Estrogen depletion and drug treatment alter the microstructure of type I collagen in bone

Meagan A. Cauble, Matthew J. Muckley, Ming Fang, Jeffrey A. Fessler, Kathleen Welch, Edward D. Rothman, Bradford G. Orr, Le T. Duong, Mark M.Banaszak Holl

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The impact of estrogen depletion and drug treatment on type I collagen fibril nanomorphology and collagen fibril packing (microstructure) was evaluated by atomic force microscopy (AFM) using an ovariectomized (OVX) rabbit model of estrogen deficiency induced bone loss. Nine month-old New Zealand white female rabbits were treated as follows: sham-operated (Sham; n = 11), OVX + vehicle (OVX + Veh; n = 12), OVX + alendronate (ALN, 600 μg/kg/wk., s.c.; n = 12), and OVX + cathepsin-K inhibitor L-235 (CatKI, 10 mg/kg, daily, p.o.; n = 13) in prevention mode for 27 weeks. Samples from the cortical femur and trabecular lumbar vertebrae were polished, demineralized, and imaged using AFM. Auto-correlation of image patches was used to generate a vector field for each image that mathematically approximated the collagen fibril alignment. This vector field was used to compute an information-theoretic entropy that was employed as a quantitative fibril alignment parameter (FAP) to allow image-to-image and sample-to-sample comparison. For all samples, no change was observed in the average FAP values; however significant differences in the distribution of FAP values were observed. In particular, OVX + Veh lumbar vertebrae samples contained a tail of lower FAP values representing regions of greater fibril alignment. OVX + ALN treatment resulted in a FAP distribution with a tail indicating greater alignment for cortical femur and less alignment for trabecular lumbar vertebrae. OVX + CatKI treatment gave a distribution of FAP values with a tail indicating less alignment for cortical femur and no change for trabecular lumbar vertebrae. Fibril alignment was also evaluated by considering when a fibril was part of discrete bundles or sheets (classified as parallel) or not (classified as oblique). For this analysis, the percentage of parallel fibrils in cortical femur for the OVX group was 17% lower than the Sham group. OVX + ALN treatment partially prevented the proportion of parallel fibrils from decreasing and OVX + CatKI treatment completely prevented a change. In trabecular lumbar vertebrae, there was no difference in the percentage of parallel fibrils between Sham and any of the other treatment groups.

Original languageEnglish
Pages (from-to)243-251
Number of pages9
JournalBone Reports
Volume5
DOIs
Publication statusPublished - 1 Dec 2016
Externally publishedYes

Keywords

  • AFM
  • Bisphosphonate
  • Cathepsin K inhibitor
  • Collagen
  • Osteoporosis
  • OVX

Cite this

Cauble, Meagan A. ; Muckley, Matthew J. ; Fang, Ming ; Fessler, Jeffrey A. ; Welch, Kathleen ; Rothman, Edward D. ; Orr, Bradford G. ; Duong, Le T. ; Holl, Mark M.Banaszak. / Estrogen depletion and drug treatment alter the microstructure of type I collagen in bone. In: Bone Reports. 2016 ; Vol. 5. pp. 243-251.
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abstract = "The impact of estrogen depletion and drug treatment on type I collagen fibril nanomorphology and collagen fibril packing (microstructure) was evaluated by atomic force microscopy (AFM) using an ovariectomized (OVX) rabbit model of estrogen deficiency induced bone loss. Nine month-old New Zealand white female rabbits were treated as follows: sham-operated (Sham; n = 11), OVX + vehicle (OVX + Veh; n = 12), OVX + alendronate (ALN, 600 μg/kg/wk., s.c.; n = 12), and OVX + cathepsin-K inhibitor L-235 (CatKI, 10 mg/kg, daily, p.o.; n = 13) in prevention mode for 27 weeks. Samples from the cortical femur and trabecular lumbar vertebrae were polished, demineralized, and imaged using AFM. Auto-correlation of image patches was used to generate a vector field for each image that mathematically approximated the collagen fibril alignment. This vector field was used to compute an information-theoretic entropy that was employed as a quantitative fibril alignment parameter (FAP) to allow image-to-image and sample-to-sample comparison. For all samples, no change was observed in the average FAP values; however significant differences in the distribution of FAP values were observed. In particular, OVX + Veh lumbar vertebrae samples contained a tail of lower FAP values representing regions of greater fibril alignment. OVX + ALN treatment resulted in a FAP distribution with a tail indicating greater alignment for cortical femur and less alignment for trabecular lumbar vertebrae. OVX + CatKI treatment gave a distribution of FAP values with a tail indicating less alignment for cortical femur and no change for trabecular lumbar vertebrae. Fibril alignment was also evaluated by considering when a fibril was part of discrete bundles or sheets (classified as parallel) or not (classified as oblique). For this analysis, the percentage of parallel fibrils in cortical femur for the OVX group was 17{\%} lower than the Sham group. OVX + ALN treatment partially prevented the proportion of parallel fibrils from decreasing and OVX + CatKI treatment completely prevented a change. In trabecular lumbar vertebrae, there was no difference in the percentage of parallel fibrils between Sham and any of the other treatment groups.",
keywords = "AFM, Bisphosphonate, Cathepsin K inhibitor, Collagen, Osteoporosis, OVX",
author = "Cauble, {Meagan A.} and Muckley, {Matthew J.} and Ming Fang and Fessler, {Jeffrey A.} and Kathleen Welch and Rothman, {Edward D.} and Orr, {Bradford G.} and Duong, {Le T.} and Holl, {Mark M.Banaszak}",
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Cauble, MA, Muckley, MJ, Fang, M, Fessler, JA, Welch, K, Rothman, ED, Orr, BG, Duong, LT & Holl, MMB 2016, 'Estrogen depletion and drug treatment alter the microstructure of type I collagen in bone', Bone Reports, vol. 5, pp. 243-251. https://doi.org/10.1016/j.bonr.2016.08.003

