Prevention and Treatment of Glucocorticoid-Induced Osteoporosis

8/27/2016 Prevention and treatment of glucocorticoid-induced osteoporosis
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®
Prevention and treatment of glucocorticoidinduced osteoporosis
Authors Section Editor Deputy Editor

Harold N Rosen, MD Clifford J Rosen, MD Jean E Mulder, MD
Kenneth G Saag, MD, MSc
Contributor disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2016. | This topic last updated: Jun 05, 2015.
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, glucocorticoidinduced bone loss should be treated
aggressively, particularly in those already at high risk for fracture (older, prior fragility fracture). In other individuals, clinical risk factor and bone density assessment may
help guide therapy. The prevention and treatment of glucocorticoidinduced bone loss will be reviewed here. The clinical features are reviewed separately. (See
"Pathogenesis, clinical features, and evaluation of glucocorticoidinduced osteoporosis".)
Many of the prevention and treatment strategies for glucocorticoidinduced bone loss are similar to those used to prevent and treat other causes of osteoporosis. (See
"Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men" and "Evaluation and treatment of premenopausal
osteoporosis".)
GENERAL MEASURES — Prevention and treatment strategies consist of attempts to reverse the glucocorticoid excess by decreasing the dose of exogenous
glucocorticoid or curing the cause of endogenous cortisol overproduction, calcium and vitamin D supplementation, and in some patients, pharmacologic therapy to
minimize further bone loss or reverse it. In an attempt to minimize bone loss, certain general principles should be followed in all patients receiving all doses of
glucocorticoids for a duration of ≥3 months [2,3].
● The glucocorticoid dose and the duration of therapy should be as low as possible, because even what are thought to be replacement doses or chronic inhaled
glucocorticoids can cause bone loss [4]. Alternative therapy should be used whenever possible. (See "Major side effects of inhaled glucocorticoids", section on
'Osteoporosis'.)
● When glucocorticoids are given, 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 be encouraged to 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.
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CALCIUM AND VITAMIN D — We agree with the American College of Rheumatology (ACR) Task Force osteoporosis guidelines, which suggest that patients taking
glucocorticoids (any dose with an anticipated duration of ≥3 months) maintain a total calcium intake of 1200 mg/day and vitamin D intake of 800 international units/day
through either diet and/or supplements [3]. (See "Calcium and vitamin D supplementation in osteoporosis".)
Glucocorticoids induce negative calcium balance by decreasing intestinal calcium absorption and increasing urinary calcium excretion. Therefore, calcium supplementation
may attenuate bone loss in patients taking glucocorticoids [5,6]. In a metaanalysis of five randomized trials comparing calcium and vitamin D (cholecalciferol or an active
vitamin D metabolite) to 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]. Two of the trials reported
the incidence of new, nontraumatic fractures. Although calcium plus vitamin D reduced the incidence of fracture, the results were not statistically significant (odds ratio
[OR] 0.6, 95% CI 0.12.4).
In one of the larger studies included in the metaanalysis, 96 patients with rheumatoid arthritis receiving lowdose 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 0.734.57) and 2.08 percent (95% CI 0.433.73), 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 highdose 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 also been evaluated for the
prevention and treatment of glucocorticoidinduced bone loss [13]. Calcitriol (1,25dihydroxyvitamin D, the most active metabolite of vitamin D) plus calcium protect against
spine bone loss more than calcium alone in patients taking glucocorticoids [10,14]. A metaanalysis 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 [15]. There was 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 [10,1618]. (See 'Bisphosphonates versus active D metabolites' below.)
CANDIDATES FOR PHARMACOLOGIC THERAPY — Patients with the highest risk for fracture are the ones most likely to benefit from drug therapy. Thus, selection of
patients based upon fracture risk, as determined by a combination of bone mineral density (BMD) and clinical risk factors, is desirable. For patients without established
osteoporosis (history of fragility fracture or BMD Tscore ≤2.5), fracture risk can be assessed using the World health Organization Fracture Risk Assessment Tool (FRAX).
FRAX estimates the 10year probability of fracture for untreated postmenopausal women and men ≥50 years, using femoral neck BMD and clinical risk factors, including
glucocorticoid exposure. In the United States, a reasonable cut point to indicate high risk is a 10year probability of hip or combined major osteoporotic fracture of ≥3 and
20 percent, respectively. 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'.)
Our approach described below is largely in agreement with various guidelines, which collectively suggest pharmacologic therapy for patients based upon assessment of
BMD and clinical risk factors for fracture (see 'Guidelines' below). However, some patients receiving glucocorticoids are at highrisk, even if they fail to meet the FRAX
criteria for intervention. 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. In addition, FRAX does not account for glucocorticoid dose or duration. Thus, intervention guidelines with or without the use of FRAX provide
only general clinical guidance. Treatment should remain individualized through shared decisionmaking between patient and clinician.
