Prevention and Treatment of Glucocorticoid-Induced Osteoporosis - UpToDate

3/3/24, 23:46 Prevention and treatment of glucocorticoid-induced osteoporosis - UpToDate
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Prevention and treatment of glucocorticoid-induced

osteoporosis
AUTHORS: Harold N Rosen, MD, Kenneth G Saag, MD, MSc
SECTION EDITOR: Clifford J Rosen, MD
DEPUTY EDITOR: Katya Rubinow, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2024.

This topic last updated: Feb 14, 2024.
INTRODUCTION
Glucocorticoid therapy is associated with an appreciable risk of bone loss, which is most
pronounced in the first few months of use. In addition, glucocorticoids increase fracture risk,
and fractures occur at higher bone mineral density (BMD) values than occur in
postmenopausal osteoporosis. The increased risk of fracture has been reported with doses
of prednisone or its equivalent as low as 2.5 to 7.5 mg daily [1]. Thus, glucocorticoid-induced
bone loss should be treated aggressively, particularly in those already at high risk for
fracture (older age, prior fragility fracture). In other individuals, clinical risk factor and bone
density assessment may help guide therapy. The prevention and treatment of glucocorticoid-
induced bone loss will be reviewed here. The clinical features are reviewed separately. (See
"Clinical features and evaluation of glucocorticoid-induced osteoporosis".)
Many of the prevention and treatment strategies for glucocorticoid-induced bone loss are
similar to those used to prevent and treat other causes of osteoporosis. (See "Overview of
the management of low bone mass and osteoporosis in postmenopausal women" and
"Treatment of osteoporosis in men" and "Evaluation and treatment of premenopausal
osteoporosis".)
GENERAL MEASURES
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In an attempt to minimize bone loss, certain general principles should be followed in all
patients receiving any dose of glucocorticoids for a duration of ≥3 months [2-4].
● The dose and the duration of glucocorticoid therapy should be as low as possible
because even what are thought to be replacement doses or chronic inhaled
glucocorticoids can cause bone loss [5]. Alternative therapy should be used whenever
possible. (See "Major side effects of inhaled glucocorticoids", section on 'Osteoporosis
and fracture risk in adults'.)
● Topical therapy (such as inhaled glucocorticoids or glucocorticoid enemas for asthma or

bowel disease, respectively) is preferred over enteral or parenteral glucocorticoids,
whenever possible.
● Patients should do weightbearing exercises to prevent both bone loss and muscle
atrophy.
● Patients should avoid smoking and excess alcohol.
● Patients should take measures to prevent falls.
CALCIUM AND VITAMIN D
● Calcium and vitamin D – We agree with the American College of Rheumatology (ACR)
Task Force osteoporosis guidelines, which suggest that all patients taking
glucocorticoids (any dose equivalent to prednisone ≥2.5 mg/day with an anticipated
duration of >3 months) achieve the reference total daily calcium intake for their age
group ( table 1). The guidelines also suggest vitamin D intake sufficient to maintain a
serum 25-hydroxyvitamin D level ≥30 to 50 ng/mL (75 to 125 nmol/L; usually 600 to 800
international units/day through either diet and/or supplements) [4]. (See "Calcium and
vitamin D supplementation in osteoporosis".)
Glucocorticoids induce negative calcium balance by decreasing intestinal calcium

absorption and increasing urinary calcium excretion [6]. Therefore, calcium
supplementation may attenuate bone loss in patients taking glucocorticoids. In a meta-
analysis of five randomized trials comparing calcium and vitamin D (cholecalciferol or
an active vitamin D metabolite) with calcium alone or placebo in patients taking
glucocorticoids, there was significant improvement in lumbar spine and radial bone
mineral density (BMD) in the calcium and vitamin D group (weighted mean difference
between treatment and control groups 2.6 and 2.5 percent, respectively) [7]. The
incidence of new, nontraumatic fractures was not significantly different (two trials, odds
ratio [OR] 0.6, 95% CI 0.1-2.4).

In one of the larger studies included in the meta-analysis, 96 patients with rheumatoid
arthritis receiving low-dose glucocorticoid therapy (mean prednisone dose 5.6 mg daily)
were randomly assigned to calcium carbonate (1000 mg of elemental calcium daily)
plus vitamin D3 (500 international units/day) or placebo [8]. The between-group
difference in the annual rate of change in BMD was 2.65 percent (95% CI 0.73-4.57) and
2.08 percent (95% CI 0.43-3.73) for the spine and trochanter, respectively, favoring
calcium and vitamin D supplementation.
Although calcium and vitamin D supplementation is necessary, it is generally not

sufficient to prevent bone loss and fracture in patients taking high-dose glucocorticoids
[9-12]. Pharmacologic therapy is often required. (See 'Candidates for pharmacologic
therapy' below and 'Bisphosphonates' below.)
● Active vitamin D metabolites – Vitamin D metabolites that are more active than
vitamin D itself, such as calcitriol and alfacalcidol, have been evaluated for the
prevention and treatment of glucocorticoid-induced bone loss [13]. Calcitriol (1,25-
dihydroxyvitamin D, the most active metabolite of vitamin D) plus calcium protects
against spine bone loss more than calcium alone in patients taking glucocorticoids
[10,14]. A meta-analysis of five trials of active vitamin D metabolites in patients exposed
to corticosteroids reported a beneficial effect of vitamin D metabolites on lumbar spine
BMD [13]. There were insufficient data to address fracture prevention.
Active vitamin D metabolites are less commonly used, however, because of the risks of
hypercalcemia and hypercalciuria in patients whose urinary calcium excretion is already
increased and because more effective therapies are available [15]. The superior efficacy
of bisphosphonates compared with an active vitamin D metabolite for preventing
glucocorticoid-induced bone loss has been demonstrated in several randomized trials
[16-21]. Although not statistically significant, one trial showed that compared with
alfacalcidol, fewer patients randomly assigned to alendronate had new vertebral
fractures (three versus eight patients) [17]. (See 'Bisphosphonates' below.)
CANDIDATES FOR PHARMACOLOGIC THERAPY
Our approach described below is largely in agreement with various guidelines, which
collectively suggest pharmacologic therapy for patients based upon fracture risk. (See
'Guidelines' below.)
Fracture risk assessment — Patients with the highest risk for fracture are the ones most
likely to benefit from drug therapy. Thus, all individuals taking glucocorticoids require an
evaluation for fracture risk. This evaluation includes assessing clinical risk factors for
fracture, and, in selected individuals, measuring bone mineral density (BMD) and calculating

