September - December 2004: 
Volume 17, Issue 3

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Prophylaxis for osteoporosis in patients receiving oral steroids
Patients with a chronic pulmonary disease often require long-term treatment with oral steroids. Prolonged use of glucocorticoids is associated with increased risk of bone loss and osteoporosis. The American College of Rheumatology (ACR) has published guidelines to prevent steroid-induced osteoporosis. The aim of this study was to investigate adherence to these guidelines in clinical practice. Medical records of 87 patients receiving oral steroids (prednisolone >10 mg/day) for at least 6 months were reviewed. Of these, 57 patients were treated by a rheumatology specialist, and 30 by a pulmonology specialist. Differences between the two groups were examined using Chi-square test. Altogether 33 patients (35%) received prophylactic treatment. Examination of between-groups variation revealed that 46% of patients treated by a rheumatologist received prophylaxis, while the respective percentage in those treated by a pulmonologist was only 23% (p<0.05). Our data suggest that only a relatively small proportion of patients receiving corticosteroid treatment are offered prophylaxis for steroid-induced osteoporosis, and this proportion is significantly lower in patients attended by pulmonary medicine specialists. Pneumon 2004, 17(3):297-303.
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Corticosteroids are used by a variety of physicians for a wide range of acute or chronic inflammatory or allergic diseases. It is also known that steroid treatment is one of the most common causes of spinal fractures due to bone loss that results in fragile bones.1-4 Therefore, treatment with oral corticoids should be used in conjunction with prophylaxis for osteoporosis.

Patients who are receiving or are about to receive prednisolone 7.5 mg/day for at least 6 months require prophylaxis. Preventive treatment should be initiated as early as possible, since the rate of bone mass loss is more rapid after the initiation of therapy and stabilizes in the long-term.5 The American College of Rheumatology (ACR) has formulated recommendations for prophylactic treatment for steroid-induced osteoporosis.6 The aim of these recommendations is to educate and update physicians on the prevention and treatment of steroid-induced osteoporosis. The present study examines the extent to which physicians, in particular pulmonologists, adhere to these recommendations and prescribe prophylactic treatment for steroid-induced osteoporosis.

Patients and methods

The study population is comprised of 87 patients receiving oral steroids (at least prednisolone 10 mg or an equivalent dose of another steroid) for at least 6 months. The mean (range) age of the patients was 57.3 (23-80) years and 20 patients were male. All patients receiving long-term corticoid treatment that attended the outpatient department or were admitted to the Pulmonary Medicine Department of the "Sotiria" Hospital of Chest Diseases, University of Athens, and the Internal Medicine Department of the Hospital of Arta in the period from 2001 through 2002 were included in the study. Of them, 57 were treated by a rheumatologist and 30 by a pulmonologist at the time of their inclusion in the study. Of the patients with rheumatic diseases, 24 had attended the Emergency Department, or were admitted to the Pulmonary Medicine Department at "Sotiria" Hospital of Chest Diseases. These patients had rheumatic disease treated by a rheumatology specialist, but were referred to or attended our clinic due to pulmonary involvement or presence of an acute respiratory disorder (most commonly an infection). The remaining patients with rheumatic disease were routinely treated by or attended the Internal Medicine Department of the Hospital of Artas seeking specialist advice. Rheumatic diseases present in study subjects included rheumatoid arthritis, systemic lupus erythematosus, polyarteritis or other forms of arteritis; pulmonary diseases included asthma, sarcoidosis, interstitial pulmonary fibrosis and granulomatoses (Table 1). Personal interviews with study subjects receiving long-term corticoid therapy were used to collect data on whether prophylaxis for corticoid-induced osteoporosis was prescribed and which prophylactic agents were used.



Table 1. Clinical characteristics of reviewed patients.