Osteoporosis prevention
● For the treatment of highrisk men ≥50 years and postmenopausal women who are initiating or are chronically treated with any dose of glucocorticoids for any
duration and have Tscores between 1.0 and 2.5, we suggest pharmacologic therapy.
● A reasonable cut point to indicate high risk that may be costeffective in some settings is a FRAX calculated 10year probability of hip or combined major osteoporotic
fracture of ≥3 or 20 percent, respectively.
● For postmenopausal women and men >50 years who have a FRAX calculated absolute risk below these cut points, we suggest pharmacologic therapy if they are
taking ≥7.5 mg/day of prednisone or its equivalent for an anticipated duration of ≥3 months.
Established osteoporosis
● For men ≥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 Tscore ≤2.5) at initial assessment, we recommend pharmacologic therapy.
This recommendation is based upon randomized trial data showing that pharmacologic therapy improves BMD in patients taking glucocorticoids [19,20] and additional
randomized trial data showing that pharmacologic therapy reduces fracture in men and postmenopausal women with osteoporosis [21]. Such patients should receive
treatment for osteoporosis even in the absence of glucocorticoid treatment. (See "Overview of the management of osteoporosis in postmenopausal women" and "The use
of bisphosphonates in postmenopausal women with osteoporosis" and "Treatment of osteoporosis in men".)
Premenopausal women and younger men — The FRAX tool was not developed for use in premenopausal women or men <40 years. In premenopausal women and
younger men included in clinical trials for glucocorticoidinduced osteoporosis (GIO), fractures were generally infrequent in both treated and control groups [12,22,23].
Fracture risk in these patients taking glucocorticoids is not clearly defined and may differ from reported fracture risk in other glucocorticoidtreated populations. In the
absence of definitive data, pharmacologic therapy needs to be individualized in premenopausal women and younger men. Potential short and longterm 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
"Epidemiology and etiology of premenopausal osteoporosis" and "Evaluation and treatment of premenopausal osteoporosis" and "Treatment of osteoporosis in men".)
● We recommend pharmacologic therapy for women with fragility fractures while receiving glucocorticoids (7.5 mg prednisone equivalent for ≥3 months) who do not
need estrogen replacement therapy because they have normal menstrual function.
● For similar women who do not have a fragility fracture but have accelerated bone loss (≥4 percent/year) while receiving glucocorticoids, we also suggest
pharmacologic therapy.
● For men <50 years of age who have a fragility fracture while receiving glucocorticoids (7.5 mg prednisone equivalent for ≥3 months), we recommend pharmacologic
therapy.
● For similar men who do not have a fragility fracture but have accelerated bone loss (≥4 percent/year), we also suggest pharmacologic therapy.
CHOICE OF THERAPY
● Men and postmenopausal women – For pharmacologic therapy for men and postmenopausal women, we favor bisphosphonates as firstline therapy. We prefer
alendronate or risedronate because of clinical trial data demonstrating efficacy in men and women with glucocorticoidinduced osteoporosis (GIO).
For such patients who cannot tolerate oral bisphosphonates or who have difficulty with the dosing requirements, intravenous (IV) zoledronic acid is an acceptable
alternative. We typically reserve parathyroid hormone (teriparatide, PTH) for patients with severe osteoporosis (Tscore of 3.5 or below even in the absence of
fractures or a Tscore of 2.5 or below plus a fragility fracture). 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.
● Premenopausal women – For premenopausal women with fractures or accelerated bone loss who do not need estrogen replacement therapy because they have
normal ovarian function, bisphosphonates are generally the drugs of choice. Teriparatide is an alternative option for such women, as long as epiphyses are fully fused.
Potential short and longterm 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 'Glucocorticoids'.)
BISPHOSPHONATES — For postmenopausal women and men, bisphosphonates, and in particular alendronate or risedronate, are the firstline drugs for the prevention
and treatment of glucocorticoidinduced bone loss. For patients who cannot tolerate or have difficulty with the dosing requirements of oral bisphosphonates, intravenous
(IV) zoledronic acid is an alternative.
There are substantial data supporting the use of antiresorptive agents, such as the bisphosphonates, for the prevention and treatment of glucocorticoidinduced bone loss.
In a metaanalysis of 13 randomized trials evaluating bisphosphonates for the prevention and treatment of glucocorticoidinduced osteoporosis (GIO), there was significant
improvement in lumbar spine (weighted mean difference 4.3 percent) and femoral neck bone mineral density (BMD) (weighed mean difference 2.1 percent) between the
treatment and placebo groups. The reduction in risk of vertebral fracture was not significant (odds ratio [OR] 0.76, 95% CI 0.371.53) [19].
