A Four-Year Randomized Controlled Trial of Hormone Replacement and Bisphosphonate, Alone or in Combination, in Women with Postmenopausal Osteoporosis

doi:10.1016/S0002-9343(98)00029-1

The American Journal of Medicine

Volume 104, Issue 3, March 1998, Pages 219-226

https://doi.org/10.1016/S0002-9343(98)00029-1 Get rights and content

Abstract

PURPOSE: Hormone replacement therapy (HRT) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density (BMD) in postmenopausal women. This 4-year prospective randomized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis.

PATIENTS AND METHODS: Seventy-two postmenopausal women (mean age 64.9 ± 0.5 years) attending metabolic bone disease outpatient clinics with established osteoporosis were randomly allocated into one of four treatment groups and monitored for 4 years. All patients enrolled in this study including the control group (n = 18) received 1.0 g elemental calcium and 400 units vitamin D per day. The HRT group (n = 18) received cyclical estrogen and progesterone; the etidronate group (n = 17) received intermittent cyclical etidronate; and the combined therapy group (n = 19) received both HRT and etidronate. BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment. Changes in height were recorded, and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation. In 40 patients (10 patients per group), analysis of bone histomorphometry was carried out after 4 years of treatment.

RESULTS: In patients who received the combined therapy, BMD increased in the lumbar spine by 10.4% (P <0.001) and in the hip by 7.0% (P <0.001) at 4 years. For patients treated with ICE, these increases were 7.3% (P <0.001) and 0.9% (P <0.05), and with HRT, the increases were 7.0% (P <0.001) and 4.8% (P <0.01) in the vertebrae and femora, respectively. The group treated with calcium and vitamin D lost 2.5% (P <0.05) and 4.4% (P <0.01) of BMD in the vertebrae and femora, respectively, after 4 years. Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora (P <0.05) in comparison with patients who were treated with HRT or etidronate alone after 4 years. In comparison with patients in the control group, there was a trend toward a lower rate of new vertebral fractures in the treatment groups. Height loss was significantly less in all three active treatment groups (HRT [P <0.001], etidronate [P <0.02], and combined therapy group [P <0.0001]), in comparison with the control group. The combined therapy group did not have a significant height loss, in comparison with the HRT (P <0.02) and the etidronate (P <0.001) groups. None of the patients had histomorphometric evidence of osteomalacia.

CONCLUSION: This 4-year randomized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis.

Section snippets

Patients

After screening 350 new patients, 72 postmenopausal Caucasian women (mean age 64.9 ± 0.5 years, range 58 to 72; median number of years since menopause 15) with established osteoporosis were enrolled. Inclusion criteria were evidence of osteoporosis as determined by at least 1 (but not more than 4) radiographically demonstrable atraumatic thoracic vertebral crush fractures, and spine BMD 2.0 standard deviations below the reference range established with normal healthy women aged 35 years, using

Results

No significant differences were observed in the demographic characteristics, biochemical measurements, or BMD in the four groups (Table 1). Assessment of dietary calcium intakes at 2 and 4 years showed about a 30% improvement compared with the baseline values in all 4 groups, but no statistical differences were seen between the groups at baseline, 2 years, or 4 years.

Discussion

This study demonstrates the effects of combining etidronate, a bisphosphonate, and HRT in postmenopausal women with “established osteoporosis.” In previous studies in similar patients, HRT or bisphosphonates were given alone 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24. Except for one trial conducted in early postmenopausal women, which found an additive effect of combining HRT and etidronate in preventing osteoporosis in early postmenopausal women [9], there are no

Acknowledgements

The author is grateful to Dr. Hari Dayal for statistical advice and analysis.

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Clinical StudiesA Four-Year Randomized Controlled Trial of Hormone Replacement and Bisphosphonate, Alone or in Combination, in Women with Postmenopausal Osteoporosis

Abstract

Section snippets

Patients

Results

Discussion

Acknowledgements

Lancet

Am J Med

Bone

Bone Min

Am J Med

Lancet

Metab Bone Dis

Lancet

Endocrin Metab Clin North Am

Metabolism

Hip fracture and the use of estrogens in postmenopausal women

NEJM

The risk of hip fracture in postmenopausal females with and without estrogen drug exposure

Am J Public Health

An epidemiologic study of hip fracture in postmenopausal women

Am J Epidemiol

Non-linear bone loss in oophorectomised women

Br J Radiol

Prospective trial of oestrogen and calcium in postmenopausal women

BMJ

Calcitonin for prevention of postmenopausal bone loss

Lancet

Bisphosphonates in Bone DiseaseFrom Laboratory to the Patient

The treatment of osteoporosis with disodium ethane-1-hydroxy-1,1-diphosphonate

J Lab Clin Med

Etidronate disodium in postmenopausal osteoporosis

Clin Pharmacol Ther

Preliminary observations of a form of coherence therapy for osteoporosis

Calcif Tissue Int

Cyclic therapy of osteoporosis with neutral phosphate and brief, high-dose pulses of etidronate

J Bone Miner Res

Coherence therapy does not prevent axial bone loss in osteoporotic womena preliminary comparative study

J Clin Endocrinol Metab

Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis

NEJM

Intermittent cyclical etidronate treatment of postmenopausal osteoporosis

NEJM

Clinical Studies
A Four-Year Randomized Controlled Trial of Hormone Replacement and Bisphosphonate, Alone or in Combination, in Women with Postmenopausal Osteoporosis