydrogel was injected into the lumbar vertebrae (L4-L6), and titanium alloy pedicle screws were implanted. Bone mineral density (BMD) measurements of the lumbar vertebrae were determined by dual x-ray absorptiometry (DXA) before and 3 months after treatment. The lumbar vertebrae were harvested and analyzed with use of microcomputed tomography, biomechanical pull-out testing, histological analysis, and Western blot analysis for bone morphogenetic protein (BMP)-2 and vascular endothelial growth factor (VEGF) expression. RESULTS: Evaluation over a 3-month study period demonstrated that the BMD of the vertebrae injected with 0.5 and 1.0 mg of simvastatin had increased by 31.25% and 31.09%, respectively, compared with vehicle-only injection (p ≤ 0.00014 for both) and increased by 32.12% and 28.16%, respectively, compared with the pre-treatment levels (p < 0.0001 for both). A single injection of simvastatin in poloxamer 407 increased trabecular volume fraction, thickness, and number and decreased trabecular separation (p ≤ 0.002). The bone formation and mineral apposition rates significantly increased (p ≤ 0.023). The percentage of osseointegration in the simvastatin 0.5 and 1-mg groups was 46.54% and 42.63% greater, respectively, than that in the vehicle-only group (p ≤ 0.006), and the maximum pull-out strength was 45.75% and 51.53% greater, respectively, than in the vehicle-only group (p ≤ 0.0005). BMP-2 and VEGF expressions were higher than for the vehicle-only injection. CONCLUSIONS: A single intraosseous injection of simvastatin in thermosensitive poloxamer 407 hydrogel stimulated bone formation, increased BMD, improved bone microstructure, promoted osseointegration, and significantly enhanced the stability of pedicle screws in calcium-restricted ovariectomized minipigs. CLINICAL RELEVANCE: These results provide rationale for evaluating intraosseous injection of simvastatin in poloxamer 407 to enhance implant fixation in patients with osteoporosis.

A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs.

UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.