Journal Home > Volume 1 , Issue 1
Nano TransMed 2022, 1(1): 9130003 https://doi.org/10.26599/NTM.2022.9130003
Review Article | Open Access | Issue | Published: 28 February 2022

Comparative efficacy and safety of bisphosphonate therapy for bone loss in individuals after middle age: A systematic review and network meta-analysis

Show Author's Information Qin Hu1,2,  Xun Pan2,  Yaxian Liang2,  Hongdan Xu2,  Jinning Gu2,  Wenting She3( ),  Huixu Xie2( )
Faculty of Dentistry, Periodontology, The University of Hong Kong, Hong Kong, China
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
Center of Stomatology, Renmin Hospital of Wuhan University, Wuhan 430061, China
Keywords:
fracture, bone loss, bisphosphonates, bone mineral density, nano-drug delivery system
Cite this article:
Hu Q, Pan X, Liang Y, et al. Comparative efficacy and safety of bisphosphonate therapy for bone loss in individuals after middle age: A systematic review and network meta-analysis. Nano TransMed, 2022, 1(1): 9130003. https://doi.org/10.26599/NTM.2022.9130003
Download citation
EndNote(RIS)
BibTeX

1858

Views

248

Downloads

Citations

0

Crossref

N/A

WoS

N/A

Scopus

N/A

CSCD

Abstract Full text Electronic supplementary material About this article
PURPOSE

The purpose of this study was to estimate the benefits and drawbacks of bisphosphonates in the treatment of osteoporosis and osteopenia in middle-aged and elderly individuals.

METHODS

We searched Ovid MEDLINE, Embase, the Web of Science, and Cochrane library databases for randomized clinical trials (RCTs) evaluating the effects of bisphosphonates and performed a network meta-analysis to summarize the direct and indirect evidence on the efficacy and safety of bisphosphonate therapy in middle-aged and elderly individuals with osteoporosis or osteopenia.

RESULTS

A total of 14 RCTs (7, 769 patients with osteoporosis or osteopenia; median age, 67 years; median follow-up, 27 months) were included in this network meta-analysis. Of these, 8, 10, 9, and 6 RCTs provided outcomes on bone mineral density changes, clinical fracture rates, vertebral fracture rates, and nonvertebral fracture rates, respectively. Regarding the primary efficacy outcome, there was a 97% probability for alendronate to be the most effective treatment approach for increasing bone mineral density and an 84% probability for zoledronate to be the most effective treatment approach for clinical fractures. Regarding vertebral fractures and safety outcomes, zoledronate showed an odds ratio (OR) of 0.45 (95% confidence intervals [CI], 0.30–0.69) relative to placebo. For nonvertebral fractures, the OR of zoledronate relative to placebo was 0.51 (95% CI 0.29–0.90).

CONCLUSIONS

This study revealed that alendronate was effective in increasing bone mineral density in middle-aged individuals and that zoledronate was a safe treatment option for osteoporosis and osteopenia, conferring a low incidence of fracture. However, further clinical studies are needed to confirm these results.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Comparative efficacy and safety of bisphosphonate therapy for bone loss in individuals after middle age: A systematic review and network meta-analysis

Show Author's information Qin Hu1,2, Xun Pan2, Yaxian Liang2, Hongdan Xu2, Jinning Gu2, Wenting She3( ), Huixu Xie2( )
Faculty of Dentistry, Periodontology, The University of Hong Kong, Hong Kong, China
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
Center of Stomatology, Renmin Hospital of Wuhan University, Wuhan 430061, China

Abstract

PURPOSE

The purpose of this study was to estimate the benefits and drawbacks of bisphosphonates in the treatment of osteoporosis and osteopenia in middle-aged and elderly individuals.

METHODS

We searched Ovid MEDLINE, Embase, the Web of Science, and Cochrane library databases for randomized clinical trials (RCTs) evaluating the effects of bisphosphonates and performed a network meta-analysis to summarize the direct and indirect evidence on the efficacy and safety of bisphosphonate therapy in middle-aged and elderly individuals with osteoporosis or osteopenia.

