Abstract
Fourier transform infrared microscopy (FT-IRM) and imaging spectroscopy (FT-IRIS) are increasingly used to analyze the molecular components of mineralized tissues. A primary advantage of these techniques is the capability to simultaneously image the quantity and quality of multiple components in histological sections at 7 µm spatial resolution. In the current study, FT-IRM and FT-IRIS were used to characterize bone mineralization in a mouse model of osteogenesis imperfecta (OI) after treatment with the bisphosphonate alendronate (ALN). This application is currently relevant since recent studies have demonstrated great promise for the treatment of children with OI with bisphosphonates, but have not identified bisphosphonate-associated bone quality changes. Growing oim/oim mice, a model of moderate-to-severe OI, were treated with ALN (73 µg ALN/kg/day for 4 weeks followed by 26 µg/kg/day for 4 weeks) or saline from 6 to 14 weeks of age, and mineralization was evaluated in femoral cortical and metaphyseal bone. Infrared vibrations of the mineral (a carbonated apatite) and the matrix phases were monitored. The relative amounts of mineral and matrix present (min:matrix), the relative amount of carbonate present in the mineral (carb:min), and the crystallinity of the mineral phase were calculated. In untreated oim/oim bone, the min:matrix was greater and the crystallinity was reduced (indicative of less mature mineral) in the primary versus the secondary spongiosa, most likely due to the presence of calcified cartilage. With ALN treatment, the oim/oim mm:matrix increased in the secondary spongiosa, but the mineral crystallinity was not changed. In the cortical bone, no changes were evident with ALN treatment. These data demonstrate that in this mouse model, ALN treatment results in increased metaphyseal bone mineralization, but does not improve mineral maturity.
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References
AL Boskey S Gadaleta C Gundberg SB Doty P Ducy G Karsenty (1998) ArticleTitleFourier transform infrared microspectroscopic analysis of bones of osteocalcin-deficient mice provides insight into the function of osteocalcin. Bone 23 187–196 Occurrence Handle1:CAS:528:DyaK1cXlvF2hur4%3D Occurrence Handle9737340
NP Camacho CM Rimnac RA Meyer Jr S Doty AL Boskey (1995) ArticleTitleEffect of abnormal mineralization on the mechanical behavior of X-linked hypophosphatemic mice femora. Bone 17 271–278 Occurrence Handle10.1016/8756-3282(95)00210-5 Occurrence Handle1:STN:280:BymD2Mrhslw%3D Occurrence Handle8541141
EP Paschalis O Jacenko B Olsen R Mendelsohn AL Boskey (1996) ArticleTitleFourier transform infrared microspectroscopic analysis identifies alterations in mineral properties in bones from mice transgenic for type X collagen. Bone 19 151–156 Occurrence Handle10.1016/8756-3282(96)00164-0 Occurrence Handle1:STN:280:ByiD3cnls1I%3D Occurrence Handle8853859
AL Boskey EP Paschalis I Binderman SB Doty (2002) ArticleTitleBMP-6 accelerates both chondrogenesis and mineral maturation in differentiating chick limb-bud mesenchymal cell cultures. J Cell Biochem 84 509–519 Occurrence Handle10.1002/jcb.10032.abs Occurrence Handle1:STN:280:DC%2BD387gt1amuw%3D%3D Occurrence Handle11813256
AL Boskey NP Camacho R Mendelsohn SB Doty I Binderman (1992) ArticleTitleFT-IR microscopic mappings of early mineralization in chick limb bud mesenchymal cell cultures. Calcif Tissue Int 51 443–448 Occurrence Handle1:STN:280:ByyD1c3ls1A%3D Occurrence Handle1451012
EP Paschalis E DiCarlo F Betts P Sherman R Mendelsohn AL Boskey (1996) ArticleTitleFTIR microspectroscopic analysis of human osteonal bone. Calcif Tissue Int 59 480–487 Occurrence Handle10.1007/s002239900161 Occurrence Handle1:CAS:528:DyaK28XnsVWitLg%3D Occurrence Handle8939775
EP Paschalis F Betts E DiCarlo R Mendelsohn AL Boskey (1997) ArticleTitleFTIR microspectroscopic analysis of human iliac crest biopsies from untreated osteoporotic bone. Calcif Tissue Int 61 487–492 Occurrence Handle10.1007/s002239900372 Occurrence Handle1:CAS:528:DyaK2sXnvVWjurs%3D Occurrence Handle9383276
