0
Original Investigation |

Suggested Guidelines for Evaluation and Treatment of Glucocorticoid-Induced Osteoporosis for the Department of Veterans Affairs FREE

Robert A. Adler, MD; Marc C. Hochberg, MD, MPH
[+] Author Affiliations

From the Endocrinology Section, McGuire Veterans Affairs Medical Center, and Departments of Internal Medicine and Preventive Medicine and Community Health, Medical College of Virginia of Virginia Commonwealth University, Richmond (Dr Adler); and Departments of Medicine and Epidemiology and Preventive Medicine, University of Maryland School of Medicine, and Department of Medicine, Maryland Veterans Affairs Health Care System, Baltimore (Dr Hochberg). Dr Adler has served on the speakers bureau of or received honoraria from Merck & Co, Procter & Gamble, and Eli Lilly Inc. Dr Hochberg has served as consultant to Aai Laboratories, Abbott Laboratories, Aventis Pharmaceutical Co Inc, Bristol Myers Squibb, Eli Lilly Inc, Genzyme Corporation, La Jolla Pharmaceutical Co, Laboratories NEGMA, Merck & Co, Novartis, Sanofi-Synthelabo, Scios Inc, and Wyeth Ayerst, and is a stock shareholder in Johnson & Johnson, Eli Lilly Inc, Merck & Co, Procter & Gamble, and Schering Plough.


Arch Intern Med. 2003;163(21):2619-2624. doi:10.1001/archinte.163.21.2619.
Text Size: A A A
Published online

Background  Glucocorticoid-induced osteoporosis is an important disorder in the predominantly male US veteran population. Department of Veterans Affairs facilities vary considerably in evaluation and management of glucocorticoid-induced osteoporosis.

Methods  We suggest how evaluation and management can take place in medical centers with and without bone mineral density measurements by dual energy x-ray absorptiometry (DXA). The proposed guidelines can be applied to other health care systems.

Results  Use of DXA can help determine fracture risk for patients taking glucocorticoid therapy and for those starting therapy for at least 3 months. Patients with low bone mineral density should be treated with a bisphosponate as should all patients about to start prednisone treatment at a dose of 7.5 mg/d or more. In facilities without DXA, most patients should be treated with bisphosphonates, the cost of which is about $30 to $35 per month. In addition, the use of urinary calcium measurements is encouraged to determine which patients might benefit from augmented vitamin D and calcium supplementation.

Conclusion  Attention to fracture risk assessment in patients undergoing glucocorticoid therapy and timely bisphosphonate treatment should lead to fewer fractures.

GLUCOCORTICOIDS are commonly prescribed for inflammatory diseases such as rheumatoid arthritis and asthma, and for decreasing the inflammatory component of chronic obstructive pulmonary disease. Although glucocorticoid therapy saves lives, important side effects are frequent, particularly with extended treatment. One important adverse effect is bone loss, which significantly increases fracture risk.1,2 Fracture of the spine may further worsen respiratory function,3 and hip fracture is associated with strikingly increased mortality and morbidity, particularly in men.4

Studies5 have shown that there is great variability in providers' knowledge about glucocorticoid-induced osteoporosis (GIOP), and many physicians,6 including those at Veterans Affairs Medical Centers (VAMCs) do not routinely administer agents that may prevent the bone loss complication of glucocorticoid therapy. Osteoporosis is often thought to be a disorder of women; and in the predominantly male population of the typical VAMC, osteoporosis may not be considered a common problem. The fact is that men and African Americans, not usually thought at high risk for osteoporosis, may experience the consequences of GIOP. Moreover, men have worse outcomes after hip fracture,7 including increased risk of death.

Much has been learned from an analysis8 of the General Practice Research Database in the United Kingdom. About 40% of those receiving glucocorticoids had respiratory disorders, and about 40% of the corticosteroid users were men. With increasing daily dosage, there was an increased risk of hip fracture, increasing to a relative risk of 2.27 for doses greater than 7.5 mg/d of prednisolone equivalent. Similar doses of prednisolone were associated with a relative risk of 5.18 for vertebral fracture. Interestingly, the risk of fracture increased soon after starting therapy and decreased toward baseline soon after stopping therapy. This implies that even the patient receiving intermittent glucocorticoid therapy may be at risk for GIOP. It is also clear that patients receiving glucocorticoids via alternate routes, such as patients with chronic obstructive pulmonary disease using inhaled triamcinolone,9 will have lower bone mineral density (BMD) than those not exposed to inhaled glucocorticoids.

A complete discussion of the pathogenesis of GIOP is beyond the scope of this article, and the reader is directed to comprehensive reviews.1014 However, several aspects of GIOP are important to mention because they help explain the severity of GIOP and the rationale for various preventive and therapeutic maneuvers. Bone undergoes a remodeling cycle in which osteoclasts first resorb bone over a period of about 2 weeks. Thereafter osteoblasts appear and fill in the resorbed area over a 3- to 4-month period. In postmenopausal osteoporosis, both bone resorption and formation are increased, but formation is unable to match resorption. In GIOP, while resorption may or may not be increased,1014 bone formation is greatly diminished. This particular mechanism may be the reason that GIOP can lead so rapidly to bone loss and increased fracture risk. Other mechanisms are also important. Glucocorticoids cause increased urinary calcium excretion and decreased intestinal absorption of calcium, possibly leading to secondary hyperparathyroidism. This results in loss of bone mineral. In addition, the general catabolic effects of glucocorticoids cause decrements of bone matrix and muscle. Glucocorticoid therapy may affect pituitary gonadotropin secretion, causing a functional hypogonadism15 in women and men. In addition, suppression of the adrenal gland by exogenous glucocorticoids decreases adrenal androgen secretion (such as dehydroepiandrosterone), which may also be related to bone loss.16,17 A summary of GIOP mechanisms is provided in Table 1.

