{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:02:58Z","timestamp":1782892978696,"version":"3.54.5"},"reference-count":90,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR081804"],"award-info":[{"award-number":["R01AR081804"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Many developmental and metabolic effects of growth hormone (GH) on vertebrate life history traits have been widely studied in biological and biomedical contexts. The scope of alterations in GH\/GH receptor (GHR) interactions has generally focused on molecular, cellular, histological, and physiological framing, leaving a gap in understanding of how the cumulative organism\u2010 and lifespan\u2010scale manifestations of morphological changes attributable to GH\/GHR perturbations may both be influenced by and also influence smaller\u2010scale study results. The pilot study conducted herein used micro\u2010computed tomography (\u03bcCT) to survey and characterize the axial and appendicular skeletons of adult male and female bGH (transgenic overexpression of bovine GH) mice and to compare them with those of age\u2010 and sex\u2010matched wild\u2010type (WT) controls. Male and female bGH mice in our sample were larger (by linear measurements of skeletal elements) and leaner but not heavier than their WT counterparts. bGH mice exhibit thoracic kyphosis and radiographically detectable incipient sacralization of the last lumbar vertebra, as well as robust and altered muscle attachment sites in both girdle and long bones, re\u2010orientation of the acetabulum, and dysmorphology of the femur at both hip and knee joints. bGH mice generally lack clear, radiologically determinable differentiation of long bone growth plates and bear larger and differently proportioned sesamoids at the elbow and knee. They are also preferentially subject to the accumulation of inferred heterotopic calcification (IHC) and other radiodense soft tissue (RST) around joints and entheses. Female bGH mice exhibit variable and aberrant morphology in the humerus, innominate, and femur not seen in other groups, and show the most size and shape variation within the four genotype \u00d7 sex groupings. Our survey illustrates widespread musculoskeletal impacts of excessive GH into adulthood in the model. These data provide an initial whole\u2010skeleton framework for further efforts characterizing molecular\u2010, cellular\u2010, and tissue\u2010scale alterations ultimately influencing the bGH mouse model skeletal phenotype. This pilot work serves to contextualize future preclinical studies as well as broader investigations into how GH and its metabolic cascade may affect vertebrate morphological and histological development, shape and size disparity, and dimorphism.<\/jats:p>","DOI":"10.1111\/joa.70198","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:08:59Z","timestamp":1782886139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cumulative effects of lifelong systemic excess growth hormone on postcranial skeletal morphology in adult mice"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-1887","authenticated-orcid":false,"given":"Joseph R.","family":"Groenke","sequence":"first","affiliation":[{"name":"Heritage College of Osteopathic Medicine, Department of Biomedical Sciences Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2239-4357","authenticated-orcid":false,"given":"Huanhuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Heritage College of Osteopathic Medicine, Department of Biomedical Sciences Ohio University  Athens Ohio USA"},{"name":"Ohio Musculoskeletal and Neurological Institute (OMNI) Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-7793","authenticated-orcid":false,"given":"Grace","family":"Lach","sequence":"additional","affiliation":[{"name":"Heritage College of Osteopathic Medicine, Department of Biomedical Sciences Ohio University  Athens Ohio USA"},{"name":"Diabetes Institute (DI) Ohio University  Athens Ohio USA"},{"name":"Institute for Molecular Medicine and Aging (IMMA) Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4471-7639","authenticated-orcid":false,"given":"Abhishek","family":"Wajpe","sequence":"additional","affiliation":[{"name":"Heritage College of Osteopathic Medicine, Department of Biomedical Sciences Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4240-9229","authenticated-orcid":false,"given":"Darlene","family":"Berryman","sequence":"additional","affiliation":[{"name":"Heritage College of Osteopathic Medicine, Department of Biomedical Sciences Ohio University  Athens Ohio USA"},{"name":"Diabetes Institute (DI) Ohio University  Athens Ohio USA"},{"name":"Institute for Molecular Medicine and Aging (IMMA) Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4561-2177","authenticated-orcid":false,"given":"John J.","family":"Kopchick","sequence":"additional","affiliation":[{"name":"Heritage College of Osteopathic Medicine, Department of Biomedical Sciences Ohio University  Athens Ohio USA"},{"name":"Diabetes Institute (DI) Ohio University  Athens Ohio USA"},{"name":"Institute for Molecular Medicine and Aging (IMMA) Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-1504","authenticated-orcid":false,"given":"Shouan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Heritage College of Osteopathic Medicine, Department of Biomedical Sciences Ohio University  Athens Ohio USA"},{"name":"Ohio Musculoskeletal and Neurological Institute (OMNI) Ohio University  Athens Ohio USA"},{"name":"Diabetes