Glucocorticoid (GC) is the main stay of treatment of many rheumatic diseases but is also an important cause of secondary osteoporosis. The long-term use of GCs increases the risk of fragility fracture at a much higher bone mineral density (BMD) than postmenopausal osteoporosis, indicating an additional deleterious effect of GC on bone quality. More than one-third of postmenopausal women receiving GC therapy developed asymptomatic vertebral fractures. A study in general practice reported an increased relative risk of vertebral and hip fractures in chronic GC users, with fracture risk proportional to the daily dose of GC. Another study also confirmed that intermittent use of high-dose GC and the cumulative GC dose was associated with an augmented risk of osteoporotic fracture.~The glycoprotein sclerostin, secreted by the osteocytes under the influence of mechanical loading, inhibits activation of the canonical Wnt pathway involved in osteoblastogenesis and hence suppresses bone formation. Moreover, sclerostin enhances resorption of the bone by stimulating the production of (RANKL) by the osteocytes. Romosozumab (ROMO) is a humanized monoclonal antibody against sclerostin. The landmark RCT has demonstrated efficacy of ROMO (210mg subcutaneously monthly) over placebo in reducing vertebral fractures by 73% at 12 months in 7180 postmenopausal women with osteoporosis of the hip at entry. The suppression of markers of bone resorption and enhancement of markers of bone formation indicates that ROMO has a dual mode of action on the bones. The efficacy of ROMO has also been tested against oral bisphosphonates. A RCT was conducted in 4093 post-menopausal women who were assigned to receive either ROMO (201mg subcutaneously monthly) or oral alendronate (70mg weekly) for 12 months, followed by open-label alendronate for another 12 months. At month 24, a 48% lower risk of new vertebral fractures was observed in the ROMO (6.2%) than the alendronate group (11.9%; p<0.001). The risk of incident hip fractures was also significantly lower in the ROMO (2%) than alendronate treated patients (3.2%; p=0.02). The frequencies of adverse events and serious adverse events, however, were similar in the two treatment arms.~There are no data regarding the efficacy of ROMO in GC-induced osteoporosis. Comparative study on the efficacy of ROMO and denosumab in post-menopausal osteoporosis is also not yet available in the literature. This prompts the current pilot study to compare the efficacy of ROMO with denosumab in high-risk patients receiving long-term GCs.
Glucocorticoid (GC) is the main stay of treatment of many rheumatic diseases but is also an important cause of secondary osteoporosis. The long-term use of GCs increases the risk of fragility fracture at a much higher bone mineral density (BMD) than postmenopausal osteoporosis, indicating an additional deleterious effect of GC on bone quality. An increased relative risk of vertebral and hip fractures is demonstrated in chronic GC users, with fracture risk proportional to the daily dose of GC. Other studies have also confirmed that intermittent use of high-dose GC and the cumulative GC dose was associated with an augmented risk of osteoporotic fracture.~Romosozumab (ROMO) is a humanized monoclonal antibody against sclerostin. The landmark RCT has demonstrated efficacy of ROMO (210mg subcutaneously monthly) over placebo in reducing vertebral fractures by 73% at 12 months in 7180 postmenopausal women with osteoporosis of the hip at entry. Another RCT has demonstrated efficacy of ROMO in reducing vertebral and hip fractures in 4093 post-menopausal women at month 24.~There are no data regarding the efficacy of ROMO in GC-induced osteoporosis. Comparative study on the efficacy of ROMO and denosumab in post-menopausal osteoporosis is also not yet available in the literature. This prompts the current pilot study to compare the efficacy of ROMO with denosumab in high-risk patients receiving long-term GCs.