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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.

*Read full-text study online at https://www.mdpi.com/2077-0383/10/14/3043/htm

Keywords: network meta-analysis; randomized controlled trial; osteoporosis; bone mineral density; risks of complications

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Supplementary Material

References

  1. Cheng, L.; Zhang, K.; Zhang, Z. Effectiveness of thiazides on serum and urinary calcium levels and bone mineral density in patients with osteoporosis: A systematic review and meta-analysis. Drug Des. Dev. Ther. 2018, 12, 3929–3935. [Google Scholar] [CrossRef]
  2. Cummings, S.R.; Melton, L.J. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002, 359, 1761–1767. [Google Scholar] [CrossRef]
  3. Vidal, M.; Thibodaux, R.J.; Neira, L.F.V.; Messina, O.D. Osteoporosis: A clinical and pharmacological update. Clin. Rheumatol. 2019, 38, 385–395. [Google Scholar] [CrossRef] [PubMed]
  4. Sattui, S.E.; Saag, K.G. Fracture mortality: Associations with epidemiology and osteoporosis treatment. Nat. Rev. Endocrinol. 2014, 10, 592–602. [Google Scholar] [CrossRef] [PubMed]
  5. Daruwalla, Z.J.; Huq, S.S.; Wong, K.L.; Nee, P.Y.; Leong, K.M.; Pillay, K.R.; Murphy, D.P. Hip fractures, preceding distal radius fractures and screening for osteoporosis: Should we be screening earlier? A minimum 10-year retrospective cohort study at a single centre. Osteoporos. Int. 2016, 27, 361–366. [Google Scholar] [CrossRef] [PubMed]
  6. Willson, T.; Nelson, S.D.; Newbold, J.; Nelson, R.E.; LaFleur, J. The clinical epidemiology of male osteoporosis: A review of the recent literature. Clin. Epidemiol. 2015, 7, 65–76. [Google Scholar]
  7. Silverman, S.L.; Kupperman, E.S.; Bukata, S.V. Fracture healing: A consensus report from the International Osteoporosis Foundation Fracture Working Group. Osteoporos. Int. 2016, 27, 2197–2206. [Google Scholar] [CrossRef]
  8. Unni, S.; Yao, Y.; Milne, N.; Gunning, K.; Curtis, J.R.; LaFleur, J. An evaluation of clinical risk factors for estimating fracture risk in postmenopausal osteoporosis using an electronic medical record database. Osteoporos. Int. 2015, 26, 581–587. [Google Scholar] [CrossRef]
  9. Anagnostis, P.; Siolos, P.; Gkekas, N.K.; Kosmidou, N.; Artzouchaltzi, A.M.; Christou, K.; Goulis, D.G. Association between age at menopause and fracture risk: A systematic review and meta-analysis. Endocrine 2019, 63, 213–224. [Google Scholar] [CrossRef]
  10. Zhu, H.; Jiang, J.; Wang, Q.; Zong, J.; Zhang, L.; Ma, T.; Zhang, L. Associations between ERalpha/beta gene polymorphisms and osteoporosis susceptibility and bone mineral density in postmenopausal women: A systematic review and meta-analysis. BMC Endocr. Disord. 2018, 18, 11. [Google Scholar] [CrossRef]
  11. Jimenez-Mola, S.; Calvo-Lobo, C.; Idoate-Gil, J.; Seco-Calvo, J. Functionality, comorbidity, complication surgery of hip fracture in older adults by age distribution. Rev. Assoc. Med. Bras. 2018, 64, 420–427. [Google Scholar] [CrossRef]
  12. Briot, K. Fracture Liaison Services. Curr. Opin. Rheumatol. 2017, 29, 416–421. [Google Scholar] [CrossRef] [PubMed]
  13. Mugnier, B.; Daumas, A.; Couderc, A.L.; Mizzi, B.; Gonzalez, T.; Amrani, A.; Villani, P. Clinical effectiveness of osteoporosis treatment in older patients: A fracture liaison service-based prospective study. J. Women Aging 2019, 31, 553–565. [Google Scholar] [CrossRef] [PubMed]
  14. Brozek, W.; Reichardt, B.; Zwerina, J.; Dimai, H.P.; Klaushofer, K.; Zwettler, E. Antiresorptive therapy and risk of mortality and refracture in osteoporosis-related hip fracture: A nationwide study. Osteoporos. Int. 2016, 27, 387–396. [Google Scholar] [CrossRef]
  15. Davidson, E.; Seal, A.; Doyle, Z.; Fielding, K.; McGirr, J. Prevention of osteoporotic refractures in regional Australia. Aust. J. Rural Health 2017, 25, 362–368. [Google Scholar] [CrossRef]
