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Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. Among high-risk postmenopausal East Asian women, romosozumab followed by alendronate was associated with lower incidences of fractures vs alendronate alone. Romosozumab demonstrates potential to address an unmet need in osteoporosis management in Asia., Introduction: Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. The global ARCH study demonstrated superiority of romosozumab followed by alendronate in reducing fracture risk in high-risk postmenopausal osteoporotic women vs alendronate alone. We report outcomes among ARCH East Asian patients., Methods: In ARCH, 4093 postmenopausal osteoporotic women with fragility fracture were randomized 1:1 to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, both followed by open-label alendronate. Primary endpoints were incidence of new vertebral fracture (VF) at 24 months and clinical fracture at primary analysis (confirmed fractures in ≥ 330 patients and all patients had opportunity to attend month 24 visit). This post hoc analysis was not powered to detect fracture-rate differences., Results: This analysis included 275 patients from Hong Kong, Korea, and Taiwan. Romosozumab followed by alendronate reduced risk of new VFs at 24 months by 60% (P = 0.11) and clinical fractures at primary analysis by 44% (P = 0.15) vs alendronate alone. Romosozumab followed by alendronate significantly increased mean bone mineral density at 24 months from baseline by a further 9.0%, 3.3%, and 3.0% at the lumbar spine, total hip, and femoral neck vs alendronate alone. Adverse event (AE) rates, including positively adjudicated serious cardiovascular AEs (1.6% vs 1.4% at 12 months for romosozumab vs alendronate), were similar across treatment groups., Conclusions: Consistent with the global analysis, romosozumab followed by alendronate was associated with lower incidences of new vertebral, clinical, non-vertebral, and hip fractures vs alendronate alone among East Asian patients.

In aged population, the association of thyroid hormones on physical performance, especially within their normal range, has yet to be elucidated. In this study, individuals with low serum free T3/free T4 were likely to have low muscle mass and impaired physical performance., Purpose: We aimed to evaluate the associations of muscle mass, strength, and physical performance with thyroid hormone in an aged euthyroid population from a community-based cohort., Methods: We examined 918 men aged over 60 years and 1215 postmenopausal women from the Ansung cohort study. Appendicular skeletal muscle mass divided by square of height (ASM/ht 2 ) was used as the muscle mass index. Hand grip strength was measured using a hydraulic dynamometer. Physical performance was assessed using the short physical performance battery (SPPB)., Results: Participants with higher tertiles of free T3 and free T3/free T4 were younger and had higher ASM/ht 2 , stronger hand grip strength, and higher SPPB scores than those in the lower tertiles. In adjusted models, men within higher tertiles of free T3 had higher ASM/ht 2 compared with those within lower tertiles (p = 0.033), whereas subjects with higher tertiles of free T4 had lower ASM/ht 2 compared with those within lower tertiles (p = 0.043). Subjects within higher tertiles of free T3/free T4 had higher ASM/ht 2 (p < 0.001) and better physical performance (p = 0.048) than those within lower tertiles after adjustments. However, free T3, free T4, or free T3/free T4 was not related to hand grip strength after adjustment for covariates., Conclusion: Our results thus indicate that in an aged euthyroid population, low serum free T3/free T4 was a better index for low muscle mass and impaired physical performance than serum free T3 or free T4 alone.

