Higher serum uric acid as a protective factor against incident osteoporotic fractures in Korean men: a longitudinal study using the National Claim Registry

Summary

In this large longitudinal study of 16,078 Korean men aged 50 years or older, we observed that baseline elevation of serum uric acid level significantly associated with a lower risk of incident fractures at osteoporosis-related sites during an average follow-up period of 3 years.

Introduction

Male osteoporosis and related fractures are becoming recognized as important public health concerns. Oxidative stress has detrimental effects on bone metabolism, and serum uric acid (UA) is known to be a strong endogenous antioxidant. In the present study, we performed a large longitudinal study with an average follow-up period of 3 years to clarify the role of UA on the risk of incident osteoporotic fractures (OFs).

Methods

A total of 16,078 Korean men aged 50 years or older who had undergone comprehensive routine health examinations were enrolled. Incident fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and proximal humerus) that occurred after the baseline examinations were identified from the nationwide claims database of the Health Insurance Review and Assessment Service of Korea by using selected International Classification of Diseases, 10th revision codes.

Results

In total, 158 (1.0 %) men developed incident OFs. The event rate was 33.1 per 10,000 person-years. Subjects without incident OFs had 6.0 % higher serum UA levels than subjects with OFs (P?=?0.001). Multivariable-adjusted Cox proportional hazard analyses adjusted for age, body mass index, glomerular filtration rate, lifestyle factors, medical and drug histories, and the presence of baseline radiological vertebral fractures revealed that the hazard ratio per standard deviation increase of baseline UA levels for the development of incident OFs was 0.829 (95 % CI?=?0.695–0.989, P?=?0.038).

Conclusions

These data provide the epidemiological evidence that serum UA may act as a protective factor against the development of incident OFs in Korean men.     

Low-intensity pulsed ultrasound is frequently used to treat fractures after osteosynthesis in elderly patients: A study using open data from the national database of health insurance claims of Japan

BackgroundThe national database of health insurance claims of Japan (NDB) includes almost all health insurance claims in Japan. Currently, we have many cases of geriatric fracture in Japan, probably due to an increase of the elderly population. The increase of geriatric fractures may influence the use of low-intensity pulsed ultrasound (LIPUS), which is used to accelerate the fracture repair process. The present state of LIPUS treatments was analyzed using the large dataset of the NDB.MethodsThe open data from the NDB that were used included receipts from April 2015 to March 2016. The total numbers of fracture treatments were counted as the sum of the claim items that were involved in fracture treatments. Two types of the insurance claim items for LIPUS treatments were counted separately: those used for delayed or non-union fractures; and those used for fractures within two weeks after osteosynthesis. Additionally, the ratio of the LIPUS treatments per the fracture treatments was calculated.ResultsIn female patients, the number of LIPUS treatments for fractures early after osteosynthesis showed a large peak in the senile generation. Additionally, the ratio of LIPUS treatments early after osteosynthesis to all osteosynthesis treatments tended to increase with age in both males and females, while the ratio of the LIPUS treatments for delayed or non-union fractures to all fracture treatments decreased with age.ConclusionsLIPUS treatments were frequently used to treat fractures early after osteosynthesis in elderly patients, probably due to the large number of fractures in the elderly population. Additionally, the ratio of LIPUS treatments early after osteosynthesis was high in both elderly female and elderly male patients, suggesting that there is a demand for early fracture repair.     

Relapsed prostate cancer with neuroendocrine differentiation and high serum levels of carcinoembryonic antigen without elevation of prostrate-specific antigen: A case report

A 62-year-old man had been treated with combined androgen blockade due to cT2bN1M0 prostate cancer, and his serum prostate-specific antigen (PSA) levels decreased and remained under the level of 0.5 ng/mL during therapy. Approximately 40 months after the initial therapy, difficulty on urination and constipation developed gradually, and serum carcinoembryonic antigen (CEA) and pro-gastrin-releasing peptide (ProGRP) levels were high at this point. He underwent transrectal and transurethral biopsy of the prostate, which revealed adenocarcinoma positive for CEA and chromogranin A. He received palliative pelvic irradiation, and oral estramustine phosphate and etoposide combined therapy. Tumor markers decreased and clinical symptoms improved for several months. The patient died of encephalopathy of unknown etiology approximately 11 months after the relapse.     

Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data

Background

Cystic fibrosis (CF) is the most common inherited disease in Caucasians, affecting around 10,000 individuals in the UK today. Prognosis has improved considerably over recent decades with ongoing improvements in treatment and care. Providing up-to-date survival predictions is important for patients, clinicians and health services planning.

Association of VKORC1-1639G>A polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine: a Korean study

Background

Abnormalities of bone metabolism may be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) of the spine. Besides its hemostatic effect, vitamin K epoxide reductase complex subunit 1 (VKORC1) plays a pivotal role in bone mineralization. The aim of this study is to investigate whether single nucleotide polymorphisms (SNPs) of the VKORC1 gene are associated with the occurrence of OPLL in a Korean population.

Method

A total of 98 patients with OPLL and 200 controls were genotyped for the VKORC1-1639G>A SNP (rs9923231) by polymerase chain reaction and restriction fragment length polymorphism analysis. All the patients (n?=?98) in this study underwent surgery (60, posterior-only approach; 36, anterior-only approach; 2, combined anterior and posterior approach) during their admission. We analyzed this association separately according to the gender and OPLL subgroup: OPLL continuous group (continuous type plus mixed type) and OPLL segmental group (segmental and localized type).

Results

We found that the genotype VKORC1-1639G>A frequency was significantly associated with the occurrence of the OPLL in the female group (adjusted odds ratio?=?5.22, 95 % confidence interval: 1.675 to 16.269, p?=?0.004). However, there was no overall association between the OPLL susceptibility and VKORC1-1639G>A polymorphism. A subgroup analysis did not show any significant correlation between VKORC1-1639G>A polymorphism and subgroup of OPLL either.

Conclusion

Our results suggest that the VKORC1-1639G>A SNP may increase susceptibility to OPLL in women. However, there was only a statistical association in the female group despite a number of stratified analyses. Therefore, the findings should be interpreted with caution, and further genetic study is needed to improve our understanding of the role of VKORC1 polymorphisms in determining the risk of OPLL occurrence.     

Utility of serum pancreatic enzyme levels in diagnosing blunt trauma to the pancreas: A prospective study with systematic review

Introduction

Reliability of serum pancreatic enzyme levels in predicting pancreatic injuries has been a parameter of interest and the present recommendations on its utility are based primarily on anecdotal observations. The aim of this study was to evaluate the utility of serum pancreatic enzyme assessment in predicting blunt pancreatic injury with imaging and surgical correlation and compare our results with a systematic review of literature till date.

Methods

A prospective cohort study conducted over 4 years in a tertiary care referral centre with 164 consecutive patients who presented to the emergency department with a history of blunt abdominal trauma and had serum pancreatic enzyme assessment, USG and subsequent diagnostic CECT were analyzed. The CT findings and AAST grade of pancreatic injury, various intra-abdominal injuries and time elapsed since injury and other associated factors were correlated with serum pancreatic enzyme levels. For systematic review of literature MEDLINE database was searched between 1940 and 2012, also the related citations and bibliographies of relevant articles were analyzed and 40 articles were included for review. We compared our results with the systematic critique of literature till date to formulate recommendations.

Results

33(21%) patients had pancreatic injury documented on CT and were graded according to AAST. Statistically significant elevated serum amylase levels were observed in patients with pancreatic and bowel injuries. However, elevated serum lipase was observed specifically in patients with pancreatic injury with or without bowel injury. Combined serum amylase and lipase showed 100% specificity, 85% sensitivity in predicting pancreatic injury. Elevated (n = 28, 85%) vs. normal (n = 5, 15%) serum amylase and lipase levels showed sole statistically significant association with time elapse since injury to admission, with a cutoff of 3 h.

Conclusions

Based on our results and the systematic review of the literature till date we conclude, persistently elevated or rising combined estimation of serum amylase and lipase levels are reliable indicators of pancreatic injury and is time dependent, nondiagnostic within 6 h or less after trauma. In resource constrained countries where CT is not available everywhere it may support a clinical suspicion of pancreatic injury and can be reliable and cost-effective as a screening tool.     

Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study

The plasma concentration of the adipocyte-derived peptide adiponectin is decreased in patients with obesity and type 2 diabetes. The adiponectin gene is located on chromosome 3q27, where a diabetes susceptibility locus has been mapped. Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies. Our aim was to assess the contribution of these SNPs in the development of features of the insulin resistance syndrome in a 3-year prospective study in approximately 4,500 French Caucasian subjects from the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. For subjects who were normoglycemic at baseline, the 3-year risk of becoming hyperglycemic (diabetes or impaired fasting glucose) was affected by two SNPs: G-11391A and T45G. For G-11391A, the risk was increased in GA carriers (odds ratio [OR] adjusted for sex [versus GG] = 1.60 [95% CI 1.16-2.20]; P = 0.004). For T45G, it was increased in GG carriers (OR [versus TT] = 2.71 [1.31-5.60]; P = 0.007). After 3 years, GG subjects had a greater increase in BMI (P = 0.009) and waist-to-hip ratio (P = 0.007). Adiponectin levels at baseline were associated with the development of hyperglycemia (P = 0.005), but the predictive effects on the risk for hyperglycemia were independent of adiponectin genotypes. In conclusion, in the DESIR study, variations at the adiponectin locus affect body weight gain, body fat distribution, and onset of hyperglycemia, as well as adiponectin levels. Adiponectin gene SNPs may have several phenotypic effects that co-occur with the development of the metabolic syndrome.     

A fifteen-year longitudinal study in young adults on the relation of physical activity and fitness with the development of the bone mass: The Amsterdam Growth And Health Longitudinal Study

Although positive effects of physical activity are often reported, there are still uncertainties about the type, intensity, duration, and frequency of these activities that are most effective for (re)modeling bone mass during youth. In the Amsterdam Growth and Health Longitudinal Study, daily physical activity and fitness were monitored from age 13 to 29 years in a group of 182 males and females. At a mean age of 28 years, bone mineral density (BMD) was measured at three sites with dual X-ray absorptiometry (DXA): in the lumbar region (lumbar BMD), the femoral neck (hip BMD), and the distal radius (wrist BMD). Physical activity (PA) was estimated from a cross-check activity interview taking in consideration all daily physical activities during the last 3 months; PA was scored in two different ways: (1) metabolic physical activity score (METPA) by weighting the intensity (multiples of basic metabolic rate [METs]) and duration (minutes per week); and (2) mechanic physical activity score (MECHPA) by weighting the peak strain (ground reaction forces as multiples of body mass) irrespective of frequency and duration of the physical activities. Physical fitness was measured with a neuromotor fitness test (composite of six strength, flexibility, and speed tests) and as cardiopulmonary fitness (maximal oxygen uptake). The physical activity and fitness scores were calculated over two age periods: during adolescence (13–16 years) and during adulthood (21–27 years). The standardized regression coefficients (corrected for gender, biological age, body composition, and calcium intake) show that weight, physical activity (both METPA and MECHPA), and neuromotor fitness during adolescence and in young adulthood are significantly and positively related with the lumbar BMD (β = 0.11–0.40) and hip BMD (β = 0.18–0.26), measured at the mean age of 28 years. This was not the case for cardiorespiratory fitness. No significant correlations at all are found with wrist BMD, a bone site that is less involved in physical activity and fitness. It can be concluded that daily physical activity during adolescence and in the young adult period is significantly related to the BMD at the lumbar spine and femoral neck at age 28 of males and females. Only neuromotor fitness and not cardiopulmonary fitness during adolescence and young adulthood is related to the BMD of males and females at age 28 years.     

Mortality in patients with trochanteric hip fractures (AO/OTA 31-A) treated with sliding hip screw versus intramedullary nail: A retrospective national registry study of 9547 patients from the Danish Fracture Database

