Aromatase mutation in men as a rare cause of osteoporosis: a case report and review of the literature.

OBJECTIVES: Oestrogen deficiency is a rare disease and leads inter alia to arthralgia and osteoporosis in men. The clinical relevance of aromatase to a functioning male metabolism has become evident since 1991, when cases of patients with oestrogen deficiency caused by aromatase mutation were first described. Only few cases are known so far, which will now be presented in a case report and review of the literature. METHODS: All available publications since the first description in 1991 dealing with loss-of-function aromatase mutation in men were summarised and our case report was added. RESULTS: The mutations that cause the aromatase protein to lose function leads to a rather heterogeneous clinical picture. It is, however, clear that oestrogens play a central role in male patients, especially in bone metabolism. Most frequently, tall stature, unclosed epiphyseal joints, and osteoporosis are detected in affected individuals as a consequence of the change in hormonal status. CONCLUSIONS: As low oestrogen is associated with arthralgia, patients with aromatase mutation may be referred to a rheumatologist. Despite aromatase deficiency being a rare disease, the study of the effects of oestrogen on male bone development provides important insights for endocrine bone regulation. It has been demonstrated that androgens alone are not sufficient for adequate skeletal development in males. The described effects of loss of oestrogens are known from the aromatase inhibitor therapy in breast cancer treatment. This work highlights the important role of oestrogens in individual health and disease in men. Molecular effects of oestrogens on bone metabolism are summarised.

Subphysiologic apolipoprotein E (ApoE) plasma levels inhibit neointimal formation after arterial injury in ApoE-deficient mice.

OBJECTIVE: Apolipoprotein E (apoE) reduces mouse atherosclerosis progression independent of plasma cholesterol level effects. A mouse artery injury model was used to examine whether apoE exhibits beneficial lipid-independent effects on neointimal formation. METHODS AND RESULTS: ApoE-deficient (apoE-/-), wild-type (WT), and transgenic apoE-/- mice (secreting apoE at different levels from adrenal glands) underwent femoral artery injury. Mice with low expression of plasma apoE (0.1% of WT) had cholesterol levels approximately half those of apoE-/- littermates (but still approximately 6x >WT). Mice with higher expression (HE; 2% to 3% of WT) of plasma apoE had cholesterol levels approximately twice those of WT. Injured WT mouse (versus apoE-/-) arteries had a smaller mean intima-to-media (I/M) ratio (0.87 versus 1.96; P<0.05). HE mice tended to have lower mean I/M ratios (1.3; P>0.05 versus apoE-/- mice). Multiple regression analysis indicated that apoE levels were significantly associated with reduced I/M ratios, but plasma cholesterol levels were not, before or after adjusting for apoE. In addition, foam cell content of the neointima and media of injured arteries, a negative prognostic indicator in postangioplasty human lesions, was inversely related to plasma apoE levels. CONCLUSIONS: Similar to its effects on atherosclerosis progression, in a mouse model of restenosis, a subphysiological level of apoE was associated with beneficial effects on lesion size/composition.