title: Parathyroid hormone treatment improves the cortical bone microstructure by improving the distribution of type I collagen in postmenopausal women with osteoporosis.
abstract: Although an important index, the level of bone mineral density (BMD) does not completely describe fracture risk. Another bone structural parameter, the orientation of type I collagen, is known to add to risk determination, independently of BMD, ex vivo. We investigated the Haversian system of transiliac crest biopsies from postmenopausal women before and after treatment with parathyroid hormone (PTH). We used the birefringent signal of circularly polarized light and its underlying collagen arrangements by confocal and electron microscopy, in conjunction with the degree of calcification by high-resolution micro-X-ray. We found that PTH treatment increased the Haversian system area by 11.92 ± 5.82 mm² to 12.76 ± 4.50 mm² (p = 0.04); decreased bright birefringence from 0.45 ± 0.02 to 0.40 ± 0.01 (scale zero to one, p = 0.0005); increased the average percent area of osteons with alternating birefringence from 48.15% ± 10.27% to 66.33% ± 7.73% (p = 0.034); and nonsignificantly decreased the average percent area of semihomogeneous birefringent osteons (8.36% ± 10.63% versus 5.41% ± 9.13%, p = 0.40) and of birefringent bright osteons (4.14% ± 8.90% versus 2.08% ± 3.36%, p = 0.10). Further, lamellar thickness significantly increased from 3.78 ± 0.11 µm to 4.47 ± 0.14 µm (p = 0.0002) for bright lamellae, and from 3.32 ± 0.12 µm to 3.70 ± 0.12 µm (p = 0.045) for extinct lamellae. This increased lamellar thickness altered the distribution of birefringence and therefore the distribution of collagen orientation in the tissue. With PTH treatment, a higher percent area of osteons at the initial degree of calcification was observed, relative to the intermediate-low degree of calcification (57.16% ± 3.08% versus 32.90% ± 3.69%, p = 0.04), with percentage of alternating osteons at initial stages of calcification increasing from 19.75 ± 1.22 to 80.13 ± 6.47, p = 0.001. In conclusion, PTH treatment increases heterogeneity of collagen orientation, a starting point from which to study the reduction in fracture risk when PTH is used to treat osteoporosis.
authors.affiliation: UCLA/Orthopaedic Hospital Department of Orthopaedic Surgery, University of California at Los Angeles, Los Angeles, CA 90095, USA. mgascenzi@mednet.ucla.edu
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Ascenzi
authors.forename: Vivian P
authors.initials: VP
authors.lastname: Liao
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Lee
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Billi
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Robert
authors.initials: R
authors.lastname: Lindsay
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
authors.forename: Jeri
authors.initials: J
authors.lastname: Nieves
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
mesh_terms: D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism / Q000648:ultrastructure*; D024042:Collagen Type I / Q000378:metabolism*; D005260:Female; D006801:Humans; D018613:Microscopy, Confocal; D017348:Microscopy, Electron, Scanning Transmission; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D017698:Postmenopause; D011859:Radiography
chemical_list: D024042:Collagen Type I; D010281:Parathyroid Hormone