Comparative efficacy of teriparatide and bisphosphonates or denosumab vs. teriparatide monotherapy in osteoporosis: a meta-analysis

IntroductionTeriparatide (TPTD), a widely used bone-promoting drug in osteoporosis (OP) treatment, may cause compensatory bone resorption with long-term monotherapy (>6 months). Combining TPTD with anti-bone resorption drugs (e.g., bisphosphonates and denosumab) could reduce bone loss, yet ex...

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Main Authors: Huan Jin, Cai Huang, Yan Zhang, Ying Dong, Qi Xiong, Di Wang, Ziyi He, Lin Shen, Chen Ma, Zixian Wang, Bo Shuai
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1605279/full
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author Huan Jin
Huan Jin
Cai Huang
Yan Zhang
Ying Dong
Qi Xiong
Di Wang
Di Wang
Ziyi He
Ziyi He
Lin Shen
Chen Ma
Zixian Wang
Bo Shuai
author_facet Huan Jin
Huan Jin
Cai Huang
Yan Zhang
Ying Dong
Qi Xiong
Di Wang
Di Wang
Ziyi He
Ziyi He
Lin Shen
Chen Ma
Zixian Wang
Bo Shuai
author_sort Huan Jin
collection DOAJ
description IntroductionTeriparatide (TPTD), a widely used bone-promoting drug in osteoporosis (OP) treatment, may cause compensatory bone resorption with long-term monotherapy (>6 months). Combining TPTD with anti-bone resorption drugs (e.g., bisphosphonates and denosumab) could reduce bone loss, yet existing randomised controlled trials (RCTs) remain inconclusive regarding their effects on bone mineral density (BMD) and bone turnover markers (BTMs). This study aimed to systematically evaluate the effect of TPTD combined with bisphosphonates or denosumab on BMD and fracture risk in OP patients, compared with TPTD monotherapy.MethodsPubMed, Embase, Cochrane Library, and Web of Science databases (until March 2025) were searched for RCTs comparing TPTD monotherapy with combination therapy. Primary outcomes included vertebral/non-vertebral fracture risk reduction and BMD changes (lumbar spine, femoral neck, hip); secondary outcomes covered BTM variations and adverse events.ResultsEight RCTs (n = 787) were meta-analysed using Review Manager 5.4. Results showed: ① No significant differences in vertebral (OR = 0.93, 95%CI 0.12–6.93) or non-vertebral fractures (OR = 0.68, 0.31–1.46) between groups. ② TPTD combined with denosumab significantly increased lumbar spine (+3.40%, 0.44–6.36), femoral neck (+4.00%, 1.96–6.04), and hip BMD (+4.25%, 3.20–5.29). Bisphosphonate combinations improved hip BMD in the short term (<24 months: +1.81%, 0.65–2.97) but not long-term (≥24 months).③ Combination therapies regulated BTMs bidirectionally: bisphosphonates suppressed P1NP (40%–80% reduction vs. monotherapy), while denosumab preserved OC levels (-8–16% vs. monotherapy).④ Safety profiles were comparable: hypercalcemia incidence (16.3% vs. 14.7%, OR = 1.22, 0.55–2.69), musculoskeletal pain (9.8% overall), with no osteonecrosis cases reported.ConclusionTPTD-denosumab combination is clinically preferable for BMD enhancement, though its long-term (>24 months) fracture risk reduction requires further validation.
