Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study

Background@#This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis. @*Methods@#Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤–2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months. @*Results@#At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (–0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively. @*Conclusion@#Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

Determinants of Bone Mass and Insulin Resistance in Korean Postmenopausal Women: Muscle Area, Strength, or Composition?

PURPOSE: Muscle mass, strength, and composition determine muscle quantity and quality. However, data on muscle properties in relation to bone mass or insulin resistance are limited in Asian populations. This study aimed to investigate the relative importance of muscle measurements in regards to their relationship with lower bone mass and insulin resistance. MATERIALS AND METHODS: In this study, 192 postmenopausal women (age, 72.39±6.07 years) were enrolled. We measured muscle cross-sectional area (CSA) and attenuation at the gluteus maximus and quadriceps muscles through quantitative computed tomography. Muscle strength and physical performance were evaluated with the hand grip test and Short Physical Performance Battery (SPPB). Pearson correlation analysis and linear regression were performed to evaluate the relationship between muscle properties and homeostatic model assessment-insulin resistance (HOMA-IR) or bone mineral density (BMD). RESULTS: Muscle CSA, hand grip strength, and SPPB score held positive correlations with spine and hip BMDs, but not with insulin resistance. In contrast, muscle attenuation of the gluteus maximus or quadriceps was inversely related to HOMA-IR (r=−0.194, p=0.018 and r=−0.292, p<0.001, respectively), but not BMD. Compared with the control group, muscle CSA was significantly decreased in patients with osteoporosis; however, decreased muscle attenuation, indicating high fat infiltration, was found only in patients with diabetes. CONCLUSION: Muscle mass, strength, and physical performance were associated with low bone mass, and accumulation of intramuscular fat, a histological hallmark of persistently damaged muscles, may play a major role in the development of insulin resistance in Korean postmenopausal women.

Site-Specific Difference of Bone Geometry Indices in Hypoparathyroid Patients

BACKGROUND: Hypoparathyroid patients often have a higher bone mineral density (BMD) than the general population. However, an increase in BMD does not necessarily correlate with a solid bone microstructure. This study aimed to evaluate the bone microstructure of hypoparathyroid patients by using hip structure analysis (HSA). METHODS: Ninety-five hypoparathyroid patients >20 years old were enrolled and 31 of them had eligible data for analyzing bone geometry parameters using HSA. And among the control data, we extracted sex-, age-, and body mass index-matched three control subjects to each patient. The BMD data were reviewed retrospectively and the bone geometry parameters of the patients were analyzed by HSA. RESULTS: The mean Z-scores of hypoparathyroid patients at the lumbar spine, femoral neck, and total hip were above zero (0.63±1.17, 0.48±1.13, and 0.62±1.10, respectively). The differences in bone geometric parameters were site specific. At the femoral neck and intertrochanter, the cross-sectional area (CSA) and cortical thickness (C.th) were higher, whereas the buckling ratio (BR) was lower than in controls. However, those trends were opposite at the femoral shaft; that is, the CSA and C.th were low and the BR was high. CONCLUSION: Our study shows the site-specific effects of hypoparathyroidism on the bone. Differences in bone components, marrow composition, or modeling based bone formation may explain these findings. However, further studies are warranted to investigate the mechanism, and its relation to fracture risk.

Cyclized Oligopeptide Targeting LRP5/6-DKK1 Interaction Reduces the Growth of Tumor Burden in a Multiple Myeloma Mouse Model

PURPOSE: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden. MATERIALS AND METHODS: A cyclized oligopeptide based on DKK1-LRP5/6 interactions was synthesized chemically, and its nuclear magnetic resonance structure was assessed. Luciferase reporter assay and mRNA expressions of osteoblast markers were evaluated after oligopeptide treatment. MOPC315.BM.Luc cells were injected into the tail vein of mice, after which cyclized oligopeptide was delivered subcutaneously 6 days a week for 4 weeks. RESULTS: The cyclized oligopeptide containing NXI motif bound to the E1 domain of LRP5/6 effectively on surface plasmon resonance analysis. It abrogated the Wnt-β-catenin signaling inhibited by DKK1, but not by sclerostin, dose dependently. RT-PCR and alkaline phosphatase staining showed increased expressions of osteoblast markers according to the treatment concentrations. Bioluminescence images showed that the treatment of cyclized oligopeptide reduced tumor burden more in oligopeptide treated group than in the vehicle group. CONCLUSION: The cyclized oligopeptide reported here may be another option for the treatment of tumor burden in multiple myeloma.

Effects of Single Vitamin D₃ Injection (200,000 Units) on Serum Fibroblast Growth Factor 23 and Sclerostin Levels in Subjects with Vitamin D Deficiency

BACKGROUND: Vitamin D deficiency remains common in all age groups and affects skeletal and non-skeletal health. Fibroblast growth factor 23 is a bone-derived hormone that regulates phosphate and 1,25-dihydroxyvitamin D homeostasis as a counter regulatory factor. 1,25-Dihydroxyvitamin D stimulates fibroblast growth factor 23 synthesis in bone, while fibroblast growth factor 23 suppresses 1,25-dihydroxyvitamin D production in the kidney. The aim of this study was to evaluate the effects of vitamin D₃ intramuscular injection therapy on serum fibroblast growth factor 23 concentrations, and several other parameters associated with bone metabolism such as sclerostin, dickkopf-1, and parathyroid hormone. METHODS: A total of 34 subjects with vitamin D deficiency (defined by serum 25-hydroxyvitamin D levels below 20 ng/mL) were randomly assigned to either the vitamin D injection group (200,000 units) or placebo treatment group. Serum calcium, phosphate, urine calcium/creatinine, serum 25-hydroxyvitamin D, fibroblast growth factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were serially measured after treatment. RESULTS: Comparing the vitamin D injection group with the placebo group, no significant changes were observed in serum fibroblast growth factor 23, parathyroid hormone, or dickkopf-1 levels. Serum sclerostin concentrations transiently increased at week 4 in the vitamin D group. However, these elevated levels declined later and there were no statistically significant differences as compared with baseline levels. CONCLUSION: Serum fibroblast factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were not affected significantly by single intramuscular injection of vitamin D₃.

Efficacy and safety of vitamin D3 B.O.N intramuscular injection in Korean adults with vitamin D deficiency

OBJECTIVE: There has been no prospective study that examined intramuscular injection of high-dose vitamin D in Korean adults. The aim of this study was to assess the efficacy and safety of high-dose vitamin D3 after intramuscular injection in Korean adults with vitamin D deficiency. METHODS: This study was a 24-week, prospective, multicenter, randomized, double-blind, placebo-controlled trial. A total of 84 subjects ≥19 and <65 years of age were randomly allocated to either the vitamin D3 or placebo group in a 2:1 ratio. After randomization, a single injection of plain vitamin D3 200,000 IU or placebo was intramuscularly administered. If serum 25-hydroxyvitamin D (25[OH]D) concentrations were <30 ng/mL on week 12 or thereafter, a repeat injection was administered. RESULTS: After a single intramuscular injection of vitamin D3 to adults with vitamin D deficiency, the proportion of subjects with serum 25(OH)D concentrations ≥30 ng/mL within 12 weeks was 46.4% in the vitamin D3 group and 3.6% in the placebo group (p < 0.0001). The proportion of subjects with serum 25(OH)D concentrations ≥30 ng/mL within 24 weeks was 73.2% in the vitamin D3 group and 3.6% in the placebo group (p < 0.0001). Mean change in serum 25(OH)D concentrations at weeks 12 and 24 after vitamin D3 injection was 12.8 ± 8.1 and 21.5 ± 8.1 ng/mL, respectively, in the vitamin D3 group, with no significant changes in the placebo group. Serum parathyroid hormone concentrations showed a significant decrease in the vitamin D3 group but no change in the placebo group. CONCLUSION: Intramuscular injection of vitamin D3 200,000 IU was superior to placebo in terms of its impact on serum 25(OH)D concentrations, and is considered to be safe and effective in Korean adults with vitamin D deficiency.

Serum γ-Glutamyl Transferase Is Inversely Associated with Bone Mineral Density Independently of Alcohol Consumption

BACKGROUND: γ-Glutamyl transferase (GGT) is a well-known marker of chronic alcohol consumption or hepatobiliary diseases. A number of studies have demonstrated that serum levels of GGT are independently associated with cardiovascular and metabolic disorders. The purpose of this study was to test if serum GGT levels are associated with bone mineral density (BMD) in Korean adults. METHODS: A total of 462 subjects (289 men and 173 women), who visited Severance Hospital for medical checkup, were included in this study. BMD was measured using dual energy X-ray absorptiometry. Cross-sectional association between serum GGT and BMD was evaluated. RESULTS: As serum GGT levels increased from the lowest tertile (tertile 1) to the highest tertile (tertile 3), BMD decreased after adjusting for confounders such as age, body mass index, amount of alcohol consumed, smoking, regular exercise, postmenopausal state (in women), hypertension, diabetes mellitus, and hypercholesterolemia. A multiple linear regression analysis showed a negative association between log-transformed serum GGT levels and BMD. In a multiple logistic regression analysis, tertile 3 of serum GGT level was associated with an increased risk for low bone mass compared to tertile 1 (odds ratio, 2.271; 95% confidence interval, 1.340 to 3.850; P=0.002). CONCLUSION: Serum GGT level was inversely associated with BMD in Korean adults. Further study is necessary to fully elucidate the mechanism of the inverse relationship.

The Role of Nuclear Factor-E2-Related Factor 1 in the Oxidative Stress Response in MC3T3-E1 Osteoblastic Cells

BACKGROUND: Reactive oxygen species (ROS) and antioxidants are associated with maintenance of cellular function and metabolism. Nuclear factor-E2-related factor 1 (NFE2L1, Nrf1) is known to regulate the expression of a number of genes involved in oxidative stress and inflammation. The purpose of this study was to examine the effects of NFE2L1 on the response to oxidative stress in osteoblastic MC3T3-E1 cells. METHODS: The murine calvaria-derived MC3T3-E1 cell line was exposed to lipopolysaccharide (LPS) for oxidative stress induction. NFE2L1 effects were evaluated using small interfering RNA (siRNA) for NFE2L1 mRNA. ROS generation and the levels of known antioxidant enzyme genes were assayed. RESULTS: NFE2L1 expression was significantly increased 2.4-fold compared to the control group at 10 µg/mL LPS in MC3T3-E1 cells (P<0.05). LPS increased formation of intracellular ROS in MC3T3-E1 cells. NFE2L1 knockdown led to an additional increase of ROS (20%) in the group transfected with NFE2L1 siRNA compared with the control group under LPS stimulation (P<0.05). RNA interference of NFE2L1 suppressed the expression of antioxidant genes including metallothionein 2, glutamatecysteine ligase catalytic subunit, and glutathione peroxidase 1 in LPS-treated MC3T3-E1 cells. CONCLUSION: Our results suggest that NFE2L1 may have a distinct role in the regulation of antioxidant enzymes under inflammation-induced oxidative stress in MC3T3-E1 osteoblastic cells.

The Effects of a High Fat Diet Containing Diacylglycerol on Bone in C57BL/6J Mice

PURPOSE: In epidemiologic and animal studies, a high fat diet (HFD) has been shown to be associated with lower bone mineral density (BMD) and a higher risk of osteoporotic fractures. Meanwhile, consuming a HFD containing diacylglycerol (DAG) instead of triacylglycerol (TAG) is known to offer metabolically beneficial effects of reductions in body weight and abdominal fat. The purpose of this study was to investigate the effects of a HFD containing DAG (HFD-DAG) on bone in mice. MATERIALS AND METHODS: Four-week-old male C57BL/6J mice (n=39) were divided into three weight-matched groups based on diet type: a chow diet group, a HFD containing TAG (HFD-TAG) group, and a HFD-DAG group. After 20 weeks, body composition and bone microstructure were analyzed using dual energy X-ray absorptiometry and micro-computed tomography. Reverse transcription-polymerase chain reaction (PCR) and real-time PCR of bone marrow cells were performed to investigate the expressions of transcription factors for osteogenesis or adipogenesis. RESULTS: The HFD-DAG group exhibited lower body weight, higher BMD, and superior microstructural bone parameters, compared to the HFD-TAG group. The HFD-DAG group showed increased expression of Runx2 and decreased expression of PPARgamma in bone marrow cells, compared to the HFD-TAG group. The HFD-DAG group also had lower levels of plasma glucose, insulin, total cholesterol, and triglyceride than the HFD-TAG group. CONCLUSION: Compared to HFD-TAG, HFD-DAG showed beneficial effects on bone and bone metabolism in C57BL/6J mice.

Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

BACKGROUND: Sclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs), which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI. METHODS: We included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years) treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years). The subjects were randomly assigned to take either 5 mg alendronate with 0.5 microg calcitriol (n=46), or placebo (n=44) for 6 months. RESULTS: Postmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8+/-13.6 pmol/L vs. 23.1+/-4.8 pmol/L, P0.05). CONCLUSION: Serum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss.

Efficacy and Safety of Weekly Alendronate Plus Vitamin D3 5600 IU versus Weekly Alendronate Alone in Korean Osteoporotic Women: 16-Week Randomized Trial

Vitamin D (vit-D) is essential for bone health, although many osteoporosis patients have low levels of 25-hydroxy-vit-D [25(OH)D]. This randomized, open-label study compared the effects of once weekly alendronate 70 mg containing 5600 IU vit-D3 (ALN/D5600) to alendronate 70 mg without additional vit-D (ALN) on the percent of patients with vit-D insufficiency [25(OH)D <15 ng/mL, primary endpoint] and serum parathyroid hormone (PTH, secondary endpoint) levels in postmenopausal, osteoporotic Korean women. Neuromuscular function was also measured. A total of 268 subjects were randomized. Overall, 35% of patients had vit-D insufficiency at baseline. After 16-weeks, there were fewer patients with vit-D insufficiency in the ALN/D5600 group (1.47%) than in the ALN group (41.67%) (p<0.001). Patients receiving ALN/D5600 compared with ALN were at a significantly decreased risk of vit-D insufficiency [odds ratio=0.02, 95% confidence interval (CI) 0.00-0.08]. In the ALN/D5600 group, significant increases in serum 25(OH)D were observed at weeks 8 (9.60 ng/mL) and 16 (11.41 ng/mL), where as a significant decrease was recorded in the ALN group at week 16 (-1.61 ng/mL). By multiple regression analysis, major determinants of increases in serum 25(OH)D were ALN/D5600 administration, seasonal variation, and baseline 25(OH)D. The least squares mean percent change from baseline in serum PTH in the ALN/D5600 group (8.17%) was lower than that in the ALN group (29.98%) (p=0.0091). There was no significant difference between treatment groups in neuromuscular function. Overall safety was similar between groups. In conclusion, the administration of 5600 IU vit-D in the ALN/D5600 group improved vit-D status and reduced the magnitude of PTH increase without significant side-effects after 16 weeks in Korean osteoporotic patients.

Analysis of 18F-fluorodeoxyglucose positron emission tomography findings in patients with pituitary lesions

BACKGROUND/AIMS: Although magnetic resonance imaging (MRI) is a good visual modality for the evaluation of pituitary lesions, it has limited value in the diagnosis of mixed nodules and some cystic lesions. We evaluated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) for patients with pituitary lesions. METHODS: 18F-FDG PET and MRI were performed simultaneously in 32 consecutive patients with pituitary lesions. The relationships between FDG uptake patterns in PET and MRI findings were analyzed. RESULTS: Of 24 patients with piuitary adenomas, 19 (79.2%) showed increased uptake of 18F-FDG in the pituitary gland on PET scans. All patients with pituitary macroadenomas showed increased 18F-FDG uptake on PET scans. Meanwhile, only five (50%) of the 10 patients with pituitary microadenomas showed positive PET scans. Interestingly, of two patients with no abnormal MRI findings, one showed increased 18F-FDG uptake on PET. For positive 18F-FDG uptake, maximum standardized uptake values (SUVmax) > 2.4 had 94.7% sensitivity and 100% specificity. In addition, SUVmax increased in proportion to the size of pituitary adenomas. Most cystic lesions did not show 18F-FDG uptake on PET scans. CONCLUSIONS: About 80% of pituitary adenomas showed positivity on PET scans, and SUVmax was related to the size of the adenomas. PET may be used as an ancillary tool for detection and differentiation of pituitary lesions.

Spontaneous Non-Traumatic Stress Fractures in Bilateral Femoral Shafts in a Patient Treated with Bisphosphonates

Bisphosphonates are potent inhibitors of bone resorption and widely used to treat osteoporosis. Extensive studies have shown that therapy with bisphosphonates improves bone density and decreases fracture risk. However, concerns have been raised about potential over-suppression of bone turnover during long-term use of bisphosphonates, resulting in increased susceptibility to and delayed healing of non-spinal fractures. We report a patient who sustained non-traumatic stress fractures in bilateral femoral shafts with delayed healing after long-term bisphosphonate therapy. She underwent open reduction and surgical internal fixation. Although bisphosphonates effectively prevent vertebral fractures, and their safety has been tested in randomized trials, we must emphasize the need for awareness of the possibility that long-term suppression of bone turnover with bisphosphonates may eventually lead to an accumulation of fatigue-induced damage and adverse skeletal effects such as delayed fracture healing.

1-34 PTH Could Reverse Impaired Bone Mineralization Induced By the Overdose of Bisphosphonate

Bisphosphonates are the mainstay of osteoporosis treatment. Despite the fact that bisphosphonates have a relatively good safety record and are tolerated well by the majority of patients, serious adverse events have been associated with their use. A 41-year-old man had been diagnosed with osteoporosis and had taken etidronate 200 mg/day daily for 2 years due to the judgmental error. He was referred for the management of refractory bone pain and generalized muscle ache. Serum calcium, phosphate, 25-hydroxy-vitamin D (25(OH)D), and immunoreactive parathyroid hormone (iPTH) were within normal range. Plain X-ray showed multiple fractures. Whole body bone scan confirmed multiple sites of increased bone uptakes. Tetracycline-labeled bone biopsy showed typical findings of osteomalacia. He was diagnosed with iatrogenic, etidronate-induced osteomalacia. The patient received daily parathyroid hormone (PTH) injection for 18 months. PTH effectively reverses impaired bone mineralization caused by etidronate misuse. Currently, he is doing well without bone pain. Bone mineral density significantly increased, and the increased bone uptake was almost normalized after 18 months. This case seems to suggest that human PTH (1-34) therapy, possibly in association with calcium and vitamin D, is associated with important clinical improvements in patients with impaired bone mineralization due to the side effect of bisphosphonate.

Seven Year-follow-up of a Brown Tumor in the Maxilla Associated with Secondary Hyperparathyroidism in End-stage Renal Failure / 대한골다공증학회지

Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD) as a result of prolonged hyperphosphatemia and hypocalcemia. Brown tumor is a rare bony complication of hyperparathyroidism as a result of increased osteoclastic activity and fibroblastic proliferation. Frequent sites of brown tumor are known as ribs, clavicles, mandible, and pelvic bone, but maxilla is very rare site. Twenty seven-year-old woman with stage V CKD on hemodialysis presented with maxillary mass which had gradually increased in size for 3 years. It was painless, but tooth derangement occurred. Initial laboratory findings revealed hypercalcemia (11.0 mg/dL), hyperphosphatemia (6.9 mg/dL), high creatinine (7.5 mg/dL), and high serum PTH (1729.9 pg/mL). The bone mineral density was significantly low (lumbar spine Z-score:

Effect of Zoledronic Acid on Acro-Osteolysis and Osteoporosis in a Patient with Hajdu-Cheney Syndrome

Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself.