Institute (DI) Ohio University  Athens Ohio USA"},{"name":"Institute for Molecular Medicine and Aging (IMMA) Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6762-3806","authenticated-orcid":false,"given":"Patrick M.","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Heritage College of Osteopathic Medicine, Department of Biomedical Sciences Ohio University  Athens Ohio USA"},{"name":"Institute for Molecular Medicine and Aging (IMMA) Ohio University  Athens Ohio USA"},{"name":"Ohio Center for Ecological and Evolutionary Studies  Athens Ohio USA"},{"name":"Earth and Space Sciences Denver Museum of Nature &amp; Science  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12546"},{"issue":"3","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1469-7998.1985.tb05622.x","article-title":"The significance of sesamoids and retro\u2010articular processes for the mechanics of joints","volume":"205","author":"Alexander R.M.","year":"1985","journal-title":"Journal of Zoology"},{"key":"e_1_2_10_4_1","first-page":"327","article-title":"Acquisition of bone mass in normal\u2009individuals and in patients with growth hormone deficiency","volume":"16","author":"Baroncelli G.I.","year":"2003","journal-title":"Journal of Pediatric Endocrinology & Metabolism"},{"issue":"3","key":"e_1_2_10_5_1","first-page":"625","article-title":"Fibrocartilage associated with human tendons and their pulleys","volume":"187","author":"Benjamin M.","year":"1995","journal-title":"Journal of Anatomy"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469\u20107580.1998.19340481.x"},{"issue":"2","key":"e_1_2_10_7_1","first-page":"281","article-title":"Loss of the fibrocartilaginous lining of the intertubercular sulcus associated with rupture of the tendon of the long head of biceps brachii","volume":"182","author":"Benjamin M.","year":"1993","journal-title":"Journal of Anatomy"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glp175"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.13091"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12994"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.156"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.0301203"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147669"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje\u201016\u20101073"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013\u20102695"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf03345496"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395\u2010017\u20100133\u2010y"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u2010185x.2011.00204.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.1993.tb26213.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201200271"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4699"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.111052"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.179325"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727\u2010185\u201042561"},{"key":"e_1_2_10_25_1","first-page":"83","article-title":"Periosteal changes in mechanically stressed rat caudal vertebrae","volume":"163","author":"Ellender G.","year":"1989","journal-title":"Journal of Anatomy"},{"issue":"1","key":"e_1_2_10_26_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0087236","article-title":"New material of Beelzebufo, a hyperossified frog (Amphibia: Anura) from the late cretaceous of Madagascar","volume":"9","author":"Evans S.E.","year":"2014","journal-title":"PLoS One"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.167452"},{"key":"e_1_2_10_28_1","first-page":"173","article-title":"Periosteal structure and development in a rat caudal vertebra","volume":"158","author":"Feik S.A.","year":"1988","journal-title":"Journal of Anatomy"},{"issue":"6","key":"e_1_2_10_29_1","first-page":"803","article-title":"Stress induced periosteal changes","volume":"68","author":"Feik S.A.","year":"1987","journal-title":"British Journal of Experimental Pathology"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00266700"},{"issue":"70","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3001845","article-title":"Growth hormone receptor deficiency is associated with a major reduction in pro\u2010aging signaling, cancer, and diabetes in humans","volume":"3","author":"Guevara\u2010Aguirre J.","year":"2011","journal-title":"Science Translational Medicine"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154\u2010020\u201009602\u20104"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010010\u20109403\u20108"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2022.101628"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335\u2010025\u201010189\u2010x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2220\/biomedres.35.69"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013\u20101899"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102\u2010021\u201001179\u20108"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003\u2010030246"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1190101"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.67"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010022\u201000702\u20106"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00256\u2010007\u20100402\u20107"},{"key":"e_1_2_10_44_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41586-020-2234-8","article-title":"Skeleton of a cretaceous mammal from Madagascar reflects long\u2010term insularity","volume":"581","author":"Krause