Efficacy of Denosumab and Zoledronic Acid in the Treatment of Idiopathic Inflammatory Myopathies Related Reduced Bone Mineral Density: a Prospective Controlled Trial

Background:

With recent advances in diagnoses and classification of idiopathic inflammatory myopathies (IIM), an increasing number of newly diagnosed cases of IIM is expected. These patients are vulnerable to the development of Glucocorticoid-induced osteoporosis (GIOP) due to impaired mobility related to musculoskeletal involvement and the relatively high doses of glucocorticoid (GC) required for disease control. Reduced bone mineral density is prevalent among IIM patients shown in the previous local study: osteoporosis and osteopenia are seen in 23.7% and 47.4% of IIM patients respectively. 10% of patients on long term GC treatment sustain a fracture and up to 30-40% of patients are found to have radiological vertebral fractures. Compared to GIOP, the treatment for patients with osteopenia is less well addressed in current guidelines for the management of GIOP. Treatment is usually indicated in patients with a previous history of prior low energy fracture and high fracture risks determined by FRAX score. However, IIMs remain a rare disease entity and IIMs patients are at particularly high risk for osteoporosis and its complications due to a relatively high dose of steroid use and functional impairment from the disease. Therefore, traditional fracture risks assessment tool might not be able to fully assess the fracture risks in this subgroup of patients.

Denosumab is a human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) and its use is associated with a reduced risk of vertebral, non-vertebral and hip fracture in post-menopausal women. A recent randomized controlled trial has shown that denosumab is more efficacious than risedronate in the improvement of BMD in GIOP patients. Denosumab has been confirmed efficacious in GIOP patients but its efficacy in high-risk osteopenia patients are not well studied. On the other hand, zoledronic acid is licensed for the treatment of GIOP and trials found zoledronic acid improve bone mineral density at the lumbar spine or femoral neck at 12 months of treatment. Current evidence comparing the efficacy between denosumab and zoledronic acid is lacking.

In this prospective study, the investigators aimed to assess the efficacy of denosumab and zoledronic acid in the treatment of IIMs patients with reduced bone mineral density.

Study methods This is a prospective open-label controlled trial. All IIMs patients followed up in Kwong Wah Hospital are invited to participate in this study. Eligibility, inclusion, and exclusion criteria are described in details in subsequent sessions. All included patients will have dual-energy X-Ray absorptiometry (DEXA) scan performed at baseline. All participants will continue calcium (1000mg daily) and vitamin D supplementation (at least 800 international unit daily). Patients with osteopenia or osteoporosis in a baseline DEXA scan will be randomized by computer-generated blocks in 1:1 ratio into receiving denosumab (treatment group) or zoledronic acid (controlled group). Denosumab is given at 60mg subcutaneously every 6 months, following the FDA approved dosage. Zoledronic acid is administered intravenously at 5mg yearly. DEXA scan will be repeated after 12 months of treatment.