Binge drinking impairs the healing of broken bones. It can do this weeks after a binge. And it can leave in its wake permanently inferior bone, according to recent studies.

One reason: alcohol slows down mesenchymal (bone, fat, and cartilage) stem cells (MSCs), in the bloodstream, trying to home to fracture sites. And when MSCs finally reach fracture sites, alcohol keeps them from properly replacing lost cells.

“Alcohol is a toxin affecting thousands of genes,” says Loyola University Molecular and Cellular Bone Biology Laboratory chief John Callaci in an interview with Bioscience Technology.

The connection is so clear that, in an upcoming study in Alcohol and Alcoholism, Callaci’s group will reveal a surprising turn of events: lithium, the common mental disorder drug, can cause MSCs to proliferate, and mitigate bone damage caused by binge-drinking.

Researchers have known for years chronic drinking impairs bone healing. But Callaci’s group has been showing, in a series of studies, that even short-term heavy drinking—binge drinking—significantly impacts bone. Between 25 to 40 percent of orthopedic trauma patients are intoxicated at hospital admission. Alcohol puts many in the hospital because it temporarily impairs their brains.

But it keeps many there because it not-so-temporarily impairs their bones.

John Callaci, PhDAt the 2013 annual meeting of the American Society for Bone and Mineral Research (ASBMR), Callaci’s group reported zeroing in on the mechanism of action. They reported finding, as before, that mice breaking limbs, after binging, experience defects in callus (bone replacement) size, tissue composition, and strength. (The mouse binges consisted of three days of drinking the equivalent of two to two-and-one-half times the legal driving limit. This is followed by a week of mouse abstinence; then another three-day mouse binge.)

But this time, when he euthanized mice on Day Seven, he also looked for, and found, undifferentiated (immature or unformed) mesenchymal tissue at the callus site of the drunken mice only, not of the control mice. (The controls’ tissue had matured normally.) And there was a “significant decrease” in osteopontin in the tissue of the drunken mice, compared to the controls.

Osteopontin is a chemokine that injured bone releases, in a normal physiological cry for help, to attract bone-building MSCs to them.

The “drunk” mice were unable to properly rouse osteopontin.

“We have hypothesized that alcohol affects stem-cell homing to fracture sites, and stem cell differentiation of these cells into mature chondrocytes and osteoblasts—the cells that heal the fractures.” The ASBMR meeting report addressed the first issue. “But it is likely that both are correct.”

Callaci’s group focuses on the external callus of bone breaks, to which bloodstream MSCs home, because that is the bone compartment apparently affected. “The periosteal callus compartment, formed from precursor cells residing in the periosteum—a membrane that covers bone--does not seem affected by alcohol,” he says. “Those local cells proliferate post-fracture and differentiate into osteoblasts. But the external callus is affected. The external callus is made of cells that migrate to the fracture site, and then differentiate into cartilage (chondrocytes) to build soft callus, and then into osteoblasts forming hard callus. That is what is affected by alcohol.”

More research is needed. It is unknown which alcohol molecules are the culprits. And it is unknown, if unlikely, whether opiates operate similarly. “We give our animals opiate derivatives for pain in these experiments. We see no evidence of inhibited healing due to those.”

But one of Callaci’s recent binge-drinking mouse papers found that free oxygen radicals are probably involved, as antioxidants can mitigate the detrimental effects of alcohol on bone. Another of his binge-drinking mouse papers found MSC transplants could mitigate effects. “Multiple things are going on probably,” he says.

Could more moderate—if regular daily—drinking also affect bone healing in humans? Possibly, he says. The mice in his papers are “alcohol naïve before their binges—unlike humans. Yet mice are profoundly impacted anyway. The bones of far less “naïve” humans could be far more dramatically impacted by alcohol than those of their diminutive drinking buddies.

Furthermore, few people actually do drink “moderately.”

“It is very common for people to reach a blood level that is two to two-and-a-half times the legal limit,” or the equivalent of what Callaci’s binging mice drink. And heart associations say moderate drinking of one four-ounce glass of wine a night for women—and two for men—may be good for the heart. But, Callaci laughs, “Not a lot of people drink that little. Have you ever poured out four ounces of wine?”

Still, genuinely moderate drinking indeed is at least neutral, and in some instances, beneficial, Callaci says. But after years of watching drunken mice stumble about his lab, “I’m careful about advocating any amount of drinking.”

His upcoming Alcohol and Alcoholism paper is titled, “Exogenous Activation of Wnt/Beta Catenin Signaling Attenuates Binge Alcohol-Induced Deficient Bone Fracture Healing.” In that paper he shows that a lithium-containing compound can help heal bones—harmed by binge-drinking—via the proliferation and differentiation of mesenchymcal stem cells.

Lithium is given to patients with manic-depression and other mental disorders. “It is possible that this type of treatment could extend to patients with non-healing fractures due to alcohol,” Callaci says. “But that is beyond the scope of the (soon to be) published study.”