Positive associations between serum levels of IGF-I and subcutaneous fat depots in young men. The Odense Androgen Study

IntroductionSerum levels of IGF-I are of growing interest due to the associations with morbidity and mortality. Despite markedly suppressed GH secretion, total IGF-I levels are often within normal range in obese adults.AimTo study associations between IGF-I and estimated muscle mass in the Odense Androgen Study population and secondly to investigate associations between serum IGF-I and regional fat depots.MethodThe Odense Androgen Study is a population-based, cross-sectional study of 776 randomly selected men aged 20–29 years. Regional lean and fat mass were measured by dual-energy X-ray absorptiometry, whereas regional muscle and fat areas were assessed by magnetic resonance imaging.ResultsAge-adjusted IGF-I levels correlated significantly with different estimates of muscle mass (r‐values between 0.15 and 0.19; p < 0.001). Using multiple linear regression, serum IGF-I correlated positively with subcutaneous adipose tissue on the abdomen (SAT) after controlling for visceral adipose tissue (VAT) in the whole group and in the subgroup of men with normal waist circumference (r-values between 0.13 and 0.15; p < 0.03). In addition, IGF-I correlated positively with subcutaneous thigh fat area (TFA) after controlling for intramyocellular lipid (imcl) r = 0.18; p < 0.004) and IGF-I correlated negatively with TFAimcl in the whole group and in the subgroup of men with normal waist circumference.ConclusionSAT and subcutaneous TFAs were positively associated with IGF-I in regression analyses. Conversely, imcl of the thigh was inversely associated with IGF-I levels. These findings emphasize the differential associations between IGF-I and regional fat deposits. Future studies may provide further insight regarding the interplay between circulating IGF-I levels and regional muscle and fat mass.     

High bone mineral apparent density in children with X-linked hypophosphatemia

Summary

Bone mineral apparent density (BMAD) in children with X-linked hypophosphatemia (XLH) was evaluated, as they are unlikely to have extra-skeletal ossifications contributing to the elevated bone mineral density of the spine in adult patients. Children with XLH also had significantly higher BMAD of the spine compared to femoral neck.

Introduction

BMAD obtained by dual-energy X-ray absorptiometry scans in children with XLH was evaluated, as they are unlikely to have the extra-skeletal ossifications contributing to the elevated bone mineral density of the spine in adult patients.

Methods

A total of 15 children with biochemically and genetically verified XLH were recruited. Anthropometric measurements were performed, and to correct for the short stature (small bones), the BMAD of the spine and the femoral neck was evaluated.

Results

Z-scores of BMAD of the spine (mean (95 % CI); 2.0 (1.3–2.7); p?<?0.001) were significantly elevated compared to reference children. Z-scores of the femoral neck (1.0 (?0.0 to 2.1); p?=?0.059) tended to be elevated. Spine Z-scores were significantly higher than the Z-scores of the femoral neck, (paired t test, p?=?0.02). BMAD of the spine was evaluated according to the Molgaard’s approach; XLH children had normal bone size of the spine for age due to a normal sitting height Z-score of ?0.4 (?1.0 to 0.1); p?=?0.1. Z-scores of bone mineral content (BMC) of the spine for bone area were elevated (1.4 (0.8–2.1); p?<?0.001). No reference data were available to allow evaluation of the BMAD of the femoral neck by the Molgaard's approach.

Conclusions

Children with XLH have an increased BMAD and a high BMC for bone area at the lumbar spine, and this was due to causes other than extra-skeletal ossifications and corrected for bone size. The BMAD of the spine was significantly higher compared to the femoral neck.     

Risk assessment tools to identify women with increased risk of osteoporotic fracture: Complexity or simplicity? A systematic review

A huge number of risk assessment tools have been developed. Far from all have been validated in external studies, more of them have absence of methodological and transparent evidence, and few are integrated in national guidelines. Therefore, we performed a systematic review to provide an overview of existing valid and reliable risk assessment tools for prediction of osteoporotic fractures. Additionally, we aimed to determine if the performance of each tool was sufficient for practical use, and last, to examine whether the complexity of the tools influenced their discriminative power. We searched PubMed, Embase, and Cochrane databases for papers and evaluated these with respect to methodological quality using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS) checklist. A total of 48 tools were identified; 20 had been externally validated, however, only six tools had been tested more than once in a population‐based setting with acceptable methodological quality. None of the tools performed consistently better than the others and simple tools (i.e., the Osteoporosis Self‐assessment Tool [OST], Osteoporosis Risk Assessment Instrument [ORAI], and Garvan Fracture Risk Calculator [Garvan]) often did as well or better than more complex tools (i.e., Simple Calculated Risk Estimation Score [SCORE], WHO Fracture Risk Assessment Tool [FRAX], and Qfracture). No studies determined the effectiveness of tools in selecting patients for therapy and thus improving fracture outcomes. High‐quality studies in randomized design with population‐based cohorts with different case mixes are needed.     