Studies demonstrating the benefits of bisphosphonates in the prevention and treatment of GIO included some premenopausal women. In premenopausal women included
in clinical trials for GIO, fractures were generally infrequent in both treated and control groups [12,22,23]. However, bisphosphonates are an option for premenopausal
women with fragility fractures or accelerated bone loss (≥4 percent/year), while receiving glucocorticoids (7.5 mg prednisone equivalent for ≥3 months), who do not need
estrogen replacement therapy because they have normal menstrual function. Bisphosphonates should be used with caution in premenopausal women given their long
skeletal retention. There is insufficient information on the potential for harm to the fetus in women who become pregnant while currently or recently receiving
bisphosphonates. (See "Evaluation and treatment of premenopausal osteoporosis", section on 'Bisphosphonates' and "Evaluation and treatment of premenopausal
osteoporosis", section on 'Glucocorticoids'.)
The therapeutic efficacy of bisphosphonates in patients with GIO has been thought to be related to their ability to promote osteoclast apoptosis (programmed cell death)
[24]. However, glucocorticoids may negate the proapoptotic effect of bisphosphonates, suggesting that these drugs may prevent glucocorticoidinduced bone loss by
prolonging the lifespan of osteoblasts [25].
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 [26]. Once weekly alendronate (70 mg) similarly improves BMD [27].
Risedronate — Risedronate is also effective for the prevention and treatment of osteoporosis, including GIO [11,28,29]. In a oneyear randomized trial of risedronate
versus placebo for the prevention of osteoporosis in 224 men and women who were beginning chronic glucocorticoid therapy, BMD of the lumbar spine was unchanged in
the risedronate treated groups, while it decreased by 2.8 percent in the placebo group (p<0.05) [11].
In another oneyear 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 [28]. 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 GIO was demonstrated in a oneyear randomized trial of IV zoledronic acid (5 mg
once) or daily oral risedronate (5 mg) in 288 subjects who recently started glucocorticoids (prevention group) and 545 patients who had been taking them for more than
three months (treatment group) [30]. In an analysis of subjects who received the study drug and had baseline and followup 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 flulike symptoms) was greater in the ZA 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 glucocorticoidinduced bone loss [9,3133]. 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 GIO. 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 alfacalcidiol (1 mcg daily) in 104 patients with established GIO, IV ibandronate resulted
in superior improvements in spine, femoral neck, and calcaneal BMD compared with alfacalcidiol (between group differences of 9.7, 3.4, and 7.9 percent, respectively) [34].
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 alfacalcidiol group (8.6 versus 22.8 percent) [35].
Bisphosphonates versus active D metabolites — The superior efficacy of bisphosphonates compared with an active vitamin D metabolite among patients receiving
glucocorticoid therapy has been demonstrated in several randomized trials [17,18,3437]. Although not statistically significant, one trial showed that compared with
alfacalcidiol, fewer patients randomly assigned to alendronate had new vertebral fractures (three versus eight patients) [18].
PARATHYROID HORMONE — Parathyroid hormone (teriparatide, PTH) is generally not used as a firstline drug for treatment or prevention of glucocorticoidinduced
osteoporosis (GIO) because of its cost, subcutaneous route of administration, and the availability of other agents. However, we suggest PTH for the treatment of GIO in
men or postmenopausal women who:
● Have severe osteoporosis (Tscore of 3.5 or below even in the absence of fractures; Tscore of 2.5 or below plus a fragility fracture) before initiating glucocorticoids.
● Have osteoporosis (Tscore below 2.5) who are unable to tolerate oral or intravenous (IV) bisphosphonates, or who have relative contraindications to
bisphosphonates (achalasia, scleroderma esophagus, esophageal strictures).
● Fail other osteoporosis therapies (fracture with loss of bone mineral density [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 estrogen replacement therapy because they have normal menstrual function.
Teriparatide is not recommended for more than two years based upon the potential risk of carcinogenicity. 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.
PTH stimulates bone formation as well as resorption, and intermittent administration stimulates formation more than resorption. Initial studies show that it is beneficial in
patients with osteoporosis (see "Parathyroid hormone therapy for osteoporosis"). 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 [38].
In randomized trials, PTH is effective in improving BMD in patients treated with glucocorticoids [20,3941]. As an example, in an 18month randomized trial of alendronate
(10 mg orally daily) versus PTH 134 (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 [20].
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 group discontinued the study
prior to completion. There was more nausea and insomnia in the teriparatide group and more rashes in the alendronate group.
In a secondary analysis by gender and menopausal status, 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 [22]. In premenopausal women, fractures were infrequent in both treatment groups. (See
"Evaluation and treatment of premenopausal osteoporosis", section on 'Glucocorticoids'.)
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
[39]. 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.
HORMONE REPLACEMENT — Glucocorticoids reduce the production of sex steroids [42]. As a result, it is logical to replace these hormones in women with amenorrhea
and hypoestrogenism (due to hypothalamic amenorrhea or primary ovarian insufficiency) or in men with confirmed hypogonadism. (See "Evaluation and management of
secondary amenorrhea" and "Management of spontaneous primary ovarian insufficiency (premature ovarian failure)" and "Testosterone treatment of male hypogonadism".)
● Premenopausal women – For premenopausal women of childbearing potential taking or initiating glucocorticoids who are hypogonadal, we suggest
estrogen/progestin replacement (eg, oral contraceptives), if not contraindicated. There is no reason to believe, however, that treatment with estrogens will benefit
young women with normal ovarian function. (See "Overview of the use of estrogenprogestin contraceptives", section on 'Contraindications'.)
In a crosssectional study of 119 perimenopausal women with asthma (65 receiving oral glucocorticoids), the asthmatic women who were not taking hormone
replacement therapy had lower mean bone mineral density (BMD) than did nonasthmatics [43]. This observation plus the extensive literature supporting the value of
estrogen in the prevention of postmenopausal osteoporosis makes it likely that estrogen therapy can help reduce or reverse bone loss in premenopausal
hypoestrogenic women treated with glucocorticoids.
● Men – Bisphosphonates are first line therapy for prevention and treatment of glucocorticoidinduced osteoporosis (GIO) in men because they are known to reduce
fracture risk. Such men who develop symptomatic hypogonadism, however, should also be treated with testosterone for its benefits on muscle, energy, and libido, as
well as on bone. (See "Treatment of osteoporosis in men", section on 'Testosterone therapy' and "Testosterone treatment of male hypogonadism", section on 'Bone
density'.)
A crossover study of 15 men with glucocorticoiddependent asthma and low baseline serum testosterone concentrations found that monthly intramuscular
administration of 250 mg testosterone reversed the deleterious effect of glucocorticoids on bone [44]. Bone density in the lumbar spine increased 5.0 percent during
testosterone therapy, compared with no change during the control period. In addition, a randomized, placebocontrolled trial of testosterone in unselected men taking
glucocorticoids described an increase in spine BMD, fat mass, and muscle strength in the testosterone versus placebo group [45].
● Postmenopausal women – Clinical trials in postmenopausal women have shown that longterm use of combined oral estrogenprogestin therapy does not reduce
the risk of coronary heart disease as was expected based on observational studies [46]. In addition, combination therapy increased the risk of breast cancer, stroke,
and venous thromboembolism. Thus, estrogen is no longer considered a firstline drug for prevention of postmenopausal osteoporosis. (See "Menopausal hormone
therapy: Benefits and risks".)
OTHER
Calcitonin — We do not use calcitonin for the treatment or prevention of glucocorticoidinduced osteoporosis (GIO) 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 longterm 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'.)
Lumbar spine bone loss is attenuated with subcutaneous or intranasal calcitonin [47,48]. However, calcitonin has not been found to reduce the risk of fractures in
glucocorticoidtreated patients. A metaanalysis of nine trials comparing calcitonin to placebo for the treatment of these patients reported no efficacy of calcitonin on femoral
neck bone mineral density (BMD) or on vertebral or nonvertebral fractures [49].
Denosumab — Until additional data are available, we do not recommend denosumab for the prevention or treatment of GIO.
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 mouse model of GIO, denosumab compared with placebo prevented bone loss [50]. In a posthoc analysis of BMD results from a randomized trial of denosumab
versus placebo in patients with rheumatoid arthritis (some receiving glucocorticoids), denosumab significantly increased mean lumbar spine and total hip BMD [51].
Effect of cessation of glucocorticoid therapy — There may be a significant increase in bone density after discontinuation of exogenous glucocorticoid therapy or
reversal of endogenous Cushing's syndrome [52,53]. One study, as an example, examined spine BMD after successful treatment for Cushing's disease in 20 patients, all of
whom had marked osteoporosis of lumbar spine and femoral neck [52]. 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.
MONITORING — There are several published guidelines for monitoring the response to osteoporosis therapy (see "Overview of the management of osteoporosis in
postmenopausal women", section on 'Monitoring'). Although all recommend followup bone mineral density (BMD) testing, there is no consensus on the optimal frequency
of monitoring and the preferred site to monitor. We typically measure BMD (dual energy xray absorptiometry [DXA]) of the lumbar spine and hip at the initiation of
glucocorticoid therapy and after one year. 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.
GUIDELINES — The American College of Rheumatology (ACR) guidelines recommend intervention based upon risk of fracture (high, medium, low), guided in part by the
World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) or by ACRprovided examples of low, medium, and highrisk patients [3,54]. Low risk is defined
by a 10year risk of a major osteoporotic fracture of 10 percent or less, medium risk 10 to 20 percent, and high risk >20 percent or a Tscore below 2.5 [3]. 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
'Candidates for therapy' and "Overview of the management of osteoporosis in postmenopausal women", section on 'Candidates for therapy'.)
In addition to calcium and vitamin D supplementation, the ACR guidelines recommend bisphosphonates for prevention of bone loss and fractures in postmenopausal
women and men ≥50 years receiving or initiating glucocorticoids with an anticipated duration of ≥3 months.
● For lowrisk patients, bisphosphonates (alendronate, risedronate, or zoledronic acid) are recommended if the prednisone dose is ≥7.5 mg/day.
● For mediumrisk patients, alendronate or risedronate is recommended for any dose of glucocorticoids, and zoledronic acid is an option for patients receiving ≥7.5
mg/day of prednisone.
● For highrisk patients, bisphosphonates are recommended for any dose and duration of glucocorticoids. Teriparatide is an option for high risk patients taking ≥5
mg/day of prednisone with anticipated duration of ≤1 month and for any dose of glucocorticoids with a duration of >1 month [3].
● For atrisk (previous fragility fracture) men <50 years and premenopausal women who do not have childbearing potential, bisphosphonates (alendronate, risedronate)
are recommended for those taking ≥5 mg of prednisone daily for more than one month. Zoledronic acid is an option for patients receiving prednisone ≥7.5 mg daily,
and zoledronic acid and teriparatide are options for patients receiving glucocorticoids for more than three months.
● The ACR provides separate therapeutic guidelines for premenopausal women of childbearing potential [3]. For high risk premenopausal women (eg, previous fragility
fracture), bisphosphonates are recommended only for those women taking ≥7.5 mg daily of glucocorticoids for more than three months. Teriparatide is an alternative
option for such women. For women taking <7.5 mg of prednisone daily or taking glucocorticoids for one to three months, the ACR panel could not reach a consensus.
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 osteoporosis in postmenopausal women", section on 'Exercise'.)
Other published guidelines largely agree with the recommendations above, except for some minor differences:
● The Royal College of Physicians recommends beginning antiresorptive therapy at the time of starting glucocorticoids in patients at high risk for fracture (eg, ≥65 years
of age, history of prior fragility fracture) [55] (see "Osteoporotic fracture risk assessment"). Bone density testing should be considered in other individuals who will be
receiving glucocorticoids for ≥3 months, and therapy considered for those with a Tscore of ≤1.5 or with a reduction of BMD >4 percent after one year. Good nutrition,
adequate dietary calcium intake, and a bisphosphonate are recommended as therapy. Alendronate, risedronate, or etidronate are its preferred bisphosphonates
because a reduction in vertebral fracture has been noted in secondary analyses.
● 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 [56]. For those at highest risk, bone protective
therapy should be started at the onset of glucocorticoid therapy. For patients who don’t meet these criteria, fracture risk should be assessed using FRAX with
intervention thresholds based upon countryspecific population fracture risks and health economic assessments. 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.
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SUMMARY AND RECOMMENDATIONS
● Glucocorticoid dose and the duration of therapy should be as low and as short as possible, 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.)
● For all patients receiving any dose of chronic glucocorticoid therapy or initiating glucocorticoids with an anticipated duration of ≥3 months, we recommend calcium and
vitamin D supplementation (Grade 1B). Most individuals require 1200 mg of elemental calcium daily, total diet plus supplement, and 800 international units of vitamin
D daily. (See 'Calcium and vitamin D' above.)
● For men ≥50 years and postmenopausal women with established osteoporosis (Tscore ≤2.5 or fragility fracture) who are receiving or are about to initiate
glucocorticoids (any dose for any duration), we recommend pharmacologic therapy (Grade 1A). (See 'Established osteoporosis' above.)
● For the treatment of high risk men ≥50 years and postmenopausal women (who are initiating or are treated with any dose of glucocorticoids for any duration) who
have Tscores between 1.0 and 2.5, we suggest pharmacologic therapy (Grade 2B). A reasonable cut point to indicate high risk that may be costeffective in some
settings is a Fracture Risk Assessment Tool (FRAX) calculated 10year probability of hip or combined major osteoporotic fracture of ≥3 or 20 percent, respectively. For
postmenopausal women and men >50 years who have a FRAX calculated absolute risk below these cut points, 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 'Osteoporosis prevention' above.)
● For premenopausal women who do not need estrogen replacement therapy because they have normal ovarian function, who have a fragility fracture while receiving
glucocorticoids (7.5 mg prednisone equivalent for ≥3 months), and who do not have contraindications to bisphosphonates or teriparatide, we recommend
pharmacologic therapy (Grade 1B). For similar women who do not have a fragility fracture but have accelerated bone loss (≥4 percent/year) while receiving
glucocorticoids, 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 (7.5 mg prednisone equivalent for ≥3 months), we recommend pharmacologic
therapy (Grade 1B). For similar men who do not have a fragility fracture but have accelerated bone loss (≥4 percent/year), we also suggest pharmacologic therapy
(Grade 2C). (See 'Premenopausal women and younger men' above.)
● For men and postmenopausal women, we suggest bisphosphonates 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 glucocorticoidinduced osteoporosis (GIO). Intravenous (IV) zoledronic
acid is an option for patients unable to tolerate oral bisphosphonates or who have difficulty with the dosing requirements. (See 'Bisphosphonates' above.)
● Parathyroid hormone (teriparatide, PTH) is generally not used as a firstline drug for treatment or prevention of GIO because of its cost, subcutaneous route of
administration, and the availability of other agents. However, for the prevention or treatment of GIO in men or postmenopausal women with osteoporosis (Tscore
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 severe osteoporosis (Tscore of 3.5 or below even in the absence of fractures or a Tscore of 2.5 or below plus a fragility fracture) and patients
who fail other osteoporosis therapies (fracture with loss of bone mineral density [BMD] in spite of compliance with therapy). (See 'Parathyroid hormone' above.)
● For premenopausal women of childbearing potential taking or initiating glucocorticoids, who are hypogonadal, we suggest estrogen/progestin replacement if not
contraindicated (Grade 2B). (See 'Hormone replacement' above and "Evaluation and treatment of premenopausal osteoporosis", section on 'Estrogen' and "Overview
of the use of estrogenprogestin contraceptives", section on 'Contraindications' and "Evaluation and treatment of premenopausal osteoporosis", section on
'Glucocorticoids'.)
● For premenopausal women of childbearing potential taking or initiating glucocorticoids (7.5 mg prednisone equivalent for ≥3 months), who do not need estrogen
replacement therapy because they have normal menstrual function, and who have a fragility fracture or accelerated bone loss (≥4 percent/year), we suggest
bisphosphonates (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 'Glucocorticoids'.)
We recommend caution when considering bisphosphonates or teriparatide in premenopausal women. 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 therapies'.)
Although estrogen replacement therapy prevents bone loss in postmenopausal women receiving glucocorticoid therapy, estrogenprogestin therapy is no longer a
firstline approach for the prevention or treatment of osteoporosis in postmenopausal women because of increased risk of breast cancer, stroke, venous
thromboembolism, and coronary disease. (See "Menopausal hormone therapy: Benefits and risks".)
● For symptomatic hypogonadal men who do not have contraindications to testosterone therapy, we recommend replacement of testosterone (Grade 1B). For
asymptomatic hypogonadal men taking highdose glucocorticoids, testosterone can also be considered for its potential benefits on muscle, energy, and libido. (See
'Hormone replacement' above and "Testosterone treatment of male hypogonadism", section on 'General principles'.)
● 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 osteoporosis in postmenopausal women", section on 'Monitoring'.)
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REFERENCES
1. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroidinduced osteoporosis: a metaanalysis. Osteoporos Int 2002; 13:777.
2. Heffernan MP, Saag KG, Robinson JK, Callen JP. Prevention of osteoporosis associated with chronic glucocorticoid therapy. JAMA 2006; 295:1300.
3. Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid
induced osteoporosis. Arthritis Care Res (Hoboken) 2010; 62:1515.
4. Zelissen PM, Croughs RJ, van Rijk PP, Raymakers JA. Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann
Intern Med 1994; 120:207.
5. Reid DM, Nicoll JJ, Smith MA, et al. Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica. Br Med J (Clin
Res Ed) 1986; 293:1463.
6. Wang WQ, Ip MS, Tsang KW, Lam KS. Antiresorptive therapy in asthmatic patients receiving highdose inhaled steroids: a prospective study for 18 months. J Allergy
Clin Immunol 1998; 101:445.
7. Homik J, SuarezAlmazor ME, Shea B, et al. Calcium and vitamin D for corticosteroidinduced osteoporosis. Cochrane Database Syst Rev 2000; :CD000952.
8. Buckley LM, Leib ES, Cartularo KS, et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to lowdose corticosteroids in patients
with rheumatoid arthritis. A randomized, doubleblind, placebocontrolled trial. Ann Intern Med 1996; 125:961.
9. Boutsen Y, Jamart J, Esselinckx W, Devogelaer JP. Primary prevention of glucocorticoidinduced osteoporosis with intravenous pamidronate and calcium: a
prospective controlled 1year study comparing a single infusion, an infusion given once every 3 months, and calcium alone. J Bone Miner Res 2001; 16:104.
10. Sambrook P, Birmingham J, Kelly P, et al. Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin. N Engl J Med 1993; 328:1747.
11. Cohen S, Levy RM, Keller M, et al. Risedronate therapy prevents corticosteroidinduced bone loss: a twelvemonth, multicenter, randomized, doubleblind, placebo
controlled, parallelgroup study. Arthritis Rheum 1999; 42:2309.
12. Saag KG, Emkey R, Schnitzer TJ, et al. Alendronate for the prevention and treatment of glucocorticoidinduced osteoporosis. GlucocorticoidInduced Osteoporosis
Intervention Study Group. N Engl J Med 1998; 339:292.
13. Recommendations for the prevention and treatment of glucocorticoidinduced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on
GlucocorticoidInduced Osteoporosis. Arthritis Rheum 2001; 44:1496.
14. Lukert BP, Raisz LG. Glucocorticoidinduced osteoporosis: pathogenesis and management. Ann Intern Med 1990; 112:352.
15. Richy F, Ethgen O, Bruyere O, Reginster JY. Efficacy of alphacalcidol and calcitriol in primary and corticosteroidinduced osteoporosis: a metaanalysis of their effects
on bone mineral density and fracture rate. Osteoporos Int 2004; 15:301.
16. Suzuki Y, Ichikawa Y, Saito E, Homma M. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under
glucocorticoid therapy. Metabolism 1983; 32:151.
17. Sambrook PN, Kotowicz M, Nash P, et al. Prevention and treatment of glucocorticoidinduced osteoporosis: a comparison of calcitriol, vitamin D plus calcium, and
alendronate plus calcium. J Bone Miner Res 2003; 18:919.
18. de Nijs RN, Jacobs JW, Lems WF, et al. Alendronate or alfacalcidol in glucocorticoidinduced osteoporosis. N Engl J Med 2006; 355:675.
19. Homik J, Cranney A, Shea B, et al. Bisphosphonates for steroid induced osteoporosis. Cochrane Database Syst Rev 2000; :CD001347.
20. Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in glucocorticoidinduced osteoporosis. N Engl J Med 2007; 357:2028.
21. MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone
density or osteoporosis. Ann Intern Med 2008; 148:197.
22. Langdahl BL, Marin F, Shane E, et al. Teriparatide versus alendronate for treating glucocorticoidinduced osteoporosis: an analysis by gender and menopausal
status. Osteoporos Int 2009; 20:2095.
23. Adachi JD, Bensen WG, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroidinduced osteoporosis. N Engl J Med 1997; 337:382.
24. Plotkin LI, Weinstein RS, Parfitt AM, et al. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 1999; 104:1363.
25. Weinstein RS, Chen JR, Powers CC, et al. Promotion of osteoclast survival and antagonism of bisphosphonateinduced osteoclast apoptosis by glucocorticoids. J
Clin Invest 2002; 109:1041.
26. Adachi JD, Saag KG, Delmas PD, et al. Twoyear effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a
randomized, doubleblind, placebocontrolled extension trial. Arthritis Rheum 2001; 44:202.
27. Stoch SA, Saag KG, Greenwald M, et al. Onceweekly oral alendronate 70 mg in patients with glucocorticoidinduced bone loss: a 12month randomized, placebo
controlled clinical trial. J Rheumatol 2009; 36:1705.
28. Reid DM, Hughes RA, Laan RF, et al. Efficacy and safety of daily risedronate in the treatment of corticosteroidinduced osteoporosis in men and women: a
randomized trial. European CorticosteroidInduced Osteoporosis Treatment Study. J Bone Miner Res 2000; 15:1006.
29. Eastell R, Devogelaer JP, Peel NF, et al. Prevention of bone loss with risedronate in glucocorticoidtreated rheumatoid arthritis patients. Osteoporos Int 2000; 11:331.
30. Reid DM, Devogelaer JP, Saag K, et al. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoidinduced osteoporosis (HORIZON): a
multicentre, doubleblind, doubledummy, randomised controlled trial. Lancet 2009; 373:1253.
31. Reid IR, King AR, Alexander CJ, Ibbertson HK. Prevention of steroidinduced osteoporosis with (3amino1hydroxypropylidene)1,1bisphosphonate (APD). Lancet
1988; 1:143.
32. Reid IR, Heap SW, King AR, Ibbertson HK. Twoyear followup of biphosphonate (APD) treatment in steroid osteoporosis. Lancet 1988; 2:1144.
