Impact on bone of an estrogen receptor-α gene loss of function mutation

被引：66

作者：

Smith, Eric P. ^{[1
]}

Specker, Bonny ^{[2
]}

Bachrach, Bert E. ^{[3
]}

Kimbro, K. S. ^{[4
,5
]}

Li, X. J. ^{[6
]}

Young, Marian F. ^{[7
]}

Fedarko, Neal S. ^{[8
]}

Abuzzahab, M. J. ^{[3
]}

Frank, Graeme R. ^{[9
]}

Cohen, Robert M. ^{[1
]}

Lubahn, Dennis B. ^{[10
]}

Korach, Kenneth S. ^{[4
]}

机构：

[1] Univ Cincinnati, Coll Med, Dept Internal Med, Div Endocrinol Diabet & Metab, Cincinnati, OH 45267 USA

[2] S Dakota State Univ, Ethel Austin Martin Program Human Nutr, Brookings, SD 57007 USA

[3] Univ Cincinnati, Coll Med, Div Endocrinol, Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA

[4] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA

[5] Emory Univ, Sch Med, Dept Hematol & Oncol, Atlanta, GA 30322 USA

[6] Wyeth Ayerst Res, Womens Hlth & Musculoskeletal Biol, Cambridge, MA 02140 USA

[7] Natl Inst Dent Craniofacial Res, Bethesda, MD 20892 USA

[8] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA

[9] Long Isl Jewish Med Ctr, Schneider Childrens Hosp, Div Pediat Endocrinol, New Hyde Pk, NY 11042 USA

[10] Univ Missouri, Dept Biochem & Child Hlth, Columbia, MO 65211 USA

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2008年 / 93卷 / 08期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1210/jc.2007-2397

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

Context: The kindred described is the only known instance of a germ line loss of function mutation of estrogen receptor ( ER)-alpha. Objective: Our objective was to assess the impact of a loss of function mutation in the ER-alpha gene on histomorphometry, bone volumetric density, bone geometry and skeletal growth, and ER-alpha heterozygosity on spine density and adult height in an extended pedigree. Design and Participants: A longitudinal follow-up of the propositus with homozygous loss of function mutation of ER-alpha and single contact evaluation of the kindred were performed. Main Outcome Measures: Iliac crest bone biopsy and peripheral quantitative computed tomography of propositus with serial measures of areal spine bone mineral density (aBMD) by dual-energy x-ray absorptiometry and bone age were performed. Members of pedigree were evaluated for ER-alpha mutation carrier status and spine aBMD. Results: Bone biopsy revealed marked osteopenia (cortex: 641 mu m), low trabecular volume (10.6%), decreased thickness (76.2 mu m), normal trabecular number, and low activation frequency (0.099/yr). Radial periosteal circumference was similar, endosteal circumference larger, and trabecular and cortical volumetric bone mineral density markedly lower (158 and 1092 mg/cm(3), respectively) than controls. Spine aBMD at age 28.5 yr (0.745 g/cm(2)) decreased to 0.684 g/cm(2) (Z score - 3.85) in 3.5 yr. Bone age advanced from 15-17.5 yr. Kindred analysis revealed that gene carriers had spine aBMD Z scores less than zero (P = 0.003), but carriers and nonmutant members were similar (-0.84 +/- 0.26 vs. -0.64 +/- 0.16). Conclusion: Homozygous ER-alpha disruption markedly affects bone growth, mineral content, and structure but not periosteal circumference. ER-alpha heterozygosity appears to not impair spine aBMD.

引用

页码：3088 / 3096

页数：9

共 40 条

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