Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats

Sarah K. Amugongo; Wei Yao; Junjing Jia; Weiwei Dai; Yu A.E. Lay; Li Jiang; Danielle Harvey; Elizabeth A. Zimmermann; Eric Schaible; Neil Dave; Robert O. Ritchie; Donald B. Kimmel; Nancy E. Lane

doi:10.1016/j.bone.2014.04.033

Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats

Sarah K. Amugongo, Wei Yao, Junjing Jia, Weiwei Dai, Yu A.E. Lay, Li Jiang, Danielle Harvey, Elizabeth A. Zimmermann, Eric Schaible, Neil Dave, Robert O. Ritchie, Donald B. Kimmel, Nancy E. Lane

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Anti-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially for many years. However their impact on cortical bone quality and bone strength is not clear. Methods: Six-month old female rats were either sham operated or ovariectomized (OVX). OVX rats were left untreated for two months and then were treated with vehicle (Veh), hPTH (1-34) (PTH), alendronate (Aln), or raloxifene (Ral) sequentially for three month intervals, for a total of three periods. Mid-tibial cortical bone architecture, mass, mineralization, and strength were measured on necropsy samples obtained after each period. Bone indentation properties were measured on proximal femur necropsy samples. Results: Eight or more months of estrogen deficiency in rats resulted in decreased cortical bone area and thickness. Treatment with PTH for 3. months caused the deposition of endocortical lamellar bone that increased cortical bone area, thickness, and strength. These improvements were lost when PTH was withdrawn without followup treatment, but were maintained for the maximum times tested, six months with Ral and three months with Aln. Pre-treatment with anti-resorptives was also somewhat successful in ultimately preserving the additional endocortical lamellar bone formed under PTH treatment. These treatments did not affect bone indentation properties. Summary: Sequential therapy that involved both PTH and anti-resorptive agents was required to achieve lasting improvements in cortical area, thickness, and strength in OVX rats. Anti-resorptive therapy, either prior to or following PTH, was required to preserve gains attributable to an anabolic agent.

Original language	English (US)
Pages (from-to)	257-268
Number of pages	12
Journal	Bone
Volume	67
DOIs	https://doi.org/10.1016/j.bone.2014.04.033
State	Published - Oct 2014
Externally published	Yes

Bibliographical note

Funding Information:
This work was funded by National Institutes of Health (NIH) Grant #s R01 AR043052 and 5K24AR048841 . The statistical analyses were supported by the National Center for Advancing Translational Sciences (NCATS), and NIH, through Grant # UL1 TR000002 . The involvement of ROR was supported by the National Institutes of Health (NIH/NIDCR) under Grant# 5R01 DE015633 to the Lawrence Berkeley National Laboratory (LBNL).

Funding Information:
This work was funded by National Institutes of Health Grants Nos. R01 AR043052 and K24 AR-048841, 1 P50 AR063043, and P50 AR060752NIH to NEL, the endowment for aging research at UC Davis to NEL, and the Center for Musculoskeletal Health at UC Davis. The sponsor played no role in this manuscript.

Keywords

Adult
Indentation
Lamellar bone
MicroCT
Mineralization
Mineralizing surface

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Amugongo, S. K., Yao, W., Jia, J., Dai, W., Lay, Y. A. E., Jiang, L., Harvey, D., Zimmermann, E. A., Schaible, E., Dave, N., Ritchie, R. O., Kimmel, D. B., & Lane, N. E. (2014). Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats. Bone, 67, 257-268. https://doi.org/10.1016/j.bone.2014.04.033

Amugongo, SK, Yao, W, Jia, J, Dai, W, Lay, YAE, Jiang, L, Harvey, D, Zimmermann, EA, Schaible, E, Dave, N, Ritchie, RO, Kimmel, DB & Lane, NE 2014, 'Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats', Bone, vol. 67, pp. 257-268. https://doi.org/10.1016/j.bone.2014.04.033

@article{dac66dd253064effb8b85fde05218b12,

title = "Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats",

abstract = "Anti-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially for many years. However their impact on cortical bone quality and bone strength is not clear. Methods: Six-month old female rats were either sham operated or ovariectomized (OVX). OVX rats were left untreated for two months and then were treated with vehicle (Veh), hPTH (1-34) (PTH), alendronate (Aln), or raloxifene (Ral) sequentially for three month intervals, for a total of three periods. Mid-tibial cortical bone architecture, mass, mineralization, and strength were measured on necropsy samples obtained after each period. Bone indentation properties were measured on proximal femur necropsy samples. Results: Eight or more months of estrogen deficiency in rats resulted in decreased cortical bone area and thickness. Treatment with PTH for 3. months caused the deposition of endocortical lamellar bone that increased cortical bone area, thickness, and strength. These improvements were lost when PTH was withdrawn without followup treatment, but were maintained for the maximum times tested, six months with Ral and three months with Aln. Pre-treatment with anti-resorptives was also somewhat successful in ultimately preserving the additional endocortical lamellar bone formed under PTH treatment. These treatments did not affect bone indentation properties. Summary: Sequential therapy that involved both PTH and anti-resorptive agents was required to achieve lasting improvements in cortical area, thickness, and strength in OVX rats. Anti-resorptive therapy, either prior to or following PTH, was required to preserve gains attributable to an anabolic agent.",

keywords = "Adult, Indentation, Lamellar bone, MicroCT, Mineralization, Mineralizing surface",

