Chronic, heavy alcohol consumption detrimentally impacts microarchitectural and mechanical properties of bone in crossed high alcohol preferring (cHAP) mice

Bone. 2026 Aug 9:118043. doi: 10.1016/j.bone.2026.118043. Online ahead of print.

ABSTRACT

Alcohol use disorder (AUD) is the most commonly diagnosed substance use disorder in the United States, with one in ten people (12 years of age and older) diagnosed as of 2023. AUD can lead to a variety of deleterious outcomes, including increased fracture risk. The reduced bone mineral density (BMD) observed in this patient population is often blamed for this increased fracture risk. However, no other routine skeletal measures are made in the clinic, suggesting AUD could induce detrimental skeletal effects outside of reduced bone mass. Consequently, animal models of AUD have been developed to assess additional measures, but many do not achieve the magnitude of blood ethanol concentrations (BECs) observed in patients with AUD. The crossed high alcohol preferring (cHAP) mouse line achieves these clinically relevant BECs through voluntary alcohol consumption, avoiding the potentially confounding effects of stress associated with forced exposure procedures. Until recently, there has been relatively little toxicological work with this line. Here, the skeletal effects of alcohol consumption in male and female cHAP mice were explored for the first time. We hypothesized 8 weeks of alcohol consumption would cause a loss of skeletal mass, architecture, and mechanical integrity. Ethanol drinking had a significant main effect on body composition measures resulting in lower total BMD in both sexes. Cortical and whole-bone mechanical measures were also lower in both sexes with ethanol drinking. While osteoclast number was not different, adipocyte numbers were higher, particularly in ethanol-drinking females. These findings indicate the cHAP mouse is a useful model of the skeletal outcomes of AUD.

PMID:42571833 | DOI:10.1016/j.bone.2026.118043