The Fracture Risk Assessment Tool Probability and Trabecular Bone Score Mediate the Relationship between Sphingosine 1-phosphate Levels and Fracture Risk

Background@#The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators. @*Methods@#Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses. @*Results@#Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22–11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01–42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28–9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28–7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk. @*Conclusions@#The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.

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.

Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism

Background@#Optimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision- making before engaging in AVS and surgery in clinical practice. @*Methods@#We conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression. @*Results@#We developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53). @*Conclusion@#We propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients.

Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism

Background@#Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors. @*Conclusion@#CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age

Background@#Guidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients 15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged 29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the 30.0 ng/dL (91.9% vs. 87.7%, P=0.590). @*Conclusion@#Patients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.

Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism

Background@#Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors. @*Conclusion@#CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age

Background@#Guidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients 15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged 29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the 30.0 ng/dL (91.9% vs. 87.7%, P=0.590). @*Conclusion@#Patients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.

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).

Potential Biomarkers to Improve the Prediction of Osteoporotic Fractures

Osteoporotic fracture (OF) is associated with high disability and morbidity rates. The burden of OF may be reduced by early identification of subjects who are vulnerable to fracture. Although the current fracture risk assessment model includes clinical risk factors (CRFs) and bone mineral density (BMD), its overall ability to identify individuals at high risk for fracture remains suboptimal. Efforts have therefore been made to identify potential biomarkers that can predict the risk of OF, independent of or combined with CRFs and BMD. This review highlights the emerging biomarkers of bone metabolism, including sphongosine-1-phosphate, leucine-rich repeat-containing 17, macrophage migration inhibitory factor, sclerostin, receptor activator of nuclear factor-κB ligand, and periostin, and the importance of biomarker risk score, generated by combining these markers, in enhancing the accuracy of fracture prediction.

Preventive Effects of Low Parathyroid Hormone Levels on Hip Fracture in Patients with Vitamin D Deficiency

BACKGROUND: The objective of the current study is to determine the role of serum parathyroid hormone (PTH) on hip fracture development by retrospectively analyzing the relationship between vitamin D and PTH levels and hip fracture prevalence. METHODS: Among 288 patients over 50 years of age, 113 patients with hip fracture and 111 controls without fracture were analyzed after excluding patients with conditions affecting bone metabolism. Bone mineral density and serum biochemical markers were measured, while demographic data were obtained. Patients were divided into 4 groups according to serum 25-hydroxy-vitamin D (25-[OH]D) and PTH levels: LowD+LowP (low 25[OH]D and PTH); LowD+HighP, (low 25[OH]D and high PTH); HighD+LowP (high 25[OH]D and low PTH); and HighD+HighP, patients with (high 25[OH]D and PTH). Measured values and percentages of patients with hip fracture in each group were then determined and compared. RESULTS: The number of patients included in the LowD+LowP, LowD+HighP, HighD+LowP, and HighD+HighP groups was 116, 17, 87, and 4, while the percentages of patients with hip fracture in the same groups were 60.3%, 88.2%, 27.6%, and 100%, respectively. The percentage of hip fracture was significantly lower in the LowD+LowP than the LowD+HighP group (P=0.049). CONCLUSIONS: Patients with low serum 25(OH)D and PTH levels showed lower hip fracture prevalence, indicating the potential protective role of low PTH levels on bone health in patients with vitamin D deficiency. Therefore, clinicians should pay more attention to the possibility of fractures in patients with vitamin D deficiency who present with high PTH levels.

Characteristics of Adrenal Incidentalomas in a Large, Prospective Computed Tomography-Based Multicenter Study: The COAR Study in Korea

PURPOSE: Previous studies on adrenal incidentalomas (AIs) are limited by their retrospective design, small numbers of patients, Western populations, or use of an outdated imaging technique. We investigated the characteristics of AIs in Korean patients and compared them with those reported in the largest retrospective study in Italy to discover the effects of improved imaging techniques and ethnicity differences. MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional observational study including 1005 Korean patients. Levels of plasma adrenocorticotrophic hormone, 24-h urinary free cortisol (UFC), serum cortisol after a 1 mg-dexamethasone suppression test, 24-h urinary fractionated metanephrine, and plasma aldosterone and plasma renin activity were measured. All AIs were characterized using computed tomography (CT). RESULTS: Compared with the results of the Italian study, AIs in Korean patients were observed more frequently in men and predominantly on the left side. Korean patients with AIs were slightly younger, and fewer patients underwent surgery. Most AIs were nonfunctional in both studies, while fewer subclinical hypercortisolism and more primary aldosteronism (PA) cases were detected in Korean patients. In our study, high UFC levels showed very low sensitivity, compared to those in the Italian study. In pheochromocytoma or PA cases, there were no hormonal differences between the studies. AIs in Korean patients were smaller, such that a lower cutoff size for detecting adrenocortical carcinoma (ACC) could be warranted. CONCLUSION: Recent advances in CT technology were leveraged to provide accurate characteristics of AIs and to detect smaller ACCs.

Bone Health in Adrenal Disorders

Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.