estimated fracture risk. The approach to evaluation is reviewed in detail separately. (See
"Clinical features and evaluation of glucocorticoid-induced osteoporosis", section on
'Evaluation'.)
BMD and fracture history — We assess prior history of fracture and other clinical risk
factors for fracture in all patients ( table 2). We measure BMD using dual-energy x-ray
absorptiometry (DXA) of the hip and spine in all individuals taking any dose of glucocorticoid
with anticipated treatment duration of ≥3 months (or if duration of therapy is uncertain).
Patients with established osteoporosis (history of fragility fracture or BMD T-score ≤-2.5) are
at high or very high risk for fracture.
Glucocorticoid exposure — Glucocorticoid exposure is a critical determinant of fracture

risk. The American College of Rheumatology (ACR) guidelines indicate that high-dose
glucocorticoid therapy (treatment with prednisone ≥30 mg daily for >30 days or cumulative
doses ≥5 g per year [or equivalent]) confers very high fracture risk, irrespective of the
presence of other clinical risk factors [4,22].
Fracture risk calculator — For patients aged ≥40 years without established osteoporosis,
fracture risk can be assessed using a fracture risk calculator, such as the Fracture Risk
Assessment Tool ( FRAX).
FRAX estimates the 10-year probability of fracture for untreated patients between ages 40
and 90 years, using femoral neck BMD and clinical risk factors, including glucocorticoid
exposure. FRAX does not account for glucocorticoid dose or duration, and therefore, FRAX
risk estimates must be corrected according to the dose of glucocorticoid [23]. For patients
taking prednisone >7.5 mg/day or equivalent, the risk estimate should be increased by 15
percent of the estimated value for major osteoporotic fracture and by 20 percent for hip
fracture [23]. (See "Osteoporotic fracture risk assessment", section on 'Fracture risk
assessment tool'.)
● Interpretation of FRAX – In North America, reasonable glucocorticoid-corrected

thresholds to indicate very high, high, moderate, and low risk of fracture are as follows
[4]:
• Very high risk – A 10-year probability of hip or combined major osteoporotic fracture
of ≥4.5 and ≥30 percent, respectively
• High risk – A 10-year probability of hip or combined major osteoporotic fracture of

≥3 but <4.5 percent and ≥20 but <30 percent, respectively
• Moderate risk – A 10-year probability of hip or combined major osteoporotic fracture

>1 but <3 percent and 10 to 19 percent, respectively

• Low risk – A 10-year probability of hip or combined major osteoporotic fracture of ≤1

and <10 percent, respectively
● Limitations of FRAX – Some patients receiving glucocorticoids are at high risk, even if
they fail to meet the FRAX criteria for high risk. As an example, for patients with
clinical risk factors for fracture, low lumbar spine BMD, but normal femoral neck BMD,
FRAX is likely to underestimate fracture risk. At very high glucocorticoid doses (eg,
prednisone ≥30 mg/day or equivalent), FRAX underestimates fracture risk even after
correction for glucocorticoid treatment [4]. Risk underestimation is also likely in
patients taking glucocorticoids because these agents are more likely to cause
osteoporosis of the spine than of the hip. FRAX similarly underestimates fracture risk in
individuals with frailty or elevated fall risk. Alternative methods for estimating fracture
risk specifically in individuals taking glucocorticoid therapy have been proposed [24].
Thus, intervention guidelines with or without the use of FRAX provide only general
clinical guidance. Treatment should remain individualized through shared decision-
making between patient and clinician.
Fracture risk assessment, including the FRAX tool and its limitations, is reviewed in
detail separately. (See "Osteoporotic fracture risk assessment", section on 'Clinical
application of fracture risk assessment' and "Osteoporotic fracture risk assessment",
section on 'Limitations'.)
Postmenopausal women and men aged ≥50 years — Pharmacologic therapy is indicated
for postmenopausal women and men ≥50 years with moderate to high risk of fracture. (See
'Fracture risk assessment' above and "Clinical features and evaluation of glucocorticoid-
induced osteoporosis", section on 'Fracture risk assessment'.)
● For men aged ≥50 years and postmenopausal women (who are initiating or are
chronically treated with any dose of glucocorticoids for any duration) who have
osteoporosis (previous fragility fracture and/or a BMD T-score ≤-2.5) at initial
assessment, we recommend pharmacologic therapy.
● For men aged ≥50 years and postmenopausal women with T-scores between -1.0 and
-2.5 who are at moderate or high estimated fracture risk and are initiating or
continuing treatment with any dose of glucocorticoids for any duration, we suggest
pharmacologic therapy. FRAX-based thresholds for estimated fracture risk are reviewed
above. (See 'Fracture risk calculator' above.)
● For postmenopausal women and men aged ≥50 years with T-scores between -1.0 and
-2.5 who have a glucocorticoid-corrected, FRAX-calculated absolute risk below these
thresholds, we suggest pharmacologic therapy if they are taking ≥7.5 mg/day of
prednisone or its equivalent for an anticipated duration of ≥3 months.

● We also suggest pharmacologic therapy for postmenopausal women and men aged
≥50 years taking glucocorticoid doses equivalent to prednisone ≥30 mg/day for >1
month, even in the absence of other risk factors for fracture.
These recommendations are based upon randomized trial data showing that pharmacologic
therapy improves BMD in patients taking glucocorticoids [25,26] and additional randomized
trial data showing that pharmacologic therapy reduces fracture in men and postmenopausal
women with established osteoporosis [27]. (See 'Efficacy' below and "Overview of the
management of low bone mass and osteoporosis in postmenopausal women" and
"Bisphosphonate therapy for the treatment of osteoporosis" and "Treatment of osteoporosis
in men".)
Premenopausal women and younger men — In the absence of definitive data, the decision
to initiate pharmacologic therapy should be individualized in premenopausal women and
younger men. The FRAX tool was not developed for use in men aged <40 years or
premenopausal women. In premenopausal women and younger men included in clinical
trials for glucocorticoid-induced osteoporosis, fractures were generally infrequent in both
treated and control groups [12,28-30]. Fracture risk in these patients taking glucocorticoids is
not clearly defined and may differ from reported fracture risk in other glucocorticoid-treated
populations. In addition, the presence or absence of hypogonadism may influence fracture
risk and decisions about nonhormonal pharmacologic therapy.
Hypogonadal patients — Glucocorticoids may increase bone resorption by decreasing

secretion of androgens and estrogens, mediated primarily by inhibition of gonadotropin
secretion [31]. Therefore, it is logical to replace these hormones in women or men with
confirmed hypogonadism, as long as there are no contraindications. (See "Evaluation and
management of secondary amenorrhea" and "Management of primary ovarian insufficiency
(premature ovarian failure)" and "Testosterone treatment of male hypogonadism".)
● Premenopausal women – For premenopausal women of childbearing potential who

are taking or initiating glucocorticoids and who are hypogonadal, we suggest
treatment of hypogonadism. (See "Functional hypothalamic amenorrhea: Evaluation
and management", section on 'Estrogen replacement'.)
In a cross-sectional study of 119 perimenopausal women with asthma (65 receiving oral
glucocorticoids), only those women who were not taking menopausal hormone therapy
had lower mean BMD than healthy, aged-matched control women [32]. This
observation plus the extensive literature supporting the value of menopausal hormone
therapy in the prevention of postmenopausal osteoporosis makes it likely that
appropriate treatment of hypogonadism can help reduce or reverse bone loss in
premenopausal, hypogonadal women treated with glucocorticoids. (See "Menopausal

hormone therapy in the prevention and treatment of osteoporosis", section on 'Efficacy

of estrogen therapy'.)
● Men – Bisphosphonates are first-line therapy for prevention and treatment of

glucocorticoid-induced osteoporosis in men because they are known to reduce fracture
risk. Men who develop symptomatic hypogonadism should also be treated with
testosterone for its benefits on muscle, energy, and libido, as well as on bone [33,34]. A
number of testosterone preparations are available for the treatment of testosterone
deficiency. (See "Treatment of osteoporosis in men", section on 'Congenital
hypogonadism' and "Testosterone treatment of male hypogonadism", section on
'Choice of testosterone regimen'.)
Eugonadal patients — In the absence of definitive data, pharmacologic therapy should be

individualized in eugonadal men and women. We generally treat such patients if they are at
moderate to high risk for fracture. (See 'Fracture risk assessment' above.)
Potential short- and long-term risks, as well as potential effects on the fetus, should be
considered as part of the decision to use bisphosphonates or teriparatide for the treatment
of premenopausal osteoporosis. An effective plan for pregnancy prevention should be
implemented. (See 'Choice of therapy' below and "Epidemiology and etiology of
premenopausal osteoporosis" and "Evaluation and treatment of premenopausal
osteoporosis".)
● For premenopausal women with normal ovarian function who have a fragility fracture
while receiving glucocorticoids, we suggest pharmacologic therapy.
● For similar women who do not have a fragility fracture but have accelerated bone loss
(≥4 percent/year) or Z-score <-3.0 while receiving glucocorticoids (7.5 mg prednisone
equivalent for ≥3 months), we also suggest pharmacologic therapy.
● For men <50 years of age who have a fragility fracture while receiving glucocorticoids,
we suggest pharmacologic therapy.
● For similar men who do not have a fragility fracture but have accelerated bone loss (≥4
percent/year) or Z-score <-3.0 while receiving glucocorticoids (7.5 mg prednisone
equivalent for ≥3 months), we also suggest pharmacologic therapy.
● We also suggest pharmacologic therapy for men aged <50 years and premenopausal
women taking prednisone ≥30 mg/day for >1 month.
CHOICE OF THERAPY

● Men and postmenopausal women – For pharmacologic therapy for men and
postmenopausal women, we favor bisphosphonates as first-line therapy. We prefer
alendronate or risedronate because of clinical trial data demonstrating efficacy in men
and women with glucocorticoid-induced osteoporosis. For such patients who cannot
tolerate oral bisphosphonates or who have difficulty with the dosing requirements or
adherence, intravenous (IV) zoledronic acid is an acceptable alternative. (See
'Bisphosphonates' below and "Bisphosphonate therapy for the treatment of
osteoporosis", section on 'Oral regimen' and "Bisphosphonate therapy for the
treatment of osteoporosis", section on 'IV regimen'.)
We typically reserve parathyroid hormone (teriparatide, PTH) for patients with very high
fracture risk (eg, T-score ≤-3.0, T-score ≤-2.5 plus fragility fracture[s], or very high
estimated fracture risk). In addition, teriparatide is an option for patients who are
unable to tolerate any of the available bisphosphonates or who continue to fracture
after one year of bisphosphonate therapy. (See 'Parathyroid hormone' below and
'Fracture risk assessment' above.)
Denosumab is also an alternate therapeutic option for those at high risk for fracture.
However, due to the increased risk of vertebral fracture after discontinuation of
denosumab, the need for a careful "exit strategy" if denosumab is stopped should be
discussed with patients prior to its initiation. (See 'Other pharmacologic therapy'
below.)
● Premenopausal women – For premenopausal women with fractures or accelerated

bone loss and with normal ovarian function, bisphosphonates are generally the drugs
of choice (see 'Bisphosphonates' below). Teriparatide is an alternative option for such
women, as long as epiphyses are fully fused (see 'Parathyroid hormone' below).
Potential short- and long-term risks, as well as potential effects on the fetus, should be
considered as part of the decision to use bisphosphonates or teriparatide for the
treatment of premenopausal osteoporosis. (See "Evaluation and treatment of
premenopausal osteoporosis", section on 'Antiresorptive therapy with
bisphosphonates' and "Evaluation and treatment of premenopausal osteoporosis",
section on 'Anabolic therapy with teriparatide'.)
We do not typically prescribe denosumab for the prevention or treatment of

glucocorticoid-induced osteoporosis in premenopausal women [35]. (See 'Other
pharmacologic therapy' below.)
EFFICACY

Bisphosphonates — Substantial data support the use of antiresorptive agents, such as the
bisphosphonates, for the prevention and treatment of glucocorticoid-induced bone loss. In a
meta-analysis of 27 randomized trials evaluating bisphosphonates (alone or in combination
with calcium and vitamin D) versus calcium and vitamin D (alone or with placebo) for the
prevention and treatment of glucocorticoid-induced osteoporosis, there was significant
improvement in lumbar spine (absolute difference 3.5 percent) and femoral neck bone
mineral density (BMD) (absolute difference 2.1 percent) in the bisphosphonate group [26].
There was a reduction in the risk of new vertebral fracture with bisphosphonates (44 versus
77 per 1000 persons in the bisphosphonate and no treatment groups, respectively, risk ratio
[RR] 0.57, 95% CI 0.35-0.91). The reduction in risk of nonvertebral fracture did not reach
statistical significance (42 versus 55 per 1000 persons, RR 0.79, 95% CI 0.47-1.33).
Few premenopausal women were included in the large clinical trials [26], and fractures were
generally infrequent in both treated and control groups [12,28,29]. Two small clinical trials
that included premenopausal women with corticosteroid-treated connective tissue diseases
(CTD) used the less potent first-generation bisphosphonate, etidronate, as the antiresorptive
agent and found successful maintenance of BMD in the women taking the drug [36,37].
The therapeutic efficacy of bisphosphonates in patients with glucocorticoid-induced

osteoporosis has been thought to be related to their ability to promote osteoclast apoptosis
(programmed cell death) [38]. However, glucocorticoids may negate the pro-apoptotic effect
of bisphosphonates, suggesting that these drugs may prevent glucocorticoid-induced bone
loss by prolonging the lifespan of osteoblasts [38,39].
● Alendronate – The efficacy of alendronate in patients receiving glucocorticoid therapy

was demonstrated in a study of 477 patients age 17 to 83 years who were randomly
assigned to receive one of two doses of alendronate or placebo [12]. The mean BMD of
the lumbar spine increased by 2.1 and 2.9 percent over 48 weeks in the patients
receiving 5 and 10 mg of alendronate daily, respectively, while decreasing 0.4 percent in
the placebo group. Femoral neck, trochanter, and total body BMD also increased
significantly in the alendronate groups ( figure 1). Those receiving alendronate had
fewer new vertebral fractures compared with placebo (2.3 versus 3.7 percent), although
fracture was not a primary outcome. These benefits were maintained for two years [40].
Once-weekly alendronate (70 mg) similarly improves BMD [41], and in a retrospective
cohort study, alendronate was associated with a significantly lower risk of hip fracture
in older patients taking oral prednisolone [42].
● Risedronate – Risedronate is also effective for the prevention and treatment of

osteoporosis, including glucocorticoid-induced osteoporosis [11,43,44]. In a one-year
study of risedronate versus placebo in 290 patients receiving glucocorticoids
(prednisone ≥7.5 mg/day for six or more months), lumbar spine and femoral neck BMD

increased by 2.7 and 1.8 percent, respectively, in the risedronate group, as compared
with no change in the placebo group [43]. The relative risk of vertebral fracture (a
secondary outcome) was reduced by 70 percent.
● Zoledronic acid – The efficacy of zoledronic acid for the prevention and treatment of
glucocorticoid-induced osteoporosis was demonstrated in a one-year, randomized trial
of IV zoledronic acid (5 mg once) or daily oral risedronate (5 mg) in 288 patients who
recently started glucocorticoids (prevention group) and 545 patients who had been
taking them for more than three months (treatment group) [45]. In an analysis of
patients who received the study drug and had baseline and follow-up BMD
measurements, zoledronic acid and risedronate increased mean BMD of the lumbar
spine in both the prevention (2.6 and 0.6 percent, respectively) and treatment (4.1 and
2.7 percent, respectively) groups. The study was not designed to evaluate fractures,
which occurred in three and five subjects in the risedronate and zoledronic acid groups,
respectively.
During the first three days, the occurrence of adverse events (predominantly
arthralgias, fever, and flu-like symptoms) was greater in the zoledronic acid group. (See
"Risks of bisphosphonate therapy in patients with osteoporosis", section on 'Risks
specific to intravenous bisphosphonates'.)
● Other bisphosphonates – Oral and IV pamidronate have been shown to prevent

glucocorticoid-induced bone loss [9,46-48]. However, pamidronate is rarely used now
that zoledronic acid is available.
There are few data evaluating the efficacy of oral ibandronate for the prevention and
treatment of glucocorticoid-induced osteoporosis. However, IV ibandronate appears to
preserve BMD. In an open-label, randomized trial of ibandronate (2 mg IV every three
months for two years) versus alfacalcidol (1 mcg daily) in 104 patients with established
glucocorticoid-induced osteoporosis, IV ibandronate resulted in superior improvements
in spine, femoral neck, and calcaneal BMD compared with alfacalcidol (between-group
differences of 9.7, 3.4, and 7.9 percent, respectively) [18]. These improvements were
sustained in a third year of treatment, and there were fewer vertebral fractures (a
secondary outcome) in the ibandronate group compared with the alfacalcidol group
(8.6 versus 22.8 percent) [19].
Parathyroid hormone — Parathyroid hormone (teriparatide, PTH) is generally not used as a

first-line drug for treatment or prevention of glucocorticoid-induced osteoporosis, because
of its cost, subcutaneous route of administration, and the availability of other agents.
However, PTH is an option for the treatment of glucocorticoid-induced osteoporosis in men
or postmenopausal women who:
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● Have very high fracture risk (eg, T-score ≤-3.0, T-score ≤-2.5 plus fragility fracture[s], or
very high estimated fracture risk) before initiating glucocorticoids. (See 'Fracture risk
assessment' above.)
● Have osteoporosis (T-score ≤-2.5, prior fragility fracture[s], or high or very high
estimated fracture risk) and are unable to tolerate oral or IV bisphosphonates or have
relative contraindications to bisphosphonates (achalasia, scleroderma esophagus,
esophageal strictures).
● Fail other osteoporosis therapies (fracture with loss of BMD in spite of compliance with
therapy).
Teriparatide is also an option for premenopausal women, as long as epiphyses are fully
fused, who have fragility fractures or accelerated bone loss (≥4 percent/year) while receiving
glucocorticoids (7.5 mg prednisone equivalent for ≥3 months) and who do not need
treatment for hypogonadism because they have normal menstrual function.
Due to the lack of proven efficacy beyond two years, a single course of teriparatide in most
patients is limited to two years duration. Treatment with an antiresorptive agent (eg,
bisphosphonates) after PTH preserves the gains in BMD achieved with PTH. Thus, for
patients who receive teriparatide as initial treatment and who remain at high risk for fracture
after discontinuation, a bisphosphonate should be started after PTH is discontinued. (See
"Parathyroid hormone/parathyroid hormone-related protein analog therapy for
osteoporosis".)
PTH stimulates bone formation as well as resorption, and intermittent administration

stimulates formation more than resorption. Because the predominant effect of
glucocorticoids on the skeleton is to reduce bone formation and bisphosphonates
(antiresorptive agents) do not address this mechanism of bone loss, treatment with PTH is
theoretically a more appealing approach [49].
In randomized trials, PTH is effective in improving BMD in patients treated with