EP Paschalis F Betts E DiCarlo R Mendelsohn AL Boskey (1997) ArticleTitleFTIR microspectroscopic analysis of normal human cortical and trabecular bone. Calcif Tissue Int 61 480–486 Occurrence Handle10.1007/s002239900371 Occurrence Handle1:CAS:528:DyaK2sXnvVWjuro%3D Occurrence Handle9383275
NP Camacho P West PA Torzilli R Mendelsohn (2001) ArticleTitleFTIR microscopic imaging of collagen and proteoglycan in bovine cartilage. Biopolymers 62 1–8 Occurrence Handle10.1002/1097-0282(2001)62:1<1::AID-BIP10>3.0.CO;2-O Occurrence Handle1:CAS:528:DC%2BD3MXnslaqsA%3D%3D Occurrence Handle11135186
K Potter LH Kidder IW Levin EN Lewis RG Spencer (2001) ArticleTitleImaging of collagen and proteoglycan in cartilage sections using Fourier transform infrared spectral imaging. Arthritis Rheum 44 846–855 Occurrence Handle10.1002/1529-0131(200104)44:4<846::AID-ANR141>3.3.CO;2-5 Occurrence Handle1:CAS:528:DC%2BD3MXpt12ltb8%3D Occurrence Handle11315924
C Marcott RC Reeder EP Paschalis DN Tatakis AL Boskey R Mendelsohn (1998) ArticleTitleInfrared microspectroscopic imaging of biomineralized tissues using a mercury-cadmium-telluride focal-plane array detector. Cell Mol Biol (Noisy-le-grand) 44 109–115 Occurrence Handle1:CAS:528:DyaK1cXit1WltLc%3D
EP Paschalis K Verdelis SB Doty AL Boskey R Mendelsohn M Yamauchi (2001) ArticleTitleSpectroscopic characterization of collagen cross-links in bone. J Bone Miner Res 16 1821–1828
DW Rowe JR Shapiro (1998) Osteogenesis Imperfecta. LV Avioli SM Krane (Eds) Metabolic bone disease and clinically related disorders. Academic Press San Diego 651–683
CL Raggio (1993) Osteogenesis imperfecta. JM Lane JH Healey (Eds) Diagnosis and management of pathologic fractures. Raven Press New York 55–64
FH Glorieux NJ Bishop H Plotkin G Chabot G Lanoue R Travers (1998) ArticleTitleCyclic administration of pamidronate in children with severe osteogenesis imperfecta [see comments]. N Engl J Med 339 947–952
H Plotkin F Rauch NJ Bishop K Montpetit J Ruck-Gibis R Travers et al. (2000) ArticleTitlePamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab 85 1846–1850 Occurrence Handle1:CAS:528:DC%2BD3cXlt1WlsLw%3D Occurrence Handle10843163
JC Marini (1998) ArticleTitleOsteogenesis imperfecta–managing brittle bones [editorial; comment]. N Engl J Med 339 986–987 Occurrence Handle10.1056/NEJM199810013391408 Occurrence Handle1:STN:280:DyaK1cvhvVKmsw%3D%3D Occurrence Handle9753715
SD Chipman HO Sweet DJ McBride Jr MT Davisson SC Marks Jr AR Shuldiner et al. (1993) ArticleTitleDefective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta. Proc Natl Acad Sci USA 90 1701–1705 Occurrence Handle1:CAS:528:DyaK3sXhs1KlsL0%3D Occurrence Handle8446583
NP Camacho CL Raggio SB Doty L Root V Zraick WA Ilg et al. (2001) ArticleTitleA controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta. Calcif Tissue Int 69 94–101 Occurrence Handle10.1007/s002230010045 Occurrence Handle1:CAS:528:DC%2BD3MXmvVOqsro%3D Occurrence Handle11683430
S Aparicio SB Doty NP Camacho EP Paschalis L Spevak R Mendelsohn et al. (2002) ArticleTitleOptimal methods for processing mineralized tissues for Fourier transform infrared microspectroscopy. Calcif Tissue Int 70 422–429 Occurrence Handle1:CAS:528:DC%2BD38Xlt1KntL4%3D Occurrence Handle12055658
D Pienkowski TM Doers MC Monier-Faugere Z Geng NP Camacho AL Boskey et al. (1997) ArticleTitleCalcitonin alters bone quality in beagle dogs. J Bone Miner Res 12 1936–1943
SJ Gadaleta EP Paschalis F Betts R Mendelsohn AL Boskey (1996) ArticleTitleFourier transform infrared spectroscopy of the solution-mediated conversion of amorphous calcium phosphate to hydroxyapatite: new correlations between X-ray diffraction and infrared data. Calcif Tissue Int 58 9–16 Occurrence Handle10.1007/s002239900004 Occurrence Handle1:CAS:528:DyaK28XmvFKisw%3D%3D Occurrence Handle8825233