RESULTS

A total of 14 RCTs (7, 769 patients with osteoporosis or osteopenia; median age, 67 years; median follow-up, 27 months) were included in this network meta-analysis. Of these, 8, 10, 9, and 6 RCTs provided outcomes on bone mineral density changes, clinical fracture rates, vertebral fracture rates, and nonvertebral fracture rates, respectively. Regarding the primary efficacy outcome, there was a 97% probability for alendronate to be the most effective treatment approach for increasing bone mineral density and an 84% probability for zoledronate to be the most effective treatment approach for clinical fractures. Regarding vertebral fractures and safety outcomes, zoledronate showed an odds ratio (OR) of 0.45 (95% confidence intervals [CI], 0.30–0.69) relative to placebo. For nonvertebral fractures, the OR of zoledronate relative to placebo was 0.51 (95% CI 0.29–0.90).

CONCLUSIONS

This study revealed that alendronate was effective in increasing bone mineral density in middle-aged individuals and that zoledronate was a safe treatment option for osteoporosis and osteopenia, conferring a low incidence of fracture. However, further clinical studies are needed to confirm these results.

Keywords: fracture, bone loss, bisphosphonates, bone mineral density, nano-drug delivery system

References(46)

1

Rachner, T. D.; Khosla, S.; Hofbauer, L. C. Osteoporosis: Now and the future. Lancet 2011, 377, 1276–1287.
DOI Google Scholar
2

Cummings, S. R.; Melton, L. J. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002, 359, 1761–1767.
DOI Google Scholar
3

Reginster, J. Y.; Burlet, N. Osteoporosis: A still increasing prevalence. Bone 2006, 38, 4–9.
DOI Google Scholar
4

Eastell, R. Treatment of postmenopausal osteoporosis. N. Engl. J. Med. 1998, 338, 736–746.
DOI Google Scholar
5

Bhandari, M.; Swiontkowski, M. Management of acute hip fracture. N. Engl. J. Med. 2017, 377, 2053–2062.
DOI Google Scholar
6

Russell, R. G. G. Bisphosphonates: The first 40 years. Bone 2011, 49, 2–19.
DOI Google Scholar
7

Russell, R. G. G.; Croucher, P. I.; Rogers, M. J. Bisphosphonates: Pharmacology, mechanisms of action and clinical uses. Osteoporos. Int. 1999, 9, S66–S80.
DOI Google Scholar
8

Rogers, M. J.; Frith, J. C.; Luckman, S. P.; Coxon, F. P.; Benford, H. L.; Mönkkönen, J.; Auriola, S.; Chilton, K. M.; Russell, R. G. G. Molecular mechanisms of action of bisphosphonates. Bone 1999, 24, 73S–79S.
DOI Google Scholar
9

De Rosa, G.; Misso, G.; Salzano, G.; Caraglia, M. Bisphosphonates and cancer: What opportunities from nanotechnology? J. Drug Deliv. 2013, 2013, 637976.
DOI Google Scholar
10

Hodgins, N. O.; Wang, J. T. W.; Al-Jamal, K. T. Nano-technology based carriers for nitrogen-containing bisphosphonates delivery as sensitisers of γδ T cells for anticancer immunotherapy. Adv. Drug Deliv. Rev. 2017, 114, 143–160.
DOI Google Scholar
11

Geng, Z.; Wang, X. G.; Yu, Y. M.; Ji, L. L.; Wang, J.; Liu, C. S. Attenuating osteoarthritis by a high efficient anti-bone resorption injectable pH-responsive bisphosphonate-conjugated nano-apatite system. Chem. Eng. J. 2021, 420, 127674.
DOI Google Scholar
12

Drake, M. T.; Clarke, B. L.; Khosla, S. Bisphosphonates: Mechanism of action and role in clinical practice. Mayo Clin. Proceed. 2008, 83, 1032–1045.
DOI Google Scholar
13

Rosen, C. J. Postmenopausal osteoporosis. N. Engl. J. Med. 2005, 353, 595–603.
DOI Google Scholar
14

Serrano, A. J.; Begoña, L.; Anitua, E.; Cobos, R.; Orive, G. Systematic review and meta-analysis of the efficacy and safety of alendronate and zoledronate for the treatment of postmenopausal osteoporosis. Gynecol. Endocrinol. 2013, 29, 1005–1014.
DOI Google Scholar
15

Karpf, D. B.; Shapiro, D. R.; Seeman, E.; Ensrud, K. E.; Johnston, C. C. Jr.; Adami, S.; Harris, S. T.; Santora Ⅱ, A. C.; Hirsch, L. J.; Oppenheimer, L. et al. Prevention of nonvertebral fractures by alendronate: A meta-analysis. JAMA, 1997, 277, 1159–1164.
DOI Google Scholar
16

