Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions. Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589

Introduction. Insufficient pain control following lower extremity surgery can increase length of stay, readmission rates, and impair postoperative outcome. It has been shown that CYP2D6 genotypes predict function of the enzyme responsible for conversion of hydrocodone to hydromorphone (active metabolite) and plasma concentration of hydromorphone best predicted analgesic response. Purpose of this study was to evaluate relationship of CYP2D6 genotypes, drug-drug interactions, and plasma drug concentrations in patients undergoing lower extremity surgery. Methods. A prospective cohort of 271 orthopedic patients undergoing lower extremity surgery including TKA, THA and trauma were queried. Patients treated with hydrocodone were enrolled and tested for plasma concentrations of hydrocodone and hydromorphone. CYP2D6 genotyping was performed. Medications co-administered with hydrocodone during perioperative and postoperative periods were queried. Results. Out of 271 patients enrolled, only 41 (15%) had detectable hydromorphone (i.e. >0.5 ng/mL). 86% were extensive (normal) metabolizers, 7% were intermediate metabolizers, 5% poor metabolizers and 2% were ultra rapid metabolizers. 179 subjects were not administered any inhibitors of CYP2D6 whereas 92 were on at least one inhibitor. 33 (18%) with no pharmacological inhibitors had detectable hydromorphone, whereas only 7 (7.6%) on inhibitors had hydromorphone detected above the lower limit of quantification (0.5ng/mL), p=0.033. Diphenhydramine, fluoxetine, hydralazine, duloxetine, bupropion and sertraline, were the most common CYP2D6 inhibitors co-administered with hydrocodone in this cohort. Conclusions. Patients' home medications and selection of various drugs in the postoperative setting could impact the pharmacokinetics and pharmacodynamics of hydrocodone leading to a diminished analgesic response. We conclude that health care providers should become familiar with the inhibitors of CYP2D6 to obtain the best response with the use of hydrocodone following lower extremity surgery. Additional work is required to determine the ideal opioid for an individual patient's genotype following lower extremity orthopedic surgery. For figures, tables, or references, please contact authors directly

Aims

The purpose of this study is to determine an individual’s age-specific prevalence of total knee arthroplasty (TKA) after cruciate ligament surgery, and to identify clinical and genetic risk factors associated with undergoing TKA.

Aims

The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury.

The rate of peri-prosthetic infection following total joint replacement continues to rise, and attempts to curb this trend have included the use of antibiotic-loaded bone cement at the time of primary surgery. We have investigated the clinical- and cost-effectiveness of the use of antibiotic-loaded cement for primary total knee replacement (TKR) by comparing the rate of infection in 3048 TKRs performed without loaded cement over a three-year period versus the incidence of infection after 4830 TKRs performed with tobramycin-loaded cement over a later period of time of a similar duration. In order to adjust for confounding factors, the rate of infection in 3347 and 4702 uncemented total hip replacements (THR) performed during the same time periods, respectively, was also examined. There were no significant differences in the characteristics of the patients in the different cohorts.

The absolute rate of infection increased when antibiotic-loaded cement was used in TKR. However, this rate of increase was less than the rate of increase in infection following uncemented THR during the same period. If the rise in the rate of infection observed in THR were extrapolated to the TKR cohort, 18 additional cases of infection would have been expected to occur in the cohort receiving antibiotic-loaded cement, compared with the number observed. Depending on the type of antibiotic-loaded cement that is used, its cost in all primary TKRs ranges between USD $2112.72 and USD $112 606.67 per case of infection that is prevented.

Cite this article: Bone Joint J 2014;96-B:65–9.