Calcium isn't the only thing in milk that's good for bones, a new study suggests. A protein present in cow's milk, as well as in human breast milk, stimulates bone-forming cells in lab dishes and induces bone growth when injected into mice, researchers have found.
The molecule, an iron-binding protein called lactoferrin, could form the basis of a new treatment for osteoporosis, says study leader Jillian Cornish of the University of Auckland in New Zealand.
When asked by the New Zealand dairy industry to search for novel substances in milk that might influence bone growth, Cornish was initially skeptical about finding anything new in what she considered to be such a thoroughly studied substance.
Her skepticism is gone. While calcium provides raw material for bone growth, other, unknown substances in milk appear to directly stimulate the activity of osteoblasts, the cells that form new bone. Cornish and her colleagues homed in on lactoferrin, which is typically found in body fluids such as tears, saliva, semen, and milk, as well as in several tissues. Immune cells called neutrophils also release it during inflammation, when the protein's antimicrobial properties come in handy.
The New Zealand team found that lactoferrin stimulates the proliferation and maturation of osteoblasts in lab dishes. It also protects the cells from apoptosis, a process that leads to cell death, the investigators report in an upcoming Endocrinology. Lactoferrin even inhibits the generation of osteoclasts, cells that counter osteoblasts by resorbing bone.
"We were absolutely stunned," says Cornish. Lactoferrin "was never known to be bone-active."
To test the protein's effects on live animals, the investigators injected it under the scalps of adult mice for 5 consecutive days. The treatment significantly accelerated the rate of new skull-bone formation. "It's a very potent molecule," says Cornish.
In mammals, lactoferrin production rises in an embryo during the last half of gestation, an indication that it promotes skeletal development. Its high concentrations in milk, particularly in colostrum, the rich milk produced immediately after a baby is born, suggest that it might also be important to newborns, says Cornish.
In another report to appear in a forthcoming Molecular Endocrinology, Cornish and her colleagues present evidence that lactoferrin affects osteoblasts by binding to cell-surface proteins called low-density lipoprotein receptors.
Although there are drugs that prevent bone resorption by osteoclasts, only one Food and Drug Administration–approved compound, parathyroid hormone, stimulates bone formation. Cornish and her colleagues may have unearthed a new bone-growing pathway, say other researchers.
"It's very exciting. It opens up a whole new area," says osteoporosis researcher Clifford J. Rosen of St. Joseph Hospital in Bangor, Maine. For lactoferrin to serve as an osteoporosis drug, investigators need to show that it can reach bone throughout the body, rather than just where it's injected, he cautions.
Department of Medicine
University of Auckland
Private Bag 92019
Clifford J. Rosen
Maine Center for Osteoporosis Research and Education
St. Joseph Hospital
Bangor, ME 04401
Lorget, F., et al. 2002. Lactoferrin reduces in vitro osteoclast differentiation and resorbing activity. Biochemical and Biophysical Research Communications 296(Aug. 16):261-266. Abstract available at [Go to].