glucocorticoids [25,50-52]. As an example, in an 18-month, randomized trial of alendronate
(10 mg orally daily) versus PTH (1-34) (teriparatide, 20 mcg subcutaneously daily) in 428 men
and women who had taken glucocorticoids for ≥3 months (≥5 mg of prednisone equivalent
daily), both treatments significantly increased BMD. However, teriparatide was associated
with a greater increase in lumbar spine (8.2 versus 3.9 percent), total hip (3.8 versus 2.4
percent), and femoral neck (4.4 versus 2.8 percent) BMD [25]. There was no difference in the
incidence of nonvertebral fractures, a secondary outcome (5.6 versus 3.7 percent), but there
were fewer new radiographic vertebral fractures (1 versus 10) in subjects randomly assigned
to teriparatide compared with alendronate. Thirty percent of subjects in each treatment
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group discontinued the study prior to completion. There was more nausea and insomnia in
the teriparatide group and more rashes in the alendronate group.
The trial was designed to have an 18-month continuation phase, with prespecified secondary
outcomes that included BMD, fractures, and adverse events at 36 months [50]. After 36
months (n = 241 subjects), increases in BMD from baseline remained significantly greater in
the teriparatide group (11 versus 5.3, 5.2 versus 2.7, and 6.3 versus 3.4 percent for lumbar
spine, total hip, and femoral neck, respectively). New vertebral fractures occurred
significantly less often in patients receiving teriparatide (3 versus 13 in the alendronate
group). The majority of vertebral fractures occurred in the first 18 months. There was no
difference in the incidence of nonvertebral fractures.
Premenopausal women with glucocorticoid-induced osteoporosis also benefit from

treatment with teriparatide [25]. In a secondary analysis of the randomized trial of
teriparatide versus alendronate in patients with glucocorticoid-induced osteoporosis, the
increase in lumbar spine BMD was significantly greater in the teriparatide group for both
premenopausal (7.0 versus 0.7 percent) and postmenopausal (7.8 versus 3.7 percent) women
[28]. In premenopausal women, fractures were infrequent in both treatment groups.
Abaloparatide, a synthetic analog of parathyroid hormone-related protein (PTHrP) has not

been evaluated as a treatment for glucocorticoid-induced osteoporosis. Its use for
osteoporosis of other etiologies is reviewed in detail elsewhere. (See "Parathyroid
hormone/parathyroid hormone-related protein analog therapy for osteoporosis".)
Other pharmacologic therapy
● Denosumab – We do not typically prescribe denosumab for the prevention or

treatment of glucocorticoid-induced osteoporosis. Denosumab improves BMD and
metrics of bone strength in individuals on glucocorticoid treatment [53-56]. However,
increased risk of vertebral fracture is evident in postmenopausal women after
discontinuation of denosumab, and the need for a careful "exit strategy" if denosumab
is stopped should be discussed with patients prior to its initiation. If denosumab is
discontinued, administering an alternative therapy (typically a bisphosphonate) to
prevent rapid bone loss and vertebral fracture is strongly advised. (See "Denosumab for
osteoporosis", section on 'Increased vertebral fractures'.)
Denosumab is a monoclonal antibody to an osteoclast differentiating factor. It inhibits

osteoclast formation, decreases bone resorption, increases BMD, and reduces the risk
of fracture. It has been used in postmenopausal women and in men undergoing
androgen deprivation therapy for prostate cancer. (See "Denosumab for osteoporosis"
and "Side effects of androgen deprivation therapy", section on 'Denosumab'.)

In a noninferiority trial evaluating denosumab versus risedronate in 505 patients

receiving glucocorticoids for ≥3 months and 290 patients who were initiating
glucocorticoids (<3 months), the increase in lumbar spine BMD was greater with
denosumab (4.4 versus 2.3 percent for glucocorticoid continuing and 3.8 versus 0.8
percent for glucocorticoid initiating) [53,54]. There was no difference in adverse events,
including the incidence of fracture (osteoporosis-related fractures, 7 and 6 percent,
respectively; new and worsening vertebral fractures in postmenopausal women, 5
percent in each group). Denosumab also increased BMD in a prospective, observational
study of 36 patients treated with glucocorticoids for pulmonary disease [57].
● Romosozumab – Few data are available about the use of romosozumab, an anabolic
based on an antibody to sclerostin, for the prevention or treatment of glucocorticoid
osteoporosis. Its use for osteoporosis is reviewed in detail elsewhere. (See "Overview of
the management of low bone mass and osteoporosis in postmenopausal women",
section on 'Romosozumab'.)
● Calcitonin – We do not use calcitonin for the treatment or prevention of glucocorticoid-

induced osteoporosis, because more effective drugs (eg, bisphosphonates,
teriparatide) are available for the prevention of bone loss and reduction of fracture risk.
Another concern is that the long-term use of calcitonin for osteoporosis has been
associated with an increase in cancer rates. (See "Calcitonin in the prevention and
treatment of osteoporosis", section on 'Concerns about the use of calcitonin'.)
MONITORING
There are several published guidelines for monitoring the response to osteoporosis therapy.
Although all recommend follow-up bone mineral density (BMD) testing, there is no
consensus on the optimal frequency of monitoring and the preferred site to monitor. (See
"Overview of the management of low bone mass and osteoporosis in postmenopausal
women", section on 'Monitoring response to initial pharmacotherapy'.)
We typically measure BMD (dual-energy x-ray absorptiometry [DXA]) of the lumbar spine and
hip at the initiation of glucocorticoid therapy and after one year.
● BMD stable or improved – If BMD is stable or improved, we measure it less frequently

(every two to three years) thereafter. If glucocorticoids are discontinued and BMD is
stable, measurement at five-year intervals may be sufficient.
● BMD decreased – The finding of a BMD decrease greater than the least significant
change or a new fracture in a treated patient should trigger additional evaluation for
contributing factors, which may include poor adherence to therapy, inadequate

gastrointestinal absorption, inadequate intake of calcium and vitamin D, or the

development of a disease or disorder with adverse skeletal effects. Switching from oral
bisphosphonates to intravenous (IV) zoledronic acid may be effective in patients with
poor absorption or poor compliance with the oral regimen. Alternative options for
patients who fail oral bisphosphonate therapy are similar to those for patients with
osteoporosis in general. (See "Overview of the management of low bone mass and
osteoporosis in postmenopausal women", section on 'BMD decreased or fracture
during therapy'.)
There may be a significant increase in bone density after discontinuation of exogenous

glucocorticoid therapy or reversal of endogenous Cushing syndrome [58,59]. One study, as
an example, examined spine BMD after successful treatment for Cushing disease in 20
patients, all of whom had marked osteoporosis of lumbar spine and femoral neck [58]. There
was no change in BMD for six months, the time required for gradual reversal of increased
osteoclastic activity, after which BMD increased. However, patients who have had a fracture
may have permanent deformity.
GUIDELINES
The American College of Rheumatology (ACR) guidelines recommend intervention based

upon risk of fracture (very high, high, moderate, low), guided in part by the Fracture Risk
Assessment Tool ( FRAX) [4,60]. FRAX is reviewed in detail elsewhere. (See "Osteoporotic
fracture risk assessment", section on 'Fracture risk assessment tool' and "Treatment of
osteoporosis in men", section on 'Patient selection' and "Overview of the management of low
bone mass and osteoporosis in postmenopausal women", section on 'Patient selection'.)
For adults ≥40 years, low, moderate, high, and very high risk are defined as follows [4,60]:
● Low risk – 10-year risk of hip or a major osteoporotic fracture of ≤1 percent and <10
percent, respectively, and hip and spine T-score >-1.0
● Moderate risk – 10-year risk of hip or a major osteoporotic fracture >1 but <3 percent
and 10 to 19 percent, respectively, or hip or spine T-score between -1.0 and -2.4
● High risk – 10-year risk of hip or a major osteoporotic fracture ≥3 but <4.5 percent and
≥20 but <30 percent, respectively, or spine or hip T-score ≤-2.5 but >-3.5
● Very high risk

• Prior fragility fracture(s) or
• 10-year risk of hip or a major osteoporotic fracture ≥4.5 percent and ≥30 percent,
respectively, or
• Hip or spine T-score ≤-3.5 or
• Glucocorticoid dose of prednisone ≥30 mg/day (or equivalent) for >30 days or
cumulative dose ≥5 g/year (or equivalent)
For adults <40 years, low, moderate, and very high risk are defined as follows [4,60]:
● Low risk – No moderate- or very high-risk factors other than glucocorticoid treatment
● Moderate risk
• Glucocorticoid dose of prednisone ≥7.5 mg/day (or equivalent) for ≥6 months and
hip or spine Z-score <-3.0 or
• Significant bone loss (bone mineral density [BMD] decline greater than the
instrument-specific least significant change)
● Very high risk – Prior fragility fracture(s) or glucocorticoid dose of prednisone ≥30
mg/day (or equivalent) or cumulative dose ≥5 g/year (or equivalent)
In addition to lifestyle modification and calcium and vitamin D supplementation, the ACR
guidelines recommend osteoporosis pharmacotherapy for adults aged ≥40 years at
moderate, high, or very high risk of major fracture. The guidelines suggest anabolic therapy
with parathyroid hormone (PTH)/parathyroid hormone-related protein (PTHrP) rather than
an antiresorptive agent in adults aged ≥40 years with very high risk of fracture, and they
suggest either denosumab or PTH/PTHrP in those with high fracture risk. In adults aged ≥40
years with moderate fracture risk and those aged <40 years with moderate or very high
fracture risk, the ACR guidelines suggest treatment with either a bisphosphonate (oral or
intravenous [IV]), PTH/PTHrP, or denosumab, without a specified order of preference [4]. For
premenopausal women of childbearing potential, confirm there are no plans for pregnancy
during the period of osteoporosis treatment and that effective contraception is utilized.
The patient should be followed yearly to determine if bone loss continues. An exercise
program should also be initiated, although this may be limited by restrictions from the
underlying illness. (See "Overview of the management of low bone mass and osteoporosis in
postmenopausal women", section on 'Exercise'.)
Other published guidelines largely agree with the recommendations above, except for some
minor differences:
● The National Osteoporosis Guideline Group in the United Kingdom recommends using
FRAX (adjusted for glucocorticoid dose) to determine assessment thresholds
(fracture probabilities for BMD testing) and intervention thresholds (fracture
probabilities for therapeutic intervention) [61,62]. In general, antiresorptive therapy
should be initiated at the time of starting glucocorticoids in patients at highest risk for
fracture (eg, ≥70 years of age, history of prior fragility fracture, or taking large doses of
glucocorticoids [ie, ≥7.5 mg prednisolone/day]). Good nutrition, adequate dietary

calcium intake, and a bisphosphonate are recommended as therapy. Alendronate or

risedronate are the preferred bisphosphonates because of efficacy and low cost.
● The International Osteoporosis Foundation and the European Calcified Tissue Society
recommend osteoporosis therapy in postmenopausal women and men who are ≥70
years, have a previous fragility fracture, or a dose of prednisolone ≥7.5 mg daily (or its
equivalent) for ≥3 months [63,64]. For those at highest risk, bone protective therapy
should be started at the onset of glucocorticoid therapy. For patients who do not meet
these criteria, fracture risk should be assessed using FRAX with intervention
thresholds based upon country-specific population fracture risks and health economic
assessments and corrected for glucocorticoid exposure. For premenopausal women
and men <50 years of age who are taking glucocorticoids for ≥3 months, osteoporosis
therapy is considered for those with a history of a fragility fracture. For all others,
treatment decisions are individualized based upon patient characteristics and clinical
judgement.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Osteoporosis".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Osteoporosis and osteopenia (low bone mass)
(The Basics)" and "Patient education: Calcium and vitamin D for bone health (The
Basics)")

● Beyond the Basics topics (see "Patient education: Osteoporosis prevention and
treatment (Beyond the Basics)" and "Patient education: Calcium and vitamin D for bone
health (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● General measures – In an attempt to minimize bone loss, glucocorticoid dose and the
duration of therapy should be as low and as short as possible, respectively, because
even replacement doses can cause bone loss. Patients should be encouraged to do
weightbearing exercises for protection against both bone loss and muscle atrophy.
Patients should avoid smoking and excess alcohol and take measures to prevent falls.
(See 'General measures' above.)
● Calcium and vitamin D – For all patients receiving any dose of chronic glucocorticoid
therapy or initiating glucocorticoids with an anticipated duration of ≥3 months, we
suggest calcium and vitamin D supplementation (Grade 2B). Most adults require 1000
to 1200 mg of elemental calcium daily, total diet plus supplement, and 800
international units of vitamin D daily ( table 1). (See 'Calcium and vitamin D' above.)
● Candidates for pharmacotherapy
• Postmenopausal women and men aged ≥50 years – For men aged ≥50 years and
postmenopausal women with established osteoporosis (T-score ≤-2.5 or prior
fragility fracture[s]) who are receiving or are about to initiate glucocorticoids (any
dose for any duration), we recommend pharmacologic therapy (Grade 1B). (See
'Postmenopausal women and men aged ≥50 years' above.)
For men aged ≥50 years and postmenopausal women with T-scores between -1.0
and -2.5 who are at moderate or high estimated fracture risk and are initiating or
continuing any dose of glucocorticoids for any duration, we suggest pharmacologic
therapy (Grade 2B). High-dose glucocorticoid treatment (prednisone ≥30 mg/day [or
equivalent] for >1 month) confers high fracture risk, irrespective of other risk
factors, and therefore warrants pharmacotherapy.
A reasonable Fracture Risk Assessment Tool (FRAX)-based threshold to indicate

moderate or higher fracture risk is a 10-year risk of hip or major osteoporotic
fracture >1 and ≥10 percent, respectively. For postmenopausal women and men
aged ≥50 years who have a FRAX-calculated absolute risk below these thresholds,
we suggest pharmacologic therapy if they are taking ≥7.5 mg/day of prednisone or
its equivalent for an anticipated duration of ≥3 months (Grade 2C). (See
'Postmenopausal women and men aged ≥50 years' above.)

• Premenopausal women and younger men – In the absence of definitive data, the
decision to initiate pharmacologic therapy should be individualized in
premenopausal women and younger men through shared decision-making between
patient and clinician. (See 'Premenopausal women and younger men' above and
"Evaluation and treatment of premenopausal osteoporosis", section on 'Secondary
cause identified'.)
- Hypogonadal patients – Glucocorticoids may increase bone resorption by

decreasing secretion of androgens and estrogens, mediated primarily by
inhibition of gonadotropin secretion. Therefore, premenopausal women or men
with confirmed hypogonadism should receive appropriate treatment (provided
no contraindications are present). (See 'Hypogonadal patients' above.)
- Eugonadal patients – For premenopausal women with normal ovarian function

who have a fragility fracture while receiving glucocorticoids or those taking
high-dose glucocorticoid therapy (prednisone ≥30 mg/day for >1 month or
cumulative dose ≥5 g/year [or equivalent]), we suggest pharmacologic therapy
(Grade 2B). For premenopausal women without fragility fracture but with
accelerated bone loss (≥4 percent/year) or Z-score <-3.0 while receiving
glucocorticoids (7.5 mg prednisone equivalent for ≥3 months), we also suggest
pharmacologic therapy (Grade 2C). (See 'Premenopausal women and younger
men' above.)
For men <50 years of age who have a fragility fracture while receiving
glucocorticoids or those taking high-dose glucocorticoid therapy (prednisone
≥30 mg/day for >1 month or cumulative dose ≥5 g/year [or equivalent]), we
suggest pharmacologic therapy (Grade 2B). For men without fragility fracture
but with accelerated bone loss (≥4 percent/year) or Z-score <-3.0 while receiving
glucocorticoids (7.5 mg prednisone equivalent for ≥3 months), we also suggest
pharmacologic therapy (Grade 2C). (See 'Premenopausal women and younger
men' above.)
● Choice of therapy
• Men and postmenopausal women – For men and postmenopausal women who
are candidates for pharmacologic therapy, we suggest bisphosphonates over other
available agents as first-line therapy (Grade 2B). We prefer weekly oral alendronate
or risedronate over other oral bisphosphonates because of clinical trial data
demonstrating efficacy in women and men with glucocorticoid-induced
osteoporosis. Intravenous (IV) zoledronic acid is an option for patients unable to
tolerate oral bisphosphonates or who have difficulty with the dosing requirements

or adherence to oral therapy. (See 'Choice of therapy' above and 'Bisphosphonates'

above.)
Parathyroid hormone (teriparatide, PTH) is generally not used as a first-line drug for
treatment or prevention of glucocorticoid-induced osteoporosis, because of its cost,
subcutaneous route of administration, and the availability of other agents. However,
for the prevention or treatment of glucocorticoid-induced osteoporosis in men or
postmenopausal women with osteoporosis (T-score below -2.5) who are unable to
tolerate any of the available bisphosphonates, we suggest PTH over other available
therapies (Grade 2B). Other candidates for PTH include patients with very high
fracture risk (eg, T-score ≤-3.0, T-score ≤-2.5 plus fragility fracture[s], very high
estimated fracture risk) and patients who fail other osteoporosis therapies (fracture
with loss of bone mineral density [BMD] in spite of compliance with therapy).
Denosumab is also an alternate therapeutic option for those at high risk for
fracture. However, due to the increased risk of vertebral fracture after
discontinuation of denosumab, the need for a careful "exit strategy" if denosumab is
stopped should be discussed with patients prior to its initiation. (See 'Choice of
therapy' above and 'Parathyroid hormone' above and 'Other pharmacologic therapy'
above.)
• Premenopausal women – For premenopausal women of childbearing potential

who are candidates for pharmacologic therapy, we suggest bisphosphonates as
first-line therapy (Grade 2B). Teriparatide is an alternative option for such women,
as long as epiphyses are fully fused. (See 'Bisphosphonates' above and 'Parathyroid
hormone' above and "Evaluation and treatment of premenopausal osteoporosis",
section on 'Choice of therapy'.)
For premenopausal women of childbearing potential, confirm there are no plans for
pregnancy during the period of osteoporosis treatment and that an effective plan
for pregnancy prevention is implemented. It is important to consider the potential
for harm to the fetus in women who become pregnant and are currently receiving
teriparatide or who are currently receiving or were recently treated with
bisphosphonates. (See "Evaluation and treatment of premenopausal osteoporosis",
section on 'Pharmacologic therapy for selected women'.)
● Monitoring – We typically measure BMD at the initiation of glucocorticoid therapy and

after one year. If BMD is stable or improved, we measure BMD less frequently (every
two to three years) thereafter. (See 'Monitoring' above and "Overview of the
management of low bone mass and osteoporosis in postmenopausal women", section
on 'Monitoring response to initial pharmacotherapy'.)

Use of UpToDate is subject to the Terms of Use.
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Topic 2034 Version 31.0

GRAPHICS
Dietary Reference Intakes for calcium and vitamin D
Calcium Vitamin
Estimated Recommen
Life stage Estimated Recommended Upper
average dietary
group average dietary level
requirement allowan
requirement allowance intake
(international (internatio
(mg/day) (mg/day) (mg/day)
units/day) units/da
Infants 0 to 6 * * 1000 ¶ ¶
months
Infants 6 to 12 * * 1500 ¶ ¶
months
1 to 3 years old 500 700 2500 400 600
4 to 8 years old 800 1000 2500 400 600
9 to 13 years old 1100 1300 3000 400 600
14 to 18 years old 1100 1300 3000 400 600
19 to 30 years old 800 1000 2500 400 600
31 to 50 years old 800 1000 2500 400 600
51 to 70 year old 800 1000 2000 400 600

males
51 to 70 year old 1000 1200 2000 400 600

females
>70 years old 1000 1200 2000 400 800
14 to 18 years old, 1100 1300 3000 400 600

pregnant/lactating
19 to 50 years old, 800 1000 2500 400 600

pregnant/lactating
* For infants, adequate intake is 200 mg/day for 0 to 6 months of age and 260 mg/day for 6 to 12
months of age.
¶ For infants, adequate intake is 400 international units/day for 0 to 6 months of age and 400
international units/day for 6 to 12 months of age.
Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Otten JJ, Hellwig JP, Meyers LD (Eds), The National
Academies Press, Washington, DC 2006. pp.530-541. Modified with permission from the National Academies Press, Copyright
© 2006, National Academy of Sciences.

