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Alveolar and Postcranial Bone Density in Postmenopausal Women Receiving Hormone/Estrogen Replacement Therapy
A Randomized, Double-blind, Placebo-Controlled Trial
Roberto Civitelli, MD;
Thomas K. Pilgram, PhD;
Mary Dotson, RDH, MPH;
Jane Muckerman, RN, BSN;
Nancy Lewandowski, RN;
Reina Armamento-Villareal, MD;
Naoko Yokoyama-Crothers, BA;
E. Eugenia Kardaris, DDS;
Jay Hauser, DDS;
Sheldon Cohen, DDS;
Charles F. Hildebolt, DDS, PhD
Arch Intern Med. 2002;162:1409-1415.
ABSTRACT
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Background We conducted a 3-year, double-blind, randomized, placebo-controlled
study to determine whether the positive effects of hormone/estrogen replacement
therapy (H/ERT) on postcranial bone density are accompanied by similar positive
effects on oral bone mass.
Methods A total of 135 postmenopausal women (aged 41-70 years) with no evidence
of moderate or severe periodontal disease were randomized to receive daily
oral conjugated estrogen (Premarin; 0.625 mg) alone or in combination with
medroxyprogesterone acetate (Prempro; 0.625 and 2.5 mg, respectively) or placebo.
All subjects received calcium carbonate (1000 mg/d) and cholecalciferol (800
IU/d) supplements. The primary efficacy end points were the changes in alveolar
crest height and alveolar bone density. Alveolar crest height was measured
on bite-wing radiographs, and changes in alveolar bone mass were assessed
by means of digital-subtraction radiography. Postcranial bone density was
measured in the lumbar spine and left proximal femur by means of dual-energy
x-ray absorptiometry.
Results Hormone/estrogen replacement therapy significantly increased alveolar
bone mass compared with placebo (+1.84% vs +0.95% [P = .04]),
and tended to improve alveolar crest height (+4.83% vs +3.46% [P = .34]). Bone mineral density of the proximal femur significantly
increased in the H/ERT compared with the placebo group (total proximal femur,
+3.59% vs +0.22% [P = .001]; neck, +2.05% vs -0.34%
[P = .02]; trochanter, +3.49% vs +0.08% [P<.001]), but not the lumbar spine (+1.01% vs +0.17% [P = .39]). Changes in alveolar bone mass correlated with bone density
changes in the total femur (r = 0.28 [P = .02]) and femoral trochanter (r = 0.25
[P = .04]) in the H/ERT but not in the placebo group.
Conclusions Postcranial and oral bone mass were increased in postmenopausal women
receiving H/ERT. Improvement in oral bone health constitutes an additional
benefit of H/ERT.
INTRODUCTION
OSTEOPOROSIS IS regarded as a risk factor for tooth loss and edentulism
in the elderly. Accordingly, it is commonly believed that estrogen deficiency,
use of corticosteroids, and other conditions leading to bone demineralization
also cause oral bone loss.1 Although cross-sectional
studies designed to examine the relationship between oral bone loss and osteoporosis
have not been universally concordant,2-6
a recent longitudinal survey demonstrated a higher degree of loss of alveolar
crest height and alveolar bone density after 2 years in osteoporotic and osteopenic
postmenopausal women relative to women with normal bone mineral density (BMD)
of the spine.7 The notion that postcranial
skeletal loss is accompanied by deterioration of oral bone health is supported
by the evidence that subjects with osteoporosis were more likely to use dentures
than were those without osteoporosis,8 and
by the demonstration of an increasing likelihood of losing teeth with decreasing
BMD at the spine and the radius in partially edentulous women.9
The same investigators later reported that women who lost teeth during a 7-year
follow-up experienced less favorable changes in BMD at the spine, femoral
neck, and total body.10 Thus, abundant epidemiological
evidence supports the hypothesis that systemic bone loss leads to tooth loss
in postmenopausal women, presumably as a consequence of oral bone loss.
One of the major risk factors for osteoporosis is estrogen deficiency.
