Objectives To evaluate the efficacy of denosumab on bone mineral density (BMD) in patients receiving long-term glucocorticoids who do not have satisfactory response to bisphosphonate treatment.
Methods Patients who were receiving long-term prednisolone treatment for their underlying medical illnesses were recruited. The inclusion criteria were: (1) adult patients ≥18 years of age; (2) Daily dose of prednisolone ≥2.5mg within 3 months of study entry; (3) Inadequate BMD response or the development of new fracture despite bisphosphonate treatment for ≥2 years. Participants were randomized to receive either: (1) Denosumab (60mg subcutaneously every 6 months) + discontinuation of bisphosphonates; or (2) Continuation of oral bisphosphonates (control group). Calcium (3g/day of caltrate), vitamin D (rocaltrol 0.25ug/day) and other medications were continued as usual. Baseline and follow-up BMD (femoral neck, femoral trochanter, total hip, lumbar spine and whole body) at 6 and 12 months were performed. Markers of bone turnover (serum osteocalcin, serum P1NP, serum CTX, and urine DPD) were also assayed at the same time points. The primary outcome was the BMD change in the lumbar spine at month 12 compared to baseline.
Results 40 patients were recruited (95% women; age 54.3±12.9 years). Underlying medical diseases were: SLE (75%), RA (23%) and others (2%). The mean duration of prednisolone therapy was 98.3±65.6 months and the mean daily dose was 4.6±2.4mg at study entry. 34 (85%) patients were postmenopausal and the mean duration of menopause was 11.8±7.3 years. The mean body mass index (BMI) was 22.2±4.0kg/m2 (25% patients had BMI <18kg/m2). The bisphosphonates being used by the patients were alendronate (80%), risedronate (10%) and ibandronate (10%). Osteopenia or osteoporosis (T scores <-1.0) of the lumbar spine and the hip occurred in 93% and 75% of the patients, respectively, at baseline. Pre-existing fracture was present in 7 (18%) patients. 20 patients were assigned to each of the treatment arms. Baseline demographic data, osteoporotic risk factors, and BMD at various sites were not significantly different between the two groups of patients. At month 12, a significant gain in BMD at the lumbar spine (+3.4±0.9%; p=0.002) and the hip (+1.4±0.6%; p=0.03) was observed in denosumab-treated patients. Conversely, the increase in BMD of the spine and total hip was not statistically significant in the control group of patients. No new fractures occurred in the participants at month 12. Minor upper respiratory tract infection was numerically more commonly reported with denosumab treatment (30% vs 10%) while other adverse events occurred at similar frequency between the two groups. One patient of each group was withdrawn from the study because of non-compliance to treatment. None of the patients withdrew from study because of adverse events.
Conclusions In patients receiving long-term glucocorticoids but not having adequate response to bisphosphonates, denosumab was effective in raising the BMD at the spine and hip after 12 months' therapy. Denosumab was well tolerated.
Disclosure of Interest None declared