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In this Q&A, Edgar Wiebe, M.D., of Charité University Medicine Berlin, discusses the findings of a study recently presented at the American College of Rheumatology annual meeting that looked at the impact of a number of factors on bone mineral density.
Rheumatic diseases are associated with increased risk of bone loss and fractures but a better understanding of the contribution of disease-specific factors, treatments such as glucocorticoids, chronic inflammation, and general and demographic risk factors may help improve outcomes for patients, according to researchers reporting at the annual meeting of the American College of Rheumatology last Friday.
In this Q&A, co-author Edgar Wiebe, of the Departments. of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Germany, discusses the findings of a study looking at the impact of a multitude of factors on bone mineral density.
The researchers used a multivariate linear regression model to identify predictors of bone mineral density as measured by dual-energy X-ray absorptiometry (DXA) in 1091 patients enrolled in the Rh-GIOP study. The average age of patients was 62, and three quarters were female (87.5% postmenopausal). The prevalence of osteoporosis assessed by DXA was 21.7%, and fragility fractures had occurred in 31.2% of patients (6.7% vertebral, 27.7% nonvertebral). Two thirds of patients (64.9%) were using glucocorticoids at a median daily dose of 5.0mg; the mean life-time total glucocorticoid dose was 17.7g (±24.6) and the mean duration of therapy was 7.8 years (±8.5). Bisphosphonates were the most commonly used anti-osteoporotic drug, and used by 12.6% of patients.
Bone mineral density, as expressed by minimum T-Score (overall, lumbar spine and femoral neck), was predicted by age, sex, menopause and BMI, bisphosphonate and denosumab treatment, as well as current glucocorticoid therapy, proton pump inhibitor intake and use of NSAIDs. Current glucocorticoid dose showed a positive correlation with bone mineral density.
The bone-specific laboratory parameters alkaline phosphatase levels and Gamma-GT were determinants of bone mineral density, but bone mineral density was not predicted by either duration or cumulative dose of glucocorticoid treatment, treatment with DMARDs or other factors relating to disease activity. Determinants for bone mineral density varied slightly at the anatomical site with disability determined by Health Assessment Questionnaire (HAQ), hyperthyroidism and sun exposure affecting only the femoral T-Score.
Why was the study conducted?
Osteoporosis remains an important comorbidity in patients with rheumatic diseases. While it is one of the most feared side effects of glucocorticoid-treatment and glucocorticoid-induced osteoporosis (GIOP) represents the most common form of secondary osteoporosis, a more comprehensive understanding of GIOP would be that treatment with glucocorticoids is just one factor in a network of interrelated factors influencing bone health in patients with systemic inflammation.
What is the most important take home from this study for rheumatologists?
The main findings of the study is that treatment with glucocorticoids did not predict a negative T-Score, in fact, glucocorticoid treatment had a positive impact on the T-Score (as did concomitant intake of NSAIDs).
I also regard this as the main take home message for rheumatologist: that the effect of glucocorticoid treatment on bone might in fact (in a real world setting, when applied wisely) be positive. It corroborates very well with what we believe is central to the prevention of osteoporosis in patients with rheumatic diseases: effectively suppressing autoimmune or auto-inflammatory processes as the key trigger for bone loss. Whether this is best achieved with or without glucocorticoids still needs to be answered. We hope to be able to contribute to addressing these questions with our research and further data in near future.
Interestingly, German guidelines for the treatment of osteoporosis (Dachverband Osteologie e.V) have been, for several years now, taking into account this potentially constructive role of glucocorticoids in patients with rheumatoid arthritis, by attenuating the relative weight of the overall negative impact of glucocorticoids in fracture risk calculation in patients with rheumatoid arthritis. Whether the same is true for other inflammatory rheumatic diseases still needs to be answered and remains a major focus of our research.
Did anything surprise you about the findings?
Looking at the results, we see that osteoporosis indeed represents a main challenge in daily care. Nearly every third patient with a rheumatic disease had sustained a fracture without adequate underlying trauma. The prevalence of osteoporosis by DXA was around 20%. The majority of patients had osteopenic values, i.e. reduced bone mass. This is in line with what we already know.
The results of this multivariate analysis bear some interesting findings. While several known factors were identified to negatively influence the T-Score, such as age, menopause, intake of proton-pump inhibitors, one might be at first surprised to find male sex in patients with rheumatic diseases to predict a lower T-score. However, when the data was looked at in more detail, male patients were more commonly represented in disease groups such as vasculitides (very high glucocorticoid-doses) and spondyloarthropathies (known to have a high risk for osteoporosis). Life-style factors that negatively influence bone health were also much more common in male patients, such as smoking, insufficient exposure to sunlight, etc. Again, bearing in mind that osteoporosis is a multifactorial disease, the effect of male sex does not seem to be that much surprising anymore.
What were the strengths of the study?
I think an important strength of this study is that we characterized the enrolled patients very well, meaning that we meticulously documented all known as well as potentially unknown factors influencing bone health, thereby permitting us to apply a very comprehensive, holistic multivariate regression model to identify the main factors that influence the T-Score. This is important, since the nature of osteoporosis in our patients is of course multifactorial: bone health is not solely influenced by one factor such as glucocorticoid treatment but by a plethora of factors.
What conditions did the patients in the study have?
Patients enrolled had various underlying rheumatic conditions: 36% rheumatoid arthritis, 23% connective tissue diseases, 14% vasculitides and 14% spondlyoarthropathies, while 13% had other rheumatic diseases, e.g. psoriasis, juvenile arthritis, polychondritis, undifferentiated arthritis, etc.
ABSTRACT 0129. “Glucocorticoid-Induced Osteoporosis in Patients with Chronic Inflammatory Rheumatic Diseases: A Multivariate Linear Regression Analysis Identifying Factors Affecting Bone Mineral Density.” The annual meeting of the American College of Rheumatology. 9:00 AM, Friday, Nov. 6, 2020.