Effects of raloxifene on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis.
BACKGROUND
Premature amenorrhea and hypoestrogenism and lack of hormone replacement therapy after menopause have been frequently reported in uremic women on dialysis. Therefore, in addition to renal osteodystrophy, postmenopausal women on dialysis could be at risk of osteoporosis. In addition, these patients are at higher risk for hyperlipidemia, arteriosclerosis, and subsequent coronary heart disease and stroke. Recent evidence has suggested that hormone replacement therapy (HRT) in postmenopausal women could have several beneficial effects as well as potentially serious risks. Great efforts have been made to identify therapeutic alternatives that would have the benefits of estrogen on brain and bone without its adverse effects on breast and endometrium. In the present study, we evaluated the effect of raloxifene, a selective estrogen receptor modulator (SERM), on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis.


METHODS
We performed a prospective, blind, placebo-controlled, and randomized study. Fifty postmenopausal women on chronic hemodialysis with proven severe osteopenia or osteoporosis by bone densitometry were selected. After a written informed consent, patients were randomized into two groups: 25 women on placebo and 25 women on the study drug, raloxifene hydrochloride, at a dose of 60 mg/day. In all patients, we performed a baseline bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, serum lipids (total low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol and triglycerides) and serum markers of bone resorption (pyridinoline crosslinks). BMD was reassessed after 1 year of therapy. Bone resorption markers were determined every 3 months for 1 year.


RESULTS
After 1 year on raloxifene therapy, lumbar spine BMD (trabecular bone) significantly improved, whereas femoral neck BMD (cortical bone) did not change significantly. No changes in BMD were observed at trabecular or cortical sites in the placebo group. Serum pyridinoline levels showed a significant decrease after 6 months on raloxifene that persisted thereafter. Low-density lipoprotein (LDL)-cholesterol decreased significantly in the raloxifene group with no changes in serum triglycerides, total cholesterol, or HDL cholesterol. No significant side effects were observed in the raloxifene group.


CONCLUSIONS
The study demonstrates that after one year on raloxifene, postmenopausal women on hemodialysis have a significant increase in trabecular BMD, decrease in bone resorption markers and LDL-cholesterol values, suggesting that SERMs could constitute a therapeutic alternative to improve bone metabolism and control of hyperlipidemia in these patients. The possible long-term effects of raloxifene remain to be determined.
Hernández
Eddy
E
Division of Nephrology, Hospital Universitario de Caracas, Universidad Central de Venezuela, Caracas, Venezuela.
Valera
Raquel
R
Alonzo
Evelyn
E
Bajares-Lilue
Mariela
M
Carlini
Raúl
R
Capriles
Freya
F
Martinis
Ruby
R
Bellorin-Font
Ezequiel
E
Weisinger
José R
JR
D000368:Aged; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D006435:Renal Dialysis
D004965:Estrogen Antagonists; D008055:Lipids; D020849:Raloxifene Hydrochloride