Observational studies indicate that estrogen deficiency is also associated
with a greater loss of the dental attachment apparatus (cementum, periodontal
ligament, and alveolar bone) than in conditions of estrogen sufficiency.7, 11 Three large observational studies12-14 in different cohorts
of postmenopausal women confirmed the potential beneficial effect of estrogen
on dental health. The number of teeth was higher and the odds of being edentulous
or using dentures were reduced in estrogen users compared with nonusers.12-14 Although the evidence
of the beneficial effect of estrogen on BMD at postcranial skeletal sites
has been well established by longitudinal trials,15
such evidence does not exist at present for alveolar bone. One noncontrolled
study of estrogen-treated women suggested a positive influence of the hormonal
treatment on jaw bone mass,16 giving further
support to the hypothesis that estrogen replacement therapy (ERT) may protect
from oral bone loss in postmenopausal women.
The objective of the present study was to determine whether the positive
effects on the postcranial skeleton that can be obtained with ERT are associated
with similar positive effects on oral bone health. By extension, protection
from alveolar bone loss or increases in oral bone mass may result in reduced
tooth loss.
SUBJECTS AND METHODS
SUBJECTS
From March 1, 1994, through April 30, 1995, 155 postmenopausal women
were recruited from patients attending the Dental Clinic of Barnes-Jewish
Hospital, St Louis, Mo. To be included in the study, a subject had to be postmenopausal
for at least 1 year, in good medical health, and ambulatory; have at least
10 teeth and no moderate or advanced periodontal disease (defined as periodontal
pockets of more than 5 mm); and have no contraindications for ERT. Excluded
were women who had more than 3 documented vertebral fractures or any previous
treatment with bisphosphonates, corticosteroids, or antiepileptics within
3 months before entry into the study; had been treated with estrogen or calcitonin
within 2 years before entering the study; had any major medical condition
that would interfere with compliance to the protocol; and had conditions associated
with abnormalities of bone metabolism such as chronic liver disease, chronic
renal failure, hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism,
multiple myeloma, or osteomalacia.
DEMOGRAPHIC DATA
A body mass index (BMI) was calculated by dividing the weight in kilograms
by the square of the height in meters. The number of teeth was recorded at
baseline and yearly until the end of the study. Cigarette smoking was estimated
by multiplying the number of packs smoked per day by the number of years of
active smoking (pack-years). Data were collected on the following factors
that affect estrogen exposure: age at menarche, history of menstrual irregularities,
use of birth control pills, number of pregnancies, number of pregnancies to
term, and months of lactation.
STUDY DESIGN
This study was a double-blind, placebo-controlled, randomized 3-year
trial followed by a 2-year, open-label extension (Figure 1). We report herein the results of the 3-year controlled
phase of the study. The study consisted of the following 2 treatment arms:
the hormone replacement therapy/ERT (H/ERT) arm and the placebo arm. Women
with an intact uterus (n = 86) were randomized to receive a combination tablet
consisting of 0.625 mg of conjugated equine estrogen and 2.5 mg of medroxyprogesterone
acetate (Prempro) once a day, or a placebo look-alike tablet. Women without
a uterus (n = 49) were randomized to receive either 0.625 mg of conjugated
equine estrogen (Premarin) once a day or a placebo look-alike tablet. All
women enrolled received daily supplements of 1000 mg of elemental calcium
as calcium carbonate and 800 IU of cholecalciferol. All women also received
dental care and cleanings every 12 months. Dental services outside of the
study were permitted as desired by the patient. This study protocol was approved
by the Human Studies Committee of Washington University Medical Center, St
Louis, and all subjects gave an informed written consent to participate in
the study.
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Figure 1. Patient recruitment and follow-up.
H/ERT indicates hormone/estrogen replacement therapy; BMD, bone mineral density.
Treatment arms are described in detail in the "Study Design" subsection of
the "Subjects and Methods" section.
