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Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), Month 24 (ODN n = 112, placebo n = 104), -36 (ODN n = 42, placebo n = 41), and - 60 (ODN n = 27, placebo n = 20), were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN- versus placebo-treated patients after 2 years' treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at Month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.At birth the neonatal skeleton contains 20-30 g Ca, it is hypothesized maternal bone mineral may be mobilized to support fetal skeletal development, though evidence of pregnancy-induced mineral mobilization is limited. We recruited healthy pregnant (n = 53) and non-pregnant non-lactating (NPNL, n = 37) women aged 30-45 years (mean 35.4 ± 3.8 years) and obtained peripheral quantitative computed tomography (pQCT) and high-resolution pQCT (HR-pQCT) scans from the tibia and radius at 14-16 and 34-36 weeks pregnancy, with a similar scan interval for NPNL. Multiple linear regression models were used to assess group differences in change between baseline and follow-up; differences are expressed as standard deviation scores (SDS) ± SEM. Decreases in vBMD outcomes were found in both groups, however, pregnancy-related decreases for pQCT total and trabecular vBMD were - 0.65 ± 0.22 SDS and - 0.50 ± 0.23 SDS greater (p less then 0.05). HR-pQCT total and cortical vBMD decreased compared to NPNL by -0.49 ± 0.24 SDS and -d by copyright. All rights reserved. This article is protected by copyright. All rights reserved.This study was conducted to examine the association between renal function and hip fracture. We followed up 352,624 Korean adults, who participated in health examinations during 2008-2009, until 2013. Kidney function was assessed by creatinine-based estimated glomerular filtration rate (eGFR) and albuminuria using urine reagent strip results. The incidence of hip fracture was examined by hospital discharge records. Hazard ratios (HRs) for hip fracture were calculated using Cox proportional hazard models after adjusting for multiple confounders. During a mean follow-up of 4.0 years, 1,177 participants suffered a hip fracture. Lower eGFR and more severe albuminuria were associated with a higher risk of hip fracture. The HRs for hip fracture were 1.89 (95% CI 1.47-2.43) and 3.75 (95% CI 2.30-6.11) among participants with eGFRs of 30-44 and 15-29 mL/min/1.73m2 relative to those with an eGFR ≥60 mL/min/1.73m2 , respectively. https://www.selleckchem.com/products/estradiol-benzoate.html The HRs were 1.30 (1.02-1.65) for moderate albuminuria, and 1.58 (1.07-2.35) for severe albuminuria (P for trend 0.002). Participants with albuminuria had a higher risk of hip fracture than those without albuminuria, even when they belonged to the same eGFR category (HR 1.75 vs. 3.30 for an eGFR of 30-44 mL/min/1.73m2 , HR 2.72 vs. 7.84 for an eGFR of 15-29 mL/min/1.73m2 ). The effects of each 10 mL/min/1.73m2 decrease in eGFR were stronger with advancing albuminuria severity (Pinteraction =0.016). In conclusion, both low eGFR and albuminuria were risk factors for incident hip fracture in Korean adults. Moreover, these factors exerted a synergistic effect on the risk of hip fracture. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The American Academy of Pediatrics recommends donor human milk (DHM) as the preferred feeding strategy for preterm infants when the milk of the mother is unavailable, based on conclusive evidence of lower rates of necrotizing enterocolitis with DHM feedings compared with preterm infant formula. The nutritional composition of DHM may differ from maternal milk for many reasons including differences in maternal characteristics, milk collection methods, and the impact of donor milk banking practices. The purpose of this systematic review is to examine the literature regarding research on the fat, protein, carbohydrate, vitamin, and mineral composition of DHM obtained through nonprofit milk banks or commercial entities. PubMed, CINAHL, and Scopus databases were searched for articles published between 1985 and 30 April, 2019. In total, 164 abstracts were screened independently by 2 investigators, and 14 studies met all inclusion criteria. Studies were predominantly small ( less then 50 samples) and measured macronutrients. Few studies assessed vitamins and minerals. Information bias was prevalent due to the use of a variety of analytical methods which influence accuracy and cross-study comparisons. Other sources of information bias included missing information regarding methods for protein and calorie assessment. Despite these limitations, existing research suggests the potential for 2-fold and greater differences in the fat, protein, and energy composition of DHM, with mean values for energy and fat often below clinical reference values expected for human milk. Further research is warranted regarding the nutritional composition of DHM, with a prioritization on measuring macronutrients and micronutrients using established reference methods. Copyright © The Author(s) 2020.
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