Osteoporosis International

, Volume 30, Issue 1, pp 59–70 | Cite as

Combination therapy with parathyroid hormone analogs and antiresorptive agents for osteoporosis: a systematic review and meta-analysis of randomized controlled trials

  • S. Lou
  • H. Lv
  • P. Yin
  • Z. Li
  • P. TangEmail author
  • Y. WangEmail author
Review Article


Combination therapy with parathyroid hormone (PTH) analogs and antiresorptive agents may be more effective than monotherapy for the treatment of osteoporosis. This study aimed to estimate the effectiveness and safety of this combination therapy for osteoporosis. MEDLINE, EMBASE, and Cochrane Library were searched from inception to May 1, 2018, including randomized controlled trials (RCTs) with a duration of at least 6 months on adults with osteoporosis treated with combination therapy versus monotherapy. Outcomes included fractures, bone mineral density (BMD) changes, and adverse events. A meta-analysis was performed using a random-effect model, to estimate risk ratios (RRs) for fractures, and mean differences (MDs) for BMD changes. A total of 19 RCTs and 2177 patients were included. Compared with monotherapy, combination therapy had an advantage of 36% (RR, 0.64; 95% confidence interval (CI), 0.42–0.98) regarding fracture risk reduction. It also appears to improve lumbar spine BMD by 4.06% (95%CI = 2.60–5.53) and total hip BMD by 1.89% (95%CI = 1.25–2.53). No RCT reported an increased risk of serious adverse events. Among patients with osteoporosis, combination therapy was superior to monotherapy regarding improvement of the lumbar spine and total hip BMD, without risk of serious adverse events. Combination therapy also had an advantage over monotherapy on fracture risk reduction. However, owing to the limited sample size, additional larger studies are required to confirm this benefit.


Anabolic Antiresorptive Bisphosphonates Bone mineral density Combination therapy Denosumab Osteoporosis Teriparatide 


Compliance with ethical standards

Conflicts of interest


Ethics approval and consent to participate

Not applicable.

Supplementary material

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Figure S1

Funnel plots for fracture events. (PNG 84 kb)

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High resolution image (TIF 942 kb)
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Figure S2

Funnel plots for the lumbar spine BMD changes. (PNG 67 kb)

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High resolution image (TIF 893 kb)
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Figure S3

Sensitivity analysis for the lumbar spine BMD changes. (PNG 247 kb)

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High resolution image (TIF 2064 kb)
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Figure S4

Meta-regression for the lumbar spine BMD changes. (PNG 110 kb)

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High resolution image (TIF 986 kb)
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Figure S5

Funnel plots for the total hip BMD changes. (PNG 66 kb)

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High resolution image (TIF 769 kb)
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Figure S6

Sensitivity analysis for the total hip BMD changes. (PNG 246 kb)

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High resolution image (TIF 2128 kb)
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Figure S7

Meta-regression for the total hip BMD changes (PNG 93 kb)

198_2018_4790_MOESM7_ESM.tif (836 kb)
High resolution image (TIF 836 kb)
198_2018_4790_MOESM8_ESM.docx (15 kb)
File S1 The full search strategies used in MEDLINE, EMBASE and the Cochrane Library. (DOCX 14 kb)
198_2018_4790_MOESM9_ESM.docx (17 kb)
ESM 9 (DOCX 17 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Department of Spine SurgeryThe First Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Department of OrthopedicsChinese PLA General HospitalBeijingPeople’s Republic of China

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