Estrogen depletion and drug treatment alter the microstructure of type I collagen in bone. / Cauble, Meagan A.; Muckley, Matthew J.; Fang, Ming; Fessler, Jeffrey A.; Welch, Kathleen; Rothman, Edward D.; Orr, Bradford G.; Duong, Le T.; Holl, Mark M.Banaszak.

In: Bone Reports, Vol. 5, 01.12.2016, p. 243-251.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Estrogen depletion and drug treatment alter the microstructure of type I collagen in bone

AU - Cauble, Meagan A.

AU - Muckley, Matthew J.

AU - Fang, Ming

AU - Fessler, Jeffrey A.

AU - Welch, Kathleen

AU - Rothman, Edward D.

AU - Orr, Bradford G.

AU - Duong, Le T.

AU - Holl, Mark M.Banaszak

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AB - The impact of estrogen depletion and drug treatment on type I collagen fibril nanomorphology and collagen fibril packing (microstructure) was evaluated by atomic force microscopy (AFM) using an ovariectomized (OVX) rabbit model of estrogen deficiency induced bone loss. Nine month-old New Zealand white female rabbits were treated as follows: sham-operated (Sham; n = 11), OVX + vehicle (OVX + Veh; n = 12), OVX + alendronate (ALN, 600 μg/kg/wk., s.c.; n = 12), and OVX + cathepsin-K inhibitor L-235 (CatKI, 10 mg/kg, daily, p.o.; n = 13) in prevention mode for 27 weeks. Samples from the cortical femur and trabecular lumbar vertebrae were polished, demineralized, and imaged using AFM. Auto-correlation of image patches was used to generate a vector field for each image that mathematically approximated the collagen fibril alignment. This vector field was used to compute an information-theoretic entropy that was employed as a quantitative fibril alignment parameter (FAP) to allow image-to-image and sample-to-sample comparison. For all samples, no change was observed in the average FAP values; however significant differences in the distribution of FAP values were observed. In particular, OVX + Veh lumbar vertebrae samples contained a tail of lower FAP values representing regions of greater fibril alignment. OVX + ALN treatment resulted in a FAP distribution with a tail indicating greater alignment for cortical femur and less alignment for trabecular lumbar vertebrae. OVX + CatKI treatment gave a distribution of FAP values with a tail indicating less alignment for cortical femur and no change for trabecular lumbar vertebrae. Fibril alignment was also evaluated by considering when a fibril was part of discrete bundles or sheets (classified as parallel) or not (classified as oblique). For this analysis, the percentage of parallel fibrils in cortical femur for the OVX group was 17% lower than the Sham group. OVX + ALN treatment partially prevented the proportion of parallel fibrils from decreasing and OVX + CatKI treatment completely prevented a change. In trabecular lumbar vertebrae, there was no difference in the percentage of parallel fibrils between Sham and any of the other treatment groups.

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KW - Osteoporosis

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Cauble MA, Muckley MJ, Fang M, Fessler JA, Welch K, Rothman ED et al. Estrogen depletion and drug treatment alter the microstructure of type I collagen in bone. Bone Reports. 2016 Dec 1;5:243-251. https://doi.org/10.1016/j.bonr.2016.08.003