Byun, J. H.; Jang, S.; Lee, S.; Park, S.; Yoon, H. K.; Yoon, B. H.; Ha, Y. C. The efficacy of bisphosphonates for prevention of osteoporotic fracture: An update meta-analysis. J. Bone Metab. 2017, 24, 37–49.
DOI Google Scholar
17

Sanderson, J.; James, M. M. S.; Stevens, J.; Goka, E.; Wong, R.; Campbell, F.; Selby, P.; Gittoes, N.; Davis, S. Clinical effectiveness of bisphosphonates for the prevention of fragility fractures: A systematic review and network meta-analysis. Bone 2016, 89, 52–58.
DOI Google Scholar
18

Kanis, J. A. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report. Osteoporos. Int. 1994, 4, 368–381.
DOI Google Scholar
19

Salanti, G.; Ades, A. E.; Ioannidis, J. P. A. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: An overview and tutorial. J. Clin. Epidemiol. 2011, 64, 163–171.
DOI Google Scholar
20

Adami, S.; Baroni, M. C.; Broggini, M.; Carratelli, L.; Caruso, I.; Gnessi, L.; Laurenzi, M.; Lombardi, A.; Norbiato, G.; Ortolani, S. et al. Treatment of postmenopausal osteoporosis with continuous daily oral alendronate in comparison with either placebo or intranasal salmon calcitonin. Osteoporos. Int. 1993, 3, 21–27.
DOI Google Scholar
21

Bone, H. G.; Downs, R. W. Jr.; Tucci, J. R.; Harris, S. T.; Weinstein, R. S.; Licata, A. A.; McClung, M. R.; Kimmel, D. B.; Gertz, B. J.; Hale, E. et al. Dose–response relationships for alendronate treatment in osteoporotic elderly women. J. Clin. Endocrinol. Metab. 1997, 82, 265–274.
DOI Google Scholar
22

Hosking, D.; Chilvers, C. E. D.; Christiansen, C.; Ravn, P.; Wasnich, R.; Ross, P.; McClung, M.; Balske, A.; Thompson, D.; Daley, M. et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N. Engl. J. Med. 1998, 338, 485–492.
DOI Google Scholar
23

Lau, E. M. C.; Woo, J.; Chan, Y. H.; Griffith, J. Alendronate prevents bone loss in Chinese women with osteoporosis. Bone 2000, 27, 677–680.
DOI Google Scholar
24

Greenspan, S. L.; Resnick, N. M.; Parker, R. A. Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: A randomized controlled trial. JAMA, 2003, 289, 2525–2533.
DOI Google Scholar
25

Hosking, D.; Adami, S.; Felsenberg, D.; Andia, J. C.; Välimäki, M.; Benhamou, L.; Reginster, J. Y.; Yacik, C.; Rybak-Feglin, A.; Petruschke, R. A. et al. Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: A randomised, placebo-controlled study. Curr. Med. Res. Opin. 2003, 19, 383–394.
DOI Google Scholar
26

Hooper, M. J.; Ebeling, P. R.; Roberts, A. P.; Graham, J. J.; Nicholson, G. C.; D'Emden, M.; Ernst, T. F.; Wenderoth, D. Risedronate prevents bone loss in early postmenopausal women: A prospective randomized, placebo-controlled trial. Climacteric 2005, 8, 251–262.
DOI Google Scholar
27

Choi, H. J.; Im, J. A.; Kim, S. H. Changes in bone markers after once-weekly low-dose alendronate in postmenopausal women with moderate bone loss. Maturitas 2008, 60, 170–176.
DOI Google Scholar
28

McClung, M. R.; Bolognese, M. A.; Sedarati, F.; Recker, R. R.; Miller, P. D. Efficacy and safety of monthly oral ibandronate in the prevention of postmenopausal bone loss. Bone 2009, 44, 418–422.
DOI Google Scholar
29

Nakamura, T.; Nakano, T.; Ito, M.; Hagino, H.; Hashimoto, J.; Tobinai, M.; Mizunuma, H.; For the MOVER Study Group. Clinical efficacy on fracture risk and safety of 0.5 mg or 1 mg/month intravenous ibandronate versus 2.5 mg/day oral risedronate in patients with primary osteoporosis. Calcif. Tissue Int. 2013, 93, 137–146.
DOI Google Scholar
30

Greenspan, S. L.; Perera, S.; Ferchak, M. A.; Nace, D. A.; Resnick, N. M. Efficacy and safety of single-dose zoledronic acid for osteoporosis in frail elderly women: A randomized clinical trial. JAMA Intern. Med. 2015, 175, 913–921.
DOI Google Scholar
31

