From Density to Structure: Growing Up and Growing Old on the Surfaces of Bone

Abstract

The reason for comparing ethnic and gender differences in skeletal mass, size, and architecture is to define the structural basis underlying the differences in fracture rates seen between these groups. Han et al. have examined histomorphometric and biochemical measurements of bone turnover in premenopausal and postmenopausal white and black women in this, and the December 1996, edition of the Journal.1, 2 The authors take us on a journey across ethnic groups, across age, and across menopause, exploring the static and dynamic parameters of bone resorption and formation on the surfaces of the iliac crest—on the endosteal surface of its trabeculae, and on the endocortical, intracortical, and periosteal surfaces of its cortex. The studies are a contribution because they answer and raise questions concerning ethnic differences in bone fragility and show us a way of thinking about the skeleton that is a little different. The main observations presented in these two manuscripts are: (i) the higher trabecular bone density in blacks is due to greater trabecular thickness not trabecular numbers; (ii) the lower bone turnover in blacks is likely to be due to the lower bone surface-to-volume ratio of their cancellous bone; (iii) the increase in bone remodeling associated with aging is similar in blacks and whites; (iv) despite the thicker trabeculae and lower bone turnover, blacks are not spared the loss of bone and the architectural disruption that accompanies advancing age. The work of Han et al. is a contribution in the broader context of the study of bone remodeling: the surface phenomenon that forms the morphological basis of bone turnover and bone loss. These studies, and a great deal of research by the senior investigator of the group, Michael Parfitt, emphasize the need to study the surfaces of the skeleton. The purpose of this review is to amplify this message by (i) drawing attention to several misconceptions regarding the earlier gain and later loss of bone that have developed because of reliance on bone densitometry as the investigative method of choice or convenience in the study of skeletal health and disease, and by (ii) demonstrating that the behavior of each of the surfaces of the skeleton, during both growth and aging, differ from one ethnic group to another and in men and women. The comparison of the remodeling behavior of these surfaces during growth and aging in women of different ethnic groups, in men of different ethnic groups, and women and men of the same ethnic group may be a step toward identifying the structural components responsible for the differing fracture patterns seen in the groups. In this computerized era, we seem to have forgotten that bone biology is the study of the behavior of the surfaces of the skeleton. In the almost 3 years from October 1993 to August 1996, there have been approximately 2438 peer-reviewed manuscripts and 511 reviews in the main English-language medical journals dealing directly or closely with osteoporosis.3 Of the peer-reviewed manuscripts, 1428 (approximately 60%) were clinical studies in humans, of which 696 (50%) involved densitometry as the main investigative tool. Bone histomorphometry appeared in 37 papers (2.6%). Of the 633 papers published in 34 issues of the Journal in the last 3 years, 302 were studies in humans, of which 165 (55%) involved densitometry while 58 (20%) used histomorphometry. Densitometry has made many important contributions to the study of the definition, epidemiology, detection, pathogenesis, prevention, and treatment of osteoporosis, but this has occurred at a price. The three-dimensional world of bone is presented as a lump sum, the net integrated result of the amounts of bone added and removed on its surfaces and from within its cortices. We obtain a mineral mass measured within a projected area or derived volume of a region called an areal or volumetric apparent "density." Areal and apparent are dropped for the sake of brevity but at the price of understanding. Increasing and decreasing density are not changes in particle number per unit area or volume as "density" implies. The complexity of the structural basis underlying the increase in bone density during growth, and decrease in bone density during aging, is not remotely conveyed by the imagery of this term. This deceptively simple word is securely entrenched in the jargon of the field and used as if it were an indivisible, unambiguous, and universally understood unit of bone. We consider the effects of dietary calcium, exercise, and drugs on bone "density," the genetic and environmental factors responsible for the increase in "density" during growth, and decrease in "density" during aging. The choice of the word matters because it affects the way we conceptualize the skeleton (or fail to), the way we develop our thinking (or fail to), and the way we direct (or misdirect) our research. I propose that the integrated projected image of bone mass produced by the photon attenua