Efficacy and Safety of Postmenopausal Osteoporosis Treatments: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Abstract

Although a range of pharmacological interventions is available, it remains uncertain which treatment for osteoporosis is more effective. This network meta-analysis study aimed to compare different drug efficacy and safety in randomized controlled trials (RCTs) for the treatment of postmenopausal osteoporosis. PubMed, EMBASE, MEDLINE, Clinicaltrial.gov, Cochrane library, Google scholar were searched up to 31 October 2020. Randomized placebo-controlled trials that reported measures of bone mineral density (BMD) percentage change and/or numbers of adverse events of postmenopausal osteoporosis patients were included. Network meta-analysis was conducted using frequentist approach. Ninety-four RCTs comprising 15,776 postmenopausal osteoporosis females were included in the network meta-analysis. Compared with placebo, most interventions showed increase in BMD change. According to surfaces under the cumulative ranking curves (SUCRAs), strontium ranelate, fluoride, and hormone replacement therapy were most effective in increasing total hip, lumbar spine, and distal radius BMD, respectively. Parathyroid hormone (PTH) was most effective in preventing new hip fracture. When taking into account all anatomic sites, bisphosphonate (BP), monoclonal antibody (mAb), and fluoride have a balanced efficacy in increasing BMD at all sites. Considering both the effectiveness of increasing BMD and preventing hip fracture, mAb, BP, and PTH are more favorable among all interventions. The treatment effects of different medications on BMD percentage change are anatomic site-dependent. After weighing anti-osteoporosis treatment efficacy against risk of complications, BP and mAb are the more favorable interventions to increase BMD at all sites and reduce the risks of hip fracture and death.

Comparative effectiveness of bisphosphonate treatments for the prevention of re-fracture in glucocorticoid-induced osteoporosis: protocol for a systematic review and meta-analysis

“…For evaluating safety of BP, rate of adverse events including cancer, cardiovascular disease, death and osteonecrosis of the jaw will be included. 13 …”

“…For evaluating safety of BP, rate of adverse events including cancer, cardiovascular disease, death and osteonecrosis of the jaw will be included. 13 Search strategies for the identification of studies Electronic searches The following electronic databases will be searched from inception to December 2021: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. The specific search strategies (for example, PubMed) are listed in box 1.…”

“…The secondary outcome will include percentage changes on the bone mineral density and incidence of re-fracture. For evaluating safety of BP, rate of adverse events including cancer, cardiovascular disease, death and osteonecrosis of the jaw will be included 13…”

Real-life short-term effectiveness of anti-osteoporotic treatments: a longitudinal cohort study

“…Efficacy of all these drugs compared to calcium plus vitamin D alone or, for some of these, against active comparators, has been broadly demonstrated in clinical trials. 2 However, robust data on effectiveness of one treatment over another are still lacking. 3 Indeed, real-life studies are commonly flawed by confounding by indication bias and protopathic bias.…”

Clinical Parameters in Osteoporosis Patients Supplemented With PMA-Zeolite at the End of 5-Year Double-Blinded Clinical Trial

“…Also, the parameters on the quality of bone collagen, and bone microarchitecture, crucial for bone strength evaluation, may remain inconclusive. So far, most of the clinical studies of osteoporosis treatments, evaluated fracture risk as a parameter of therapeutic effect, but comparing the incidence of fractures regardless of the incidence of trauma or fall down ( 1 , 8 ). One possible approach for example, to assess the clear reduction of fracture risk in a treatment regimen may be within a long-term follow-up where the probability of potential fallings is increased.…”