Management of Low Bone Mineral Density in
Aliya Khan, MD, FRCPC, FACP
McMaster University, Department of Medicine, Hamilton ON
Objective: To review evidence for management of low bone density
in premenopausal women and to establish practical guidelines for
management of low bone density in this population by family
Method: A search of MEDLINE for relevant articles published
between January 1990 and May 2004 was conducted. Articles
retrieved were graded by level of evidence. Recommendations for
diagnosis and therapy were based on evidence from randomized
controlled trials and expert consensus.
Results: Low bone density in premenopausal women is not
associated with the same increased risk of fracture seen in older
women. In the absence of fragility fractures and loss of height, it
may be a reflection of low peak bone mass and may represent the
normal variation in bone mineral density (BMD). Women may have
low bone density secondary to an underlying skeletal or systemic
disorder. Common causes of low bone density in premenopausal
women include ovulatory disturbances and low body weight.
Conclusion: Osteoporosis is diagnosed in the premenopausal female
population in the presence of fragility fractures and is not based
solely on the results of BMD testing. Secondary causes of bone
loss should be excluded, and any underlying condition contributing
to low bone density should be corrected. Antiresorptive therapy
has been evaluated only in those premenopausal women who are
on glucocorticoid therapy and in those with primary
hyperparathyroidism. Only in these conditions has antiresorptive
therapy been shown to improve BMD.
Objectif : Analyser les résultats en ce qui concerne la prise en charge
de la faible densité osseuse chez les femmes préménopausées et
établir, à l’intention des médecins de famille, des lignes directrices
pratiques pour la prise en charge de la faible densité osseuse.
Méthode : Nous avons mené une recherche dans MEDLINE en vue
d’en tirer les articles pertinents publiés entre janvier 1990 et mai
2004. Les articles ainsi sélectionnés ont par la suite été classés
selon leur niveau de résultat. Les recommandations en matière de
diagnostic et de traitement ont été fondées sur des résultats issus
d’essais comparatifs randomisés et de consensus de spécialistes.
Résultats : La faible densité osseuse chez les femmes
préménopausées n’est pas associée à la même hausse du risque
de fracture que celle que connaissent les femmes d’âge avancé.
En l’absence de fractures de fragilisation et d’une diminution de la
taille, il est possible que la présence d’une faible densité osseuse
soit le reflet d’un faible pic de la masse osseuse et qu’elle
s’inscrive dans le cours normal de la variation de la densité
minérale osseuse (DMO). Il est également possible que les
femmes présentent une faible densité osseuse en raison d’un
trouble squelettique ou systémique sous-jacent. Parmi les causes
courantes de la faible densité osseuse chez les femmes
préménopausées, on trouve les troubles ovulatoires et la présence
d’un faible poids corporel.
Conclusion : Chez les femmes préménopausées, on rend un
diagnostic d’ostéoporose en présence de fractures de fragilisation
et non pas seulement en fonction des résultats de
l’ostéodensitométrie. Les causes secondaires de perte osseuse
devraient d’abord être écartées et l’on devrait procéder à la
correction de tout état sous-jacent contribuant à la présence d’une
faible densité osseuse. Le recours à un traitement aux inhibiteurs
de la résorption osseuse n’a été évalué que chez les femmes
préménopausées qui bénéficient d’un traitement aux
glucocorticoïdes et chez celles qui présentent une
hyperparathyroïdie primaire. Le traitement aux inhibiteurs de la
résorption osseuse ne s’est avéré efficace, pour l’amélioration de
la DMO, que dans ces situations.
J Obstet Gynaecol Can 2005;27(4):345–349
and 40 years.1Bone density follows a bell curve distri-
bution and is usually expressed as the number of standard
deviations (SD) a bone density figure is above or below the
mean value for young healthy adults (the “T score”).
30 and 40 years have a T score of –2.5 or less.2,3Low bone
density has been identified in the young healthy population
at increasing rates because bone density assessments are
being performed at the request of patients. Osteoporosis is
diagnosed in the premenopausal female population in the
presence of fragility fractures and is not based solely on the
results of a BMD test.1Premenopausal women experienc-
ing fragility fractures should be further evaluated to deter-
mine why fractures are occurring in an estrogen-replete
woman. This assessment may require a bone biopsy to
gility in the premenopausal period.
ow bone mineral density (BMD) is present in approxi-
mately 15% of healthy women between the ages of 30
APRIL JOGC AVRIL 2005 ?
Key Words: Premenopausal women, low bone density,
Competing interests: None declared.
Received on November 1, 2004
Accepted on January 31, 2005
This review focuses on low bone density in premenopausal
women and reviews the underlying pathophysiology,
advances in diagnosis, and therapy. Low bone density in
and it is essential for family physicians to be able to manage
this condition appropriately.
An advanced MEDLINE search was conducted to identify
all published randomized controlled trials (RCTs) evaluat-
ing low bone density in premenopausal women. The search
was limited to English-language articles published from
January 1990 to May 2004. The term “low bone density”
was cross-matched with “premenopausal women” with the
MeSH headings “management” and “pathophysiology.”
Articles reporting RCTs with appropriate randomization
The World Health Organization (WHO) defines osteopo-
rosis as a progressive systemic disease characterized by low
bone density and microarchitectural deterioration in bone
that predisposes patients to increased bone fragility and
fracture.1The WHO criteria for diagnosis of osteoporosis,
using T scores, are applicable only to postmenopausal
women. These criteria were not intended to apply to
premenopausal women with low bone density.1Low bone
tion follows a bell curve distribution, and approximately
15% of young healthy women have a T score of less than
–1.0. Approximately 0.5% of young healthy women have a
T score of –2.5 or less.2Thus there are variations in bone
mineral densities similar to variations in height. In the nor-
mal population, those individuals at the upper or the lower
end ofthenormalbellcurve mayrepresentthenormalvari-
ation in BMD. This may not be reflective of underlying
pathology and may not be associated with increased frac-
ture risk in the premenopausal period.1In premenopausal
women not experiencing fragility fractures or height loss, it
is important to consider that low bone density may there-
fore simply reflect an underlying low peak bone mass. Low
peak bone mass results from genetically determined peak
bone density, possibly influenced by such environmental
factors as exercise, dietary calcium intake, smoking, and
alcohol consumption during the teenage and young adult
Low bone density in young women is not associated with
the same increased risk of fracture seen in older women.
Premenopausal women, being younger, have a significantly
lower risk of fracture than do typical postmenopausal
not have the increased rates of bone turnover seen in
young woman with low bone density is significantly less
than that in a postmenopausal woman.4–6Age is an inde-
pendent risk factor for fracture, and low BMD in a
postmenopausal, older woman is associated with a signifi-
cantly higher fracture rate.1
Bone density testing should be completed in those women
with identifiable causes of bone loss.1Indications for BMD
testing in premenopausal women include glucocorticoid
therapy, premature ovarian failure (primary or secondary),
diseases and conditions associated with bone loss
(Table 1), and fragility fractures.
uated to ensure there are no secondary causes of bone loss
cal assessment includes a complete history and physical
examination with appropriate laboratory investigations to
exclude common conditions associated with bone loss.7
It is advisable to evaluate thyroid, liver, and renal function.
hyperthyroidism and in the presence of malignancy. Low
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Table 1. Secondary causes of bone loss1
Diseases or conditions
Hypogonadism (primary and secondary)
Growth hormone deficiency
Connective tissue disorders
Hepatic disorders (primary biliary cirrhosis)
Inflammatory bowel disease
Anticonvulsants (e.g., phenytoin, phenobarbital)
• Heparin (long-term)
• Cytotoxic chemotherapy
• Gonadotropin-releasing hormone (GnRH) agonists
•Depo medroxyprogesterone acetate (DMPA)
serum calcium is seen in individuals with vitamin D defi-
ciency or malabsorption. Malabsorption of calcium and
vitamin D can result in low BMD as well as osteomalacia.
Reduced 24-hour urinary excretion of calcium is an early
indicator of inadequate calcium intake or malabsorption. If
the 24-hour urinary excretion of calcium does not normal-
ity of malabsorptionor celiac disease should be considered.
Assessment of antiendomysial and antigliadin antibodies
can assist in the diagnosis of celiac disease.
It is important to ensure that young women with low BMD
are estrogen-replete. Subclinical estrogen deficiency has
Amenorrhea associated with estrogen deficiency causes
accelerated bone loss. Menstrual regularity is an important
factor in the achievement of peak bone mass and for the
maintenance of BMD in women in the premenopausal
period.1,8–11It is important to ensure that women with low
subclinical.1Elevations in serum follicle-stimulating hor-
mone (FSH) of more than 20 mIU/L have been associated
with increased bone turnover activity and progressive bone
loss in the perimenopausal period.10,12Therefore, a detailed
assessment of menstrual status is important because
women with low BMD.8–10
The usefulness of bisphosphonates in premenopausal
women with low BMD, in the absence of glucocorticoid
therapy, is unknown. Bisphosphonate therapy has been
glucocorticoid therapy. Glucocorticoid therapy is associ-
ated with an increase in the rate of bone turnover.
