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Overview Page 2
Study shows that much
of the BMD gained from
osteoporosis therapy is lost
after discontinuation
There have been conflicting reports on the
effects of discontinuing osteoporosis therapy
on bone mass. Both normal and accelerated
rates of bone loss have been observed.1-6 A
recent randomized controlled trial of 489
women aged 65-77 showed that discontinuation
of hormone replacement therapy
and/or calcitriol results in a loss of much
of the bone mineral density (BMD) gained
on treatment.7 Most of this loss occurred
in the first year after discontinuation. Results
of this trial were published in The Journal
of Clinical Endocrinology & Metabolism.
In the treatment phase of the trial, women
were randomized to one of four groups:
(1) ERT/HRT [conjugated equine estrogens
(0.625 mg/day); medroxyprogesterone
(2.5 mg/day) was added if the woman had
a uterus], (2) calcitriol (0.25 µg bid, (3) the
combination of both, or (4) placebo. After
three years, treatment was discontinued and
the women were asked to volunteer for two
years of follow-up. Of the original group
of 489, there were 233 who completed a
fourth year of no treatment and 178 who
completed a fifth year of no treatment. The
BMD of the spine, proximal femur, and total
body was measured at six-month intervals
during the treatment phase and at 12-month
intervals during the follow-up phase.
Discontinuation of ERT/HRT and the combination
of ERT/HRT plus calcitriol resulted
in rapid bone loss at all measured skeletal
sites. Most of the bone loss occurred during
the first year, with very little additional loss
during the second year (Table1). Spine BMD
in the estrogen-treated groups remained
higher than baseline, but this was statistically
significant only on the combination
treatment. Total body BMD remained significantly
higher than placebo in all treatment
groups (Figure 1). At year five, the mean
BMD was 1.2-3.5% higher in the hormonetreated
groups and 0.3-1.4% higher in the
calcitriol-treated group compared with that
in the placebo group.
The effect of estrogen
withdrawal on bone markers resulted in
a return to baseline of both urine N-telopeptides
and serum osteocalcin, confirming
correlation with the increase in bone
resorption. Calcitriol withdrawal also led
to an increase in urinary N-telopeptides.
In addition, the serum PTH (suppressed
by calcitriol therapy) returned to baseline
and calcium absorption (increased by the
therapy) returned to baseline.
The authors conclude that withdrawal of
ERT/HRT and/or calcitriol treatment in late
postmenopausal women results in increased
bone resorption and accelerated bone loss.
However, two years after discontinuation, a
small residual beneficial effect on bone mass
remained; this effect was greater in the combination
treatment group. The results of
this trial are of particular interest in the
context of the WHI trial, the results of
which have led to the cessation of ERT/HRT
in millions of American women.
REFERENCES
-
Lindsay R, Hart DM, MacLean A, et al. Bone
response to termination of estrogen treatment.
Lancet. 1978;1:1325-1327.
-
Horsman A, Nordin BE, Crilly RG. Effect on bone of
withdrawal of estrogen therapy. Lancet. 1979;2:33.
-
Fogelman I, Bessent RG, Cohen HN, et al. Skeletal
uptake of diphosphonate. Method for prediction
of postmenopausal osteoporosis. Lancet. 1980;
2:667-670.
-
Tremollieres FA, Pouilles JM, Ribot C. Withdrawal
of hormone replacement therapy is associated
with significant vertebral bone loss in postmenopausal
women. Osteop Int. 2001;12:385-390.
-
Christiansen C, Christensen MS, Transbol I. Bone
mass in postmenopausal women after withdrawal
of estrogen/gestagen replacement therapy.
Lancet. 1981;1:459-461.
-
Greendale GA, Espeland M, Slone S, et al. Bone
mass response to discontinuation of long-term
hormone replacement therapy. Arch Intern Med.
2002;162:665-672.
-
Gallagher JC, Prema BR, Haynatzki G, et al. Effect
of discontinuation of estrogen, calcitriol, and the
combination of both on bone density and bone
markers. J Clin Endocrinol Metab. 2002;
87:4914-4923.
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