bone mineralization density distribution; bone turnover; mathematical model; osteoporosis; risedronate treatment
Abstract :
[en] The heterogeneous distribution of mineral content in trabecular bone reflects the continuous renewal of bone material in bone remodeling and the subsequent increase in mineral content in the newly formed bone packets. The bone mineralization density distribution (BMDD) is typically used to describe this nonuniform mineral content of the bone matrix. Our mathematical model describes changes of the BMDD of trabecular bone as a function of bone resorption and deposition rates and the mineralization kinetics in a newly formed bone packet. Input parameters used in the simulations were taken from experimental studies. The simulations of the time evolution of the BMDD after increase in bone turnover (perimenopausal period) resulted in a shift of the BMDD toward lower values of the mineral content. Transiently, there was a broadening of the BMDD configuration partly showing two peaks, which points to a strongly heterogeneous distribution of the mineral. Conversely, when the remodeling rate was reduced (antiresorptive therapy), the BMDD shifted toward higher values of the mineral content. There was a transient narrowing of the distribution before broadening again to reach the new steady state. Results from this latter simulation are in good agreement with measurements of the BMDD of patients after 3 and 5 yr of treatment with risedronate. Based on available experimental data on bone remodeling, this model gives reliable predictions of changes in BMDD, an important factor of bone material quality. With the availability of medications with a known effect on bone turnover, this knowledge opens the possibility for therapeutic manipulation of the BMDD.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Ruffoni, Davide ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Mécanique des matériaux biologiques et bioinspirés
Effect of Temporal Changes in Bone Turnover on the Bone Mineralization Density Distribution: A Computer Simulation Study
Publication date :
2008
Journal title :
Journal of Bone and Mineral Research
ISSN :
0884-0431
eISSN :
1523-4681
Publisher :
Wiley-Blackwell, Hoboken, United States - New Jersey
Volume :
23
Issue :
12
Pages :
1905-1914
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Alliance for Better Bone Health
Commentary :
Dr Phipps is a full-time employee of Procter & Gamble Pharmaceuticals and a member of the Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and sanofi-aventis). Funding for the study on the BMDD with risedronate treatment was provided by the Alliance for Better Bone Health. All other authors state that they have Do conflicts of interest.
WHO Study Group 1994 Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis. World Health Organization, Geneva, Switzerland.
Seeman E, Delmas PD 2006 Mechanisms of disease - bone quality - the material and structural basis of bone strength and fragility. N Engl J Med 354:2250-2261.
Bouxsein ML 2003 Bone quality: An old concept revisited. Osteoporos Int 14:S1-S2.
Felsenberg D, Boonen S 2005 The bone quality framework: Determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27:1-11.
Weiner S, Wagner HD 1998 The material bone: Structure mechanical function relations. Annu Rev Mater Sci 28:271-298.
Hernandez CJ, Gupta A, Keaveny TM 2006 A biomechanical analysis of the effects of resorption cavities on cancellous bone strength. J Bone Miner Res 21:1248-1255.
Gibson LJ 2005 Biomechanics of cellular solids. J Biomech 38:377-399.
Fratzl P, Gupta HS, Paschalis EP, Roschger P 2004 Structure and mechanical quality of the collagen-mineral nano-composite in bone. J Mater Chem 14:2115-2123.
Eriksen EF 1986 Normal and pathological remodeling of human trabecular bone: 3-dimensional reconstruction of the remodeling sequence in normals and in metabolic bone-disease. Endocr Rev 7:379-408.
Parfitt AM 1994 Osteonal and hemi-osteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 55:273-286.
Boivin G, Meunier PJ 2003 Methodological considerations in measurement of bone mineral content. Osteoporos Int 14:S22-S27.
Robling AG, Castillo AB, Turner CH 2006 Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8:455-498.
Fratzl P, Weinkamer R 2007 Nature's hierarchical materials. Prog Mater Sci 52:1263-1334.
Jaasma MJ, Bayraktar HH, Niebur GL, Keaveny TM 2002 Biomechanical effects of intraspecimen variations in tissue modulus for trabecular bone. J Biomech 35:237-246.
van der Linden JC, Birkenhager-Frenkel DH, Verhaar JAN, Weinans H 2001 Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution. J Biomech 34:1573-1580.
Turner CH 2002 Biomechanics of bone: Determinants of skeletal fragility and bone quality. Osteoporos Int 13:97-104.
Ruegsegger P, Koller B, Muller R 1996 A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int 58:24-29.
Roschger P, Fratzl P, Eschberger J, Klaushofer K 1998 Validation of quantitative backscattered electron imaging for the measurement of mineral density distribution in human bone biopsies. Bone 23:319-326.
Roschger P, Paschalis EP, Fratzl P, Klaushofer K 2008 Bone mineralization density distribution in health and disease. Bone 42:456-466.
Roschger P, Gupta HS, Berzlanovich A, Ittner G, Dempster DW, Fratzl P, Cosman F, Parisien M, Lindsay R, Nieves JW, Klaushofer K 2003 Constant mineralization density distribution in cancellous human bone. Bone 32:316-323.
Zoehrer R, Roschger P, Paschalis EP, Hofstaetter JG, Durchschlag E, Fratzl P, Phipps R, Klaushofer K 2006 Effects of 3-and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women. J Bone Miner Res 21:1106-1112.
Ruffoni D, Fratzl P, Roschger P, Klaushofer K, Weinkamer R 2007 The bone mineralization density distribution as a fingerprint of the mineralization process. Bone 40:1308-1319.
Eriksen EF, Hodgson SF, Eastell R, Cedel SL, Ofallon WM, Riggs BL 1990 Cancellous bone remodeling in type-I (postmenopausal) osteoporosis: Quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels. J Bone Miner Res 5:311-319.
Recker R, Lappe J, Davies KM, Heaney R 2004 Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients. J Bone Miner Res 19:1628-1633.
Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ 1997 Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest 100:1475-1480.
Eriksen EF, Melsen F, Sod E, Barton I, Chines A 2002 Effects of long-term risedronate on bone quality and bone turnover in women with postmenopausal osteoporosis. Bone 31:620-625.
Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R 2003 Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: A paired study before and after treatment. J Clin Endocrinol Metab 88:1150-1156.
Hernandez CJ, Beaupre GS, Carter DR 2003 A theoretical analysis of the changes in basic multicellular unit activity at menopause. Bone 32:357-363.
Garnero P, SornayRendu E, Chapuy MC, Delmas PD 1996 Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 11:337-349.
Ebeling PR, Atley LM, Guthrie JR, Burger HG, Dennerstein L, Hopper JL, Wark JD 1996 Bone turnover markers and bone density across the menopausal transition. J Clin Endocrinol Metab 81:3366-3371.
van der Linden JC, Verhaar JA, Pols HA, Weinans H 2003 A simulation model at trabecular level to predict effects of anti-resorptive treatment after menopause. Calcif Tissue Int 73:537-544.
Borah B, Dufresne TE, Chmielewski PA, Johnson TD, Chines A, Manhart MD 2004 Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. Bone 34:736-746.
Stauber M, Muller R 2006 Age-related changes in trabecular bone microstructures: Global and local morphometry. Osteoporos Int 17:616-626.
Mellstrom DD, Sorensen OH, Goemaere S, Roux C, Johnson TD, Chines AA 2004 Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif Tissue Int 75:462-468.
Ste-Marie LG, Sod E, Johnson T, Chines A 2004 Five years of treatment with risedronate and its effects on bone safety in women with postmenopausal osteoporosis. Calcif Tissue Int 75:469-476.
