Pregnancy-Associated Osteoporosis
Pregnancy-associated osteoporosis was
first reported more than forty years ago. At
that time researchers had identified four
post-pregnancy patients with varying degrees of
spinal osteoporosis. In 1955, researchers
reported five women who experienced vertebral
fractures following delivery. While other cases
of pregnancy-associated osteoporosis have since
been identified, studies surrounding pregnancy
and bone have offered conflicting results,
including no changes in bone density, and even
increases at specific sites. It appears that if
pregnancy-associated osteoporosis does exist, it
is probably quite rare. (By 1996, eighty cases
had been reported in the literature.) It is also
a condition that is difficult to adequately
investigate, given the inability to perform
maternal radiologic exams.
Pregnancy-associated osteoporosis tends to be
identified in the postpartum period (56%) or the
third trimester (41%). Affected women usually
present with back pain, loss of height, and
vertebral fractures. Hip pain and fracture of
the femur are less common but have been
reported. The condition usually appears during
the first pregnancy, tends to be temporary and
usually does not recur. It is not entirely clear
whether this disorder is a consequence of
pregnancy or whether it occurs because of
pre-existing conditions in the pregnant woman.
Studies have shown that only a minority of these
patients have risk factors, such as heparin or
glucocorticoid exposure. On the other hand, it
is possible that genetic factors play a role in
the development of pregnancy-associated
osteoporosis. In a study by Dunne and
associates, mothers of patients with the
condition had significantly more fractures than
controls.
Theoretically, pregnancy-associated
osteoporosis is believed to occur because of the
stress on maternal calcium stores and an
increase in urinary calcium excretion. Yet, the
intestinal absorption of calcium is increased
during pregnancy--especially in the second and
third trimesters. The body also responds to
fetal calcium demands by increasing total
1,25-dihydroxyvitamin D levels. These two
mechanisms help to satisfy the increased demand
for calcium during pregnancy. Other physiologic
changes during pregnancy that may actually be
protective of bone include the third trimester
estrogen surge and increased bone-loading due to
weight gain. Clearly, there is much to be
learned about bone remodeling during pregnancy
and why some women become prone to bone loss and
even fracture.
Lactation and Bone Loss
Studies have shown that the majority of women
with pregnancy-associated osteoporosis are
breastfeeding at the time of diagnosis. Duration
of lactation has ranged from one week to seven
months. Bone loss tends to be greatest in
skeletal sites with the highest concentration of
trabecular bone. Reductions in bone density by
three to five percent at the lumbar spine are
common.
Two physiologic occurrences may be
responsible for bone loss during lactation.
First, there is an increased calcium demand from
maternal bone. This demand varies from woman to
woman based on the amount of breast milk
produced and upon the duration of lactation.
Secondly, because of elevated prolactin levels,
women who breastfeed tend to be in a
hypoestrogenic state.
Though significant amounts of bone mineral
can be lost during breastfeeding, the loss of
bone tends to be transient. Studies have
consistently shown significant trends in bone
loss during lactation, with full recovery of
bone density by six months after weaning.
Kalkwarf and Specker reported women who
experience an earlier resumption of menses lose
less bone during lactation and recover more bone
after weaning. Other studies have identified
similar trends in bone loss, with full recovery
of bone density by six months following the
cessation of breastfeeding.
Parity and Osteoporosis Risk
Much of the research reports an increase in
bone density with increasing parity (the number
of pregnancies a woman delivers past 28 weeks
gestation.) The positive effect on bone density
has been seen in both pre and postmenopausal
women. Parity appears to have a protective
effect against fracture, as well. In an arm of
the Leisure World study, Paganini-Hill and
others concluded that women with three or more
children had a 30-40 percent reduction in hip
fracture risk when compared to nulliparous women
(those who have never given birth). The validity
of studies that use nulliparous women as
controls has been criticized, however. Many have
suggested that nulliparous women may not be
appropriate studies of parity since they have
not demonstrated the ability to conceive and to
support fetal growth and development. Such women
may have a hormonal environment that impedes
conception and negatively impacts bone density.
In
1979, the
United States
Food and Drug Administration
(FDA) introduced a
classification of fetal risks
due to
pharmaceuticals. This was
based on a similar system that
was introduced in Sweden just
one year earlier. The
United States FDA has the
following definitions for the
pregnancy categories:
|
United States FDA
Pharmaceutical Pregnancy
Categories |
|
Pregnancy Category A |
Adequate and
well-controlled studies
have failed to
demonstrate a risk to
the fetus in the first
trimester of pregnancy
(and there is no
evidence of risk in
later trimesters). |
|
Pregnancy Category B |
Animal reproduction
studies have failed to
demonstrate a risk to
the fetus and there are
no adequate and
well-controlled studies
in pregnant women OR
Animal studies which
have shown an adverse
effect, but adequate and
well-controlled studies
in pregnant women have
failed to demonstrate a
risk to the fetus in any
trimester. |
|
Pregnancy Category C |
Animal reproduction
studies have shown an
adverse effect on the
fetus and there are no
adequate and
well-controlled studies
in humans, but potential
benefits may warrant use
of the drug in pregnant
women despite potential
risks. |
|
Pregnancy Category D |
There is positive
evidence of human fetal
risk based on adverse
reaction data from
investigational or
marketing experience or
studies in humans, but
potential benefits may
warrant use of the drug
in pregnant women
despite potential risks. |
|
Pregnancy Category X |
Studies in animals or
humans have demonstrated
fetal abnormalities
and/or there is positive
evidence of human fetal
risk based on adverse
reaction data from
investigational or
marketing experience,
and the risks involved
in use of the drug in
pregnant women clearly
outweigh potential
benefits. |
One characteristic of the FDA
definitions of the pregnancy
categories is that the FDA
requires a relatively large
amount of high-quality data on a
pharmaceutical for it to be
defined as Pregnancy Category A.
As a result of this, many drugs
that would be considered
Pregnancy Category A in other
countries are allocated to
Category C by the FDA.
|
medication |
Category |
|
Actonel |
Category C |
|
Fosamax |
Category C |
|
Boniva |
Category C |
|
Forteo |
Category C |
|
Didronel |
Category C |
|
Evista |
Category X |
|
Miacalcin |
Category C |
|
Zometa |
Category D |
|
Aredia (Pamidronate |
Category D |
|
Reclast |
Category D |
|