33. Gallacher SJ, Fenner JA, Anderson K, et al. Intravenous pamidronate in the treatment of osteoporosis associated with corticosteroid dependent lung disease: an
open pilot study. Thorax 1992; 47:932.
34. Ringe JD, Dorst A, Faber H, et al. Threemonthly ibandronate bolus injection offers favourable tolerability and sustained efficacy advantage over two years in
established corticosteroidinduced osteoporosis. Rheumatology (Oxford) 2003; 42:743.
35. Ringe JD, Dorst A, Faber H, et al. Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroidinduced osteoporosis: results from a
longterm comparative study. Osteoporos Int 2003; 14:801.
36. Kikuchi Y, Imakiire T, Yamada M, et al. Effect of risedronate on highdose corticosteroidinduced bone loss in patients with glomerular disease. Nephrol Dial
Transplant 2007; 22:1593.
37. Fujii N, Hamano T, Mikami S, et al. Risedronate, an effective treatment for glucocorticoidinduced bone loss in CKD patients with or without concomitant active
vitamin D (PRIUSCKD). Nephrol Dial Transplant 2007; 22:1601.
38. Carpinteri R, Porcelli T, Mejia C, et al. Glucocorticoidinduced osteoporosis and parathyroid hormone. J Endocrinol Invest 2010; 33:16.
39. Saag KG, Zanchetta JR, Devogelaer JP, et al. Effects of teriparatide versus alendronate for treating glucocorticoidinduced osteoporosis: thirtysixmonth results of a
randomized, doubleblind, controlled trial. Arthritis Rheum 2009; 60:3346.
40. Lane NE, Sanchez S, Modin GW, et al. Parathyroid hormone treatment can reverse corticosteroidinduced osteoporosis. Results of a randomized controlled clinical
trial. J Clin Invest 1998; 102:1627.
41. Glüer CC, Marin F, Ringe JD, et al. Comparative effects of teriparatide and risedronate in glucocorticoidinduced osteoporosis in men: 18month results of the
EuroGIOPs trial. J Bone Miner Res 2013; 28:1355.
42. MacAdams MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med 1986; 104:648.
43. Laatikainen AK, Kröger HP, Tukiainen HO, et al. Bone mineral density in perimenopausal women with asthma: a populationbased crosssectional study. Am J Respir
Crit Care Med 1999; 159:1179.
44. Reid IR, Wattie DJ, Evans MC, Stapleton JP. Testosterone therapy in glucocorticoidtreated men. Arch Intern Med 1996; 156:1173.
45. Crawford BA, Liu PY, Kean MT, et al. Randomized placebocontrolled trial of androgen effects on muscle and bone in men requiring longterm systemic glucocorticoid
treatment. J Clin Endocrinol Metab 2003; 88:3167.
46. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's
Health Initiative randomized controlled trial. JAMA 2002; 288:321.
47. Luengo M, Pons F, Martinez de Osaba MJ, Picado C. Prevention of further bone mass loss by nasal calcitonin in patients on long term glucocorticoid therapy for
asthma: a two year follow up study. Thorax 1994; 49:1099.
48. Montemurro L, Schiraldi G, Fraioli P, et al. Prevention of corticosteroidinduced osteoporosis with salmon calcitonin in sarcoid patients. Calcif Tissue Int 1991; 49:71.
49. Cranney, A, Welch, V, Adachi, J, et al. Calcitonin for preventing and treating corticosteroidinduced osteoporosis. Cochrane Database of Systematic Reviews 2000;
CD001983.
50. Hofbauer LC, Zeitz U, Schoppet M, et al. Prevention of glucocorticoidinduced bone loss in mice by inhibition of RANKL. Arthritis Rheum 2009; 60:1427.
51. Dore RK, Cohen SB, Lane NE, et al. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent
glucocorticoids or bisphosphonates. Ann Rheum Dis 2010; 69:872.
52. Hermus AR, Smals AG, Swinkels LM, et al. Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome. J Clin Endocrinol Metab
1995; 80:2859.
53. Pocock NA, Eisman JA, Dunstan CR, et al. Recovery from steroidinduced osteoporosis. Ann Intern Med 1987; 107:319.
54. http://mail3.rheumatology.org/practice/clinical/guidelines/ACR_2010_GIOP_Recomm_Clinicians_Guide.pdf (Accessed on January 14, 2011).
55. Royal College of Physicians, 2002 Glucocorticoidinduced osteoporosis: A concise guide to prevention and treatment.
http://bookshop.rcplondon.ac.uk/contents/pub8964206b70b14749769ee1bf4948458468.pdf (Accessed on May 06, 2013).
56. Lekamwasam S, Adachi JD, Agnusdei D, et al. A framework for the development of guidelines for the management of glucocorticoidinduced osteoporosis.
Osteoporos Int 2012; 23:2257.
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