Arthritis Care & Research

Vol. 62, No. 11, November 2010, pp 1515–1526
DOI 10.1002/acr.20295
© 2010, American College of Rheumatology
SPECIAL ARTICLE

American College of Rheumatology 2010
Recommendations for the Prevention and
Treatment of Glucocorticoid-Induced Osteoporosis
JENNIFER M. GROSSMAN,1 REBECCA GORDON,2 VEENA K. RANGANATH,1 CHAD DEAL,3
LIRON CAPLAN,4 WEILING CHEN,1 JEFFREY R. CURTIS,5 DANIEL E. FURST,1 MAUREEN MCMAHON,1
NIVEDITA M. PATKAR,5 ELIZABETH VOLKMANN,1 AND KENNETH G. SAAG5

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are in-
tended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR
considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding
their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recom-
mendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guide-
lines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolu-
tion of medical knowledge, technology, and practice.

These recommendations have been reviewed and endorsed associated with significant morbidity and mortality. Osteo-
by the American Society for Bone and Mineral Research. porosis, with resultant fractures, constitutes one of these
morbid complications and is associated with significant
pain and disability. A rapid decline in bone mineral den-
INTRODUCTION
sity (BMD) begins within the first 3 months of glucocorti-
Although glucocorticoids may effectively be used in the coid use and peaks at 6 months, followed by a slower,
management of many inflammatory conditions, their use is
MD (University of Minnesota, Minneapolis), Cathleen Co-
1
Jennifer M. Grossman, MD, Veena K. Ranganath, MD, lon-Emeric, MD, MHSc (Duke University, Durham, NC),
Weiling Chen, MA, Daniel E. Furst, MD, Maureen McMa- Chad Deal, MD (Cleveland Clinic, Cleveland, OH), Joseph
hon, MD, MSc, Elizabeth Volkmann, MD: University of Cal- Flood, MD (Musculoskeletal Medical Specialists, Columbus,
ifornia, Los Angeles; 2Rebecca Gordon, MD: VA Greater Los OH), Theodore Hahn, MD (VA Greater Los Angeles Health-
Angeles Healthcare System and University of California, care System GRECC and University of California, Los An-
Los Angeles; 3Chad Deal, MD: Cleveland Clinic, Cleveland, geles), Amye Leong, MBA (Healthy Motivation, Santa Bar-
Ohio; 4Liron Caplan, MD: University of Colorado, Denver; bara, CA), Michael Maricic, MD (University of Arizona,
5
Jeffrey R. Curtis, MD, MPH, Nivedita M. Patkar, MD, Tucson), Anthony Sebba, MD (University of South Florida,
MSPH, Kenneth G. Saag, MD, MSc: University of Alabama, Tampa), Stuart Silverman, MD (University of California, Los
Birmingham. Angeles).
Dr. Deal has received consultant fees, speaking fees, Members of the Expert Advisory Panel: Johannes W. J.
and/or honoraria (more than $10,000 each) from Lilly, Bijlsma, MD (University of Utrecht, Utrecht, The Nether-
Amgen, and Genentech. Dr. Curtis has received consultant lands), Chad Deal, MD (Cleveland Clinic, Cleveland, OH),
fees, speaking fees, and/or honoraria (less than $10,000 Nancy Lane, MD (University of California, Davis), Marc
each) from Eli Lilly and Procter & Gamble, and (more than Hochberg, MD, MPH (University of Maryland, Baltimore),
$10,000 each) from Novartis, Amgen, Roche/Genentech, and Willem Lems, MD (Vrije Universiteit Medical Centre, Am-
Merck. Dr. Saag has received consultant fees, speaking fees, sterdam, The Netherlands), Catherine MacLean, MD, PhD
and/or honoraria (less than $10,000 each) from Merck, Lilly, (WellPoint, Inc., Thousand Oaks, CA).
Novartis, Aventis, Genentech, AstraZeneca, Pfizer, and The American College of Rheumatology is an independent
Horizon. professional, medical, and scientific society which does not
Members of the Core Executive Panel: Jennifer M. Gross- guarantee, warrant, or endorse any commercial product or
man, MD, Veena K. Ranganath, MD, Weiling Chen, MA, service.
Daniel E. Furst, MD, Maureen McMahon, MD, MSc, Eliza- Address correspondence to Jennifer M. Grossman, MD,
beth Volkmann, MD, Rebecca Gordon, MD, Kenneth G. UCLA, 1000 Veteran Avenue, Room 32-59, Rehabilitation
Saag, MD, MSc, Jeffrey R. Curtis, MD, MPH, Nivedita M. Building, Los Angeles, CA 90095. E-mail: jgrossman@
Patkar, Liron Caplan, MD. mednet.ucla.edu.
