Kentaro Iwakiri

Effect of simvastatin on steroid-induced osteonecrosis evidenced by the serum lipid level and hepatic cytochrome P4503A in a rabbit model

ObjectiveThis study was designed to investigate the efficacy of lipid-lowering agents in preventing steroid-induced osteonecrosis and the mechanism by which they do so in a rabbit model.MethodsFemale Japanese white rabbits were randomly allocated to receive probucol (group P), pravastatin (group PS), simvastatin (group SS), or saline (group C) for 6 weeks (n = 15 in groups P, PS, and SS; n = 30 in group C). Methylprednisolone (20 mg/kg) was injected at 3 weeks after starting treatment, and the femurs were histologically examined bilaterally 3 weeks after methylprednisolone injection. Midazolam clearance was measured before treatment and before methylprednisolone injection to determine hepatic cytochrome P4503A (CYP3A) levels.ResultsThe incidence of osteonecrosis in the proximal metaphysis of the femurs in groups PS and SS was significantly lower than in group C (P < 0.05 and P < 0.0001, respectively), whereas it did not differ between groups P and C. It was significantly lower in group SS than in group PS (P < 0.05). Plasma concentrations of lipids (low-density lipoprotein, triglyceride, free fatty acid, and total cholesterol) in groups P, PS, and SS were significantly lower than in group C; and hepatic CYP3A levels were significantly higher in group SS than in groups P or PS after treatment (P < 0.005 for both).ConclusionsSimvastatin and pravastatin significantly reduced the incidence of steroid-induced osteonecrosis in rabbits. Simvastatin was more effective in reducing the incidence of the disease, and increased CYP3A activity is a possible mechanism for this effect.

Low hepatic cytochrome P450 3A activity is a risk for corticosteroid-induced osteonecrosis

Osteonecrosis of the femoral head (ONFH) is one of the major side effects of corticosteroid therapy. Because corticosteroids are metabolized by hepatic cytochrome P450 (CYP) 3A, a low endogenous activity of this enzyme may contribute to the pathogenesis of ONFH. The purpose of this study was to examine the possible association of hepatic CYP3A activity and the susceptibility to ONFH in patients treated with corticosteroids.

In vivo comparison of wear particles between highly crosslinked polyethylene and conventional polyethylene in the same design of total knee arthroplasties

Reduction of wear with highly crosslinked polyethylene (HXLPE) has been reported in in vitro and in vivo studies of total hip prostheses. However, use of HXLPE in total knee prostheses is still controversial. The aim of this study was to compare in vivo polyethylene wear particle generation of HXLPE with that of conventional polyethylene in total knee prostheses of the same design. Synovial fluid was obtained from four knees with HXLPE inserts and three knees with conventional polyethylene inserts at 1 year after operation. Polyethylene particles were isolated and examined using a scanning electron microscope and image analyzer. The total number of particles in each knee was 0.28 +/- 0.12 x 10(6) in HXPLE group (mean +/- standard error) and 6.87 +/- 2.85 x 10(6) in conventional polyethylene group (p = 0.040). Particle size (equivalent circle diameter) was 0.64 +/- 0.07 microm in HXPLE group and 1.21 +/- 0.21 microm in conventional polyethylene group (p = 0.030). Particle shape (aspect ratio) was 1.33 +/- 0.10 in HXLPE and 1.88 +/- 0.19 in conventional polyethylene (p = 0.035). Thepercentage of particles of submicron size was greater than 90% in HXLPE group and 55% in conventional polyethylene group. Except for the material of the polyethylene insert, the design and material of prostheses were completely the same in both groups. The HXLPE insert generated fewer, smaller, and rounder polyethylene wear particles than the conventional polyethylene insert in the early stage after surgery.

Early Biological Fixation of Porous Implant Coated With Paste-Retaining Recombinant Bone Morphogenetic Protein 2

The aim of this study was to evaluate the period required for stable initial bone-implant fixation with recombinant human bone morphogenetic protein 2 (rhBMP-2) in the bone marrow of a rabbit model. The porous implants being coated with β-tricalcium phosphate/polylactide-polyethylene glycol paste with 15, 30, or 60 μg of rhBMP-2 (n = 10) were implanted into animals in 3 experimental groups. In 2 control groups, the test implants were coated without rhBMP or no paste. In all groups, the implant was inserted for 3 and 6 weeks. At 3 weeks after implantation, the BMP-treated implants in the 2 lower dose groups had significantly more bone ingrowth to the implant surface than did the control groups, and the greatest effect occurred in the 30-μg rhBMP-2 group animals.

Waterless Hand Rub Versus Traditional Hand Scrub Methods for Preventing the Surgical Site Infection in Orthopedic Surgery

Study Design. A retrospective cohort study with prospectively collected data. Objective. The aim of this study was to compare SSI incidences, the cost of hand hygiene agents, and hand hygiene time between the traditional hand scrub and the waterless hand rub protocols before orthopedic surgery. Summary of Background Data. Surgical site infections (SSI) prolong hospitalization and are a leading nosocomial cause of morbidity and a source of excess cost. Recently, a waterless hand rub protocol comprising alcohol based chlorhexidine gluconate for use before surgery was developed, but no studies have yet examined its utility in orthopedic surgery. Methods. Fourteen hundred consecutive patients who underwent orthopedic surgery (spine, joint replacement, hand, and trauma surgeries) in our hospital since April 1, 2012 were included. A total of 712 cases underwent following traditional hand scrub between April 1, 2012 and April 30, 2013 and 688 cases underwent following waterless hand rub between June 1, 2013 and April 30, 2014. We compared SSI incidences within all and each subcategory between two hand hygiene protocols. All patients were screened for SSI within 1 year after surgery. We compared the cost of hand hygiene agents and hand hygiene time between two groups. Results. The SSI incidences were 1.3% (9 of 712) following the traditional protocol (2 deep and 7 superficial infections) and 1.1% (8 of 688) following the waterless protocol (all superficial infections). There were no significant differences between the two groups. The costs of liquids used for one hand hygiene were about

Increased hepatic cytochrome P4503A activity decreases the risk of developing steroid-induced osteonecrosis in a rabbit model.

2 for traditional hand scrub and less than

Wear particle analysis of highly crosslinked polyethylene isolated from a failed total hip arthroplasty

1 for waterless hand rub. The mean hand hygiene time was 264 seconds with the traditional protocol and 160 seconds with the waterless protocol. Conclusion. Waterless hand rub with an alcohol based chlorhexidine gluconate solution can be a safe, quick, and cost-effective alternative to traditional hand scrub. Level of Evidence: 3