Double-blind, placebo-controlled study of the effects of tibolone on bone mineral density in postmenopausal osteoporotic women with and without previous fractures

Abstract

A 2-year placebo-controlled, randomized, two-center prospective study was carried out to assess the effects of tibolone (Org OD14, Livial) on trabecular and cortical bone mass and bone biochemistry parameters in elderly postmenopausal women with and without previous fractures. In total, 107 subjects, 71 with fractures and 36 without fractures, were randomized to tibolone (n = 64) or placebo (n = 43). Their mean age was 63.1 years. Bone mineral density (BMD) (g/cm2) was assessed at baseline and every 6 months for 2 years by dual-energy X-ray absorptiometry (DXA). Mean baseline values were 0.79 and 0.80 for the lumbar spine in the tibolone and placebo groups, respectively, and for the femoral neck 0.64 in both groups. Serum and urinary bone biochemistry parameters were measured concurrently. An analysis of variance (ANOVA) model including center and group was applied. The completers' group was the primary subset for the analysis; the intention-to-treat (ITT) group was also analyzed. Results are expressed as the percentage change at 24 months and the annual rate of change percentage year. The tibolone group showed an overall mean increase (vs. placebo) in BMD at the lumbar spine of 7.2% (p < 0.001) and for the femoral neck 2.6% (p < 0.001). In subjects with previous fractures increases were 6.0% and 4.0% for the lumbar spine and femoral neck, while in those with no fractures, respective changes were 8.9% and 1.1%. Overall changes in the placebo group were 0.9% and -1.6% for the lumbar spine and femoral neck, respectively. A significant fall in bone biochemistry parameters showed that tibolone inhibits osteoclastic activity. In conclusion we have found that tibolone 2.5 mg induces significant increases of trabecular and cortical bone mass in elderly postmenopausal osteoporotic women with and without previous fractures.

Randomized, Double-masked, 2-year Comparison of Tibolone with 17β-Estradiol and Norethindrone Acetate in Preventing Postmenopausal Bone Loss

“…These data, in agreement with previous studies in late menopausal women [31,33], show that tibolone 2.5 mg, tibolone 1.25 mg or E 2 / NETA effectively prevent bone loss in a wide range of subjects. Longer studies would be needed to determine the effect of these findings on the incidence of fractures.…”

“…Results from this randomized, double-masked study confirm those from smaller, placebo-controlled [31][32][33][34] or comparative trials of tibolone treatment [35][36][37]. Furthermore, this is the first study to compare directly the effects of tibolone and continuous combined conventional HRT on bone density.…”

“…The efficacy of tibolone in preventing bone loss in early and late postmenopausal women hs previously been demonstrated in studies controlled against untreated participants [23,30], placebo [31][32][33][34] or sequential HRT [35][36][37]. Although tibolone is as effective at maintaining BMD as sequential HRT, no study comparing the effects on bone of tibolone with those of continuous combined conventional HRT has been published.…”

Management of age-related osteoporosis and prevention of associated fractures

“…The effects of 1.25–2.5 mg daily have been studied for improvements in surrogate markers of bone turnover and bone density improvements at the hip and lumbar spine. Increases in bone density have ranged from 3.6% to 7.2% at the lumbar spine and 2.6% to 4.6% at the femoral neck, though data on fracture reduction is currently lacking ( Thiebaud et al 1998 ; Pavlov et al 1999 ; Rymer et al 2001 ; Roux et al 2002 ).…”

Tibolone and its effects on bone: a review

“…The thickness of the lines is proportional to the weight of that study center in meta-analysis64,[71][72][73] Climacteric Downloaded from informahealthcare.com by University of Toronto on 11/04/14 The thickness of the lines is proportional to the weight of that study center in meta-analysis64,[71][72][73] Climacteric Downloaded from informahealthcare.com by University of Toronto on 11/04/14…”