Gut found to exert control over bone
The combination of estrogen plus progestin, which women stopped taking in droves following the news that it may increase their risk of breast cancer, may decrease their risk of colorectal cancer, according to a report published in the January issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.
Full Post: Estrogen plus progestin therapy may decrease risk of colorectal cancer
When it comes to remodeling our bones-an ongoing process of break down and renewal that goes on throughout adulthood–researchers have new evidence that our guts play a surprisingly important role.
The findings point toward novel methods for increasing bone mass in patients with diseases characterized by impaired bone formation, including postmenopausal osteoporosis, according to the report in the November 26th issue of the journal Cell, a Cell Press publication.
“This is totally new,” said Gerard Karsenty of Columbia University. “We had no clue that the gut had control over bone, and in such a powerful manner.”
Too much serotonin released by the gut leads to a decline in bone mass; too little and bones bulk up beyond what is normal, their study shows. While serotonin is most familiar for its effects on the brain, 95 percent of all serotonin in the body is actually produced by the gut, Karsenty explained. Just what that serotonin did, however, had remained a matter of considerable debate.
The current study was aimed at clearing up the role of a gene that encodes LDL-receptor related protein 5 (LRP5), one of the most intensely studied regulators of bone remodeling. Patients with a genetic mutation that leads to a loss of that protein’s function have a rare disease known as osteoporosis pseudoglioma (OPPG), characterized by a severe decline in bone formation and other symptoms. Other, presumably activating, mutations in LRP5 cause high bone mass syndrome. “That different mutations in this gene cause two bone diseases of opposite nature underscores the critical importance in the regulation of bone formation of the pathway or pathways controlled by Lrp5,” the researchers said.
Earlier studies had suggested LRP5 might operate on bone through one developmental pathway, but Karsenty’s team wasn’t convinced that was the whole story. They’ve now confirmed that hunch.
They find that the bones of mice lacking Lrp5 show a rise in the activity of an enzyme called tryptophan hydroxylase 1 (Tph1). Tph1 limits the rate of serotonin production in the gut from the amino acid tryptophan. (Amino acids are the building blocks of proteins.) In other words, mice without Lrp5 have too much Tph1, leading them to overproduce gut serotonin.
Further study showed that decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice, and that gut- but not bone-specific Lrp5 inactivation decreases bone formation. Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents bone loss in mice who have had their ovaries removed, a condition that mimics menopause.
Although the findings were made in mice, Karsenty says they have direct application to understanding bone remodeling in humans, and to the development of treatments designed to increase bone mass.
” This is not a mouse story,” Karsenty said. “From the beginning it was a human story that we’ve now worked out in the mouse.”
The findings suggest that OPPG and high bone mass syndrome are actually more gut- than bone-originating diseases. It also provides an explanation for another observation: that patients with autism who have high blood serotonin levels often have osteoporosis. Patients taking synthetic serotonin reuptake inhibitors (SSRIs) chronically, a class of antidepressant drugs that increase extracellular serotonin concentration, can also have reduced bone mass, the researchers noted. They emphasized however, that it’s too soon to say whether this new connection between gut serotonin and bone will explain that side effect of the drugs or not.
So, given the gut’s newfound pull over bone, might diet play a role?
While the researchers did show in mice that a diet low in the tryptophan-the raw ingredient for serotonin’s manufacture–can have an effect on bone mass, at least in the Lrp5-deficient mice, Karsenty thinks that serotonin inhibiting drugs are a more likely method than diet for building bone mass in people. Coincidentally, however, one of the highest sources of tryptophan is the Thanksgiving turkey.
A review article which is published in the current issue of the European Journal Psychotherapy and Psychosomatics analyzes the relationship between depression and bone metabolism. This study reveals that the association between psychiatric illness, in particular depression, and osteoporosis has been the subject of a growing body of research yielding various findings, although most identify
Full Post: Osteoporosis? Look out for depression
The Department of Biomedical Engineering at Stony Brook University received a $1.8 million grant from the National Institutes of Health (NIH) to investigate the biologic and physical mechanisms of very low-magnitude mechanical signals and how they strengthen bone and muscle. Led by Clinton Rubin, Ph.D., SUNY Distinguished Professor and Chair of Biomedical Engineering, and Stefan
Full Post: Non-pharmacologic interventions for the control of osteoporosis and obesity
New research reveals that computed tomography (CT) colonography, also known as virtual colonoscopy, has the potential to screen for two diseases at once-colorectal cancer and osteoporosis, both of which commonly affect adults over age 50. Results of the study will be presented today at the annual meeting of the Radiological Society of North America (RSNA).
Full Post: Virtual colonoscopy has potential to screen for colorectal cancer and osteoporosis at same time
Patients who start and eventually stop regimens of a common class of osteoporosis drugs called bisphosphonates may be unable to benefit from parathyroid hormone (PTH), which can rebuild bone mass lost due to advanced stage osteoporosis. PTH has been proven to increase the volume and strength of the honeycomb-like bone infrastructure, the inner mesh that
Full Post: Osteoporosis drugs may prevent future bone growth
Researchers at the University of Toronto, Faculty of Medicine, Toronto, Canada, have discovered that adiponectin, a protein secreted from adipocytes, is a metabolic link that can explain, in part, the known positive relationship between obesity and both bone mineral density and reduced susceptibility to fractures. This study appears in the December issue of Experimental Biology
Full Post: Adiponectin is a metabolic link between obesity and bone mineral density