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 microm), low trabecular volume (10.6%), decreased thickness (76.2 microm), 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.
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 microm), low trabecular volume (10.6%), decreased thickness (76.2 microm), 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.
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Authors: C Castelo-Branco; J J Vicente; F Figueras; A Sanjuan; M J Martínez de Osaba; E Casals; F Pons; J Balasch; J A Vanrell Journal: Maturitas Date: 2000-02-15 Impact factor: 4.342
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Authors: Aaron W James; Alexander A Theologis; Samantha A Brugmann; Yue Xu; Antoine L Carre; Philipp Leucht; Katherine Hamilton; Kenneth S Korach; Michael T Longaker Journal: PLoS One Date: 2009-09-22 Impact factor: 3.240