Denosumab vs Alendronate in Postmenopausal Osteoporosis
Denosumab vs Alendronate in Postmenopausal Osteoporosis
The aim of this study was to perform a head-to-head comparison of efficacy and safety profile between 60 mg denosumab (Den) subcutaneously (SC) per 6 months (Q6M) and 70 mg alendronate (Aln) orally per week (QW) for postmenopausal women with low bone mineral density. We searched electronic databases comparing efficacy and safety of Den SC Q6M and Aln QW in postmenopausal women. The primary outcomes of efficacy evaluation in included trials were incidence of clinical fracture in both groups and bone mineral density (BMD) at different skeletal sites. And adverse events (AEs), including incidence of neoplasms and infections, were considered as secondary outcomes. Following the instructions of 'Cochrane Handbook for systematic Reviews of Interventions 5.0.2', we identified eligible studies, evaluated the methodological quality and abstracted relevant data. Four heterogeneous randomised controlled trials (RCTs) involving 1942 women were identified. The results of review showed low evidence quality that supported the hypothesis the denosumab vs. alendronate could reduce risk of fracture [OR (95% CI) 1.42 (0.84 to 2.40), 11 more women per 1000 (from 4 fewer to 36 more), p = 0.19] but the moderate to high quality evidence suggesting treatment with 60 mg Den SC Q6M was more effective for postmenopausal women in increasing BMD [at distal radius (DR), total hip (TH), lumbar spine (LS), and femoral neck (FN)]. Hazards of neoplasms [OR (95% CI) 1.10 (0.65 to 1.86), 3 more per 1000 (from 10 fewer to 24 more), p = 0.62] or infections [OR (95% CI) 0.95 (0.79 to 1.15), 12 fewer per 1000 (from 53 fewer to 33 more,), p = 0.62] were appeared to be similar.Our review suggested within 1 year 60 mg Den SC Q6M treatment was more effective in increasing bone mass but could not reduce the fracture risk to a greater extent than 70 mg Aln QW therapy. Also the Den SC Q6M therapy did not increase the risks of neoplasms and infections compared with Aln QW.
Osteoporosis, most cases of which occur in postmenopausal women and is defined by low BMD, is a common contributor to an estimated 90% of all hip and spine fractures in white American women aged 65–84 years. The therapeutic goal is to increase the bone mass, improve the bone strength and ultimately to reduce the fracture incidence.
Alendronate (Aln), a classic antiresorptive agent, is one of the most widely prescribed class of therapy for osteoporosis. It could significantly reduce the bone turnover by binding to bone and inhibiting the bone resorption. Aln was reported to reduce 45% risk of hip fractures of postmenopausal osteoporotic women. However, only a few patients fully adhere to its long therapeutic duration because of the gastrointestinal disorder and inconveniences. A recent study reported only 30.6% of patients adhered to one dose of Aln per week (QW) after 1-year treatment.
Receptor activator of nuclear factor- κ B ligand (RANKL) is a cytokine essential for osteoclast differentiation, activation, and survival. The RANKL inhibitor denosumab is a fully human monoclonal IgG2 antibody, which potently reduces bone resorption with accompanying increases in bone mineral density (BMD) by binding RANKL. 60 mg Den subcutaneously (SC) per 6 months (Q6M) as been well documented to improve the patients' compliances, reduce the bone remodeling, and increase the bone mass. A significant 42% reduction in fracture incidence could be identified in a recent meta-analysis in postmenopausal women of denosumab treatment compared with the placebo control. However, RANK activation by RANKL is also necessary for T-cell growth and dendritic cell function, inhibition of its action was supposed to simultaneously influence the immune system, leading to high susceptibility of infections and neoplasms.
The efficacy of two agents appeared similar according to two recent meta-analysis: when compared with placebo groups, 42% with Den therapy and 45% with Aln treatment in fracture risk reduction could be found respectively. But to our knowledge, the number and sample size of the relevant RCTs performing such head-to-head comparison between both agents was relative small. Until now no meta-analysis had been published on this topic.
Thus, it is meaningful to carry out this meta-analysis to evaluate whether Den would be more effective in reducing risk of fracture and increasing bone mass without increasing the risk of neoplasms and infections in postmenopausal women compared with Aln.
