{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:39:45Z","timestamp":1788475185612,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to determine the effects of \u00df-hydroxy-\u00df-methylbutyrate (HMB) supplementation during pregnancy on postpartum bone tissue quality by assessing changes in trabecular and compact bone as well as in hyaline and epiphyseal cartilage. The experiment was carried out on adult 6-month-old female spiny mice (Acomys cahirinus) divided into three groups: pregnant control (PregCont), pregnant HMB-treated (supplemented with 0.02 g\/kg b.w of HMB during the second trimester of pregnancy, PregHMB), and non-pregnant females (NonPreg). Cross-sectional area and cortical index of the femoral mid-shaft, stiffness, and Young modulus were significantly greater in the PregHMB group. Whole-bone mineral density was similar in all groups, and HMB supplementation increased trabecular number. Growth plate cartilage was the thinnest, while the articular cartilage was the thickest in the PregHMB group. HMB supplementation increased the content of proteoglycans in the articular cartilage and the percentage of immature collagen content in metaphyseal trabeculae and compact bone. In summary, dietary HMB supplementation during the second trimester of pregnancy intensifies bone metabolic processes and prevents bone loss during pregnancy.<\/jats:p>","DOI":"10.3390\/ijms22063047","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T01:47:47Z","timestamp":1615945667000},"page":"3047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["\u03b2-Hydroxy-\u03b2-Methylbutyrate (HMB) Supplementation Prevents Bone Loss during Pregnancy\u2014Novel Evidence from a Spiny Mouse (Acomys cahirinus) Model"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7574-2653","authenticated-orcid":false,"given":"Ewa","family":"Tomaszewska","sequence":"first","affiliation":[{"name":"Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-016X","authenticated-orcid":false,"given":"Janine","family":"Donaldson","sequence":"additional","affiliation":[{"name":"School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1700-0317","authenticated-orcid":false,"given":"Jakub","family":"Kosi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Orthopaedics, Medical University in Lublin, Jaczewskiego St. 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5873-9666","authenticated-orcid":false,"given":"Piotr","family":"Dobrowolski","sequence":"additional","affiliation":[{"name":"Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka St. 19, 20-033 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Tomczyk-Warunek","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Orthopaedics, Medical University in Lublin, Jaczewskiego St. 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5039-009X","authenticated-orcid":false,"given":"Monika","family":"Hu\u0142as-Stasiak","sequence":"additional","affiliation":[{"name":"Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka St. 19, 20-033 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9678-541X","authenticated-orcid":false,"given":"Krzysztof","family":"Lamorski","sequence":"additional","affiliation":[{"name":"Bohdan Dobrza\u0144ski Institute of Agrophysics of the Polish Academy of Sciences, Do\u015bwiadczalna St. 4, 20-290 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Laskowska-Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4118-6302","authenticated-orcid":false,"given":"Siemowit","family":"Muszy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Blicharski","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Orthopaedics, Medical University in Lublin, Jaczewskiego St. 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9747-8817","authenticated-orcid":false,"given":"Tomasz","family":"Blicharski","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Orthopaedics, Medical University in Lublin, Jaczewskiego St. 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s00726-013-1592-z","article-title":"Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: A systematic review of randomized trials","volume":"45","author":"Molfino","year":"2013","journal-title":"Amino Acids"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00726-015-2067-1","article-title":"The role of leucine and its metabolites in protein and energy metabolism","volume":"48","author":"Duan","year":"2016","journal-title":"Amino Acids"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-7075-9-77","article-title":"Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice","volume":"9","author":"Bruckbauer","year":"2012","journal-title":"Nutr. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/1028415X.2016.1145376","article-title":"Effects of beta-hydroxy-beta-methyl butyrate on working memory and cognitive flexibility in an animal model of aging","volume":"20","author":"Hankosky","year":"2017","journal-title":"Nutr. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"679","DOI":"10.7205\/MILMED-D-13-00421","article-title":"Beta-Hydroxy-beta-methylbutyrate improves bone properties and attenuates the depression of protein synthesis during a simulated sustained operation","volume":"179","author":"Henning","year":"2014","journal-title":"Mil. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.exger.2015.02.012","article-title":"Beta-Hydroxy-beta-methylbutyrate (HMB) supplementation and resistance exercise significantly reduce abdominal adiposity in healthy elderly men","volume":"64","author":"Stout","year":"2015","journal-title":"Exp. Gerontol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1177\/0148607108322403","article-title":"Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta-hydroxy-betamethylbutyrate (HMB), L-arginine, and L-lysine","volume":"33","author":"Baier","year":"2009","journal-title":"J. Parenter. Enteral Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1097\/00005768-200012000-00023","article-title":"Betahydroxy-beta-methylbutyrate ingestion, part II: Effects on hematology, hepatic and renal function","volume":"32","author":"Gallagher","year":"2000","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1093\/jn\/130.8.1937","article-title":"Betahydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors","volume":"130","author":"Nissen","year":"2000","journal-title":"J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1177\/014860710402800265","article-title":"Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters","volume":"28","author":"Rathmacher","year":"2004","journal-title":"J. Parenter. Enteral Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1550-2783-10-6","article-title":"International Society of Sports Nutrition Position Stand: Beta-hydroxy-beta-methylbutyrate (HMB)","volume":"10","author":"Wilson","year":"2013","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/rda.12657","article-title":"Effects of dietary supplementation of beta-hydroxy-beta-methylbutyrate on sow performance and mRNA expression of myogenic markers in skeletal muscle of neonatal piglets","volume":"51","author":"Wan","year":"2016","journal-title":"Reprod. Domest. Anim."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/jpn.13060","article-title":"Maternal HMB treatment affects bone and hyaline cartilage development in their weaned piglets via the leptin\/osteoprotegerin system","volume":"103","author":"Tomaszewska","year":"2019","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_14","first-page":"341","article-title":"Influence of oral administration of HMB to pregnant dams on calbindin expression in the dentate gyrus of the hippocampus during postnatal development in spiny mice offspring","volume":"73","author":"Rycerz","year":"2017","journal-title":"Med. Wet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/jpn.12234","article-title":"Dietary supplementation of bhydroxy-b-methylbutyrate in animals\u2014A review","volume":"99","author":"Ostaszewski","year":"2015","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Blicharski, T., Tomaszewska, E., Dobrowolski, P., Hu\u0142as-Stasiak, M., and Muszy\u0144ski, S. (2017). A metabolite of leucine (\u03b2-hydroxy-\u03b2-methylbutyrate) given to sows during pregnancy alters bone development of their newborn offspring by hormonal modulation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179693"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.bone.2007.02.018","article-title":"Prenatal programming of skeletal development in the offspring: Effects of maternal treatment with \u03b2-hydroxy-\u03b2-methylbutyrate (HMB) on femur properties in pigs at slaughter age","volume":"40","author":"Tatara","year":"2007","journal-title":"Bone"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"40.e1","DOI":"10.1016\/j.ajog.2016.07.041","article-title":"First evidence of a menstruating rodent: The spiny mouse (Acomys cahirinus)","volume":"216","author":"Bellofiore","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_19","first-page":"E78","article-title":"Hormones in perinatal at and spiny mouse: Relation to altricial and precocial timing of birth","volume":"251","author":"Lamers","year":"1986","journal-title":"Am. J. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"F273","DOI":"10.1152\/ajprenal.00400.2004","article-title":"The spiny mouse (Acomys cahirinus) completes nephrogenesis before birth","volume":"289","author":"Dickinson","year":"2005","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1159\/000232562","article-title":"Neuroprotective properties of melatonin in a model of birth asphyxia in the spiny mouse (Acomys cahirinus)","volume":"31","author":"Hutton","year":"2009","journal-title":"Dev. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R129","DOI":"10.1530\/REP-20-0354","article-title":"Animal models of human pregnancy and placentation: Alternatives to the mouse","volume":"160","author":"Carter","year":"2020","journal-title":"Reproduction"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2041-9139-5-33","article-title":"Two waves of anisotropic growth generate enlarged follicles in the spiny mouse","volume":"5","author":"Montandon","year":"2014","journal-title":"EvoDevo"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.neuroscience.2011.05.012","article-title":"A maternal diet supplemented with creatine from mid-pregnancy protects the newborn spiny mouse brain from birth hypoxia","volume":"194","author":"Ireland","year":"2011","journal-title":"Neuroscience"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ajog.2007.10.790","article-title":"Maternal creatine: Does it reach the fetus and improve survival after an acute hypoxic episode in the spiny mouse (Acomys cahirinus)?","volume":"198","author":"Ireland","year":"2008","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1177\/0023677218769921","article-title":"The African spiny mouse (Acomys spp.) as an emerging model for development and regeneration","volume":"52","author":"Pinhero","year":"2018","journal-title":"Lab. Anim."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"dev167718","DOI":"10.1242\/dev.167718","article-title":"Model systems for regeneration: The spiny mouse, Acomys cahirinus","volume":"147","author":"Maden","year":"2020","journal-title":"Development"},{"key":"ref_28","first-page":"316","article-title":"Characteristics of somatic development in the maturation period","volume":"6","year":"2006","journal-title":"Post. Nauk Med."},{"key":"ref_29","first-page":"77","article-title":"Risk factors for osteoporosis, with particular emphasis on the correct development and metabolism of bone tissue","volume":"8","author":"Rabijewski","year":"2017","journal-title":"Inf. Forum"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.6065\/apem.2017.22.1.1","article-title":"Bone modeling, remodeling, and skeletal health in children and adolescents: Mineral accrual, assessment and treatment","volume":"22","author":"Maggioli","year":"2017","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy (2001). Osteoporosis, prevention and treatment. J. Am. Med. Assoc., 285, 765\u2013795.","DOI":"10.1001\/jama.285.6.785"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1385\/JCD:3:2:177","article-title":"Bone mineral density in diagnosis of osteoporosis: Reference population, definition of peak bone mass, and measured site determine prevalence","volume":"3","author":"Larsson","year":"2000","journal-title":"J. Clin. Densitom."},{"key":"ref_33","unstructured":"Br\u0119borowicz, G.H. (2020). Obstetrics and Gynecology, PZWL. [3rd ed.]."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ecl.2005.09.004","article-title":"Calcium and bone disorders during pregnancy and lactation","volume":"35","author":"Kovacs","year":"2006","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_35","first-page":"832","article-title":"Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation","volume":"18","author":"Kovacs","year":"1997","journal-title":"Endocr. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1385\/ENDO:17:1:49","article-title":"Bone mineral changes during pregnancy and lactation","volume":"17","author":"Kalkwarf","year":"2002","journal-title":"Endocrine"},{"key":"ref_37","first-page":"97","article-title":"Pregnancy and lactation-associated osteoporosis","volume":"2","author":"Szymczak","year":"2019","journal-title":"Forum Reumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/j.1471-0528.1996.tb09845.x","article-title":"Changes in bone density and biochemical markers of bone turnover in pregnancy-associated osteoporosis","volume":"103","author":"Khastgir","year":"1996","journal-title":"Br. J. Obstet. Gynaecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1007\/s00198-015-3149-3","article-title":"Presentation and management of osteoporosis presenting in association with pregnancy or lactation","volume":"26","author":"Kovacs","year":"2015","journal-title":"Osteoporos. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/S0140-6736(85)92861-2","article-title":"Osteoporosis of pregnancy","volume":"325","author":"Smith","year":"1985","journal-title":"Lancet"},{"key":"ref_41","first-page":"8","article-title":"Preliminary study of time dependent influence of maternal nutrition with addition of \u03b2-hydroxy-\u03b2-methlbutyrate on body weight and selected organs weight in the new born spiny mice (Acomys cahrinus) offspring","volume":"19","author":"Tomczyk","year":"2016","journal-title":"Electron. J. Pol. Agricult. Univ."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2527\/jas.53971","article-title":"Effect of beta-hydroxy beta-methyl butyrate supplementation of sows in late gestation and lactation on sow production of colostrum and milk and piglet performance","volume":"90","author":"Flummer","year":"2012","journal-title":"J. Anim. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.2527\/1994.7292331x","article-title":"Colostral milk fat percentage and pig performance are enhanced by feeding the leucine metabolite beta-hydroxy-beta-methyl butyrate to sows","volume":"72","author":"Nissen","year":"1994","journal-title":"J. Anim. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hu, L., Kristensen, N.B., Krogh, U., and Theil, P.K. (2020). Net absorption and metabolism of \u03b2-hydroxy-\u03b2-methyl butyrate during late gestation in a pig model. Nutrients, 12.","DOI":"10.3390\/nu12020561"},{"key":"ref_45","first-page":"2167","article-title":"Maternal nutrition with \u0392-hydroxy-\u0392-methylbutyrate as strong determinants of the development of newborn offspring in pigs","volume":"4","author":"Tomaszewska","year":"2015","journal-title":"J. Neonat. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1515\/bvip-2015-0084","article-title":"Effect of HMB and 2-Ox administered during pregnancy on bone properties in primiparous and multiparous minks (Neivison vison)","volume":"59","author":"Tomaszewska","year":"2015","journal-title":"Bull. Vet. Inst. Pulawy"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1017\/S0007114516000465","article-title":"Dietary supplementation with \u03b2-hydroxy-\u03b2-methylbutyrate calcium during the early postnatal period accelerates skeletal muscle fibre growth and maturity in intrauterine growth-retarded and normal-birth-weight piglets","volume":"115","author":"Wan","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1550-2783-9-18","article-title":"Beta-hydroxy-beta-methylbutyrate blunts negative age-related changes in body composition, functionality and myofiber dimensions in rats","volume":"9","author":"Wilson","year":"2012","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_49","first-page":"84","article-title":"Short- and long-term consequences on biochemical markers after fundectomy in pigs supplemented with 3-hydroxy-3-methylbutyrate and alpha-ketoglutarate","volume":"123","author":"Adaszek","year":"2010","journal-title":"Berl. Munch. Tierarztl. Wochenschr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.fct.2008.11.021","article-title":"Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues","volume":"47","author":"Holecek","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1042\/cs0940405","article-title":"Bone mineral changes during pregnancy and lactation: A longitudinal cohort study","volume":"94","author":"Kolthoff","year":"1998","journal-title":"Clin. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1359\/jbmr.2000.15.1.129","article-title":"The effect of pregnancy on bone density and bone turnover","volume":"15","author":"Naylor","year":"2000","journal-title":"J. Bone Miner. Res."},{"key":"ref_53","first-page":"101","article-title":"Understanding bone strength: Size isn\u2019t everything","volume":"29","author":"Jepsen","year":"2011","journal-title":"Bone"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1016\/j.jbiomech.2010.06.019","article-title":"In vivo tibial stiffness is maintained by whole bone morphology and cross-sectional geometry in growing female mice","volume":"43","author":"Main","year":"2010","journal-title":"J. Biomech."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/0021-9290(89)90226-1","article-title":"The area moment of inertia of the tibia: A risk factor for stress fractures","volume":"22","author":"Milgrom","year":"1989","journal-title":"J. Biomech."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1002\/jbmr.5650081113","article-title":"Interrelationships between densitometric, geometric, and mechanical properties of rat femora: Inferences concerning mechanical regulation of bone modeling","volume":"8","author":"Ferretti","year":"1993","journal-title":"J. Bone Miner. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/8756-3282(93)90150-9","article-title":"Determination of femur structural properties by geometric and material variables as a function of body weight in rats. Evidence of sexual dimorphism","volume":"14","author":"Ferretti","year":"1993","journal-title":"Bone"},{"key":"ref_58","unstructured":"Zaidi, N. (2020). Bone anatomy and structure. Encyclopedia of Bone Biology, Academic Press."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.rcl.2010.02.014","article-title":"Physiology of bone loss","volume":"48","author":"Clarke","year":"2010","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1007\/s00198-017-4165-2","article-title":"Pregnancy-related fractures: A retrospective study of a French cohort of 52 patients and review of the literature","volume":"28","author":"Laroche","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00198-017-4239-1","article-title":"Subsequent fracture risk of women with pregnancy and lactation-associated osteoporosis after a median of 6 years of follow-up","volume":"29","author":"Kyvernitakis","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1007\/s10067-018-4185-0","article-title":"Clinical characteristics and bisphosphonates treatment of rare pregnancy- and lactation-associated osteoporosis","volume":"37","author":"Li","year":"2018","journal-title":"Clin. Rheumatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00223-015-0028-z","article-title":"Pregnancy and lactation-associated osteoporosis: Bone histomorphometric analysis and response to treatment with zoledronic acid","volume":"97","author":"Grizzo","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1002\/jbmr.3750","article-title":"Women with pregnancy and lactation\u2013associated osteoporosis (PLO) have low bone remodeling rates at the tissue level","volume":"34","author":"Cohen","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0142-9612(99)00213-6","article-title":"Review: Tissue engineering for regeneration of articular cartilage","volume":"21","author":"Temenoff","year":"2000","journal-title":"Biomaterials"},{"key":"ref_66","first-page":"283","article-title":"Function of proteoglycans in the extracellular matrix","volume":"43","author":"Yanagishita","year":"1993","journal-title":"Acta Pathol. Jpn."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2519\/jospt.1998.28.4.203","article-title":"Composition and dynamics of articular cartilage: Structure, function, and maintaining healthy state","volume":"28","author":"Cohen","year":"1998","journal-title":"J. Orthop. Sports Phys. Ther."},{"key":"ref_68","first-page":"135","article-title":"Age-related modifications in articular cartilage","volume":"11","year":"2017","journal-title":"Geriatria"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.theriogenology.2019.02.003","article-title":"Maternal \u03b2-hydroxy-\u03b2-methylbutyrate (HMB) supplementation during pregnancy affects early folliculogenesis in the ovary of newborn piglets","volume":"128","author":"Dobrowolski","year":"2019","journal-title":"Theriogenology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 purified diets for laboratory rodents: Final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-7075-9-39","article-title":"Effects of combined maternal administration with alpha-ketoglutarate (AKG) and \u03b2-hydroxy-\u03b2-methylbutyrate (HMB) on prenatal programming of skeletal properties in the offspring","volume":"9","author":"Tatara","year":"2012","journal-title":"Nutr. Metab."},{"key":"ref_72","unstructured":"EFSA (2011). Scientific Opinion on the substantiation of health claims related to \u03b2-hydroxy \u03b2-methylbutyrate monohydrate (HMB) alone or in combination with \u03b1-ketoisocaproic acid (KIC) and reduction of muscle tissue damage during exercise (ID 1577, 1584), increase in lean body mass (ID 1579, 1582, 1583), increase in muscle strength (ID 1578, 1583, 1587), increase in endur-ance performance (ID 1580, 1581), skeletal muscle tissue repair (ID 1586) and faster recovery from muscle fatigue after exer-cise (ID 1576, 1585) pursuant to Article 13(1) of Regulation (EC) No 1924\/2006. EFSA J., 9, 2227."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1439-0396.2000.00272.x","article-title":"The leucine metabolite 3-hydroxy-3-methylbutyrate (HMB) modifies protein turnover in muscles of laboratory rats and domestic chickens in vitro","volume":"84","author":"Ostaszewski","year":"2000","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1113\/jphysiol.2013.253203","article-title":"Effects of leucine and its metabolite betahydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism","volume":"591","author":"Wilkinson","year":"2013","journal-title":"J. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1007\/s00421-014-2854-5","article-title":"The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: A randomized, double-blind, placebo-controlled study","volume":"114","author":"Wilson","year":"2014","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Tomaszewska, E., Muszy\u0144ski, S., Kuc, D., Dobrowolski, P., Lamorski, K., Donaldson, J., \u015awietlicka, I., Mielnik-B\u0142aszczak, M., Paluszkiewicz, P., and Parada-Turska, J. (2019). Chronic dietary supplementation with kynurenic acid, a neuroactive metabolite of tryptophan, decreased body weight without negative influence on densitometry and mandibular bone biomechanical endurance in young rats. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0226205"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.bone.2010.08.023","article-title":"BoneJ: Free and extensible bone image analysis in ImageJ","volume":"47","author":"Doube","year":"2010","journal-title":"Bone"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2478\/aoas-2019-0003","article-title":"Bone homeostasis in experimental fumonisins intoxication of rats","volume":"19","author":"Rudyk","year":"2019","journal-title":"Ann. Anim. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/jbmr.1805","article-title":"Standardized nomenclature, symbols, and units for bone histomorphometry: A 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee","volume":"28","author":"Dempster","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.2478\/aoas-2020-0044","article-title":"Acrylamide-induced prenatal programming of bone structure in mammal model","volume":"20","author":"Tomaszewska","year":"2020","journal-title":"Ann. Anim. Sci."},{"key":"ref_81","first-page":"97","article-title":"Collagen and Picrosirius Red Staining: A polarized light assessment of fibrillar hue and spatial distribution","volume":"22","author":"Rich","year":"2017","journal-title":"J. Morphol. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1111\/j.1439-0396.2012.01319.x","article-title":"Morphological changes of the cartilage and bone in newborn piglets evoked by experimentally induced glucocorticoid excess during pregnancy","volume":"97","author":"Tomaszewska","year":"2013","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/3047\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:36:49Z","timestamp":1760161009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/3047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,17]]},"references-count":83,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22063047"],"URL":"https:\/\/doi.org\/10.3390\/ijms22063047","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,17]]}}}