Elsevier

Joint Bone Spine

Volume 81, Issue 6, December 2014, Pages 493-501
Joint Bone Spine

Recommendations
2014 update of recommendations on the prevention and treatment of glucocorticoid-induced osteoporosis

https://doi.org/10.1016/j.jbspin.2014.10.001Get rights and content

Abstract

Objectives

To update the recommendations on the prevention and treatment of glucocorticoid-induced osteoporosis issued in 2003 by the French National Authority for Health (HAS). This update was performed under the aegis of the Bone Section of the French Society for Rheumatology (SFR) and Osteoporosis Research and Information Group (GRIO), in collaboration with four French learned societies (primary-care, gastroenterology, internal medicine, and nephrology).

Methods

A task force composed of members of the medical specialties involved in managing patients with glucocorticoid-induced osteoporosis conducted a systematic literature review according to the method developed by the HAS then used the results to develop updated recommendations.

Results

These recommendations are intended for all physicians involved in the management of patients who are scheduled to start, or are taking, long-term glucocorticoid therapy (≥ 3 months) in any dose and for any reason. In postmenopausal women and men older than 50 years of age, treatment is warranted in the presence of any of the following risk factors for fracture: history of bone frailty fracture after 50 years of age, bone mineral density T-score ≤ −2.5 at one or more sites, age ≥ 70 years, and dosage ≥ 7.5 mg/d prednisone-equivalent for longer than 3 months. Bisphosphonates can be used in all these situations; teriparatide can be given as first-line therapy in patients at high fracture risk but is reimbursed by the French statutory health insurance system only in patients having two or more prevalent vertebral fractures. The fracture risk is lower in nonmenopausal women and in men younger than 50 years of age, in whom treatment decisions should rest on a case-by-case evaluation.

Conclusion

These recommendations are intended to clarify the pharmacological management 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.

Section snippets

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)

  • P.N. Sambrook et al.

    Bisphosphonates and glucocorticoid osteoporosis in men: results of a randomized controlled trial comparing zoledronic acid with risedronate

    Bone

    (2012)
  • A. Giusti et al.

    Atypical fractures of the femur and bisphosphonate therapy: a systematic review of case/case series studies

    Bone

    (2010)
  • L.J. Walsh et al.

    Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross-sectional study

    BMJ

    (1996)
  • E. Soucy et al.

    A Canadian survey on the management of corticosteroid-induced osteoporosis by rheumatologists

    J Rheumatol

    (2000)
  • L. Fardet et al.

    Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years

    Rheumatology (Oxford)

    (2011)
  • R. Ramsey-Goldman

    Missed opportunities in physician management of glucocorticoid-induced osteoporosis?

    Arthritis Rheum

    (2002)
  • L.M. Buckley et al.

    Variations in physicians’ judgments about corticosteroid-induced osteoporosis by physician specialty

    J Rheumatol

    (1998)
  • J.R. Guzman-Clark et al.

    Barriers in the management of glucocorticoid-induced osteoporosis

    Arthritis Rheum

    (2007)
  • D.H. Solomon et al.

    Management of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis: rates and predictors of care in an academic rheumatology practice

    Arthritis Rheum

    (2002)
  • M. Duyvendak et al.

    Corticosteroid-induced osteoporosis prevention: longitudinal practice patterns in The Netherlands 2001–2005

    Osteoporos Int

    (2007)
  • D. Brask-Lindemann et al.

    Time trends for alendronate prescription practices in women with chronic obstructive pulmonary disease and women exposed to systemic glucocorticoids

    Osteoporos Int

    (2013)
  • C. Wibaux et al.

    Évolution de la prise en charge de l’ostéoporose cortisonique au sein du réseau rhumatisme inflammatoire chronique du Nord-Pas-de-Calais entre 2007 et 2010

    Rev Rhum

    (2010)
  • K.R. Koetz et al.

    Bone mineral density is not significantly reduced in adult patients on low-dose glucocorticoid replacement therapy

    J Clin Endocrinol Metab

    (2012)
  • J.M. Grossman et al.

    American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis

    Arthritis Care Res (Hoboken)

    (2010)
  • S. Lekamwasam et al.

    A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis

    Osteoporos Int

    (2012)
  • E. Canalis et al.

    Glucocorticoid-induced osteoporosis: pathophysiology and therapy

    Osteoporos Int

    (2007)
  • T.P. van Staa et al.

    The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis

    Osteoporos Int

    (2002)
  • S. Cohen et al.

    Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study

    Arthritis Rheum

    (1999)
  • D.M. Reid et al.

    Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study

    J Bone Miner Res

    (2000)
  • R.F. Laan et al.

    Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study

    Ann Intern Med

    (1993)
  • R. McKenzie et al.

    Decreased bone mineral density during low dose glucocorticoid administration in a randomized, placebo-controlled trial

    J Rheumatol

    (2000)
  • M. Vis et al.

    Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFkappaB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis

    Ann Rheum Dis

    (2006)
  • C.A. Wijbrandts et al.

    Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arrest of bone loss

    Ann Rheum Dis

    (2009)
  • T.P. Van Staa et al.

    Use of oral corticosteroids and risk of fractures

    J Bone Miner Res

    (2000)
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