Age-Dependent Association of Height Loss with Incident Fracture Risk in Postmenopausal Korean Women

Background Height loss is a simple clinical measure associated with increased fracture risk. However, limited data exists on the association between height loss and fracture risk in postmenopausal Korean women. It is unknown whether this association varies with age. Methods Data on height loss over a 6-year period were collected from a community-based longitudinal follow-up cohort (Ansung cohort of the Korean Genome and Epidemiology Study). Incident fractures were defined based on self-reported fractures after excluding those due to severe trauma or toes/fingers. The association between incident fractures and height loss was investigated using a Cox proportional hazards model. Results During a median follow-up of 10 years after the second visit, 259/1,806 participants (median age, 64 years) experienced incident fractures. Overall, a 1 standard deviation (SD) decrease in height (1.6 cm/median 5.8 years) was associated with 9% increased risk of fracture (hazard ratio [HR], 1.09; P=0.037), which lost statistical significance after adjustment for covariates. When stratified into age groups (50–59, 60–69, 70 years or older), a 1 SD decrease in height remained a robust predictor of fracture in the 50 to 59 years age group after adjusting for covariates (adjusted hazard ratio [aHR], 1.52; P=0.003), whereas height loss was not an independent predictor of fracture in the 60 to 69 (aHR, 1.06; P=0.333) or the 70 years or older age groups (aHR, 1.05; P=0.700; P for interaction <0.05, for all). Conclusion Height loss during the previous 6 years was associated with an increased 10-year fracture risk in postmenopausal women in their 50s

Effect of Oral Supplementation with Branched-chain Amino Acid (BCAA) during Radiotherapy in Patients with Hepatocellular Carcinoma: A Double-Blind Randomized Study

PURPOSE: The present study evaluated whether oral supplementation with a branched-chain amino acid (BCAA) improves the biochemical and amino acid profiles of liver tumor patients undergoing radiotherapy. MATERIALS AND METHODS: Patients were randomly assigned to one of 2 groups: a group given oral supplementation with BCAA granules (LIVACT granules; Samil Pharm Co., Korea, each granule containing L-isoleucine 952 mg, L-leucine 1,904 mg, and L-valine 1,144 mg) during radiotherapy, or a placebo group. Physical and biochemical examinations and measurements, including subjective symptoms, Child-Pugh class, body mass index, plasma albumin concentration, and plasma amino acid profiles were monitored. RESULTS: Fifty were enrolled between November 2005 and November 2006. We also analyzed data from 37 hepatocellular carcinoma (HCC) patients in order to evaluate a more homogenous group. The two groups of patients were comparable in terms of age, gender, Child-Pugh score, and underlying hepatitis virus type. Serum albumin, total protein, liver enzymes, and cholesterol showed a tendency to increase in the BCAA group. In this group, the percentage of cases that reverted to normal serum albumin levels between 3 and 10 weeks after administration of BCAA was significantly higher (41.18%) than in the placebo group (p=0.043). CONCLUSION: Oral supplementation with a BCAA preparation seems to help HCC patients undergoing radiotherapy by increasing the BCAA concentration.ope

Resorption controls bone anabolism driven by PTH receptor signaling in osteocytes

The contribution of remodeling-based bone formation coupled to osteoclast activity versus modeling-based bone formation that occurs independently of resorption, to the anabolic effect of PTH remains unclear. We addressed this question using transgenic mice with activated PTH receptor signaling in osteocytes that exhibit increased bone mass and remodeling, recognized skeletal effects of PTH elevation. Direct inhibition of bone formation was accomplished genetically by overexpressing the Wnt antagonist Sost/sclerostin; and resorption-dependent bone formation was inhibited pharmacologically with the bisphosphonate alendronate. We found that bone formation induced by osteocytic PTH receptor signaling on the periosteal surface depends on Wnt signaling but not on resorption. In contrast, bone formation on the endocortical surface results from a combination of Wnt-driven increased osteoblast number and resorption-dependent osteoblast activity. Moreover, elevated osteoclasts and intracortical/calvarial porosity is exacerbated by overexpressing Sost and reversed by blocking resorption. Furthermore, increased cancellous bone is abolished by Wnt inhibition but further increased by blocking resorption. Thus, resorption induced by PTH receptor signaling in osteocytes is critical for full anabolism in cortical bone, but tempers bone gain in cancellous bone. Dissecting underlying mechanisms of PTH receptor signaling would allow targeting actions in different bone compartments, enhancing the therapeutic potential of the pathway

Assessment of Bone Quality using Finite Element Analysis Based upon Micro-CT Images

BACKGROUND: To evaluate the feasibility of a micro-image based finite element model to determine the efficacy of sequential treatments on the bone quality in a rat osteoporosis model. METHODS: Rat osteoporosis and treated osteoporosis models were established with the bone loss, restore and maintain concept. Thirty Sprague-Dawley rats were used in this study. A sham operation or ovariectomy was performed at 20 weeks after birth, which was followed by the respective sequential trials as follows: (1) sham-operation only, (2) ovariectomy only, (3) ovariectomized rats with parathyroid hormone maintenance, (4) ovariectomized rats treated with PTH for 5 weeks and then withdrawal, (5) ovariectomized rats treated with PTH for 5 weeks and then with 17 beta-estradiol, and (6) ovariectomized rats treated with parathyroid hormone for 5 weeks and then treated with zoledronate. The histomorphometry indices were determined using the micro-images from a micro-computed tomogram. Finite element analysis was carried out to determine the mechanical properties (Stiffness and Young's modulus) of the vertebra bodies. The differences in properties between the groups were compared using ANOVA and a Bonferroni's multiple group comparison procedure. RESULTS: The histomorphometry and mechanical properties were significantly better in groups (3) and (6) than in the groups (1) and (2) (p < 0.05). The stiffness (sigma(s)) and Young's modulus (E) was highest in group (3) following by group (6). CONCLUSIONS: Finite element analysis based on micro-images provides a useful tool that reflects the changes in micro-structural and mechanical properties of a rat vertebral body with the bone loss, restore and maintain concept.ope

