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Constitutional Thinness: Unusual Human Phenotype of Low Bone Quality

Departments of Endocrinology (B.G., N.G., C.B., B.E.) and Psychiatry (F.L.), and Nuclear Medicine Laboratory (D.F.), Centre Hospitalier Universitaire Saint Etienne, 42055 Saint Etienne, France; Institut National de la Santé et de la Recherche Médicale U890 (M.Z., M.-H.L.-P., T.T., L.V.), F-42023 Saint Etienne, France; and Endocrinology Department (B.G.), Universitatea de Medicina si Farmacie, 700229 Iasi, Romania

Address all correspondence and requests for reprints to: Bruno Estour, Endocrinology Department, Centre Hospitalier Universitaire Saint Etienne, 42055 Saint Etienne, Cedex 2, France. E-mail: bruno.estour{at}chu-st-etienne.fr.

Context: Low fat mass and hormonal or nutritional deficiencies are often incriminated in bone loss related to thinness. Constitutional thinness has been described in young women with low body mass index (BMI) but close-to-normal body composition, physiological menstruation, no hormonal abnormalities, and no anorexia nervosa (AN) psychological profile.

Objective: Our objective was to determine whether constitutional thinness is associated with impaired bone quality.

Design, Setting, and Participants: This was an observational, cross-sectional study on 25 constitutionally thin and 44 AN young women with similar low BMI (<16.5 kg/m²) and 28 age-matched controls.

Main Outcome Measures: Femoral and lumbar spine bone mineral density by dual-energy x-ray absorptiometry, distal tibia and radius bone architecture and breaking strength by three-dimensional peripheral quantitative computed tomography, and bone turnover markers were determined.

Results: Constitutionally thin subjects displayed a higher percentage of fat mass than AN subjects but had similar lumbar and femoral bone mineral density, which were significantly lower than in controls (P < 0.001). Constitutionally thin subjects displayed more markedly impaired trabecular and cortical bone parameters in the distal tibia than in the radius. AN bone structure was impaired only in subjects with a long history of disease. Calculated breaking strength was decreased in constitutional thinness and long-standing AN in both the radius and the tibia. Bone markers in constitutionally thin subjects were similar to those of controls. Osteoprotegerin to receptor activator of nuclear factor B ligand ratio was higher in constitutionally thin subjects than in controls or AN women.

Conclusions: Young women with constitutional thinness present an unexpectedly high prevalence of low bone mass (44%) associated with small bone size, overall diminished breaking strength, but normal bone turnover. Mechanisms related to insufficient skeletal load and/or genetics are proposed to explain this new phenotype of impaired bone quality.

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