Risedronate did not block the maximal anabolic effect of PTH in aged rats

Wei Yao, Ming Su, Qing Zhang, Xiaoyan Tian, Rebecca B. Setterberg, Cindy Blanton, Mark W. Lundy, Roger Phipps, Webster S S Jee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The study was designed to investigate if pre-treating rats with a therapeutic equivalent dose of risedronate blunted the anabolic effects of PTH, and whether a withdrawal period prior to PTH treatment would alter any effect of risedronate on PTH treatment. Skeletally mature rats were treated for 18 weeks with vehicle, risedronate, or risedronate for 8 weeks followed by vehicle for 10 weeks (withdrawal period). At the end of this period, animals were treated for a further 12 weeks with PTH or PTH vehicle. Trabecular and cortical bone mass were monitored by serial pQCT, or by DXA and microCT. Bone histomorphometry was performed on the proximal tibiae and tibial shafts for bone turnover parameters at week 40. Risedronate alone moderately increased while PTH alone markedly increased trabecular bone mass at the proximal tibial (35% and 200%, respectively) and lumbar vertebral body (14% and 36%, respectively). The maximum bone gains were similar with and without pretreatment with risedronate as compared to the PTH alone. Continuous administration of risedronate for 18 weeks prior to PTH treatment had lower percentage increases in proximal tibial BMD during the first 8 weeks of PTH treatments, and had lower active bone forming surface and bone formation rates after being treated with PTH 12 weeks as compared to the PTH alone group. However, with the 10-week withdrawal period, risedronate did not blunt the stimulatory effect of PTH on osteoblast activity as shown by similar bone formation rates as with PTH alone. Our findings suggest that while risedronate pretreatment may slow the bone anabolic response to PTH, a withdrawal period prior to PTH treatment allows osteoblastic activity to respond normally to PTH stimulation.

Original languageEnglish (US)
Pages (from-to)813-819
Number of pages7
JournalBone
Volume41
Issue number5
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

Anabolic Agents
Bone and Bones
Osteogenesis
Risedronate Sodium
X-Ray Microtomography
Bone Remodeling
Osteoblasts
Tibia

Keywords

  • Bone morphology
  • PTH
  • Risedronate
  • Withdrawal

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Yao, W., Su, M., Zhang, Q., Tian, X., Setterberg, R. B., Blanton, C., ... Jee, W. S. S. (2007). Risedronate did not block the maximal anabolic effect of PTH in aged rats. Bone, 41(5), 813-819. https://doi.org/10.1016/j.bone.2007.07.005

Risedronate did not block the maximal anabolic effect of PTH in aged rats. / Yao, Wei; Su, Ming; Zhang, Qing; Tian, Xiaoyan; Setterberg, Rebecca B.; Blanton, Cindy; Lundy, Mark W.; Phipps, Roger; Jee, Webster S S.

In: Bone, Vol. 41, No. 5, 11.2007, p. 813-819.