Table Graphic Jump LocationTable 1. Mechanisms of Glucocorticoid-Induced Osteoporosis

These mechanisms are complicated by the reasons for which patients are prescribed glucocorticoids: conditions such as chronic obstructive pulmonary disease and inflammatory arthritides that decrease one's ability to exercise (and therefore decrease bone mass) can be associated with bone loss even when glucocorticoids are not used as therapy. In summary, the patient receiving glucocorticoids has many reasons to be at risk of fracture.

Not all patients receiving glucocorticoid therapy have fractures, and stratification of risk would target therapy to those at highest risk. From the study of Van Staa et al,8 it is clear that all doses of glucocorticoids increase fracture risk and the risk increases with higher doses. In other types of osteoporosis, measurements of bone mass predict fracture risk.18 Patients with GIOP appear to fracture at the same BMD as patients with other forms of osteoporosis,19 although some studies20 suggest that fracture can occur at higher bone density. History of fragility fracture and age are also important risk factors for future fracture. A new study21 suggests that patients older than 70 years treated with glucocorticoids are at such higher risk for vertebral fracture that treatment can be started without measurement of BMD.

The standard method for assessing bone mass is dual energy x-ray absorptiometry (DXA) of the spine and hip. This essentially risk-free measurement of central bone density is available in many VAMCs and many other clinical settings. While there are other methods to measure bone density (quantitative computed tomography) and bone quality (quantitative ultrasound of bone), the most widely used and accepted method is DXA of the spine and hip. DXA measurements are also needed to assess the response to therapy. New methods to use these measurements in determining 5- or 10-year fracture risk are being developed.22

Osteoporosis cannot be diagnosed by blood or urine tests, but there are a few tests to help in management of patients treated with glucocorticoids. Urinary calcium excretion, as measured in a 24-hour urine sample or estimated from a spot or 2-hour timed urinary calcium-to-creatinine ratio may be helpful in following patients' response to calcium and vitamin D supplementation. Some authorities23 have suggested measurements of the major circulating vitamin D metabolite, 25-hydroxyvitamin D, to decide which patients need additional vitamin D treatment beyond usual doses (400-800 IU/d). Patients with low urinary calcium excretion may have malabsorption, the evaluation of which should include 25-hydroxyvitamin D levels. High levels of urinary calcium excretion may be seen in some patients with osteoporosis and in patients who have excessive calcium and/or vitamin D intake. Serum markers of bone formation, such as osteocalcin,24 may be lowered by even the first dose of prednisone therapy, but there is little clinical use of such markers. Measurements of serum and urinary markers of bone resorption are also of little clinical usefulness at this time.25 Assessment of gonadal status by measurement of serum testosterone or estradiol levels plus the pituitary gonadotropins luteinizing hormone and follicle-stimulating hormone, may help decide which patients will likely improve from hormone replacement therapy. Many VAMCs can measure testosterone, luteinizing hormone, and follicle-stimulating hormone by automated testing that costs approximately $6 per test. In the community, these tests cost much more. Serum estradiol levels are usually measured by commercial laboratories, and the cost per test is approximately $75. For most men taking long-term glucocorticoid therapy, sex hormone testing is indicated for men who are candidates for testosterone replacement (eg, those without prostate hyperplasia or carcinoma). For premenopausal women, clinical assessment of estrogen status may be adequate.

Adjustment of Glucocorticoid Therapy

Using shorter-acting glucocorticoids (eg, prednisone instead of dexamethasone) and alternate-day therapy help to minimize adverse effects in general, and use of topical or inhaled glucocorticoids may help prevent osteoporosis. Nonetheless, application of glucocorticoids to the skin (particularly with occlusive dressings) and normal doses of inhaled steroids can have a deleterious effect on BMD.9

Calcium and Vitamin D

There is evidence that oral calcium and vitamin D supplementation can prevent bone loss in patients receiving lower doses (<20 mg/d of prednisone) of glucocorticoid therapy. In controlled trials of other agents,26 "placebo" groups receiving calcium at 800 to 1000 mg/d (elemental calcium) as well as vitamin D (doses of 250-400 IU/d) did not lose bone from the spine or certain sites in the hip, despite taking up to 15 mg of prednisone per day. These data corroborate those of a 2-year study27 of prevention of bone loss by calcium and vitamin D in patients with rheumatoid arthritis receiving an average prednisone dose of about 6 mg/d. Thus, for patients receiving low-dose prednisone therapy, calcium and vitamin D supplementation appears to be a cost-effective way28 to prevent GIOP. In the VAMC, the monthly cost for daily supplementation with 1 g of elemental calcium in the form of calcium carbonate and 400 U of vitamin D in the form of a multivitamin tablet is $3.16. This cost is considerably less than other treatments, as shown in Table 2.

