Jae Suk Chang

Association between Bone Mineral Density and LDL Receptor-Related Protein 5 Gene Polymorphisms in Young Korean Men

Recently, It has been reported that the LDL receptor-related protein 5 (LRP5) regulates bone formation, and that mutations of the gene cause osteoporosis-pseudoglioma syndrome or high bone mass phenotypes. However, the mutations cannot explain a genetic trait for osteoporosis in the general population because of their rarity. From 219 Korean men aged 20-34 yr, we looked for six known polymorphisms causing amino acid changes in the LRP5 coding region, and investigated their association with bone mineral density (BMD) at the following anatomical sites: lumbar spine (L2-L4) and the left proximal femur (femoral neck, Wards triangle, trochanter and shaft). We found that the Q89R polymorphism was significantly associated with BMD at the femoral neck and Wards triangle (p=0.004 and <0.001, respectively). However, after adjusting for age, weight and height, a statistically significant association only occurred at the Wards triangle (p=0.043), and a marginal association was observed at the femoral neck (p=0.098). No A400V, V667M, R1036Q and A1525V polymorphisms were found, and no statistically significant association was found between the A1330V polymorphism and BMD at any sites. Although we failed to demonstrate a clear association between the LRP5 polymorphism and peak bone mass in young men, the present study suggests that larger-scale studies on the Q89R polymorphism need to be performed.

Association of the OSCAR Promoter Polymorphism With BMD in Postmenopausal Women

In an effort to identify genetic polymorphisms in potential candidate genes for osteoporosis, 10 variants were identified in the OSCAR gene using direct DNA sequencing, and 560 postmenopausal women were genotyped at five SNP loci, using the TaqMan method. The rare allele (G allele) of OSCAR‐2322A>G (SNP in the 5′ flanking region) showed significant association with lower BMD at various bone sites in postmenopausal women (n = 560).

Usefulness of adding SPECT/CT to 99mTc-hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte imaging for diagnosing prosthetic joint infections.

Objective This study evaluated the usefulness of adding single-photon emission computed tomography (SPECT)/computed tomography (CT) (SPECT/CT) to technetium Tc 99m (99mTc) hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte imaging for diagnosing infections in hip or knee joint prostheses. Methods The 99mTc-HMPAO-labeled leukocyte scans of 164 patients (71 with hip prostheses and 93 with knee prostheses) with clinically suspected prosthetic infections were reviewed retrospectively. Planar images were taken 4 to 6 and 21 to 26 hours after injecting the labeled leukocytes and SPECT/CT images were obtained 4 to 6 hours after the injection. The final diagnosis of infection was based on pathologic findings (n = 70), bacteriological data (n = 61), or clinical follow-up (n = 33). Results Of the 164 patients, 89 patients had a diagnosis of prosthetic joint infections. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the planar images alone were 82.0%, 88.0%, 89.0%, 80.5%, and 84.8%, respectively. When the planar images were combined with SPECT, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 91.0%, 88.0%, 90.0%, 89.2%, and 89.6%, respectively. When the planar images were combined with SPECT/CT, these values increased further to 93.3%, 93.3%, 94.3%, 92.1%, and 93.3%, respectively. Adding CT to SPECT resulted in a greater increase in sensitivity and specificity for hip prosthesis infections than for knee prosthesis infections. SPECT/CT mainly contributed by precisely localizing the anatomical site of the active inflammatory lesion and by delineating the extent of the lesion after diagnosis with SPECT. Conclusions Single-photon emission computed tomography/CT combined with 99mTc-HMPAO-labeled leukocyte imaging was useful for diagnosing prosthesis infections, particularly in hip prosthesis infections, as it improved diagnostic accuracy and provided anatomical localization data.

Validation of FRAX without BMD: An age-related analysis of the Fifth Korean National Health and Nutrition Examination Survey (KNHANES V-1, 2010)

Although the Fracture Risk Assessment Tool (FRAX) is widely used to evaluate probabilities of fractures, there is no consensus regarding whether it is accurate when bone mineral density (BMD) is not included. This cross-sectional study aimed to compare the 10-year predicted fracture probabilities calculated using FRAX with and without BMD. Data were collected from the 2010 Fifth Korean National Health and Nutrition Examination Survey, and 2706 participants (1260 men and 1446 women) aged 50-90 years were analyzed. Ten-year predicted probabilities for major osteoporotic and hip fractures were calculated using the FRAX model. In men, the 10-year probabilities without BMD were 3.9±1.8% and 1.3±1.4% for major osteoporotic and hip fractures, respectively. In women, the 10-year probabilities without BMD were 7.7±4.4% and 2.6±2.9% for major osteoporotic and hip fractures, respectively. These probabilities were significantly correlated with the probabilities calculated using FRAX with BMD (all, p<0.001). When participants were divided into 10-year age groups and compared with the 10-year predicted fracture probability with BMD, the 10-year predicted fracture probability without BMD was lower in men 50-59 years old, similar to men 60-69 years old, and higher in men ≥70 years old. The FRAX scores without BMD were generally lower for all women. The FRAX model without BMD appears to be a slightly lower fracture probability compared to that calculated with BMD, especially in younger participants. Although these results have important clinical implications for areas with limited ability to evaluate BMD, they must be confirmed by a large prospective study.

