Reduction of Vertebral Fracture Risk in Postmenopausal Women With Osteoporosis Treated With Raloxifene&lt;SUBTITLE&gt;Results From a 3-Year Randomized Clinical Trial&lt;/SUBTITLE&gt;

Ettinger, Bruce; Black, Dennis M.; Mitlak, Bruce; Knickerbocker, Ronald K.; Nickelsen, Thomas; Genant, Harry K.; Christiansen, Claus; Delmas, Pierre D.; Zanchetta, José R.; Stakkestad, Jacob A.; Glüer, Claus C.; Krueger, Kathryn A.; Cohen, Fredric J.; Eckert, Stephen; Ensrud, Kristine E.; Avioli, Louis V.; Lips, Paul; Cummings, Steven R.

doi:10.1001/jama.282.7.637

Cited by 2,933 publications

(441 citation statements)

References 30 publications

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“…Other antiresorptive treatments, such as alendronate and raloxifene, have also been shown to reduce the risk of first vertebral fracture, although the reductions in risk were smaller than the effect reported here for risedronate [15,16].…”

Section: Discussioncontrasting

confidence: 67%

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Heaney

Zizic²,

Fogelman

et al. 2002

Osteoporos Int

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Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score = -3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg ( n = 328) or placebo ( n = 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P = 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P = 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P = 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause.

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Section: Discussioncontrasting

confidence: 67%

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Heaney

Zizic²,

Fogelman

et al. 2002

Osteoporos Int

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“…Effectiveness For vertebral fracture, defined as 20 per cent reduction in vertebral height, the Multiple Outcomes of Raloxifene Evaluation (MORE) study 18 found a relative risk (RR) in women with osteoporosis or severe osteoporosis of 0.65 (95% CI 0.53-0.79) at 60mg and 0.54 (95% CI 0.44-0.67) at 120mg in favour of raloxifene compared with placebo. The evidence did not demonstrate that raloxifene has a preventive effect on nonvertebral fracture or hip fractures, except in a post-hoc analysis in a group with severe osteoporosis.…”

Section: Sermsmentioning

confidence: 99%

Recommended treatment and prevention of osteoporosis

Bhalla¹

2009

Prescriber

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“…The effects of raloxifene on bone mineral density and fracture risk after 3 years’ use in post-menopausal women were recently reported [8]. The Multiple Outcomes of Raloxifene Evaluation (MORE) study was commenced in 1994 to examine the skeletal effects of raloxifene.…”

Section: Raloxifene: a Second-generation Sermmentioning

confidence: 99%

Selective Oestrogen Receptor Modulators

Burger

2000

Horm Res Paediatr

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Selective oestrogen receptor modulators (SERMs) are compounds which act like oestrogens in some target tissues but which antagonise their effects in others. The first example of a SERM (referred to as a first-generation compound) was tamoxifen, for which oestrogen-like agonist activity on bone was seen to occur simultaneously with oestrogen antagonist activity on the breast. An unwanted effect of tamoxifen was its oestrogen-like action on the endometrium. Second-generation compounds have since been developed, most notably raloxifene, which has oestrogen-like actions on bone, lipids and the coagulation system, and oestrogen antagonist effects on the breast and uterus. Raloxifene has undergone very extensive, prospective, placebo-controlled, randomised trial evaluation, in which anti-fracture efficacy (to date only for vertebral fracture) has been accompanied by a major reduction in the incidence of new breast cancer. The compound is similar to placebo in its uterine effects, and similar to oestrogen in causing a two- to threefold increase in the risk of venous thromboembolism. Its lipid effects are similar to those of oestrogen, except for a relatively small effect on high-density lipoprotein cholesterol, and no significant effect on triglycerides. Data on cardiovascular event rates are not yet available; data on cognitive function are preliminary and, to date, reassuring. The mechanisms by which the same compound can exert oestrogen agonist effects on one target and antagonist effects on another are still being clarified. Important aspects include the fact that the oestrogen receptor undergoes different conformational changes according to the ligand. Thus the crystal structure of oestradiol bound to the oestrogen receptor differs from that of raloxifene bound to the same receptor. The existence of two oestrogen receptor subtypes may also be relevant. Mechanisms include differing interactions with various domains of the oestrogen receptor, and tissue-specific recruitment of steroid receptor co-activators and co-repressors may underlie some of the tissue-specific effects. The SERMs may be the prototype for other selective steroid receptor modulators, for example the androgen and progesterone receptors. The development of tissue target-specific agents is an exciting advance in endocrine pharmacology and can be extended to agents, such as tibolone, which exert some of their tissue specificity through their metabolites.

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Reduction of Vertebral Fracture Risk in Postmenopausal Women With Osteoporosis Treated With Raloxifene<SUBTITLE>Results From a 3-Year Randomized Clinical Trial</SUBTITLE>

Abstract: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

Cited by 2,933 publications

References 30 publications

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Recommended treatment and prevention of osteoporosis

Selective Oestrogen Receptor Modulators

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