Members of the Task Force Panel: Robert Adler, MD Submitted for publication December 4, 2009; accepted in
(McGuire VA Medical Center, Richmond, VA), Gary Bryant, revised form July 6, 2010.

1515

respectively (11. they provide expert opinion and evidence- diagnostic approach for some patients receiving glucocor. ployed in developing the ACR recommendations for the coid use as a clinical risk factor (19). Rather.5–7. less than one- third received BMD testing or had documented use of calcium and vitamin D supplementation (13–15). the American College of Rheumatology (ACR) ment. These tions have become available. A number of treatment options for the prevention and management of glucocorticoid-induced osteoporosis (GIOP) are now available. the inclusion of medications ap- Since even rigorously developed guidelines have limi. proved for use in the treatment of osteoporosis in the US.3). Despite the availability of therapies to reduce the risk of fractures. To narrow the scope of the work and be- vote on the specific recommendations). RAND/UCLA ⫽ Research and Development/University of California at Los Angeles. We Angeles (RAND/UCLA) method. tify patients at highest risk for fracture have also been nor are they intended to serve as indicators of quality of developed. Advisory Panel set the following restrictions for our rec- The 2010 recommendations are reported below. which is described in more detail (17). ticoids. and a systematic cause of limited available data in certain areas. Furthermore. In order to revise these recommendations on behalf of Topic development. the ACR. More recently. ticoid-induced osteoporosis (GIOP) recommendations develop- In 2001. In a large meta- analysis. particu. In some populations. Groups responsible for each component of the glucocor- larly among men and younger women (14 –16). there has been some controversy regarding the dose at which an increased risk of fracture occurs. An increased risk of both vertebral and nonvertebral fractures has been re- ported with dosages of prednisolone or equivalent as low as 2. Updated approaches to iden.12). the National Osteoporosis Foundation incorporated the 10-year absolute probability of fracture calculated by The methods used to update the ACR GIOP recommenda- the FRAX tool (18) into their guidelines for the treatment tions followed the same general principles that were em- and prevention of osteoporosis and included glucocorti. with no significant difference in relative risk between men and women (6). the Expert literature review (methodology described in detail below).0 mg dosages of pred- nisone (4). Simi- larly.1516 Grossman et al steady loss with continued use (1). .5 mg daily. the term “recommendations” to describe this work. and this risk may relate more strongly to daily rather than to cumulative doses of glucocorticoids (2. Figure 1. Bone density alone may not be the sole reliable care. based guidance on the prevention and treatment of GIOP. In MATERIALS AND METHODS 2008. However. ommendations: first. To update the recommendations. when a more informal consensus approach was used illustrates this process. a primary Core Executive Panel utilized the we incorporated the existing concepts from the 2001 Research and Development/University of California at Los guidelines and also refined the scope of the project. the use of bisphosphonate therapy is low. published their Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (17). Figure 1 2001. matologists with expertise in GIOP. as some smaller studies have found no appreciable decline in bone density with mean daily 8. Both alendronate and risedr- onate improve BMD and decrease the risk of vertebral fractures in patients treated with glucocorticoids (7–10). the use of biologic and nonbiologic disease-modifying anti- methodology for guideline development has evolved since rheumatic drugs in rheumatoid arthritis (20). prior and current use of oral glucocorticoids in- creased the risk of any type of fracture. since fracture in patients receiving glucocorticoids may occur independently of a decline in bone mass (6). recommendations should not supplant clinical judgment. reappraisal and update of the 2001 recommendations. many patients receiving long-term glucocorti- coid therapy do not receive any interventions to prevent or treat osteoporosis. Collectively. which employed alendronate and risedronate. including guideline ment of the recommendations and the Task Force Panel to development. additional therapies and new tations in informing individual patient care. we selected data on therapies included in the previous recommenda. teriparatide and zoledronic acid have demonstrated efficacy in the management of GIOP with increases in BMD above that of the comparator arms. or prednisone ⬍5 mg/day (5). the assistance of 2 expert convened an Expert Advisory Panel comprised of 6 rheu- panels (the Expert Advisory Panel to frame the develop. these factors support the need for a below. Since their development.

number of scenarios to a total that was manageable by the Task Force Panel and were clinically meaningful as well. the Hispanic and Asian categories were not used in lation absent. A Because the FRAX equations are dynamic and will study using Medicare claims data found that osteoporosis likely be refined over time (changes occurred in October and fracture risk prevalence were 2-times higher for . the Expert Advisory Panel defined a may confront logistical limitations in calculating a FRAX 10-year risk of a major osteoporotic fracture of 10% or less score within the clinic setting. B. Because the FRAX scores for the patient classification based on an approximation of FRAX 3. age ⱖ50 years with a history of glucocorticoid use at high. African American men. and low-risk were presumed absent. ⫺2. with all other risk factors in the FRAX calcu- white. Expert Advisory Panel did not want to limit the GIOP ples of patients that were typical of low-. We next constructed the clinical scenarios that would be used by the Task Force Panel to develop the recommen- dations.1002/ (ISSN)2151-4658). High-. medium-. white men. The complete set of scenarios is available in the Supple- mentary Appendix (available in the online version of this article at http://onlinelibrary. current smoker.0. using age. 2008 [FRAX version 2. medium. or the European Union. we col- lapsed multiple risk factors for fractures into 3 fracture risk categories: high. for other ethnic/racial groups using typical patient exam- teoporosis Foundation) (22). and greater than 20% were constructed to provide clinicians with examples of or a T score of less than or equal to ⫺2.5. Typical examples of postmenopausal women and men the calculation of the FRAX score (secondary osteoporosis. For example. race. evidence-based estimates of absolute fracture risk and was created for the purpose of quantitatively integrating numerous clinical factors into a clinically use- ful risk prediction model (22). An example of a clinical scenario was “In a high risk patient starting glucocorticoids with an anticipated duration of ⬎3 months or on long-term therapy. ⫺1. Determining risk category cost-effective treatment recommended by the National Os. 10 –20% as medium risk.5). and low risk. third. An average body mass index (BMI) of 25 kg/m2 was also assumed. African American women. a 65-year-old white man receiving the rating process.com/journal/10. and D. Using the over. T score.0. the exclusion of GIOP in the pediatric population. the exclu- sion of inhaled glucocorticoids. medium-.0 race/ethnicity categories of Hispanic and Asian fell con. and 75 years of age). second. race/ethnicity (white and African American). and dated specifically for glucocorticoid-treated cohorts.0. which of the following medications would be appropriate to use based on a range of glucocorticoid doses?” followed by the list of all potential medications to treat or prevent GIOP. and 4. and parental history of a hip fracture) in A. and recommendations by requiring the use of FRAX. age (55.0]) and because the equations have not been vali- either the actual FRAX tool to define low-. 3.2010 GIOP Recommendations 1517 Canada. me- prior fracture. which included only the more extreme glucocorticoids with a T score of ⫺1. In an effort to make the process of evaluating the clinical scenarios both feasible and clinically meaningful.5 at the total hip would be considered a medium-risk patient if other risk factors listed in categories of African American and white. guided in part by the FRAX risk assessment tool (21). the same panel recognized that health care providers FRAX calculator. and the presence of glucocorticoids sistently between the scores for African American and for the calculation. 65. white women. Glucocorticoid use was assumed to be present for all subjects.wiley. The FRAX tool uses updated. medium-. femoral neck density T scores (0. dium. and low risk of fracture in the absence of other risk factors matoid arthritis.5 or a history of a typical patients to “match” their individual patient with fragility fracture as high risk (which is the threshold for the most closely fitting category. More- high-risk categories (as shown in Figure 2). C. To determine the cut points for each of the risk categories. and fourth. ⫺1. The remaining variables used in Figure 2. chronic alcohol use. and ⫺2. rheu. the exclusion of GIOP in the transplant populations. ples may be more complicated because of limited data.0] and September 2009 [FRAX ver- The Expert Advisory Panel recommended the use of sion 3. sex. Recommendations for this type of medium- modifications and compressions were done to reduce the risk patient are found in Tables 2. the Expert Advisory Panel rated 48 patient examples that were derived by permuting each of the following 4 variables in all possible combina- tions: sex. Figures 2A–D as low risk. Therefore. All of these Table 1 were absent. the high-risk patients or the reliance by clinicians upon exam. and obtaining the corresponding major osteoporotic and hip fracture FRAX scores.

The RAND/UCLA Appropriateness prevalent glucocorticoid use. These factors (Table 1) need to be considered data for evaluation of clinical scenarios used to illustrate in the health care provider’s assessment of the patient and the key permutations of potential clinical interventions for may shift an individual into a greater risk category the evaluation and management of GIOP. reason that clinicians would move a patient to a higher The function of the evidence report was to provide the risk category.wiley.29 –76) meeting inclusion BMD but a fracture risk that is similar to African Ameri. did not have RCT data as supportive evidence. We priateness of a treatment based on patient-specific symp- searched Medline (through PubMed) by applying MeSH toms. Hispanics and whites have a lower criteria for the evidence report.12. risedronate. current each RCT and CCT. score for the 53 included articles was 2. JMG). In postmenopausal women in Three reviewers screened each title and abstract for rel- the US. Details of the search strategy are listed in Supplementary Low body mass index Appendix A (available in the online version of this article Parental history of hip fracture at http://onlinelibrary. to calculate the 10-year probability of a major osteoporotic Jadad scores are based on a 5-point scale. such as those involving repeat BMD testing. those receiving higher doses are likely to have a scores suggesting higher-quality studies. VKR. and consuming three or more alcoholic drinks outcomes. Canada.26). which incorporates elements of the nom- fessional research librarian.1002/(ISSN) Current smoking 2151-4658). The principal inves- fractures (25. with higher fracture. Clinical factors that may shift an individual to a greater risk category for glucocortcoid-induced to GIOP. Searches for calcium. This score indicated that the articles as a nous pulse glucocorticoids may also increase the risk of whole were of only moderate quality. criteria and these publications formed the basis of the cans (24).1518 Grossman et al testosterone were performed in a similar manner. and Hispanic Americans than complete the search. This process resulted in a BMD and highest fracture risk. we also osteoporosis conducted similar searches of EMBase in CENTRAL (28). report that was used in the next phase of the recommen- domized clinical trials (RCTs) or controlled clinical trials dations development. tions.com/journal/10. and practice guidelines. clinical scenarios and formed the basis for the evidence vitamin D. Relevant meta- that exceeds the least significant change may be another analyses (78 – 84) were also described in the report. Annual Intravenous pulse glucocorticoid usage Meeting of the American Society for Bone and Mineral Re- Declining central bone mineral density measurement that search. may be increased in patients who have additional risk LC. qualitative literature reviews and expert-identified atic review of the therapies currently approved for the articles were used to summarize existing evidence. This treatment of postmenopausal osteoporosis or GIOP in the summarized data helped to guide the development of the US. or both. we replicated the search strat. EV. sample size. Some clinical (low3medium. The method headings and relevant keywords with references from Janu. smoking. Articles were limited to ran. zoledronic ment of experts to yield a statement regarding the appro- acid. This technique has previously . evidence report. scenarios. study characteristics. and quality assessment (calculated using the per day). calcitonin. We conducted a system. and European Calcific Tissue Society European Sym- exceeds the least significant change posium on Calcified Tissues were manually searched for relevant RCTs. combines a systematic review of the scientific literature ary 1966 through August 28. teriparatide. With the assistance of a pro. Asian Americans. Method (85– 87). The Core Executive Panel and Expert Advi- sory Panel members contributed expert-identified studies to whites.44 (interquartile Higher cumulative glucocorticoid dose (3) and intrave. vitamin D. or medium3high). medical history. and Asians have the lowest total of 53 articles (7–9. but limited Table 1. abstracts from the 2007–2008 ACR ⱖ3 alcoholic drinks per day Higher daily glucocorticoid dose Annual Scientific Meeting. (CCTs) of human subjects reported in English with an available abstract. 2008 using Cochrane’s Highly with expert opinion and yields specific criteria of appro- Selective Search Strategy (28) to improve the specificity of priateness that can be used as the basis for review criteria. Accepted articles were then reviewed Fracture risk in the “typical patient” (Figures 2A—D) independently by 2 of the 7 reviewers (RG. the search. was used to generate the recom- egy employed in the Comparative Effectiveness of Treat. A declining central BMD measurement tigator (JMG) adjudicated discrepant results. Using the Cochrane Handbook’s guidance. inal and Delphi method. ibandronate. For (such as low BMI. estrogen. or the European Union as well as calcium.11. MM. parental history of hip fracture. mendations presented in this report. and test results. range 1–3). NMP. European League Against Rheu- Higher cumulative glucocorticoid dose matism annual European Congress of Rheumatology. African Americans have the highest BMD and evance to the specific aims of the predefined inclusion lowest fracture risk. The RAND/UCLA ments for Low Bone Density (including Osteoporosis) Report Appropriateness Method was developed to combine the prepared for the Agency for Health Care Research and best available scientific evidence with the collective judg- Quality for alendronate. and strontium (27). The study duration must have been ⱖ6 RAND/UCLA Appropriateness Method used by the months and all subjects were required to have incident or Task Force Panel. Since FRAX uses an average glucocorticoid dose 5-point Jadad score) (77) were reported in tabular form. Additionally. and the consensus on the relevant data factors that were presumed to be absent in our scenarios was entered into a standardized data abstraction form. African Americans (23). and testosterone. The mean Jadad greater absolute fracture risk than estimated by the FRAX. In those situa- Systematic literature review.

where 1 ⫽ appropriate and 9 ⫽ not appropri. to risk factors for premenopausal patients arose that were ios and definitions of all variables were provided by e-mail not adequately addressed by the systematic review. panel members and discussed in a subsequent conference ate. glucocor. The Task Force fore. were provided to each from the panelist voting fell in the 1 to 3 range and there voting member. The clinical scenarios specifically did not attempt to The Task Force Panel independently rated the appropri. There- and discussed during a conference call. therapy in hypogonadal patients. the clinical scenarios with varying fracture risk. more of the 10 voting panelists rating the scenario in the . endocrinology. and duration. and a patient care round of voting determined the updated recommenda- advocate. recommendations are for an anticipated or prevalent duration of ⱖ3 months of glucocorticoids. The results of the second matology. Statistical analysis. Results from the first round of voting were tabulated call.and medium-risk patients. the Task Force Panel.2010 GIOP Recommendations 1519 Figure 3.89). including range and median as dividual scenarios were endorsed when the median score well as the panelist’s own ranking. been described as the best systematic method of combin. mous voting by the Task Force Panel alone occurred using ing expert opinion and evidence (88. voting for premenopausal women and for men age Panel was asked to use the evidence as summarized in the ⬍50 years without prior fragility fracture was deferred evidence report as well as their own clinical judgment to until an additional literature search to identify non-RCT/ rate the appropriateness of employing a particular therapy in the context of each clinical scenarios using a 9-point CCT studies had been performed and disseminated to Likert scale. and presented at a face-to-face panel meeting comprised of the Core Expert Panel and Task Force Panel. the same scale. tions. Recommendations applying to in- rized anonymous scores. additive therapy and testosterone and estrogen as primary which consisted of 10 individuals from the fields of rheu. prioritize the use of one drug over another when both were ateness of the specific interventions within the context of deemed appropriate in a particular circumstance. Vitamin D and calcium were evaluated as As the first step in this process. At the face-to-face meeting. Areas of discrepancy as well as areas of was no disagreement. additional questions related ticoid dose. Disagreement was defined as 3 or agreement were discussed and a second round of anony. * ⫽ for low. Approach to postmenopausal women and men age ⬎50 years initiating or receiving glucocorticoid therapy. Instructions for grading scenar. received the evidence report and case scenarios. and geriatrics. The summa.

RESULTS We used the AGREE instrument to help assure that the updated recommendations covered all the important do. Although few RCTs were using the smallest dose of glucocorticoid for the shortest performed exclusively in premenopausal patients. Quality of Care Committee. stakeholder involvement. and followup of all patients receiving of evidence A. GIOP. ticoids used or expected to be used for at least 3 months. pert opinion.e.wiley. many duration possible was recommended as an important strat- studies did include premenopausal women as part of the egy to minimize osteoporosis risk. data were derived cerning counseling for lifestyle modifications and fol- from a single RCT or nonrandomized study. data were derived from multiple RCTs or a glucocorticoid therapy. the Supplementary Appendix entitled Clinician’s Guide pendence. These studies were therefore included dose of glucocorticoids that does not accelerate bone loss when determining the evidence grade for recommenda. ex.1520 Grossman et al Figure 4. Absence of comments and recommendations. 4 to 9). ACR risk evaluation are also available (92. The panel rec- . or increase fracture risk (3). data were derived from consensus.. Since there may be no overall cohort. the absence of a recommendation generally implied only inadequate or conflicting evidence. applicability.com/journal/10. or case series. that a treatment was inappropriate in particular settings. counseling for life- American College of Cardiology (91) as follows: 1) for level style modifications. In addition to the recommendations listed. Tables 2 and 3.93). pred ⫽ prednisone. rigor of development.1002/(ISSN)2151-4658). The results of the modified RAND/UCLA method pro- mains and attributes (90). a draft of the evidence report observing their gait. (available in the online version of this article at http:// onlinelibrary. could include asking patients about previous falls and tional manuscript review. In addition to tradi. Rating the strength of evidence. 2) for level B evidence. Only positive state. The 17 recommendations con- meta-analysis. and 3) for lowup of patients receiving glucocorticoids are shown in level C evidence. A variety of other approaches to fall was submitted to the ACR Guidelines Subcommittee. The AGREE instrument grades duced the recommendations shown below. The strength of evi- dence was graded using the methods reported by the Recommendations for assessment. recommendations for counsel- tions for premenopausal women and men younger than ing and assessment are extended to all doses of glucocor- age 50 years. which were incorpo- any recommendation should not be construed to suggest rated into the final recommendations. middle or highest tertiles (i. A synopsis of the recommendations are shown in clarity and presentation. Figures 3 and 4 elements of validity and includes 6 sections: scope and represent proposed approaches to the management of purpose. Approach to premenopausal women and men age ⬍50 years initiating or receiving glucocorticoid therapy. and editorial inde. The panel recommended that an assessment of fall risk ACR review of recommendations. and ACR Board of Directors for ments were included in the recommendations.

Recommendations on counseling for lifestyle Table 4. coid therapy. apy has already been initiated. D measurement Annual height measurement C Recommendations for high-risk postmenopausal glu- Assessment of incident fragility fracture C cocorticoid-treated women and glucocorticoid-treated Assessment of osteoporosis medication C compliance men age >50 years. While grade 2 and 3 vertebral fractures classified achieve therapeutic levels (97). fracture. the results of the previous Calcium and vitamin D supplementation counseling BMD.5 mg/day prednisone A vitamin D intake OR Fall risk assessment C Zoledronic acid for ⱖ7.000 IU/day are 2 target dosing regimens.and medium-risk patients.5 mg/day prednisone* B for those initiating or currently High-risk patient† receiving prednisone ⱖ5 mg/day or its Alendronate A equivalent OR Calcium intake (supplement plus oral A Risedronate A intake) 1. tiating prescription therapy for high-risk patients. † Any anticipated dose or duration of glucocorticoids justifies ini- ommended that clinicians consider vertebral fracture as. or dosages of Recommendations for low.500 mg/day* OR Vitamin D supplementation* A Zoledronic acid* B OR * Recommendations for calcium and vitamin D supplementation Teriparatide‡ B are for any dose or duration of glucocorticoids.99). or prevalent glucocorticoid therapy of a duration of at least 3 months (unless otherwise noted) Level of Recommendation evidence Level of Recommendations evidence Weight-bearing activities C Smoking cessation C Low-risk patient Avoidance of excessive alcohol C Alendronate for ⱖ7.2010 GIOP Recommendations 1521 Table 2.95). the BMD. risk factors for fracture. and the rate of change of was recommended for all patients beginning glucocorti. >3 months were to start prescription osteoporosis therapy for patients Level of with an anticipated glucocorticoid usage duration of ⱖ3 Recommendation evidence months or those on prevalent glucocorticoid therapy for at least 3 months. sessment (VFA). Pharmacologic recommendations for modification and assessment of patients starting postmenopausal women and men age >50 years starting glucocorticoids at any dose with an anticipated duration glucocorticoid therapy with an anticipated duration of >3 months >3 months. the panel noted that more research is needed to the frequency of testing include the presence of additional improve the specificity of grade 1 fractures noted on ver. Vitamin D supplementation to achieve “ther- apeutic” levels of 25-hydroxyvitamin D.200–1. Consistent with the National Osteo- porosis Foundation Guidelines (19) that suggest treatment . Factors that will influence fracture. 800 –1. Recommended monitoring for patients receiving ticoid-treated men age >50 years. The glucocorticoid dose warranting thera- Consider serial bone mineral density C peutic intervention represents the practitioner’s intended testing average daily dose and varies according to the specific Consider annual serum 25-hydroxyvitamin C medication being considered. the interval of such testing have been shown to have high specificity for vertebral remains controversial (98. whether or not osteoporosis ther- tebral fracture assessment.5 mg/day prednisone A intake (⬎2 drinks per day) OR Nutritional counseling on calcium and C Risedronate for ⱖ7. or conventional spine imaging because vertebral fractures are often asymptomatic. as shown in Table 4. rather than a dura- tion of ⬎3 months. * Head-to-head comparison data available in the Discussion sec- tion. The recommendations prevalent glucocorticoid therapy for a duration of for low.5 mg/day prednisone* B Baseline dual x-ray absorptiometry C Medium-risk patient Serum 25-hydroxyvitamin D level C Alendronate for any dose of glucocorticoids A Baseline height C OR Assessment of prevalent fragility fractures C Risedronate for any dose of glucocorticoids A Consider radiographic imaging of the C OR spine or vertebral fracture assessment Zoledronic acid for ⱖ7. ment recommendations for patients receiving steroids who glucocorticoids can interfere with vitamin D absorption would otherwise be considered a low or medium risk and may necessitate a higher supplementation dose to (94. especially in the setting of significant ‡ For ⱖ5 mg/day prednisone with a duration ⱕ1 month and for any height loss or a history of back pain consistent with a dose of glucocorticoids with a duration ⬎1 month. and might change treat. however.and medium-risk post- menopausal glucocorticoid-treated women and glucocor- Table 3. Head-to-head comparison data available in the Discussion section. the dose of steroids. Although serial bone den- according to the Genant semiquantitative method (96) sity testing was recommended.

While these recommendations improve upon previous hydroxyvitamin D measurement. based on the iterative formal group process.5 C mg/day DISCUSSION OR Teriparatide if prednisone C Developed using state-of-the-art validated methodology ⱖ7. and the risk of these medications to a fetus. these . and glucocorticoid use is dose related. Men younger than age 50 years were con. OR dations were similar to those for postmenopausal women Teriparatide for any dose* B Childbearing potential and for men except that the anticipated duration of glu- Alendronate if prednisone ⱖ7. categorization of high. For Nonchildbearing potential these reasons. premenopausal women “average” dose or exposure. The mg/day panel suggested this area warranted further research. cal. Recom. while the pre. fragility fracture rosis therapy even in the absence of glucocorticoid use. For those of nonchildbearing potential.5 mg/day* currently not applicable to premenopausal women or men younger than age 40 years. which relied on mendations for counseling and monitoring are now T scores. and premeno. Furthermore. Alendronate if receiving prednisone A sidered together with the premenopausal women. advance over previous recommendations. height and 25. this report provides the up- dated ACR recommendations for adult patients receiving * Head-to-head comparison data available in the Discussion section. Further- as consistent a risk factor for fracture in GIOP when com. data for recommendation tion. the OR risk factors that influence fracture propensity in these pop. mass in the spine before the hip. OR Risedronate if prednisone ⱖ7. the computer pausal women of childbearing potential with a history of a modeling underlying FRAX uses only the bone density fragility fracture. The newer therapies zoledronic acid and value for the hip. The FRAX tool is prednisone ⱖ7. evaluation for prevalent statements. tients’ overall clinical risk profiles. and low risk for fracture tebral fracture assessment or radiographic imaging of the assessment of patients is based largely on the FRAX tool spine and calcium and vitamin D supplementation for any (21). FRAX alone cannot tosterone are no longer endorsed. and this may be an issue in GIOP.1522 Grossman et al when the 10-year risk of major osteoporotic fractures is Table 5. This represents an taining baseline and followup BMD measurement. Recommendations for premenopausal women ⱖ20% (our high-risk group). the recommen. more. recommendation 1–3 MONTHS OF GLUCOCORTICOIDS Recommendations for premenopausal women and men Nonchildbearing potential age <50 years. Thus.5 A cocorticoids required to trigger therapy was 3 months. drugs with OR shorter half-lives were recommended (as shown in Table Zoledronic acid for any dose* B 5). the long-term Childbearing potential—Inadequate safety of medications used to treat GIOP in this popula. insofar as there is limited evidence for the treat- ⱖ5 mg/day ment of GIOP in both these populations.5 mg/day* for guideline development. Several of the clinical risk factors contributing recommendations are delineated for postmenopausal to FRAX do not take into account dose response but use women and men over age 50 years. However. and men under age 50 years with a history of mended that these patients receive prescription osteopo. Since BMD may not be replace clinical judgment in risk stratification. oral glucocorticoid therapy. underestimation of fracture risk. weight-bearing activities. and consideration for ver. Updated pharmacologic to consider. the Task Force Panel recom. the panel concluded that they could make Alendronate for any dose A recommendations only for those with a prevalent fragility OR fracture who were clearly at higher risk for additional Risedronate for any dose A fracture. These 2 ⱖ5 mg/day populations were thought to represent a similar patient OR Risedronate if receiving prednisone A group. medium. is not well defined. For women of childbearing potential. these recom- excessive alcohol intake. Zoledronic acid if receiving B ulations have not been well defined. expanded to include fall risk assessment. there is good evi- not of childbearing potential and men under the age of 50 dence that the risk associated with alcohol consumption years with a history of a fragility fracture. leading to a possible viously included therapies estrogen replacement and tes. hence the recommendations for a duration of glucocorti. they are not without their limitations. limiting pared with other forms of osteoporosis (6). The and incident fragility fractures. The 2001 recommendations included counseling those patients receiving glucocorti- coid therapy on smoking cessation or avoidance. Additionally. and there are limitations to FRAX that are important duration of glucocorticoid use. Grade of coids of ⬍1 month (Table 4). and ob. mendations are guided in part by the FRAX score or pa- cium and vitamin D intake and supplementation. since teriparatide are now recommended along with alendronate patients receiving glucocorticoids frequently lose bone and risedronate for the treatment of GIOP. Also. either ⱖ3 MONTHS OF GLUCOCORTICOIDS from current or previous exposure.

and all authors ap- or intramuscular glucocorticoids without daily oral doses. Patkar. The recommendations for premenopausal women and Study conception and design. Lukert B. very little literature exists regarding the risk of All authors were involved in drafting the article or revising it and treatment for patients who receive intermittent pulse critically for important intellectual content. testosterone. Volkmann.11. Caplan. fracture rates were low and did not differ between the 2 tions is limited by the quality of the available evidence. Chen.73. dations support the use of a variety of therapies. Patkar.83. 1. With more than an estimated 1 million patients tions.39: 1383–9. Gross- and this population was not addressed in these recommen. Johnell O.50.98: the need for further research. for fracture risk and the treatment of GIOP in this popula. and ralox. this panel discussed the use of osteoporosis epidemiology of GIOP and despite an increased number of therapies for patients with chronic renal insufficiency and higher-quality clinical trials in recent years. Chen.1002/ icantly more than in the patients receiving risedronate at (ISSN)2151-4658) that need to be considered when evalu. Pols HA. Abenhaim L. In an 18. Buckley LM. evidence to make disease-specific recommendations. Therapies that were approved after the original should be individualized (100). younger men are constrained by the paucity of evidence Caplan. Vacek PM. Deal. however. Zhang B. recommend the use of the following agents: ibandronate.12). Analysis and interpretation of data. Despite significant advances in the understanding of the thermore. Johansson H. AUTHOR CONTRIBUTIONS ditionally. Cooper SM. 22:1055–9. Additionally. estrogen. of the data were considered insufficient for the panel to 5. Ad. while these recommendations do not 6. Sambrook PN. QJM 2005. Eisman JA. The panel did knowledge still exist. Low bone density in premenopausal patients has Chen. reflecting the (20 ␮g/day) was more effective than alendronate (10 mg/ populations studied in clinical trials and the differing day) at improving spine and hip BMD and reducing the risk– benefit values of the agents. with the same BMD in postmenopausal patients (102).27:465– 83. Saag. Saag. Patkar. de Laet C. 191– 8. Cooper C. McMahon. and cumulative doses. management of calcium. and phosphorus in patients with chronic renal insufficiency (101). thereby restricting Oral corticosteroids and fracture risk: relationship to daily the conclusions that can be drawn (7–9. Saag. Guidelines exist for the literature review are not included in these recommendations. fracture risk. both treat- the evidence report available in the Supplementary Ap. The ab. Rheumatology (Oxford) 2000. Curtis. GIOP has wide-reaching consequences. Deal.wiley. (30. Leufkens HG. Van Staa TP. Volkmann. Ann Rheum Dis 1986. McMahon. and these areas were not specifically considered by the panels. Champion GD. Furst. noting that these decisions Addendum. Leib ES. J Rheumatol 1995. Endocrinol Metab Clin North Am tion of 4 that were limited to premenopausal patients) 1998. In a 1-year trial. been associated with a lower fracture risk when compared Caplan. sity of patients with rheumatoid arthritis. strued as counseling against treatment for premenopausal Cooper C. et al. Leufkens HG. de Laet C. but as an indication of fracture in patients using oral glucocorticoids. condition. A simple score for estimating the long-term risk of women and young male patients. Yeates MG. every set of recommenda. tion. in the US receiving a prescription for glucocorticoids The Task Force Panel discussed the incremental impact yearly (16). Despite the fact that some limited data address their 4. The vertebral ating individuals. . It is anticipated that GIOP recom- not reach a consensus in this population due to limited mendations will undergo future revisions as new evidence evidence.2010 GIOP Recommendations 1523 updated recommendations have added a greater number of month study with additional 36-month data. Grossman. the majority of RCTs (with the excep. Ranganath. While the recommen. proved the final version to be submitted for publication. Gordon.com/journal/10. McMahon. Furst. Cartularo KS. sidered for these patients. data analysis. is developed. Lane NE. teriparatide thresholds around glucocorticoid dosing. Grossman. Popck NA. Grossman. Deal. risk of new vertebral fractures (11. Ranganath. vitamin D. arms. At 12 months. there are 2 recent LJ III. Kanis JA. 3. Geusens P. 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