Association of Bone Marrow Sphingosine 1-phosphate Levels with Osteoporotic Hip Fractures

Background Sphingosine 1-phosphate (S1P) has been discovered to be a critical regulator of bone metabolism. Very recently, we found that higher circulating S1P levels were associated with higher rate of prevalent osteoporotic fracture in human. Methods This was a cross-sectional study of 16 patients who underwent hip replacement surgeries. Bone marrow fluids were obtained during hip surgeries, and the S1P levels were measured using a competitive enzyme-linked immunosorbent assay (ELISA) assay. Bone mineral densities (BMDs) at various skeletal sites were obtained using dual energy X-ray absorptiometry. Results Among 16 patients, 4 patients were undergone operations due to hip fractures, and the others were done by any other causes. Bone marrow S1P levels were significantly lower in patients with hip fractures than in those without, before and after adjusting for confounding factors (P=0.047 and 0.025, respectively). We failed to demonstrate significant associations between bone marrow S1P levels and any BMD values (γ=0.026-0.482, P=0.171-0.944). Conclusions In conjunction with our previous findings, these suggest that the effects of gradient between peripheral blood and bone marrow, but not S1P itself, may be the most critical on bone metabolism.

How can MRI change the treatment strategy in apparently isolated greater trochanteric fracture

INTRODUCTION The purpose of this study was to evaluate the proportion of greater trochanter (GT) fractures with occult extension to the intertrochanteric region on magnetic resonance imaging (MRI) among apparently isolated GT fractures and to investigate the use of MRI for formulating a treatment strategy in patients with isolated GT fractures. PATIENTS AND METHODS This retrospective cohort study reviewed 37 patients with isolated GT fractures on plain radiography. Surgical or conservative treatment was decided according to MRI findings. We divided patients into 3 groups according to the extension of the fracture line. In group 1, the fracture line was within the lateral one-third in the coronal plane. In group 2, the fracture line extended from the lateral one-third to the medial one-third. In group 3, the fracture line extended over the medial one-third and/or to the medial cortex of the femur. Conservative treatment was performed in groups 1 and 2, and surgical treatment was performed in group 3. The clinical results, radiography findings, and MRI findings were investigated. RESULTS MRI revealed hidden intertrochanteric fractures (groups 2 [n = 10] and 3 [n = 4]) in 38% of apparently isolated GT fractures on radiography. No displacement was found in groups 1 (n = 23) and 2. Of the 4 patients in group 3, 3 were treated surgically and achieved good functional results and 1 refused to undergo surgery and finally developed complete intertrochanteric fracture. This patient presented 5 days later with increased hip pain, and radiography demonstrated displacement of the fracture, prompting surgical intervention. CONCLUSIONS The evaluation of apparently isolated GT fractures using MRI can be useful to diagnose the extent of the occult fracture and determine the treatment strategy.

The timing of bone SPECT to predict osteonecrosis after internal fixation of femur neck fractures

BACKGROUND Bone SPECT can be used after a femur neck fracture to assess the circulation of the femoral head in the immediate postoperative period because the blood supply is one of the major factors affecting bone uptake of radiotracer on bone scintigraphy. The purpose of our present study was to investigate whether osteonecrosis of the femoral head (OFH) after internal fixation of femoral neck fracture could be predicted by early and late bone SPECT. METHODS This retrospective cohort study enrolled 44 patients (33 women; mean age, 66.9 years) who underwent surgical fixation for femoral neck fractures. Early and late bone SPECT images were obtained within 2 weeks postoperatively and at 3 months postoperatively. Patients were followed up for a minimum of 24 months (average, 34 months). RESULTS OFH developed in 9 out of 44 patients but no patient showed nonunion. Seventeen patients with normal femoral head uptake on early bone SPECT were healed. Of 27 patients with decreased femoral head uptake on early bone SPECT, 2 patients developed OFH on radiography before 3 months postoperatively, 18 patients recovered to normal uptake on the late SPECT, and the remaining 7 patients still showed decreased uptake on the late SPECT at 3 months postoperatively. All of these 7 cases finally developed OFH on radiography. CONCLUSION Bone SPECT can reliably predict the possibility of OFH with after femoral neck fracture at least 3 months after surgery, while early bone SPECT showed low specificity. STUDY DESIGN Clinical.