Side effects of glucocorticoids and specific aspects of laboratory monitoring for osteoporosis in patients with ulcerative colitis

Objective: development of the most significant approach to laboratory monitoring of adverse effects of glucocorticoids in patients with ulcerative colitis (UC). Materials and methods: the study included 205 patients of both sexes, aged 18–44 years, with chronic relapsing ulcerative colitis of moderate severity. The control group consisted of 25 apparently healthy individuals matched for age and sex. Based on the extent of colonic involvement, two clinical groups were identified: Group 1 comprised 118 patients with left-sided colitis, and Group 2 comprised 87 patients with extensive (total) disease. In accordance with clinical guidelines, patients who failed to achieve remission with 5-aminosalicylic acid preparations received systemic glucocorticoids (GC) at a dosage of 1 mg/kg/day for a maximum of 12 weeks. Patients who developed steroid-dependent osteoporosis during therapy were assigned to subgroups 1A (n=23) and 2A (n=21), while those without signs of steroidinduced osteopenia were assigned to subgroups 1B (n=95) and 2B (n=66). To facilitate early diagnosis of osteoporosis in these patients, the following laboratory parameters were assessed: serum levels of total and ionized calcium, phosphorus, magnesium, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP) activity, and concentrations of cathepsin K, sRANKL, and osteoprotegerin; urinary levels of calcium, phosphorus, hydroxyproline, and deoxypyridinoline; and cathepsin K levels in gingival fluid. Statistical analysis was performed using the Statistica 12.0 software package; differences were considered significant at p<0.05. Results: the earliest and most pronounced changes in bone resorption markers during long-term GC therapy were observed when assessing the activity of the proteolytic enzyme cathepsin K in gingival fluid and the level of the soluble ligand sRANKL in serum. A step-by-step analysis of the prognostic value of laboratory parameters for identifying ulcerative colitis patients at high risk of osteoporosis during maintenance steroid therapy established the following as significant predictors: baseline blood TNF-α concentration, cathepsin K content in gingival fluid, and serum sRANKL levels following the completion of the first course of steroids. Conclusions: to monitor the resorptive side effects of systemic glucocorticoid therapy in patients with ulcerative colitis, it is advisable to measure cathepsin K activity in gingival fluid using an enzyme immunoassay. A non-invasive method for assessing steroid-induced osteoporosis based on measuring cathepsin K concentration in gingival fluid has been proposed.

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