Raloxifene modulates interleukin-6 and tumor necrosis factor-alpha synthesis in vivo: results from a pilot clinical study.
Raloxifene (RAL), a selective estrogen receptor modulator, is indicated for the prevention and treatment of postmenopausal osteoporosis. RAL, by decreasing bone turnover, prevents bone loss and microarchitecture damage, reducing the incidence of osteoporotic fractures. Our previous in vitro data demonstrated that RAL modulates osteoclast activity by, at least in part, an IL-6- and TNF-alpha-dependent mechanism. In this study we evaluated the effects of RAL treatment (60 mg/d) on circulating levels of these cytokines in 14 postmenopausal women with osteoporosis. Lumbar bone density (determined by dual energy x-ray absorptiometry) and IL-6 and TNF-alpha levels were measured before and after 6 and 24 months of therapy. After 24 months, RAL increased bone density. IL-6 and TNF-alpha expression, elevated before treatment, significantly decreased (50% and 30%, respectively) after 6 months. This effect was sustained up to the end of the treatment (75% and 35%, respectively). Thus, our data show that RAL can modulate circulating levels of cytokines involved in osteoclastogenesis and bone resorption, suggesting that modulation of soluble factors could play a pivotal role in the mechanisms of the osteoprotective effect of RAL.
Gianni
Walter
W
Unità Operativa Geriatria Oncologica, INRCA, Rome, Italy.
Ricci
Andrea
A
Gazzaniga
Paola
P
Brama
Marina
M
Pietropaolo
Maria
M
Votano
Sergio
S
Patanè
Francesco
F
Aglianò
Anna Maria
AM
Spera
Giovanni
G
Marigliano
Vincenzo
V
Ammendola
Sergio
S
Agnusdei
Donato
D
Migliaccio
Silvia
S
Scandurra
Roberto
R
D015519:Bone Density / Q000187:drug effects; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D010865:Pilot Projects; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D020849:Raloxifene Hydrochloride; D020845:Selective Estrogen Receptor Modulators; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors