Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF-alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis.
BACKGROUND
Osteoporosis that is encountered frequently in postmenopausal women, may cause an increased incidence of vertebral and iliac fractures that are associated with excess morbidity. Raloxifene hydrochloride, a selective oestrogen receptor modulator, has been shown to increase bone mineral density and decrease biochemical markers of bone turnover in postmenopausal women, without stimulatory effects on breast or uterus. Levels of proinflammatory cytokines, including IL-6, and TNF-alpha and TGF-beta1 which are important cytokines involved in remodeling, have been evaluated previously in in vitro studies of osteoporosis. However, there seems to be a paucity of in vivo research concerned with changes in these cytokines in osteoporosis.


OBJECTIVE
In this study, we evaluated the effects of raloxifene (Evista); Lilly Pharmaceutical Co. USA, 60 mg/day) on biochemical bone turnover markers, serum parathyroid hormone, and 25-OH vitamin D, as well as the serum levels of IL-6, TNF-alpha and TGF-beta1, in 22 postmenopausal, osteoporotic women before and after 12 weeks of raloxifene treatment.


METHODS
Well-matched, postmenopausal, non-osteoporotic control subjects were also enrolled in the study. Serum levels of all the parameters were measured in postmenopausal, osteoporotic women at baseline and end of the study.


RESULTS
It was found that serum osteocalcin and parathyroid hormone, and urine deoxypyridinoline levels decreased to normal levels with treatment. Serum 25-OH vitamin D levels after treatment in the patient group were higher than those in the control group. Serum IL-6, TNF-alpha and TGF-beta1 levels did not change significantly with treatment. However, serum levels of IL-6 and TGF-beta1 in the patient group after treatment, decreased to levels lower than those found in the control group. Serum TNF-alpha levels in the patient group before and after treatment, were lower than those in the control group.


CONCLUSIONS
Raloxifene treatment reduces bone turnover biochemical markers, parathyroid hormone and induces 25-OH vitamin D in postmenopausal women. Moreover, it also affects some serum cytokine levels in the postmenopausal period.
Ozmen
Bilgin
B
Celal Bayar University, Medical Faculty, Department of Internal Medicine, Division of Endocrinology and Metabolism, Manisa, Turkey.
Kirmaz
Cengiz
C
Aydin
Kadir
K
Kafesciler
Sabriye O
SO
Guclu
Feyzullah
F
Hekimsoy
Zeliha
Z
D000596:Amino Acids / Q000187:drug effects / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000187:drug effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects; D014807:Vitamin D / Q000097:blood