  16. Lyu, H.; Jundi, B.; Xu, C.; Tedeschi, S.K.; Yoshida, K.; Zhao, S.; Solomon, D.H. Comparison of Denosumab and Bisphosphonates in Patients With Osteoporosis: A Meta-Analysis of Randomized Controlled Trials. J. Clin. Endocrinol. Metab. 2019, 104, 1753–1765. [Google Scholar] [CrossRef] [PubMed]
  17. Pispati, A.; Pandey, V.; Patel, R. Oral Bisphosphonate Induced Recurrent Osteonecrosis of Jaw with Atypical Femoral Fracture and Subsequent Mandible Fracture in the Same Patient: A Case Report. J. Orthop. Case Rep. 2018, 8, 85–88. [Google Scholar]
  18. Black, D.M.; Abrahamsen, B.; Bouxsein, M.L.; Einhorn, T.; Napoli, N. Atypical Femur Fractures—Review of epidemiology, relationship to bisphosphonates, prevention and clinical management. Endocr. Rev. 2019, 40, 333–368. [Google Scholar] [CrossRef]
  19. Knopp-Sihota, J.A.; Cummings, G.G.; Homik, J.; Voaklander, D. The association between serious upper gastrointestinal bleeding and incident bisphosphonate use: A population-based nested cohort study. BMC Geriatr. 2013, 13, 36. [Google Scholar] [CrossRef] [PubMed]
  20. Palacios, S.; Silverman, S.L.; de Villiers, T.J.; Levine, A.B.; Goemaere, S.; Brown, J.P.; Chines, A.A. A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: Effects on bone density and fracture. Menopause 2015, 22, 806–813. [Google Scholar] [CrossRef]
  21. Weaver, C.M.; Alexander, D.D.; Boushey, C.J.; Dawson-Hughes, B.; Lappe, J.M.; LeBoff, M.S.; Wang, D.D. Calcium plus vitamin D supplementation and risk of fractures: An updated meta-analysis from the National Osteoporosis Foundation. Osteoporos. Int. 2016, 27, 367–376. [Google Scholar] [CrossRef]
  22. Peng, L.; Luo, Q.; Lu, H. Efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: A systematic review and meta-analysis. Medicine 2017, 96, e8659. [Google Scholar] [CrossRef] [PubMed]
  23. Wang, G.; Sui, L.; Gai, P.; Li, G.; Qi, X.; Jiang, X. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Jt. Res. 2017, 6, 452–463. [Google Scholar] [CrossRef] [PubMed]
  24. Tan, X.; Wen, F.; Yang, W.; Xie, J.Y.; Ding, L.L.; Mo, Y.X. Comparative efficacy and safety of pharmacological interventions for osteoporosis in postmenopausal women: A network meta-analysis (Chongqing, China). Menopause 2019, 26, 929–939. [Google Scholar] [CrossRef] [PubMed]
  25. Liu, G.F.; Wang, Z.Q.; Liu, L.; Zhang, B.T.; Miao, Y.Y.; Yu, S.N. A network meta-analysis on the short-term efficacy and adverse events of different anti-osteoporosis drugs for the treatment of postmenopausal osteoporosis. J. Cell Biochem. 2018, 119, 4469–4481. [Google Scholar] [CrossRef] [PubMed]
  26. Yang, L.; Kang, N.; Yang, J.C.; Su, Q.J.; Liu, Y.Z.; Guan, L.; Hai, Y. Drug efficacies on bone mineral density and fracture rate for the treatment of postmenopausal osteoporosis: A network meta-analysis. Eur. Rev. Med. Pharm. Sci. 2019, 23, 2640–2668. [Google Scholar]
  27. Yang, X.C.; Deng, Z.H.; Wen, T.; Luo, W.; Xiao, W.F.; Zhao, R.B.; Li, Y.S. Network Meta-Analysis of Pharmacological Agents for Osteoporosis Treatment and Fracture Prevention. Cell Physiol. Biochem. 2016, 40, 781–795. [Google Scholar] [CrossRef]
  28. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. BMJ 2009, 339, b2535. [Google Scholar] [CrossRef]
  29. Allon, R.; Levy, Y.; Lavi, I.; Kramer, A.; Barzilai, M.; Wollstein, R. How to Best Predict Fragility Fractures: An Update and Systematic Review. Isr. Med Assoc. J. IMAJ 2018, 20, 773–779. [Google Scholar]
  30. Gao, Y.N.; Wu, Y.C.; Lin, S.Y.; Chang, J.Z.; Tu, Y.K. Short-term efficacy of minimally invasive treatments for adult obstructive sleep apnea: A systematic review and network meta-analysis of randomized controlled trials. J. Med. Assoc. 2019, 118, 750–765. [Google Scholar] [CrossRef]
