Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

Chih-Hsing Wu^{1

2}, Wei-Chieh Hung^{3

4

5}, Ing-Lin Chang⁶, Tsung-Ting Tsai⁷, Yin-Fan Chang¹, Eugene V McCloskey⁸, Nelson B Watts⁹, Michael R McClung¹⁰, Chun-Feng Huang¹¹, Chung-Hwan Chen^{12

13

14

15}, Kun-Ling Wu^{16

17}, Keh-Sung Tsai¹⁸, Ding-Cheng Chan^{19

18

20}, Jung-Fu Chen²¹, Shih-Te Tu²², Jawl-Shan Hwang²³, Weibo Xia²⁴, Toshio Matsumoto²⁵, Yoon-Sok Chung²⁶, Cyrus Cooper^{27

28}, John A Kanis^{29

30}, Rong-Sen Yang³¹, Wing P Chan^{32

33}

Affiliations

¹ Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Institute of Geriatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Department of Family Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
⁴ Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.
⁵ Medicine for International Student, I-Shou University, Kaohsiung, Taiwan.
⁶ Department of Orthopaedics, ChangHua Christian Hospital, ChangHua, Taiwan.
⁷ Department of Orthopedics, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Taiwan.
⁸ Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK.
⁹ Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, USA.
¹⁰ The Oregon Osteoporosis Center, Portland, OR, USA.
¹¹ Department of Family Medicine, National Yang Ming University Hospital, I-Lan, Taiwan.
¹² Orthopaedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹³ Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁴ Department of Orthopaedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City, Taiwan.
¹⁵ Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
¹⁶ Department of Family Medicine, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan City, Taiwan.
¹⁷ Outpatient Clinic Department, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan City, Taiwan.
¹⁸ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
¹⁹ Superintendent Office, National Taiwan University Hospital Chu-Tung Branch, Taiwan.
²⁰ Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan.
²¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
²² Division of Endocrinology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
²³ Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Taiwan.
²⁴ Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
²⁵ Fujii Memorial Institute of Medical Sciences, University of Tokushima, Japan.
²⁶ Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea.
²⁷ MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
²⁸ Oxford National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK.
²⁹ Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
³⁰ Centre for Metabolic Bone Diseases, University of Sheffield Medical School, UK.
³¹ Department of Orthopaedics, College of Medicine, National Taiwan University & Hospital, Taipei, Taiwan.
³² Department of Radiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
³³ Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

PMID: 33195764
PMCID: PMC7645632
DOI: 10.1016/j.bonr.2020.100729

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

Chih-Hsing Wu et al. Bone Rep. 2020.

. 2020 Oct 27:13:100729.

doi: 10.1016/j.bonr.2020.100729. eCollection 2020 Dec.

Authors

Affiliations

¹ Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Institute of Geriatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Department of Family Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
⁴ Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.
⁵ Medicine for International Student, I-Shou University, Kaohsiung, Taiwan.
⁶ Department of Orthopaedics, ChangHua Christian Hospital, ChangHua, Taiwan.
⁷ Department of Orthopedics, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Taiwan.
⁸ Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK.
⁹ Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, USA.
¹⁰ The Oregon Osteoporosis Center, Portland, OR, USA.
¹¹ Department of Family Medicine, National Yang Ming University Hospital, I-Lan, Taiwan.
¹² Orthopaedic Research Centre, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹³ Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁴ Department of Orthopaedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City, Taiwan.
¹⁵ Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
¹⁶ Department of Family Medicine, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan City, Taiwan.
¹⁷ Outpatient Clinic Department, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan City, Taiwan.
¹⁸ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
¹⁹ Superintendent Office, National Taiwan University Hospital Chu-Tung Branch, Taiwan.
²⁰ Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan.
²¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
²² Division of Endocrinology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
²³ Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Taiwan.
²⁴ Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
²⁵ Fujii Memorial Institute of Medical Sciences, University of Tokushima, Japan.
²⁶ Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea.
²⁷ MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
²⁸ Oxford National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK.
²⁹ Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
³⁰ Centre for Metabolic Bone Diseases, University of Sheffield Medical School, UK.
³¹ Department of Orthopaedics, College of Medicine, National Taiwan University & Hospital, Taipei, Taiwan.
³² Department of Radiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
³³ Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

PMID: 33195764
PMCID: PMC7645632
DOI: 10.1016/j.bonr.2020.100729

Abstract

Objectives: Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture.

Method: The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with -1.0 > bone mineral density (BMD) T-score > -2.5 (low bone mass) and those with BMD T-score ≤ -2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up.

Results: Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36-0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%-5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%-3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures.

Conclusion: The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis.

Keywords: Fracture; Low bone mass; Osteopenia; Osteoporosis; Primary prevention.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
Meta-analysis of the effect of bisphosphonate on reducing vertebral fractures in postmenopausal women with osteopenia/osteoporosis.

**Fig. 2**
Bone mineral density differences between bisphosphonate and placebo groups. Differences after 1 year of follow up at A, the lumbar spine and B, the total hip. Differences after 2 years of follow up at C, the lumbar spine and D, the total hip.

See this image and copyright information in PMC

References

1. Ascott-Evans B.H., Guanabens N., Kivinen S., Stuckey B.G., Magaril C.H., Vandormael K. Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. Arch. Intern. Med. 2003;163(7):789–794. - PubMed
1. Barrionuevo P., Kapoor E., Asi N., Alahdab F., Mohammed K., Benkhadra K. Efficacy of pharmacological therapies for the prevention of fractures in postmenopausal women: a network meta-analysis. J. Clin. Endocrinol. Metab. 2019;104(5):1623–1630. - PubMed
1. Binkley N., Bone H., Gilligan J.P., Krause D.S. Efficacy and safety of oral recombinant calcitonin tablets in postmenopausal women with low bone mass and increased fracture risk: a randomized, placebo-controlled trial. Osteoporos. Int. 2014;25(11):2649–2656. - PMC - PubMed
1. Black D.V.E., Eastell R. Annual Meeting of the American Bone and Mineral Research Society, Montreal, Quebec, Canada. 2018. Change in BMD as a surrogate for fracture risk reduction in osteoporosis trials: results from pooled, individual-level patient data from the FNIH Bone Quality Project.
1. Bock O., Borst H., Beller G., Armbrecht G., Degner C., Martus P. Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo muCT. Bone. 2012;50(1):317–324. - PubMed

Grants and funding

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

Affiliations

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources