Effects of Nonsteroidal Anti-Inflammatory Drugs on Transforming Growth Factor-β Expression and Bioactivity in Rat Osteoblast-Enriched Cultures

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to suppress bone remodeling in normal and repaired bones. Our previous results indicated that ketorolac and indomethacin suppressed proliferation, stimulated early differentiation, and induced apoptosis in cultured osteoblasts. Transforming growth factor-b (TGF-b) has been reported to enhance proliferation, suppress differentiation, and prevent apoptosis in osteoblasts. We proposed that one pathway of NSAID effects on osteoblast function might be through inhibition of the expression and/or bioactivity of TGF-b in osteoblasts. We tested the effects of ketorolac and indomethacin on the expression of TGF-b1 mRNA and protein and the bioactivity of TGF-b in osteoblast-enriched cultures derived from fetal calvaria. The effects of prostaglandin E1 (PGE1) and PGE2 on TGF-b expression and bioactivity were also examined in order to understand more about the role of prostaglandins in osteoblast function. Simultaneously, we estimated whether these NSAID effects on osteoblasts were prostaglandin-related. The results showed that 24-hour treatments with both PGEs and theoretic therapeutic concentrations of ketorolac and indomethacin had no significant effects on the levels of either transcription or translation of TGF-b or the post-translational function of TGF-b in osteoblasts. These results suggest that NSAIDs do not affect osteoblast function through changes in TGF-b action in osteoblasts

Impact of National Health Insurance on the Survival Rate of Patients with Osteosarcoma In Taiwan: Review of 74 Patients

The 2-year survival rate for high-grade osteosarcoma was 46.9% before the introduction of National Health Insurance (NHI) in Taiwan on March 1, 1995, but increased to 73.8% after the implementation of NHI. The 5-year survival rate also increased, from 37.5% to 63.6%. Between May 1990 and May 2001, 74 patients with high-grade osteosarcoma were treated at our hospital. Median age was 17 years (range, 7-63 years). Inadequate surgical margins, poor histologic response to chemotherapy, advanced stage of disease, and incomplete treatment were strongly associated with poor prognosis. Before NHI, 10 patients had incomplete treatment, mainly because of unaffordable medical fees. After NHI, only three patients had incomplete treatment, due to personal reasons. Patient survival improved dramatically with advances in multiagent chemotherapy, but it was the NHI that enabled patients to complete expensive treatment courses, including preoperative neoadjuvant chemotherapy, limb-salvage surgery, and postoperative adjuvant chemotherapy. The NHI also improved the accessibility of medical care, with more patients presenting in the early stages of disease and, as a result, it not only improved survival rate but also increased the number of patients undergoing limb-salvage surgery. We concluded that the NHI significantly improved the survival rate for patients with osteosarcoma in Taiwan

Biomechanical investigation of dynamic hip screw and wire fixation on an unstable intertrochanteric fracture

Abstract Background Although use of a dynamic hip screw (DHS) for stable intertrochanteric hip fracture fixation has been successfully applied in fracture healing for more than 20 years, DHS fixation on unstable intertrochanteric fractures still has a high failure rate, especially in patients with osteoporosis. Although the wire fixation is usually incorporated with orthopedic device to treat fracture, the wiring techniques are developed through experiences. Thus, this study is objective to investigate the biomechanical property of different wire fixation methods incorporated with DHS system to provide the lesser trochanter fragment stable fixation on osteoporotic TypeA2.1 fracture for enhancing stability after bone reduction. Results Sawbone testing results demonstrated higher maximum load, stiffness, and energy in a DHS with wire fixation compared with DHS fixation only. In static biomechanical testing of a cadaver femur, we compared the stiffness of five fixation models and then tested a fatigue failure model in cycle loading with DHS fixation only. Wiring fixation can enhance stability and the cut-out failure model in the fatigue test was identical to the clinical failure model. Conclusions Lesser trochanteric fragment fixation is a crucial concern in the stability of an A2.1 unstable fracture, and the combination of a wiring technique with a DHS seems beneficial for achieving better stability. The addition of an antirotational greater trochanter is likely to enhance stability through wiring of the greater trochanter

Management Strategy for Unicameral Bone Cyst

The management of a unicameral bone cyst varies from percutaneous needle biopsy, aspiration, and local injection of steroid, autogenous bone marrow, or demineralized bone matrix to the more invasive surgical procedures of conventional curettage and grafting (with autogenous or allogenous bone) or subtotal resection with bone grafting. The best treatment for a unicameral bone cyst is yet to be identified. Better understanding of the pathology will change the concept of management. The aim of treatment is to prevent pathologic fracture, to promote cyst healing, and to avoid cyst recurrence and re-fracture. We retrospectively reviewed 17 cases of unicameral bone cysts (12 in the humerus, 3 in the femur, 2 in the fibula) managed by conservative observation, curettage and bone grafting with open reduction and internal fixation, or continuous decompression and drainage with a cannulated screw. We suggest percutaneous cannulated screw insertion to promote cyst healing and prevent pathologic fracture. We devised a protocol for the management of unicameral bone cysts

A novel single pulsed electromagnetic field stimulates osteogenesis of bone marrow mesenchymal stem cells and bone repair.

Pulsed electromagnetic field (PEMF) has been successfully applied to accelerate fracture repair since 1979. Recent studies suggest that PEMF might be used as a nonoperative treatment for the early stages of osteonecrosis. However, PEMF treatment requires a minimum of ten hours per day for the duration of the treatment. In this study, we modified the protocol of the single-pulsed electromagnetic field (SPEMF) that only requires a 3-minute daily treatment. In the in vitro study, cell proliferation and osteogenic differentiation was evaluated in the hBMSCs. In the in vivo study, new bone formation and revascularization were evaluated in the necrotic bone graft. Results from the in vitro study showed no significant cytotoxic effects on the hBMSCs after 5 days of SPEMF treatment (1 Tesla, 30 pulses per day). hBMSC proliferation was enhanced in the SPEMF-treated groups after 2 and 4 days of treatment. The osteogenic differentiation of hBMSCs was significantly increased in the SPEMF-treated groups after 3-7 days of treatment. Mineralization also increased after 10, 15, 20, and 25 days of treatment in SPEMF-treated groups compared to the control group. The 7-day short-course treatment achieved similar effects on proliferation and osteogenesis as the 25-day treatment. Results from the in vivo study also demonstrated that both the 7-day and 25-day treatments of SPEMF increased callus formation around the necrotic bone and also increased new vessel formation and osteocyte numbers in the grafted necrotic bone at the 2nd and 4th weeks after surgery. In conclusion, the newly developed SPEMF accelerates osteogenic differentiation of cultured hBMSCs and enhances bone repair, neo-vascularization, and cell growth in necrotic bone in mice. The potential clinical advantage of the SPEMF is the short daily application and the shorter treatment course. We suggest that SPEMF may be used to treat fractures and the early stages of osteonecrosis

Ethanol May Suppress Wnt/β-catenin Signaling on Human Bone Marrow Stroma Cells: A Preliminary Study

Ethanol and glucocorticoids are risk factors associated with osteonecrosis. Previous reports suggest ethanol and glucocorticoids induce adipogenesis, decrease osteogenesis in bone marrow stroma cells, and produce intracellular lipid deposits resulting in death of osteocytes. The Wnt/β-catenin signal pathway is involved in the regulation of homeostasis of bone and we presume glucocorticoids and ethanol may induce osteonecrosis in humans through a similar mechanism as in rodents. We hypothesized (1) ethanol, like glucocorticoids, decreases osteogenesis and increases adipogenesis through the Wnt/β-catenin signaling pathway in human bone marrow stromal cells; and (2) ethanol decreases intranuclear translocation of β-catenin. We found both dexamethasone and ethanol decrease the gene and protein expression of osteogenesis and increase that of adipogenesis through Wnt signaling-related genes by semiquantitative and quantitative polymerase chain reaction and Western blot. Ethanol hampered intranuclear translocation of β-catenin by immunofluorescence analysis. The data suggest the Wnt/β-catenin signaling pathway may be associated with ethanol-induced osteonecrosis