{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T20:29:38Z","timestamp":1758054578576,"version":"3.44.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Patients with type 2 diabetes mellitus (T2DM) have decreased bone turnover levels. However, there are few studies comparing the anti-osteoporosis effects of anabolic drugs and anti-resorptive drugs in patients with T2DM. Thus, this study was designed to compare the changes in bone mineral density (BMD) and bone turnover levels in mice and postmenopausal osteoporotic patients, both with and without T2DM, following treatment with rhPTH(1-34) or alendronate (ALN).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the animal study, the mouse model of T2DM (DM mice) was established by high-fat diet (60% from fat) feeding and streptozotocin injection (100 mg\/kg) in C57BL\/6 mice. Both DM and control (CON) mice were then randomly assigned to receive either normal saline, rhPTH or ALN treatment. In the clinical study, a single-center, prospective, open-label, randomized controlled clinical trial was conducted. Postmenopausal patients with osteoporosis (OP) and postmenopausal patients with both osteoporosis and type 2 diabetes (DOP) were recruited and randomly assigned to receive either rhPTH(1-34) or ALN treatment for a period of one year. Changes in BMD and bone turnover levels were assessed in all groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to CON mice, DM mice exhibited decreased bone mass, impaired bone microstructure and, decreased levels of bone turnover markers, including procollagen type I intact N-terminal (P1NP) and C terminal cross-linking telopeptide of type I collagen (CTX). rhPTH(1-34) could reverse the low bone turnover observed in DM mice and had a better effect on improving BMD, bone volume per tissue volume (BV\/TV), trabecular number in femoral trabecular bone, as well as BMD, BV\/TV, and trabecular thickness in lumbar trabecular bone. In the clinical trial, at baseline, patients with DOP also exhibited decreased levels of bone turnover markers, including P1NP, CTX and osteocalcin. For patients with DOP, rhPTH(1-34) had a better effect than ALN on BMD improvement at the lumbar spine. Notably, the effect of ALN on lumbar spine improvement in patients with DOP was even smaller than that in patients with OP alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Initiating treatment with rhPTH(1-34) may provide greater clinical benefits to patients with diabetic bone disease characterized by low bone turnover levels.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1657481","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T05:29:12Z","timestamp":1757914152000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of rhPTH(1-34) and alendronate on the treatment of type 2 diabetic bone disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Huijuan","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingdan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peipei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongni","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiru","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingnan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lige","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-017-4183-0","article-title":"Risk of low-energy fracture in type 2 diabetes patients: a meta-analysis of observational studies","volume":"28","author":"Jia","year":"2017","journal-title":"Osteoporosis Int"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115457","article-title":"The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: A systematic review and meta-analysis update","volume":"137","author":"Vilaca","year":"2020","journal-title":"Bone"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1052592","article-title":"A narrative review of diabetic bone disease: Characteristics, pathogenesis, and treatment","volume":"13","author":"Wu","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1530\/eje-16-0652","article-title":"Mechanisms in endocrinology: Diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis","volume":"176","author":"Hygum","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s13098-024-01388-8","article-title":"Association between bone turnover markers, bone mineral density, and serum osteoglycine in middle-aged men with Type 2 Diabetes mellitus","volume":"16","author":"Mostafa","year":"2024","journal-title":"Diabetol Metab Syndrome"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14501","article-title":"Characteristics of bone metabolism in postmenopausal women with newly diagnosed type 2 diabetes mellitus","volume":"95","author":"Li","year":"2021","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2019.1618266","article-title":"An update on therapies for the treatment of diabetes-induced osteoporosis","volume":"19","author":"Mohsin","year":"2019","journal-title":"Expert Opin Biol Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01292","article-title":"Bisphosphonates, old friends of bones and new trends in clinics","volume":"64","author":"Barbosa","year":"2021","journal-title":"J Med Chem"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.7.1547","article-title":"Effect of alendronate on bone mineral density and biochemical markers of bone turnover in type 2 diabetic women: the fracture intervention trial","volume":"27","author":"Keegan","year":"2004","journal-title":"Diabetes Care"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-015-0071-9","article-title":"Efficacy and safety of risedronate in osteoporosis subjects with comorbid diabetes, hypertension, and\/or dyslipidemia: A post hoc analysis of phase III trials conducted in Japan","volume":"98","author":"Inoue","year":"2016","journal-title":"Calcified Tissue Int"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-010-9450-4","article-title":"Are antiresorptive drugs effective against fractures in patients with diabetes","volume":"88","author":"Vestergaard","year":"2011","journal-title":"Calcified Tissue Int"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/nejm200105103441904","article-title":"Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis","volume":"344","author":"Neer","year":"2001","journal-title":"New Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.06.017","article-title":"Teriparatide in patients with osteoporosis and type 2 diabetes","volume":"91","author":"Schwartz","year":"2016","journal-title":"Bone"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/s0026-0495(98)90027-0","article-title":"Nongenetic mouse models of non-insulin-dependent diabetes mellitus","volume":"47","author":"Luo","year":"1998","journal-title":"Metabol: Clin Experimen"},{"key":"B16","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s13098-021-00732-6","article-title":"Exercise improves bone formation by upregulating the Wnt3a\/\u03b2-catenin signalling pathway in type 2 diabetic mice","volume":"13","author":"Chen","year":"2021","journal-title":"Diabetol Metab Syndrome"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.116320","article-title":"Postnatal deletion of \u03b2-catenin in preosteoblasts regulates global energy metabolism through increasing bone resorption and adipose tissue fibrosis","volume":"156","author":"Song","year":"2022","journal-title":"Bone"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24929","article-title":"Bisphosphonate treatment of type I diabetic mice prevents early bone loss but accentuates suppression of bone formation","volume":"230","author":"Coe","year":"2015","journal-title":"J Cell Physiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3930","article-title":"Abaloparatide at the same dose has the same effects on bone as PTH (1-34) in mice","volume":"35","author":"Le Henaff","year":"2020","journal-title":"J Bone Mminer Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-017-0873-0","article-title":"Postnatal deletion of \u03b2-catenin in osterix-expressing cells is necessary for bone growth and intermittent PTH-induced bone gain","volume":"36","author":"Yu","year":"2017","journal-title":"J Bone Miner Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2015.07.017","article-title":"Teriparatide versus alendronate for the preservation of bone mineral density after total hip arthroplasty - A randomized controlled trial","volume":"31","author":"Kobayashi","year":"2016","journal-title":"J Arthroplasty"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.367","article-title":"Skeletal phenotype of the leptin receptor\u2013deficient db\/db mouse","volume":"26","author":"Williams","year":"2011","journal-title":"J Bone Mminer Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e22147","DOI":"10.1096\/fj.202101610R","article-title":"Activation of osteoblast ferroptosis via the METTL3\/ASK1-p38 signaling pathway in high glucose and high fat (HGHF)-induced diabetic bone loss","volume":"36","author":"Lin","year":"2022","journal-title":"FASEB J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41413-022-00198-w","article-title":"Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis","volume":"10","author":"Yang","year":"2022","journal-title":"Bone Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.3390\/nu16081220","article-title":"Diabetic rats induced using a high-fat diet and low-dose streptozotocin treatment exhibit gut microbiota dysbiosis and osteoporotic bone pathologies","volume":"16","author":"Huang","year":"2024","journal-title":"Nutrients"},{"key":"B26","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41413-024-00399-5","article-title":"Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus","volume":"13","author":"Xian","year":"2025","journal-title":"Bone Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-024-03926-w","article-title":"The paradox of bone mineral density and fracture risk in type 2 diabetes","volume":"85","author":"Li","year":"2024","journal-title":"Endocrine"},{"key":"B28","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1002\/jbmr.3240","article-title":"Diabetes and deficits in cortical bone density, microarchitecture, and bone size: framingham HR-pQCT study","volume":"33","author":"Samelson","year":"2018","journal-title":"J Bone Mminer Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae452","article-title":"Risk factors for bone microarchitecture impairments in older men with type 2 diabetes - the mrOS study","volume":"110","author":"Faraj","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-019-05053-z","article-title":"Association between trabecular bone score and type 2 diabetes: a quantitative update of evidence","volume":"30","author":"Ho-Pham","year":"2019","journal-title":"Osteoporosis Int"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab027","article-title":"Investigation of mechanical, material, and compositional determinants of human trabecular bone quality in type 2 diabetes","volume":"106","author":"Sihota","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B32","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.tem.2022.11.003","article-title":"Contributors to impaired bone health in type 2 diabetes","volume":"34","author":"Sheu","year":"2023","journal-title":"Trends Endocrinol Metabol: TEM"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155342","article-title":"Poliumoside protects against type 2 diabetes-related osteoporosis by suppressing ferroptosis via activation of the Nrf2\/GPX4 pathway","volume":"125","author":"Xu","year":"2024","journal-title":"Phytomedicine"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c05632","article-title":"A novel anti-osteoporosis mechanism of VK2: interfering with ferroptosis via AMPK\/SIRT1 pathway in type 2 diabetic osteoporosis","volume":"71","author":"Jin","year":"2023","journal-title":"J Agric Food Chem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2337\/db21-0573","article-title":"Exercise-linked skeletal irisin ameliorates diabetes-associated osteoporosis by inhibiting the oxidative damage-dependent miR-150-FNDC5\/pyroptosis axis","volume":"71","author":"Behera","year":"2022","journal-title":"Diabetes"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.116101","article-title":"Continuous subcutaneous insulin infusion ameliorates bone structures and mechanical properties in type 2 diabetic rats by regulating bone remodeling","volume":"153","author":"Shi","year":"2021","journal-title":"Bone"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00093.2019","article-title":"Anomalous bone changes in ovariectomized type 2 diabetic rats: inappropriately low bone turnover with bone loss in an estrogen-deficient condition","volume":"317","author":"Aeimlapa","year":"2019","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6191468","article-title":"Low bone turnover markers in young and middle-aged male patients with type 2 diabetes mellitus","volume":"2020","author":"Liu","year":"2020","journal-title":"J Diabetes Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4186","article-title":"Bone tissue composition in postmenopausal women varies with glycemic control from normal glucose tolerance to type 2 diabetes mellitus","volume":"36","author":"Hunt","year":"2021","journal-title":"J Bone Mminer Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1546","article-title":"Circulating osteogenic precursor cells in type 2 diabetes mellitus","volume":"97","author":"Manavalan","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.09.058","article-title":"High glucose prevents osteogenic differentiation of mesenchymal stem cells via lncRNA AK028326\/CXCL13 pathway","volume":"84","author":"Cao","year":"2016","journal-title":"Biomed Pharmacother"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.11.080","article-title":"High glucose inhibits proliferation and differentiation of osteoblast in alveolar bone by inducing pyroptosis","volume":"522","author":"Yang","year":"2020","journal-title":"Biochem Biophys Res Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2807","article-title":"High glucose inhibits receptor activator of nuclear factor\u2212\u03baB ligand-induced osteoclast differentiation via downregulation of v\u2212ATPase V0 subunit d2 and dendritic cell\u2212specific transmembrane protein","volume":"11","author":"Xu","year":"2015","journal-title":"Mol Med Rep"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2021.36.e239","article-title":"Effects of advanced glycation end products on differentiation and function of osteoblasts and osteoclasts","volume":"36","author":"Park","year":"2021","journal-title":"J Korean Med Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-016-0336-x","article-title":"Diabetes and bone marrow adiposity","volume":"14","author":"Kim","year":"2016","journal-title":"Curr Osteoporosis Rep"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2014.01.002","article-title":"FFAs-ROS-ERK\/P38 pathway plays a key role in adipocyte lipotoxicity on osteoblasts in co-culture","volume":"101","author":"Dong","year":"2014","journal-title":"Biochimie"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802805RR","article-title":"Activation of ROS\/MAPKs\/NF-\u03baB\/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis","volume":"33","author":"An","year":"2019","journal-title":"FASEB J"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1954","article-title":"Inhibition of osteoblastic bone formation by nuclear factor-kappaB","volume":"15","author":"Chang","year":"2009","journal-title":"Nat Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1210\/en.2019-00239","article-title":"Teriparatide improves bone and lipid metabolism in a male rat model of type 2 diabetes mellitus","volume":"160","author":"Nomura","year":"2019","journal-title":"Endocrinology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"481","DOI":"10.3390\/medicina58040481","article-title":"Effect of teriparatide on bone mineral density and trabecular bone score in type 2 diabetic patients with osteoporosis: A retrospective cohort study","volume":"58","author":"Munekawa","year":"2022","journal-title":"Med (Kaunas Lithuania)"},{"key":"B51","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.bone.2018.07.013","article-title":"Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporosis and comorbidities or risk factors for fractures: Integrated analysis of 4 prospective observational studies","volume":"116","author":"Langdahl","year":"2018","journal-title":"Bone"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/bf02877778","article-title":"Influence of type 2 diabetes mellitus on bone mineral density response to bisphosphonates in late postmenopausal osteoporosis","volume":"24","author":"Dagdelen","year":"2007","journal-title":"Adv Ther"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4389","article-title":"Anabolic actions of PTH in murine models: two decades of insights","volume":"36","author":"Zweifler","year":"2021","journal-title":"J Bone Mminer Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1657481\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T05:29:13Z","timestamp":1757914153000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1657481\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":53,"alternative-id":["10.3389\/fendo.2025.1657481"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1657481","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]},"article-number":"1657481"}}