author = "Amugongo, {Sarah K.} and Wei Yao and Junjing Jia and Weiwei Dai and Lay, {Yu A.E.} and Li Jiang and Danielle Harvey and Zimmermann, {Elizabeth A.} and Eric Schaible and Neil Dave and Ritchie, {Robert O.} and Kimmel, {Donald B.} and Lane, {Nancy E.}",

note = "Funding Information: This work was funded by National Institutes of Health (NIH) Grant #s R01 AR043052 and 5K24AR048841 . The statistical analyses were supported by the National Center for Advancing Translational Sciences (NCATS), and NIH, through Grant # UL1 TR000002 . The involvement of ROR was supported by the National Institutes of Health (NIH/NIDCR) under Grant# 5R01 DE015633 to the Lawrence Berkeley National Laboratory (LBNL). Funding Information: This work was funded by National Institutes of Health Grants Nos. R01 AR043052 and K24 AR-048841, 1 P50 AR063043, and P50 AR060752NIH to NEL, the endowment for aging research at UC Davis to NEL, and the Center for Musculoskeletal Health at UC Davis. The sponsor played no role in this manuscript. ",

year = "2014",

month = oct,

doi = "10.1016/j.bone.2014.04.033",

language = "English (US)",

volume = "67",

pages = "257--268",

journal = "Bone",

issn = "8756-3282",

publisher = "Elsevier Inc.",

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T1 - Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats

AU - Amugongo, Sarah K.

AU - Yao, Wei

AU - Jia, Junjing

AU - Dai, Weiwei

AU - Lay, Yu A.E.

AU - Jiang, Li

AU - Harvey, Danielle

AU - Zimmermann, Elizabeth A.

AU - Schaible, Eric

AU - Dave, Neil

AU - Ritchie, Robert O.

AU - Kimmel, Donald B.

AU - Lane, Nancy E.

N1 - Funding Information: This work was funded by National Institutes of Health (NIH) Grant #s R01 AR043052 and 5K24AR048841 . The statistical analyses were supported by the National Center for Advancing Translational Sciences (NCATS), and NIH, through Grant # UL1 TR000002 . The involvement of ROR was supported by the National Institutes of Health (NIH/NIDCR) under Grant# 5R01 DE015633 to the Lawrence Berkeley National Laboratory (LBNL). Funding Information: This work was funded by National Institutes of Health Grants Nos. R01 AR043052 and K24 AR-048841, 1 P50 AR063043, and P50 AR060752NIH to NEL, the endowment for aging research at UC Davis to NEL, and the Center for Musculoskeletal Health at UC Davis. The sponsor played no role in this manuscript.

PY - 2014/10

Y1 - 2014/10

N2 - Anti-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially for many years. However their impact on cortical bone quality and bone strength is not clear. Methods: Six-month old female rats were either sham operated or ovariectomized (OVX). OVX rats were left untreated for two months and then were treated with vehicle (Veh), hPTH (1-34) (PTH), alendronate (Aln), or raloxifene (Ral) sequentially for three month intervals, for a total of three periods. Mid-tibial cortical bone architecture, mass, mineralization, and strength were measured on necropsy samples obtained after each period. Bone indentation properties were measured on proximal femur necropsy samples. Results: Eight or more months of estrogen deficiency in rats resulted in decreased cortical bone area and thickness. Treatment with PTH for 3. months caused the deposition of endocortical lamellar bone that increased cortical bone area, thickness, and strength. These improvements were lost when PTH was withdrawn without followup treatment, but were maintained for the maximum times tested, six months with Ral and three months with Aln. Pre-treatment with anti-resorptives was also somewhat successful in ultimately preserving the additional endocortical lamellar bone formed under PTH treatment. These treatments did not affect bone indentation properties. Summary: Sequential therapy that involved both PTH and anti-resorptive agents was required to achieve lasting improvements in cortical area, thickness, and strength in OVX rats. Anti-resorptive therapy, either prior to or following PTH, was required to preserve gains attributable to an anabolic agent.

AB - Anti-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially for many years. However their impact on cortical bone quality and bone strength is not clear. Methods: Six-month old female rats were either sham operated or ovariectomized (OVX). OVX rats were left untreated for two months and then were treated with vehicle (Veh), hPTH (1-34) (PTH), alendronate (Aln), or raloxifene (Ral) sequentially for three month intervals, for a total of three periods. Mid-tibial cortical bone architecture, mass, mineralization, and strength were measured on necropsy samples obtained after each period. Bone indentation properties were measured on proximal femur necropsy samples. Results: Eight or more months of estrogen deficiency in rats resulted in decreased cortical bone area and thickness. Treatment with PTH for 3. months caused the deposition of endocortical lamellar bone that increased cortical bone area, thickness, and strength. These improvements were lost when PTH was withdrawn without followup treatment, but were maintained for the maximum times tested, six months with Ral and three months with Aln. Pre-treatment with anti-resorptives was also somewhat successful in ultimately preserving the additional endocortical lamellar bone formed under PTH treatment. These treatments did not affect bone indentation properties. Summary: Sequential therapy that involved both PTH and anti-resorptive agents was required to achieve lasting improvements in cortical area, thickness, and strength in OVX rats. Anti-resorptive therapy, either prior to or following PTH, was required to preserve gains attributable to an anabolic agent.

KW - Adult

KW - Indentation

KW - Lamellar bone

KW - MicroCT

KW - Mineralization

KW - Mineralizing surface

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Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats

Abstract

Bibliographical note

Keywords

Access

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