Upper Limb Bone Health: Cadaveric, Imaging and Clinical Studies With Special Emphasis on Peripheral Quantitative Computed Tomography

Introduction

Osteoporotic fractures are a major health care problem. A radial fracture is an important risk factor for osteoporosis that should initiate the assessment of bone health.

Purpose

To validate pQCT measures of bone in aged cadaveric radii.
To examine side-side differences in radial bone variables after disuse.
To test a novel intervention for secondary prevention of osteoporosis after an index radial fracture.

Methods

Study Design: Part I: Parts IA and IB are descriptive cadaveric studies. Part 2: Cross-sectional observational studies of bone response to disuse; Part 3: Part 3A is a 6-month intervention of secondary prevention of osteoporosis following a fragility fracture. Part 3B uses a questionnaire to ascertain barriers to investigation after fracture.

Participants: Part I: Cadaveric specimens from women (73 to 88 years) for Parts IA and IB. Part 2A: Women (52-87 years) who sustained a distal radius fracture and Part 2B: women and men (52 to 79 years) who had suffered a stroke. Part 3A: Women and men (50-90 years) with a fragility fracture; and Part 3B: physicians in British Columbia.

Results Part I: With different pQCT acquisition-analysis protocols, total bone area varied by 3-34%; cortical area varied by 3-30% and total content by 6-45% from a criterion standard. Total bone content of the distal radius explained between 74 and 81% of bone strength. Part 2: There was a significant decrease in bone strength in participants who had upper limb disuse because of stroke or fracture. Part 3: A patient and physician intervention improved bone health investigation rate by a factor of 3.1 times (RR) after fragility fracture. BC doctors reported few barriers to investigating osteoporosis.

Summary: Peripheral QCT acquisition and analysis protocols significantly influenced outcome variables. Patients do not have "normal" bone strength after fracture or stroke. In particular, there is an increased risk for non-dominant radial fractures to have lower bone strength and be associated with poorer limb function, compared with a dominant radial fracture. Physicians report no barriers to investigation after a fragility radial fracture and a systematic intervention may best address secondary prevention of osteoporosis.

Year	Entry
1998	Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. October 1998;355(suppl):S7-S21.
2002	Brown JP, Josse RG; Scientific Advisory Council of the Osteoporosis Society of Canada. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. Can Med Assoc J. November 12, 2002;167(suppl 10):S1-S34.
1994	Parfitt AM. Osteonal and hemi‐osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem. July 1994;55(3):273-286.
2002	Currey JD. Bones: Structure and Mechanics. Princeton, NJ: Princeton University Press; 2002.
1996	Müller R, Hahn M, Vogel M, Delling G, Rüegsegger P. Morphometric analysis of noninvasively assessed bone biopsies: comparison of high-resolution computed tomography and histologic sections. Bone. March 1996;18(3):215-220.
2003	Kontulainen S, Sievänen H, Kannus P, Pasanen M, Vuori I. Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls. J Bone Miner Res. February 2003;18(2):352-359.
2001	Lanyon L, Skerry T. Postmenopausal osteoporosis as a failure of bone's adaptation to functional loading: a hypothesis. J Bone Miner Res. November 2001;16(11):1937-1947.
2000	Kanis JA, Johnell O, Oden A, Sernbo I, Redlund-Johnell I, Dawson A, De Laet C, Jonsson B. Long-term risk of osteoporotic fracture in Malmö. Osteoporos Int. September 2000;11(8):669-674.
1994	Spadaro JA, Werner FW, Brenner RA, Fortino MD, Fay LA, Edwards WT. Cortical and trabecular bone contribute strength to the osteopenic distal radius. J Orthop Res. March 1994;12(2):211-218.
2003	Muller ME, Webber CE, Bouxsein ML. Predicting the failure load of the distal radius. Osteoporos Int. June 2003;14(4):345-352.
1999	Cuddihy M-T, Gabriel SE, Crowson CS, O’Fallon WM, Melton LJ III. Forearm fractures as predictors of subsequent osteoporotic fractures. Osteoporos Int. June 1999;9(6):469-475.
1996	Augat P, Reeb H, Claes LE. Prediction of fracture load at different skeletal sites by geometric properties of the cortical shell. J Bone Miner Res. September 1996;11(9):1356-1363.
1984	Ashman RB, Cowin SC, Van Buskirk WC, Rice JC. A continuous wave technique for the measurement of the elastic properties of cortical bone. J Biomech. 1984;17(5):349-361.
1996	Genant HK, Engelke K, Fuerst T, Glüer C, Grampp S, Harris ST, Jergas M, Lang T, Lu Y, Majumdar S, Mathur A, Takada M. Noninvasive assessment of bone mineral and structure: state of the art. J Bone Miner Res. June 1996;11(6):707-730.
1987	Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: standardization of nomenclature, symbols, and units: report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res. December 1987;2(6):595-610.
2002	Turner CH. Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int. February 2002;13(2):97-104.
2004	Elliot-Gibson V, Bogoch ER, Jamal SA, Beaton DE. Practice patterns in the diagnosis and treatment of osteoporosis after a fragility fracture: a systematic review. Osteoporos Int. October 2004;15(10):767-778.
1995	Louis O, Boulpaep F, Willnecker J, Van den Winkel P, Osteaux M. Cortical mineral content of the radius assessed by peripheral QCT predicts compressive strength on biomechanical testing. Bone. March 1995;16(3):375-379.
2002	Eckstein F, Lochmüller E-M, Lill CA, Kuhn V, Schneider E, Delling G, Müller R. Bone strength at clinically relevant sites displays substantial heterogeneity and is best predicted from site-specific bone densitometry. J Bone Miner Res. January 2002;17(1):162-171.
1986	Mosekilde L, Mosekilde L. Normal vertebral body size and compressive strength: relations to age and to vertebral and iliac trabecular bone compressive strength. Bone. 1986;7(3):207-212.
1995	Turner CH, Owan I, Takano Y. Mechanotransduction in bone: role of strain rate. Am J Physiol Endocrinol Metab. September 1995;269(3):E438-E442.
2000	Fritton SP, McLeod KJ, Rubin CT. Quantifying the strain history of bone: spatial uniformity and self-similarity of low-magnitude strains. J Biomech. March 2000;33(3):317-325.
2003	Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Bone loss and bone size after menopause. NEJM. July 24, 2003;349(4):327-334.
2001	Currey JD. Bone strength: what are we trying to measure? Calcif Tiss Int. April 2001;68(4):205-210.
1999	Adami S, Gatti D, Braga V, Bianchini D, Rossini M. Site-specific effects of strength training on bone structure and geometry of ultradistal radius in postmenopausal women. J Bone Miner Res. January 1999;14(1):120-124.
2000	Haapasalo H, Kontulainen S, Sievänen H, Kannus P, Järvinen M, Vuori I. Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: a peripheral quantitative computed tomography study of the upper arms of male tennis players. Bone. September 2000;27(3):351-357.
