Alendronate Increases Spine and Hip Bone Mineral Density
in Women With Postmenopausal Osteoporosis Who Failed to
Respond to Intermittent Cyclical Etidronate
N. B. WATTS and P. BECKER
Emory University School of Medicine, Atlanta, GA, USA
In a U.S. multicenter study of intermittent cyclical etidronate
treatment for postmenopausal osteoporosis, approximately
20% of patients were nonresponders, defined as failure to
increase spine bone mineral density. In contrast, essentially
all patients who received 10 mg of alendronate daily in U.S.
phase III trials showed some increase in spine bone mineral
density. The current study was undertaken to determine the
response to alendronate therapy in women with postmeno-
pausal osteoporosis who were nonresponders to intermittent
cyclical etidronate therapy. Twenty-five women with post-
menopausal osteoporosis (mean ؎ SD: 65.1 ؎ 1.9 years of
age), previously treated with intermittent cyclical etidronate
with no increase of spine bone mineral density, and who
agreed to be changed to alendronate, were recruited from a
university out-patient clinic specializing in the treatment of
osteoporosis for a prospective observational study. Measure-
ments included bone mineral density of the lumbar spine and
proximal femur (by dual-energy X-ray absorptiometry) and
biochemical markers of bone remodeling (serum bone-spe-
cific alkaline phosphatase by immunoassay and urine deoxy-
pyridinoline by high-pressure liquid chromatography). Pa-
tients had received intermittent cyclical etidronate for 3.3 ؎
0.4 years, during which time their bone density declined at
spine and hip sites. They were then changed to alendronate
10 mg/day, which they received for 1.3 ؎ 0.1 years; after
treatment with alendronate, bone mineral density increased
significantly at the lumbar spine (4.4 ؎ 0.7% annualized, p <
0.0001) and at all hip sites. Bone markers also changed
significantly after alendronate treatment: urine deoxypyr-
idinoline fell from 6.8 ؎ 0.8 to 5.5 ؎ 0.6 mol/mol creatinine
(p < 0.0001) and serum bone-specific alkaline phosphatase
rose from 4.6 ؎ 0.5 to 11.9 ؎ 1.0 ng/mL (p < 0.0001). Upper
gastrointestinal side effects forced 4 of 25 patients (16%) to
discontinue alendronate. Alendronate increases bone density
at the spine and hip in patients who have not responded to
intermittent cyclical etidronate therapy. Changes in bone
markers suggest that alendronate causes more complete sup-
pression of bone resorption and less inhibition (or stimula-
tion) of bone formation. (Bone 24:65–68; 1999) © 1999 by
Elsevier Science Inc. All rights reserved.
Key Words: Etidronate; Alendronate; Bisphosphonate; Bone
mineral density; Responder; Therapy.
Introduction
Current therapies offer great promise for most patients with
postmenopausal osteoporosis. However, not all patients respond.
Approximately 10%–15% of women who are treated with estro-
gen continue to lose bone.
5,7
In a study of injectable calcitonin,
only patients who had high-turnover osteoporosis showed an
increase in spine bone mineral density, and only 32% of the
patients were in the high-turnover group.
1
In a U.S. multicenter
study of intermittent cyclical etidronate (ICE), approximately
20% of treated patients failed to show an increase in spine bone
mineral density.
3,10
Alendronate sodium, a second-generation bisphosphonate,
became available in September 1995. Essentially all patients who
received 10 mg of alendronate daily in the U.S. phase III trials
showed some increase in spine bone mineral density.
8
To our knowledge, no studies have examined the effect of
alternate therapy in “nonresponders.” We sought to determine the
effect of treatment with alendronate in women with postmeno-
pausal osteoporosis who had failed to respond to intermittent
cyclical etidronate, as defined by no increase of spine bone
mineral density after intermittent cyclical etidronate therapy.
Materials and Methods
Subjects
Patients were recruited from a university out-patient clinic spe-
cializing in the treatment of osteoporosis. Women with post-
menopausal osteoporosis, defined as having bone mineral density
Ͼ2.5 SD below mean peak bone mass at the spine, hip, or both,
were eligible for entry if: (1) they had been treated with inter-
mittent cyclical etidronate for Ն1 year; (2) spine bone mineral
density had not increased (or it had decreased); and (3) they were
willing to change to alendronate therapy. Patients with secondary
forms of osteoporosis or active upper gastrointestinal problems
were excluded.
The intermittent cyclical etidronate regimen consisted of 400
mg/day of etidronate for 14 days, repeated every third month.
Alendronate was given as one 10 mg tablet daily. Patients were
instructed to take their medication (either etidronate or alendro-
Address for correspondence and reprints: Nelson B. Watts, M.D., The
Emory Clinic, Inc., 1365 Clifton Road NE, Atlanta, GA 30322. E-mail:
nwatts@emory.edu
Presented in part at the 17th annual meeting of the American Society
for Bone and Mineral Research, Cincinnati, OH, September 10, 1997.
Bone Vol. 24, No. 1
January 1999:65–68
65
© 1999 by Elsevier Science Inc. 8756-3282/99/$19.00
All rights reserved. PII S8756-3282(98)00144-6