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Title: The structural and biomechanical basis of the gain and loss of bone strength in women and men.
Austin Authors: Seeman, Ego 
Affiliation: Department of Endocrinology and Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Melbourne 3084, Australia
Issue Date: 1-Mar-2003
Publication information: Endocrinology and Metabolism Clinics of North America; 32(1): 25-38
Abstract: Structural failure (fracture) is a problem in biomechanics. Its solution resides, in part, in identifying the material and structural properties of bone that determine its mechanical resistance to structural failure. Bones must be stiff so that they do not bend when loaded, otherwise movement against gravity would not be possible. However, bones must also be flexible, otherwise their ability to absorb energy by elastic and plastic deformation will decrease and the energy imparted will be dissipated only by microdamage or complete fracture. Thus, failure may occur if bones deform too much (exceeding their peak strain) or too little (exceeding their peak stress). Phylogeny and ontogeny make bone "just right" for the functions it is predicted to perform, but the genetic material was not warned about the increased longevity the female enjoys after ovarian failure. Age-related and menopause-related abnormalities in bone remodeling produce loss of the material and structural properties that no longer keep bone "just right". High remodeling reduces the mineral content of bone tissue resulting in loss of stiffness (resistance to shortening in compression and lengthening in tension when loaded). Sex hormone deficiency increases the volume of bone resorbed and reduces the volume of bone formed in each BMU. Solutions to the biomechanic problem will emerge provided that the material and structural properties of bone that determine its strength are measured and studied. Drugs are available to reduce remodeling rate so that there is more time for completion of secondary mineralization to restore bone stiffness. If remodeling is suppressed too much the production of microdamage may increase as homogeneous and highly mineralized bone is less resistant to microdamage progression while reduced remodeling targeted to microdamage may result in microdamage accumulation. Drugs are available to reduce osteoclastic bone resorption and increase osteoblastic bone formation, which together will restore bone balance in the BMU and so prevent further loss of bone mass, prevent thinning and loss of trabeculae, thinning of cortices, and progression of porosity. These approaches prevent the progression of fragility but will not restore bone architecture. Even if a positive BMU balance is achieved, drugs that reduce remodeling are unlikely to reverse the structure damage. Slow remodeling means there are too few remodeling foci depositing their small net positive bone volume to progressively thicken cortices or trabeculae. Agents that are anabolic, that increase bone formation on the periosteal and endosteal surfaces are needed to restore the structure of bone. Other articles in this volume address this challenge. We do not understand the proportional contributions made by differences in bone size, cortical thickness, trabecular number, thickness, connectivity, tissue mineral content, microdamage burden, osteocyte density, porosity, to differences in spine and hip fracture rates within a sex, between sexes, between races, or between treatment, and control arms in clinical trials. The challenge for the future is to measure these specific materials and structural determinants of bone strength. Whether a combination of these material and structural properties will more accurately identify women likely to sustain fractures, or improve approaches to drug therapy is unknown. The quest to eliminate fragility fractures is a distant horizon seen through a glass darkly at this time.
Gov't Doc #: 12699291
Type: Journal Article
Subjects: Animals
Biomechanical Phenomena
Bone Development.physiology
Bone Remodeling.physiology
Bone and Bones.anatomy & histology.physiology
Appears in Collections:Journal articles

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