Bone Mineral Density Response to Estrogen Replacement in Frail Elderly Women

Villareal, Dennis T.; Binder, Ellen F.; Williams, Daniel B.; Schechtman, Kenneth B.; Yarasheski, Kevin E.; Kohrt, Wendy M.

doi:10.1001/jama.286.7.815

Cited by 75 publications

(51 citation statements)

References 44 publications

(55 reference statements)

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“…Similar increases in spine BMD induced by pharmacotherapy are associated with a 30-50% reduction invertebral fracture risk (17). Furthermore, this 2-y change is similar to or larger than that which results from 2 y of oral estrogen (12-5%) (18)(19)(20), bisphosphonates (14%) (21)(22)(23), and selective estrogen receptor modulators (11-2%) (24,25). The robustness of these findings is supported by the increase of '2% in spine BMD that occurred when women in the placebo group crossed over to DHEA supplementation in year 2.…”

Section: 85mentioning

confidence: 67%

Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone

Weiss¹,

Shah²,

Fontana³

et al. 2009

The American Journal of Clinical Nutrition

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Background: Age-related reductions in serum dehydroepiandrosterone (DHEA) concentrations may be involved in bone mineral density (BMD) losses. Objective: The objective was to determine whether DHEA supplementation in older adults improves BMD when co-administered with vitamin D and calcium. Design: In year 1, a randomized trial was conducted in which men (n ¼ 55) and women (n ¼ 58) aged 65-75 y took 50 mg/d oral DHEA supplements or placebo. In year 2, all participants took open-label DHEA (50 mg/d). During both years, all participants received vitamin D (16 lg/d) and calcium (700 mg/d) supplements. BMD was measured by using dual-energy X-ray absorptiometry. Concentrations of hormones and bone turnover markers were measured in serum. Results: In men, no difference between groups occurred in any BMD measures or in bone turnover markers during year 1 or year 2. The free testosterone index and estradiol increased in the DHEA group only. In women, spine BMD increased by 1.7 6 0.6% (P ¼ 0.0003) during year 1 and by 3.6 6 0.7% after 2 y of supplementation in the DHEA group; however, in the placebo group, spine BMD was unchanged during year 1 but increased to 2.6 6 0.9% above baseline during year 2 after the crossover to DHEA. Hip BMD did not change. Testosterone, estradiol, and insulin-like growth factor 1 increased in the DHEA group only. In both groups, serum concentrations of bone turnover markers decreased during year 1 and remained low during year 2, but did not differ between groups. Conclusion: DHEA supplementation in older women, but not in men, improves spine BMD when co-administered with vitamin D and calcium. This trial was registered at clinicaltrials.gov as NCT00182975.

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Section: 85mentioning

confidence: 67%

Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone

Weiss¹,

Shah²,

Fontana³

et al. 2009

The American Journal of Clinical Nutrition

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“…20,21 Compliance and retention were similar in all groups. Fifty-one percent (48/94) to 63% (59/93) of participants were adherent, which was defined as taking 80% of both medications during the study (TABLE 2) (criteria previously cited in other estrogen trials 22,23 ). Retention was 90% (337/373) for all participants after 3 years ( Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Combination Therapy With Hormone Replacement and Alendronate for Prevention of Bone Loss in Elderly Women

Greenspan¹,

Resnick²,

Parker³

2003

JAMA

133

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Dr Greenspan has had research support and has been on the speaker's bureau and a consultant for Merck Research Laboratories,Rahway, NJ. Dr Parker has been a consultant for Merck Research Laboratories.Context Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis, but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown.Objective To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe, and how they compare with monotherapy in community-dwelling elderly women.Design Randomized, double-blind, placebo-controlled, clinical trial.Setting and Participants Five hundred seventy-three community-dwelling women age 65 years or older were screened: 485 completed screening and 373 (aged 65 to 90 years) were randomized following a 3-month, open-label, run-in phase with hormone replacement and alendronate placebo. The trial was conducted at a single academic US medical center from January 1996 to May 2001.Interventions Participants were randomly assigned in a 2ϫ2 factorial design to receive hormone replacement (conjugated equine estrogen, 0.625 mg/d, with or without medroxyprogesterone, 2.5 mg/d) and alendronate, 10 mg daily, both agents, or neither. All participants received calcium and vitamin D supplements. Main Outcome MeasuresAnnualized change in bone mineral density of the hip and spine and occurrence of adverse events.Results Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy, with mean (SD) increases of 5.9% (3.8) at the total hip, 10.4% (5.4) at the posteroanterior lumbar spine, and 11.8% (6.8) at the lateral lumbar spine. Mean (SD) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone (4.2% [3.8] vs 3.0% [4.9]; PϽ.05, respectively), and alendronate resulted in more responders to therapy. All therapies were well tolerated and participant retention was 90% at 3 years.Conclusions Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort. Alendronate was superior to hormone replacement, and combination therapy was superior to either therapy alone. Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy.

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“…Observational studies reveal 50% lower fracture rates among women taking hormones than in women who are not, 26,27 and there is strong clinical trial evidence for a favorable effect of postmenopausal estrogen treatment, with or without progestin, on bone mineral density in various populations, including older women. 28,29 However, the clinical trial evidence for an effect on fractures has been limited. 30,31 Our earlier report from the HERS main trial revealed little difference between the hormone and placebo groups in risk of any type of fracture.…”

Section: Fracturementioning

confidence: 99%