Table Graphic Jump LocationTable 2. Monthly Costs of Therapy for Glucocorticoid-Induced Osteoporosis at a Veterans Affairs Medical Center
Calcitonin

Although some small studies have shown that subcutaneous29 or intranasal30 calcitonin can be used in the management of GIOP, larger blinded studies31,32 have not shown much effect of calcitonin beyond that from the calcium and vitamin D used for both placebo and active drug groups. While calcitonin has been found to have an analgesic effect33 that may be helpful in patients with painful fracture, it is not approved by the Food and Drug Administration (FDA) for GIOP.

Bisphosphonates

There are now several excellent studies demonstrating the effectiveness of bisphosphonate therapy in preventing or treating GIOP in both men and women. Two randomized studies34,35 showed that etidronate disodium given in cyclic fashion (400 mg orally daily for 2 weeks every 3 months) could prevent bone loss and vertebral fracture in patients just starting glucocorticoids at doses of 7.5 mg of prednisone or more. In more recent studies of newer bisphosphonates, alendronate sodium36,37 and risedronate sodium38,39 have been shown to successfully prevent and treat GIOP. In the alendronate study,36 the relative risk of spine fracture defined by morphometric analysis of x-ray films was 0.6 in the men and women taking alendronate. In the 2-year blinded extension,37 continued alendronate therapy was shown to dramatically decrease the incidence of morphometric vertebral fractures. In a study of risedronate in patients receiving long-term glucocorticoid therapy,38 the vertebral fracture rate was decreased by 70% in 1 year in men and women who received risedronate. This was confirmed by another randomized, controlled, double-blinded study39 of risedronate in patients beginning glucocorticoid therapy. Thus, there is high-quality evidence that bisphosphonate therapy can decrease fracture risk and increase bone density in patients about to start glucocorticoid therapy and in patients already taking prednisone or its equivalents. The FDA has approved alendronate for treatment of GIOP. The approved dose is 5 mg/d, except for postmenopausal women not receiving hormone replacement therapy, for whom the approved dose is 10 mg/d. Risedronate sodium at 5 mg/d is FDA approved for both prevention and treatment of GIOP. Trials of alendronate sodium, 70 mg once weekly, and risedronate sodium, 35 mg once weekly, in GIOP are currently in progress. A recent study40 suggests that intravenous pamidronate disodium may be used as an alternative to oral bisphosphonates to prevent GIOP, but this is not FDA-approved therapy. A summary of bisphosphonate treatment regimens that have not yet received FDA approval is listed below.

There is evidence that these regimens will increase BMD in postmenopausal osteoporosis, and there are ongoing studies to determine if these regimens are applicable to GIOP. Patients prefer the weekly regimens, and compliance may be better. In addition, for patients unable to tolerate oral bisphosphonates, intravenous pamidronate has been widely used off label, despite lack of fracture efficacy data. Nonetheless, there is reason to believe that these alternatives may be of benefit to many patients. Etidronate is widely used for GIOP in other countries. As discussed below, teriparatide, an active fragment of parathyroid hormone (PTH), has been approved for postmenopausal osteoporosis and for primary or hypogonadal osteoporosis in men. It is likely to be useful in GIOP.

Anabolic Agents

The antiresorptive agents, such as bisphosphonates, fill in the remodeling space, but drugs that actually increase bone formation would make great sense in a disorder marked by decreased bone formation. Fluoride has anabolic effects in bone. Even though it increased BMD in patients with GIOP,41 fracture rate was not decreased. More recently, intermittent PTH1-34 fragment has been used in postmenopausal women with osteoporosis42 and GIOP43 as an anabolic agent. This seemingly contradictory effect of PTH is well demonstrated by a study,43 in which postmenopausal women taking glucocorticoid treatment as well as sex hormone replacement therapy were given a fragment of PTH (containing amino acids 1-34) as a daily injection. Women who received the PTH fragment had a dramatic increase in BMD, as measured by DXA and by quantitative computed tomography. Although there are no fracture data from the study of PTH in patients with GIOP, a different preparation of the same fragment (teriparatide) decreased vertebral fracture risk in women with postmenopausal osteoporosis.44 Parathyroid hormone fragment (teriparatide) has also been shown45 to markedly increase BMD in men with idiopathic osteoporosis. Finally, in one recent study46 of postmenopausal osteoporosis, patients received 1 year of PTH therapy followed by 1 year of alendronate therapy, resulting in dramatic increases in BMD. It is likely that various types of combination therapy will be successfully tested in GIOP. Teriparatide, the PTH fragment used in some of the studies described above, has now been approved for postmenopausal osteoporosis and for men with primary or hypogonadal osteoporosis.

Sex Hormone Replacement Therapy

In men made hypogonadal by glucocorticoid therapy it makes intuitive sense to replace androgens. In a study by Reid et al,47 men with GIOP due to lung diseases were found to have low serum testosterone levels. Replacement of testosterone resulted in increased BMD. In postmenopausal women with rheumatoid arthritis, hormone replacement therapy increases BMD.48 Thus, at this stage in our knowledge, hormone replacement therapy (testosterone or estrogen with or without progestin) is indicated for many patients with GIOP. However, the sorts of cautions in using such agents (eg, increase in hormone-sensitive tumors) apply to patients with GIOP. An alternative to hormone replacement therapy for women is the selective estrogen receptor modulator raloxifene, which has been demonstrated49 to be an effective treatment for postmenopausal osteoporosis. There are no data available on the use of raloxifene in postmenopausal women with GIOP.

In an ideal world, all patients receiving glucocorticoid treatment or about to start should be assessed by DXA. However, not all VAMCs have densitometers. An overall management strategy is shown in Table 3.

Table Graphic Jump LocationTable 3. General Strategy for Glucocorticoid-Induced Osteoporosis
Patients Already Taking Glucocorticoids for More Than 3 Months

In VAMCs with densitometers, bone density of the spine and hip should be measured. For patients with bone density–defined osteoporosis or marked osteopenia, treatment is listed below. For VAMCs without a densitometer, there are at least 2 alternatives: (1) It may be possible to send the patient to another VAMC with a densitometer. Each VISN (Veterans Integrated Service Network, a group of hospitals and clinics with centralized management) is likely to have at least 1 densitometer. In some cases, DXA at a community medical facility may be available. (2) For patients taking glucocorticoids for more than 3 months and without other risk factors for osteoporosis, conservative therapy (1000 mg/d of calcium and 400-800 U of vitamin D per day) can be considered. Note that patients taking more than 7.5 mg of prednisone equivalent per day are at much higher risk for bone loss than patients taking lower doses. Patients with risk factors other than glucocorticoid therapy (eg, older age, history of fracture, postmenopausal or low testosterone level, current cigarette smoking, low calcium intake) should be considered for pharmacologic therapy with a nitrogen-containing bisphosphonate. The problem with the latter approach is that some patients who do not have GIOP will be treated, and it will be impossible to determine the response to therapy. As can be seen from Table 2, the cost of pharmacologic therapy with either alendronate or risedronate is about $33 per month, in addition to the cost of calcium and vitamin D.

In many VAMCs, the Pharmacy Database can be used to identify patients taking long-term glucocorticoid therapy. Clinical reminders can be added to electronically ordered prescriptions to ask the practitioner if preventive measures have been instituted for each patient.

Patients Starting Glucocorticoid Therapy

All patients starting use of glucocorticoids (and expected to need them for at least 3 months) should be offered calcium supplementation (1 g/d elemental calcium) and vitamin D (400-800 IU/d), with monitoring of 24-hour urinary calcium or urinary calcium-creatinine ratio (when measured in milligrams per deciliter divided by milligrams per deciliter, the ratio should be between 0.05 and 0.16). Patients receiving lower-dose glucocorticoid therapy (≤5 mg/d prednisone equivalent) will likely maintain bone on this regimen.27 For patients starting moderate-dose glucocorticoid therapy (5-7.5 mg/d prednisone) bone densitometry should be performed to determine which patients need bisphosphonate therapy. In VAMCs without DXA testing, a case can be made to treat all patients who will need more than 3 months of prednisone at doses of 5 mg/d or more. From the studies of van Staa et al,50 the daily dose of glucocorticoid was more important than the cumulative dose. Increased fracture risk was seen in the medium-dose range (2.5-7.5 mg/d of prednisolone, approximately 3-9 mg/d of prednisone). For patients who will need more than 7.5 mg of prednisone daily, bisphosphonate therapy with alendronate or risedronate is clearly indicated. The study of Naganathan et al21 suggests that all glucocorticoid-treated patients older than 70 years should receive bisphosphonate therapy, but it will be necessary to have other studies support their conclusion.

Although there are no studies large enough to determine whether sex hormone replacement therapy lowers fracture risk in GIOP, the data suggest that the addition of estrogen, a selective estrogen receptor modulator, or testosterone replacement will have a salutary effect on BMD in patients with GIOP. New treatments from anabolic agents such as PTH hold promise for even greater prevention of fracture.

Other Measures

For all patients at risk for osteoporosis, preventing falls is of great importance. A recent study51 suggests that the use of hip protectors for frail elders with osteoporosis is very effective in preventing hip fracture.

Patients With Sarcoidosis

Patients with sarcoidosis may be treated with glucocorticoids and may be at risk for osteoporosis. Most of the studies of this disorder have been in Italy,52 and patients have responded to bisphosphonate therapy. Most US veterans with sarcoidosis are African American and may be at somewhat lower risk for GIOP. However, sarcoidosis can cause a vitamin D excess syndrome due to activation of vitamin D in the sarcoid granulomas. This can lead to hypercalciuria and hypercalcemia, which could be exacerbated by standard therapy for GIOP, supplementary calcium and vitamin D. In a retrospective analysis of patients with sarcoidosis at a VAMC,53 hypercalciuria was found be uncommon and no patients had hypercalcemia, despite some patients having been treated with supplements. In all patients with GIOP, it is prudent to measure serum calcium and urinary calcium (with creatinine) levels in a spot or 24-hour urine sample before and 4 to 8 weeks after starting calcium and vitamin D supplementation. These same tests should be done periodically thereafter.

Patients Undergoing Organ Transplantation

In several VAMCs, patients may undergo transplantation of the kidney, lung, liver, bone marrow, or heart. Patients receive antirejection medications that include glucocorticoids and other drugs such as cyclosporine54 that may be toxic to bone. These patients are at very high risk for bone loss and fracture, and they require careful, individualized therapy. A full discussion of this topic55 is beyond these guidelines, but all transplant patients should be referred to a physician specializing in osteoporosis for management of their bone loss.

The reader is directed to guidelines for GIOP issued by a United Kingdom Consensus Group56 and to the recently revised guidelines for GIOP issued by the American College of Rheumatology.57 The strategy for veterans with GIOP can be applied to other managed care settings and to patients in general. The costs of tests, availability of BMD testing, and costs of therapy will vary with the clinical setting.

Corresponding author and reprints: Robert A. Adler, MD, Endocrinology Section (111-P), McGuire Veterans Affairs Medical Center, Richmond, VA 23249 (e-mail: robert.adler@med.va.gov).

Accepted for publication January 17, 2003.

We thank Lenore M. Buckley, MD, MPH, for her careful review of the manuscript.

This article reflects the opinions of the authors and not those of the Department of Veterans Affairs.

Saag  KKoehnke  RCaldwell  J  et al.  Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med. 1994;96115- 123
PubMed
LoCasio  VBonnucci  EImbimbo  B  et al.  Bone loss after glucocorticoid therapy. Calcif Tissue Int. 1984;36435- 438
PubMed
Lyles  KWGold  DTShipp  KMPieper  CFMartinez  SMulhausen  PL Association of osteoporotic vertebral compression fractures with impaired functional status. Am J Med. 1993;94595- 601
PubMed
Keene  GSParker  MPryor  GA Mortality and morbidity after hip fracture. BMJ. 1993;3071248- 1250
PubMed
Buckley  LMMarquez  MHudson  JO  et al.  Variations in physicians' judgments about corticosteroid induced osteoporosis by physician specialty. J Rheumatol. 1998;252195- 2202
PubMed
Elliott  MEFarrah  RMBinkley  NCCarnes  MLGudmundsson  A Management of glucocorticoid-induced osteoporosis in male veterans. Ann Pharmacother. 2000;341380- 1384
PubMed
Block  JEStubbs  H Hip fracture-associated mortality reconsidered. Calcif Tissue Int. 1997;6184
PubMed
Van Staa  TPLeufkens  HGAbenhaim  LZhang  BCooper  C Use of oral corticosteroids and risk of fractures. J Bone Miner Res. 2000;15993- 1000
PubMed
The Lung Health Study Research Group, Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med. 2000;3431902- 1909
PubMed
Adler  RARosen  CJ Glucocorticoids and osteoporosis. Endocrinol Metab Clin North Am. 1994;23641- 654
PubMed
Lukert  BPRaisz  LG Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med. 1990;112352- 364
PubMed
Pearce  GTabensky  DADelmas  PDBaker  HWSeeman  E Corticosteroid-induced bone loss in men. J Clin Endocrinol Metab. 1998;83801- 806
PubMed
Manolagas  SC Corticosteroids and fractures: a close encounter of the third cell kind. J Bone Miner Res. 2000;151001- 1005
PubMed
Canalis  EGiustina  A Glucocorticoid-induced osteoporosis: summary of a workshop. J Clin Endocrinol Metab. 2001;865681- 5685
PubMed
MacAdams  MRWhite  RHChipps  BE Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med. 1986;104648- 651
PubMed
Wild  RABuchanan  JRMyers  CDemers  LM Declining adrenal androgens: an association with bone loss in aging women. Proc Soc Exp Biol Med. 1987;186355- 360
PubMed
Zeilissen  PMJCroughs  RJMvan Rijk  PPRaymakers  JA Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann Intern Med. 1994;120207- 210
PubMed
Deng  HWLi  JLLi  JDavies  KMRecker  RR Heterogeneity of bone mineral density across skeletal sites and its clinical implications. J Clin Densitom. 1998;1339- 353
Selby  PLHalsey  JPAdams  KR  et al.  Corticosteroids do not alter the threshold for vertebral fracture. J Bone Miner Res. 2000;15952- 956
PubMed
Luengo  MPicado  CDel Rio  LGuanabens  NMontserrat  JMSetoain  J Vertebral fractures in steroid dependent asthma and involutional osteoporosis: a comparative study. Thorax. 1991;46803- 806
PubMed
Naganathan  VJones  GNash  PNicholson  GEisman  JSambrook  PN Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use. Arch Intern Med. 2000;1602917- 2925
PubMed
Kanis  JABlack  DCooper  C  et al.  A new approach to the development of assessment guidelines for osteoporosis. Osteoporos Int. 2002;13527- 536
PubMed
Libanati  CRBaylink  DJ Prevention and treatment of glucocorticoid-induced osteoporosis. Chest. 1992;1021426- 1435
PubMed
Godschalk  MFDowns  RW Effect of short-term glucocorticoids on serum osteocalcin in healthy young men. J Bone Miner Res. 1988;13113- 115
Chiodini  ICarnevale  VTorlontano  M  et al.  Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing's syndrome. J Clin Endocrinol Metab. 1998;831863- 1867
PubMed
Amin  SLaValley  MPSimms  RWFelson  DT The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression. J Bone Miner Res. 2002;171512- 1526
PubMed
Buckley  LMLeib  ESCartularo  KSVacek  PMCooper  SM Calcium and vitamin D supplementation prevents bone loss in the spine secondary to low dose corticosteroids in patients with rheumatoid arthritis: a randomized, double blind, placebo-controlled trial. Ann Intern Med. 1996;125961- 968
PubMed
Buckley  LMHillner  BE A cost-effectiveness analysis of calcium and vitamin D supplementation, etidronate, and alendronate in the prevention of vertebral fractures in women treated with glucocorticoids. J Rheumatol. 2003;30132- 138
PubMed
Healey  JHPaget  SAWilliams-Russo  P  et al.  A randomized controlled trial of salmon calcitonin to prevent bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica. Calcif Tissue Int. 1996;5873- 80
PubMed
Adachi  JDBensen  WGBell  MJ  et al.  Salmon calcitonin nasal spray and the prevention of corticosteroid-induced osteoporosis. Br J Rheumatol. 1997;36255- 259
PubMed
Sambrook  PBirmingham  JKelly  PKempler  SPocock  NAEisman  JA Prevention of corticosteroid osteoporosis: a comparison of calcium, calcitriol, and calcitonin. N Engl J Med. 1993;3281747- 1752
PubMed
Kotaniemi  APiirainen  HPaimela  L  et al.  Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active RA receiving low dose glucocorticoids? J Rheumatol. 1996;231875- 1879
PubMed
Lyritis  GPTsakalakos  NMagiasis  BKarachalios  TYiatzides  ATsekoura  M Analgesic effect of salmon calcitonin in osteoporotic vertebral fractures: a double-blind placebo-controlled clinical study. Calcif Tissue Int. 1991;49369- 373
PubMed
Adachi  JDBensen  WGBrown  J  et al.  Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med. 1997;337382- 387
PubMed
Roux  COriente  PLaan  R  et al.  Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. J Clin Endocrinol Metab. 1998;831128- 1133
PubMed
Saag  KGEmkey  RSchnitzer  TJ  et al.  Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med. 1998;339292- 299
PubMed
Adachi  JDSaag  KGDelmas  PD  et al.  Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids. Arthritis Rheum. 2001;44202- 211
PubMed
Reid  DMHughes  RALaan  RFJM  et al.  Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. J Bone Miner Res. 2000;151006- 1013
PubMed
Cohen  SLevy  RMKeller  M  et al.  Risedronate therapy prevents corticosteroid-induced bone loss. Arthritis Rheum. 1999;422309- 2318
PubMed
Boutsen  YJamart  JEsselinckx  WDevogelaer  JP Primary prevention of glucocorticoid-induced osteoporosis with intravenous pamidronate and calcium: a prospective controlled 1-year study comparing a single infusion, an infusion given once every 3 months, and calcium alone. J Bone Miner Res. 2001;16104- 112
PubMed
Lems  WFJacobs  JWBijlsma  JW  et al.  Effect of sodium fluoride on the prevention of corticosteroid-induced osteoporosis. Osteoporos Int. 1997;7575- 582
PubMed
Lindsay  RNieves  JFormica  C  et al.  Randomized controlled study of the effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on estrogen with osteoporosis. Lancet. 1997;350550- 555
PubMed
Lane  NESanchez  SModin  GWGenant  HKPierini  EArnaud  CD Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. J Clin Invest. 1998;1021627- 1633
PubMed
Neer  RMArnaud  CDZanchetta  JR  et al.  Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;3441434- 1441
PubMed
Kurland  ESCosman  FMcMahon  DJRosen  CJLindsay  RBilezikian  JP Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab. 2000;853069- 3076
PubMed
Rittmaster  RSBolognese  MEttinger  MP  et al.  Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab. 2000;852129- 2134
PubMed
Reid  IRWattie  DJEvans  MCStapleton  JP Testosterone therapy in glucocorticoid-treated men. Arch Intern Med. 1996;1561173- 1177
PubMed
Hall  GMDaniels  MDoyle  DVSpector  TD Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids. Arthritis Rheum. 1994;371499- 1505
PubMed
Delmas  PDEnsrud  KEAdachi  JD  et al.  Efficacy of raloxifene on vertebral fracture risk in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab. 2002;873609- 3617
PubMed
van Staa  TPLeufkens  HMGAbenhaim  LZhang  BCooper  C Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology. 2000;391383- 1389
PubMed
Kannus  PParkkari  JNiemi  S  et al.  Prevention of hip fracture in elderly people with use of a hip protector. N Engl J Med. 2000;3431506- 1513
PubMed
Gonnelli  SRottoli  PCepollaro  C  et al.  Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients. Calcif Tissue Int. 1997;61382- 385
PubMed
Adler  RAFunkhouser  HLPetkov  VIBerger  MM Glucocorticoid-induced osteoporosis (GIOP) in patients with sarcoidosis. Am J Med Sci. 2003;3251- 6
PubMed
Epstein  S Immunosuppressant drugs and bone disease: a clinician's perspective. J Clin Densitom. 1998;1317- 321
Rodino  MAShane  E Osteoporosis after organ transplantation. Am J Med. 1998;104459- 469
PubMed
Eastell  RReid  DMCompston  J  et al.  A UK consensus group on management of glucocorticoid-induced osteoporosis: an update. J Intern Med. 1998;244271- 292
PubMed
American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis, Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum. 2001;441496- 1503
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1. Mechanisms of Glucocorticoid-Induced Osteoporosis
Table Graphic Jump LocationTable 2. Monthly Costs of Therapy for Glucocorticoid-Induced Osteoporosis at a Veterans Affairs Medical Center
Table Graphic Jump LocationTable 3. General Strategy for Glucocorticoid-Induced Osteoporosis

References

Saag  KKoehnke  RCaldwell  J  et al.  Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med. 1994;96115- 123
PubMed
LoCasio  VBonnucci  EImbimbo  B  et al.  Bone loss after glucocorticoid therapy. Calcif Tissue Int. 1984;36435- 438
PubMed
Lyles  KWGold  DTShipp  KMPieper  CFMartinez  SMulhausen  PL Association of osteoporotic vertebral compression fractures with impaired functional status. Am J Med. 1993;94595- 601
PubMed
Keene  GSParker  MPryor  GA Mortality and morbidity after hip fracture. BMJ. 1993;3071248- 1250
PubMed
Buckley  LMMarquez  MHudson  JO  et al.  Variations in physicians' judgments about corticosteroid induced osteoporosis by physician specialty. J Rheumatol. 1998;252195- 2202
PubMed
Elliott  MEFarrah  RMBinkley  NCCarnes  MLGudmundsson  A Management of glucocorticoid-induced osteoporosis in male veterans. Ann Pharmacother. 2000;341380- 1384
PubMed
Block  JEStubbs  H Hip fracture-associated mortality reconsidered. Calcif Tissue Int. 1997;6184
PubMed
Van Staa  TPLeufkens  HGAbenhaim  LZhang  BCooper  C Use of oral corticosteroids and risk of fractures. J Bone Miner Res. 2000;15993- 1000
PubMed
The Lung Health Study Research Group, Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med. 2000;3431902- 1909
PubMed
Adler  RARosen  CJ Glucocorticoids and osteoporosis. Endocrinol Metab Clin North Am. 1994;23641- 654
PubMed
Lukert  BPRaisz  LG Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med. 1990;112352- 364
PubMed
Pearce  GTabensky  DADelmas  PDBaker  HWSeeman  E Corticosteroid-induced bone loss in men. J Clin Endocrinol Metab. 1998;83801- 806
PubMed
Manolagas  SC Corticosteroids and fractures: a close encounter of the third cell kind. J Bone Miner Res. 2000;151001- 1005
PubMed
Canalis  EGiustina  A Glucocorticoid-induced osteoporosis: summary of a workshop. J Clin Endocrinol Metab. 2001;865681- 5685
PubMed
MacAdams  MRWhite  RHChipps  BE Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med. 1986;104648- 651
PubMed
Wild  RABuchanan  JRMyers  CDemers  LM Declining adrenal androgens: an association with bone loss in aging women. Proc Soc Exp Biol Med. 1987;186355- 360
PubMed
Zeilissen  PMJCroughs  RJMvan Rijk  PPRaymakers  JA Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann Intern Med. 1994;120207- 210
PubMed
Deng  HWLi  JLLi  JDavies  KMRecker  RR Heterogeneity of bone mineral density across skeletal sites and its clinical implications. J Clin Densitom. 1998;1339- 353
Selby  PLHalsey  JPAdams  KR  et al.  Corticosteroids do not alter the threshold for vertebral fracture. J Bone Miner Res. 2000;15952- 956
PubMed
Luengo  MPicado  CDel Rio  LGuanabens  NMontserrat  JMSetoain  J Vertebral fractures in steroid dependent asthma and involutional osteoporosis: a comparative study. Thorax. 1991;46803- 806
PubMed
Naganathan  VJones  GNash  PNicholson  GEisman  JSambrook  PN Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use. Arch Intern Med. 2000;1602917- 2925
PubMed
Kanis  JABlack  DCooper  C  et al.  A new approach to the development of assessment guidelines for osteoporosis. Osteoporos Int. 2002;13527- 536
PubMed
Libanati  CRBaylink  DJ Prevention and treatment of glucocorticoid-induced osteoporosis. Chest. 1992;1021426- 1435
PubMed
Godschalk  MFDowns  RW Effect of short-term glucocorticoids on serum osteocalcin in healthy young men. J Bone Miner Res. 1988;13113- 115
Chiodini  ICarnevale  VTorlontano  M  et al.  Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing's syndrome. J Clin Endocrinol Metab. 1998;831863- 1867
PubMed
Amin  SLaValley  MPSimms  RWFelson  DT The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression. J Bone Miner Res. 2002;171512- 1526
PubMed
Buckley  LMLeib  ESCartularo  KSVacek  PMCooper  SM Calcium and vitamin D supplementation prevents bone loss in the spine secondary to low dose corticosteroids in patients with rheumatoid arthritis: a randomized, double blind, placebo-controlled trial. Ann Intern Med. 1996;125961- 968
PubMed
Buckley  LMHillner  BE A cost-effectiveness analysis of calcium and vitamin D supplementation, etidronate, and alendronate in the prevention of vertebral fractures in women treated with glucocorticoids. J Rheumatol. 2003;30132- 138
PubMed
Healey  JHPaget  SAWilliams-Russo  P  et al.  A randomized controlled trial of salmon calcitonin to prevent bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica. Calcif Tissue Int. 1996;5873- 80
PubMed
