Real-World Safety and Effectiveness of Denosumab in Patients with Osteoporosis: A Prospective, Observational Study in South Korea

Background@#The efficacy and safety of denosumab have been established in a phase 3, randomized, placebo-controlled trial in Korean postmenopausal women with osteoporosis. This postmarketing surveillance study was aimed to investigate the safety and effectiveness of denosumab in Korean real-world clinical practice. @*Methods@#Patients with osteoporosis who had received denosumab per the Korean approved indications in the postmarketing setting between September 2014 and September 2019 were enrolled. The primary endpoint was the incidence of adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was the percent change from baseline in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck. @*Results@#Of the 3,221 patients enrolled, 3,185 were included in the safety analysis set; 2,973 (93.3%) were female, and the mean± standard deviation (SD) age was 68.9±9.9 years. The mean±SD study period was 350.0±71.4 days. AEs, fatal AEs, and ADRs occurred in 19.3%, 0.8%, and 1.6%, respectively. The most frequent AEs, occurring in >0.5% of patients, were dizziness (0.7%), arthralgia (0.7%), back pain (0.6%), and myalgia (0.6%). Hypocalcemia occurred in 0.3% of patients. There were no cases of osteonecrosis of the jaw and atypical femoral fracture. Mean±SD percent change from baseline in BMD of the lumbar spine, total hip, and femoral neck was 7.3%±23.6%, 3.6%±31.4%, and 3.2%±10.7%, respectively. @*Conclusion@#The safety and effectiveness of denosumab in Korean patients with osteoporosis in this study were comparable with those in the Korean randomized controlled trial, with no new safety findings.

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).

Optimal Radial Motor Nerve Conduction Study Using Ultrasound in Healthy Adults

OBJECTIVE: To obtain reference values, to suggest optimal recording and stimulation site for radial motor nerve conduction study (RmNCS), and to analyze the correlation among RmNCS parameters, demographics and ultrasonography (US) findings. METHODS: A total of 55 volunteers participated in this study. We hypothesized that ‘lateral edge of spiral groove (A)’ was the optimal stimulation site, and the ‘largest cross-sectional area (CSA) of extensor indicis proprius (EIP) muscle (B)’ was the optimal recording site. The surface distance between ‘A’ and the lateral epicondyle of the humerus divided by upper arm length, was named the spiral groove ratio. The surface distance between ‘B’ and the ulnar styloid process divided by forearm length, was named the EIP ratio. Using US, we identified these sites, and further conducted RmNCS. RESULTS: Data was collected from 100 arms of the 55 volunteers. Mean amplitude and latency were 5.7±1.1 mV and 5.7±0.5 ms, respectively, at the spiral groove, and velocity between elbow and spiral groove was 73.7±7.0 m/s. RmNCS parameters correlated significantly with height, weight, arm length, and CSA of the EIP muscle. Spiral groove ratio and EIP ratio were 0.338±0.03 and 0.201±0.03, respectively; both values were almost the same, regardless of age, sex and handedness. CONCLUSION: We established a reference value and standardized method of RmNCS using US. Optimal RmNCS can be conducted by placing the recording electrode 20% (about one-fifth) of forearm length from the ulnar styloid process, and stimulating at 34% (about one-third) of the humeral length from the lateral epicondyle.

Hirayama Disease with Proximal Involvement

Hirayama disease is a slowly progressing benign motor neuron disease that affects the distal upper limb. A 29-year-old man visited the hospital with a 1-year history of weakened left proximal upper limb. He was diagnosed with Hirayama disease 9 years ago, while there was no further progression of the muscle weakness afterward. Atrophy and weakness was detected in proximal upper limb muscles. Magnetic resonance imaging and somatosensory evoked potentials were normal. Needle electromyography showed abnormal findings in proximal upper limb muscles. Our patient had Hirayama disease involving the proximal portion through secondary progression. Clinical manifestation and accurate electromyography may be useful for diagnosis. Rare cases with progression patterns as described here are helpful and have clinical meaning for clinicians.

The Relationship of Serum Homocysteine Levels with Lumbar and Femoral Bone Mineral Density

BACKGROUND: Recently, an elevated serum homocysteine level has been reported to be associated with increased fracture risk and reduced bone mineral density (BMD). So far, little research has been done to evaluate such association in Korean population. Therefore, we investigated the association between serum homocysteine levels and BMD in Korean adults. METHODS: The subjects consisted of 2,750 adults who visited a health promotion center at a university hospital from January 2005 to March 2006. Self-administered questionnaires provided information about lifestyle and medical history. Fasting plasma samples were collected and BMD of the lumbar spine and femoral neck were obtained by dual energy X-ray absorptiometry. To adjust for menopausal state, the female subjects were divided into three groups according to age (< or =45 yrs, 46~55 yrs, 55 yrs <). Multiple linear regression analysis was used to evaluate the association between serum homocysteine levels and BMD in each gender and age group. RESULTS: The results adjusted for alcohol and smoking history showed significant association between serum homocysteine levels and BMD in women (Lumbar spine: beta=-0.006, P=0.015, Femoral neck: beta=-0.065, P=0.012) but not in men (Lumbar spine: beta=0.001, P=0.240, Femoral neck: beta=0.001, P=0.242). With analyses by three age groups, plasma homocysteine level was associated with both lumbar and femoral BMD in age 46~55 women (Lumbar spine: beta=-0.014, P=0.024, Femoral neck: beta= -0.007, P=0.019). CONCLUSION: Our study suggests that increased serum homocysteine level is an independent risk factor for low BMD among women, especially perimenopausal women. Further studies about the sexual differences and the mechanisms linking serum homocysteine level to BMD are needed.

Smoking Status and Augmentation Index in Korean Male Subjects

BACKGROUND: Smoking is a major risk factor of cardiovascular morbidity and mortality. Arterial stiffness has been identified as an important determinant of cardiovascular risk. Augmentation index is an indicator of arterial stiffness, which can be quantified noninvasively. The goal of this study was to assess the effect of current smoking status on augmentation index (AIx) in Korean male subjects. METHODS: A total of 70 males without clinical cardiovascular diseases were studied in this cross sectional study. AIx was measured in 35 current smokers and 35 nonsmokers by recording pressure waveforms using radial applanation tonometry in a SphygmoCor device. RESULTS: Augmentation index was significantly higher in the current smokers (19.4+/-12.9% vs. 9.7+/-12.8%; P<0.05). A multiple regression model confirmed that smoking status was independently associated with arterial stiffness (beta=0.350, P<0.001). CONCLUSION: Current smoking is associated with increased augmentation index, which is a marker of cardiovascular disease. Further studies are required to investigate clinical applications of arterial stiffness.

Weight Loss Reduce hsCRP Levels in Korean Premenopausal Obese Women

BACKGROUND: Obesity has been proposed as a risk factor for cardiovascular diseases. CRP has been proposed as an independent risk factor for cardiovascular diseases, and has been associated with body weight and body fatness. It has been known that weight reduction reduces CRP. We examined the hypothesis that weight loss can reduce plasma CRP levels in Korean, obese premenopausal women. METHODS: In a sample of 36 Korean obese (BMI 25.00~47.02 kg/m2), premenopausal (22~48 years) women, we measured hsCRP, plasma lipid profiles, blood glucose, body weight, body mass indexes, body fatness and intra abdominal body fat area. A 12-week weight reduction program was conducted in 36 obese women. When the program was finished, fat distribution, hsCRP and lipid profile test was repeated. The effects of weight loss on CRP levels were tested by means of paired t-test and nonparametric Wilcoxon signed rank test. RESULTS: We found that plasma CRP level was positively associated with body weight, body mass index, body fatness, CT-measured abdominal visceral and subcutaneous fat area. After a 12-week weight loss protocol, the average weight loss was 7.97+/-3.46 kg (P<0.0001) with loss of fat mass 5.29+/-0.59 kg, and 1.98+/-1.20 kg lean body mass. Plasma CRP levels were both positively associated with plasma CRP level reductions (P=0.0437). CONCLUSION: Obesity and adiposity influenced significantly on plasma CRP in Korean premenopausal women on cross sectional basis. Moreover, 12-week caloric restriction induced weight loss decreased plasma CRP levels. Weight loss represents an intervention to reduce plasma CRP and can mediate to reduce cardiovascular disease risk in Korean obese premenopausal women.