BackgroundWhether trochanteric hip fractures (AO/OTA 31-A) should be treated with an intramedullary nail (IMN) or sliding hip screw (SHS) is debated. Recent studies suggest an association between IMN and excess mortality rates compared to SHS, but higher quality studies fail to show this association. Furthermore, there is an increased usage of IMN with sparse evidence supporting this rise. Our aim was to compare mortality rates between IMN and SHS in patients with AO/OTA 31-A fractures. Secondarily, to investigate choice of implant in relation to fracture subtype.MethodsThis national registry study is based on data from the Danish Fracture Database (DFDB). Data were retrieved on patients aged ≥65 years treated for a non-pathological AO/OTA type 31-A fracture with IMN or SHS from January 1, 2012 to December 31, 2018. Data from DFDB were merged with data from the Danish Civil Registration System (CRS) for time of death. Mortality rates were recorded at 30 days, 90 days, and 1 year and presented as crude mortality and adjusted for age, gender, ASA-class, and AO/OTA-subtype.ResultsA total of 9,547 patients were included. The mean age was 83 years, 69% were female, and 55% were ASA-class 3–5. We found higher mortality rates for IMN-patients at 30 days, 90 days, and 1 year. The crude relative mortality risk for IMN was also significantly higher at both 30 days (1.20) and 90 days (1.11). Adjusted relative mortality risk for IMN was 1.12 [0.96; 1.31] at 30-days, 1.03 [0.91; 1.17] at 90-days, and 1.01 [0.92; 1.11] at 1 year. Most patients suffered a 31-A2 fracture (56%) and, overall, 74% of patients were treated with IMN.ConclusionWe found significantly increased crude relative mortality risk at 30 days and 90 days in patients treated with IMN. However, when adjusting for confounders the two groups had similar mortality risks. In total, 74% of all patients in this cohort were treated with IMN.Level of evidenceThis study has level of evidence: III.     

A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study.

A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) has recently been associated with bone mineral density (BMD) in postmenopausal Japanese women. It is not known whether this effect is also present in European populations and whether it is caused by lower peak bone mass or accelerated postmenopausal bone loss. MTHFR genotyping was done in 1748 healthy postmenopausal Danish women participating in a prospective study of risk factors for osteoporosis. At the time of enrollment, 3-24 months after last menstrual period, the less prevalent genotype (TT, 8.7% of the population) was associated with significantly lower BMD at the femoral neck (ANOVA, p < 0.05), total hip (p < 0.01), and spine (p < 0.05 adjusted for lifestyle covariates, p = 0.06 without adjustment). The mean difference was between 0.1 and 0.3 SD, depending on measurement site. MTHFR genotype added significantly to prediction of BMD by weight and age. Fracture incidence was increased more than 2-fold in subjects with the TT genotype (risk ratio [RR], 2.6; 95% CI 1.2-5.6). This remained significant when the Cox analysis was controlled for BMD (RR, 2.4; 95% CI 1.1-5.2). No differences in serum osteocalcin, bone-specific alkaline phosphatase, and 25-OH-vitamin D were found between genotypes. The response to hormone replacement therapy (HRT) did not differ, but the association of the TT genotype with reduced BMD was maintained at the total hip after 5 years of HRT. The MTHFR TT genotype is associated with low BMD and increased fracture incidence in early postmenopausal women.     

Effects on bone geometry,density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism: A case‐control study using HR‐pQCT

Patients with primary hyperparathyroidism (PHPT) have continuously elevated parathyroid hormone (PTH) and consequently increased bone turnover with negative effects on cortical (Ct) bone with preservation of trabecular (Tb) bone. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a new technique for in vivo assessment of geometry, volumetric density, and microarchitecture at the radius and tibia. In this study we aimed to evaluate bone status in women with PHPT compared with controls using HR‐pQCT. The distal radius and tibia of 54 women—27 patients with PHPT (median age 60, range 44–75 years) and 27 randomly recruited age‐matched healthy controls (median age 60, range 44–76 years)—were imaged using HR‐pQCT along with areal bone mineral density (aBMD) by dual‐energy X‐ray absorptiomentry (DXA) of the ultradistal forearm, femoral neck, and spine (L1–L4). Groups were comparable regarding age, height, and weight. In the radius, patients had reduced Ct area (Ct.Ar) (p = .008), Ct thickness (Ct.th) (p = .01) along with reduced total (p = .002), Ct (p = .02), and Tb (p = .02) volumetric density and reduced Tb number (Tb.N) (p = .04) and increased Tb spacing (Tb.sp) (p = .05). Ct porosity did not differ. In the tibia, no differences in HR‐pQCT parameters were found. Moreover, patients had lower ultradistal forearm (p = .005), spine (p = .04), and femoral neck (p = 0.04) aBMD compared with controls. In conclusion, a negative bone effect of continuously elevated PTH with alteration of HR‐pQCT assessed geometry, volumetric density, and both trabecular and cortical microarchitecture in radius but not tibia was found along with reduced aBMD by DXA at all sites in female patients with PHPT. © 2010 American Society for Bone and Mineral Research