  31. Kendler, D.L.; Marin, F.; Zerbini, C.A.F.; Russo, L.A.; Greenspan, S.L.; Zikan, V.; Lopez-Romero, P. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): A multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 2018, 391, 230–240. [Google Scholar] [CrossRef]
  32. Saag, K.G.; Petersen, J.; Brandi, M.L.; Karaplis, A.C.; Lorentzon, M.; Thomas, T.; Grauer, A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N. Engl. J. Med. 2017, 377, 1417–1427. [Google Scholar] [CrossRef]
  33. Cummings, S.R.; San Martin, J.; McClung, M.R.; Siris, E.S.; Eastell, R.; Reid, I.R.; Trial, F. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med. 2009, 361, 756–765. [Google Scholar] [CrossRef]
  34. Cosman, F.; Crittenden, D.B.; Adachi, J.D.; Binkley, N.; Czerwinski, E.; Ferrari, S.; Grauer, A. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N. Engl. J. Med. 2016, 375, 1532–1543. [Google Scholar] [CrossRef]
  35. Watts, N.B.; Grbic, J.T.; Binkley, N.; Papapoulos, S.; Butler, P.W.; Yin, X.; McClung, M. Invasive Oral Procedures and Events in Postmenopausal Women With Osteoporosis Treated With Denosumab for Up to 10 Years. J. Clin. Endocrinol. Metab. 2019, 104, 2443–2452. [Google Scholar] [CrossRef]
  36. Wu, J.; Zhang, Q.; Yan, G.; Jin, X. Denosumab compared to bisphosphonates to treat postmenopausal osteoporosis: A meta-analysis. J. Orthop. Surg. Res. 2018, 13, 194. [Google Scholar] [CrossRef]
  37. Sanderson, J.; Martyn-St James, M.; Stevens, J.; Goka, E.; Wong, R.; Campbell, F.; Davis, S. Clinical effectiveness of bisphosphonates for the prevention of fragility fractures: A systematic review and network meta-analysis. Bone 2016, 89, 52–58. [Google Scholar] [CrossRef]
  38. Marjoribanks, J.; Farquhar, C.; Roberts, H.; Lethaby, A.; Lee, J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst. Rev. 2017, 1, CD004143. [Google Scholar] [CrossRef]
  39. Haguenauer, D.; Welch, V.; Shea, B.; Tugwell, P.; Wells, G. Fluoride for treating postmenopausal osteoporosis. Cochrane Database Syst. Rev. 2000, CD002825. [Google Scholar] [CrossRef]
  40. Gupta, M.; Gupta, N. Bisphosphonate Related Jaw Osteonecrosis. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2018. [Google Scholar]
  41. Kilic, E.; Doganay, O. Current management concepts for bisphosphonate-related osteonecrosis of the jaw: A review. Gen. Dent. 2018, 66, e1–e5. [Google Scholar]
  42. Nicolatou-Galitis, O.; Schiødt, M.; Mendes, R.A.; Ripamonti, C.; Hope, S.; Drudge-Coates, L.; Van den Wyngaert, T. Medication-related osteonecrosis of the jaw: Definition and best practice for prevention, diagnosis, and treatment. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2019, 127, 117–135. [Google Scholar] [CrossRef]
  43. Gallacher, S.J.; Dixon, T. Impact of treatments for postmenopausal osteoporosis (bisphosphonates, parathyroid hormone, strontium ranelate, and denosumab) on bone quality: A systematic review. Calcif. Tissue Int. 2010, 87, 469–484. [Google Scholar] [CrossRef]
  44. Finkelstein, J.S.; Wyland, J.J.; Lee, H.; Neer, R.M. Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis. J. Clin. Endocrinol. Metab. 2010, 95, 1838–1845. [Google Scholar] [CrossRef]
  45. Lou, S.; Lv, H.; Li, Z.; Zhang, L.; Tang, P. Combination therapy of anabolic agents and bisphosphonates on bone mineral density in patients with osteoporosis: A meta-analysis of randomised controlled trials. BMJ Open 2018, 8, e015187. [Google Scholar] [CrossRef]
  46. Lou, S.; Wang, L.; Wang, Y.; Jiang, Y.; Liu, J.; Wang, Y. Combination therapy of anabolic and nonbisphosphonates antiresorptive agents for the treatment of osteoporosis: A meta-analysis. Medicine 2017, 96, e9534. [Google Scholar] [CrossRef]
  47. Lou, S.; Lv, H.; Yin, P.; Li, Z.; Tang, P.; Wang, Y. Combination therapy with parathyroid hormone analogs and antiresorptive agents for osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Osteoporos. Int. 2019, 30, 59–70. [Google Scholar] [CrossRef]
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