Sources: Dietary reference intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Panthothenic acid, Biotin,
and Choline (1998); Dietary reference intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids (2000); Dietary Reference
Intake reports of the Food and Nutrition Board, Institute of Medicine (2010). These reports may be accessed via www.nap.edu.
Graphic 71669 Version 18.0

Clinical risk factors for fracture independent of bone mineral density
Advancing age
Previous fracture
Glucocorticoid therapy
Parental history of hip fracture
Low body weight
Current cigarette smoking
Excessive alcohol consumption
Rheumatoid arthritis
Secondary osteoporosis (eg, hypogonadism or premature menopause, malabsorption, chronic liver

disease, inflammatory bowel disease)
Data from: Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int 2005; 16:581.

Benefit of alendronate in glucocorticoid-treated patients
Effect of alendronate (5 or 10 mg/day) or placebo on bone mineral density in 477 patients receiving an
average daily dose of at least 7.5 mg of prednisone per day or its equivalent. The mean bone mineral
density of the lumbar spine increased by 2.1 and 2.9 percent over 48 weeks in the patients receiving 5
and 10 mg of alendronate daily, respectively, while decreasing 0.4 percent in the placebo group (top
left panel). Femoral neck, trochanter, and total body bone mineral density also increased significantly
in the alendronate groups.
Data from: Saag KG, Emkey R, Schnitzer TJ, et al. Alendronate for the prevention and treatment of glucocorticoid-induced
osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 1998; 339:292.

Contributor Disclosures
Harold N Rosen, MD No relevant financial relationship(s) with ineligible companies to
disclose. Kenneth G Saag, MD, MSc Grant/Research/Clinical Trial Support: Allena Pharmaceuticals
[Gout, CKD]; Amgen [Osteoporosis]; Arthrosi Therapeutics [Gout]; Dyve Biosciences [Gout]; Horizon
Pharma, PLC [Gout]; LG Chem [Gout]; Radius Health, Inc [Osteoporosis]; Shanton Pharma [Gout];
Swedish Orphan Biovitrum AB [Gout]; Takeda [Osteoporosis]; Ultragenyx [Osteoporosis]. All of the
relevant financial relationships listed have been mitigated. Clifford J Rosen, MD No relevant financial
relationship(s) with ineligible companies to disclose. Katya Rubinow, MD No relevant financial
relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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3/3/24, 23:46 Prevention and treatment of glucocorticoid-induced osteoporosis - UpToDate

Official reprint from UpToDate®

Prevention and treatment of glucocorticoid-induced

Literature review current through: Feb 2024.

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● Topical therapy (such as inhaled glucocorticoids or glucocorticoid enemas for asthma or

● Patients should avoid smoking and excess alcohol.

● Patients should take measures to prevent falls.

CALCIUM AND VITAMIN D

Glucocorticoids induce negative calcium balance by decreasing intestinal calcium

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Although calcium and vitamin D supplementation is necessary, it is generally not

CANDIDATES FOR PHARMACOLOGIC THERAPY

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Glucocorticoid exposure — Glucocorticoid exposure is a critical determinant of fracture

● Interpretation of FRAX – In North America, reasonable glucocorticoid-corrected

• High risk – A 10-year probability of hip or combined major osteoporotic fracture of

• Moderate risk – A 10-year probability of hip or combined major osteoporotic fracture

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• Low risk – A 10-year probability of hip or combined major osteoporotic fracture of ≤1

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Hypogonadal patients — Glucocorticoids may increase bone resorption by decreasing

● Premenopausal women – For premenopausal women of childbearing potential who

https://www.uptodate.com/contents/prevention-and-treatment-of-glucocorticoid-induced-osteoporosis/print?search=major side effects of sistemic… 6/29

hormone therapy in the prevention and treatment of osteoporosis", section on 'Efficacy

● Men – Bisphosphonates are first-line therapy for prevention and treatment of

Eugonadal patients — In the absence of definitive data, pharmacologic therapy should be

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● Premenopausal women – For premenopausal women with fractures or accelerated

We do not typically prescribe denosumab for the prevention or treatment of

https://www.uptodate.com/contents/prevention-and-treatment-of-glucocorticoid-induced-osteoporosis/print?search=major side effects of sistemic… 8/29

The therapeutic efficacy of bisphosphonates in patients with glucocorticoid-induced

● Alendronate – The efficacy of alendronate in patients receiving glucocorticoid therapy

● Risedronate – Risedronate is also effective for the prevention and treatment of

https://www.uptodate.com/contents/prevention-and-treatment-of-glucocorticoid-induced-osteoporosis/print?search=major side effects of sistemic… 9/29

● Other bisphosphonates – Oral and IV pamidronate have been shown to prevent

Parathyroid hormone — Parathyroid hormone (teriparatide, PTH) is generally not used as a

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PTH stimulates bone formation as well as resorption, and intermittent administration

In randomized trials, PTH is effective in improving BMD in patients treated with

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Premenopausal women with glucocorticoid-induced osteoporosis also benefit from

Abaloparatide, a synthetic analog of parathyroid hormone-related protein (PTHrP) has not

Other pharmacologic therapy

● Denosumab – We do not typically prescribe denosumab for the prevention or

Denosumab is a monoclonal antibody to an osteoclast differentiating factor. It inhibits

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In a noninferiority trial evaluating denosumab versus risedronate in 505 patients

● Calcitonin – We do not use calcitonin for the treatment or prevention of glucocorticoid-

● BMD stable or improved – If BMD is stable or improved, we measure it less frequently

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gastrointestinal absorption, inadequate intake of calcium and vitamin D, or the

There may be a significant increase in bone density after discontinuation of exogenous

The American College of Rheumatology (ACR) guidelines recommend intervention based

● Very high risk

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calcium intake, and a bisphosphonate are recommended as therapy. Alendronate or

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