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The Effect of Ethanol Consumption on Composition and Morphology of Femur Cortical Bone in Wild-Type and ALDH2*2-Homozygous Mice.

ABSTRACT: ALDH2 inactivating mutation (ALDH2*2) is the most abundant mutation leading to bone morphological aberration. Osteoporosis has long been associated with changes in bone biomaterial in elderly populations. Such changes can be exacerbated with elevated ethanol consumption and in subjects with impaired ethanol metabolism, such as carriers of aldehyde dehydrogenase 2 (ALDH2)-deficient gene, ALDH2*2. So far, little is known about bone compositional changes besides a decrease in mineralization. Raman spectroscopic imaging has been utilized to study the changes in overall composition of C57BL/6 female femur bone sections, as well as in compound spatial distribution. Raman maps of bone sections were analyzed using multilinear regression with these four isolated components, resulting in maps of their relative distribution. A 15-week treatment of both wild-type (WT) and ALDH2*2/*2 mice with 20% ethanol in the drinking water resulted in a significantly lower mineral content (p < 0.05) in the bones. There was no significant change in mineral and collagen content due to the mutation alone (p > 0.4). Highly localized islets of elongated adipose tissue were observed on most maps. Elevated fat content was found in ALDH2*2 knock-in mice consuming ethanol (p < 0.0001) and this effect appeared cumulative. This work conclusively demonstrates that that osteocytes in femurs of older female mice accumulate fat, as has been previously theorized, and that fat accumulation is likely modulated by levels of acetaldehyde, the ethanol metabolite.

SUBMITTER: Malkovskiy AV

PROVIDER: S-EPMC8092984 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aromatase inhibitor treatment in breast cancer is associated with accelerated bone loss and an increased risk of fracture. Bisphosphonates (BPs) are the mainstay treatment of aromatase inhibitor-associated bone loss (AIBL), which might improve femoral bone at key locations prone to fracture. To test this hypothesis, we performed three-dimensional cortical bone mapping based on quantitative computed tomography (QCT) scans in postmenopausal women with early breast cancer who were receiving aromatase inhibitors. Data of subjects who had both baseline and at least one follow-up QCT at Severance Hospital (South Korea) between 2005 and 2015 were analyzed (BP users, n = 93; BP non-users, n = 203). After exclusion of BP users with low medication persistence (proportion of days covered: <50%), BP users and non-users were 1:1 matched (n = 54 for each group) in terms of age, lumbar spine volumetric bone mineral density (LSvBMD), femoral neck areal BMD (FNaBMD), and total hip areal BMD (THaBMD). During a median follow-up of 2.1 years, BP use attenuated bone loss in LSvBMD (+7.2% vs. -3.8%, p < 0.001), FNaBMD (+1.3% vs. -2.7%, p < 0.001), and THaBMD (-0.3% vs. -2.5%, p = 0.024). BP had a protective effect on cortical parameters of femoral bone: estimated cortical thickness (CTh) (+3.3% vs. + 0.1%, p = 0.007) and cortical mass surface density (CMSD, cortical mass per unit surface area was calculated by multiplying cortical BMD with CTh) (+3.4% vs. -0.3%, p < 0.001). CMSD increased by up to 15% at key locations such as the superior part of the femoral neck and greater trochanter. BP prevented the thinning of average CTh of the femoral neck (-1.4% vs. -6.1%, p < 0.001), particularly at the superior anterior quadrant of femoral neck (absolute difference: +12.8% point vs. non-users). Compared to BP non-users, BP users had improved cross-sectional moment of inertia (+4.4% vs. -0.7%, p = 0.001) and less increase in buckling ratio (+1.3% vs. + 7.5%, p < 0.001). In summary, BP use prevented cortical bone deficits observed in AIBL at key locations of the proximal femur.

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The Effect of Ethanol Consumption on Composition and Morphology of Femur Cortical Bone in Wild-Type and ALDH2*2-Homozygous Mice.

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