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Miika Värri,1 Leo Niskanen,2 Tomi-Pekka Tuomainen,3 Risto Honkanen,1,4 Heikki Kröger,1,5 Marjo T Tuppurainen1,6 1Kuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; 2Department of Endocrinology and Metabolism, Abdominal Centre, Helsinki University Hospital, Universities of Helsinki and Eastern Finland, Helsinki, Finland; 3Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 4Lapland Hospital District, Rovaniemi, Finland; 5Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland; 6Department of Obstetrics and Gynaecology, Kuopio University Hospital, Kuopio, FinlandCorrespondence: Miika VärriKuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, FinlandTel +358503655083Fax +358 17 172 611Email mvarri@uef.fiPurpose: Atherosclerosis (AS) and osteoporosis (OP) are common causes of morbidity and mortality in postmenopausal women and are connected via an unknown mechanistic link. Metabolite profiling of blood samples may allow the identification of new biomarkers and pathways for this enigmatic association.Patients and Methods: We studied the difference in 148 metabolite levels from serum samples in postmenopausal women with AS and OP compared with those in healthy participants in this cross-sectional study. Quantitative AS was assessed by carotid artery intima-media thickness (cIMT) and carotid artery calcifications (CACs) by ultrasound, as well as OP by femoral neck (FN) bone mineral density (BMD) and 148 metabolic measures with high-throughput proton (1H) nuclear magnetic resonance (NMR) in serum samples from 280 postmenopausal (PM) women. Subjects were a randomly selected subsample from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The final study population included the following groups: OP with CAC (n=16, group I), non-OP with no CAC (n=59, group II), high cIMT tertile with OP (n=11, group III) and low cIMT tertile without OP (n=48, group IV).Results: There were differences in several metabolite levels between groups I and II. The acetate level was lower in group I compared to that in group II (group I mean ± SD: 0.033 ± 0.0070; group II: 0.041 ± 0.014, CI95%: 0.018‒0.15, p=0.014). The result was similar with diacylglycerol (p=0.002), leucine (p=0.031), valine (p=0.022) and several very low-density lipoprotein (VLDL) metabolite levels, which were lower in group I compared to those in group II. However, no associations were found in adjusted analyses with total body (TB) fat mass (FM), age and statin use (p> 0.05).Conclusion: Our novel study found differences in the metabolite profiling of altered amino acid and lipoprotein metabolism in participants with OP and AS compared with those in healthy women. The causative mechanisms remain unknown and further studies are needed.Keywords: metabolomics, carotid artery calcification, postmenopausal women, osteoporosis, carotid intima-media thickness, acetate

In long-term prospective studies, dual-energy X-ray absorptiometry (DXA) devices need to be inevitably changed. It is essential to assess whether systematic differences will exist between measurements with the new and old device. A group of female volunteers (21-72 years) underwent anteroposterior lumbar spine L2-L4 (n = 72), proximal femur (n = 72), and total body (n = 62) measurements with the Prodigy and the iDXA scanners at the same visit. The bone mineral density (BMD) measurements with these two scanners showed a high linear association at all tested sites (r = 0.962-0.995; p < 0.0001). The average iDXA BMD values were 1.5%, 0.5%, and 0.9% higher than those of Prodigy for lumbar spine (L2-L4) (p < 0.0001), femoral neck (p = 0.048), and total hip (p < 0.0001), respectively. Total body BMD values measured with the iDXA were -1.3% lower (p < 0.0001) than those measured with the Prodigy. For total body, lumbar spine, and femoral neck, the BMD differences as measured with these two devices were independent of subject height and weight. Linear correction equations were developed to ensure comparability of BMD measurements obtained with both DXA scanners. Importantly, use of equations from previous studies would have increased the discrepancy between these particular DXA scanners, especially at hip and at spine. [ABSTRACT FROM AUTHOR]

Objectives: Carotid artery calcifications (CAC) and high carotid artery intima-media thickness (cIMT) are associated with low bone mineral density (BMD) by unknown mechanisms in postmenopausal women. Leptin, adiponectin and estradiol may mediate these associations. Our aim was to study the relationships of the aforementioned factors to bone health (BMD) and carotid atherosclerosis (CAC and cIMT).Method: Participants (n = 290, mean age 73.6 years) for this cross-sectional OSTPRE-BBA study (Kuopio Osteoporosis Risk Factor and Prevention - Bone, Brain and Atherosclerosis) were randomly selected from the OSTPRE cohort in 2009. Femoral neck and total body BMDs, trunk and total body fat mass were measured with dual-energy X-ray absorptiometry, and cIMT (mm) and CAC (no/yes) were measured with B-type ultrasound. Free estradiol, adiponectin and leptin were measured from serum samples.Results: Circulating estradiol levels were associated with leptin (β = 0.131, p < 0.001), but not with adiponectin (p > 0.05), when adjusted for total body fat mass. There were no associations between estradiol tertiles and BMDs, or with cIMT or CAC. Adiponectin levels were inversely associated with femoral neck BMD (p = 0.019, β = -0.138) and total body BMD (p = 0.009, β = -0.142), adjusted for total body fat mass, age, current smoking and estradiol, but showed no relationship with CAC or cIMT. Leptin levels were not associated with BMDs or cIMT; but the odds ratio was 1.5 between the CAC and leptin quartiles (p = 0.014), adjusted for total body fat mass, age, statin use and calcium intake.Conclusion: The adipokines are associated with vascular calcification and low BMD. Moreover, estradiol was not independently associated with BMD or CAC. [ABSTRACT FROM AUTHOR]

The Osteoporosis Risk Factor and Prevention-Fracture Prevention Study (OSTPRE-FPS) was a randomized population-based open trial (n=593). The supplementation group (n=287) received daily cholecalciferol 800 IU + calcium 1,000 mg for [...]

The article discusses a study on the current concepts about the feasibility of using conventional hormone therapy (HT) and selective estrogen receptor modulators (SERMs) against bone loss and fractures in women. It cites the use of estrogen for preventing and treating osteoporosis although conventional doses may increase the incidence of serious adverse events like breast cancer, venous thromboembolism and stroke. It concludes that low-dose HT maybe appropriate for women with menopausal symptoms and low fracture risk while SERMs such as raloxifene, bazedoxifene and lasofoxifene can be considered for younger postmenopausal women at greater risk for vertebral fractures and women with increased risk of breast cancer.

Objective: The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level.Study Design: The OSTPRE-FPS was a randomized population-based open-trial with 3-year follow-up. The supplementation group (n=1566) received daily cholecalciferol 800IU+calcium carbonate 1000mg, while the control group (n=1573) received no supplementation or placebo. A randomly selected subsample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements.Main Outcome Measure: The occurrence of falls was the primary outcome of the study. The participants in the subsample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year.Results: In the entire trial population (ETP), there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group (risk ratio was 0.98, 95% CI 0.92-1.05, P=0.160). The supplementation was not associated with single or multiple falls in the ETP. However, in the subsample, multiple fall incidence decreased by 30% (odds ratio (OR) 0.70, 95% CI 0.50-0.97, P=0.034) in the supplementation group. Further, the supplementation decreased the incidence of multiple falls requiring medical attention (OR 0.72, 95% CI 0.53-0.97, P=0.031) in the ETP. The mean compliance in the entire trial population was 78% and in the subsample 79%.Discussion: Overall, the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls. However, the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention: this finding requires confirmation. [ABSTRACT FROM AUTHOR]

Abstract: Screening of osteoporosis using peripheral bone measurements has become more common, even though diagnostic discrepancies are known to exist between peripheral dual-energy X-ray (pDXA) or quantitative ultrasound (QUS) and central DXA measurements. Values of diagnostic parameters such as bone mineral density, speed of (ultra)sound, and broadband ultrasound attenuation are affected by bone size and soft tissue composition. However, their significance for the discordance between peripheral and central techniques is unclear. In this study, bone status and total body composition of 139 women (mean age 68.3yr [1.7 SD], mean body mass index 26.5kg/m2 [3.6 SD]) were assessed by 3 GE Lunar devices. Heel pDXA and heel QUS were conducted using peripheral instantaneous X-ray imaging (PIXI) and Achilles, respectively, and central DXA measurements were taken at the posterior-anterior lumbar spine (L2–L4) and at the left femoral neck using Prodigy. Positive significant associations were found between body height or fat (%) and most DXA or QUS parameters. The discordance between the site-dependent DXA or QUS T-score values typically increased (p <0.05) as a function of body weight or fat (%), but not with body height. On an average, body adiposity accounted for less than 11% of the differences between the techniques; however, increase of total body fat from 20% to 45% led to a discrepancy of one T-score between DXAHEEL and QUSHEEL. To avoid diagnostic bias, comparative assessment of the devices using the same population is recommended. [Copyright &y& Elsevier]

This study compared the lipid profile after three and six cycles of treatment with NuvaRing® delivering 15 μg ethinylestradiol and 120 μg etonogestrel daily with a combined oral contraceptive (COC) containing ethinylestradiol 30 μg and levonorgestrel 150 μg. In the NuvaRing group 40 women were treated and 43 in the COC group. Compared with baseline, total cholesterol did not change in either group. NuvaRing did not affect HDL, but HDL, HDL2 and HDL3 levels decreased with the COC. In contrast, HDL2 increased with NuvaRing at cycle 3. LDL increased after cycles 3 and 6 with COC, and decreased after three cycles of NuvaRing treatment. Apolipoprotein A-1 levels increased with NuvaRing, but decreased with COC; apolipoprotein B and triglycerides increased, and lipoprotein(a) decreased in both groups. Sex hormone-binding globulin increased markedly more with NuvaRing, whereas corticosteroid-binding globulin levels increased less. These changes reflect the lower androgenicity of etonogestrel versus levonorgestrel and show that NuvaRing has a minimal effect on lipid profile. [Copyright &y& Elsevier]