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Am Fam Physician. 1998;58(4):955

Hormone replacement therapy is currently accepted as treatment for postmenopausal osteoporosis, with a 50 percent reduction in fractures, especially of the hip, related to this condition. Bisphosphonates are also known to increase bone mass. Wimalawansa conducted this randomized controlled trial to determine if there was a synergistic effect on bone mineral density when hormone replacement therapy and etidronate, a bisphosphonate, were used together in women with established postmenopausal osteoporosis.

Patients were excluded from the study if they had surgically-induced menopause or secondary osteoporosis, or if they had previously used medications that affect calcium metabolism. All 72 patients were encouraged to engage in mild exercise and to make lifestyle modifications as needed. All patients received 1 g of elemental calcium and 400 units of vitamin D daily. Three treatment groups and a control group were included in the study. The hormone replacement therapy group received 0.625 mg of premarin and 150 mg of norgestrel daily for 12 days each month; the etidronate group received 400 mg of etidronate daily for 14 days every 12 weeks; and the combined therapy group received hormone replacement therapy and etidronate in the above dosages.

To determine bone mineral density, patients had radiograph absorptiometric measurements of the spine and hip at baseline and at two and four years after beginning treatment. Lateral radiographs of the spine were also taken at baseline and at four years, to determine the occurrence of new vertebral fractures. Patients in the control group lost 0.9 percent of spinal bone mineral density at two years and 2.5 percent at four years. Patients in the hormone replacement therapy group and the etidronate group experienced no significant increases in spinal bone mineral density. In contrast, the combined therapy group showed a significant increase in spinal bone mineral density at year two and year four. Similarly, the patients in the combined treatment group had significant increases in hip bone mineral density at four years over the control and treatment groups. The combined treatment group also had a much lower fracture rate (17 per 1,000 patient years) when compared with the control group (89 per 1,000 patient years).

The author concludes that the combination of hormone replacement therapy plus etidronate can increase spinal and hip bone mineral density and prevent vertebral fractures in postmenopausal women with known osteoporosis. A long-term study is necessary to assess the impact on fracture rates.

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Copyright © 1998 by the American Academy of Family Physicians.

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