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ASSESSMENT OF POSTCRANIAL BMD
Bone mineral density of the lumbar spine and proximal left femur was
measured by means of dual-energy x-ray absorptiometry, with a bone densitometer
(Hologic QDR-2000; Hologic Inc, Waltham, Mass). At our center, the precision
of this technique is 1.12% at the lumbar spine and 1.27% at the total proximal
femur.17 Bone mineral density was expressed
as grams per square centimeters. Bone mineral density measurements were performed
at baseline and every 12 months thereafter for 3 years.
ASSESSMENT OF ALVEOLAR BONE
Depending on the number of remaining teeth, up to 7 vertical bite-wing
radiographs per patient were obtained, using customized film-positioning,
beam-alignment devices with occlusal registration material. Dental radiographs
were obtained at baseline and repeated every 12 months. A single bite-wing
radiograph (chosen by lot) was obtained a second time in 111 patients at baseline
to determine measurement reliability. To obtain quantitative measurements
of the alveolar bone, bite-wing radiographs were digitized at 50 µm
spatial resolution and 12-bit gray scale resolution. We made 2 types of measurements.
First, we calculated a linear measurement of the alveolar crest height as
the distance from the cementoenamel junction to the alveolar crest (CEJ-AC);
second, we performed a radiodensity measurement (we herein use the terms alveolar bone radiodensity and alveolar
bone mass interchangeably). In brief, after the digitized radiographic
images were enhanced, CEJ-AC measurements were made by one of us (N.Y.-C.)
at the mesial, distal, and midtooth areas (at the points of maximum bone loss)
of each tooth for up to 28 teeth per patient (the third molars were not measured).
We used method error (ME; SD of the differences between baseline and repeated
baseline radiographic measurements divided by the square root of 2)18 to determine CEJ-AC measurement reliability, which
was 0.22 mm. Additional details on CEJ-AC measurements and their reliabilities
are given elsewhere.19-20 Since
the CEJ-AC is an inverse measurement of crest height, a decrease over time
in the CEJ-AC distance indicates an increase in alveolar crest height (ie,
a gain in alveolar bone). However, for consistency with all the other measurements,
changes indicating a gain in alveolar bone height are indicated as positive.
For alveolar bone radiodensity measurements, baseline and follow-up digitized
radiographs of alveolar bone were registered using ANALYZE software (Mayo
Foundation, Rochester, Minn), cropped automatically to ensure image homology,
and histogram matched to correct for exposure and processing errors. Radiodensities
were determined for regions of interest corresponding to the alveolar bone
between the roots of the posterior teeth. The coefficient of variation of
the ME18
(CVME= [2ME/(1 + 2)] x 100) was used to determine the reliability of this method, which was
2.29%. As for alveolar crest height, an increase in alveolar bone mass is
expressed as a positive change. A mean CEJ-AC distance and a mean alveolar
bone radiodensity were calculated for each patient for data analysis.
ASSESSMENT OF ADVERSE EVENTS
Since the active medications included estrogen, mammograms were obtained
at baseline and repeated at years 2 and 4. Subjects complaining of breakthrough
or abundant vaginal bleeding were referred to a gynecologist for further evaluation
and for endometrial biopsy, if necessary. Subjects were questioned at each
visit about adverse events. Telephone calls from patients reporting adverse
events were also recorded. Adverse events were counted and classified as serious
or minor, regardless of whether they were believed to be related to the active
medications. Those events that resulted in death, hospitalization, cancer,
or permanent disability or that were considered life-threatening were categorized
as serious adverse events. Excessive loss of BMD was also considered a serious
adverse event and was defined as a 5% loss at 1 year or a 10% loss at 2 years
at any postcranial site. In such cases, the participant was offered the choice
to discontinue the study. All categories and frequencies of adverse events
are reported herein.
ASSESSMENT OF COMPLIANCE
Compliance with the regimen of study medications was assessed by a pharmacist
every 6 months by counting the remaining tablets in the bottles returned by
patients at each scheduled refill. Adherence to treatment was similar in both
treatment groups; 59 (88%) of 67 women receiving placebo and 53 (78%) of 68
women receiving estrogen took more than 80% of study medication.
