Scientists pinpoint gene that carries osteoporosis risk

While heredity is known to play a major role in an individual's likelihood of developing osteoporosis, until recently scientists could only point to a handful of genes that appear to confer this risk. However, all that has begun to change, and a recent Canadian study has made the latest addition to the list of genes potentially related to osteoporosis.

A report appearing in the journal Cell Metabolism named inositol polyphosphate 4-phosphatase type IIa (Inpp4ba) as a gene that, when disabled, may lead to the relatively rapid onset of osteoporosis.

This discovery may contribute to more targeted preventive medicine for people who are found to have certain variants of the gene.

A bone-mass-regulating strip of DNA, Inpp4ba helps control the number of osteoclasts found in bone. These specialized cells break down bone minerals, just as their sister cells - called osteoblasts - operate in concert by building up bone matrix.

When a healthy equilibrium is established, osteoblasts and osteoclasts maintain proper bone density. However, researchers found that when Inpp4ba was deactivated in laboratory mice, the animals' osteoclast levels went through the roof.

An imbalance in favor of these mineral-dissolving cells can quickly lead to low bone density and, in time, osteoporosis, the team said.

Lead author Matthieu Ferron, of the Clinical Research Institute of Montreal, first wrote on the subject in 2005, in a PhD dissertation submitted to the University of Montreal.

The team - which hails from both institutions, as well as Canada's McGill University and the Washington University School of Medicine in St. Louis - said that the study of the predisposition for low bone mass must encompass osteoporosis origins at the genetic level, as well as those of a larger scale.

"The overall objective of our research is to understand the molecular and cellular mechanisms that determine the balance between bone formation and resorption [breakdown]," co-author Jean Vacher wrote.

Many pharmaceutical treatments for osteoporosis operate by inhibiting the formation of osteoclasts, which in turn allows osteoblasts to rebuild bone. For instance, this is the primary mechanism of action of bisphosphonates, a class of medications that is widely prescribed for low bone density.

The ability to treat osteoporosis on a genetic level is still some years away, but many scientists have expressed enthusiasm over the possibility of slowing bone loss - or reducing the risk of it - by "switching" specific genes on or off.

In the case of Inpp4ba, the ability to reactivate the gene if it has been silenced could lead to novel therapies for bone loss. For now, such treatments are unavailable.

That said, the authors noted that, at the very least, doctors may be able to determine which patients are at a higher risk of osteoporosis by delivering genetic tests that search for particular variants of Inpp4ba. Improvements in risk detection could potentially avert millions of instances of progressive bone loss.

Currently, 10 million Americans have been diagnosed with osteoporosis, according to the National Osteoporosis Foundation.