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 logitudinal 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 “sensecent” osteoblast is fully responsive to growth factor stimulation. To complicate matters further, both circulatory and skeletal IFG regulatory systems are extremely redundant. Changes in serum IFGs may lead to compensatory alterations in 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, maya, in the end, be either a mirror or a rirage of skeletal IGF action! Clinical trials with “replacement” doses of GH or IGF-I are underway. But, critical efidence 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. But, until these findings are validated, scientists and clinicians will have difficulty judging the role of growth factors in halting, or reversing, the inexorable consequences of aging.     

Does skeletal anatomy reflect adaptation to locomotor patterns? cortical and trabecular architecture in human and nonhuman anthropoids

Although the correspondence between habitual activity and diaphyseal cortical bone morphology has been demonstrated for the fore- and hind-limb long bones of primates, the relationship between trabecular bone architecture and locomotor behavior is less certain. If sub-articular trabecular and diaphyseal cortical bone morphology reflects locomotor patterns, this correspondence would be a valuable tool with which to interpret morphological variation in the skeletal and fossil record. To assess this relationship, high-resolution computed tomography images from both the humeral and femoral head and midshaft of 112 individuals from eight anthropoid genera (Alouatta, Homo, Macaca, Pan, Papio, Pongo, Trachypithecus, and Symphalangus) were analyzed. Within-bone (sub-articular trabeculae vs. mid-diaphysis), between-bone (forelimb vs. hind limb), and among-taxa relative distributions (femoral:humeral) were compared. Three conclusions are evident: (1) Correlations exists between humeral head sub-articular trabecular bone architecture and mid-humerus diaphyseal bone properties; this was not the case in the femur. (2) In contrast to comparisons of inter-limb diaphyseal bone robusticity, among all species femoral head trabecular bone architecture is significantly more substantial (i.e., higher values for mechanically relevant trabecular bone architectural features) than humeral head trabecular bone architecture. (3) Interspecific comparisons of femoral morphology relative to humeral morphology reveal an osteological \"locomotor signal\" indicative of differential use of the forelimb and hind limb within mid-diaphysis cortical bone geometry, but not within sub-articular trabecular bone architecture.     

Homogenization theory and digital imaging: A basis for studying the mechanics and design principles of bone tissue

Bone tissue is a complex multilevel composite which has the ability to sense ad respond to its mechanical environment. It is believed that bone cells called osteocytes within the bone matrix sense the mechanical environment and determine whether structural alterations are needed. At present it is not known, however, how loads are transferred from the whole bone level to cells. A computational procedure combining representative volume element (RVE) based homogenization theory with digital imaging is proposed to estimate strains at various levels of bone structure. Bone tissue structural organization and RVE based analysis are briefly reviewed. The digital image based computational procedure was applied to estimate strains in individual trabeculae (first-level microstructure). Homogenization analysis of an idealized model was used to estimate strains at one level of bone structure around osteocyte lacunae (second-level trabecular microstructure). The results showed that strain at one level of bone structure is amplified to a broad range at the next microstructural level. In one case, a zeor-level tensile principal strain of 495 muE engendered strains ranging between -1000 and 7000 muE in individual trabeculae (first-level microstructure). Subsequently, a first-level tensile principal strains of 1325 muE within an inidividual trabecula engendered strains ranging between 782 and 2530 muE around osteocyte lacunae. Lacunar orientation was found to influence strains around osteocyte lacunae much more than lacunar ellipticity. In conclusion, the computational procedure combining homogenization theory with digital imaging can proveide estimates of cell level strains within whole bones. Such results may be used to bridge experimental studies of bone adaptation at the whole bone and cell culture level. (c) 1994 John Wiley & Sons, Inc.     

Dynamic bone remodeling in later Pleistocene fossil hominids

Histomorphometric analysis of femoral and tibial diaphyseal fragments from seven Late Archaic and three Early Modern humans are compared with those of the Pecos, a pre-Columbian Native American population. The ten samples, from Broken Hill (EM-793), Shanidar 2, 3, 4, 5, and 6, Tabun 1, and Skhul 3, 6, and 7, provide age-at-death results consistent with earlier estimates for most individuals. The Pleistocene groups exhibit less bone turnover and smaller osteons than Recent populations. Resorption and formation were both coupled and balanced in these Pleistocene populations, but the overall vigor of individual cells from both the osteoclast and osteoblast cell lines was less than in Recent populations. Thus the greater bone mass in Later Pleistocene members of the genus Homo is not the result of higher levels of bone turnover, at least among adults. © 1996 Wiley-Liss, Inc.     

Effects of age,sex, and heredity on measures of bone mass in baboons (Papio hamadryas)

Abstract: Bone mass and bone density were estimated in 219 pedigreed baboons (Papio hamadryas) by radiographic morphometry of the left second metacarpal. Compact bone width (total bone width – medullary canal diameter) and bone ratio (compact bone width/total bone width) decreased with increasing age squared in both sexes. The heritability of medullary canal diameter was 0.64±0.11, of compact bone width was 0.40±0.15 and of bone ratio was 0.67±0.13. The results indicate baboons are a useful model for studies of age, sex and genetic effects on bone mass.