Treatment of Established Postmenopausal Osteoporosis with Raloxifene: A Randomized Trial

Abstract

Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems. We conducted a 1-year prospective, randomized, double-blind trial in 143 postmenopausal osteoporotic women (mean ؎ SD age, 68.4 ؎ 5.0 years) with at least one prevalent vertebral fractures and low bone mineral density (BMD), comparing groups receiving raloxifene at 60 mg/day (RLX60) or 120 mg/day (RLX120) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding, thrombophlebitis, breast abnormalities, or increased endometrial thickness (assessed by ultrasonography). As compared with controls, the changes in values over 1 year for RLX60 and RLX120, respectively, were significant for serum bone alkaline phosphatase (؊14.9%, ؊8.87%), serum osteocalcin (؊20.7%, ؊17.0%), and urinary C-telopeptide fragment of type I collagen/creatinine (؊24.9%, ؊30.8%), markers of bone turnover; for serum total cholesterol (؊7.0% for RLX60) and low density lipoprotein cholesterol (LDL) (؊11.4% for RLX60) and for the LDL/HDL cholesterol ratio (؊13.2%, ؊8.3%). BMD increased significantly in the total hip (1.66% for RLX60) and ultradistal radius (2.92%, 2.50%). There were nonsignificant trends toward increases over controls in BMD for lumbar spine, total body, and total hip (for RLX120). Using a >15% cutoff definition, raloxifene had no effect on incident fractures, but using a >30% cutoff, there was a dose-related reduction (p ‫؍‬ 0.047). We conclude that raloxifene therapy is well tolerated, reduces serum lipids, and does not stimulate the uterus or breasts. It has beneficial effects on bone, although, under the conditions of this study, these appear to be of a smaller magnitude than have been reported with estrogen therapy. (J Bone Miner Res 1998;13:1747-1754)

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia

“…Other studies have reported a similar decrease in BTM in response to raloxifene for CTX measured using other methods [1,2,25] and for total PINP measured by a different autoanalyser method [26] . The changes in BTM occur earlier and are of a greater magnitude than the change in bone density.…”

“…Raloxifene is a selective estrogen receptor modulator (SERM) that has beneficial effects on bone and lipids with no detrimental effects on the breast or endometrium [1,2] and is licensed for the treatment and prevention of osteoporosis [3] . Raloxifene treatment results in an increase in bone mineral density (BMD), reduction in bone turnover markers (BTM) and reduced risk of vertebral fractures [4][5][6] .…”

Tratamento da osteoporose pós-menopausa

“…Os moduladores de receptor de estrógeno de segunda geração como raloxifeno, não têm efeito agonista nos tecidos reprodutivos. Há vários trabalhos de uso clínico de raloxifeno 60 mg em osteoporose pós menopausa (1,2). Há um estudo do efeito de raloxifeno sobre a incidência de fraturas, mostrando redução de fraturas vertebrais em radiografia em 50% no período de 24 meses; o estudo continua para avaliação de 36 meses (3).…”

Raloxifeno e osteoporose: revisão de um novo modulador seletivo do receptor de estrógeno

“…O clomifeno já está em uso clínico há vários anos para tratamento de infertilidade feminina, enquanto droloxifeno, idoxifeno e toremifeno ainda estão em fase II/III de pesquisas clínicas. A estrutura do raloxifeno está representada na figura l. A parte inferior da estrutura do raloxifeno liga-se ao receptor de estrógeno, enquanto a cadeia lateral básica se liga à um sítio diferente e leva às propriedades antagonistas do composto (8,9).…”

“…Porém, raloxifeno não causa estimulação endometrial (tabela 1). Em estudos clínicos recentes, raloxifeno mostrou efeitos benéficos no esqueleto (8,9), o que levou à aprovação do raloxifeno para a prevenção e tratamento de osteoporose no Brasil. Nesta revisão, abordaremos aspectos pré-clínicos/clínicos gerais atuais do raloxifeno e suas perspectivas para o futuro.…”