Elsevier

Bone

Volume 39, Issue 2, August 2006, Pages 253-259
Bone

High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: A cross-sectional outpatient study

https://doi.org/10.1016/j.bone.2006.02.005Get rights and content

Abstract

Glucocorticoid (GC)-induced osteoporosis mostly affects trabecular bone of vertebrae. Only 30% of vertebral fractures are symptomatic, yet both clinical and radiological vertebral fractures have been associated with increased mortality and morbidity. The aims of this cross-sectional, outpatient-based study were to measure the prevalence of asymptomatic vertebral fractures in a large sample of post-menopausal women given GCs for different diseases; to compare prevalence of asymptomatic vertebral fractures according to disease, GC treatment and major risk factors; and to assess the quality of life in GC users with and without asymptomatic vertebral fractures. 551 patients referring to 39 centers as outpatients for their programmed follow-up and satisfying the inclusion criteria were included in the analysis. Each patient underwent structured medical interview (including dose and duration of GC therapy, major risk factors for osteoporosis, the quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) and a back function score questionnaire), thoraco-lumbar radiographs and subsequent morphometry; for 253 and 437 patients, respectively, lumbar spine bone mineral density (BMD) assessed by dual energy X-ray absorptiometry and calcaneal bone stiffness assessed by quantitative ultrasonometry were available. The prevalence of asymptomatic vertebral fractures resulted >37%, with >14% of patients having two or more asymptomatic vertebral fractures and was much higher than that found in epidemiological studies on healthy women. Distribution of asymptomatic vertebral fractures along the spine showed a bimodal pattern, with two peaks at T7 and T11. The prevalence of asymptomatic vertebral fractures clearly increased with age. Differences in prevalence among diseases were evidenced. When controlled for age, GC cumulative dose, duration of therapy and personal history of fractures, the adjusted prevalences were 30.77% for systemic lupus erythematosus, 33.78% for rheumatoid arthritis, 37.78% for asthma/chronic obstructive pulmonary disease, 43.20% for polymyalgia rheumatica and 43.36% for diseases grouped as “other vasculitides/connective tissue diseases”. No significant association was found with GC cumulative dose and duration of therapy. Established risk factors for osteoporosis (except for age, years since menopause and personal history of fractures), lumbar spine BMD, calcaneal stiffness and QUALEFFO score were not associated with number and severity of asymptomatic vertebral fractures. Underlying disease is likely to contribute to the risk of fracture, but disease by itself could not be dissected from GC regimen. Vertebral fractures should be looked for carefully in all post-menopausal women receiving long-term systemic GCs since they can be asymptomatic and are scarcely predictable.

Introduction

Since half a century ago, synthetic glucocorticoids (GCs) are worldwide used in clinical practice for their anti-inflammatory and immunosuppressive properties. Their administration is laden with a host of side effects that gain importance in patients with chronic and debilitating diseases. GCs are used by an estimated 0.5% to 0.9% of the general population; notably, GC use is much more frequent in aging people, in which it adds to a number of well-known risk factors for osteoporosis [1], [2], [3]. It is held, in fact, that GC-induced osteoporosis is the most common form of secondary osteoporosis. Despite the availability of safe and effective treatments such as bisphosphonates and consistent recommendations of a number of medical societies and specialty groups [4], [5], awareness is low in both patients and physicians, and only a minority of patients on GC treatment undergo measures to prevent or treat GC-induced osteoporosis [3], [6].

Systemic GC treatment rapidly induces bone loss and increases fracture risk. Trabecular bone is preferentially affected: therefore, vertebrae, which consist mostly of trabecular bone, are a major target of GCs deleterious effects, as already noticed by H. Cushing in 1932 [7], [8]. It has been estimated that only 30% of vertebral fractures are symptomatic. On the other hand, both clinical and radiological vertebral fractures have been associated with increased mortality and morbidity [9], [10], [11], [12], [13]. Data on prevalence of vertebral fractures in GC-treated patients are scarce. Most data from observational studies relate to single diseases and small series of patients and are not comparable, due to different methods of assessment of vertebral fractures [14]. Recent trials on the treatment of GC-induced osteoporosis always include a baseline radiological evaluation of vertebral fractures in enrolled patients; however, these large clinical trials have limitations because of inherent selection bias [15]. The largest epidemiological study published to date, based on the United Kingdom General Practice Research Database and a very recent meta-analysis of data from seven cohort studies, involved over 240,000 and 42,000 patients, respectively, yet, the prevalence of vertebral fractures was clearly underestimated since only clinical vertebral fractures were reported [16], [17]. No study has assessed the association between vertebral fractures and the quality of life in GC-treated patients.

The aims of the present study were to measure the prevalence of asymptomatic vertebral fractures in a large sample of post-menopausal women who were treated with GCs for different diseases in about 40 centers; to compare prevalence of asymptomatic vertebral fractures according to disease, GC treatment and concomitant major risk factors; to assess the health-related quality of life in GC users with and without asymptomatic vertebral fractures. A qualifying choice was the recruitment on an outpatient basis of post-menopausal women who were referring to their physicians for the programmed follow-up of their disease and not for back pain or other symptoms suggestive for spinal fracture. The prevalence of asymptomatic vertebral fractures in an ample cohort was expected to provide reliable information on subclinical GC-induced osteoporosis in daily practice.

Section snippets

Study population

Thirty-nine Italian centers of academic and non-academic hospitals dealing with diseases relevant to internal medicine were involved. In each center, between January 2001 and June 2002, experienced clinicians recruited up to 30 consecutive post-menopausal women referred by their family physicians as outpatients for their programmed specialist visit and satisfying the following inclusion criteria: age >45 years; menopause since at least 1 year; current GC treatment started at least 6 months

Results

Of 948 eligible patients, about 40% were discarded as a consequence of the stringent criteria adopted for analysis; 551 patients were analyzed. Notably, when all the available data on the 948 eligible patients and those on the final subset of 551 patients were considered, descriptive statistics were almost equal for the main demographic and clinical features, witnessing for missing-at-random (Table 1). As illustrated in Table 2, the prevalence of asymptomatic vertebral fractures resulted

Discussion

The present study was designed to obtain information unbiased by selection of patients who could present to specialized centers dealing with osteoporosis due to symptoms or physician awareness of the deleterious effects of their corticosteroid regimen. Patients who were recruited were referred by their family physicians for specialist visit in a programmed follow-up for the underlying disease and are representative of the vast population of patients with complex chronic diseases requiring a

Acknowledgments

Dr. Daniela de Feo and Dr. Ruben Giorgino are employees of Procter & Gamble Italy, which supported the study. Dr. A. Dovio has been awarded one of the 2004 Prizes from the Società Italiana di Medicina Interna.

Preliminary results of this study were partly reported in two poster presentations at the 25th Annual Meeting of the American Society for Bone and Mineral Research, September 19–23, 2003—Minneapolis, USA.

The Glucocorticoid Induced Osteoporosis Vertebral deformity Evaluation (GIOVE) study

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