Osteoporosis is a debilitating and incurable bone condition that impacts millions of people around the world.
It occurs when the body loses bone faster than it can replace it, leaving the skeleton prone to fractures.
Stem cell treatments could be a cutting-edge solution, preventing fractures and even possibly reversing some bone loss.
Mesenchymal stem/stromal cells (MSCs) are the precursors of osteoblasts – the cells that create and repair bone.
MSCs can be harvested from marrow, the spongy tissue that exists at the center of bones, and then, they can be grown into large numbers in the lab.
Scientists have long been fascinated by this possibility. But there's a catch: when MSCs are infused back into the bloodstream of mice, very few actually end up where they need to be.
A first-in-human clinical trial, published in Cell, has now provided a fix with immense potential.
Researchers in Spain have shown that MSCs can be engineered with a 'return address' for bone marrow, possibly leading to bone growth.
Their trial tracked 10 female patients older than 50 with advanced osteoporosis.
After receiving a single infusion of their own engineered MSCs, enveloped in a special sugar, the patients showed a 94 percent sustained decrease in fragility fractures over the following two years.
Across the group, fractures fell from an average of eight per year in the two years before infusion to 0.5 per year in the two years afterward.
Watch the video below for a summary of the findings:
Reducing fragility fractures is the foremost goal of all current osteoporosis therapies, and yet this particular stem cell treatment also showed other benefits, too.
Four months after the infusion, bone biopsies revealed some positive signs.
Across the group, the average area occupied by bone tissue increased by around 70 percent.
The findings raise the possibility that this new MSC-technique can reverse some of the bone loss caused by osteoporosis, rather than simply slowing it.
The current study did not track the MSCs once they were infused into patients with osteoporosis, but markers that indicate bone formation remained elevated for half a year after the medicine was given.
Two years after the infusion, participants reported a decrease in bone pain of 34 percent and a reduction in disability scores of 30 percent.
Co-author Robert Sackstein holds intellectual-property rights to the cell-engineering technology used in the trial.
He and his colleagues have already shown that in diabetic mice, engineered MSCs can travel to the pancreas, where they can reverse the disease.
It's possible that similar techniques could be achieved for osteoporosis.
In mice, scientists have shown that when MSCs are decorated with a special sugar coating, they can re-enter bone, ultimately leading to tissue generation.
In the recent human trial, the decreased fracture incidence after MSC infusions could not be ascribed to lifestyle changes, the authors explain.
"Moreover, it cannot be attributed to medication modifications… since no fractures occurred throughout the post-infusion period in those patients… "
Ajit Varki, a physician-scientist at UC San Diego who wasn't involved in the study, told Nature's Elie Dolgin that the results are "quite remarkable."
The trial, said Varki, "showed an almost 100 percent efficacy sustained for several years – and no side effects".
But just because fractures fell does not prove this therapy can reverse the symptoms of osteoporosis.
This novel treatment showed statistically significant changes in bone turnover markers, bone tissue area, and bone mineral density.
But is that due to MSCs making it back into the bone, as they appear to do in mice?
The human trial did not follow the MSC cells after infusion, so there is no way to know how many reached the bone or how long they stayed there.
On LinkedIn, physician Jan Schaefer calls this a "fascinating experiment," but says the verdict is a few years away.
"MSCs are 20 to 30 micrometers across, larger than a lung capillary, so on the first pass through the circulation 50 to 80 percent of them lodge in the lungs," explains Schaefer.
"Of the rest, very few find their way into bone marrow on their own. You can have a potentially useful cell circulating and achieve almost nothing, because it never reaches the tissue you want to treat."
It's possible that the results seen in this current trial had nothing to do with the MSCs at all.
There was no control group, and most of the women were taking other osteoporosis drugs. They all were suffering from difficulties with fractures at the time.
Fracture risk is not constant. A group selected at its worst moment, argues Schaefer, is more likely to look better later on, on its own.
Scientists at the University of Murcia in Spain are now preparing a follow-up trial among a larger cohort of patients with advanced osteoporosis.
Related: Choice of Tea or Coffee Might Affect Risk of Osteoporosis in Older Women
This study will randomize participants to receive one of three treatments: engineered MSCs derived from their own bone marrow, engineered MSCs from a healthy donor, or no MSC treatment at all.
We will soon know more about whether this breakthrough technique to tag MSCs works in humans.
The research has been published in Cell.
This article was fact-checked by Fiona MacDonald and edited by Fiona MacDonald. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.