October 7, 2013
For years, doctors have observed a strange effect of alcohol abuse: People who drink heavily are more likely break their bones, and the risk can’t be fully explained by more frequent careless falls and alcohol-induced car accidents.
“As an orthopedic surgery resident, time after time, I see people come in with broken limbs while under the influence of alcohol,” says Roman Natoli, a doctor at Loyola University in Chicago.
Statistics suggest that their risk of a bone fracture is equal to that of a non-drinker a decade or two older than them, and they also tend to go through a slower healing process, filled with more frequent complications.
The reasons for this haven’t been entirely clear. Evidence suggested it had something to do with the way alcohol interfered with the activity of osteoblasts (the cells that synthesize new bone growth), while osteoclasts (the cells that remove old, damaged bone tissue) continued work as usual, leaving small cavities where new tissue was supposed to form. Data also indicated that the problem was dose-dependent—the more alcohol people drank, the greater the problem.
To find out the exact nature of the issue, Natoli and a group of medical researchers from Loyola did the logical thing: They got some mice rather intoxicated.
Specifically, the doctors, who presented their findings yesterday at the American Society for Bone and Mineral Research’s annual meeting, sought to simulate the effects of a single intense bout of binge drinking on mice who’d suffered a bone fracture.
To do so, they gave mice levels of alcohol that were roughly equivalent to a human with .20 blood alcohol content, several times the legal limit for driving. For an average person, reaching this level would require drinking about 6-9 drinks in an hour, and would likely lead to confusion, disorientation, dizziness, exaggerated emotions and severe risk of injury.
We have no idea if the mice experienced mood swings, but the doctors did look closely at the way their tibias healed after an induced fracture, as compared to induced fractures in a control group of mice that hadn’t had any alcohol. They found that, in the mice who’d gone through the alcohol binge, the callus—the mass of temporary bone tissue formed by osteoblasts in the gap between the two broken bone ends—was less dense and softer.
They also uncovered a few underlying reasons why this might be the case. For one, the body generates new bone tissue by recruiting immature stem cells to the site of the break, where they develop into osteoblasts and mature bone cells. The researchers found, however, that one of the main two proteins that the body uses to bring these stem cells to the fracture site—a protein called osteopontin, or OPN—was present in much lower levels in the mice who’d had so much alcohol.
Additionally, the alcohol-exposed mice seemed to suffer from a general problem that affects a range of cellular functions: oxidative stress. In essence, this type of stress results for an overabundance of oxidizing molecules—such as peroxides and free radicals—that can damage a variety of cell components, including proteins and DNA. It’s been implicated in a huge range of disorders in humans (including cancer, heart failure and Alzheimer’s).
The mice who’d been drinking had much higher levels of a molecule that scientists use as a proxy marker for oxidative stress (malondialdehyde), which jibes with previous studies that show alcohol can lead to higher production of oxidizing molecules and interfere with the body’s ability to break them down, especially in the liver. These higher stress levels, the researchers say, could inhibit bone growth and healing for reasons we still don’t fully understand.
If these findings apply to effects of drinking on the bone-healing process in humans, they could suggest some intriguing novel therapies for speeding bone growth in people who suffer from alcoholism, and perhaps even in non-drinkers. “The basic goal is to get these fractures to heal normally,” Natoli says.
One possibility that his team plans to test in future studies is injecting mice with extra stem cells, so that even with diminished quantities of the stem cell-recruiting protein OPN, they’d be able to get sufficient levels to the healing site. Another option could be giving mice an antioxidant called NAc, which combats oxidative stress throughout the body, perhaps speeding bone healing as well.
Of course, potential remedies notwithstanding, the findings should serve as a warning: if you’re a heavy drinker, your bones are likely weaker and have more difficulty healing. The silver lining, though, comes from other research, which has indicated that the problem is reversible—simply abstain from alcohol, and your bones will eventually regain most of their density and be able to heal normally again.
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