Tags

Type your tag names separated by a space and hit enter

Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.
BMJ. 2023 05 02; 381:e068033.BMJ

Abstract

OBJECTIVE

To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors.

DESIGN

Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.

DATA SOURCES

Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES

Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events.

RESULTS

The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision.

CONCLUSIONS

The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO CRD42019128391.

Links

PMC Free PDF

Authors+Show Affiliations

Händel MN
Parker Institute, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark. Department of Clinical Research, Odense Patient Data Explorative Network, University of Southern Denmark, Odense, Denmark.
Cardoso I
Parker Institute, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark.
von Bülow C
Parker Institute, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark. Occupational Science, User Perspectives and Community-Based Interventions, Department of Public Health, University of Southern Denmark, Odense C, Denmark.
Rohde JF
Parker Institute, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark.
Ussing A
Parker Institute, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark.
Nielsen SM
Parker Institute, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.
Christensen R
Parker Institute, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.
Body JJ
Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
Brandi ML
FirmoLab, FIRMO Foundation, Florence, Italy.
Diez-Perez A
Department of Internal Medicine, Institut Hospital del Mar of Medical Investigation, Autonomous University of Barcelona and CIBERFES (Frailty and Healthy Aging Research Network), Instituto Carlos III, Barcelona, Spain.
Hadji P
Frankfurt Centre of Bone Health, Frankfurt and Philipps-University of Marburg, Marburg, Germany.
Javaid MK
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Lems WF
WF Lems Department of Rheumatology, Amsterdam UMC, VUmc, Amsterdam, Netherlands.
Nogues X
IMIM (Hospital del Mar Medical Research Institute), Parc de Salut Mar, Pompeu Fabra University, Barcelona, Spain.
Roux C
INSERM U 1153, Hospital Paris-Centre, University of Paris, Paris, France.
Minisola S
Department of Clinical, Internal, Anaesthesiologic, and Cardiovascular Sciences, Rome University, Rome, Italy.
Kurth A
Department of Orthopaedic and Trauma Surgery, Marienhaus Klinikum Mainz, Major Teaching Hospital, University Medicine Mainz, Mainz, Germany.
Thomas T
Université Jean Monnet Saint-Étienne, CHU de Saint-Etienne, Rheumatology Department, INSERM U1059, F-42023, Saint-Etienne, France.
Prieto-Alhambra D
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK. Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands.
Ferrari SL
Division of Bone Diseases, Geneva University Hospital, Geneva, Switzerland.
Langdahl B
Departments of Clinical Medicine and of Endocrinology and Internal Medicine, Aarhus University, Aarhus, Denmark.
Abrahamsen B
Department of Clinical Research, Odense Patient Data Explorative Network, University of Southern Denmark, Odense, Denmark. Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK. Department of Medicine, Holbæk Hospital, Holbæk, Denmark.

MeSH

HumansFemaleBone Density Conservation AgentsNetwork Meta-AnalysisPostmenopauseDenosumabReceptor, Parathyroid Hormone, Type 1OsteoporosisOsteoporotic FracturesDiphosphonatesSpinal FracturesRisk Reduction BehaviorOsteoporosis, PostmenopausalRandomized Controlled Trials as Topic

Pub Type(s)

Systematic Review
Meta-Analysis
Journal Article

Language

eng

PubMed ID

37130601

Citation

Händel, Mina Nicole, et al. "Fracture Risk Reduction and Safety By Osteoporosis Treatment Compared With Placebo or Active Comparator in Postmenopausal Women: Systematic Review, Network Meta-analysis, and Meta-regression Analysis of Randomised Clinical Trials." BMJ (Clinical Research Ed.), vol. 381, 2023, pp. e068033.
Händel MN, Cardoso I, von Bülow C, et al. Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. BMJ. 2023;381:e068033.
Händel, M. N., Cardoso, I., von Bülow, C., Rohde, J. F., Ussing, A., Nielsen, S. M., Christensen, R., Body, J. J., Brandi, M. L., Diez-Perez, A., Hadji, P., Javaid, M. K., Lems, W. F., Nogues, X., Roux, C., Minisola, S., Kurth, A., Thomas, T., Prieto-Alhambra, D., ... Abrahamsen, B. (2023). Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. BMJ (Clinical Research Ed.), 381, e068033. https://doi.org/10.1136/bmj-2021-068033
Händel MN, et al. Fracture Risk Reduction and Safety By Osteoporosis Treatment Compared With Placebo or Active Comparator in Postmenopausal Women: Systematic Review, Network Meta-analysis, and Meta-regression Analysis of Randomised Clinical Trials. BMJ. 2023 05 2;381:e068033. PubMed PMID: 37130601.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. AU - Händel,Mina Nicole, AU - Cardoso,Isabel, AU - von Bülow,Cecilie, AU - Rohde,Jeanett Friis, AU - Ussing,Anja, AU - Nielsen,Sabrina Mai, AU - Christensen,Robin, AU - Body,Jean-Jacques, AU - Brandi,Maria Luisa, AU - Diez-Perez,Adolfo, AU - Hadji,Peyman, AU - Javaid,Muhammad Kassim, AU - Lems,Willem Frederik, AU - Nogues,Xavier, AU - Roux,Christian, AU - Minisola,Salvatore, AU - Kurth,Andreas, AU - Thomas,Thierry, AU - Prieto-Alhambra,Daniel, AU - Ferrari,Serge Livio, AU - Langdahl,Bente, AU - Abrahamsen,Bo, Y1 - 2023/05/02/ PY - 2023/5/4/medline PY - 2023/5/3/pubmed PY - 2023/5/2/entrez SP - e068033 EP - e068033 JF - BMJ (Clinical research ed.) JO - BMJ VL - 381 N2 - OBJECTIVE: To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. DESIGN: Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. DATA SOURCES: Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. RESULTS: The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision. CONCLUSIONS: The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019128391. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/37130601/Fracture_risk_reduction_and_safety_by_osteoporosis_treatment_compared_with_placebo_or_active_comparator_in_postmenopausal_women:_systematic_review_network_meta_analysis_and_meta_regression_analysis_of_randomised_clinical_trials_ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓3 ↑198]

Related Citations

More