Dietary potassium may neutralize acid load and reduce calcium loss from the bone, leading to beneficial effect on bone mineral density. In this nationwide Korean population study, dietary potassium intake was associated with improved bone mineral density in older men and postmenopausal women., Introduction: Nutrition is a major modifiable factor that affects bone health. The accompanying anion in dietary potassium may act as an alkaline source by neutralizing the acid load and reducing calcium loss from the bone. We aimed to evaluate the association between dietary potassium intake and bone mineral density (BMD) in the Korean population., Methods: We analyzed a total of 3135 men aged >50 years and 4052 postmenopausal women from the Korean National Health and Nutrition Examination Survey (KNHANES). Lumbar spine, total hip, and femur neck BMD were measured using dual energy X-ray absorptiometry. The daily food intake was assessed using a food frequency questionnaire., Results: When we divided the participants into tertiles based on the intake of potassium intake, the highest potassium intake tertile group showed a significantly higher total hip and femur neck BMD as compared to lower tertile groups (0.914 ± 0.004, 0.928 ± 0.003, 0.925 ± 0.004 mg/day across the tertiles, P = .014 for total hip; 0.736 ± 0.003, 0.748 ± 0.003, 0.750 ± 0.004 mg/day, P = .012 for femur neck). Postmenopausal women in the highest potassium intake tertile group showed significantly higher lumbar, total hip, and femur neck BMD as compared to those in lower potassium intake tertile groups (0.793 ± 0.004, 0.793 ± 0.003, 0.805 ± 0.004 mg/day across the tertiles, P = .029 for lumbar spine; 0.766 ± 0.003, 0.770 ± 0.002, 0.780 ± 0.003 mg/day, P = .002 for total hip; 0.615 ± 0.003, 0.619 ± 0.002, 0.628 ± 0.003 mg/day, P = .002 for femur neck)., Conclusions: Dietary potassium intake was positively associated with BMD in men aged >50 years and postmenopausal women, indicating the beneficial effects of dietary potassium intake on bone health.

Little is known about the association between vitamin D deficiency and the skeletal phenotypes in primary hyperparathyroidism (PHPT) patients. A low 25-hydroxyvitamin D level was associated with a low bone mineral density and deteriorated hip geometry in women with PHPT in an Asian population where vitamin D deficiency is prevalent., Introduction: Few studies have examined the effect of vitamin D deficiency on the bone health of primary hyperparathyroidism (PHPT) patients., Methods: We investigated the skeletal effects of vitamin D deficiency in 79 PHPT patients by assessing bone mineral density (BMD), the trabecular bone score (TBS), and hip geometry, which were measured using dual-energy X-ray absorptiometry (27 men with median age 60 years [53;69]; 52 postmenopausal women with median age of 57 years [53;67]). Cross-sectional data were collected from subjects enrolled in an ongoing PHPT cohort study at Seoul National University Hospital from March 2008 to December 2015., Results: We classified PHPT patients according to 25-hydroxyvitamin D (25(OH)D) levels (<20 vs. ≥20 ng/ml). After adjusting for age and body mass index, women with vitamin D deficiency had lower BMDs at the lumbar spine (LS) and femur neck (FN) than women who had sufficient levels of vitamin D (LS, 0.903 ± 0.138 vs. 0.998 ± 0.184 g/cm 2 ; FN, 0.715 ± 0.084 vs. 0.791 ± 0.113 g/cm 2 ; P < 0.05). However, the total hip BMD and the TBS were not significantly different between the two groups. In the hip geometry analysis, the cross-sectional area, cross-sectional moment of inertia, and section modulus were also significantly lower in women with vitamin D deficiency than in those without. No significant difference was found in the BMD, TBS, or hip geometry according to 25(OH)D levels in men., Conclusion: Vitamin D deficiency may be associated with a low BMD and deteriorated hip geometry in postmenopausal women with PHPT.

In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index., Introduction: AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer., Methods: We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >-2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry., Results: BMD significantly decreased from baseline to 5 years at the lumbar spine (-6.15%), femur neck (-7.12%), and total hip (-6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (-2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD., Conclusions: Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs.

