What are the predictors and prevalence of pseudotumor and elevated metal ions after large-diameter metal-on-metal THA?

BACKGROUND: Soft tissue masses, or "pseudotumors," around metal-on-metal total hip arthroplasty (MoM THA) have been reported frequently; however, their prevalence remains unknown. Several risk factors, including elevated metal ion levels, have been associated with the presence of pseudotumor, although this remains controversial. QUESTIONS/PURPOSES: The goals of this study were to (1) determine the prevalence of pseudotumors after large-diameter head MoM THA; (2) identify risk factors associated with pseudotumor formation and elevated metal ion levels; and (3) determine the early failure rate of large-diameter MoM THA. METHODS: Between December 2005 and November 2012, 258 hips (215 patients) underwent large-diameter head primary MoM THA at our institution. Clinical followup was obtained in 235 hips (91%). Using an inclusion criteria of a minimum followup of 1 year, a subset of 191 hips (mean followup, 4 years; range, 1-7 years) was recruited for high-resolution ultrasound screening for the presence of pseudotumor. Whole blood cobalt and chromium ion levels, UCLA activity level, WOMAC score, patient demographics as well as surgical, implant, and radiographic data were collected. Bivariate correlations and multivariate log-linear regression models were used to compare the presence of pseudotumor and elevated metal ions with all other factors. RESULTS: Ultrasound detected a solid, cystic, or mixed mass in 20% hips (38 of 191). No correlation was found between the presence of pseudotumor and any risk factor that we examined. After controlling for confounding variables, elevated cobalt ions were correlated (p<0.001, R=0.50, R2=0.25) with smaller femoral head size, the presence of bilateral MoM THA, and female sex. Elevated chromium ions were correlated (p<0.001, R=0.59, R2=0.34) with smaller femoral head size, presence of bilateral MoM THA, and lower body mass index. The overall survival of MoM THA was 96% at a mean followup of 4.5 years (range, 2-8 years). CONCLUSIONS: With the numbers available, we found no associations between the presence of pseudotumor and the potential risk factors we analyzed, including elevated metal ion levels. Further work is needed to explain why larger femoral head sizes resulted in lower metal ion levels despite being associated with higher early failure rates in joint registry data. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression to diabetes and response to troglitazone.

CONTEXT: The common P12A polymorphism in PPARG (a target for thiazolidinedione medications) has been consistently associated with type 2 diabetes. OBJECTIVE: We examined whether PPARG P12A affects progression from impaired glucose tolerance to diabetes, or responses to preventive interventions (lifestyle, metformin, or troglitazone vs. placebo). PATIENTS: This study included 3548 Diabetes Prevention Program participants. DESIGN: We performed Cox regression analysis using genotype at PPARG P12A, intervention, and their interactions as predictors of diabetes incidence. We also genotyped five other PPARG variants implicated in the response to troglitazone and assessed their effect on insulin sensitivity at 1 yr. RESULTS: Consistent with prior cross-sectional studies, P/P homozygotes at PPARG P12A appeared more likely to develop diabetes than alanine carriers (hazard ratio, 1.24; 95% confidence interval, 0.99-1.57; P=0.07) with no interaction of genotype with intervention. There was a significant interaction of genotype with body mass index and waist circumference (P=0.03 and 0.002, respectively) with the alanine allele conferring less protection in more obese individuals. Neither PPARG P12A nor five other variants significantly affected the impact of troglitazone on insulin sensitivity in 340 participants at 1 yr. CONCLUSIONS: The proline allele at PPARG P12A increases risk for diabetes in persons with impaired glucose tolerance, an effect modified by body mass index. In addition, PPARG P12A has little or no effect on the beneficial response to troglitazone.

TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program.

BACKGROUND: Common polymorphisms of the transcription factor 7-like 2 gene (TCF7L2) have recently been associated with type 2 diabetes. We examined whether the two most strongly associated variants (rs12255372 and rs7903146) predict the progression to diabetes in persons with impaired glucose tolerance who were enrolled in the Diabetes Prevention Program, in which lifestyle intervention or treatment with metformin was compared with placebo. METHODS: We genotyped these variants in 3548 participants and performed Cox regression analysis using genotype, intervention, and their interactions as predictors. We assessed the effect of genotype on measures of insulin secretion and insulin sensitivity at baseline and at one year. RESULTS: Over an average period of three years, participants with the risk-conferring TT genotype at rs7903146 were more likely to have progression from impaired glucose tolerance to diabetes than were CC homozygotes (hazard ratio, 1.55; 95 percent confidence interval, 1.20 to 2.01; P<0.001). The effect of genotype was stronger in the placebo group (hazard ratio, 1.81; 95 percent confidence interval, 1.21 to 2.70; P=0.004) than in the metformin and lifestyle-intervention groups (hazard ratios, 1.62 and 1.15, respectively; P for the interaction between genotype and intervention not significant). The TT genotype was associated with decreased insulin secretion but not increased insulin resistance at baseline. Similar results were obtained for rs12255372. CONCLUSIONS: Common variants in TCF7L2 seem to be associated with an increased risk of diabetes among persons with impaired glucose tolerance. The risk-conferring genotypes in TCF7L2 are associated with impaired beta-cell function but not with insulin resistance. (ClinicalTrials.gov number, NCT00004992. [ClinicalTrials.gov]).