A rational use of glucocorticoids in patients with early arthritis has a minimal impact on bone mass
© Monica Ibañez et al.; licensee BioMed Central Ltd. 2010
Received: 23 July 2009
Accepted: 23 March 2010
Published: 23 March 2010
Glucocorticoid (GC)-induced osteoporosis is a frequent complication in patients with rheumatoid arthritis. However, little information exists about the consequences of GC use in patients with early arthritis. Here we describe the variables underlying the use of GC in early arthritis, as well as its effect on bone-mineral density.
Data from 116 patients in our early arthritis register were analyzed (90 women; median age, 52.5 years, interquartile range (IQR, 38.5-66); 6-month median disease duration at entry (IQR, 4-9)). In this register, the clinical and treatment information was recorded systematically, including the cumulative GC dose. Lumbar spine, hip, and forearm bone-mineral density (BMD) measurements were performed at entry and after a 2-year follow-up. A multivariate analysis was performed to establish the variables associated with the use of GCs, as well as those associated with variations in BMD.
Of the patients with early arthritis studied, 67% received GCs during the 2-year follow-up. GCs were more frequently prescribed to elderly patients, those with higher basal disease activity and disability, and patients with positive rheumatoid factor. When adjusted for these variables, GCs were less frequently prescribed to female patients. The use of GCs was associated with an increase of BMD in the ultradistal region of the forearm, although it induced a significant loss of BMD in the medial region of the forearm. No relevant effect of GC was noted on the BMD measured at other locations.
The frequent use of GCs as a "bridge therapy" in patients with early arthritis does not seem to be associated with relevant loss of bone mass. Moreover, cumulative GC administration might be associated with an increase of juxtaarticular BMD.
Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease that has been associated with disability, the existence of comorbidities, and decreased life expectancy [1, 2]. The use of glucocorticoids (GCs) to treat RA offers rapid antiinflammatory effects and the capacity to arrest radiologic progression [3–6]. However, long-term GC use may cause multiple adverse events, even at low doses [7, 8]. Therefore, an individual evaluation is required to establish the best risk/benefit ratio for their prescription [9, 10].
One of the most striking side effects of this drug is GC-induced osteoporosis (GIOP), a complication in patients with RA that can be prevented [11–13]. The prevalence of OP in RA patients is higher than that in the normal population, ranging from 20% to 37% [14, 15], although this figure increases to almost 50% among postmenopausal women after long-term steroid use . However, establishing the real contribution of GCs to OP in RA is challenging because bone mineral loss is of multifactorial origin in these patients, and it may be influenced by inflammatory cytokines, inactivity, GCs, disease-modifying antirheumatic drugs (DMARDs), as well as the classic risk factors for OP.
Despite the different studies focusing on OP, little information is available regarding the use of GCs in patients with early arthritis. Nevertheless, it has been suggested that using GC in these patients does not affect bone mass, as has been observed in the long-term disease, probably because controlling inflammatory activity at early stages may prevent bone loss [17–19].
The aim of this study was to analyze the patterns of GC use and the reasons for its use in a population of early arthritis patients. In addition, we studied the impact of different factors on the evolution of mineral bone content in these patients, including GC use.
Materials and methods
Patients and study design
Baseline population characteristics
Total (n = 116)
RA (n = 78)
UA (n = 38)
Female gender, n (%)
Disease duration (mo)
Rheumatoid factor, n (%)
Anti-CCP, n (%)
Comorbidities: n (%)
Menopause (% of women)
Age at menopause (years)
Smoking n (%)
Exercise (rare/moderate/intense) (%)
Body mass index (kg/m2)
Prior personal fractures (%)
Prior family fractures (%)
The study includes data from patients followed up over a period of 2 years and who were evaluated at four visits during this period. The following data were collected and entered into an electronic database: clinical and demographic information, including the 28 tender and swollen joint counts (TJCs and SJCs, respectively); global disease assessment by patient (GDAP) and physician (GDAPh) on a 100-mm visual analogue scale; and basic laboratory tests including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF: by nephelometry; positive if >20 IU/ml), and serum antibodies directed against cyclic citrullinated peptide (anti-CCP: ELISA, Euro-Diagnostica Immunoscan RA; positive at >50 IU/ml). The four-component disease-activity score based on 28-joint counts and ESR (DAS28) was calculated as described previously . The patients also completed the validated Spanish version of the Health Assessment Questionnaire (HAQ) to assess functional ability .
Comorbidity of other medical conditions was evaluated during the follow-up period, including that of hypertension, diabetes mellitus, and thyroid dysfunction. Other known factors that affect bone mass were also assessed, such as body mass index (BMI) expressed in kilograms per square meter, age at menopause, daily calcium intake (0-500 mg, 500-1,000 mg, or >1,000 mg), exercise (sedentary, moderate, or intense aerobic exercise), smoking, and clinical fractures (vertebral, peripheral, or both) before inclusion in our register and during the follow-up period.
Information about disease-modifying antirheumatic drugs (DMARDs) treatment during the follow-up period, the dose of prednisone at each visit, and the cumulative GC dose (as a prednisone equivalent) also were obtained. Regarding the latter, we separately collected the cumulative dose of GCs prescribed orally and that administered as joint and soft-tissue injections (see Additional file 1 for further information). Most injections were performed in the knee or shoulder; no wrist injections were performed, although a few injections were administered into the small joints of the hand, mainly proximal interphalangeal.
Bone-mineral density measurement
Dual-energy x-ray absorptiometry (DXA) scans were performed on a Hologic QDR-4500/W Elite densitometer (Hologic Inc., Bedford, MA, USA), and the bone mineral density (BMD) was expressed in grams per square centimeter. Lumbar spine, hip, and nondominant forearm DXA scans were carried out at the patient's first (median disease duration, 7 months (IQR, 4-9)) and last visit in the study (median disease duration, 32.5 months (IQR, 29-35)). The densitometer was calibrated daily by using a quality assurance spine phantom of known bone mineral content (BMC) supplied by the manufacturer. The in vivo short-term coefficient of variation for our DXA machine was 0.9% for measurements at the lumbar spine level and 1.4% for the duplicate total hip measurements in 10 healthy subjects (data not shown).
We calculated the yearly variation in BMD at each location as follows: ΔBMD = (BMDfinal - BMDbaseline) × 365/number of days between both measurements. The results of these variables are presented as milligrams per square centimeter per year.
The descriptive analysis was performed by calculating the means and standard deviations (SDs) of quantitative variables with a gaussian distribution. The median and the interquartile range (IQR) were calculated if the variables did not display a normal distribution. An estimate of the proportions was calculated for qualitative variables. Unless otherwise stated, Student's t test was applied to compare the means of variables with a normal distribution, and the Mann-Whitney or Kruskall-Wallis tests were used for variables that did not have a normal distribution. Fisher's test was used to compare the categoric variables.
Because one third of the patients did not take GCs during the follow-up period, we used the zip command of Stata 9.2 for Windows (StataCorp LP, College Station, TX, USA) to analyze the cumulative dose of GCs. This command defines a zero-inflated Poisson regression that enables us to analyze both the reasons underlying the zero counts (no GCs prescribed) and those associated with the cumulative GC dose. All variables associated with a P ≤ 0.15 in the bivariate analysis were included as independent variables, both to estimate the Poisson regression of the dependent variable (cumulative GC dose in milligrams per month) and in the inflate option of the zip command. This option specifies the equation that determines whether the observed count is zero. The final model was then reached by using stepwise backward estimates, removing all variables with P > 0.15.
A generalized linear model was applied to assess the independent effect of different variables on the ΔBMD at the lumbar spine, hip, and forearm. We used the glm command of Stata 9.2 to define the linear regression of all the variables with a P value ≤ 0.15. The final model was then reached by using stepwise backward estimations, removing all variables with P > 0.15. Subsequently, the cumulative GC dose was forced into the model to determine whether it affected the variation in BMD once the model was adjusted for the variables considered relevant. To assess whether oral and intraarticular/soft tissue injection had equivalent effects on BMD, we also developed a model with two independent variables, one for the cumulative GC dose prescribed orally and another for the cumulative GC dose administered as soft-tissue and joint injections. However, this model did not provide more information than the model that included the effect of the global cumulative GC dose.
