Background/Purpose

To evaluate the efficacy of denosumab on bone mineral density (BMD) in long-term glucocorticoid users who have inadequate response to oral 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 (<2% increase in BMD or remaining osteoporotic) or the development of new fracture despite oral bisphosphonates 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.  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, P1NP and CTX) were also assayed at the same time points.  The primary outcome was the difference of lumbar spine BMD at month 12 between the two groups.

Results

42 women were recruited (age 54.7±12.9 years)- 21 shifted to denosumab and 21 continued on bisphosphonates.  Underlying medical diseases were: SLE (76%) and RA (24%).  The duration of prednisolone therapy was 101±66.3 months and the daily dose was 4.4±2.1mg.  30 (71%) patients were postmenopausal and the mean duration of menopause was 12.3±7.2 years.  The mean body mass index (BMI) was 22.3±4.1kg/m² (21% patients had BMI <18kg/m²).  The bisphosphonates being used by the patients were alendronate (79%), risedronate (12%) and ibandronate (10%).  Pre-existing vertebral fracture was present in 7 (17%) patients and 3 patients (7%) had a family history of fragility fractures.  Baseline demographic data, osteoporotic risk factors, and BMD at various sites were not significantly different between the two groups.  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, whereas the corresponding change was +1.5±0.4% (p=0.001) and +0.80±0.5% (p=0.12) in the bisphosphonate group.  The spinal BMD at month 12 was significantly higher in the denosumab than bisphosphonate group after adjustment for baseline BMD values, age and other parameters (p=0.03).  No new fractures occurred in any participants at month 12.  Minor upper respiratory tract infection was more commonly reported with denosumab treatment (33% vs 5%; p=0.045) 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.  None of the patients withdrew from study because of adverse events.

Conclusion

In patients receiving long-term glucocorticoids but not having adequate response to bisphosphonates, shifting to denosumab was more effective in raising the BMD at the spine after 12 months’ therapy.  Denosumab was well tolerated.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/denosumab-for-long-term-glucocorticoid-users-who-have-inadequate-response-to-the-bisphosphonates-a-12-month-randomized-control-trial/