Bone Density and Low-Dose Estrogen, Progesterone, Calcium, and Vitamin D
Clinical Reviews-With Comments from Lynn Keegan, RN, PhD, HNC, FAAN
Bone Density and Low-Dose Estrogen, Progesterone, Calcium, and Vitamin D
Source: Recker RR, et al. The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial. Ann Intern Med 1999;130:897-904.
Context: Hormone replacement therapy (HRT), the mainstay of osteoporosis prevention, is limited because of dose-related risks, side effects, and patient acceptance. The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women.
Objective: To determine the bone- sparing effect of continuous low-dose HRT in elderly women.
Subjects: One hundred twenty-eight healthy white women (age > 65 years) with low bone mass recruited by word-of-mouth and by local advertisement.
Design and Setting: Randomized, double-blind, placebo-controlled trial in university osteoporosis research and clinical center. The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less.
Intervention: The intervention was continuous therapy with 0.3 mg/d conjugated equine estrogen and 2.5 mg/d medroxyprogesterone, or matching placebo. Sufficient calcium supplementation was given to bring all calcium intakes above 1,000 mg/d in both groups; supplemental oral 25-hydroxy-vitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups.
Measurements: Bone mineral density of the spine, hip, total body, and forearm; serum total alkaline phosphatase and serum osteocalcin levels at six-month intervals; and 24-hour urine creatinine and hydroxyproline excretion at baseline, 12 months, and 42 months.
Results: During 3.5 years of observation, spinal bone mineral density increased by 3.5% (P < 0.001) in an intention-to-treat analysis and by 5.2% among patients with greater than 90% adherence to therapy. Significant in-creases were seen in total body and forearm bone density (P < 0.01). Symptoms related to HRT (breast tenderness, spotting, pelvic discomfort, and mood changes) were mild and short-lived.
Conclusion: Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other, higher-dose HRT regimens in elderly women. This combination is well-tolerated by most patients.
Comment: Hormone replacement therapy may deserve another look from a new perspective, this time for its bene-fit as a bone protector. The National Institutes of Health recommends that postmenopausal women receiving HRT should consume 1,000 mg of calcium daily and that postmenopausal women not using HRT should take 1,500 mg per day. Despite this study’s finding, clearly there is still controversy about the HRT of choice: synthetic, natural, or dietary.
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