This study evaluated the use of low-dose chest computed tomography (LDCT) for detecting bone fragility. LDCT-measured vertebral bone attenuation by volumetric methods showed good correlation with bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA, and good diagnostic performance for identifying osteoporosis and compression fractures. The results of this study suggest the feasibility of obtaining comprehensive information on bone health in subjects undergoing LDCT., Introduction: Osteoporosis is a prevalent but underdiagnosed disease that increases fracture risk. This study evaluated the utility of vertebral attenuation derived from low-dose chest computed tomography (LDCT) compared to dual-energy x-ray absorptiometry (DXA) for detecting bone fragility., Methods: A total of 232 subjects (78 men and 154 women) aged above 50 years who underwent both LDCT and DXA within 30 days were evaluated. LDCT-measured bone attenuation in Hounsfield units (HU) of four vertebrae (T4, T7, T10, and L1) was evaluated using volumetric methods for correlation with DXA-measured bone mineral density (BMD) and for the diagnosis of compression fractures, osteoporosis, and low BMD (osteoporosis or osteopenia) in men and women, with DXA measurements as the reference standard., Results: The average attenuation of the four vertebrae showed strong correlation with DXA-measured BMD of the lumbar spine (r = 0.726, p < 0.05). In receiver-operating characteristic (ROC) analyses, the area under the curve (AUC) across LDCT-measured thresholds of the average attenuation to distinguish compression fractures was 0.827, and a threshold of 129.5 HU yielded 90.9 % sensitivity and 64.4 % specificity. Similarly, average attenuation showed high AUCs and good diagnostic performance for detecting osteoporosis and low BMD in both men and women. Among 44 subjects with compression fractures, the average bone attenuation showed strong negative correlation with both the worst fracture grade (r = -0.525, p < 0.05) and cumulative fracture grade score (r = -0.633, p < 0.05)., Conclusion: LDCT-measured bone attenuation by volumetric methods showed good correlation with BMD measured by DXA and good diagnostic performance for identifying bone fragility.

Unlabelled: The effects of diabetes medications on risk of fracture were investigated using the South Korea nationwide claims database. We demonstrated that the use of dipeptidyl peptidase-4 inhibitor could be associated with decreased risk of fracture. Thiazolidinedione use was associated with about 60 % increased risk of fracture in real clinical practice., Introduction: The effects of diabetes medication on fracture have important clinical health consequences, since most diabetes patients are at high risk of fracture. We aimed to investigate the effect of diabetes medication on fracture risk., Methods: The nationwide medical claim database in South Korea was investigated. Among 2,886,555 subjects with antidiabetes prescriptions, 207,558 subjects aged 50 years and older, who initiated diabetes medication from 2008 to 2011, were analyzed. The subjects were classified based on diabetes medication classes: non-user (insufficient exposure), metformin (MET), sulfonylurea (SU), alpha-glucosidase inhibitor (AGI), MET + SU, MET + thiazolidinedione (TZD), MET + dipeptidyl peptidase-4 inhibitor (DPP4-I), and SU + TZD., Results: A total of 5996 fractures were observed. The fracture rate varied significantly across type of diabetes medications, with MET + DPP4-I combination group having the lowest rate and SU + TZD combination group having the highest rate. Compared to non-users, MET + DPP4-I inhibitor combination group had significantly reduced composite fracture risk (hazard ratio (HR) = 0.83, P = 0.025) and significantly reduced vertebral fracture risk (HR = 0.73, P = 0.013) in the unadjusted analysis. Compared to MET + SU users, MET + DPP4-I users showed a trend of lower non-vertebral fracture risk (HR = 0.82, P = 0.086) after adjusting for all confounding variables. Patients using TZD had significantly increased risk of fracture (HR = 1.59, P < 0.001) compared with patients not using TZDs adjusting for all confounding variables., Conclusions: The results of this nationwide study showed a trend that DPP4 inhibitor might have a protective effect on bone metabolism compared with SU, when added to MET. Clinicians should take these results into consideration when prescribing diabetes medication, especially in elderly patients or those at high risk or fracture.