D.W.","year":"2020","journal-title":"Nature"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/02724634.2014.976129"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaf170"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.4158\/ep15939.ra"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.68.6.768"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003\u20100035"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014\u20101572"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2019\u201000167"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2024.152532"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010024\u201001230\u2010z"},{"key":"e_1_2_10_54_1","first-page":"45","article-title":"Excessive growth hormone contributes to heterotopic ossification in Achilles tendon","author":"Liu H.","journal-title":"American Journal of Sports Medicine"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a003895"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016\u20101952"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.110978"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/1749\u20104877.12927"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9975"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010022\u201000649\u20108"},{"issue":"1","key":"e_1_2_10_61_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1159\/000064765","article-title":"Influence of growth hormone on accretion of bone mass","volume":"58","author":"Monson J.P.","year":"2002","journal-title":"Hormone Research"},{"issue":"1","key":"e_1_2_10_62_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1242\/dev.21.1.97","article-title":"Variation of the lumbar vertebrae of mice at two environmental temperatures","volume":"21","author":"Munro K.M.","year":"1969","journal-title":"Development"},{"key":"e_1_2_10_63_1","unstructured":"Olarescu N.C. Gunawardane K. Hansen T.K. M\u00f8ller N.&J\u00f8rgensen J.O.L.(2015)\u201cNormal physiology of growth hormone in normal adults.\u201d.https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK279056\/"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008\u20101199"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102265.2002.01560.x"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/news030915\u201013"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.06.024"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2023.02.010"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102\u2010021\u201001191\u2010y"},{"key":"e_1_2_10_70_1","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2025"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evad033"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102\u2010015\u20100657\u20102"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.3103"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010849107"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100180505"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2008.04.003"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0898\u20106568(03)00005\u20106"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2015.20.1.8"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1986"},{"issue":"2","key":"e_1_2_10_80_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nmeth.2811","article-title":"BoxPlotR: a web tool for generation of box plots","volume":"11","author":"Spitzer M.","year":"2014","journal-title":"Nature Methods"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010025\u201002022\u20109"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137045"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1998.13.4.706"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1177\/153537020122600211"},{"issue":"5","key":"e_1_2_10_85_1","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1152\/jappl.1985.58.5.1572","article-title":"Patellar tendon matrix changes associated with aging and voluntary exercise","volume":"58","author":"Vailas A.C.","year":"1985","journal-title":"Journal of Applied Physiology"},{"issue":"2","key":"e_1_2_10_86_1","first-page":"117","article-title":"Expression of metallothionein\u2010human growth hormone fusion genes in transgenic mice results in disproportionate skeletal gigantism","volume":"55","author":"Wolf E.","year":"1991","journal-title":"Growth, Development, and Aging"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.0763\u201022"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.867921"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmammal\/gyaa010"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00276\u2010011\u20100828\u20104"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42470"}],"container-title":["Journal of Anatomy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joa.70198","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/joa.70198","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joa.70198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:09:10Z","timestamp":1782886150000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joa.70198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":90,"alternative-id":["10.1111\/joa.70198"],"URL":"https:\/\/doi.org\/10.1111\/joa.70198","archive":["Portico"],"relation":{},"ISSN":["0021-8782","1469-7580"],"issn-type":[{"value":"0021-8782","type":"print"},{"value":"1469-7580","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"2025-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"joa.70198"}}