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Fractures Between the Ages of 20 and 50 Years Increase Women's Risk of Subsequent Fractures
Fiona Wu, FRACP;
Barbara Mason, BSc;
Anne Horne, MBChB;
Ruth Ames, NZCS;
Judith Clearwater, BSc;
Michael Liu, MBChB;
Margaret C. Evans, BSc;
Gregory D. Gamble, MSc;
Ian R. Reid, MD
Arch Intern Med. 2002;162:33-36.
ABSTRACT
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Background Perimenopausal and postmenopausal fractures are well-recognized, strong,
independent predictors of subsequent fractures. However, it is unknown whether
premenopausal fractures are predictive of postmenopausal fractures.
Objective To determine whether self-reported fractures sustained before the age
of 50 years are associated with fractures after this age.
Subjects and Methods Cross-sectional study of 1284 women (mean ± SD age, 73 ±
4 years) who were 10 or more years' postmenopausal and who were recruited
from electoral rolls in Auckland, New Zealand. Detailed information on their
fracture, medical, menstrual, alcohol, and smoking histories was obtained
using a standardized questionnaire.
Results Nine percent of the women reported fractures before the age of 20 years;
7%, between the ages of 20 and 50 years; and 29%,after the age of 50 years.
Fractures sustained between the ages of 20 and 50 years were associated with
a 74% increase in the risk of fractures after the age of 50 years (odds ratio,
1.74; 95% confidence interval, 1.12-2.70), while fractures occurring before
the age of 20 years were not (odds ratio, 1.01; confidence interval, 0.66-1.56).
Multivariate analysis showed that after bone density, age, maternal history
of hip fractures, age at menopause, weight, history of hormone replacement
therapy, and smoking and alcohol histories were adjusted for, a history of
fractures between the ages of 20 and 50 years remained a significant independent
predictor of risk of fractures after the age of 50 years (risk ratio, 1.83;
confidence interval, 1.12-2.76).
Conclusions Any fracture (unrelated to motor vehicle accidents) sustained between
the ages of 20 and 50 years is associated with increased risk of fractures
after the age of 50 years. Therefore, this is an important clinical risk factor
that points to the need for bone density measurement, consideration of lifestyle
modification, and antiosteoporosis therapies in these women.
INTRODUCTION
THE RELATIONSHIP between bone density and fracture risk has been well
documented in many prospective studies. There is also evidence that in postmenopausal
women, the occurrence of a fracture signals an increased risk of subsequent
fractures, independent of the bone density.1-8
Indeed, a history of fracture is the single most important factor in evaluating
future fracture risk. However, many women reach menopause with a history of
premenopausal fractures, yet it is unknown whether premenopausal fractures
are in any way predictive of subsequent postmenopausal fracture risk. The
fact that fractures both in childhood9 and
in premenopausal life10-12
are associated with reduced bone density suggests that these women may be
at increased risk. If this were true, then asking about premenopausal fracture
history would be an important and cost-free addition to the clinical evaluation
of women wishing to make decisions regarding the prevention of osteoporotic
fractures. The present study addresses this important clinical question by
determining whether self-reported fractures sustained before the age of 50
years are associated with fractures after this age.
SUBJECTS AND METHODS
SUBJECTS
The study population comprised 1284 women, 10 or more years' postmenopausal,
who were recruited by postal invitations, that were sent to names selected
from electoral rolls. None of the women had disorders of calcium metabolism;
renal, thyroid, or hepatic dysfunction; or other major systemic illness. All
women were independently mobile. Prior to entry, they had not been using hormone
replacement therapy or other drugs known to affect bone and calcium metabolism
in the previous year.
STUDY PROTOCOL
The subjects answered a questionnaire regarding their medical, menstrual,
smoking, alcohol, and fracture histories. They were asked to recall the number
and site of fractures, the age at which fracture was sustained, and the mechanism
of injury. Fractures resulting from motor vehicle accidents were excluded
from analysis. Fractures were classified as occurring before the age of 20
years, between the ages of 20 and 50 years, and after the age 50 years. Data
from 3 women with premature menopause (natural or surgical) before the age
of 40 years were excluded from the analysis.
MEASUREMENTS
Bone mineral density was assessed using a dual-energy x-ray absorptiometer
(Lunar Expert; Lunar Radiation Corp, Madison, Wis). Scans of the whole body
and proximal femur were performed. Height was measured with a stadiometer
(Harpenden; Holtain Ltd, Crymych, Wales), and weight (wearing light indoor
clothing) was measured with electronic scales.
STATISTICAL ANALYSIS
Differences in continuous normally distributed variables were tested
between those women with fractures after the age of 50 years and those without
using t test analysis. Differences in categorical
data between fracture groups were sought using  2 analysis
without continuity correction. The presence of at least 1 fracture before
the age of 50 years was compared with the presence of at least 1 fracture
after the age of 50 years using the McNemar procedure. Odds ratios were also
used to assess the strength of association between history of previous fractures
and subsequent fracture risk and to provide adjustment for planned subgroup
analyses. Cox proportional hazards models were constructed to assess the independent
predictive effect of individual clinical risk factors and bone mineral density
measurements on fracture risk after the age of 50 years. Cox proportional
hazards models were constructed using the follow-up time from the age of 50
years to the year of the present questionnaire for the women without fractures
and from the age of 50 years to the year of the first fracture for the women
with fractures. Clinical, anthropometric, and lifestyle factors were treated
as independent variables and were entered into models with a variety of iterative
procedures (stepwise, backward, forward selection) with a P value of .15 for entry into the model. Parsimony, goodness-of-fit
statistics, and biological plausibility enabled the choice of the final model.
Except where otherwise stated, data are presented as mean ± SD
and 95% confidence interval. A 5% significance level was maintained throughout
these analyses. All tests were 2-tailed. The SAS version 6.12 (SAS Institute,
Cary, NC) was used for all analyses.
RESULTS
Table 1 presents the characteristics
of the study population. The 2 groups of women with and without a history
of fractures after the age of 50 years were similar. However, the former group
was on average 10 months older at the time of answering the questionnaire
and had lower bone mineral densities. Current alcohol intake was similar between
the 2 groups and was low as a whole: 23.0% of all the women in the study never
drank, and only 3.8% took more than 2 drinks per day. Women who had fractures
before the age of 50 years had lower bone mineral densities than those without
such a history (total body: 1.02 ± 0.09 g/cm2 vs 1.04 ±
0.10 g/cm2, P = .01; femoral neck: 0.81
± 0.10 g/cm2 vs 0.83 ± 0.13 g/cm2, P = .07).
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Table 1. Characteristics of the Study Population
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Four hundred ninety-four women reported a total of 721 fractures. Of
these, 126 fractures were reported by 111 women before the age of 20 years,
95 fractures by 90 women between the ages 20 and 50 years, and 500 fractures
by 367 women after the age of 50 years. Three hundred thirty-two women reported
sustaining only 1 fracture, and 162 women reported sustaining more than 1
fracture. Table 2 shows the distribution
of the fractures by site.
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Table 2. Fracture Distribution According to Site
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Table 3 shows the odds ratios
and 95% confidence intervals (CIs) of sustaining a fracture after the age
of 50 years in terms of fracture history. Fractures before the age of 20 years
were not associated with fractures after the age of 50 years. Fractures sustained
between the ages of 20 and 50 years were associated with subsequent fractures
after the age of 50 years, with an odds ratio of 1.74 (95% CI, 1.12-2.70).
Post hoc analysis of the data from the 20- to 50-year-old group divided according
to the decade in which their original fracture occurred showed similar trends
across the decades. The analysis was also performed substituting each woman's
age at menopause instead of age 50 years as the cutoff between premenopausal
and postmenopausal fractures, and similar results were obtained. Age 50 years
as the cutoff was preferred because it circumvents the problem of determining
the age at menopause, which can be particularly difficult in women who have
undergone a hysterectomy.
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Table 3. Distribution of Women With Fractures After Age 50 Years According
to Previous Fracture History
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To assess the independent predictive value of fracture history before
age 50 years on the risk of subsequent fractures, Cox proportional hazards
models for the time to first fracture after age 50 years were developed. History
of fractures between ages 20 and 50 years and total bone density consistently
emerged from the models constructed as independent predictors of fracture
risk after age 50 years. The following variables were entered into the final
model: the history (yes/no) of fractures between 20 and 50 years, total bone
density (expressed as Z score), age, body weight, age at menopause, smoking
(previous or current), alcohol consumption of more than 2 drinks per day,
history of hormone replacement therapy, and maternal history of hip fractures.
Because a history of fractures before the age of 20 years was not significantly
associated with fractures after the age of 50 years, it was omitted from the
model. Fracture history between the age of 20 and 50 years was associated
with a risk ratio of 1.83 (95% CI, 1.12-2.76; P =
.003) and the total bone density with a risk ratio of 0.79 (95% CI, 0.68-0.91;
P = .005); ie, a history of fractures between the ages of 20 and 50 years
was associated with an 83% increase in the risk of fractures after the age
of 50 years, and an increase in Z score of 1 decreased the risk by 21%. Hip
bone density could be substituted for total body bone density in this model
and produces similar result.
COMMENT
The major finding of this study is that any fracture (excluding those
related to motor vehicle accidents) occurring between the ages of 20 and 50
years is associated with an increased risk of fractures after the age of 50
years. This increased risk is independent of age, bone density, body weight,
alcohol intake, and history of smoking. The increase in risk of further fractures
is comparable to that associated with the classic osteoporotic risk factors,
such as low bone density, low body weight, maternal history of hip fractures,
smoking, and prior osteoporotic fractures.13
The central message of our study is that a history of fractures between the
ages of 20 and 50 years identifies women at increased risk of having subsequent
fractures. Indeed, having a fracture between the ages of 20 and 50 years resulted
in a 74% increase in the risk of fractures after the age of 50 years. However,
the incidence of fractures between the ages of 20 and 50 years is low (7%).
Thus, the presence of fractures between the ages of 20 and 50 years is helpful
in identifying only some of those postmenopausal women who will require bone
density measurement and treatment. Our study was not designed to elucidate
the mechanisms behind this association; factors likely to be involved include
bone quality and strength, fall frequency, and protective neuromuscular responses
to falls. Nonetheless, this does not detract from the importance of a premenopausal
fracture history as a clinical risk factor. It should be an integral part
of fracture risk assessment, helping to determine who should undergo bone
densitometry and who should be offered therapies to increase bone mass.
While there has been a growing awareness in recent years that fractures
in the perimenopausal and postmenopausal periods are predictive of later fractures,
the significance of premenopausal fractures has not really been addressed.
Honkanen et al14 reported an association between
fractures occurring between the ages of 20 and 34 years and those occurring
in the perimenopausal period (age, 35-57 years), the hazard ratio being 1.9
(95% CI, 1.6-2.3). Johansson and Mellström15
carried out a study similar to the present one and found that a fracture occurring
before the age of 40 years was associated with a relative risk of fracture
occurring after the age of 50 years of 1.20 (95% CI, 0.95-1.53). However,
the women in that study ranged in age from 46 years upward, so the ascertainment
of postmenopausal fractures must have been very incomplete, because most women
still had many postmenopausal years before them. The design of the present
study has substantially overcome this problem by having an average time of
24 years since menopause in the study population and, possibly as a result,
found a much higher risk associated with premenopausal fracture. Together,
these findings suggest that the risk of sustaining fractures is a life-long
trait, probably reflecting the interaction of an individual's bone mass, bone
quality, fall frequency, and neuromuscular protective response to falls.
Fractures occurring in childhood and young adulthood (before the age
of 20 years) were not associated with increased fractures after the age of
50 years in this study. This finding may be because the mechanisms of fractures
are different in this age group. Children and adolescents probably sustain
more fractures through playing, sports, and accidents, so fracture risk may
reflect lifestyle and risk-taking behavior as much as skeletal factors. In
adults and older women, fractures may be more dependent on other factors,
such as bone strength, soft tissue composition, and frailty. These variables
are more likely to be consistent between early and later adult life than between
childhood and the sixth and seventh decades of life and could explain the
lack of association between fractures occurring before the age of 20 years
and after the age of 50 years.
This study is based on the retrospective self-report of fractures. The
failure to recall a fracture or its year of occurrence might have biased our
results. Accuracy of self-reports is site and severity dependent. The positive
predictive values are 98% to 100% for self-reported wrist and forearm fractures,
85% to 95% for ankle and lower leg fractures, 100% for hip fractures, and
84% for all fractures. Minor fractures in the hand and foot often remain unreported.16 While the validity of self-reports of past fractures
is not perfect, with problems of both overreporting and underreporting, it
is relatively accurate for major fractures such as those of the wrist, ankle,
and hip. There is evidence that the predictive value of a history of a postmenopausal
fracture on subsequent fractures is site dependent.1, 4, 8
It is possible that the same applies to premenopausal fractures.14
Therefore, those major premenopausal fractures that are reported accurately
by women may be more significant than minor fractures, which are less accurately
reported.
The present finding that any fracture occurring between the ages of
20 and 50 years is associated with increased risk of fractures after the age
of 50 years has important implications for clinical practice. Whatever the
underlying mechanisms, such a history should be considered a significant clinical
risk factor when decisions are being made regarding the need for bone density
measurement and the use of therapeutic interventions in postmenopausal women.
