Biomechanical background for a noninvasive assessment of bone strength and muscle-bone interactions.

New concepts and methods of study in bone biomechanics defy the prevailing idea that bone strength is determined by a systemically-controlled "mineralized mass" which grows until reaching a peak and then is lost at individually-specific rates. In case of bones, "mass" represents actually the substratum of a structure, the stiffness of which does not depend on the mass, but on the intrinsic stiffness and the spatial distribution of the mineralized material. A feed-back system called "bone mechanostat" seems to orient the osteoblastic and osteoclastic processes of bone, modeling and remodeling, according to the sensing by osteocytes of strains caused in the structure by mechanical usage of the skeleton, in specific directions as determined principally by the customary contractions of regional muscles and impact forces. The endocrine-metabolic systems, crucial for the normal skeletal development, modulate the work of osteocytes, blasts and clasts in a systemic way (i.e., not related to a specific direction of the stimuli). Therefore, they tend actually to interact with, rather than contribute to, the biomechanical control of bone structure. Furthermore, no feed-back loop enabling a cybernetic relationship of those systems with bone is known. Instead of passively letting hormones regulate their "mass" in order to optimize their strength, bones would actively self-regulate their architecture following an anisotropic pattern in order to optimize their stiffness (the only known variable to be ever controlled in the skeleton) and strength "despite of" the endocrine systems. Three practical questions derive from those ideas: 1. Osteoporoses are not "intense osteopenias" but "osteopenic fragilities". 2. The diagnosis of osteopenia could be solved densitometrically; but that of bone fragility is a biomechanical problem which requires auxiliary resources for evaluating the stiffness and the spatial distribution of the mineralized material. 3. Osteopenias and osteoporoses should be on time evaluated as related to the mass or strength of the regional muscles, respectively, in order to differentiate between the "primary" (intrinsic lesion of the mechanostat) or "secondary" (systemic) etiologies and the biomechanical origin (disuse) in each case, with important therapeutic implications.

[1]  D Vashishth,et al.  Bone stiffness predicts strength similarly for human vertebral cancellous bone in compression and for cortical bone in tension. , 2000, Bone.

[2]  L. Claes,et al.  Prediction of fracture load at different skeletal sites by geometric properties of the cortical shell , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  J. Zanchetta,et al.  Effects of Teriparatide [Recombinant Human Parathyroid Hormone (1–34)] on Cortical Bone in Postmenopausal Women With Osteoporosis , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  W. Landis The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix. , 1995, Bone.

[5]  S. Majumdar,et al.  Correlation of Trabecular Bone Structure with Age, Bone Mineral Density, and Osteoporotic Status: In Vivo Studies in the Distal Radius Using High Resolution Magnetic Resonance Imaging , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  O. Johnell,et al.  Prediction of fracture from low bone mineral density measurements overestimates risk. , 2000, Bone.

[7]  H. Frost Skeletal structural adaptations to mechanical usage (SATMU): 2. Redefining Wolff's Law: The remodeling problem , 1990, The Anatomical record.

[8]  Yuehuei H. An,et al.  Mechanical testing of bone and the bone-implant interface , 1999 .

[9]  G R Cointry,et al.  Analysis of biomechanical effects on bone and on the muscle-bone interactions in small animal models. , 2001, Journal of musculoskeletal & neuronal interactions.

[10]  V. Preedy,et al.  Skeletal muscle : pathology, diagnosis and management of disease , 2002 .

[11]  H. Frost,et al.  Bone mass, bone strength, muscle–bone interactions, osteopenias and osteoporoses , 2003, Mechanisms of Ageing and Development.

[12]  Ala M Mohamed,et al.  Bone loss and bone size after menopause. , 2003, The New England journal of medicine.

[13]  J. Currey The effect of porosity and mineral content on the Young's modulus of elasticity of compact bone. , 1988, Journal of biomechanics.

[14]  J. Compston,et al.  Connectivity of cancellous bone: assessment and mechanical implications. , 1994, Bone.

[15]  F. G. Evans,et al.  The mechanical properties of bone. , 1969, Artificial limbs.

[16]  Timothy G. Lohman,et al.  Dual-Energy X-Ray Absorptiometry , 2005 .

[17]  K. Faulkner,et al.  Bone Matters: Are Density Increases Necessary to Reduce Fracture Risk? , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  W C Hayes,et al.  Biomechanics of fracture risk prediction of the hip and spine by quantitative computed tomography. , 1991, Radiologic clinics of North America.

[19]  J. Zanchetta,et al.  Densitometric and tomographic analyses of musculoskeletal interactions in humans. , 2000, Journal of musculoskeletal & neuronal interactions.

[20]  R. B. Ashman,et al.  Young's modulus of trabecular and cortical bone material: ultrasonic and microtensile measurements. , 1993, Journal of biomechanics.

[21]  J. Currey The design of mineralised hard tissues for their mechanical functions. , 1999, The Journal of experimental biology.

[22]  M. Visser,et al.  Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass. Health, Aging, and Body Composition Study--Dual-Energy X-ray Absorptiometry and Body Composition Working Group. , 1999, Journal of applied physiology.

[23]  M. Laval-jeantet,et al.  CT image analysis of the vertebral trabecular network in vivo , 1992, Calcified Tissue International.

[24]  H. Frost From Wolff's law to the Utah paradigm: Insights about bone physiology and its clinical applications , 2001, The Anatomical record.

[25]  H. Frost,et al.  Perspectives: Some Roles of Mechanical Usage, Muscle Strength, and the Mechanostat in Skeletal Physiology, Disease, and Research , 1998, Calcified Tissue International.

[26]  L. Lanyon Osteocytes, strain detection, bone modeling and remodeling , 2005, Calcified Tissue International.

[27]  Frost Hm,et al.  The mechanostat: a proposed pathogenic mechanism of osteoporoses and the bone mass effects of mechanical and nonmechanical agents. , 1987 .

[28]  G. Marotti,et al.  The osteocyte as a wiring transmission system. , 2000, Journal of musculoskeletal & neuronal interactions.

[29]  H. Genant,et al.  Bone Densitometry and Osteoporosis , 1998, Springer Berlin Heidelberg.

[30]  P Zioupos,et al.  Mechanical properties and the hierarchical structure of bone. , 1998, Medical engineering & physics.

[31]  H. Plotkin,et al.  Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. , 1998, Bone.

[32]  J. Zanchetta,et al.  Mechanical validation of a tomographic (pQCT) index for noninvasive estimation of rat femur bending strength. , 1996, Bone.

[33]  Analysis of the Structure and Strength of Bones in Celiac Disease Patients , 2003 .

[34]  Harold M. Frost,et al.  The Utah paradigm of skeletal physiology: an overview of its insights for bone, cartilage and collagenous tissue organs , 2000, Journal of Bone and Mineral Metabolism.

[35]  R. Capozza,et al.  Noninvasive Analysis of Bone Mass, Structure and Strength , 2002 .

[36]  高田信二郎 3.骨塩定量分析器:Dual energy X-ray absorptiometry を用いた骨密度および軟部組織組成の解析 , 2003 .

[37]  P. Antich,et al.  Bone Elasticity and Ultrasound Velocity Are Affected by Subtle Changes in the Organic Matrix , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[38]  H. Frost Defining osteopenias and osteoporoses: another view (with insights from a new paradigm). , 1997, Bone.

[39]  F. Rauch,et al.  The development of bone strength at the proximal radius during childhood and adolescence. , 2001, The Journal of clinical endocrinology and metabolism.

[40]  H. Frost,et al.  The mechanostat: a proposed pathogenic mechanism of osteoporoses and the bone mass effects of mechanical and nonmechanical agents. , 1987, Bone and mineral.

[41]  S. A. Wainwright,et al.  Mechanical Design in Organisms , 2020 .

[42]  O. Johnell,et al.  Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures , 1996 .

[43]  U. Koch,et al.  Bone-muscle strength indices for the human lower leg. , 2000, Bone.

[44]  G. Wassmer,et al.  Influence of puberty on muscle area and cortical bone area of the forearm in boys and girls. , 2000, The Journal of clinical endocrinology and metabolism.

[45]  C T Rubin,et al.  Functional strains and cortical bone adaptation: epigenetic assurance of skeletal integrity. , 1990, Journal of biomechanics.

[46]  J. Ferretti Peripheral Quantitative Computed Tomography for Evaluating Structural and Mechanical Properties of Small Bone , 1999 .

[47]  J. Ferretti Biomechanical Properties of Bone , 1998 .

[48]  J. Kanis,et al.  DIAGNOSIS OF OSTEOPOROSIS , 2016 .

[49]  J. Kanis,et al.  Practical guide for the use of bone mineral measurements in the assessment of treatment of osteoporosis: A position paper of the european foundation for osteoporosis and bone disease , 2005, Osteoporosis International.

[50]  C. Reiners,et al.  Bone Quality Parameters of the Distal Radius as Assessed by pQCT in Normal and Fractured Women , 2001, Osteoporosis International.

[51]  H. Frost,et al.  On new opportunities for absorptiometry. , 1998, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[52]  Susan R. Johnson,et al.  Osteoporosis prevention, diagnosis, and therapy. , 2001, JAMA.

[53]  L E Lanyon,et al.  Functional strain in bone tissue as an objective, and controlling stimulus for adaptive bone remodelling. , 1987, Journal of biomechanics.

[54]  D. Felsenberg,et al.  Comments on the Hypotheses Underlying Fracture Risk Assessment in Osteoporosis as Proposed by the World Health Organization , 1999, Calcified Tissue International.

[55]  W. Jee,et al.  Integrated Bone Tissue Physiology: Anatomy and Physiology , 2001 .

[56]  L. Mosekilde,et al.  Estimation of vertebral body strength by dual photon absorptiometry in elderly individuals: comparison between measurements of total vertebral and vertebral body bone mineral. , 1993, Bone.