Too little calcium may reprogram stem cells, permanently compromising bone--even fostering later osteoporosis
ANAHEIM – Calcium makes bones strong. But a new animal study suggests that to do this, ample calcium may need to be available from birth. Too little in the early weeks of life may reprogram certain stem cells – those in the marrow – in ways that permanently compromise bone structure. Perhaps even fostering osteoporosis.
Explains Chad Stahl, a nutritional physiologist at North Carolina State University in Raleigh, the perturbed cell programming that his team witnessed in calcium-deprived baby pigs suggests their bones may never get as strong as they should. One reason: The affected mesenchymal stem cells appear more likely to mature into fat than into bone-forming cells, or osteoblasts.
A quick caveat up front: This research, presented April 25 at the annual meeting of the American Society of Nutrition, is preliminary. For instance, although Stahl’s group plans to follow calcium-deprived baby pigs into adulthood to confirm that their initially weakened bones cannot recover, such studies are not yet underway. That means the researchers also can’t demonstrate how the early propensity for affected stem cells to morph into fat (not bone) will play out.
But the changes they’ve chronicled thus far don’t auger well for bone health, he says. (Moreover, he points out, studies by others have shown that in contrast to full-term, full-size babies, preemies and small-for-gestational-age infants are more likely to grow into teens or adults with weak bones. This isn’t necessarily a calcium issue, but does suggest early programming may affect long-term bone health.)
For the new study, Stahl and his coworkers fed one dozen day-old pigs (a common animal model of the human infant) a nutritionally balanced milk diet. Another dozen neonatal pigs got milk that was the same in all respects except for its having just half as much calcium. After 18 days, the researchers compared the piggies’ bones.
As expected, animals fed low-calcium milk developed wimpier one. Computed tomography (X-ray) scans showed that the mineral density of their shank bones was 8 percent lower than in piglets getting a full quota of calcium. The deficient animals’ bones were also 22 percent less able to resist torsion and roughly 20 percent less able to withstand flexing than were the bones of baby pigs that had gotten a healthy diet.
“These were clearly detectable differences after just 18 days,” Stahl reports. “But what we found particularly interesting was that the proliferation rate of those mesenchymal stem cells; it was reduced by half with calcium deficiency. That’s a pretty massive reduction.”
I asked about the mechanism and Stahl says he doesn’t know. Then again, he says that the reduced proliferation “kind of makes sense. If you don’t need as many bone-forming cells, you probably won’t make them.” It’s one way the body can conserve its energy for other essentials.
Based on these findings, Stahl and his colleagues performed a second set of tests where they extracted mesenchymal stem cells from the bone marrow of these piglets and put them in dishes to grow. Cells from the deficient animals grew 44 percent more slowly.
When the scientists added some signaling compounds that the body uses to prompt stem cells to mature, a greater share of the cells from calcium-deficient piglets turned into fat cells rather than osteoblasts.
Clearly, there’s more work to be done. But Stahl claims that his group’s new studies are the first to demonstrate that a short term nutritional perturbation early in life “has the potential for a life-long impact on bone.”
But do newborn babies encounter this kind of calcium deprivation? Maybe not quite this bad, Stahl says, but yes some won’t get nearly as much calcium as others. For instance, there is considerable variation in the amount of calcium present in breast milk, which he says some scientists suspect has to do with the moms lacking enough vitamin D. (The hormonal form of this vitamin is essential for the efficient use of calcium.) And some moms just can’t make enough milk to fuel their babies’ efficient growth.
As for long term implications: Once mesenchymal stem cells mature into marrow-dwelling fat cells, there’s no going back. So every stem cell taking this career path further reduces the number of cells available to later make bone. He says it also suggests why osteoporotic bone has more fat in its marrow than does healthy bone – and why “some people view osteoporosis as the obesity of bone.”