W Traub T Arad U Vetter S Weiner (1994) ArticleTitleUltrastructural studies of bones from patients with osteogenesis imperfecta. Matrix Biol 14 337–345 Occurrence Handle10.1016/0945-053X(94)90200-3 Occurrence Handle1:STN:280:ByqC38flt1A%3D Occurrence Handle7827757
U Vetter ED Eanes JB Kopp JD Termine PG Robey (1991) ArticleTitleChanges in apatite crystal size in bones of patients with osteogenesis imperfecta. Calcif Tissue Int 49 248–250 Occurrence Handle1:STN:280:By2C3czls1M%3D Occurrence Handle1760768
U Vetter MA Weis M Morike ED Eanes DR Eyre (1993) ArticleTitleCollagen crosslinks and mineral crystallinity in bone of patients with osteogenesis imperfecta. J Bone Miner Res 8 133–137 Occurrence Handle1:STN:280:ByyC1c3mt1U%3D Occurrence Handle8442432
NP Camacho L Hou TR Toledano WA Ilg CF Brayton CL Raggio et al. (1999) ArticleTitleThe material basis for reduced mechanical properties in oim mice bones. J Bone Miner Res 14 264–272 Occurrence Handle1:STN:280:DyaK1M7jt1Gnuw%3D%3D Occurrence Handle9933481
P Fratzl O Paris K Klaushofer WJ Landis (1996) ArticleTitleBone mineralization in an osteogenesis imperfecta mouse model studied by small-angle x-ray scattering. J Clin Invest 97 396–402 Occurrence Handle1:CAS:528:DyaK28Xht1Omu7w%3D Occurrence Handle8567960
WJ Landis (1995) ArticleTitleThe strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix. Bone 16 533–544 Occurrence Handle10.1016/8756-3282(95)00076-P Occurrence Handle1:CAS:528:DyaK2MXlvFGntr4%3D Occurrence Handle7654469
NP Camacho WJ Landis AL Boskey (1996) ArticleTitleMineral changes in a mouse model of osteogenesis imperfecta detected by Fourier transform infrared microscopy. Connect Tissue Res 35 259–265 Occurrence Handle1:CAS:528:DyaK2sXhvFantb8%3D Occurrence Handle9084664
B Grabner WJ Landis P Roschger S Rinnerthaler H Peterlik K Klaushofer et al. (2001) ArticleTitleAge- and genotype-dependence of bone material properties in the osteogenesis imperfecta murine model (oim). Bone 29 453–457 Occurrence Handle10.1016/S8756-3282(01)00594-4 Occurrence Handle1:STN:280:DC%2BD3Mnlt1WnsA%3D%3D Occurrence Handle11704498
P Roschger P Fratzl K Klaushofer G Rodan (1997) ArticleTitleMineralization of cancellous bone after alendronate and sodium fluoride treatment: a quantitative backscattered electron imaging study on minipig ribs. Bone 20 393–397 Occurrence Handle10.1016/S8756-3282(97)00018-5 Occurrence Handle1:CAS:528:DyaK2sXjsV2iur0%3D Occurrence Handle9145235
P Roschger S Rinnerthaler J Yates GA Rodan P Fratzl K Klaushofer (2001) ArticleTitleAlendronate increases the degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29 185–191 Occurrence Handle10.1016/S8756-3282(01)00485-9 Occurrence Handle1:CAS:528:DC%2BD3MXlvFWkurk%3D Occurrence Handle11502482
NP Camacho S Rinnerthaler EP Paschalis R Mendelsohn AL Boskey P Fratzl (1999) ArticleTitleComplementary information on bone ultrastructure from scanning small angle x-ray scattering and Fourier transform infrared microscopy. Bone 25 287–293 Occurrence Handle10.1016/S8756-3282(99)00165-9 Occurrence Handle1:STN:280:DyaK1MvitlehsQ%3D%3D Occurrence Handle10495132
S Bohic C Rey A Legrand H Sfihi R Rohanizadeh C Martel A Barbier G Daculsi (2000) ArticleTitleCharacterization of the trabecular rat bone mineral: effect of ovariectomy and bisphosphonate treatment. Bone 26 341–348 Occurrence Handle10.1016/S8756-3282(99)00276-8 Occurrence Handle1:CAS:528:DC%2BD3cXhslaksrw%3D Occurrence Handle10719276
R Rohanizadeh RZ LeGeros S Bohic P Pilet A Barbier G Daculsi (2000) ArticleTitleUltrastructural properties of bone mineral of control and tiludronate-treated osteoporotic rat. Calcif Tissue Int 67 330–336 Occurrence Handle10.1007/s002230001141 Occurrence Handle1:CAS:528:DC%2BD3cXntlOlu7Y%3D Occurrence Handle11000348
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Camacho, N., Carroll, P. & Raggio, C. Fourier Transform Infrared Imaging Spectroscopy (FT-IRIS) of Mineralization in Bisphosphonate-treated oim/oim Mice . Calcif Tissue Int 72, 604–609 (2003). https://doi.org/10.1007/s00223-002-1038-1
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DOI: https://doi.org/10.1007/s00223-002-1038-1