Description of the use of glucocorticoids
The prescription of GCs was associated with male gender and the more-advanced age of the patients. In addition, a tendency was noted to prescribe GCs more frequently to those patients with a higher baseline DAS28 and HAQ, although this was not statistically significant in our cohort. In those patients who received GCs, the cumulative dose was significantly higher in men, in older patients, in those patients with seropositive arthritis or a worse functional status, in those with a higher disease activity at baseline, as well as in those treated with combined DMARD therapy. An inverse relation between cumulative GC dose and disease duration at baseline was also observed. Once adjusted for all these variables, patients with UA received higher doses of prednisone than did those with RA. More-extensive information on the motives underlying GC prescription and the cumulative GC dose is provided in Additional file 3.
Effect of glucocorticoids on bone mass
Variables associated with the variation in bone-mineral density (mg/cm2/year) at different sites in patients with early arthritis
Coeff ± SD
Coeff ± SD
Coeff ± SD
Coeff ± SD
Coeff ± SD
Age (by year)
0.3 ± 0.1
0.2 ± 0.1
6.1 ± 3.6
8.7 ± 4.1
-6.4 ± 3.3
-3.5 ± 1.4
6.9 ± 3.9
6.7 ± 3.6
-19.5 ± 4.8
-10.3 ± 5.3
-13.7 ± 3.9
-10.3 ± 4
-0.3 ± 0.1
-0.2 ± 0.1
-2.3 ± 1.6
0.01 ± 0.02
-0.01 ± 0.02
0.05 ± 0.02
-0.001 ± 0.009
-0.05 ± 0.02
The most intriguing finding in our study was that the use of GCs has no relevant impact on bone mass in patients with early arthritis. Earlier studies that focused on the effect of GCs on bone mass in patients with early arthritis maintained fixed low doses of GC for long periods, or alternatively, they involved a schedule that tapered the doses of these drugs from high to low doses and then withdrew the GC, or maintained it at low doses for a long period [18, 25]. However, in our early-arthritis clinic, no preestablished therapeutic protocol existed, and GCs were prescribed mainly as a bridging therapy in patients with more-severe forms of the disease, on average starting at 15 mg/day of prednisone and then gradually tapering to its withdrawal ~14 months later. No more than 50% of patients received GCs orally, and only 17.3% of patients were under treatment with GCs at the end of the study. In addition, the prescription of the drug was adjusted to the profile of comorbidity, the disease severity, and the patients' preferences. Thus, the prescription of GCs was more frequent in older patients (possibly related to the tendency to be less aggressive with DMARDs because of their higher comorbidity) and male patients (independent of age and disease activity), probably because women are more worried about the cosmetic side effects of GCs, and they reject high doses or long steroid treatments.
Unexpectedly, after adjustment for confounding factors in the multivariate analysis, patients with UA received more cumulative doses of GCs than did RA patients. This may reflect the preference in our center to use GCs instead of DMARDs in patients who do not meet ACR criteria for RA, at least during the first months of the follow-up.
The main variables associated with bone loss in patients with early arthritis are similar to those affecting the general population: the menopause and comorbidities such as diabetes or thyroid disorders. Interestingly, despite the limited number of patients in our study, we could detect an association between disease activity and bone loss in the lumbar spine, ultradistal forearm, and the total hip measurements, as suggested previously . However, we did not find any relation between the annual variation of BMD and other factors such as calcium intake, exercise, smoking, personal or family history of fractures, or BMI (data not shown). The failure to demonstrate such a relation may reflect the limited number of patients, or perhaps, these factors may have less weight in the variation in bone mineral content in patients with arthritis than among the general population.
Intriguingly, a trend was noted toward higher bone mineral content in patients with hypertension at two of the sites where bone mass was measured. This increase might be related to the relatively high use of thiazides in association with renin-angiotensin antagonists in patients with hypertension in our country , particularly given that both kinds of drugs have been associated with improvements in BMD [28–31].
In accordance with previous studies in early arthritis, we did not find a significant correlation between cumulative doses of GCs and BMD variation at the lumbar spine or hip [18, 19, 26]. Nevertheless, our most relevant finding was at the forearm, where BMD has not previously been evaluated. We observed a clear association of the cumulative GC dose with an increase in BMD at the ultradistal forearm. This finding is probably related to the rapid and strong control of inflammation by GCs and most likely to its ability to arrest osteoclast function . In this regard, GIOP was recently proposed to be mediated through the upregulation of a receptor activator for nuclear factor κB ligand (RANKL) expression and the inhibition of osteoprotegerin expression [33–35]. However, with regard to RA synovitis, the levels of multiple cytokines with osteoclast-inducing activity, including RANKL, are elevated , and intraarticular GC decreases synovial RANKL expression . This latter finding may be related to the increase in juxtaarticular BMD described here, which might also be associated with the ability of GC to impair joint destruction in early RA .
By contrast, moderate bone loss was found at the mid-forearm, where 95% is cortical bone. It is tempting to hypothesize that these effects might be explained by the development of secondary hyperparathyroidism due to the influence of GC on calcium metabolism [38, 39]. Indeed, three patients had symptomatic fractures during follow-up (Additional file 4), two of which were peripheral fractures associated with cortical weakness.
One possible limitation of our study is the limited number of patients studied. However, we think that this deficit can be balanced by the exhaustive data collected in a highly controlled population. In addition, BMD was evaluated in six different anatomic locations. Thus, if we found a weak association at several locations, we could assume that it would have been less likely to have occurred by chance. It might also be argued that 2 years is a short period in which to study variations in BMD. However, it is well known that the effect of GC on bone mass occurs soon after exposure. It would have been interesting to measure BMD every 6 months during the follow-up period, although our schedule of BMD assessment was based on the follow-up recommendations for osteoporotic patients .
Among our patients with early arthritis, GCs were prescribed mainly as a bridge therapy to elderly patients, men, and patients with severe forms of the disease. This pattern of use, starting on average with 15 mg/d of prednisone and tapering toward withdrawal about 1 year later, does not seem to represent a relevant risk factor for bone loss. Furthermore, the cumulative GC dose correlated with an increase of juxtaarticular BMD, once adjusted for the classic variables associated with primary OP.
serum antibodies directed to cyclic citrullinated peptide
disease-modifying antirheumatic drugs
receptor activator for nuclear factor κB ligand
This work was funded by grants from the Instituto de Salud Carlos III: FIS 05/2044, to I G-A, and FIS 03/0911, to A G-V. The work of I G-A was funded in part by a grant to promote the research work in the Spanish National Health Service from the Instituto de Salud Carlos III (Programa de Intensificación de la Labor Investigadora).
- Sokka T, Abelson B, Pincus T: Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol. 2008, 26: S35-61.PubMedGoogle Scholar
- Carmona L, Gonzalez-Alvaro I, Balsa A, Angel Belmonte M, Tena X, Sanmarti R: Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates of disease severity. Ann Rheum Dis. 2003, 62: 897-900. 10.1136/ard.62.9.897.PubMed CentralView ArticlePubMedGoogle Scholar
- Jones G, Halbert J, Crotty M, Shanahan EM, Batterham M, Ahern M: The effect of treatment on radiological progression in rheumatoid arthritis: a systematic review of randomized placebo-controlled trials. Rheumatology (Oxford). 2003, 42: 6-13. 10.1093/rheumatology/keg036.View ArticleGoogle Scholar
- Svensson B, Boonen A, Albertsson K, Heijde van der D, Keller C, Hafstrom I: Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial. Arthritis Rheum. 2005, 52: 3360-3370. 10.1002/art.21298.View ArticlePubMedGoogle Scholar
