There are a host of medications that cause bone loss. Glucocorticoids (corticosteroids such as cortisone and prednisone) prescribed for reducing inflammation, have long been known to be the biggest offender. But another commonly prescribed group of medications, the selective serotonin reuptake inhibitors or SSRIs, have also come under scrutiny.

Serotonin is a neurotransmitter made from the amino acid tryptophan. It has been studied most extensively for its role in mood regulation. Approximately 1 to 2 percent of the body’s production of serotonin is in the brain. SSRIs work by blocking serotonin re-uptake thereby increasing its availability within nerve synapses. The more serotonin available at the synapses, the better a person’s mood. But the effects of serotonin are not limited to mood enhancement. This neurotransmitter is also involved in a person’s response to hunger, sex, and sleep. In addition, it has neuro-regulatory effects in other parts of the body outside of the brain.

The rest of the body’s serotonin is produced outside of the brain. Here it is involved with regulating activity of the heart, the gastrointestinal tract, and yes, the remodeling activity of bones. In recent years, doctors began to recognize a link between the use of SSRI medications and the diagnosis of osteoporosis. We are now beginning to understand why.

The majority (95%) of the body’s serotonin is synthesized in the gut (duodenum). Here, serotonin stimulates peristalsis (gut motility) and increases vascular permeability. In 2008, scientists (Yadav et al.) at Columbia University discovered that serotonin was involved in yet another function–the regulation of bone remodeling. What the researchers found was that elevated levels of gut-derived serotonin can enter the circulation* and find its way to bone. Here, it inhibits bone formation by shutting down the cellular activity of osteoblasts (bone forming cells). This startling finding literally rocked the world of bone biology. Now we were seeing a possible connection between gut-derived serotonin, the enhancement of its activity by SSRIs, and bone loss.

In the September issue of Bone (2012) a review of the literature by Rizzoli et al. (European Society for Clinical and Economic Aspects of Osteoporosis) concluded that there is a link between the use of anti-depressant medications and increased risk of fracture. “The body of evidence suggests that SSRIs should be added to the list of medications that contribute to osteoporosis.” The evidence is fairly clear now that SSRIs contribute to bone loss. But many questions still remain. Do SSRIs increase both brain serotonin levels and raise levels of gut-derived serotonin? Do SSRIs enhance the spillage of serotonin into the bloodstream and increase levels in bone marrow where it is now known to shut down bone formation? The answers to these questions appear to be yes but further research is necessary.

* In an earlier blog article, I wrote about MPV** (mean platelet volume) and its correlation to bone loss. Serotonin is carried predominantly by platelets in the blood. As MPV increases (a sign of inflammation and the release of large immature platelets), bone mineral density decreases. This correlation may well go beyond just the connection of inflammation to bone loss. When platelets are activated, one of the signaling molecules*** that they release is…serotonin! Only time will tell if this suspicious connection is involved in the development of osteoporosis (my bet is that it does).  As new research solves the mysteries of the serotonin/bone connection we, no doubt, will benefit in our ability to help reduce fracture risk. In the meantime, if you have osteopenia or osteoporosis and your MPV is elevated, increase your fruit and vegetable intake, supplement with curcumin, and take OsteoStim for its powerful antioxidant and bone building potential. Elevated MPV is also an indication of increased cardiovascular risk so talk with your doctor if it is high.

** MPV is a value commonly reported on a CBC lab test.

*** Activated platelets also release nucleotides such as ATP, ADP, UTP and UDP. Stay tuned for a future blog article on the effect of the extracellular nucleotide system on bone.

Rizzoli R., et al. 2012. Antidepressant medications and osteoporosis. Bone 51(3):606-613