STATISTICAL ANALYSIS
The study was powered to detect a 0.25-mm change in alveolar crest height,
a clinically significant change, with  and  (type I and II error
rates) set at .05 and .20, respectively. On the basis of a previous pilot
study,21 we determined that 40 patients per
treatment arm would be required to unambiguously detect such a change. Expecting
approximately a 40% dropout rate, we targeted enrollment to 67 subjects per
treatment arm. Data were analyzed on an intention-to-treat basis. All missing
data from subjects who had at least the baseline measurements were replaced
with the last value obtained (last value carried forward). Of the 135 subjects
entered into the study (68 in the estrogen arm and 67 in the placebo arm),
37 (11 in the H/ERT arm and 26 in the placebo arm) dropped out after the first
(baseline) visit; 4 (3 in the estrogen arm and 1 in the placebo arm), after
the second visit; 8 (5 in the estrogen arm and 3 in the placebo arm), after
the third visit; and 86 subjects (49 in the estrogen arm and 37 in the placebo
arm) completed the entire study (Figure 1).
Measured values were analyzed as raw data and with the final value expressed
as a percentage of the baseline value; only the latter results are presented
herein. Alveolar radiodensity values are expressed and analyzed only as percentages
of baseline values. Data collected at a nominal or ordinal scale of measurement
were analyzed with contingency tables. When 80% or more of the table's cells
had expected values of greater than 5,  2 tests were used;
in all other cases, 2-tailed Fisher exact tests were used. Data collected
at an interval scale of measurement were analyzed by t
tests when simple changes were examined, or by multivariate analysis of variance
when repeated measures were included. The P values
reported for the multivariate analysis of variance are for the interaction
between time and drug arm. The role of demographic and historical variables
was examined by including them as an additional variable in the model.
We analyzed the association between changes in bone measurements in
different locations by calculating the Pearson correlation coefficient of
the changes of each variable from baseline to the end of the study. We analyzed
the data using JMP software (SAS Institute Inc, Cary, NC).
RESULTS
One hundred thirty-five women aged 41 to 70 years underwent randomization
and follow-up in the study. Almost all were white (n = 127 [94.1%]), reflecting
the ethnic group distribution of patients referred to the Barnes-Jewish Hospital
Dental Clinic. Women in the H/ERT arm were approximately 2 years older than
the women in the placebo arm, but the number of years since menopause was
not different between the 2 groups (Table
1). Both arms of the study were well matched for BMI, smoking history,
total number of pregnancies, number of pregnancies to term, alveolar crest
height, and number of teeth at baseline. Bone mineral density was not a criterion
for entry into the study. Average densities of the lumbar spine and all regions
of interest on the proximal femur were similar in both arms of the study and
in the osteopenia range.
ALVEOLAR BONE
The overall pattern was for alveolar bone mass to increase at a statistically
significant level in both arms of the study, and for the increase in bone
mass to be greater in the H/ERT group than in the placebo group. The difference
between groups was statistically significant for alveolar bone mass, but not
for the crest height (Figure 2).
There was a 4.83% increase in alveolar crest height in the H/ERT group (P = .001) and a 3.46% increase in the placebo group (P = .001). The 1.37% greater increase in the H/ERT group
compared with the control group was not statistically significant (P = .34). There was a 1.84% increase in alveolar bone mass in the H/ERT
group (P<.001), and a 0.95% increase in the placebo
group (P<.001). The 0.90% greater increase in
the H/ERT group was statistically significant (P
= .04).
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Figure 2. Changes in oral bone variables
in women treated with hormone/estrogen replacement therapy (H/ERT) or placebo.
Data represent mean ± SE obtained from 67 women in the placebo arm
and 68 in the H/ERT arm and reflect an intention-to-treat analysis. P values represent the significance level of treatment effect estimated
by multivariate analysis of variance. Treatment arms are described in detail
in the "Study Design" subsection of the "Subjects and Methods" section.
