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The increased use of transgenic mice as experimental animals provides new opportunities to study the biology of fracture repair. We have developed a technique for the production of a standard closed experimental fracture in the mouse tibia. A 0.2 mm stainless-steel rod was introduced into the medullary cavity and the pre-nailed tibial shaft was fractured by an impact device, which resulted in a reproducible transverse or slightly oblique fracture pattern. The intramedullary rod maintained axial alignment, and the fractures united without displacement. On the basis of measurements of callus geometry, four-point bending tests, biochemical analyses, and quantitative histology, the progress of callus formation and remodeling occurred in a predictable sequence of healing phases. The ultimate bending loads of the fractures increased with time, reaching 74% of the strength of intact control tibias in 4 weeks. The stiffness values of the fractures returned to normal levels and, as determined radiographically, the fractures united by external callus in 4 weeks. Radiographically, callus size, cross-sectional callus area, and callus mass peaked at 2 weeks and decreased thereafter, indicating the start of external remodeling. Histologically, the amount of mesenchymal tissue was maximal at days 5 and 7. The callus cartilage area peaked at day 9; at its maximum, it accounted for 46% of the total callus area. Early periosteal formation of membranous new bone, followed by endochondral ossification, resulted in a linear increase of callus bone during the healing process. The healing sequence of the mouse tibial fracture was similar to that seen in the rat tibia.(ABSTRACT TRUNCATED AT 250 WORDS)

Background and purpose Immediate implant stability is a key factor for success in cementless total hip arthroplasty (THA). Low bone mineral density (BMD) and age-related geometric changes of the proximal femur may jeopardize initial stability and osseointegration. We compared migration of hydroxyapatite-coated femoral stems in women with or without low systemic BMD.Patients and methods 61 female patients with hip osteoarthritis were treated with cementless THA with anatomically designed hydroxyapatite-coated femoral stems and ceramic-ceramic bearing surfaces (ABG-II). Of the 39 eligible patients between the ages of 41 and 78 years, 12 had normal systemic BMD and 27 had osteopenia or osteoporosis. According to the Dorr classification, 21 had type A bone and 18 had type B. Translational and rotational migration of the stems was evaluated with radiostereometric analysis (RSA) up to 2 years after surgery.Results Patients with low systemic BMD showed higher subsidence of the femoral stem during the first 3 months after surgery than did those with normal BMD (difference = 0.6, 95% CI: 0.1–1.1; p = 0.03). Low systemic BMD (odds ratio (OR) = 0.1, CI: 0.006–1.0; p = 0.02), low local hip BMD (OR = 0.3, CI: 0.1–0.7; p = 0.005) and ageing (OR = 1.1, CI: 1.0–1.2; p = 0.02) were risk factors for delayed translational stability. Ageing and low canal flare index were risk factors for delayed rotational stabilization (OR = 3, CI: 1.1–9; p = 0.04 and OR = 1.1, CI: 1.0–1.2; p = 0.02, respectively). Harris hip score and WOMAC score were similar in patients with normal systemic BMD and low systemic BMD.Interpretation Low BMD, changes in intraosseous dimensions of the proximal femur, and ageing adversely affected initial stability and delayed osseointegration of cementless stems in women.

The optimal pore size for bone ingrowth is claimed to be 100-400 microm. With the use of a highly standardized experimental model, the present study reevaluated whether a pore size of 100 microm is the threshold value for bone ingrowth into porous structures under non-load-bearing conditions. Titanium triangle-shaped plates 250 or 500 microm thick were perforated with the use of a laser in order to create standard-sized holes ( 50, 75, 100, and 125 microm) in multiple rows. The amount of bone ingrowth through the implant holes was studied in the cancellous bone of the distal rabbit femur. Twelve weeks after implantation, detailed analysis of bone ingrowth was performed with computerized image analysis of backscattered electron imaging techniques of scanning electron microscopy. The results showed that the amount of ingrown new bone was independent of the pore size and implant thickness. The median value for bone ingrowth varied between 64 and 78%. A striking feature was the formation of secondary osteonal structures even in the smallest holes. Based on these results, there is no threshold value for new bone ingrowth in pore sizes ranging from 50 to 125 microm under non-load-bearing conditions.

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ABSTRACT:We examined the presence of circulating plastic adherent multipotent mesenchymal stem cells (MSCs) in fracture patients. Three patient groups (n = 10-18) were evaluated, including elderly females with a femoral neck fracture treated with cemented hemiarthroplasty, an age-and sex-matched group with hip osteoarthritis (OA) treated with cemented total hip arthroplasty (THA), and younger adults with surgically treated lower extremity fractures. The presence of circulating MSCs pre-and postoperatively was compared to bone marrow (BM) MSCs from the same subjects. Criteria for identifying MSCs included cell surface markers (CD105+, CD73+, CD90+, CD45−, CD14−), proliferation through several passages as well as osteogenic, chondrogenic, and adipogenic differentiation. Plastic adherent MSCs were found in peripheral blood (PB) from 22% of hip fracture patients, 46% of younger fracture patients, and in none of 63 pre-and postmenopausal women with hip OA. When detectable, circulating MSCs appeared between 39 and 101 h after fracture. PB derived MSCs did not differ from BM derived MSCs, except for a small population (<15%) of CD34+ cells among PB derived MSCs. This initial study indicates mobilization of MSCs into the circulation in response to fracture, even in very old patients, while circulating MSCs were not detectable before or after elective THA.

Bone grafting procedures are undergoing a major shift from autologous and allogeneic bone grafts to synthetic bone graft substitutes. Bioactive glasses are a group of synthetic silica-based bioactive materials with bone bonding properties first discovered by Larry Hench. They have several unique properties compared with other synthetic bioresorbable bioactive ceramics, such as calcium phosphates, hydroxyapatite (HA) and tricalcium phosphate (TCP). Bioactive glasses have different rates of bioactivity and resorption rates depending on their chemical compositions. The critical feature for the rate of bioactivity is a SiO 2 content <60% in weight. In vivo, the material is highly osteoconductive and it seems to promote the growth of new bone on its surface. In a recent study, the activity of the material was found even to overshadow the effect of BMP-2 gene therapy. In vivo, there is a dynamic balance between intramedullary bone formation and bioactive glass resorption. Recent studies of molecular biology have shown that bioactive glass induces a high local turnover of bone formation and resorption. Many osteoporotic fracture patients are candidates for concurrent treatment with bisphosphonates and bioceramic bone graft substitutes. Since osteopromotive silicabased bioactive glasses induce accelerated local bone turnover, adjunct antiresorptive agents may affect the process. However, a recent study showed that an adjunct antiresorptive therapy (zoledronic acid) is even beneficial for bone incorporation of bioactive glass. Based on these observations, bioactive glasses are a promising group of unique biomaterials to act as bone graft substitutes.