Growth hormone, insulin-like growth factors, and the senescent skeleton: Ponce de Leon's Fountain revisited?
As the population ages, the prevalence of osteoporosis will continue to rise. Yet, the mechanisms leading to age-related bone loss remain poorly defined. Furthermore, extensive longitudinal studies of bone mass, especially in the three decades beyond menopause, have not been completed. Although calciotropic hormones, growth hormone (GH), and insulin-like growth factor-I (IGF-I) change with age, it is not certain if these changes are responsible for age-related bone loss. Nor is it clear if the "senescent" osteoblast is fully responsive to growth factor stimulation. To complicate matters further, both circulatory and skeletal IGF regulatory systems are extremely redundant. Changes in serum IGFs may lead to compensatory alterations in IGF receptor number, IGF binding protein (IGFBP) synthesis, or IGFBP catabolism. What is measured in serum, may, in the end, be either a mirror or a mirage of skeletal IGF action! Clinical trials with "replacement" doses of GH or IGF-I are underway. But, critical evidence does not yet support the concept that a true "sommatopause" alters bone remodeling. Moreover, only scarce data exist that GH augments bone formation or prevents bone loss in the elderly. As clinicians expand the use of recombinant growth factors to elders, ethical and clinical issues surrounding administration of the new "fountain of youth" will be revisited. For basic scientists studying skeletal growth factors and their relationship to senescence, significant questions remain unanswered. New technological advances will provide clues about the basic mechanisms of skeletal aging.(ABSTRACT TRUNCATED AT 250 WORDS)
Rosen
C J
CJ
St. Joseph Hospital, Bangor, Maine 04401.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015519:Bone Density / Q000502:physiology; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology; D002648:Child; D005260:Female; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000502:physiology; D010024:Osteoporosis / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone