Soluble transforming growth factor-␤ (TGF-␤)/bone morphogenetic protein (BMP)-binding proteins are widely distributed in mammalian tissues and control cytokine access to membrane signaling receptors. The serum and bone-resident glycoprotein ␣2-HS-glycoprotein/fetuin (ASHG) binds to TGF-␤/BMP cytokines and blocks TGF-␤1 binding to cell surface receptors. Therefore, we examined bone growth and remodeling phenotypes in ASHG-deficient mice. The skeletal structure of Ahsg ؊/؊ mice appeared normal at birth, but abnormalities were observed in adult Ahsg ؊/؊ mice. Maturation of growth plate chondrocytes was impaired, and femurs lengthened more slowly between 3 and 18 months of age in Ahsg ؊/؊ mice. However, bone formation was increased in Ahsg ؊/؊ mice as indicated by greater cortical thickness, accelerated trabecular bone remodeling, and increased osteoblast numbers on bone surfaces. The normal age-related increase in cortical thickness and bone mineral density was accelerated in Ahsg ؊/؊ mice and was associated with increased energy required to fracture. Bone formation in response to implanted BMP cytokine extended further from the implant in Ahsg ؊/؊ compared with Ahsg ؉/؉ mice, confirming the interaction between ASHG and TGF-␤/BMP cytokines in vivo. Our results demonstrate that ASHG blocks TGF-␤-dependent signaling in osteoblastic cells, and mice lacking ASHG display growth plate defects, increased bone formation with age, and enhanced cytokine-dependent osteogenesis.

The purpose of this study was to compare extraction socket healing in 8 patients after implantation with either xenogenic bovine bone (n = 5 sites), demineralized freeze‐dried bone (DFDBA) (n = 3 sites), autologous bone (n = 3 sites), or human bone morphogenetic proteins in an osteocalcein/osteonectin carrier (hBMP/NCP) (n = 2 sites). Three of the patients received 6 commercially pure micro screws which were fixed into extraction sockets, after which the sockets were implanted with either bovine bone (n = 3 sites), DFDBA (n = 2 sites) or intraoral autologous bone (n = 1 site). Biopsies of the extraction sockets were taken from 3 to 6 months after treatment (average, 4.6 months). For comparison of healing between the implanted materials, histologie evaluation and bone scores were determined. Bone scores of 0 indicated an absence of new bone, with dead implanted bone particles entrapped within connective tissue, while a score of 3 indicated the entire field consisted of vital bone. Biopsies from bovine bone sockets revealed dead implanted particles surrounded by connective tissue. Isolated sections showed host bone in contact with the bovine bone particles. Bone scores ranged from 0 to 3. Biopsies from DFDBA‐implanted sites revealed dead particles entrapped with dense connective tissue. The bone scores ranged from 0 to 1. Biopsies from sites implanted with hBMP/NCP revealed a combination of woven and lamellar bone with bone scores of 3. Five of the 6 micro screws were processed and evaluated. One screw was mobile at the time of removal and was not evaluated. Bone scores were used to compare new bone formation adjacent to the micro screws. Bone scores ranged from 0 to 2. A score of 0 indicated non‐vital implant material in contact with host bone and connective tissue in contact with implant; 2 indicated vital bone in contact with the majority of the implant surface. Retrieved sockets with micro screws implanted with bovine bone (n = 2) demonstrated a connective tissue interface between the screws and the surrounding tissues (bone score 0). The adjacent tissues showed dead bovine particles entrapped within fibrous tissue. Retrieved screws implanted with DFDBA (n = 2) were surrounded by connective tissue, with dead bone particles enmeshed within fibrous tissue (bone score 0). The screw implanted with intra‐oral autologous bone was primarily surrounded by vital bone with a connective tissue interface (bone score 1). Three implant threads were in contact with bone. The results of this study indicate that bovine bone, DFDBA, and intraoral autologous bone do not promote extraction socket healing. Sockets implanted with hBMP/NCP contained vital woven and lamellar bone. Xenogenic bovine bone and DFDBA did not contribute to bone to micro screw contacts and are not recommended for enhancement of vital bone to implant contacts. Intraoral autogenous bone also does not appear to significantly contribute to bone to implant contacts. Intraoral autologous bone, xenogenic bone, and DFDBA appear to interfere with normal extraction so...

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%–12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

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The utilization of a demineralized bone matrix putty appeared to allow for complete closure of critical sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks.