Glucocorticoid-induced osteoporosis in rheumatic diseases

Abstract

Glucocorticoids (GCs) are widely used in medicine for their immunosuppressive and anti-inflammatory effects. They are prescribed to patients with systemic inflammatory diseases and are frequently used in the fields of internal medicine (rheumatology, hematology, pulmonology, gastroenterology, etc), dermatology and transplant medicine. In rheumatology practice, initially, there was considerable enthusiasm about these drugs because of the striking relief of symptoms observed in patients with rheumatoid arthritis (RA) who were treated with GCs. However, GCs soon became known for their deleterious effects on bone. When the wide array of potentially serious adverse effects became apparent, the use of GCs decreased. More recently the careful administration of GCs to patients with RA and other rheumatic diseases generally has become accepted. The side-effects of GCs are numerous, even in low dosages. One of the most important side effects of GC use is osteoporosis. As less as five mg (of prednisolone or equivalent) daily can lead to a decrease in bone mineral density (BMD) and an increased risk of fractures. In this thesis several studies in patients with a rheumatic disease treated with GCs are described. We conclude that in RA patients treated with GCs there is a two-fold increase in the number of vertebral deformities compared to RA patients not treated with GCs. Every 1-milligram (mg) increase in daily GC dosage increases the risk of a vertebral deformity with 5%. Bone metabolism in RA patients is altered. In comparison to healthy controls, bone resorption in RA patients is increased and bone formation is normal to slightly decreased. This uncoupling of bone resorption and formation leads to bone loss. A meta-analysis showed that activated vitamin D3 metabolites like alfacalcidol are effective in prevention of glucocorticoid-induced osteoporosis (GIOP). In a randomized, double-placebo, double-blind clinical trial in 201 patients with a rheumatic disease starting treatment with GCs in a dosage of 7,5 mg/day or higher, bisphosphonates like alendronate, however, appeared to be more effective than alfacalcidol in prevention of GIOP. In patients with a rheumatic disease and a mean age of 60 years starting GC treatment in a dosage of 7,5 mg/day or higher, both alendronate and alfacalcidol are not cost-effective. Only in patients with a high base risk (i.e. high age, fracture history, GC dosages above 15 mg/day, etc) these medications can be more cost-effective. Measurement of bone markers for prediction of BMD in patients treated with GCs is not useful. Bisphosphonate therapy should be initiated immediately in patients starting GCs in a dosage of 15 mg/day or higher and/or with a vertebral fracture after the fifth decade, and in postmenopausal women and men over 70 years of age starting with a GC dosage between 7,5 to 15 mg/day. Measurement of BMD in this group is not recommended