The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Effects of Recombinant Human IGF-I and Oral Contraceptive Administration on Bone Density in Anorexia Nervosa
Abstract
Over 90% of women with anorexia nervosa demonstrate osteopenia, and almost 40% demonstrate osteoporosis at one or more skeletal sites. In addition to estrogen deficiency causing an increase in bone resorption, nutritional effects on the GH-IGI-I axis may contribute to the severe bone loss in this population by decreasing bone formation. We tested the hypothesis that recombinant human IGF-I (rhIGF-I) would increase bone density in women with anorexia nervosa and furthermore assessed the effects of combined rhIGF-I and oral contraceptive administration (OCP) in this population. Sixty osteopenic women with Diagnosis and Statistical Manual of Mental Disorders IV Revised confirmed anorexia nervosa [age (25.2 +/- 0.7 yr, range 18-38 yr), body mass index (17.8 +/- 0.3 kg/m(2) ), spinal bone mineral density T score (-2.1 +/- 0.1 SD) were randomized to one of four treatment groups [rhIGF-I (30 microg/kg sc twice daily) and a daily oral contraceptive (Ovcon 35, 35 microg ethinyl estradiol and 0.4 mg norethindrone], rhIGF-I alone (30 microg/kg sc twice daily), oral contraceptive alone, or neither treatment for 9 months. All subjects received calcium 1500 mg/d and a standard multivitamin containing 400 IU of vitamin D. Administration of rhIGF-I was placebo controlled and blinded to subjects. The rhIGF-I was titrated to maintain IGF-I levels within the age-adjusted normal range for each patient and was well tolerated. The effects of rhIGF-I and OCP were analyzed simultaneously among all subjects in a factorial analysis and in an analysis of the four individual treatment groups. Anteroposterior spinal bone density increased significantly in response to rhIGF-I (1.1% +/- 0.5% vs. -0.6% +/- 0.8%, P = 0.05, all rhIGF-I vs. all placebo treated, respectively, by analysis of covariance). In contrast, OCP did not result in increased bone density (0.8% +/- 0.6% vs. -0.4% +/- 0.8%, P = 0.21, all OCP vs. all non-OCP treated, respectively, by analysis of covariance). However, bone density increased to the greatest extent in the combined treatment group (rhIGF-I and OCP), compared with control patients receiving no active therapy (1.8% +/- 0.8% vs. 0.3% +/- 0.6% vs. -0.2% +/- 0.8% vs. -1.0% +/- 1.3%, rhIGF-I and OCP vs. rhIGF-I alone vs. OCP alone vs. no active therapy, P < 0.05 for rhIGF-I and OCP vs. no active therapy). These data demonstrate that osteopenic women with anorexia nervosa treated with rhIGF-I showed more beneficial changes in bone density, compared with patients not treated with rhIGF-I. Antiresorptive therapy with OCP is not sufficient to improve bone density in undernourished patients, but such therapy may augment the effects of rhIGF-I in a combined treatment strategy. Further long-term studies are needed to investigate the effects of rhIGF-I and combined anabolic/antiresorptive strategies on bone in women with anorexia nervosa.
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“Therefore, changes in BMC and BMD of the lumbar spine are detected more quickly and are of greater magnitude than at other sites (hip and radius), as also evidenced in response to other treatments, for example, PTH [39,40], IGF-1, and contraceptive steroids [11,41,42].”
From Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women (2011) · cites this paper as [11]
In the citing paper
“It is therefore possible that, besides putative direct effects of leptin, multiple neuroendocrine changes in response to metreleptin treatment, that is, increased IGF-1 concentration and restoration of euthyroid status, might be involved because the lumbar spine is more sensitive to the bone trophic effect of these mediators than the hip and the forearm [11,43,44].”
From Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women (2011) · cites this paper as [11]
In the citing paper
“other studies have shown that BMD at various skeletal sites, including the ones we measured, does not change significantly over 9 to 30 months in untreated young women with exercise-induced amenorrhea; changes from baseline typically range from an increase of approximately 0.5% to a decline of approximately 2.5% [11,41,42].”
From Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women (2011) · cites this paper as [11]
In the citing paper
“Many of the therapies designed to improve the hormonal abnormalities associated with this condition (estrogen, insulin-like growth factor 1 [IGF-1], and dehydroepiandrosterone), isolated or in combination [11], have no consistent or only mild favorable effects on BMD [12,13].”
From Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women (2011) · cites this paper as [11]
In the citing paper
“Alterations in the growth hormone axis, particularly low IGF1 concentrations, also have been proposed to contribute to bone loss associated with anorexia nervosa (27, 28, 31, 32).”
From Leptin is an effective treatment for hypothalamic amenorrhea (2011) · cites this paper as [32]
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Metadata
- Authors
- Grinspoon, S., Thomas, L., Miller, K., Herzog, D., & Klibanski, A.
- Affiliations
- Massachusetts General Hospital (US)
- Neuroendocrine Unit (S.G., L.T., K.M., A.K.), Boston, Massachusetts 02114
- Harvard University (US)
- Corresponding author
- Grinspoon, Steven
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2002-06-01
- Volume
- 87
- Issue
- 6
- Pages
- 2883-2891
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2138117830
- Cited by
- 334
- References
- 24
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 13 · 2020: 4 · 2019: 9 · 2018: 12 · 2017: 14 · 2016: 16 · 2015: 8 · 2014: 28 · 2013: 17 · 2012: 15
- FWCI
- 17.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- National Institutes of Health
- Genentech
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK052625, P30DK040561)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- anorexia nervosa, recombinant human IGF-I, oral contraceptives, bone mineral density, osteopenia, osteoporosis, bone loss, estrogen deficiency, somatotropic axis, spine bone density, women's health, calcium and vitamin D supplementation, bone resorption
- MeSH terms
- Adult, Anorexia Nervosa, Calcium, Contraceptives, Oral, Drug Combinations, Drug Therapy, Combination, Ethinyl Estradiol, Female, Humans, Insulin-Like Growth Factor I, Norethindrone, Recombinant Proteins, Reference Values, Biomarkers, Bone Density, Bone Remodeling
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