Unlabelled: A daughter's bone mineral density (BMD) is significantly correlated with her mother's BMD, but the daughter's body mass index (BMI) could modulate this association. Maternal inheritance dominantly affects daughters with a lower BMI, but BMI could compensate for hereditary influences in daughters with a higher BMI in terms of daughter's BMD., Introduction: Achieving optimal peak bone mass at a young age is the best way to protect against future osteoporosis and subsequent fractures. Although environmental components influence bone mass accrual, but peak bone mass is largely programmed by inheritance. The aims of this study were to investigate the influence of maternal inheritance on the daughter's bone mass and to assess whether these influences differ according to the daughter's body mass index (BMI)., Methods: We used data obtained from the 2010 Korean National Health and Nutrition Examination Survey V and included 187 mother-daughter pairs. Bone mineral density (BMD) was measured at the lumbar spine (LS), femur neck (FN), and total hip (TH) by using dual-energy X-ray absorptiometry (DXA). The daughter group was stratified into two groups according to the mean BMI (21.4 kg/m(2))., Results: The daughters' BMD correlated significantly with both their BMI and their mothers' Z-score for each skeletal site. In the daughters with a lower BMI (≤21.4 kg/m(2)), the BMDs at the FN and TH were affected more by the mothers' Z-score than by the daughters' BMI. Meanwhile, the influence of the daughters' BMI on their BMD was higher than that of their mothers' Z-score in daughters with a higher BMI (>21.4 kg/m(2)). Moreover, the mothers' Z-scores were a significant predictor of their daughters having Z-scores < -1.0 only in daughters with a lower BMI., Conclusions: This study suggests that maternal inheritance is an important determinant of the daughters' bone mass, but that this hereditary factor may vary according to the daughters' BMI.

Summary: In a prospective community-based cohort study, we investigated the relationship between trabecular bone score (TBS) and regional fat depots in 1474 Korean postmenopausal women. TBS was positively related with subcutaneous fat and negatively related with visceral fat., Introduction: The effect of fat distribution (visceral/subcutaneous) on bone quality or microarchitecture has rarely been investigated due to measurement difficulty. We aimed to investigate the relationship between TBS reflecting bone microarchitecture and regional fat depots in Korean women., Methods: Cross-sectional data evaluation was made from subjects participating in an ongoing prospective community-based cohort study since 2001. A total of 1474 postmenopausal women in the Ansung cohort were analyzed. Regional body fat mass, bone mineral density (BMD) at the lumbar spine, and total hip and lumbar spine TBS were measured by dual energy X-ray absorptiometry (DXA)., Results: In an age-adjusted partial correlation analysis, TBS was not associated with total fat mass, but negatively associated with trunk fat mass. However, TBS was positively related with leg (r = 0.102, P < 0.05) and gynoid fat mass (r = 0.086, P < 0.05) and negatively related with android fat mass (r = -0.106; P < 0.05). In linear regression models controlling age, BMI, and physical activity, android fat was inversely associated with TBS (β = -0.595, P < 0.001), whereas gynoid fat was positively associated with TBS (β = 0.216, P < 0.001). Lumbar spine and total hip BMDs revealed positive associations with total and all regional fat depots regardless of fat distribution., Conclusion: Our findings suggest that relatively large visceral fat and small subcutaneous fat may have a detrimental effect on TBS, a bone microarchitecture index.

Summary: Our study showed that serum osteocalcin levels are closely related to glucose metabolism in men of all ages and younger women. This association disappeared in postmenopausal women in which increases bone turnover rates. The association between serum osteocalcin levels and glucose homeostasis should be interpreted according to age and sex., Introduction: Osteocalcin, a marker of bone formation, appears to be associated with glucose homeostasis. We investigated the age- and sex-specific association of serum osteocalcin level with variables related to glucose metabolism., Methods: This study was based on cross-sectional analysis from 719 participants aged 20-85 years after excluding patients taking antidiabetic or antiosteoporotic drugs. The subjects were divided into four groups according to age and sex as follows: men <50 years (n = 131), men ≥50 years (n = 191), women <50 years (n = 108), and women ≥50 years (n = 279). Anthropometric and biochemical variables including insulin resistance (HOMA-IR) and β cell function (HOMA-β) from a 75-g oral glucose tolerance test, and serum 25-OH-vitamin D and parathyroid hormone levels were measured., Results: The serum osteocalcin level was significantly higher in women aged ≥50 years compared with women <50 years (20.4 ± 7.8 vs. 17.9 ± 6.8 ng/ml, p < 0.001), but there was no difference between men aged ≥50 years and men <50 years (16.4 ± 5.9 vs. 16.8 ± 6.0 ng/ml, p = 0.905). The participants diagnosed with diabetes had lower serum osteocalcin levels than normal or prediabetic participants. Multivariable regression analyses including HOMA-IR and HOMA-β indicated that serum osteocalcin levels had a negative and independent association with HbA1c levels in men and women aged <50 years, but not in women ≥50 years., Conclusions: Low osteocalcin levels are associated with impaired glucose metabolism in men and premenopausal women. The osteocalcin levels may be determined by factors related to bone metabolism in postmenopausal women. Our data suggest that the serum levels of osteocalcin associated with glucose homeostasis should be interpreted according to age and sex.

Summary: Lumbar spine trabecular bone score (TBS) was significantly decreased in active acromegaly patients. TBS may be useful to assess the skeletal fragility in acromegaly in which bone mineral density (BMD) is not sufficient to represent bone strength and explain the high incidence of fragility fractures in acromegaly patients., Introduction: Although the data on BMD are controversial, patients with acromegaly have an increased risk of fragility fracture. We examined the lumbar spine TBS to explain the skeletal deterioration in acromegaly patients., Methods: We included 14 men and 19 women acromegaly patients who underwent dual-energy X-ray absorptiometry at the time of diagnosis from 2000 to 2014 at Seoul National University Hospital. Ninety-nine age-, sex- and body mass index-matched controls were recruited. Biochemical parameters, lumbar spine TBS, and BMD at all sites were measured. Gonadal status was evaluated at diagnosis., Results: Lumbar spine TBS was lower in acromegaly patients than in controls in both genders (1.345 ± 0.121 vs. 1.427 ± 0.087, P = 0.005 in men; 1.356 ± 0.082 vs. 1.431 ± 0.071, P = 0.001 in women). In contrast, BMD at all sites did not differ between the two groups. Hypogonadal acromegaly patients (men, n = 9; women, n = 12) had lower TBS values compared with controls both in men and women (all P < 0.05), although BMD at all sites were similar for the two groups. In eugonadal acromegaly patients, lumbar spine TBS was lower than in women controls only (P = 0.041)., Conclusions: Skeletal microarchitecture was deteriorated in acromegaly patients as assessed by TBS, which seems to be a consequence of growth hormone excess as well as hypogonadism, especially in women.

Unlabelled: Trabecular bone scores (TBS) have recently been developed as a diagnostic tool to assess bone texture. We studied thyroid status and TBS in a population-based cohort and demonstrated that high-normal thyroxine levels are associated with low TBS in healthy euthyroid postmenopausal women., Introduction: Increased thyroid hormone levels affect bone mineral density (BMD) and, if untreated, increase the risk of fracture. However, the relationship between thyroid function and bone microarchitecture has not yet been established. Trabecular bone scores (TBS) are gray-level textural measurements of dual energy X-ray absorptiometry (DXA) images. The TBS has been proposed as an indirect index of bone microarchitecture. The goal of this study was to characterize the relationship between thyroid function and TBS in euthyroid men and postmenopausal euthyroid women., Methods: A total of 1376 euthyroid subjects (648 postmenopausal women and 728 men) were recruited from a community-based cohort in Korea. Free thyroxine (fT4) levels, thyroid stimulating hormone (TSH) levels, BMD, and TBS were measured and compared., Results: There was no significant relationship between either fT4 or TSH levels and BMD in men and women. Multiple linear regression analysis showed that high-normal fT4 levels were negatively correlated with TBS (β = -0.111; P = 0.002, after adjusting for both age and body mass index [BMI]) in postmenopausal women. In men, however, there was no significant correlation between fT4 levels and TBS. TSH levels were not significantly associated with TBS in either men or women., Conclusion: Higher fT4 levels within the normal reference range are associated with deterioration of trabecular microarchitecture in healthy euthyroid postmenopausal women.