                    Treated by a pulmonologist (30 patients)      Treated by a rheumatologist (57 patients)

Age                                       57.7 ± 3                                                        58.3 ± 1.8

Sex (M/F)                                 8/22                                                               12/45

Diagnosis        Asthma                                          15              Vasculitis                                     24

                        Sarcoidosis                                     7              Rheumatoid arthritis                    15

                        Idiopathic Pulmonary Fibrosis         5              Systemic lupus erythematosus      9

                        Other conditions                             3              Sjφgren syndrome                         3

                                                                                               Other conditions                           6


Statistical analysis

Differences between the two study groups were assessed using Chi square test; a p value of <0.05 was taken as indicative of statistical significance. Correlations were assessed using multiple correlation analysis (SPSS, Version 8.0 -PC, Chicago, USA).


Altogether 33 (35%) patients received prophylaxis for osteoporosis. In the group of patients who were treated by a rheumatologist, prophylaxis was offered in 46% of the patients, whereas the respective percentage in the group treated by a pulmonologist was just 23% (p <0.05) (Figure 1).

Image 1

Supplementation with calcium and vitamin D was the treatment of choice for osteoporosis prophylaxis in both groups (42-31.5% in the rheumatologist-treated group; 23-13.3% in the pulmonologist-treated group).

Pulmonologists were found to prescribe bisphosphonates more often compared to rheumatologists (13% vs. 7.8%, respectively); this difference was not statistically significant though (Table 2). None of the patients in this study was prescribed hormone replacement therapy (HRT); calcitonin was prescribed in few patients.


Table 2. Prescribed prophylactic treatment.

                                                            Calcium             Vitamin D              Calcitonin       Bisphosphonates

Pulmonologists (57 patients treated)    24/57 (42%)        18/57 (31.5%)         7/57 (12%)            5/57 (8.7%)

Rheumatologists (30 patients treated) 7/30     (23%)   4/30     (13.3%)            1/30     (3.3%)  4/30     (13%)


Our results indicate that only a small proportion of patients receive prophylaxis for steroid-induced osteoporosis; furthermore, this proportion is lower among patients with pulmonary disease compared with patients with rheumatic disease.

The pathophysiology of steroid-induced osteoporosis is complex. Steroids are most likely to alter normal bone turnover through their effect on calcium homeostasis (increased renal loss and reduced intestinal absorption),8 reduced secretion of sex hormones,9-10 and bone remodeling imbalance with reduced bone formation and increased bone resorption.11 A direct inhibitory effect of steroids on the number and function of osteoblasts and the induction of osteoblast and osteocyte apoptosis is held responsible for reduced bone formation. On the other hand, increased bone resorption and reduced bone strength are probably caused by secondary hyperparathyroidism due to the negative calcium balance.11 Typically, bone resorption is more marked in trabecular than in cortical bone,12 resulting in pathologic fractures and osteonecrosis (avascular necrosis) of the epiphyses.13 This type of necrosis affects mainly the hip and is considered to result from disturbances in the local microcirculation; high pressure on intraosseus vessels, arterial occlusion by fat emboli, as well as pathologic local minor fractures may conduce to osteonecrosis.14

Patients with pulmonary and rheumatic diseases often require long-term systematic steroid treatment. Such patients, in particular postmenopausal women, have a high risk of bone loss. According to the American College of Rheumatology (ACR) guidelines first published in 199615 and then revised in 20016, in view of the emergence of new evidence,16-19 bone loss should be followed-up biannually in steroid-treated patients not receiving prophylaxis for osteoporosis, and annually in those offered prophylactic treatment. Prophylaxis for steroid-induced osteoporosis includes supplementation with calcium, vitamin D and bisphosphonates (Appendix 1).


Appendix 1

These guidelines rely on large population-based studies indicating that current prophylactic treatment regimens for corticoid-induced osteoporosis include vitamin D alone, calcium alone or in combination with vitamin D, as well as calcitonin alone or in combination treatment. Such regimens appear to reduce bone loss, but fracture risk remains unchanged. Combined treatment with calcium and vitamin D may prevent bone loss; calcium supplementation alone is ineffective. Hormone replacement therapy (HRT) with estrogen and progesterone in postmenopausal women receiving long-term low-dose steroid treatment is apparently adequate treatment for the prevention of bone loss as long as it is not contraindicated; however, the efficacy of HRT in women receiving high-dose steroid therapy has not been adequately investigated. The recent epidemiologic study "Women Health Initiative" has filled in some of the missing evidence and showed that HRT produces a 33% reduction in spinal and hip fractures, and a 24% reduction in all fractures, at the cost of increased risk for breast cancer and cardiovascular disease.20 In addition, there are some reports of men with low serum testosterone levels due to hypogonadism secondary to long-term steroid treatment. In these men bone mass increased (almost by 4%) with monthly intramuscular injections of testosterone for 12 months.21-22 Observational studies in premenopausal female athletes with menstrual irregularities showed that those who received oral contraceptives had a higher bone mineral density (BMD) than those who did not.23-24

The results of five large randomized clinical trials all agree that bisphosphonates (etidronate, alendronate) are effective in the prophylaxis and treatment of osteoporosis,25,30 with minimal side effects, primarily from the gastrointestinal tract.25,31 Patients with proven low bone mass taking long-term steroid therapy, or patients with osteoporotic fractures should receive bisphosphonates in combination with calcium and vitamin D. Bisphosphonates are also the treatment of choice for osteoporosis prophylaxis.

Prophylaxis with calcitonin given via either subcutaneous injections or intranasal inhalation is not recommended. However, it is an accepted alternative in patients who have contraindication to, or cannot tolerate bisphosphonates. Anabolic agents have the ability to increase bone mass in steroid-treated patients, but they are not recommended since they do not protect the patient from fractures.

The American College of Rheumatology believes that the majority of physicians, even rheumatology and pulmonology specialists who have great experience in systematic steroid treatment, do not prescribe prophylactic treatment for osteoporosis.6 In a recent large study conducted in Great Britain, the medical records of 633 women receiving long-term steroid treatment were reviewed; 47% of these women received prophylaxis for osteoporosis (calcium, bisphosphonates or hormone replacement therapy). This proportion reduced with advancing age, and was lower in female patients with rheumatoid arthritis or asthma compared to other diseases (p <0.01).32 Other specialists prescribe prophylaxis for osteoporosis even more infrequently, most probably because these guidelines have not been adequately diffused. The reasons for failure to prescribe prophylactic treatment are multifold. Some of the most common reasons include advanced patient age, concomitant diseases in some cases, and patient shift to another attending physician.33 In addition, many physicians are not aware that men and premenopausal women, too, are at risk for osteoporosis if they are being treated with corticosteroids.34-35 Even tually, physicians may be unfamiliar and therefore unwilling to prescribe prophylactic treatment for osteoporosis; it is essential that physicians are constantly updated regarding individualization of prophylactic treatment.33 In addition to the above-mentioned considerations, the healthcare system in Greece, in particular, has a major impact on practice variations; the attending physician recommends a treatment, another physician or a house officer affiliated with the patient's insurance fund writes the prescription in the appropriate form, and the insurance inspector is the one to eventually subscribe reimbursement or not. Thus, in many cases, the patient does not get to receive the indicated treatment, although the attending physician has recommended it.

In the present study, the proportion of patients receiving prophylactic treatment for osteoporosis was 35%. Our results are similar to those reported in other published studies indicating low percentages of physician adherence to international guidelines for the prevention of steroid-induced osteoporosis, which vary from 35.3%33 to just 8%.36 This situation has to change. Bone loss during treatment with steroids is not only almost certain to occur, but it may also entail major health problems, because, besides pain, it is associated with a high risk for spinal fractures, which may lead to permanent disability. Awareness of the relevant guidelines and prescribing of prophylactic treatment according to these guidelines should be spread among physicians of all specialties so as patients at risk for steroid-induced osteoporosis receive optimal care.




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