{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:11:05Z","timestamp":1792642265289,"version":"4.5.0"},"reference-count":73,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,1,1]]},"abstract":"<jats:p>Insulin-dependent diabetes mellitus (IDDM) is associated with increased risk of osteopenia\/osteoporosis in humans. The mechanisms accounting for diabetic bone loss remain unclear. Pharmacologic inducers of IDDM, such as streptozotocin, mimic key aspects of diabetes in rodents, allow analysis at the onset of diabetes, and induce diabetes in genetically modified mice. However, side effects of streptozotocin, unrelated to diabetes, can complicate data interpretation. The nonobese diabetic (NOD) mouse model develops diabetes spontaneously without external influences, negating side effects of inducing agents. Unfortunately, in this model the onset of diabetes is unpredictable, occurs in a minority of male mice, and can only be studied in a single mouse strain. To validate the relevance of the more flexible streptozotocin-induced diabetes model for studying diabetes-associated bone loss, we compared its phenotype to the spontaneously diabetic NOD model. Both models exhibited hyperglycemia and loss of body, fat pad, and muscle weight. Furthermore, these genetically different and distinct models of diabetes induction demonstrated similar bone phenotypes marked by significant trabecular bone loss and increased bone marrow adiposity. Correspondingly, both diabetic models exhibited decreased osteocalcin mRNA and increased adipocyte fatty acid-binding protein 2 mRNA levels in isolated tibias and calvaria. Taken together, multiple streptozotocin injection-induced diabetes is a valid model for understanding the acute and chronic pathophysiologic responses to diabetes and their mechanisms in bone.<\/jats:p>","DOI":"10.1210\/en.2006-1006","type":"journal-article","created":{"date-parts":[[2006,10,20]],"date-time":"2006-10-20T00:53:30Z","timestamp":1161305610000},"page":"198-205","source":"Crossref","is-referenced-by-count":238,"title":["Bone Loss and Increased Bone Adiposity in Spontaneous and Pharmacologically Induced Diabetic Mice"],"prefix":"10.1210","volume":"148","author":[{"given":"Sergiu","family":"Botolin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura R.","family":"McCabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614052189100_R1","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.2337\/diacare.27.12.2790","article-title":"Diabetes incidence in 0- to 14-year age-group in Italy: a 10-year prospective study.","volume":"27","author":"Carle","year":"2004","journal-title":"Diabetes Care"},{"key":"2020071614052189100_R2","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.2337\/diacare.27.7.1623","article-title":"Type 1 diabetes among sardinian children is increasing: the Sardinian diabetes register for children aged 0\u201314 years (1989\u20131999).","volume":"27","author":"Casu","year":"2004","journal-title":"Diabetes Care"},{"key":"2020071614052189100_R3","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/S0140-6736(04)17357-1","article-title":"The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes.","volume":"364","author":"Gillespie","year":"2004","journal-title":"Lancet"},{"key":"2020071614052189100_R4","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.2337\/diabetes.51.12.3353","article-title":"The rise of childhood type 1 diabetes in the 20th century.","volume":"51","author":"Gale","year":"2002","journal-title":"Diabetes"},{"key":"2020071614052189100_R5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0168-8227(01)00365-5","article-title":"Report of the Committee on the classification and diagnostic criteria of diabetes mellitus.","volume":"55","author":"Kuzuya","year":"2002","journal-title":"Diabetes Res Clin Pract"},{"key":"2020071614052189100_R6","first-page":"1194","article-title":"Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus.","volume":"80","author":"Bouillon","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614052189100_R7","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF03343726","article-title":"Osteopenia in insulin-dependent diabetes mellitus; 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