New study reveals optimal drug sequencing for postmenopausal osteoporosis treatment

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In a recent study published in eClinicalMedicine, researchers compared the effectiveness and safety of available sequential treatments for the long-term management of postmenopausal osteoporosis (PMO) in women.

Study: Safety and efficacy of sequential treatments for postmenopausal osteoporosis: a network meta-analysis of randomised controlled trials. Image Credit: Pixel-Shot/Shutterstock.comStudy: Safety and efficacy of sequential treatments for postmenopausal osteoporosis: a network meta-analysis of randomised controlled trials. Image Credit: Pixel-Shot/


Osteoporosis (OP) adversely affects many postmenopausal women, which increases their bone fragility and risk of bone fracture due to decreased bone mineral density (BMD). By 2030, PMO might affect ~13.2 million American women aged ≥50.

Most patients with OP survive for a long duration; however, they constantly require treatment. Thus, guidelines recommend sequential treatments for OP patients.

However, there is uncertainty surrounding the optimal sequential order of administering anti-resorptive agents (AR) and anabolic agents (AB), drugs currently used for OP treatment.

Consequently, there is a need for robust evidence to guide and justify the clinical selection of different sequential treatments for OP. 

About the study

In the present study, researchers first conducted a thorough search on, EMBASE, PubMed, Web of Science, and the Cochrane Library from start to September 19, 2023, to identify randomized clinical trials (RCTs) involving sequential OP treatments and reporting PMO-related outcomes.

Next, they conducted a network meta-analysis (NMA) using the multivariate random effects technique to evaluate five sequential interventions of PMO: i) ABtAR; ii) ARtAAR; iii) ARtAB; iv) ABtC; and v) ARtC and used the surface under the cumulative ranking curve (SUCRA) to evaluate results.

The first intervention group switched from an AB to an AR, the second involved a transition from one AR to another AR regimen, the third involved a shift from an AR to an AB treatment, and the fourth and fifth involved a switch from an AB to an AB and AR combined regimen, and from an AR to a combined regimen, respectively. 

The study outcomes were vertebral fracture risk, the percentage change in BMD in different body parts (e.g., hips), and all safety parameters after switching treatment.

Finally, the team assessed the certainty of evidence using the Confidence in the Network Meta-Analysis (CINeMA) framework. 

This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.


This study included 19 RCTs comprising 18,416 participants with a mean age of 71.2 years, published between 2003 and 2021.

The intervention ARtC exhibited a significantly lower risk of vertebral fractures than other interventions, with a risk ratio (RR) of 0.11 and 95% confidence intervals (CIs). ARtC was also the best treatment for preventing vertebral fractures in stage two (SUCRA 81.5%).

Interventions ABtAR and ARtAB in the second stage also markedly reduced the incidence of vertebral fractures, with ABtAR being most suited to reduce total fractures (SUCRA: 94.3%).

The ABtC and ABtAR groups also showed a higher improvement in lumbar spine BMD. SUCRA cumulative probability indicated that ARtAAR caused the most significant change in lumbar spine BMD, with the highest SUCRA of 69.4%.

Moreover, ARtAAR was superior to other treatments in improving femoral neck BMD with a 77.3% probability and total hip BMD with a 96.1% probability.

The incidence of stage two adverse events (AEs) was lowest in the ABtAR group (SUCRA 83.2%) compared with the ARtAAR and monotherapy groups. The authors noted no difference in safety outcomes in other comparisons. Furthermore, ABtC (SUCRA 86.2%) had the lowest proportion of discontinuations, suggesting its high tolerability.


This study is a comprehensive data synthesis on sequential treatments for women with PMO, providing robust evidence supporting its rational clinical use.

ABtAR and ARtAAR were associated with significant fracture reduction and BMD improvements compared with monotherapies after treatment switching. 

Combination treatment after AB, i.e., ABtC, protected just the lumbar spine part because it could improve the percentage change of BMD and reduce the incidence of vertebral fractures.

ARtAB reduced non-vertebral fractures and improved the lumbar spine BMD compared with non-sequential regimens. 

Furthermore, ARtC ranked first in reducing the incidence of vertebral fractures in the second stage based on the NMA. However, more data on ARtC and ARtAB is needed to understand their efficacy fully. 

Overall, the study data may serve as a valuable reference for patients, caregivers, clinicians, and policymakers to inform future clinical practice, guidelines, and policies about the sequential treatment of osteoporosis.

Journal reference:
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.


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