Bisphosphonates reduce bone turnover and therefore con-
stitute an effective treatment option in premenopausal
women who have been treated with glucocorticoids.13–16
Women who have not been treated with glucocorticoids
and who are estrogen replete may have normal bone turn-
over rates. Suppressing bone turnover further with a
bisphosphonate may not be safe or effective in improving
bone density or reducing fracture risk. This patient popula-
tion should be assessed in a specialized metabolic bone
clinic before antiresorptive therapy is implemented.
premenopausalwomenwithsecondarycauses of boneloss,
suchas glucocorticoid use
thyroidism.13Bisphosphonates are retained in the skeleton
for a long time, and they may be released from the skeleton
several years after treatment, possibly in a subsequent preg-
nancy. The effects of bisphosphonates on the developing
fetal skeleton are not known. Alendronate use has been
hyperparathyroidism and has been shown to be effective in
improving BMD in this population.17Alendronate and
risedronate are both effective in improving BMD in
therapyis of proven benefitin
or primary hyperpara-
Management of Low Bone Mineral Density in Premenopausal Women
APRIL JOGC AVRIL 2005 ?
Table 2. Investigations in premenopausal women with low bone mineral density
Serum calcium (albumin corrected)
Liver function tests (including alkaline phosphatase)
Serum FSH and estradiol
24 hour urinary excretion of calcium, creatinine
Optional additional investigations
Serum 25-hydroxy vitamin D
Serum parathyroid hormone
CBC: complete blood count; ESR: erythrocyte sedimentation rate; TSH: thyroid-stimulating hormone;
FSH: follicle-stimulating hormone.
has not been evaluated in premenopausal women with low
BMD in the absence of secondary causes of osteoporosis.
Lifestyle modification should always be encouraged in
premenopausal women to improve BMD. Modifications
include weight-bearing exercise, adequate dietary calcium
intake, cessation of smoking, limited caffeine, and avoid-
ance of excessive alcohol consumption.18
Women who are estrogen-deficient, either clinically or
subclinically, may benefit from estrogen supplementation.
After excluding secondary causes of bone loss, it is impor-
tant to ensureadequate
supplementation, in addition to recommending lifestyle
changes. Maintenance of normal body weight (a body mass
index of 20–25 kg/m2) and a daily exercise program are of
value in maintaining BMD.18Women should be strongly
advised to stop smoking and to limit their intake of alcohol,
coffee, and phosphorus-containing soft drinks.18Estrogen
supplementation, either in the form of oral contraceptives
or 17-? estradiol in combination with a progestin, may be
considered to prevent progressive bone loss. Estrogen
supplementation is associated with improvements in BMD
progesterone in women with ovulatory disturbance has
been shown to result in significant gains in BMD in a ran-
domized, placebo-controlled prospective study over 1
year.20Prospective data are needed to evaluate further the
effect of menstrual cycles with a short luteal phase on
BMD. Further evaluation of interventions with estrogen or
progesteronesupplementationis also warranted.In women
who are not estrogen deficient, the role of estrogen
supplementation is controversial.
Combined oral contraceptives (OCs) may exhibit a protec-
tive effect on bone density in premenopausal and
onstrated a negative effect.21,22Data from the Canadian
Multicentre Osteoporosis Study indicated that OC users
had decreased BMD at the trochanter and spine, compared
with nonusers.23However, OC users also had increased
rates of smoking and alcohol use and had a higher preva-
lence of menstrual irregularity before OC use, compared
with nonusers.23Thus prospective data are required to
assess the effects of OCs on BMD in premenopausal
women. Depot medroxyprogesterone acetate (DMPA)
inhibits LH and FSH release and results in suppression of
ovarian synthesis of estradiol and progesterone.24,25DMPA
use has been associated with decreased BMD at the lumbar
Low BMD in any premenopausal woman may be due to a
factors such as an inadequate calcium intake, excessive
alcohol intake, use of tobacco, low body weight, and estro-
gen deficiency can contribute to a lower peak bone mass or
to bone loss in the premenopausal years. Osteoporosis in
premenopausal women is diagnosed in the presence of fra-
gility fractures and is not based solely on the results of a
BMD test. Secondary causes of bone loss should be
excluded, and any underlying condition contributing to low
bone density should be corrected. Antiresorptive therapy
has been evaluated only in those premenopausal women
who are on glucocorticoid therapy and in those with pri-
mary hyperparathyroidism. Only in these conditions has
antiresorptive therapy been shown to improve BMD.
The issue of low bone density in premenopausal women
warrants further study.
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