Low-Dose Hormone Replacement Therapy and Alendronate for Osteoporosis
|Osteopenia Osteoporosis||Drug: Alendronate Drug: Estrogen/progestin therapy||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Clinical Trial of Continuous Low-Dose Hormone Replacement Therapy Combined With Alendronate in Postmenopausal Women With Low Bone Density|
|Study Start Date:||October 1999|
|Estimated Study Completion Date:||September 2004|
Clinical trials of estrogen/progestin replacement therapy (HRT) and a bisphosphonate, alendronate (ALN), have demonstrated that both are effective in causing gains in bone mass and preventing bone loss and fractures in postmenopausal women. The FDA has approved both these drugs for prevention and treatment of fractures, and both are widely used in clinical practice. Because both are approved and effective, and they work by different mechanisms, many patients and their physicians ask whether both should be taken in combination, particularly in cases of severe disease. The question is asked frequently because of the high incidence of osteoporosis among women and the need for long-term prevention and treatments that often last decades.
Indeed, physicians are using ALN and HRT together without adequate scientific support for the assumption that the combination is more effective than either given alone.
Clinical trials are now underway to test conventional doses of HRT given as conjugated equine estrogens (CEE), 0.625 mg/day or its equivalent, combined with ALN, 10 mg/day. However, researchers are not studying the bone-sparing effectiveness of the combined administration of ALN and low-dose continuous HRT given as CEE, 0.3 mg/d, along with medroxyprogesterone, 2.5 mg/d (MP). This low-dose continuous HRT regimen is attractive because of better convenience, better patient tolerance, and reduced risk of breast cancer and other safety concerns associated with conventional higher doses. Further, we have recently demonstrated that the bone-sparing effect of this regimen is comparable to that of higher doses.
The long-term objective of this study is to test the hypothesis that the combined therapy shows a greater bone effect than does either treatment given alone. Our specific aim is to conduct a 3.5 year, randomized, double-blind, controlled trial of low-dose, continuous HRT combined with alendronate, 10 mg/d (ALN), in three groups (72 people per group) of estrogen-deprived postmenopausal women over age 60. We will give Group 1 low-dose HRT, Group 2 ALN, and Group 3 both low-dose HRT and ALN. We will give calcium and vitamin D supplements to people in all three groups.
The primary outcome measures will be spine bone mineral density (SpBMD) and total hip bone mineral density (HipBMD) measured by dual energy X-ray absorptiometry (DXA). Secondary outcome measures will be total body bone mineral content and forearm bone mineral content. In addition, we will perform studies to characterize the mechanism of the effects of these regimens. These studies will consist of measurements of urinary bone resorption markers, serum bone formation markers, calcium excretion, calcium absorption, and application of a model developed in our laboratory to estimate and compare the magnitudes of the anabolic effects (if any) of all three interventions on SpBMD and HipBMD.
We have reported data showing that both agents have an anabolic effect on bone in humans, meaning that they cause an increase in bone mass beyond that explained by a remodeling transient brought about by reduction in bone remodeling rates. Further, research has shown that HRT and ALN affect bone by different mechanisms. Thus, this combination may have an additive effect on bone resulting in bone gain beyond that previously seen with other interventions. This project will provide much-needed information to physicians and their patients on the benefits and safety of this combination regimen so that they can make "evidence-based" decisions on the choice of interventions to prevent and treat osteoporosis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000430
|United States, Nebraska|
|Creighton University Osteoporosis Research Center|
|Omaha, Nebraska, United States, 68131|
|Principal Investigator:||Robert R. Recker, MD||Creighton University Osteoporosis Research Center|
|Study Director:||Joan M. Lappe, PhD, RN||Creighton University Osteoporosis Research Center|