Unlabelled: Dietary vitamin C intake showed significant positive associations with BMD in postmenopausal women, especially with vitamin D deficiency., Introduction: Although there is a positive role of vitamin C in osteoblastogenesis, debate remains about the contribution of vitamin C to bone mineral density (BMD) in humans., Methods: Data were derived from the Fourth Korean National Health and Nutrition Examination Survey. Dietary information was assessed using a 24-h dietary recall questionnaire. BMD was measured by dual-energy X-ray absorptiometry at the lumbar and hip., Results: A total of 1,196 postmenopausal women aged 50 years and older were stratified into tertiles by daily dietary vitamin C intake. After adjusting for traditional confounders, dietary vitamin C intake tertile was significantly positively associated with BMD at all sites (R = 0.513 for lumbar spine (LS) and R = 0.657 for femoral neck (FN), P < 0.05 for each). The subjects with osteoporosis had significantly lower dietary vitamin C intake than did subjects without osteoporosis (74.4 ± 66.2 vs 94.1 ± 78.6 mg/day for LS and 65.5 ± 56.6 vs 94.3 ± 79.2 mg/day for FN, respectively, P < 0.001). The multiple-adjusted odds ratio for osteoporosis for dietary vitamin C <100 mg/day was 1.790 (95 % CI 1.333-2.405, P < 0.001). However, the significant association between vitamin C intake and BMD was only observed in subjects with vitamin D deficiency and aged 50-59 years or >70 years., Conclusion: Dietary vitamin C intake was positively associated with BMD in postmenopausal women, and inadequate vitamin C intake could increase the risk of osteoporosis.

Unlabelled: We determined the incidence of second hip fracture and evaluated whether compliant and persistent users of bisphosphonate had a lower incidence of second hip fracture after prior hip fracture, from a national claim registry., Introduction: Bisphosphonate is prescribed worldwide for the primary prevention of osteoporotic fracture. However, the association between adherent use of bisphosphonate and prevention of second hip fracture is unclear. Our purpose was to determine whether the adherent use of bisphosphonate was associated with a decreased risk of second hip fracture in South Korea, using a nationwide database., Methods: From 2007 to 2011, first and second hip fractures were identified using the ICD-10 and procedure code form from the nationwide database of the Health Insurance Review and Assessment Service. Compliant use of bisphosphonate was defined as a patient medication possession ratio of 80 or more. Persistent users were defined patients with a refill gap of 30 days or less. We compared the incidence of second hip fracture in compliant and persistent users and non-users., Results: Among 59,782 patients with first hip fracture, in this study, 1,336 second hip fracture occurred after the initial hip fracture during the study period. The mean age at the first hip fracture was 75.4 years (range, 50 to 100 years). The cumulative 1-year, 2-year, and 3-year incidence of second hip fracture was 1.0% (552/59,782), 1.9% (1,123/59,782), and 2.2% (1,336/59,782), respectively. After multivariate analysis, compliant and persistent use of bisphosphonate was significantly independent protectors for second hip fracture (HR, 0.595; 95% CI, 0.400-0.885; HR, 0.433; 95% CI, 0.327-0.573, respectively)., Conclusions: Compliant and persistent use of bisphosphonate decreases the risk of second hip fracture, in terms of secondary prevention.

Summary: Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs., Introduction: Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples., Methods: A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis., Results: Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta)., Conclusion: Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.

Summary: We evaluated trends in the incidences of typical and atypical hip fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data obtained from the Health Insurance Review and Assessment Service (HIRA)., Introduction: Recently, atypical hip fractures in the subtrochanteric region have been reported among patients on bisphosphonate. However, the association between atypical hip fracture and bisphosphonate is controversial. We evaluated trends in the incidences of typical and atypical hip fracture in relation to bisphosphonate use in Korea from 2006 to 2010, using nationwide data obtained from the HIRA., Methods: All new visits or admissions to clinics or hospitals for a typical and atypical hip fractures were recorded nationwide by HIRA using the ICD-10 code classification. Typical and atypical hip fractures were defined as femoral neck/intertrochanteric and subtrochanteric fracture, respectively. Bisphosphonate prescription data were also abstracted from the HIRA database., Results: The absolute number of typical and atypical hip fracture increased during the study period. Although age-adjusted incidence rates of typical hip fractures were stable in men and women, those of atypical hip fractures increased in women. Nationally, the annual numbers of prescriptions of bisphosphonate also increased during the study period., Conclusions: The results of this study suggest a possible causal relationship between bisphosphonate use and the increased incidence of atypical hip fracture in Korea.

Unlabelled: Many diabetic patients with vertebral fractures remain undiagnosed and untreated. We found that more than two-thirds of osteoporotic diabetic women could not be identified for pharmacological treatment according to the NOF guidelines if without radiographic vertebral assessment. This study shows the importance of radiographic vertebral assessment for identifying patients who need treatment for osteoporosis in diabetic women., Introduction: Diagnosis of vertebral fracture (VF) is important for identifying patients who need pharmacologic therapy for osteoporosis. However, many patients with vertebral fractures remain undiagnosed and untreated. This study evaluated the number of patients with VFs who would be unrecognized as candidates for osteoporosis treatments according to the National Osteoporosis Foundation (NOF) Clinician’s Guidelines to the Treatment of Osteoporosis, among postmenopausal diabetic Korean women without spinal imaging., Methods: A total of 873 postmenopausal diabetic women were enrolled. Lateral plain radiographs of the thoracolumbar spine and total hip BMD were obtained. The Fracture Risk Assessment Tool (FRAX®) probability was computed using the algorithm available online at http://www.shef.ac.uk/FRAX (South Korea version). The subjects with and without VFs were classified into candidates for osteoporosis treatment [Tx+by NOF] and not candidates for osteoporosis treatment [Tx−by NOF] according to the NOF pharmacologic treatment guidelines, regardless of the presence of VFs., Results: Forty-six percent of postmenopausal diabetic womenhad morphometric VFs. Among the subjects with morphometric VFs, only 2% of the patients had previously diagnosed VFs by medical doctors. In addition, 73.6% of the patients with VFs were not included in the [Tx+by NOF] group, given the assumption of no radiographic diagnosis of VFs., Conclusions: With regard to increased risk of VFs in postmenopausal Korean women with type 2 diabetes mellitus, radiographic vertebral assessment would be useful for the clinical identification of osteoporosis and fractures.

Summary: Although obesity and osteoporosis are important public health problems, the effect of fat mass on bone mass remains controversial. This study demonstrated that fat mass was inversely related to bone mineral content, and abdominal obesity was significantly associated with bone mineral content independent of total fat mass., Introduction: Obesity and osteoporosis, two disorders of body composition, have become increasingly important public health problems throughout the world. However, the effect of fat mass on bone mass remains controversial. This study investigates the effect of fat mass and regional fat distribution on bone mass within a community-dwelling cohort., Methods: A total of 3,042 subjects (1,284 men, 362 premenopausal women, and 1,396 postmenopausal women) were studied. Fat mass, percent fat mass, lean mass, percent lean mass, and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry., Results: Fat mass and percent fat mass decreased significantly across increasing tertiles of BMC in all three subgroups (men, premenopausal and postmenopausal women). In contrast, lean mass and percent lean mass increased significantly across tertiles of BMC in men, and a similar trend was also identified in postmenopausal women. Interestingly, although correlation analysis showed a positive association between fat mass and BMC (p < 0.05), this association became negative after controlling for age and weight (p < 0.05). Finally, in premenopausal and postmenopausal women, subjects with the lowest waist circumference (WC) had the highest BMC in the higher three quartiles of percent fat mass after adjusting for age and weight (p < 0.05), indicating that abdominal obesity is associated with BMC independent of total fat mass., Conclusion: This study demonstrated that fat mass was inversely related to BMC after removing the mechanical loading effect in Korean men and women. Moreover, abdominal obesity as measured by WC was significantly associated with BMC independent of total fat mass.