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spelling doaj-art-c8d53ef684dd4064aeca2b5605d15c652025-08-20T02:33:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.16052791605279Comparative efficacy of teriparatide and bisphosphonates or denosumab vs. teriparatide monotherapy in osteoporosis: a meta-analysisHuan Jin0Huan Jin1Cai Huang2Yan Zhang3Ying Dong4Qi Xiong5Di Wang6Di Wang7Ziyi He8Ziyi He9Lin Shen10Chen Ma11Zixian Wang12Bo Shuai13Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCollege of Sports Medicine, Wuhan Sports University, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pain, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of internal medicine, Rongjun Hostipal of Hubei, Wuhan, ChinaDepartment of internal medicine, Rongjun Hostipal of Hubei, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCollege of Sports Medicine, Wuhan Sports University, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCollege of Sports Medicine, Wuhan Sports University, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaIntroductionTeriparatide (TPTD), a widely used bone-promoting drug in osteoporosis (OP) treatment, may cause compensatory bone resorption with long-term monotherapy (>6 months). Combining TPTD with anti-bone resorption drugs (e.g., bisphosphonates and denosumab) could reduce bone loss, yet existing randomised controlled trials (RCTs) remain inconclusive regarding their effects on bone mineral density (BMD) and bone turnover markers (BTMs). This study aimed to systematically evaluate the effect of TPTD combined with bisphosphonates or denosumab on BMD and fracture risk in OP patients, compared with TPTD monotherapy.MethodsPubMed, Embase, Cochrane Library, and Web of Science databases (until March 2025) were searched for RCTs comparing TPTD monotherapy with combination therapy. Primary outcomes included vertebral/non-vertebral fracture risk reduction and BMD changes (lumbar spine, femoral neck, hip); secondary outcomes covered BTM variations and adverse events.ResultsEight RCTs (n = 787) were meta-analysed using Review Manager 5.4. Results showed: ① No significant differences in vertebral (OR = 0.93, 95%CI 0.12–6.93) or non-vertebral fractures (OR = 0.68, 0.31–1.46) between groups. ② TPTD combined with denosumab significantly increased lumbar spine (+3.40%, 0.44–6.36), femoral neck (+4.00%, 1.96–6.04), and hip BMD (+4.25%, 3.20–5.29). Bisphosphonate combinations improved hip BMD in the short term (<24 months: +1.81%, 0.65–2.97) but not long-term (≥24 months).③ Combination therapies regulated BTMs bidirectionally: bisphosphonates suppressed P1NP (40%–80% reduction vs. monotherapy), while denosumab preserved OC levels (-8–16% vs. monotherapy).④ Safety profiles were comparable: hypercalcemia incidence (16.3% vs. 14.7%, OR = 1.22, 0.55–2.69), musculoskeletal pain (9.8% overall), with no osteonecrosis cases reported.ConclusionTPTD-denosumab combination is clinically preferable for BMD enhancement, though its long-term (>24 months) fracture risk reduction requires further validation.https://www.frontiersin.org/articles/10.3389/fphar.2025.1605279/fullosteoporosisteriparatide monotherapybisphosphonatesdenosumabvertebral fracturesbone mineral density
spellingShingle Huan Jin
Huan Jin
Cai Huang
Yan Zhang
Ying Dong
Qi Xiong
Di Wang
Di Wang
Ziyi He
Ziyi He
Lin Shen
Chen Ma
Zixian Wang
Bo Shuai
Comparative efficacy of teriparatide and bisphosphonates or denosumab vs. teriparatide monotherapy in osteoporosis: a meta-analysis
Frontiers in Pharmacology
osteoporosis
teriparatide monotherapy
bisphosphonates
denosumab
vertebral fractures
bone mineral density
title Comparative efficacy of teriparatide and bisphosphonates or denosumab vs. teriparatide monotherapy in osteoporosis: a meta-analysis
title_full Comparative efficacy of teriparatide and bisphosphonates or denosumab vs. teriparatide monotherapy in osteoporosis: a meta-analysis
title_fullStr Comparative efficacy of teriparatide and bisphosphonates or denosumab vs. teriparatide monotherapy in osteoporosis: a meta-analysis
title_full_unstemmed Comparative efficacy of teriparatide and bisphosphonates or denosumab vs. teriparatide monotherapy in osteoporosis: a meta-analysis
title_short Comparative efficacy of teriparatide and bisphosphonates or denosumab vs. teriparatide monotherapy in osteoporosis: a meta-analysis
title_sort comparative efficacy of teriparatide and bisphosphonates or denosumab vs teriparatide monotherapy in osteoporosis a meta analysis
topic osteoporosis
teriparatide monotherapy
bisphosphonates
denosumab
vertebral fractures
bone mineral density
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1605279/full
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