Recommendations2014 update of recommendations on the prevention and treatment of glucocorticoid-induced osteoporosis
Introduction
The prevalence of glucocorticoid exposure in the general population is high, about 1% overall and up to 4.5% among postmenopausal women [1], [2], [3], [4]. The most common diagnoses leading to long-term glucocorticoid therapy are joint diseases (rheumatoid arthritis [RA], polymyalgia rheumatica [PMR], and connective tissue diseases), lung diseases (asthma and chronic obstructive pulmonary disease [COPD]), and chronic inflammatory bowel disease (IBD) [3]. A study of The Health Improvement Network (THIN) database on 4.5 million adults in the UK showed a 30% increase in the annual prevalence of glucocorticoid therapy over the 20-year enrolment period, with differences across underlying diagnoses [3]. Thus, the use of glucocorticoid therapy decreased among patients with asthma, COPD, or Crohn's disease; remained stable in those with ulcerative colitis; and increased in patients with RA or PMR [3]. However, the prevalence of new prescriptions of long-term glucocorticoid therapy for RA decreased over time, suggesting changes in treatment practices related to the introduction of new drugs such as biological agents [3].
Glucocorticoid exposure is the leading cause of secondary osteoporosis and the most common cause of osteoporosis in young adults [5]. Although effective osteoporosis drugs are available, they are used for osteoporosis prevention in only a minority of patients exposed to long-term glucocorticoid therapy. Oddly enough, concomitant risk factors for osteoporosis (large number of comorbidities and concomitant treatments), which increase the need for prevention, are the factors most often associated with failure to prescribe preventive therapy [6], [7], [8], [9], [10]. Nevertheless, studies have documented increases in the prescription of bisphosphonates for patients receiving long-term glucocorticoid therapy in The Netherlands (54% in 2005 versus 38% in 2001; P = 0.001), as well as in Denmark in patients with COPD [10], [11]. Data obtained in France showed that only 30% of postmenopausal women taking long-term oral glucocorticoid therapy in dosages ≥ 7.5 mg/d of prednisone-equivalent were given bisphosphonate therapy in 2007, and this proportion was not higher in 2010 [12]. No data from France are available on the frequency and time trends of bisphosphonate therapy in patients with other inflammatory diseases.
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Objectives and methods
These recommendations are intended for all physicians involved in the prevention and treatment of osteoporosis induced by long-term (≥ 3 months) exposure to glucocorticoid therapy in any dosage and for any reason. Recent data establish that glucocorticoid replacement therapy is not associated with bone loss [13].
These recommendations review the principles of pharmacological therapy for glucocorticoid-induced osteoporosis in the light of current indications, efficacy, and safety. They indicate
Pathophysiology of glucocorticoid-induced osteoporosis
Glucocorticoids in pharmacological dosages exert adverse effects on bone-tissue via both direct and indirect mechanisms [16], [17], [18] (Fig. 1). They directly alter bone cell metabolism. Their indirect effects are mediated by a variety of mechanisms including decreased intestinal absorption of calcium, increased urinary excretion of calcium, glucocorticoid-induced hypogonadism, and glucocorticoid-induced myopathy responsible for an increased risk of falls [17]. The main net effect is
History of fracture
A previous peripheral fracture is the strongest risk factor for vertebral fractures in patients with RA [33]. As indicated above, the frequency of prevalent vertebral fractures is underestimated due to the mildness of the symptoms, which is probably ascribable to the analgesic effect of glucocorticoids.
Risk factors related to patient characteristics
In addition to glucocorticoid exposure, a number of patient characteristics may influence the fracture risk. Characteristics that are relevant in both males and females include age, risk factors
Fracture risk evaluation in patients taking, or scheduled to take, long-term glucocorticoid therapy
Given the rapid onset of bone loss and early fracture risk increase after glucocorticoid therapy initiation, a baseline evaluation of the fracture risk is recommended in all patients starting oral glucocorticoid therapy expected to last longer than 3 months; in the absence of a baseline evaluation, the fracture risk should be evaluated in patients on oral glucocorticoid therapy (Grade A). This evaluation is recommended regardless of the glucocorticoid dosage (Grade A). The identification of
Evaluation of treatment adherence
As with all drugs used to treat chronic conditions, osteoporosis drugs are effective only when taken as ordered. Several studies have shown that poor treatment adherence translates into decreased efficacy. Clinical follow-up may be sufficient to assess adherence (Professional consensus).
Role for bone mineral density (BMD) measurement during follow-up
Given the rapid onset of bone loss, annual BMD measurement is recommended during the first 2 years of glucocorticoid therapy in the absence of osteoporosis drug therapy or at the end of an osteoporosis drug
Safety of osteoporosis drugs
Clinical trials in glucocorticoid-induced osteoporosis included fewer patients and involved shorter follow-ups compared to studies of postmenopausal osteoporosis. Thus, few data are available on patients given long-term osteoporosis drug therapy. The safety profiles of bisphosphonates and teriparatide seem comparable to those seen in postmenopausal osteoporosis. Patients treated with bisphosphonates should be informed of the very small risk of jaw osteonecrosis and atypical femoral fracture.
Disclosure of interest
K. B.: occasional interventions: fees for work as an expert or speaker for Amgen, Lilly, MSD, Novartis, and Servier; indirect interests: funding for research programs and investigator fees from Lilly.
B. C.: occasional interventions: fees for work as an expert or speaker for Amgen, Ferring, Lilly, Medtronic, MSD, Novartis, Roche Diagnostics, Rottapharm, and Servier; indirect interests: funding for research programs and investigator fees from Amgen, Novartis, and Servier.
C. R.: occasional
Acknowledgments
We are indebted to the members of the multidisciplinary review committee: Breuil Véronique (rheumatologist, Nice), Chapurlat Roland (rheumatologist, Lyon), Escourrou Brigitte (primary-care physician, Toulouse), Loïc Guillevin (internist, Paris), Hebuterne Xavier (gastroenterologist, Nice), Joseph Jean-Philippe (primary-care physician, Bordeaux), Levesque Hervé (internist, Rouen), and Reimund Jean Marie (gastroenterologist, Caen).
References (68)
- et al.
Regional differences in treatment for osteoporosis. The Global Longitudinal Study of Osteoporosis in Women (GLOW)
Bone
(2011) - et al.
Secondary osteoporosis in patients with an osteoporotic fracture
Best Pract Res Clin Rheumatol
(2009) Glucocorticoids, osteocytes, and skeletal fragility: the role of bone vascularity
Bone
(2010)Glucocorticoid-induced osteoporosis and osteonecrosis
Endocrinol Metab Clin North Am
(2012)- et al.
High prevalence of asymptomatic vertebral fractures in postmenopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study
Bone
(2006) - et al.
Official Positions for FRAX® clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX® of the 10 year risk of fracture from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®)
J Clin Densitom
(2011) - et al.
Vertebral fracture assessment: the 2007 ISCD official positions
J Clin Densitom
(2008) - et al.
2012 update of French guidelines for the pharmacological treatment of postmenopausal osteoporosis
Joint Bone Spine
(2012) - et al.
Use of calcium supplementation and the risk of coronary heart disease in 52–62-year-old women: the Kuopio Osteoporosis Risk Factor and Prevention Study
Maturitas
(2009) - et al.
Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial
Lancet
(2009)