1993	Nevitt MC, Cummings SR; Study of Osteoporofic Fractures Research Group. Type of fall and risk of hip and wrist fractures: the study of osteoporotic fractures. J Am Geriatr Soc. November 1993;41(11):1226-1234.
2004	Rubin C, Recker R, Cullen D, Ryaby J, McCabe J, McLeod K. Prevention of postmenopausal bone loss by a low‐magnitude, high‐frequency mechanical stimuli: a clinical trial assessing compliance, efficacy, and safety. J Bone Miner Res. March 2004;19(3):343-351.
1996	Biewener AA, Fazzalari NL, Konieczynski DD, Baudinette RV. Adaptive changes in trabecular architecture in relation to functional strain patterns and disuse. Bone. July 1996;19(1):1-8.
2002	Lochmüller E-M, Groll O, Kuhn V, Eckstein F. Mechanical strength of the proximal femur as predicted from geometric and densitometric bone properties at the lower limb versus the distal radius. Bone. January 2002;30(1):207-216.
1991	Jones DB, Nolte H, Scholübbers J-G, Turner E, Veltel D. Biochemical signal transduction of mechanical strain in osteoblast-like cells. Biomaterials. March 1991;12(2):101-110.
1989	Weinreb M, Rodan GA, Thompson DD. Osteopenia in the immobilized rat hind limb is associated with increased bone resorption and decreased bone formation. Bone. 1989;10(3):187-194.
2004	Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Miner Res. March 2004;19(3):360-369.
2001	Rubin C, Turner AS, Bain S, Mallinckrodt C, McLeod K. Low mechanical signals strengthen long bones. Nature. August 9, 2001;412(6847):603-604.
2001	Wiktorowicz ME, Goeree R, Papaioannou A, Adachi JD, Papadimitropoulos E. Economic implications of hip fracture: health service use, institutional care and cost in Canada. Osteoporos Int. May 2001;12(4):271-278.
1999	Kreiger N, Tenenhouse A, Joseph L, Mackenzie T, Poliquin S, Brown JP, Prior JC, Rittmaster RS. The Canadian Multicentre Osteoporosis study (CaMos): background, rationale, methods. Can J Aging. 1999;18(3):376-387.
1978	McKibbin B. The biology of fracture healing in long bones. J Bone Joint Surg. May 1978;60B(2):150-162.
1973	Hounsfield GN. Computerized transverse axial scanning (tomography), I: description of system. Br J Radiol. 1973;46:1016-1022.
1997	Kohrt WM, Ehsani AA, Birge SJ. Effects of exercise involving predominantly either joint-reaction or ground-reaction forces on bone mineral density in older women. J Bone Miner Res. August 1997;12(8):1253-1261.
1997	Burr DB. Muscle strength, bone mass, and age‐related bone loss. J Bone Miner Res. 1997;12(10):1547-1551.
1995	Duncan RL, Turner CH. Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tiss Int. December 1995;57(5):344-358.
1996	Hangartner TN, Gilsanz V. Evaluation of cortical bone by computed tomography. J Bone Miner Res. October 1996;11(10):1518-1525.
1986	Riggs BL, Melton LJ III. Involutional osteoporosis. NEJM. June 26, 1986;314(26):1676-1686.
2004	Nägele E, Kuhn V, Vogt H, Link TM, Müller R, Lochmüller E-M, Eckstein F. Technical considerations for microstructural analysis of human trabecular bone from specimens excised from various skeletal sites. Calcif Tiss Int. 2004;75(1):15-22.
1984	Parfitt AM. Age-related structural changes in trabecular and cortical bone: cellular mechanisms and biomechanical consequences. Calcif Tiss Int. 1984;36(suppl 1):S123-S128.
1993	Turner CH, Burr DB. Basic biomechanical measurements of bone: a tutorial. Bone. 1993;14(4):595-608.
2002	Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA. October 16, 2002;288(15):1889-1897.
1998	Augat P, Iida H, Jiang Y, Diao E, Genant HK. Distal radius fractures: mechanisms of injury and strength prediction by bone mineral assessment. J Orthop Res. August 1998;16(5):629-635.
1993	Linde F, Sørensen HCF. The effect of different storage methods on the mechanical properties of trabecular bone. J Biomech. 1993;26(10):1249-1252.
2000	Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA III, Berger M. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res. April 2000;15(4):721-739.
1997	Burr DB, Forwood MR, Fyhrie DP, Martin RB, Schaffler MB, Turner CH. Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res. January 1997;12(1):6-15.
1982	Ruff CB, Hayes WC. Subperiosteal expansion and cortical remodeling of the human femur and tibia with aging. Science. September 3, 1982;217(4563):945-948.
1995	McKee MD, Nanci A. Osteopontin and the bone remodeling sequence: colloidal-gold immunocytochemistry of an interfacial extracellular matrix protein. Annals NY Acad Sci. 1995;760(1):177-189.
1987	Frost HM. Bone “mass” and the “mechanostat”: a proposal. Anat Rec. September 1987;219(1):1-9.
2002	Burr DB, Robling AG, Turner CH. Effects of biomechanical stress on bones in animals. Bone. May 2002;30(5):781-786.
1987	Aaron JE, Makins NB, Sagreiya K. The microanatomy of trabecular bone loss in normal aging men and women. Clin Orthop Relat Res. February 1987;215:260-271.
