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Peter G Whang

Publications and source records attributed to Peter G Whang.

5 recordsLinked to original sources

The effects of RANK blockade and osteoclast depletion in a model of pure osteoblastic prostate cancer metastasis in bone.

Adenocarcinoma of the prostate exhibits a clear propensity for bone and is associated with the formation of osteoblastic metastases. It has previously been suggested that osteoclast activity may be necessary for the development of these osteoblastic metastases based on data from lytic and mixed lytic-blastic tumors. Here we investigate the effects of complete in vivo osteoclast depletion via the blockade of receptor activator of NF:kappaB (RANK) on the establishment and progression of purely osteoblastic (LAPC-9 cells) bone lesions induced by human prostate cancer cells using a SCID mouse intratibial injection model. The subcutaneous administration of the RANK antagonist (15 mg/kg) RANK:Fc did not prevent the formation of purely osteoblastic lesions, indicating that osteoclasts may not be essential to the initial development of osteoblastic metastases. However, RANK:Fc protein appeared to inhibit the progression of established osteoblastic lesions, suggesting that osteoclasts may be involved in the subsequent growth of these tumors once they are already present. In contrast, RANK:Fc treatment effectively blocked the establishment and progression of purely osteolytic lesions formed by PC-3 cells, which served as a positive control. These results indicate that in vivo RANK blockade may not be effective for the prevention of osteoblastic metastasis but may potentially represent a novel therapy that limits the growth of established metastatic CaP lesions in bone.

Animals↗

Osteoinductivity of commercially available demineralized bone matrix. Preparations in a spine fusion model.

BACKGROUND: Although autogenous bone is the most widely used graft material for spinal fusion, demineralized bone matrix preparations are available as alternatives or supplements to autograft. They are prepared by acid extraction of most of the mineralized component, with retention of the collagen and noncollagenous proteins, including growth factors. Differences in allograft processing methods among suppliers might yield products with different osteoinductive activities. The purpose of this study was to compare the efficacy of three different commercially available demineralized bone matrix products for inducing spinal fusion in an athymic rat model. METHODS: Sixty male athymic rats underwent spinal fusion and were divided into three groups of eighteen animals each. Group I received Grafton Putty; Group II, DBX Putty; and Group III, AlloMatrix Injectable Putty. A control group of six animals (Group IV) underwent decortication alone. Six animals from each of the three experimental groups were killed at each of three intervals (two, four, and eight weeks), and the six animals from the control group were killed at eight weeks. At each of the time-points, radiographic and histologic analysis and manual testing of the explanted spines were performed. RESULTS: The spines in Group I demonstrated higher rates of radiographically evident fusion at eight weeks than did the spines in Group III or Group IV (p < 0.05). Manual testing of the spines at four weeks revealed variable fusion rates (five of six in Group I, two of six in Group II, and none of six in Group III). At eight weeks, all six spines in Group I, three of the six in Group II, and no spine in Group III or IV had fused. Histologic analysis of the spines in Groups I, II, and III demonstrated varying amounts of residual demineralized bone matrix and new bone formation. Group-I spines demonstrated the most new bone formation. CONCLUSIONS: This study demonstrated differences in the osteoinductive potentials of commercially available demineralized bone matrices in this animal model.

Animals↗

Extended-duration low-molecular-weight heparin prophylaxis following total joint arthroplasty.

Patients undergoing total joint arthroplasty are predisposed to the development of venous thromboembolic disease, including deep venous thrombosis and pulmonary embolism. Despite a standard course of postoperative prophylaxis, orthopedic patients remain at significant risk for late venous thromboembolic complications, resulting in considerable morbidity and mortality. Since routine screening for asymptomatic deep venous thrombosis with duplex ultrasound has not been found to be effective, the practice of extended out-of-hospital prophylaxis with low-molecular-weight heparin after total joint arthroplasty has been proposed in order to better protect these patients from delayed venous thromboembolic events. Multiple controlled, randomized clinical trials have shown that extended-duration low-molecular-weight heparin therapy significantly reduces the incidence of asymptomatic venous thromboembolic events following total hip arthroplasty, although no similar benefit has been observed in patients undergoing total knee arthroplasty. There are currently no comparative studies assessing the efficacy of long-term venous thromboembolic prophylaxis with oral anti-coagulant agents. Extending low-molecular-weight heparin therapy is not associated with any increase in major bleeding complications, but it may result in more frequent minor bleeding episodes. In addition, the cost-effectiveness of prolonging low-molecular-weight heparin treatment has not yet been firmly established. Although there is evidence supporting the use of extended out-of-hospital low-molecular-weight heparin prophylaxis after total hip arthroplasty, this strategy has not gained widespread acceptance in North America because of concerns regarding its adverse effects, cost-effectiveness, and uncertain patient compliance. There is general agreement that prophylaxis is needed after hospital discharge, and a minimum of 10 to 14 days of prophylaxis has been shown to be both safe and effective. However, further studies are necessary to determine the optimal duration of treatment.

Anticoagulants↗