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POSTCRANIAL BMD
The overall pattern in postcranial bone was for the H/ERT group to gain
BMD and for the placebo group to maintain BMD (Figure 3). The amount of BMD gain for the H/ERT group and the difference
in BMD change between the H/ERT and placebo groups were statistically significant
for the femur, but not for the spine. Women in the H/ERT group experienced
a 2.05% increase in BMD in the femoral neck (P =
.003), compared with a 0.34% decrease in density for the women in the placebo
group (P = .74), for a difference of 2.39% between
the groups (P = .02). In the total femur, the gain
in the H/ERT group was 3.59% (P<.001) compared
with 0.22% (P = .71), for a difference of 3.37% (P = .001). In the trochanter, the gain in the H/ERT group
was 3.49% (P<.001) compared with 0.08% (P = .86), for a difference of 3.42% (P<.001). In the lumbar spine, the changes at the end of 3 years
were a gain of 1.01% for women in the H/ERT group (P
= .11) and a gain of 0.17% in the placebo group (P
= .82), with a difference of 0.84% between the groups (P = .39).
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Figure 3. Changes in postcranial bone density
in women treated with hormone/estrogen replacement therapy (H/ERT) or placebo.
Data represent mean ± SE obtained from 67 women in the placebo arm
and 68 in the H/ERT arm and reflect an intention-to-treat analysis. P values represent the significance level of treatment effect estimated
by multivariate analysis of variance. Treatment arms are described in detail
in the "Study Design" subsection of the "Subjects and Methods" section.
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Although none of the demographic or historical variables differed at
a statistically significant level between the arms of the study, those showing
a trend for a difference were examined for influence on the study outcome.
None of them altered the findings of the study.
CORRELATIONS BETWEEN ORAL AND POSTCRANIAL BMD CHANGES
We found positive correlations between changes in the alveolar crest
height and the BMD of the lumbar spine and femoral neck among H/ERT-treated
patients, indicating that an increase in postcranial BMD is accompanied by
an increase in alveolar crest height (Table
2). By contrast, no significant correlations were found between
any measures of postcranial BMD and alveolar crest height in the placebo-treated
women. Likewise, BMD changes at most femoral regions were positively correlated
with changes in alveolar BMD in women receiving H/ERT, whereas no similar
correlations were observed among the placebo-treated women (Table 2).
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Table 2. Correlations Between Changes on Alveolar and Postcranial Bone
Density*
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NUMBER OF TEETH
At the end of the 3-year study, there was no difference in the mean
number of remaining teeth between the H/ERT (24.24 ± 3.69) and placebo
(24.47 ± 3.47) groups, and there was no difference in the average number
of teeth lost per patient between the H/ERT (0.47 ± 0.92) and placebo
(0.35 ± 0.54) groups. Furthermore, no significant correlation was seen
in the number of teeth lost and oral bone measures during the 3-year study
in both groups.
ADVERSE EVENTS AND PATIENT RETENTION
Adverse events developed in 39 women in the placebo and 57 women in
the H/ERT groups (Table 3). Only
4 (6%) of 68 women in the H/ERT group and 3 (4%) of 67 in the placebo group
experienced adverse events that can be categorized as serious. The frequency
of serious adverse events in the H/ERT group was lower than that reported
during the larger Postmenopausal Estrogen/Progestin Interventions trial, where
the incidence of life-threatening events was 12.7% in the estrogen-treated
group and 4.6% in the placebo group.15
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Table 3. Adverse Events During Trial*
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Forty-nine (36.3%) of the 135 women left the study prematurely, 30 (45%)
of 67 from the placebo group and 19 (28%) of 68 from the H/ERT group. Of these
49 subjects, 23 (47%) withdrew because of an adverse event, 13 (19%) of 67
from the placebo group and 10 (15%) of 68 from the H/ERT group. Of the subjects
who reported serious adverse events, a total of 4 withdrew from the study,
2 in each group (Table 4). These
included 2 women in the H/ERT group (one with a new diagnosis of breast cancer
and another with a new diagnosis of endometrial cancer) and 2 women in the
placebo group (one with a fractured ankle and another who experienced an excessive
decrease in bone density). The other 3 subjects with serious adverse events
(1 in the placebo group with colon cancer, 1 in the H/ERT group with a transient
ischemic attack requiring hospitalization, and 1 in the H/ERT group with excessive
bone density loss) elected to continue in the study. The higher withdrawal
rate in the placebo group relative to the H/ERT group was unexpected. We believe
this finding may relate to some patients having entered the study in hopes
of receiving H/ERT. Some of the women assigned to placebo may have suspected
they were not taking the active medication, and they requested active treatment
from their physician, thus violating the protocol or they simply lost interest
or failed to return for follow-up.
