Kang Pengde

Lovastatin inhibits adipogenesis and prevents osteonecrosis in steroid-treated rabbits

OBJECTIVES To investigate in vivo effects of lovastatin on inhibition of adipogenesis, an important mechanism of steroid-induced osteonecrosis, and on prevention of occurrence of steroid-induced osteonecrosis in rabbits. METHODS Fifty-four rabbits were intramuscularly injected once with 20mg/kg of methylprednisolone acetate (MPSL). Then, they were divided into two groups: lovastatin was given in Group I and placebo was given in Group II. And another 16 rabbits were injected with physiologic saline (PS) as a control (Group III). Hematological examination was performed for serum lipid levels. Both the femora and the humeri were histopathologically examined for the presence of osteonecrosis before the injection and 1, 2, 4 and 12 weeks after the injection. RESULTS The serum lipid levels were significantly higher in Group II than in Groups I and III 1, 2 and 4 weeks after the injection. The incidence of osteonecrosis was significantly higher in Group II (69%) than in Group I (36%) and Group III (0%). Pathological examination showed less serious adipogenesis and bone death in Group I than in Group II. The size and area of the fat cells in the bone marrow were significantly smaller in Group I (47.5+/-1.3 microm, 25%) and Group III (41.7+/-1.6 microm, 12%) than in Group II (59.8+/-6.3 microm, 51%) (P< 0.001). CONCLUSION Lovastatin can prevent development of steroid-induced osteonecrosis in rabbits by inhibiting adipogenesis. Future evaluation on the effectiveness of lovastatin in the clinical practice is still necessary.

Tranexamic Acid Administration in Primary Total Hip Arthroplasty: A Randomized Controlled Trial of Intravenous Combined with Topical Versus Single-dose Intravenous Administration

BACKGROUND The use of tranexamic acid (TXA) in primary total hip arthroplasty is well documented. However, considering the potential side effects, including deep vein thrombosis and pulmonary embolism, the ideal method of providing TXA to patients undergoing total hip arthroplasty remains controversial. The objective of this trial was to assess the efficacy and safety of intravenous (IV) administration combined with topical administration of TXA regarding postoperative blood loss and transfusion rates in patients treated with primary unilateral total hip arthroplasty. METHODS In this prospective, randomized controlled trial, 150 patients were divided into three groups: the combined group (IV administration of 15 mg/kg of TXA combined with topical administration of 1 g/100 mL of TXA), the single IV group (IV administration of 15 mg/kg of TXA), and the placebo group. The primary outcomes included blood-loss variables (total, intraoperative, and drainage blood loss; changes in hemoglobin, hematocrit, and platelet concentration; and amount of IV transfusion fluid) and transfusion values (frequency of transfusion and number of transfused blood units). The secondary outcomes included the length of the hospital stay, range of hip motion, Harris hip score, and prevalences of deep vein thrombosis and pulmonary embolism. RESULTS The total blood loss in the combined group (mean and standard deviation, 835.49 ± 343.50 mL) was significantly reduced (p < 0.05) in comparison with that in the single IV group (1002.62 ± 366.85 mL) and placebo group (1221.11 ± 386.25 mL). The combined group also had fewer transfusions in comparison with the single IV and placebo groups (1, 8, and 19, respectively; p < 0.05). There was no difference among the 3 groups with regard to the rates of deep vein thrombosis or pulmonary embolism. CONCLUSIONS Intravenous combined with topical administration of TXA in patients undergoing a primary unilateral total hip arthroplasty significantly reduced postoperative bleeding and the transfusion rate. Studies with more patients and longer follow-up are needed to confirm whether this promising combined strategy is safe with regard to thromboembolic complications. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

No Decreased Infection Rate When Using Antibiotic-Impregnated Cement in Primary Total Joint Arthroplasty

There has been much debate and controversy about the routine use of antibiotic-impregnated bone cement in primary total joint arthroplasty. The purpose of this study was to undertake a meta-analysis to determine whether the use of antibiotic-impregnated bone cement would reduce the incidence of infection after primary total joint arthroplasty. Of 313 citations identified for screening, 6 trials reporting 26,791 patients were eligible for data extraction and meta-analysis. The authors found no statistically significant difference between antibiotic-impregnated bone cement and plain bone cement in terms of the incidence of infection. The results indicated that the use of antibiotic-impregnated bone cement in primary total joint arthroplasty did not lead to a decrease in the rate of infection.

Efficiency of Cell Therapy to GC-Induced ONFH: BMSCs with Dkk-1 Interference Is Not Superior to Unmodified BMSCs

Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a hip disorder, and it threatens patients who require megadose of steroid therapies. Nowadays, no valid therapies can reverse the development of GC-induced ONFH once it occurs. Stem cell therapy to GC-induced ONFH would be a promising choice. Although the pathogenesis of GC-induced ONFH is not yet fully clear, Dickkopf-1 (Dkk-1) upregulated by excessive GC use, which hinders the canonical Wnt pathway, could be an explanation. Thus, the aim of the present work lies in investigating the efficiency of the allograft bone marrow stem cells (BMSCs) with Dkk-1 interference in preventing the progression of the GC-induced ONFH. Lentivirus-meditated Dkk-1 RNAi was introduced into BMSCs which was exposed to dexamethasone (10−6 mol/L) in vitro. This interference blocked Dkk-1 overexpression by GC and afterwards prompted the transduction of Wnt/β-catenin in which the Runx2 and PPARγ were upregulated and downregulated, respectively. Thus, the osteogenesis was promoted while adipogenesis was inhibited. In vivo, GC-induced ONFH rats were treated by allotransplantation of BMSCs with Dkk-1 interference, and the progression of the disease was prevented. However, the effects were not significantly superior to treatment with nongenetically modified or normal BMSCs.