Adachi  JDBensen  WGBell  MJ  et al.  Salmon calcitonin nasal spray and the prevention of corticosteroid-induced osteoporosis. Br J Rheumatol. 1997;36255- 259
PubMed
Sambrook  PBirmingham  JKelly  PKempler  SPocock  NAEisman  JA Prevention of corticosteroid osteoporosis: a comparison of calcium, calcitriol, and calcitonin. N Engl J Med. 1993;3281747- 1752
PubMed
Kotaniemi  APiirainen  HPaimela  L  et al.  Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active RA receiving low dose glucocorticoids? J Rheumatol. 1996;231875- 1879
PubMed
Lyritis  GPTsakalakos  NMagiasis  BKarachalios  TYiatzides  ATsekoura  M Analgesic effect of salmon calcitonin in osteoporotic vertebral fractures: a double-blind placebo-controlled clinical study. Calcif Tissue Int. 1991;49369- 373
PubMed
Adachi  JDBensen  WGBrown  J  et al.  Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med. 1997;337382- 387
PubMed
Roux  COriente  PLaan  R  et al.  Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. J Clin Endocrinol Metab. 1998;831128- 1133
PubMed
Saag  KGEmkey  RSchnitzer  TJ  et al.  Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med. 1998;339292- 299
PubMed
Adachi  JDSaag  KGDelmas  PD  et al.  Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids. Arthritis Rheum. 2001;44202- 211
PubMed
Reid  DMHughes  RALaan  RFJM  et al.  Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. J Bone Miner Res. 2000;151006- 1013
PubMed
Cohen  SLevy  RMKeller  M  et al.  Risedronate therapy prevents corticosteroid-induced bone loss. Arthritis Rheum. 1999;422309- 2318
PubMed
Boutsen  YJamart  JEsselinckx  WDevogelaer  JP Primary prevention of glucocorticoid-induced osteoporosis with intravenous pamidronate and calcium: a prospective controlled 1-year study comparing a single infusion, an infusion given once every 3 months, and calcium alone. J Bone Miner Res. 2001;16104- 112
PubMed
Lems  WFJacobs  JWBijlsma  JW  et al.  Effect of sodium fluoride on the prevention of corticosteroid-induced osteoporosis. Osteoporos Int. 1997;7575- 582
PubMed
Lindsay  RNieves  JFormica  C  et al.  Randomized controlled study of the effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on estrogen with osteoporosis. Lancet. 1997;350550- 555
PubMed
Lane  NESanchez  SModin  GWGenant  HKPierini  EArnaud  CD Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. J Clin Invest. 1998;1021627- 1633
PubMed
Neer  RMArnaud  CDZanchetta  JR  et al.  Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;3441434- 1441
PubMed
Kurland  ESCosman  FMcMahon  DJRosen  CJLindsay  RBilezikian  JP Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab. 2000;853069- 3076
PubMed
Rittmaster  RSBolognese  MEttinger  MP  et al.  Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab. 2000;852129- 2134
PubMed
Reid  IRWattie  DJEvans  MCStapleton  JP Testosterone therapy in glucocorticoid-treated men. Arch Intern Med. 1996;1561173- 1177
PubMed
Hall  GMDaniels  MDoyle  DVSpector  TD Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids. Arthritis Rheum. 1994;371499- 1505
PubMed
Delmas  PDEnsrud  KEAdachi  JD  et al.  Efficacy of raloxifene on vertebral fracture risk in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab. 2002;873609- 3617
PubMed
van Staa  TPLeufkens  HMGAbenhaim  LZhang  BCooper  C Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology. 2000;391383- 1389
PubMed
Kannus  PParkkari  JNiemi  S  et al.  Prevention of hip fracture in elderly people with use of a hip protector. N Engl J Med. 2000;3431506- 1513
PubMed
Gonnelli  SRottoli  PCepollaro  C  et al.  Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients. Calcif Tissue Int. 1997;61382- 385
PubMed
Adler  RAFunkhouser  HLPetkov  VIBerger  MM Glucocorticoid-induced osteoporosis (GIOP) in patients with sarcoidosis. Am J Med Sci. 2003;3251- 6
PubMed
Epstein  S Immunosuppressant drugs and bone disease: a clinician's perspective. J Clin Densitom. 1998;1317- 321
Rodino  MAShane  E Osteoporosis after organ transplantation. Am J Med. 1998;104459- 469
PubMed
Eastell  RReid  DMCompston  J  et al.  A UK consensus group on management of glucocorticoid-induced osteoporosis: an update. J Intern Med. 1998;244271- 292
PubMed
American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis, Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum. 2001;441496- 1503
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 46

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics