Estrogen, androgen, and the pathogenesis of bone fragility in women and men.
During growth, estrogen deficiency in females may produce increased bone size as a result of removal of inhibition of periosteal apposition, while failed endosteal apposition produces thin cortices and trabeculae in the smaller bone. In males, androgen deficiency produces reduced periosteal and endosteal apposition, reduced bone size, and cortical and trabecular thickness. At completion of longitudinal growth, advancing age is associated with emergence of a negative bone balance in each basic multicellular unit (BMU) because of reduced bone formation. Bone loss occurs, but slowly because the remodeling rate is slow. In midlife, in females, estrogen deficiency increases remodeling rate, increases the volume of bone resorbed, and decreases the volume of bone formed in each of the numerous BMUs remodeling bone on its endosteal (endocortical, trabecular, intracortical) surfaces so bone loss accelerates. In males, remodeling rate remains slow and is driven largely by reduced bone formation in the BMU. Hypogonadism in 20% to 30% of elderly men contributes to bone loss. In both sexes, calcium malabsorption and secondary hyperparathyroidism may partly be sex-hormone dependent and contributes to cortical bone loss. Concurrent periosteal apposition partly offsets endosteal bone loss, but less so in women than in men. More women than men fracture because their smaller skeleton incurs greater architectural damage and adapts less by periosteal apposition. Sex hormone deficiency during growth and aging is pivotal in the pathogenesis of bone fragility.
Seeman
Ego
E
Department of Endocrinology, Austin Hospital, Heidelberg 3084, Melbourne, Australia. egos@unimelb.edu.au
D015502:Absorptiometry, Photon; D000367:Age Factors; D000368:Aged; D000728:Androgens / Q000172:deficiency*; D015519:Bone Density / Q000502:physiology; D001862:Bone Resorption / Q000503:physiopathology*; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005598:Fractures, Spontaneous / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000175:diagnosis / Q000503:physiopathology*; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012737:Sex Factors
D000728:Androgens; D004967:Estrogens