- van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW: Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med. 2002, 136: 1-12.View ArticlePubMedGoogle Scholar
- Wassenberg S, Rau R, Steinfeld P, Zeidler H: Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2005, 52: 3371-3380. 10.1002/art.21421.View ArticlePubMedGoogle Scholar
- Caplan L, Wolfe F, Russell AS, Michaud K: Corticosteroid use in rheumatoid arthritis: prevalence, predictors, correlates, and outcomes. J Rheumatol. 2007, 34: 696-705.PubMedGoogle Scholar
- McDonough AK, Curtis JR, Saag KG: The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol. 2008, 20: 131-137. 10.1097/BOR.0b013e3282f51031.View ArticlePubMedGoogle Scholar
- Gonzalez-Alvaro I, Hernandez-Garcia C, Villaverde Garcia V, Vargas E, Ortiz AM: [Variations in the drug treatment of rheumatoid arthritis in Spain]. Med Clin (Barc). 2002, 118: 771-776.View ArticleGoogle Scholar
- Thiele K, Buttgereit F, Huscher D, Zink A: Current use of glucocorticoids in patients with rheumatoid arthritis in Germany. Arthritis Rheum. 2005, 53: 740-747. 10.1002/art.21467.View ArticlePubMedGoogle Scholar
- Curtis JR, Westfall AO, Allison J, Becker A, Melton ME, Freeman A, Kiefe CI, MacArthur M, Ockershausen T, Stewart E, Weissman N, Saag KG: Challenges in improving the quality of osteoporosis care for long-term glucocorticoid users: a prospective randomized trial. Arch Intern Med. 2007, 167: 591-596. 10.1001/archinte.167.6.591.View ArticlePubMedGoogle Scholar
- Solomon DH, Katz JN, La Tourette AM, Coblyn JS: Multifaceted intervention to improve rheumatologists' management of glucocorticoid-induced osteoporosis: a randomized controlled trial. Arthritis Rheum. 2004, 51: 383-387. 10.1002/art.20403.View ArticlePubMedGoogle Scholar
- van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C: Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford). 2000, 39: 1383-1389. 10.1093/rheumatology/39.12.1383.View ArticleGoogle Scholar
- Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK: Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000, 43: 522-530. 10.1002/1529-0131(200003)43:3<522::AID-ANR7>3.0.CO;2-Y.View ArticlePubMedGoogle Scholar
- Sinigaglia L, Nervetti A, Mela Q, Bianchi G, Del Puente A, Di Munno O, Frediani B, Cantatore F, Pellerito R, Bartolone S, La Montagna G, Adami S: A multicenter cross sectional study on bone mineral density in rheumatoid arthritis: Italian Study Group on Bone Mass in Rheumatoid Arthritis. J Rheumatol. 2000, 27: 2582-2589.PubMedGoogle Scholar
- Nolla JM, Fiter J, Gomez Vaquero C, Mateo L, Valverde J, Roig Escofet D: [Study of bone mineral density in postmenopausal women with rheumatoid arthritis treated with low dose glucocorticoids]. Med Clin (Barc). 2000, 114: 452-453.View ArticleGoogle Scholar
- Dolan AL, Moniz C, Abraha H, Pitt P: Does active treatment of rheumatoid arthritis limit disease-associated bone loss?. Rheumatology (Oxford). 2002, 41: 1047-1051. 10.1093/rheumatology/41.9.1047.View ArticleGoogle Scholar
- Guler-Yuksel M, Bijsterbosch J, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Hulsmans HM, de Beus WM, Han KH, Breedveld FC, Dijkmans BA, Allaart CF, Lems WF: Changes in bone mineral density in patients with recent onset, active rheumatoid arthritis. Ann Rheum Dis. 2008, 67: 823-828. 10.1136/ard.2007.073817.View ArticlePubMedGoogle Scholar
- Habib GS, Haj S: Bone mineral density in patients with early rheumatoid arthritis treated with corticosteroids. Clin Rheumatol. 2005, 24: 129-133. 10.1007/s10067-004-0989-1.View ArticlePubMedGoogle Scholar
- Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.View ArticlePubMedGoogle Scholar
- Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, Putte van de LB, van Riel PL: Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995, 38: 44-48. 10.1002/art.1780380107.View ArticlePubMedGoogle Scholar
- Esteve-Vives J, Batlle-Gualda E, Reig A: Spanish version of the Health Assessment Questionnaire: reliability, validity and transcultural equivalency: Grupo para la Adaptacion del HAQ a la Poblacion Espanola. J Rheumatol. 1993, 20: 2116-2122.PubMedGoogle Scholar
- Liu G, Peacock M, Eilam O, Dorulla G, Braunstein E, Johnston CC: Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis of osteoporosis in elderly men and women. Osteoporos Int. 1997, 7: 564-569. 10.1007/BF02652563.View ArticlePubMedGoogle Scholar
- Pye SR, Reid DM, Adams JE, Silman AJ, O'Neill TW: Radiographic features of lumbar disc degeneration and bone mineral density in men and women. Ann Rheum Dis. 2006, 65: 234-238. 10.1136/ard.2005.038224.PubMed CentralView ArticlePubMedGoogle Scholar
- Engvall IL, Svensson B, Tengstrand B, Brismar K, Hafstrom I: Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthritis: experiences from a two-year randomized study. Arthritis Res Ther. 2008, 10: R128-10.1186/ar2542.PubMed CentralView ArticlePubMedGoogle Scholar
- Book C, Karlsson M, Akesson K, Jacobsson L: Disease activity and disability but probably not glucocorticoid treatment predicts loss in bone mineral density in women with early rheumatoid arthritis. Scand J Rheumatol. 2008, 37: 248-254. 10.1080/03009740801998747.View ArticlePubMedGoogle Scholar
- Garcia del Pozo J, Ramos Sevillano E, de Abajo FJ, Mateos Campos R: [Use of antihypertensive drugs in Spain (1995-2001)]. Rev Esp Cardiol. 2004, 57: 241-249. 10.1157/13059106.PubMedGoogle Scholar
- Asaba Y, Ito M, Fumoto T, Watanabe K, Fukuhara R, Takeshita S, Nimura Y, Ishida J, Fukamizu A, Ikeda K: Activation of renin-angiotensin system induces osteoporosis independently of hypertension. J Bone Miner Res. 2009, 24: 241-250. 10.1359/jbmr.081006.View ArticlePubMedGoogle Scholar
- Bolland MJ, Ames RW, Horne AM, Orr-Walker BJ, Gamble GD, Reid IR: The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women. Osteoporos Int. 2007, 18: 479-486. 10.1007/s00198-006-0259-y.View ArticlePubMedGoogle Scholar
- Lynn H, Kwok T, Wong SY, Woo J, Leung PC: Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese. Bone. 2006, 38: 584-588. 10.1016/j.bone.2005.09.011.View ArticlePubMedGoogle Scholar
- Schoofs MW, Klift van der M, Hofman A, de Laet CE, Herings RM, Stijnen T, Pols HA, Stricker BH: Thiazide diuretics and the risk for hip fracture. Ann Intern Med. 2003, 139: 476-482.View ArticlePubMedGoogle Scholar
- Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, Ross FP, Teitelbaum SL: Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest. 2006, 116: 2152-2160. 10.1172/JCI28084.PubMed CentralView ArticlePubMedGoogle Scholar
- Hofbauer LC, Gori F, Riggs BL, Lacey DL, Dunstan CR, Spelsberg TC, Khosla S: Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology. 1999, 140: 4382-4389. 10.1210/en.140.10.4382.PubMedGoogle Scholar
- Sivagurunathan S, Muir MM, Brennan TC, Seale JP, Mason RS: Influence of glucocorticoids on human osteoclast generation and activity. J Bone Miner Res. 2005, 20: 390-398. 10.1359/JBMR.041233.View ArticlePubMedGoogle Scholar
- Vidal NO, Brandstrom H, Jonsson KB, Ohlsson C: Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids. J Endocrinol. 1998, 159: 191-195. 10.1677/joe.0.1590191.View ArticlePubMedGoogle Scholar
- Goldring SR: Periarticular bone changes in rheumatoid arthritis: pathophysiological implications and clinical utility. Ann Rheum Dis. 2009, 68: 297-299. 10.1136/ard.2008.099408.View ArticlePubMedGoogle Scholar
- Makrygiannakis D, af Klint E, Catrina SB, Botusan IR, Klareskog E, Klareskog L, Ulfgren AK, Catrina AI: Intraarticular corticosteroids decrease synovial RANKL expression in inflammatory arthritis. Arthritis Rheum. 2006, 54: 1463-1472. 10.1002/art.21767.View ArticlePubMedGoogle Scholar
- Canalis E, Mazziotti G, Giustina A, Bilezikian JP: Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007, 18: 1319-1328. 10.1007/s00198-007-0394-0.View ArticlePubMedGoogle Scholar
- Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A: Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab. 2006, 17: 144-149. 10.1016/j.tem.2006.03.009.View ArticlePubMedGoogle Scholar
- El Maghraoui A, Roux C: DXA scanning in clinical practice. QJM. 2008, 101: 605-617. 10.1093/qjmed/hcn022.View ArticlePubMedGoogle Scholar
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