Cold Exposure Reduces Trabecular and Cortical Bone in Wildtype and Dio2‑Deficient Mice

New controlled animal experiments found that housing mice in cold conditions caused measurable losses in both trabecular and cortical bone, a finding that matters for anyone who practices regular cold plunges or monitors long-term cold exposure. Researchers report that one week of cold altered osteoclast and osteoblast activity and that after four weeks mice showed a significant reduction in trabecular number and cortical thickness. “We observed that cold exposure for 1 week differentially affected osteoclastogenesis and osteoblast activity, which caused a significant reduction of trabecular number and cortical thickness after 4 weeks.”

The investigators tested multiple housing regimens. In one set of experiments mice were kept at thermoneutral 30 °C, room 22 °C, or cold 6 °C for one or four weeks. Earlier work used developmental exposures from 3 weeks of age up to 6 or 12 weeks at 26 °C versus cooler 20 °C (N = 8 per group) and found that “cool housed mice ate more but had lower body fat at 20 °C versus 26 °C” and that “mice at 20 °C had markedly lower distal femur trabecular bone volume fraction, thickness, and connectivity density and lower midshaft femur cortical bone area fraction versus mice at 26 °C (p < .05 for all).”

Additional adult experiments using C57BL/6 mice exposed to 4–6 °C for eight weeks beginning at 12 weeks of age produced comparable results: “CT mice exhibited significantly reduced bone mass and more compromised bone microstructures compared to RT mice.” Those cold-treated mice showed lower bone mineral density, lower trabecular bone volume fraction, fewer and thinner trabeculae, and decreased cortical thickness. Histology and dynamic labeling confirmed fewer osteoblasts, more osteoclasts, impaired mineralization, and reduced bone formation rates.

Mechanistic clues were mixed but instructive for the cold-plunge community. Brown adipose tissue thermogenesis rose as temperature fell, “UCP1 expression in BAT was inversely related to temperature”, but increased nonshivering thermogenesis appeared insufficient to prevent bone loss. The team also tested the thyroid-activation hypothesis: cold induces type II iodothyronine deiodinase (DIO2) in thermogenic fat, which converts T4 to active T3, but the investigators report that “Dio2 deficiency in male and female mice did not affect the cold-induced reduction of trabecular and cortical bone mass, thereby demonstrating that this process does not depend on thyroid hormone activation.”

Other signals merit follow-up. Lipidomic profiling showed “a remarkable reduction of specific lipid species after cold exposure,” and separate exosome experiments suggested plasma-derived exosomes influence bone metabolism: exosomes from room-temperature plasma increased femur length and osteoblast number in cold mice but did not reduce osteoclast counts, and researchers noted it is “plausible that CT-EXO may mediate bone loss induced by cold exposure.”

For readers who take regular cold plunges, these murine results do not prove identical effects in people, but they add a clear experimental signal that sustained cold exposure can tilt bone remodeling toward loss. Pay attention to exposure duration and baseline conditions: the studies used varied definitions of thermoneutrality and cold (20 °C, 6 °C, 4–6 °C), different ages and sexes, and different durations, all of which affect outcomes. Next steps include human-focused studies, detailed lipidomic identification, and testing whether shorter or intermittent plunges carry the same risk.