A randomized controlled trial comparing the efficacy of denosumab, teriparatide or combination of denosumab and teriparatide on bone microarchitecture in patients being initiated on glucocorticoids
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- PGIMER
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- To assess the percent change in BMD at the lumbar spine and femoral neck at the end of intervention.
研究概览
简要总结
Osteoporosis is the most common typeof metabolic bone disease that is estimated to affect more than 200 millionpeople in the world(1). The prevalence of osteoporosis has risensignificantly and will likely increase in the near future due to the agingpopulation. Glucocorticoid (GC) therapyis used for the treatment of several diseases such as connective tissue disorders, vasculitis,tuberculosis, inflammatory bowel diseases, etc., Glucocorticoid is given insupraphysiological doses in all these diseases. Published literature showsthat 1-2% of the adult population is on oral glucocorticoids for various therapeuticindications(2). Long-term Glucocorticoid (LTGC) therapy isassociated with an increased risk of vertebral and non-vertebral fractures(3).
Various studies done in the pastconsistently show deleterious effects of glucocorticoids even with a dose of2.5 mg of prednisone for more than 3 months duration(4). The risk of fractures in patients who are on long-term glucocorticoids is higher in patients even with a normal bone mineraldensity measured with Dual energy-Xray-Absorptiometry(DXA)(5). This is because there are many other factors thatpredispose a person to fractures apart from dual-energy X-ray absorptiometry.The risk of fracture is increased at a higher BMD level in patients withGlucocorticoid-induced osteoporosis (GIO) when compared to post-menopausalosteoporosis(6). Hence, various fracture risk assessment tools likeFRAX have been used to identify patients who are at a higher risk ofdeveloping fractures(7).
There is an increased risk offragility fractures in patients who are being initiated on long-termglucocorticoids. Multiple randomized controlled trials have been done in thepast with various drugs such as risedronate, zoledronate, denosumab, and teriparatide(8–16). All these drugs have been approved for thetreatment of osteoporosis(5,17). Bisphosphonates are the oldest group of drugsthat have been proven to be effective in the prevention of glucocorticoid-inducedosteoporosis. Multiple RCTs comparing denosumab either with placebo or withbisphosphonates have shown a superior efficacy of denosumab in improving BMD in the lumbar spine(8,9,18,19). A systematic review and meta-analysishave shown that denosumab is superior to bisphosphonates in improving thelumbar spine and distal radius BMD at 12 months(20). Denosumab was superior compared tobisphosphonates in suppressing P1NP and CTX at 12 months(20). Teriparatide is found to be more effective inimproving BMD in the Lumbar spine and Femoral neck compared to denosumab(21,22). Teriparatide is superior to denosumab inreducing the risk of vertebral fractures however there is no difference in therisk reduction of non-vertebral fractures(22,23).
The effect of the combination therapy ofdenosumab and teriparatide has not been studied in the primary prevention ofosteoporosis in patients with long-term glucocorticoids. However, RCT done inpatients with postmenopausal osteoporosis has shown a superior efficacy of combinationtherapy with teriparatide and denosumab in increasing the BMD in patients with post-menopausalosteoporosis compared to either of the drugs given alone (24,25). Thedata on microarchitectural changes in patients on long-term glucocorticoids andthe effect of these drugs on these microarchitectural changes is also scarce inthe literature. Moreover, the effect of these drugs in the prevention of GIOhas not yet been studied in our population. Most of the studies done in thepast in GIO assessed the changes in bone mineral density with variousmodalities of therapy for the prevention of osteoporosis. Very few studies havestudied the changes in bone microarchitecture using High resolution peripheralquantitative computed tomography (HR-pQCT) or bone biopsy.
Hence, the present study will beundertaken to compare the efficacy of the teriparatide and denosumab, alone orboth combined together, in patients who are being initiated on long-termglucocorticoid therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Permuted block randomization, fixed
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Day(s) 至 80.00 Day(s)（—）
- 性别
- All
入选标准
- •Age > 18 years
- •Patients who are being started on glucocorticoids for various therapeutic indications.
- •Steroid dose > 2.5 mg Prednisone (or equivalent dose of other steroids) per day for at least three months.
- •Patients who are willing to give informed consent.
排除标准
- •Baseline eGFR < 45 ml/min/1.73 m2
- •Patients who have received steroid dose of more than 2.5 mg per day for more than 3 months in the past 1 year
- •Pregnant females.
- •Females with reproductive age group if they will plan for pregnancy for the next 2 years.
- •Patients with intrinsic bone disorders (FD or Skeletal dysplasia).
- •Patients on drugs affecting bone health or received anti-osteoporotic therapy
- •Patients with secondary causes of osteoporosis (Endogenous Cushing Syndrome, Hyperprolactinemia, Primary hyperparathyroidism, CKD, Hypoparathyroidism etc.,)
- •Patients with structural abnormalities, kyphoscoliosis, hip replacement or surgical implants that may affect DXA study.
- •History of chronic diseases which can directly affect bone and mineral metabolism, like Rheumatoid arthritis, Ankylosing spondylitis, Marfan syndrome, EDS, Celiac disease, and Inflammatory bowel disease.
- •Patients who are not willing to give informed consent.
结局指标
主要结局
To assess the percent change in BMD at the lumbar spine and femoral neck at the end of intervention.
时间窗: •9 - 12 months
次要结局
- 1. To assess the dynamic changes in the BMD parameters(2. To assess the dynamic changes in bone microarchitecture parameters using high resolution peripheral quantitative CT)