1980	Thompson DD. Age changes in bone mineralization, cortical thickness, and Haversian canal area. Calcif Tiss Int. December 1980;31(1):5-11.
1976	Schlenker RA, VonSeggen WW. The distribution of cortical and trabecular bone mass along the lengths of the radius and ulna and the implications forin vivo bone mass measurements. Calcif Tiss Res. December 1976;20(1):41-52.
1995	Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM; Study of Osteoporotic Fractures Research Group. Risk factors for hip fracture in white women. NEJM. March 23, 1995;332(12):767-773.
2002	Bass SL, Saxon L, Daly RM, Turner CH, Robling AG, Seeman E, Stuckey S. The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: a study in tennis players. J Bone Miner Res. December 2002;17(12):2274-2280.
1998	Müller R, Van Campenhout H, Van Damme B, Van der Perre G, Dequeker J, Hildebrand T, Rüegsegger P. Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography. Bone. July 1998;23(1):59-66.
1993	Myers ER, Hecker AT, Rooks DS, Hipp JA, Hayes WC. Geometric variables from DXA of the radius predict forearm fracture load in vitro. Calcif Tiss Int. March 1993;52(3):199-204.
1998	Mosekilde L. The effect of modelling and remodelling on human vertebral body architecture. Technol Health Care. December 1998;6(5-6):287-297.
1969	Rockoff SD, Sweet E, Bleustein J. The relative contribution of trabecular and cortical bone to the strength of human lumbar vertebrae. Calcif Tiss Res. December 1969;3(1):163-175.
1998	Singer BR, McLauchlan GJ, Robinson CM, Christie J. Epidemiology of fractures in 15 000 adults: the influence of age and gender. J Bone Joint Surg. March 1998;80B(2):243-248.
2003	Seeman E. Periosteal bone formation: a neglected determinant of bone strength. NEJM. July 24, 2003;349(4):320-323.
1996	Gordon CL, Webber CE, Adachi JD, Christoforou N. In vivo assessment of trabecular bone structure at the distal radius from high-resolution computed tomography images. Phys Med Biol. March 1996;41(3):495-508.
1996	Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. May 18, 1996;312(7041):1254-1259.
1996	Burr DB, Milgrom C, Fyhrie D, Forwood M, Nyska M, Finestone A, Hoshaw S, Saiag E, Simkin A. In vivo measurement of human tibial strains during vigorous activity. Bone. May 1996;18(5):405-410.
1999	Burger EH, Klein-Nulend J. Mechanotransduction in bone: role of the lacunocanalicular network. FASEB J. May 1999;12(9001):S101-S112.
1994	Courtney AC, Wachtel EF, Myers ER, Hayes WC. Effects of loading rate on strength of the proximal femur. Calcif Tiss Int. 1994;55(1):53-58.
2004	Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S. Population-based study of age and sex differences in bone volumetricdensity, size, geometry, and structure at different skeletal sites. J Bone Miner Res. December 2004;19(12):1945-1954.
1993	Parfitt AM. Morphometry of bone resorption: introduction and overview. Bone. ;14(3):435-441.
1993	McCalden RW, McGeough JA, Barker MB, Court-Brown CM. Age-related changes in the tensile properties of cortical bone: the relative importance of changes in porosity, mineralization, and microstructure. J Bone Joint Surg. 1993;75A(8):1193-1205.
1998	Mosley JR, Lanyon LE. Strain rate as a controlling influence on adaptive modeling in response to dynamic loading of the ulna in growing male rats. Bone. October 1998;23(4):313-318.
1985	Rubin CT, Lanyon LE. Regulation of bone mass by mechanical strain magnitude. Calcif Tiss Int. 1985;37(4):411-417.
1995	Forwood MR, Turner CH. Skeletal adaptations to mechanical usage: results from tibial loading studies in rats. Bone. October 1995;17(4)(suppl):197S-205S.
1997	Frost HM. On our age‐related bone loss: insights from a new paradigm. J Bone Miner Res. October 1997;12(10):1539-1546.
1994	Frost HM. Wolff's law and bone's structural adaptations to mechanical usage: an overview for clinicians. Angle Orthod. June 1994;64(3):175-188.

Year

Entry

1998

Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. October 1998;355(suppl):S7-S21.

2002

Brown JP, Josse RG; Scientific Advisory Council of the Osteoporosis Society of Canada. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. Can Med Assoc J. November 12, 2002;167(suppl 10):S1-S34.

1994

Parfitt AM. Osteonal and hemi‐osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem. July 1994;55(3):273-286.

2002

Currey JD. Bones: Structure and Mechanics. Princeton, NJ: Princeton University Press; 2002.

1996

Müller R, Hahn M, Vogel M, Delling G, Rüegsegger P. Morphometric analysis of noninvasively assessed bone biopsies: comparison of high-resolution computed tomography and histologic sections. Bone. March 1996;18(3):215-220.