Mortality and Causes of Death in Patients With Osteogenesis Imperfecta: A Register‐Based Nationwide Cohort Study

Osteogenesis imperfecta (OI) is a hereditary connective tissue disease that causes frequent fractures. Little is known about causes of death and length of survival in OI. The objective of this work was to calculate the risk and cause of death, and the median survival time in patients with OI. This study was a Danish nationwide, population‐based and register‐based cohort study. We used National Patient Register data from 1977 until 2013 with complete long‐term follow‐up. Participants comprised all patients registered with the diagnosis of OI from 1977 until 2013, and a reference population matched five to one to the OI cohort. We calculated hazard ratios for all‐cause mortality and subhazard ratios for cause‐specific mortality in a comparison of the OI cohort and the reference population. We also calculated all‐cause mortality hazard ratios for males, females, and age groups (0 to 17.99 years, 18.00 to 34.99 years, 35.00 to 54.99 years, 55.00 to 74.99 years, and >75 years). We identified 687 cases of OI (379 women) and included 3435 reference persons (1895 women). A total of 112 patients with OI and 257 persons in the reference population died during the observation period. The all‐cause mortality hazard ratio between the OI cohort and the reference population was 2.90. The median survival time for males with OI was 72.4 years, compared to 81.9 in the reference population. The median survival time for females with OI was 77.4 years, compared to 84.5 years in the reference population. Patients with OI had a higher risk of death from respiratory diseases, gastrointestinal diseases, and trauma. We were limited by the lack of clinical information about phenotype and genotype of the included patients. Patients with OI had a higher mortality rate throughout their life compared to the general population. © 2016 American Society for Bone and Mineral Research.     

Effects of Odanacatib on the Radius and Tibia of Postmenopausal Women: Improvements in Bone Geometry,Microarchitecture, and Estimated Bone Strength

The cathepsin K inhibitor odanacatib (ODN), currently in phase 3 development for postmenopausal osteoporosis, has a novel mechanism of action that reduces bone resorption while maintaining bone formation. In phase 2 studies, odanacatib increased areal bone mineral density (aBMD) at the lumbar spine and total hip progressively over 5 years. To determine the effects of ODN on cortical and trabecular bone and estimate changes in bone strength, we conducted a randomized, double‐blind, placebo‐controlled trial, using both quantitative computed tomography (QCT) and high‐resolution peripheral (HR‐p)QCT. In previously published results, odanacatib was superior to placebo with respect to increases in trabecular volumetric BMD (vBMD) and estimated compressive strength at the spine, and integral and trabecular vBMD and estimated strength at the hip. Here, we report the results of HR‐pQCT assessment. A total of 214 postmenopausal women (mean age 64.0 ± 6.8 years and baseline lumbar spine T‐score –1.81 ± 0.83) were randomized to oral ODN 50 mg or placebo, weekly for 2 years. With ODN, significant increases from baseline in total vBMD occurred at the distal radius and tibia. Treatment differences from placebo were also significant (3.84% and 2.63% for radius and tibia, respectively). At both sites, significant differences from placebo were also found in trabecular vBMD, cortical vBMD, cortical thickness, cortical area, and strength (failure load) estimated using finite element analysis of HR‐pQCT scans (treatment differences at radius and tibia = 2.64% and 2.66%). At the distal radius, odanacatib significantly improved trabecular thickness and bone volume/total volume (BV/TV) versus placebo. At a more proximal radial site, odanacatib attenuated the increase in cortical porosity found with placebo (treatment difference = –7.7%, p = 0.066). At the distal tibia, odanacatib significantly improved trabecular number, separation, and BV/TV versus placebo. Safety and tolerability were similar between treatment groups. In conclusion, odanacatib increased cortical and trabecular density, cortical thickness, aspects of trabecular microarchitecture, and estimated strength at the distal radius and distal tibia compared with placebo. © 2014 American Society for Bone and Mineral Research     

Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases

Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12-13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown.     

Vitamin D status and PTH in young men: a cross‐sectional study on associations with bone mineral density,body composition and glucose metabolism

Objective Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross‐sectional study in young men and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function. Design and Participants The study population consisted of 783 men aged 20–29 years. Measurements Bone mineral density (BMD) of the total hip, femoral neck and lumbar spine was measured. dual‐energy X‐ray absorptiometry was used to evaluate total body fat mass (BFAT). Visceral fat mass and abdominal subcutaneous fat mass (ViFM and ScFM) were assessed using magnetic resonance imaging. A radioimmunoassay was used to measure the level of 25‐hydroxy vitamin D (25OHD). Results The prevalence of vitamin deficiency (serum 25OHD < 50 nm ) was 6·3% during summer and 43·6% during winter. Serum 25OHD was associated with BMD at all sites and inversely associated with bone‐specific alkaline phosphatase and directly with carboxyterminal telopeptide of type‐1‐collagen. 25OHD and PTH were inversely associated with BFAT, whereas 25OHD also was inversely associated with body mass index, waist–hip ratio, ViFM and ScFM after adjustment for confounders. The associations were found only to be present in participants with insufficient levels of 25OHD. 25‐Hydroxy vitamin D and PTH were inversely related to insulin resistance in vitamin‐insufficient participants only. No associations between PTH or 25OHD and blood pressure were noted. Conclusion The study showed a high prevalence of 25OHD deficiency in young, northern European men, which was significantly associated with decreased BMD. PTH and 25OHD were found to be inversely related to the markers of insulin resistance.