Serum serotonin levels and bone in rheumatoid arthritis patients

Abstract

In rheumatoid arthritis (RA), a disease characterized by bone loss, increased levels of serotonin have been reported. Recent studies have demonstrated a role for circulating serotonin as a regulator of osteoblastogenesis, inhibiting bone formation. Thus, we measured serum serotonin levels (SSL) in a Portuguese sample of 205 RA patients and related these to anthropometric variables, disease parameters, serum bone biomarkers, and bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry at several sites (total proximal femur, lumbar spine, left hand, and left second proximal phalange). SSL were inversely associated with body mass index (BMI) in RA women (r = - 0.218; p = 0.005), independent of exposure to biologics and/or bisphosphonates. Among biologic naïves, there was an inverse association between SSL and osteoprotegerin in RA women (r = - 0.260; p = 0.022). Serum β-CTX and dickkopf-1 were strongly associated with SSL in RA men not treated with bisphosphonates (r = 0.590; p < 0.001/r = 0.387; p = 0.031, respectively). There was also an inverse association between SSL and sclerostin in RA men (r = - 0.374; p < 0.05), stronger among biologic naïve or bisphosphonates-unexposed RA men. In crude models, SSL presented as a significant negative predictor of total proximal femur BMD in RA women as well as in postmenopausal RA women. After adjustment for BMI, disease duration, and years of menopause, SSL remained a significant negative predictor of total proximal femur BMD only in postmenopausal RA women. Our data reinforce a role, despite weak, for circulating serotonin in regulating bone mass in RA patients, with some differences in terms of gender and anatomical sites.

Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases

“…RA is a chronic autoimmune inflammatory disease with typical characteristics of chronic inflammation and joint damage (71). Activated platelets and increased serum levels of 5-HT have been reported; high levels may be a negative predictor of bone mineral density in RA for suppressing osteoblasts (72). It has been demonstrated that 5-HT activates 5-HT 1B receptors on osteoblasts and inhibits their proliferation by activating proteinkinase A and cAMP-response element binding protein signaling pathway (73).…”

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

“…In RA patients, increased levels of circulating serotonin, possibly released by activated platelets, have been reported. In the authors’ opinion, this finding may represent a negative predictor of bone mineral density in RA associated with a suppression of osteoblasts [ 64 , 65 ]. Serotonin levels are also elevated in RA SFs, where it induces synovial plasma extravasation via the release of inflammatory mediators [ 66 , 67 ].…”

Coronary artery calcium score in female rheumatoid arthritis patients: Associations with apolipoproteins and disease biomarkers

“…Hypertension was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90 mm Hg or taking antihypertensive medication, dyslipidemia as total cholesterol ≥ 200 mg/dL or taking antidyslipidemic agents, diabetes as a fasting glucose ≥ 126 mg/dL or taking hypoglycemic agents . The included population integrates a larger group already characterized in terms of myocardial perfusion scintigraphy as well as circulating serotonin levels and LRP5 polymorphisms . The selection of patients for this specific study was purely based on equipment availability and conducted regardless of patient characteristics.…”