The Korean urban rural elderly cohort study: study design and protocol

BACKGROUND: Korea is one of the fastest aging countries and is expected to become a super-aged society within 12 years. The Korean Urban Rural Elderly (KURE) study was developed to evaluate the epidemiological characteristics and establish the prevention and management of major disorders of the elderly in Korea. METHODS/DESIGN: The KURE study is a community-based prospective cohort study on health, aging, and common geriatric disorders of Korean elderly persons aged at least 65 years. To construct a cohort reflecting both urban and rural areas, we selected 2 representative communities in the country. To establish multidisciplinary approaches to geriatric health, this study was performed by researchers in the divisions of geriatrics, preventive medicine, endocrinology, and sociology. The baseline examinations began in 2012; the study will follow more than 4,000 elderly Koreans over 10 years. The first and second follow-up health examinations will be performed every 4 years. Every 2 years after each health examination, inter-assessment interview will be conducted to improve participant retention. DISCUSSION: The KURE study will provide longitudinal epidemiologic data on health, aging, and common geriatric disorders of the elderly in Korea. This is a comprehensive, multidisciplinary study of the elderly with respect to biological, physical, socio-economic, and environmental factors. The results of this study will contribute to improve public health and welfare policies for the aging society in Korea

BUROSUMAB IN TUMOR-INDUCED OSTEOMALACIA

Patients with tumor-induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X-linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti-fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open-label, intraindividual dose-adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient-reported outcomes. Safety was assessed based on treatment-emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6-minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment-related TEAEs of grade ≥3 and no treatment-related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated

Elevated morbidity and mortality in patients with chronic idiopathic hypophosphatemia: a nationwide cohort study

BackgroundChronic idiopathic hypophosphatemia (CIH) induced by X-linked hypophosphatemic rickets or tumor-induced osteomalacia is a rare inherited or acquired disorder. However, due to its rarity, little is known about the epidemiology and natural course of CIH. Therefore, we aimed to identify the prevalence and long-term health outcomes of CIH patients.MethodsUsing the Korean Health Insurance Review and Assessment claims database, we evaluated the incidence of hypophosphatemia initially diagnosed from 2003 to 2018. After excluding secondary conditions that could change serum phosphorus levels, we identified 154 patients (76 men and 78 women) with non-secondary and non-renal hypophosphatemia. These hypophosphatemic patients were compared at a ratio of 1:10 with age-, sex-, and index-year-matched controls (n = 1,540).ResultsIn the distribution of age at diagnosis, a large peak was observed in patients aged 1–4 years and small peaks were observed in ages from 40–70 years. The age-standardized incidence rate showed non-statistically significant trend from 0.24 per 1,000,000 persons in 2003 to 0.30 in 2018. Hypophosphatemic patients had a higher risk of any complication (adjusted hazard ratio [aHR], 2.17; 95% confidence interval [CI], 1.67–2.69) including cardiovascular outcomes, chronic kidney disease, hyperparathyroidism, osteoporotic fractures, periodontitis, and depression. Hypophosphatemic patients also had higher risks of mortality and hospitalization than the controls (aHR, 3.26; 95% CI, 1.83–5.81; and aHR, 2.49; 95% CI, 1.97–3.16, respectively).ConclusionThis first nationwide study of CIH in South Korea found a bimodal age distribution and no sex differences among patients. Hypophosphatemic patients had higher risks of complications, mortality, and hospitalization compared to age- and sex-matched controls

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

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

Socioeconomic inequalities in obesity among Korean women aged 19-79 years: the 2016 Korean Study of Women’s Health-Related Issues

OBJECTIVES While the prevalence of obesity in Asian women has remained stagnant, studies of socioeconomic inequalities in obesity among Asian women are scarce. This study aimed to examine the recent prevalence of obesity in Korean women aged between 19 years and 79 years and to analyze socioeconomic inequalities in obesity. METHODS Data were derived from the 2016 Korean Study of Women’s Health-Related Issues. The chi-square test and logistic regression analysis were used to analyze the associations between socioeconomic factors and obesity using Asian standard body mass index (BMI) categories: low (<18.5 kg/m2 ), normal (18.5-22.9 kg/m2 ), overweight (23.0-24.9 kg/m2 ), and obese (≥25.0 kg/ m2 ). As inequality-specific indicators, the slope index of inequality (SII) and relative index of inequality (RII) were calculated, with adjustment for age and self-reported health status. RESULTS Korean women were classified into the following BMI categories: underweight (5.3%), normal weight (59.1%), overweight (21.2%), and obese (14.4%). The SII and RII revealed substantial inequalities in obesity in favor of more urbanized women (SII, 4.5; RII, 1.4) and against of women who were highly educated (SII, -16.7; RII, 0.3). Subgroup analysis revealed inequalities in obesity according to household income among younger women and according to urbanization among women aged 65-79 years. CONCLUSIONS Clear educational inequalities in obesity existed in Korean women. Reverse inequalities in urbanization were also apparent in older women. Developing strategies to address the multiple observed inequalities in obesity among Korean women may prove essential for effectively reducing the burden of this disease