Abstract and Introduction
Abstract
The aim of this study was to perform a head-to-head comparison of efficacy and safety profile between 60 mg denosumab (Den) subcutaneously (SC) per 6 months (Q6M) and 70 mg alendronate (Aln) orally per week (QW) for postmenopausal women with low bone mineral density. We searched electronic databases comparing efficacy and safety of Den SC Q6M and Aln QW in postmenopausal women. The primary outcomes of efficacy evaluation in included trials were incidence of clinical fracture in both groups and bone mineral density (BMD) at different skeletal sites. And adverse events (AEs), including incidence of neoplasms and infections, were considered as secondary outcomes. Following the instructions of 'Cochrane Handbook for systematic Reviews of Interventions 5.0.2', we identified eligible studies, evaluated the methodological quality and abstracted relevant data. Four heterogeneous randomised controlled trials (RCTs) involving 1942 women were identified. The results of review showed low evidence quality that supported the hypothesis the denosumab vs. alendronate could reduce risk of fracture [OR (95% CI) 1.42 (0.84 to 2.40), 11 more women per 1000 (from 4 fewer to 36 more), p = 0.19] but the moderate to high quality evidence suggesting treatment with 60 mg Den SC Q6M was more effective for postmenopausal women in increasing BMD [at distal radius (DR), total hip (TH), lumbar spine (LS), and femoral neck (FN)]. Hazards of neoplasms [OR (95% CI) 1.10 (0.65 to 1.86), 3 more per 1000 (from 10 fewer to 24 more), p = 0.62] or infections [OR (95% CI) 0.95 (0.79 to 1.15), 12 fewer per 1000 (from 53 fewer to 33 more,), p = 0.62] were appeared to be similar.Our review suggested within 1 year 60 mg Den SC Q6M treatment was more effective in increasing bone mass but could not reduce the fracture risk to a greater extent than 70 mg Aln QW therapy. Also the Den SC Q6M therapy did not increase the risks of neoplasms and infections compared with Aln QW.
Introduction
Osteoporosis, most cases of which occur in postmenopausal women and is defined by low BMD, is a common contributor to an estimated 90% of all hip and spine fractures in white American women aged 65–84 years. The therapeutic goal is to increase the bone mass, improve the bone strength and ultimately to reduce the fracture incidence.
Alendronate (Aln), a classic antiresorptive agent, is one of the most widely prescribed class of therapy for osteoporosis. It could significantly reduce the bone turnover by binding to bone and inhibiting the bone resorption. Aln was reported to reduce 45% risk of hip fractures of postmenopausal osteoporotic women. However, only a few patients fully adhere to its long therapeutic duration because of the gastrointestinal disorder and inconveniences. A recent study reported only 30.6% of patients adhered to one dose of Aln per week (QW) after 1-year treatment.
Receptor activator of nuclear factor- κ B ligand (RANKL) is a cytokine essential for osteoclast differentiation, activation, and survival. The RANKL inhibitor denosumab is a fully human monoclonal IgG2 antibody, which potently reduces bone resorption with accompanying increases in bone mineral density (BMD) by binding RANKL. 60 mg Den subcutaneously (SC) per 6 months (Q6M) as been well documented to improve the patients' compliances, reduce the bone remodeling, and increase the bone mass. A significant 42% reduction in fracture incidence could be identified in a recent meta-analysis in postmenopausal women of denosumab treatment compared with the placebo control. However, RANK activation by RANKL is also necessary for T-cell growth and dendritic cell function, inhibition of its action was supposed to simultaneously influence the immune system, leading to high susceptibility of infections and neoplasms.
The efficacy of two agents appeared similar according to two recent meta-analysis: when compared with placebo groups, 42% with Den therapy and 45% with Aln treatment in fracture risk reduction could be found respectively. But to our knowledge, the number and sample size of the relevant RCTs performing such head-to-head comparison between both agents was relative small. Until now no meta-analysis had been published on this topic.
Thus, it is meaningful to carry out this meta-analysis to evaluate whether Den would be more effective in reducing risk of fracture and increasing bone mass without increasing the risk of neoplasms and infections in postmenopausal women compared with Aln.
Source...