Younger women who have had a fracture will be alerted to the need to optimize
modifiable risk factors for osteoporosis, such as cessation of smoking, ensuring
adequate dietary calcium intake, moderation of alcohol and caffeine consumption,
and participation in regular physical activity.
AUTHOR INFORMATION
Accepted for publication March 13, 2001.
This study was funded in part by the Health Research Council of New
Zealand, Auckland.
Presented as an abstract at the Austalian New Zealand Bone and Mineral
Society Annual Scientific Meeting, Hamilton Island, Australia, November 7,
2000.
Corresponding author: Ian R. Reid, MD, Department of Medicine, University
of Auckland, Private Bag 92019, Auckland, New Zealand (e-mail: i.reid{at}auckland.ac.nz).
From the Department of Medicine, University of Auckland, Auckland,
New Zealand.
REFERENCES
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1. Gärdsell P, Johnell O, Nilsson BE, Nilsson JA. The predictive value of fracture, disease, and falling tendency for
fragility fractures in women. Calcif Tissue Int. 1989;45:327-330.
ISI
| PUBMED
2. Ross PD, Davies JW, Epstein RS, Wasnich RD. Pre-existing fractures and bone mass predict vertebral fracture incidence. Ann Intern Med. 1991;114:919-923.
3. Ross PD, Genant HK, Davis JW, Miller P, Wasnich RD. Predicting vertebral fracture incidence from prevalent fractures and
bone density among non-black, osteoporotic women. Osteoporos Int. 1993;3:120-126.
FULL TEXT
|
ISI
| PUBMED
4. Wasnich RD, Davis JW, Ross PD. Both spine and non-spine prevalent fractures increase the risk of fractures. J Bone Miner Res. 1992;7(suppl 1):S138.
5. Liberman UA, Weiss SR, Broll J, et al. Effect of oral alendronate on bone mineral density and the incidence
of fractures in postmenopausal osteoporosis. N Engl J Med. 1995;333:1437-1443.
FREE FULL TEXT
6. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis
treated with raloxifene: results from a 3-year randomized clinical trial. JAMA. 1999;282:637-645.
FREE FULL TEXT
7. Tromp AM, Ooms ME, Popp-Snijders C, Roos JC, Lips P. Predictors of fractures in elderly women. Osteoporos Int. 2000;11:134-140.
FULL TEXT
|
ISI
| PUBMED
8. Klotzbuecher CM, Ross PD, Landsman PB, Abott TA, Berger M. Patients with prior fractures have an increased risk of future fractures:
a summary of the literature and statistical synthesis. J Bone Miner Res. 2000;15:721-739.
FULL TEXT
|
ISI
| PUBMED
9. Goulding A, Cannan R, Williams EJ, Gold RW, Taylor RW, Lewis-Barned NJ. Bone mineral density in girls with forearm fractures. J Bone Miner Res. 1998;13:143-148.
FULL TEXT
|
ISI
| PUBMED
10. Goulding A, Gold E, Walker R, Lewis-Barned NJ. Women with past history of bone fracture have low spinal bone density
before menopause. N Z Med J. 1997;110:232-233.
ISI
| PUBMED
11. Horowitz M, Wishart JM, Bochner M, Need AG, Chatterton BE, Nordin BE. Mineral density of bone in the forearm in premenopausal women with
fracture wrists. BMJ. 1988;297:1314-1315.
12. Cox ML, Khan SA, Gau DW, Cox SAL, Hodkinson HM. Determinants of forearm bone density in premenopausal women: a study
in one general practice. Br J Gen Pract. 1991;41:194-196.
ISI
| PUBMED
13. Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. N Engl J Med. 1995;332:767-773.
FREE FULL TEXT
14. Honkanen R, Tuppuraninen M, Kroger H, Alhava E, Puntila E. Associations of early premenopausal fractures with subsequent fractures
vary by sites and mechanisms of fractures. Calcif Tissue Int. 1997;60:327-331.
FULL TEXT
|
ISI
| PUBMED
15. Johansson C, Mellström D. An earlier fracture as a risk factor for new fracture and its association
with smoking and menopausal age in women. Maturitas. 1996;24:97-106.
FULL TEXT
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ISI
| PUBMED
16. Honkanen K, Honkanen R, Heikkinen L, Kröger H, Saarikoski S. Validity of self-reports of fractures in perimenopausal women. Am J Epidemiol. 1999;150:511-516.
FREE FULL TEXT
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