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Table 4. Reasons for Discontinuation*
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COMMENT
The preventive effect of H/ERT on postmenopausal bone loss and osteoporosis
is established.15 Observational studies have
demonstrated that estrogen treatment also prevents bone loss in the mandibular/alveolar
bone.11, 16 A direct effect of
estrogen on oral bone loss as measured by BMD changes over time, however,
has not been explored. To our knowledge, our study is the first to demonstrate
in a prospective, controlled fashion that H/ERT benefits the postcranial skeleton
and produces a significant improvement in alveolar bone mass.
In addition to the clear, statistically significant increase of alveolar
bone mass after 3 years of treatment, we also observed an increase in alveolar
crest height in the H/ERT-treated patients, although this increase was not
significantly greater than that for non–H/ERT-treated subjects. The
increase in alveolar crest height in all subjects may seem surprising, as
it implies an expansion of the alveolar bone. Although periosteal bone expansion
is theoretically possible in the alveolar bone, a simpler alternative explanation
may be that a denser alveolar process may project as a higher crest, simply
because of its increased peripheral density. Regardless of the causes for
the observed changes in the linear measurement of alveolar bone, the effect
of H/ERT on the densitometric variables of oral bone mass was unambiguous.
Therefore, the overall findings imply that the dental attachment apparatus
is strengthened by H/ERT in postmenopausal women. Furthermore, the positive
effects of H/ERT on alveolar and postcranial bone mass were correlated at
most sites, including the spine and the alveolar crest height, where treatment
effects were not significantly different from those of the placebo group,
indicating that the benefits of H/ERT on alveolar bone are most likely mediated
by its systemic action on bone remodeling.
Epidemiological studies have shown a relationship between systemic bone
loss and oral bone health, suggesting that tooth loss may be a manifestation
of osteoporosis.22-23 This relationship
was more apparent in women with edentulism.24-25
A substantial body of evidence supports the notion that edentulous women are
more likely to have low BMD than dentate women.8-9,24
Although no data directly link loss in alveolar crest height or alveolar bone
to tooth loss, in a relatively large cohort of postmenopausal women, those
with osteoporosis had lower mandibular bone mass and thinner cortex at the
gonion and had lost a significantly higher number of teeth than did nonosteoporotic
women.24 Therefore, it is reasonable to say
that alveolar bone loss is the most important contributor to tooth loss and
edentulism in women with osteoporosis.
By contrast, estrogen users have more teeth and a lower prevalence of
edentulism than nonusers, as indicated by at least 3 large retrospective cohort
studies.12-14
Specifically, in the Leisure World cohort, the proportion of women with edentulism
decreased with duration of estrogen exposure,13
and in the Framingham Heart Study cohort, duration of ERT was an independent
predictor of the number of remaining teeth.12
We did not find differences in the numbers of teeth lost or remaining at the
end of the study between the 2 groups, as tooth loss was minimal during the
study. This result is not surprising, as the study was not powered to detect
differences in tooth loss, which would be a relatively rare event during a
3-year period in women in good oral health. In any case, our positive results
on alveolar bone mass support the conclusions of the existing observational
studies, reinforcing the notion that H/ERT strengthens the tooth attachment
apparatus, thus improving dental health. This conclusion is highly relevant
for clinical practice, since progressive loss of bony support for teeth after
menopause may result in costly, lengthy, uncomfortable treatments, with eventual
tooth loss and the inconvenience of wearing prosthetic appliances.
In the presence of periodontal disease and poor oral hygiene, systemic
bone loss plays a lesser role than oral disease in disrupting the attachment
apparatus. This was not the case for our patient population, who did not have
clinically significant periodontal disease. The women in the placebo group
who received calcium and cholecalciferol supplements and regular dental care
during the study actually experienced a significant increase in alveolar bone
density and a slight improvement in alveolar crest height. Thus, dental care
and dietary supplementation with calcium and cholecalciferol may be sufficient
to prevent postmenopausal oral bone loss and produce positive effects on dental
health. This conclusion is consistent with that of a previous report, which
demonstrated a lower incidence of tooth loss in postmenopausal women taking
calcium supplements with or without cholecalciferol relative to subjects who
were not using dietary supplements.10 Therefore,
our results support a public health recommendation for regular dental care
and sufficient calcium and cholecalciferol intake to maintain oral health
in postmenopausal women.
This study has some limitations. Most important is the higher dropout
rate in the placebo group relative to the H/ERT arm. This may have reduced
the significance of some of the differences between groups, although the intention-to-treat
analysis overcomes the potential bias that may be introduced by excluding
the noncompleters from the final analysis. Another limitation is the enrollment
of women in good dental health, and therefore at low risk for alveolar bone
loss and tooth loss. This was a deliberate choice, because we wanted to test
the hypothesis that estrogen affects the alveolar bone through its action
on bone remodeling as it does in the rest of the skeleton. Including subjects
with significant periodontal disease may have resulted in oral bone loss,
thus increasing the chances of detecting a treatment effect, but it would
have precluded the distinction between a systemic and a local effect of estrogen,
which can interfere with locally produced inflammatory cytokines that stimulate
bone resorption. Finally, the response to H/ERT in the lumbar spine was less
than in the proximal femur, whereas the opposite is usually seen after hormonal
therapy. There are several possible reasons for this unexpected result, although
all are speculative. Most of our subjects had been postmenopausal for more
than 5 years, and thus past the stage of accelerated bone loss which mainly
affects trabecular bone. Furthermore, several women in our cohort had high
BMIs. A high level of body fat diminishes the accuracy and the precision of
dual-energy x-ray absorptiometry of the spine. Finally, some degree of spondyloarthritis
in the more elderly women may have contributed to a further increase in the
variability of the dual-energy x-ray absorptiometry measurements of the spine.
CONCLUSIONS
Hormone/estrogen replacement therapy benefits postcranial bone density
and produces significant improvement in oral bone mass. Thus, improved oral
bone health constitutes an additional therapeutic benefit of ERT in postmenopausal
women. Research should be encouraged to develop simple dental radiographic
methods for identification of women with low alveolar bone mass for further
evaluation and consideration of treatment strategies to prevent bone loss
and/or increase bone mass. Routine dental visits could then represent a convenient
setting for identification of subjects with or at risk for osteoporosis.
AUTHOR INFORMATION
Accepted for publication October 15, 2001.
This work was supported by grant DE09861 from the National Institutes
of Health, Bethesda, Md. Additional support was provided by Wyeth-Ayerst Laboratories,
St Davids, Pa, and by Smith-Kline Beecham, Parsippany, NJ.
This study was presented in part at the 78th General Session of the
International Association for Dental Research, Washington, DC, April 68, 2000;
the 4th World Congress on Osteoporosis, Chicago, Ill, June 17, 2000; and the
11th North American Menopause Society Meeting, Orlando, Fla, September 8,
2000.
Corresponding author and reprints: Roberto Civitelli, MD, Division
of Bone and Mineral Diseases, Barnes-Jewish Hospital, North Campus, Mailstop
90-32-656, 216 S Kingshighway Blvd, St Louis, MO 63110 (e-mail: rcivitel{at}im.wustl.edu).
From the Division of Bone and Mineral Diseases, Department of Internal
Medicine (Drs Civitelli and Armamento-Villareal and Mss Muckerman and Lewandowski),
the Department of Radiology (Drs Pilgram and Hildebolt and Ms Yokoyama-Crothers),
and the Department of Dentistry (Ms Dotson and Drs Kardaris, Hauser, and Cohen),
Washington University School of Medicine and Barnes-Jewish Hospital, St Louis,
Mo. Dr Civitelli has stock ownership with Wyeth, Madison, NJ.
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