Sci. Aging Knowl. Environ., 30 April 2003
Less Mucus, More Bone
Allergy provoker thins skeleton
Key Words: calcitriol histidine decarboxylase mastocytosis ovariectomy
Antiallergy meds could do more than help lovers smell springtime flowers without sneezing; the drugs might also strengthen bones. Mice unable to make histamine, the molecule that causes miserable allergy symptoms, have extra-thick skeletons, according to new research. Furthermore, histamine deficiency protects mice from bone loss in simulated menopause, the work shows. The results reveal how histamine influences bone metabolism and suggest that antihistamines might combat osteoporosis.
Cells that build bone are locked in a tug-of-war with cells that break it down. In premenopausal women, the hormone estrogen trips up the bone destroyers. When menopause turns off the estrogen tap, demolition cells can outpace construction crews and weaken the skeleton, resulting in osteoporosis (see "More Than a Hot Flash"). Much is known about the molecular details of bone growth (see "Losing Balance" and "The Plot Thickens on Thin Bones"), but some observations have suggested an additional mechanism. Extremely allergic people who have high concentrations of histamine coursing through their bloodstreams have abnormally low bone density, and postmenopausal women taking antihistamine medication acquire denser bones than do their antihistamine-free peers. Fitzpatrick and colleagues suspected that histamine plays a role in bone metabolism.
To investigate, the team engineered mice that lack the enzyme that makes histamine. The animals were healthy except for physiological responses that require histamine, such as allergic reactions. Bones in the histamine-deficient animals were 10% to 15% thicker than those in normal mice. To determine whether pumped-up bone formation contributes to the increased bone mass, the researchers injected a dye that incorporates into new bone; the dye revealed that histamine deficiency stimulates a dramatic increase in bone formation. Previous work showed that high histamine concentrations in blood coincide with low concentrations of activated vitamin D, which trucks calcium into bones. So the team indirectly measured how much vitamin D-activating and -deactivating enzymes the critters were making: Histamine-deficient mice had two to three times more messenger RNA (mRNA) for the activating enzyme than normal and only a fraction of the normal amount of deactivating enzyme mRNA, suggesting that histamine deficiency increases bone formation by powering up vitamin D.
The team also counted how many bone-destroying cells the mice carried. Animals without histamine had fewer of these demolition cells than did mice that could make the compound. This observation indicates that histamine promotes the duplication of bone-eradicating cells as well as the loss of bone-producing cells; antihistamine drugs might reverse these activities. The group also removed the ovaries from female mice, a process that simulates menopause, and found that a lack of histamine reduced the amount of bone loss.
The results are exciting, says molecular biologist Sylvia Christakos of New Jersey Medical School in Newark, because the team figured out the mechanism of antihistamine protection. Whether histamine functions similarly in humans needs to be determined, she says, but antihistamines might enhance current osteoporosis therapies aimed at boosting bone formation. If the results pan out, making springtime conducive to new love might also make it conducive to new bones.
April 30, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150