Borah B, Ritman EL, Dufresne TE, Jorgensen SM, Liu S, Sacha J, Phipps RJ, Turner RT 2005 The effect of risedronate on bone mineralization as measured by micro-computed tomography with synchrotron radiation: Correlation to histomorphometric indices of turnover. Bone 37:1-9.
Borah B, Dufresne TE, Ritman EL, Jorgensen SM, Liu S, Chmielewski PA, Phipps RJ, Zhou XJ, Sibonga JD, Turner RT 2006 Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: Sequential triple biopsy studies with micro-computed tomography. Bone 39:345-352.
Fratzl P, Roschger P, Fratzl-Zelman N, Paschalis EP, Phipps R, Klaushofer K 2007 Evidence that treatment with risedronate in women with postmenopausal osteoporosis affects bone mineralization and bone volume. Calcif Tissue Int 81:73-80.
Seeman E 2007 Is a change in bone mineral density a sensitive and specific surrogate of anti-fracture efficacy? Bone 41:308-317.
Heaney RP 1994 The bone-remodeling transient: Implications for the interpretation of clinical studies of bone mass change. J Bone Miner Res 9:1515-1523.
Heaney RP 2003 Is the paradigm shifting? Bone 33:457-465.
Roschger P, Dempster DW, Zhou H, Paschalis EP, Silverberg SJ, Shane E, Bilezikian JP, Klaushofer K 2007 New observations on bone quality in mild primary hyperparathyroidism as determined by quantitative backscattered electron imaging. J Bone Miner Res 22:717-723.
Boivin G, Meunier PJ 2002 Changes in bone remodeling rate influence the degree of mineralization of bone. Connect Tissue Res 43:535-537.
Roschger P, Plenk H, Klaushofer K, Eschberger J 1995 A new scanning electron-microscopy approach to the quantification of bone mineral distribution: Backscattered electron image grey-levels correlated to calcium K-alpha-line intensities. Scanning Microsc 9:75-88.
Roschger P, Fratzl P, Eschberger J, Klaushofer K 1999 Response to the letter to the editor by E. G. Vajda and J. G. Skedros. Bone 24:620-621.
Recker R, Lappe J, Davies K, Heaney R 2000 Characterization of perimenopausal bone loss: A prospective study. J Bone Miner Res 15:1965-1973.
Jerome CP 1989 Estimation of the bone mineral density variation associated with changes in turnover rate. Calcif Tissue Int 44:406-410.
Hernandez CJ, Beaupre GS, Marcus R, Carter DR 2001 A theoretical analysis of the contributions of remodeling space, mineralization, and bone balance to changes in bone mineral density during alendronate treatment. Bone 29:511-516.
Lacy ME, Bevan JA, Boyce RW, Geddes AD 1994 Antiresorptive drugs and trabecular bone turnover: Validation and testing of a computer model. Calcif Tissue Int 54:179-185.
Bjarnason NH 2004 Ten years of alendronate treatment for osteoporosis in postmenopausal women. N Engl J Med 351:190-192.
Martin RB 1991 On the significance of remodeling space and activation rate changes in bone remodeling. Bone 12:391-400.
Hazelwood SJ, Martin RB, Rashid MM, Rodrigo JJ 2001 A mechanistic model for internal bone remodeling exhibits different dynamic responses in disuse and overload. J Biomech 34:299-308.
Martin RB 1984 Porosity and specific surface of bone. Crit Rev Biomed Eng 10:179-222.
Le Veque LR 2002 Finite Volume Methods for Hyperbolic Problems. Cambridge University Press, Cambridge, UK.
Zizak I, Roschger P, Paris O, Misof BM, Berzlanovich A, Bernstorff S, Amenitsch H, Klaushofer K, Fratzl P 2003 Characteristics of mineral particles in the human bone/cartilage interface. J Struct Biol 141:208-217.
Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L, Amin S, Rouleau PA, Khosla S 2008 A population-based assessment of rates of bone loss at multiple skeletal sites: Evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res 23:205-214.