Guidelines for the Management of Adrenal Incidentaloma: the Korean Endocrine Society, Committee of Clinical Practice Guidelines / 대한내과학회지

An adrenal incidentaloma is an adrenal mass found in an imaging examination performed for reasons unrelated to suspected adrenal disease. The prevalence of adrenal incidentaloma increases with age; there is no gender difference, but it is often accompanied by obesity, diabetes mellitus, or hypertension. The detection of adrenal incidentaloma is expected to rise with the rapid development of imaging technology and increasing frequency of imaging studies. The Korean Endocrine Society is promoting appropriate practice guidelines to meet the rising incidence of adrenal incidentaloma, in cooperation with the Korean Adrenal Gland and Endocrine Hypertension Study Group. In this paper, we discuss important core issues for treating adrenal incidentaloma, along with the most important factors for healthcare providers who treat and manage affected patients. Initially, we identified 47 recommendations using the Delphi technique, after evaluating core propositions. We reduced these to the 20 most critical recommendations.

Clinical Guidelines for the Management of Adrenal Incidentaloma

An adrenal incidentaloma is an adrenal mass found in an imaging study performed for other reasons unrelated to adrenal disease and often accompanied by obesity, diabetes, or hypertension. The prevalence and incidence of adrenal incidentaloma increase with age and are also expected to rise due to the rapid development of imaging technology and frequent imaging studies. The Korean Endocrine Society is promoting an appropriate practice guideline to meet the rising incidence of adrenal incidentaloma, in cooperation with the Korean Adrenal Gland and Endocrine Hypertension Study Group. In this paper, we discuss important core issues in managing the patients with adrenal incidentaloma. After evaluating core proposition, we propose the most critical 20 recommendations from the initially organized 47 recommendations by Delphi technique.

The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women

BACKGROUND: Despite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women. METHODS: A total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria. RESULTS: Before and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (P=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73). CONCLUSION: This study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women.

Replication of Caucasian Loci Associated with Osteoporosis-related Traits in East Asians

BACKGROUND: Most reported genome-wide association studies (GWAS) seeking to identify the loci of osteoporosis-related traits have involved Caucasian populations. We aimed to identify the single nucleotide polymorphisms (SNPs) of osteoporosis-related traits among East Asian populations from the bone mineral density (BMD)-related loci of an earlier GWAS meta-analysis. METHODS: A total of 95 SNPs, identified at the discovery stage of the largest GWAS meta-analysis of BMD, were tested to determine associations with osteoporosis-related traits (BMD, osteoporosis, or fracture) in Korean subjects (n=1,269). The identified SNPs of osteoporosis-related traits in Korean subjects were included in the replication analysis using Chinese (n=2,327) and Japanese (n=768) cohorts. RESULTS: A total of 17 SNPs were associated with low BMD in Korean subjects. Specifically, 9, 6, 9, and 5 SNPs were associated with the presence of osteoporosis, non-vertebral fractures, vertebral fractures, and any fracture, respectively. Collectively, 35 of the 95 SNPs (36.8%) were associated with one or more osteoporosis-related trait in Korean subjects. Of the 35 SNPs, 19 SNPs (54.3%) were also associated with one or more osteoporosis-related traits in East Asian populations. Twelve SNPs were associated with low BMD in the Chinese and Japanese cohorts. Specifically, 3, 4, and 2 SNPs were associated with the presence of hip fractures, vertebral fractures, and any fracture, respectively. CONCLUSIONS: Our results identified the common SNPs of osteoporosis-related traits in both Caucasian and East Asian populations. These SNPs should be further investigated to assess whether they are true genetic markers of osteoporosis.

Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized, Double-Blind, Placebo-Controlled Trial with Open-Label Extension

PURPOSE: The efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study. MATERIALS AND METHODS: Women aged 60 to 90 years with a T-score of <-2.5 and ≥-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg. RESULTS: Baseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals. CONCLUSION: Denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.

Vitamin D Repletion in Korean Postmenopausal Women with Osteoporosis

PURPOSE: Up to 71% of South Korean postmenopausal women have vitamin D deficiency {serum 25-hydroxyvitamin D [25(OH) D] level <50 nmol/L}. Data on vitamin D supplementation was collected during the screening phase of an efficacy/safety study of denosumab in Korean postmenopausal women with osteoporosis. This report describes the effect of vitamin D supplementation on repletion to 25(OH)D levels ≥50 nmol/L in Korean postmenopausal women with osteoporosis. MATERIALS AND METHODS: Vitamin D levels of Korean postmenopausal women (60-90 years old) were measured by extracting 25(OH)D2 and 25(OH)D3 from serum samples via protein precipitation and using liquid chromatography with tandem mass spectrometry detection. Calibration curves were constructed from the mass chromatograms to obtain total vitamin D levels. Subjects with serum 25(OH)D levels <50 nmol/L were supplemented with 1000 IU of vitamin D tablets during the 2.5-month-long screening period. Dose, frequency, and duration were determined by the investigator. If repletion was achieved (≥50 nmol/L) on retest, subjects were eligible to be rescreened for study entry. RESULTS: Of 371 subjects screened, 191 (52%) required vitamin D supplementation, and 88% (168 of 191) were successfully repleted. More than half of the subjects (58%) who were successfully repleted received doses of 2000 IU daily. The mean time to successful repletion was 31 days (standard deviation 8.4 days; range 11-48 days). CONCLUSION: Supplementation with daily median doses of 2000 IU vitamin D successfully repleted 88% of Korean postmenopausal women with osteoporosis within 48 days to a serum vitamin D level of 50 nmol/L.

Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis

BACKGROUND: The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis. METHODS: This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period. RESULTS: After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment. CONCLUSION: The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

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.