A Case of Primary Hyperparathyroidism Caused by Solitary Parathyroid Adenoma That was Not Detected by Both Ultrasonography and Sestamibi Scan

Thanks to advances in assay techniques and routine measurements in serum chemical analysis, primary hyperparathyroidism has become far more frequently detected, and the number of asymptomatic patients has substantially increased. In the majority of patients (85%), a solitary adenoma is the underlying cause of primary hyperparathyroidism. Surgical excision is the treatment of choice for most cases of primary hyperparathyroidism; this procedure has a relatively high success rate. In the past decade, improvements in preoperative imaging have played a major role in a targeted operative approach, which allows for minimally invasive surgery to be performed. The success of parathyroid surgery depends on the accurate preoperative localization of parathyroid adenoma. In this study, we report the case of a 54 year-old woman with primary hyperparathyroidism who presented with left buttock and leg pain. For localization of the parathyroid lesion, an ultrasonography and a 99mTc-sestamibi scan were initially performed, but these attempts failed to localize the lesion. We then carried out contrast-enhanced CT; thereafter, a single parathyroid adenoma was detected. Therefore, in patients with negative results on both ultrasonography and 99mTc-sestamibi scan, contrast-enhanced CT may prove helpful for preoperative parathyroid localization.

Primary Bilateral Adrenal Non-Hodgkin's Lymphoma Presented with Adrenal Insufficiency: A Case Report

Primary adrenal lymphoma is a very rare disease and it is known to have a poor prognosis. We report here on a case of primary adrenal insufficiency that was secondary to primary bilateral adrenal lymphoma. A 54-year old man was hospitalized because of easy fatigability, weight loss and consistent malaise for 6 months. The physical examination revealed hyperpigmentation on the anterior chest and hypotension. According these findings and symptoms, we did a rapid ACTH stimulation test with a clinical suspicion of adrenal insufficiency. He showed an inadequate adrenal response and so he was diagnosed with adrenal insufficiency. The abdominal CT images showed bilateral huge adrenal masses and increased uptake of the adrenal glands on PET. The pathologic diagnosis by ultrasound-guided gun biopsy of the right adrenal gland was diffuse large B cell lymphoma. The patient was administered combination chemotherapy with the R-CHOP regimen, and after 8-cycles of chemotherapy, he achieved complete remission of tumor according to the image studies and he recovered his adrenal function. Primary adrenal lymphoma, although a rare disease, should be considered in patients with bilateral enlargement of the adrenal glands and when the adrenal glands show increased uptake on a PET scan, and especially there is adrenal insufficiency.

Characteristics of Body Fat, Body Fat Percentage and Other Body Composition for Koreans from KNHANES IV

Accurate measurement of fat mass has become increasingly important with the increasing incidence of obesity. We assessed fat and muscle mass of Koreans with the Korea National Health and Nutrition Examination Survey IV (KNHANES IV). We studied 10,456 subjects (aged 20 to 85 yr; 4,476 men, 5,980 women). Fat and muscle mass were measured by dual-energy x-ray absorptiometry. Reference values of body compositions were obtained using the LMS method. The fat mass index (FMI, body fat mass/height2; kg/m2) of Korean men did not correlate with age (P = 0.452), but those of Korean women (P 9 kg/m2) in men and 2.7% (FMI > 13 kg/m2) in women. It is concluded that the muscle mass decreases and obesity increases with aging in Korean men, whereas both fat mass and obesity increase with aging in Korean women.

Modifications of T-Scores by Quantitative Ultrasonography for the Diagnosis of Osteoporosis in Koreans

To identify a proper T-score threshold for the diagnosis of osteoporosis in Koreans using quantitative ultrasonography (QUS), normative data from 240 females and 238 males (ages 20-29 yr) were newly generated. Then, the osteoporosis prevalence estimate for men and women over 50 yr of age was analyzed using previous World Health Organization (WHO) methods and heel QUS. T-scores were calculated from the normative data. There were definite negative correlations between age and all of the QUS parameters, such as speed of sound (SOS), broadband ultrasound attenuation (BUA), and estimated heel bone mineral density (BMD) (p<0.0001). After applying the recently determined prevalence of incident vertebral fracture in Koreans over 50 yr of age (11.6% and 9.1%, female vs male, respectively) to the diagnosis of osteoporosis by T-scores from heel BMD as measured by QUS, it was revealed that applicable T-scores for women and men were -2.25 and -1.85, respectively. These data suggest that simply using a T-score of -2.5, the classical WHO threshold for osteoporosis, underestimates the true prevalence when using peripheral QUS. Further prospective study of the power of QUS in predicting the absolute risk of fracture is needed.