Nakamura, T.; Fukunaga, M.; Nakano, T.; Kishimoto, H.; Ito, M.; Hagino, H.; Sone, T.; Taguchi, A.; Tanaka, S.; Ohashi, M. et al. Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: Two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study). Osteoporos. Int. 2017, 28, 389–398.
DOI Google Scholar
32

Reid, I. R.; Horne, A. M.; Mihov, B.; Stewart, A.; Garratt, E.; Wong, S.; Wiessing, K. R.; Bolland, M. J.; Bastin, S.; Gamble, G. D. Fracture prevention with zoledronate in older women with osteopenia. N. Eng. J. Med. 2018, 379, 2407–2416.
DOI Google Scholar
33

Liu, Z.; Li, C. W.; Mao, Y. F.; Liu, K.; Liang, B. C.; Wu, L. G.; Shi, X. L. Study on zoledronic acid reducing acute bone loss and fracture rates in elderly postoperative patients with intertrochanteric fractures. Orthop. Surg. 2019, 11, 380–385.
DOI Google Scholar
34

Karabatsos, G.; Talbott, E.; Walker, S. G. A Bayesian nonparametric meta-analysis model. Res. Synth. Methods 2015, 6, 28–44.
DOI Google Scholar
35

Handl, J.; Knowles, J.; Kell, D. B. Computational cluster validation in post-genomic data analysis. Bioinformatics 2005, 21, 3201–3212.
DOI Google Scholar
36

Jung, Y.; Park, H.; Du, D. Z.; Drake, B. L. A decision criterion for the optimal number of clusters in hierarchical clustering. J. Glob. Optim. 2003, 25, 91–111.
DOI Google Scholar
37

Imaz, I.; Zegarra, P.; González-Enríquez, J.; Rubio, B.; Alcazar, R.; Amate, J. M. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: Systematic review and meta-analysis. Osteoporos. Int. 2010, 21, 1943–1951.
DOI Google Scholar
38

Nayak, S.; Greenspan, S. L. A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk. Osteoporos. Int. 2019, 30, 705–720.
DOI Google Scholar
39

Yeam, C. T.; Chia, S.; Tan, H. C. C.; Kwan, Y. H.; Fong, W.; Seng, J. J. B. A systematic review of factors affecting medication adherence among patients with osteoporosis. Osteoporos. Int. 2018, 29, 2623–2637.
DOI Google Scholar
40

Viswanathan, M.; Reddy, S.; Berkman, N.; Cullen, K.; Middleton, J. C.; Nicholson, W. K.; Kahwati, L. C. Screening to prevent osteoporotic fractures: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2018, 319, 2532–2551.
DOI Google Scholar
41

Lumley, T. Network meta-analysis for indirect treatment comparisons. Stat. Med. 2002, 21, 2313–2324.
DOI Google Scholar
42

Cipriani, A.; Higgins, J. P. T.; Geddes, J. R.; Salanti, G. Conceptual and technical challenges in network meta-analysis. Ann. Intern. Med. 2013, 159, 130–137.
DOI Google Scholar
43

Zhu, W. W.; Xu, R. Y.; Du, J. Y.; Fu, Y.; Li, S.; Zhang, P.; Liu, L. K.; Jiang, H. B. Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. FASEB J. 2019, 33, 5208–5219.
DOI Google Scholar
44

Bilezikian, J. P. Osteonecrosis of the jaw-do bisphosphonates pose a risk? N. Engl. J. Med. 2006, 355, 2278–2281.
DOI Google Scholar
45

Alsalleeh, F.; Keippel, J.; Adams, L.; Bavitz, B. Bisphosphonate- associated osteonecrosis of jaw reoccurrence after methotrexate therapy: A case report. J. Endod. 2014, 40, 1505–1507.
DOI Google Scholar
46

Ulmner, M.; Jarnbring, F.; Törring, O. Osteonecrosis of the jaw in Sweden associated with the oral use of bisphosphonate. J. Oral Maxillofac. Surg. 2014, 72, 76–82.
DOI Google Scholar
File
ntm-1-1-9130003_ESM.pdf (1.3 MB)
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 09 January 2021
Revised: 17 February 2022
Accepted: 18 February 2022
Published: 28 February 2022
Issue date: March 2022

Copyright

© The Author(s) 2022. Nano TransMed published by Tsinghua University Press.

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 51641305) and an open fund of Guangdong Provincial Key Laboratory of Stomatology.

Rights and permissions

The articles published in this open access journal are distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Return