{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:35:01Z","timestamp":1789047301240,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Abaloparatide is an osteoanabolic therapy used in patients at high risk of fracture; however, the breadth of evidence across routes, comparators, and sequential strategies has not yet been comprehensively summarized. This study aimed to evaluate the efficacy and safety of abaloparatide for reducing fractures and improving bone mineral density (BMD) in adults with osteoporosis. Methods: Following PRISMA 2020, we searched PubMed, Embase, CENTRAL, and Web of Science (2016\u20132024) for randomized controlled trials and comparative real-world studies. Additional meta-analyses and network meta-analyses were included as contextual evidence but not pooled to avoid double-counting. Primary outcomes were vertebral, non-vertebral, and hip fractures; secondary outcomes included percentage change in BMD and safety endpoints. Random-effects models were used; heterogeneity, influence analyses, and prediction intervals were examined. Risk of bias was assessed using RoB 2 and AMSTAR 2. Results: Nine quantitative evidence sources met the criteria. Abaloparatide reduced vertebral fractures (RR 0.13\u20130.21) and showed moderate reductions in non-vertebral fractures. Lumbar spine BMD increased substantially, while hip and femoral neck gains were smaller and heterogeneous. Hypercalcemia risk was consistently lower compared to teriparatide. Transdermal delivery was less effective, and sequential abaloparatide \u2192 antiresorptive therapy further reduced fractures. Serious adverse events were not increased. Conclusions: Abaloparatide provides strong vertebral protection, significant BMD improvement, and shows a favorable calcemic profile, with moderate certainty for non-vertebral effects. Evidence in men and long-term safety remains limited.<\/jats:p>","DOI":"10.3390\/jcm15020673","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:12:04Z","timestamp":1768403524000},"page":"673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Efficacy and Safety of Abaloparatide in Osteoporosis: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Marco","family":"Bonifacio","sequence":"first","affiliation":[{"name":"Private Practitioner, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4894-9456","authenticated-orcid":false,"given":"Marco","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Spinal Unit, CTO Hospital, ASL Roma 2, 00145 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Lucchetti","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy Unit, ASL Roma 4, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Giuseppe","family":"Musorrofiti","sequence":"additional","affiliation":[{"name":"Department of Ergonomics, University eCampus, 22060 Novedrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"La Cava","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery, San Paolo Hospital of Civitavecchia, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Chiappetta","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitation Medicine, ASL Rieti, 02100 Rieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Fiorino","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-0314","authenticated-orcid":false,"given":"Alberto","family":"Lo Gullo","sequence":"additional","affiliation":[{"name":"UOSD Rheumatology, Papardo Hospital of Messina, 98158 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Conforti","sequence":"additional","affiliation":[{"name":"Local Health Rheumatology Unit, San Paolo Hospital of Civitavecchia, ASL Roma 4, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shen, Y., Huang, X., Wu, J., Lin, X., Zhou, X., Zhu, Z., Pan, X., Xu, J., Qiao, J., and Zhang, T. (2022). The global burden of osteoporosis, low bone mass, and its related fracture in 204 countries and territories, 1990\u20132019. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.882241"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/13697137.2021.1951206","article-title":"Osteoporosis and fractures in women: The burden of disease","volume":"25","author":"Lorentzon","year":"2022","journal-title":"Climacteric"},{"key":"ref_3","unstructured":"Porter, J.L., and Varacallo, M.A. (2025, October 01). Osteoporosis. StatPearls\u2014NCBI Bookshelf, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK441901\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1177\/2151458513502039","article-title":"Patients\u2019 response toward an automated orthopedic osteoporosis intervention program","volume":"4","author":"Varacallo","year":"2013","journal-title":"Geriatr. Orthop. Surg. Rehabil."},{"key":"ref_5","unstructured":"Varacallo, M., Seaman, T.J., Jandu, J.S., and Pizzutillo, P. (2023). Osteopenia. StatPearls, StatPearls Publishing."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1007\/s00198-021-05900-y","article-title":"The clinician\u2019s guide to prevention and treatment of osteoporosis","volume":"33","author":"LeBoff","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4158\/GL-2020-0524SUPPL","article-title":"American association of clinical endocrinologists\/american college of endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update","volume":"26","author":"Camacho","year":"2020","journal-title":"Endocr. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/s41584-024-01094-9","article-title":"Evidence-Based Guideline for the management of osteoporosis in men","volume":"20","author":"Fuggle","year":"2024","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.mcna.2014.03.007","article-title":"Osteoporosis and its complications","volume":"98","author":"Varacallo","year":"2014","journal-title":"Med. Clin. N. Am."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cheng, C.H., Chen, L.R., and Chen, K.H. (2022). Osteoporosis due to hormone imbalance: An overview of the effects of estrogen deficiency and glucocorticoid overuse on bone turnover. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031376"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s11914-024-00892-0","article-title":"Nutrition and Osteoporosis Prevention","volume":"22","author":"Rizzoli","year":"2024","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"182","DOI":"10.7326\/M22-0684","article-title":"Effectiveness and Safety of Treatments to Prevent Fractures in People with Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians","volume":"176","author":"Ayers","year":"2023","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115516","DOI":"10.1016\/j.bone.2020.115516","article-title":"Treatment of postmenopausal osteoporosis with bone-forming and antiresorptive treatments: Combined and sequential approaches","volume":"139","author":"Langdahl","year":"2020","journal-title":"Bone"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"777","DOI":"10.4158\/EP-2019-0596","article-title":"Anabolic therapy and optimal treatment sequences for patients with osteoporosis at high risk for fracture","volume":"26","author":"Cosman","year":"2020","journal-title":"Endocr. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00774-024-01536-0","article-title":"Clinical effects of teriparatide, abaloparatide, and romosozumab in postmenopausal osteoporosis","volume":"43","author":"Ebina","year":"2025","journal-title":"J. Bone Miner. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kondapalli, A.V., and Walker, M.D. (2021). Postoperative Bone Mineral Health Optimization in the Geriatric Patient. Geriatric Hip Fractures: A Practical Approach, Springer International Publishing.","DOI":"10.1007\/978-3-030-78969-5_11"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1097\/GME.0000000000001321","article-title":"Comparative efficacy and safety of pharmacological interventions for osteoporosis in postmenopausal women: A network meta-analysis (Chongqing, China)","volume":"26","author":"Tan","year":"2019","journal-title":"Menopause"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1111\/imj.70061","article-title":"First-line treatment of osteoporosis with osteoanabolic therapy: A new opportunity","volume":"55","author":"Aleksova","year":"2025","journal-title":"Intern. Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Acanfora, M., Vassallo, A., Valsecchi, F., and Bolamperti, F.M. (2025). Denosumab Discontinuation: The Abaloparatide plus Bisphosphonate Metronomic Sequential Approach. Authorea Preprints.","DOI":"10.22541\/au.175683892.26048418\/v1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s40261-021-01008-7","article-title":"Phase 1b evaluation of abaloparatide solid microstructured transdermal system (Abaloparatide-sMTS) in postmenopausal women with low bone mineral density","volume":"41","author":"Miller","year":"2021","journal-title":"Clin. Drug Investig."},{"key":"ref_21","unstructured":"Li, N. (2023). Osteoporosis, (Bone) Fractures and Fracture Liaison Services: Health-Related Quality of Life, Clinical and Economic Outcomes. [Ph.D. Thesis, Maastricht University]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41574-020-00426-5","article-title":"Emerging insights into the comparative effectiveness of anabolic therapies for osteoporosis","volume":"17","author":"Estell","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1080\/03007995.2020.1824897","article-title":"Abaloparatide: An anabolic treatment to reduce fracture risk in postmenopausal women with osteoporosis","volume":"36","author":"Miller","year":"2020","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Oladapo, O.P. (2020). Investigating Analogues of Parathyroid Hormone (PTH) and PTH-Related Peptide (PTHrP) Using UMR106-01 Osteocytic Cells to Determine Anabolic and Catabolic Response Ratios and Predict In Vivo Responses, University of Toronto.","DOI":"10.1210\/jendso\/bvaa046.639"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1210\/endrev\/bnab005","article-title":"Physiological and pharmacological roles of PTH and PTHrP in bone using their shared receptor, PTH1R","volume":"42","author":"Martin","year":"2021","journal-title":"Endocr. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Martin, T.J. (2022). PTH1R actions on bone using the cAMP\/protein kinase a pathway. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.833221"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.clinthera.2023.12.010","article-title":"The Safety and Efficacy of abaloparatide on postmenopausal osteoporosis: A systematic review and meta-analysis","volume":"46","author":"Xu","year":"2024","journal-title":"Clin. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, L., Ji, B., and Xia, C. (2025). Efficacy and safety of abaloparatide, denosumab, teriparatide, oral bisphosphonates, and intravenous bisphosphonates in the treatment of male osteoporosis: A systematic review and Bayesian network meta-analysis. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1558560"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e11880","DOI":"10.1016\/j.heliyon.2022.e11880","article-title":"Efficacy and safety of pharmacologic therapies for prevention of osteoporotic vertebral fractures in postmenopausal women","volume":"9","author":"Wei","year":"2022","journal-title":"Heliyon"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13018-023-03595-x","article-title":"Is abaloparatide more efficacious on increasing bone mineral density than teriparatide for women with postmenopausal osteoporosis? An updated meta-analysis","volume":"18","author":"Hong","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00198-025-07440-1","article-title":"PTH1 receptor agonists for fracture risk: A systematic review and network meta-analysis","volume":"36","author":"Beaudart","year":"2025","journal-title":"Osteoporos. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s40520-023-02478-9","article-title":"Efficacy of osteoporosis pharmacological treatments in men: A systematic review and meta-analysis","volume":"35","author":"Beaudart","year":"2023","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s13018-025-05545-1","article-title":"Efficacy and safety of sequential therapy for primary osteoporosis with bone formation promoters followed by bone resorption inhibitors: A meta-analysis","volume":"20","author":"Liu","year":"2025","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1001\/jama.2016.11136","article-title":"Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women with Osteoporosis","volume":"316","author":"Miller","year":"2016","journal-title":"JAMA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/jbmr.4877","article-title":"Efficacy and Safety of Transdermal Abaloparatide in Postmenopausal Women with Osteoporosis: A Randomized Study","volume":"38","author":"Lewiecki","year":"2023","journal-title":"J. Bone Miner. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/673\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:24:40Z","timestamp":1768404280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["jcm15020673"],"URL":"https:\/\/doi.org\/10.3390\/jcm15020673","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]}}}