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Skeleton May Sustain Damage Due To Use Of Anti-Depressants - for Bowriver

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http://tinyurl.com/34xftg

A Norwegian study has revealed that anti-depressants like Fluoxitine, more

familiarly known as Prozac may inflict damage upon the human skeleton.// The

Norwegian University of Science and Technology's (NTNU) researcher Bjorn I.

Gustafsson has revealed that anti-depressants contribute towards impeding the

activity of bone building cells, while raising the production of substances

which lead to the breakdown of the bone mass. As many as 400,000 Norwegians use

anti-depressants daily.

Gustafsson's research has focused on Fluoxetine, but other anti-depressants are

believed to have similar side effects.

Anti-depressants increase the amount of serotonin in the brain. Serotonin is an

important neurotransmitter, and most of the body's serotonin is produced by

specific cells in the stomach and intestinal system.

The research suggests that the anti-depressants affect the balance between bone

producing osteoblasts, and osteoclasts that break down bones.

There are no records of long-term effects of anti-depressants on human beings,

but researchers in the Netherlands and the US are trying to collect the relevant

data.

Here's the study abstract mentioned in the article and then the more recent

study at the bottom. " We found a slightly diminished bone quality, reflected in

a lower bone tissue strength, which was compensated by changes in bone

geometry. "

J Cell Biochem. 2006 May 1;98(1):139-51.

Serotonin and fluoxetine modulate bone cell function in vitro.

Gustafsson BI, Thommesen L, Stunes AK, Tommeras K, Westbroek I, Waldum HL,

Slørdahl K, Tamburstuen MV, Reseland JE, Syversen U.

Department of Internal Medicine, Sections for Gastroenterology and

Endocrinology, St Olavs University Hospital HF, Trondheim, Norway.

bjorn.gustafsson@...

Recent studies have proposed a role for serotonin and its transporter in

regulation of bone cell function. In the present study, we examined the in vitro

effects of serotonin and the serotonin transporter inhibitor fluoxetine " Prozac "

on osteoblasts and osteoclasts. Human mononuclear cells were differentiated into

osteoclasts in the presence of serotonin or fluoxetine. Both compounds affected

the total number of differentiated osteoclasts as well as bone resorption in a

bell-shaped manner. RT-PCR on the human osteoclasts demonstrated several

serotonin receptors, the serotonin transporter, and the rate-limiting enzyme in

serotonin synthesis, tryptophan hydroxylase 1 (Tph1). Tph1 expression was also

found in murine osteoblasts and osteoclasts, indicating an ability to produce

serotonin. In murine pre-osteoclasts (RAW264.7), serotonin as well as fluoxetine

affected proliferation and NFkappaB activity in a biphasic manner. Proliferation

of human mesenchymal stem cells (MSC) and primary osteoblasts (NHO), and 5-HT2A

receptor expression was enhanced by serotonin. Fluoxetine stimulated

proliferation of MSC and murine preosteoblasts (MC3T3-E1) in nM concentrations,

microM concentrations were inhibitory. The effect of fluoxetine seemed direct,

probably through 5-HT2 receptors. Serotonin-induced proliferation of MC3T3-E1

cells was inhibited by the PKC inhibitor (GF109203) and was also markedly

reduced when antagonists of the serotonin receptors 5-HT2B/C or 5-HT2A/C were

added. Serotonin increased osteoprotegerin (OPG) and decreased receptor

activator of NF-kappaB ligand (RANKL) secretion from osteoblasts, suggesting a

role in osteoblast-induced inhibition of osteoclast differentiation, whereas

fluoxetine had the opposite effect. This study further describes possible

mechanisms by which serotonin and the serotonin transporter can affect bone cell

function.

J Cell Biochem. 2007 May 15;101(2):360-8.

Long-term fluoxetine administration does not result in major changes in bone

architecture and strength in growing rats.

Westbroek I, Waarsing JH, van Leeuwen JP, Waldum H, Reseland JE, Weinans H,

Syversen U, Gustafsson BI.

Department of Cancer Research and Molecular Medicine, Faculty of Medicine,

Norwegian University of Science and Technology, Trondheim, Norway.

Many studies have indicated that serotonin and its transporter play a role in

bone metabolism. In this study we investigated the effect of selective serotonin

re-uptake inhibitor (SSRI), fluoxetine (Prozac) on bone architecture and quality

in growing female rats. We therefore administrated rats with clinically relevant

doses of fluoxetine for a period of 6 months. DXA scans were performed during

the treatment period in order to follow parameters as body weight, fat

percentage and BMD. After 6 months of treatment, femurs were used to analyze

bone architecture and bone strength, by means of microCT scans and three-point

bending assays, respectively. We found a slightly diminished bone quality,

reflected in a lower bone tissue strength, which was compensated by changes in

bone geometry. As leptin and adiponectin could be possible factors in the

serotonergic regulation of bone metabolism, we also determined the levels of

these factors in plasma samples of all animals. Leptin and adiponectin levels

were not different between the control group and fluoxetine-treated group,

indicating that these factors were not involved in the observed changes in bone

geometry and quality.

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