Research output: Contribution to journalArticle

Yao, W, Su, M, Zhang, Q, Tian, X, Setterberg, RB, Blanton, C, Lundy, MW, Phipps, R & Jee, WSS 2007, 'Risedronate did not block the maximal anabolic effect of PTH in aged rats', Bone, vol. 41, no. 5, pp. 813-819. https://doi.org/10.1016/j.bone.2007.07.005
Yao W, Su M, Zhang Q, Tian X, Setterberg RB, Blanton C et al. Risedronate did not block the maximal anabolic effect of PTH in aged rats. Bone. 2007 Nov;41(5):813-819. https://doi.org/10.1016/j.bone.2007.07.005
Yao, Wei ; Su, Ming ; Zhang, Qing ; Tian, Xiaoyan ; Setterberg, Rebecca B. ; Blanton, Cindy ; Lundy, Mark W. ; Phipps, Roger ; Jee, Webster S S. / Risedronate did not block the maximal anabolic effect of PTH in aged rats. In: Bone. 2007 ; Vol. 41, No. 5. pp. 813-819.
@article{86abbcaecb68445ba61ea6f78a627e87,
title = "Risedronate did not block the maximal anabolic effect of PTH in aged rats",
abstract = "The study was designed to investigate if pre-treating rats with a therapeutic equivalent dose of risedronate blunted the anabolic effects of PTH, and whether a withdrawal period prior to PTH treatment would alter any effect of risedronate on PTH treatment. Skeletally mature rats were treated for 18 weeks with vehicle, risedronate, or risedronate for 8 weeks followed by vehicle for 10 weeks (withdrawal period). At the end of this period, animals were treated for a further 12 weeks with PTH or PTH vehicle. Trabecular and cortical bone mass were monitored by serial pQCT, or by DXA and microCT. Bone histomorphometry was performed on the proximal tibiae and tibial shafts for bone turnover parameters at week 40. Risedronate alone moderately increased while PTH alone markedly increased trabecular bone mass at the proximal tibial (35{\%} and 200{\%}, respectively) and lumbar vertebral body (14{\%} and 36{\%}, respectively). The maximum bone gains were similar with and without pretreatment with risedronate as compared to the PTH alone. Continuous administration of risedronate for 18 weeks prior to PTH treatment had lower percentage increases in proximal tibial BMD during the first 8 weeks of PTH treatments, and had lower active bone forming surface and bone formation rates after being treated with PTH 12 weeks as compared to the PTH alone group. However, with the 10-week withdrawal period, risedronate did not blunt the stimulatory effect of PTH on osteoblast activity as shown by similar bone formation rates as with PTH alone. Our findings suggest that while risedronate pretreatment may slow the bone anabolic response to PTH, a withdrawal period prior to PTH treatment allows osteoblastic activity to respond normally to PTH stimulation.",
keywords = "Bone morphology, PTH, Risedronate, Withdrawal",
author = "Wei Yao and Ming Su and Qing Zhang and Xiaoyan Tian and Setterberg, {Rebecca B.} and Cindy Blanton and Lundy, {Mark W.} and Roger Phipps and Jee, {Webster S S}",
year = "2007",
month = "11",
doi = "10.1016/j.bone.2007.07.005",
language = "English (US)",
volume = "41",
pages = "813--819",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Risedronate did not block the maximal anabolic effect of PTH in aged rats

AU - Yao, Wei

AU - Su, Ming

AU - Zhang, Qing

AU - Tian, Xiaoyan

AU - Setterberg, Rebecca B.

AU - Blanton, Cindy

AU - Lundy, Mark W.

AU - Phipps, Roger

AU - Jee, Webster S S

PY - 2007/11

Y1 - 2007/11

N2 - The study was designed to investigate if pre-treating rats with a therapeutic equivalent dose of risedronate blunted the anabolic effects of PTH, and whether a withdrawal period prior to PTH treatment would alter any effect of risedronate on PTH treatment. Skeletally mature rats were treated for 18 weeks with vehicle, risedronate, or risedronate for 8 weeks followed by vehicle for 10 weeks (withdrawal period). At the end of this period, animals were treated for a further 12 weeks with PTH or PTH vehicle. Trabecular and cortical bone mass were monitored by serial pQCT, or by DXA and microCT. Bone histomorphometry was performed on the proximal tibiae and tibial shafts for bone turnover parameters at week 40. Risedronate alone moderately increased while PTH alone markedly increased trabecular bone mass at the proximal tibial (35% and 200%, respectively) and lumbar vertebral body (14% and 36%, respectively). The maximum bone gains were similar with and without pretreatment with risedronate as compared to the PTH alone. Continuous administration of risedronate for 18 weeks prior to PTH treatment had lower percentage increases in proximal tibial BMD during the first 8 weeks of PTH treatments, and had lower active bone forming surface and bone formation rates after being treated with PTH 12 weeks as compared to the PTH alone group. However, with the 10-week withdrawal period, risedronate did not blunt the stimulatory effect of PTH on osteoblast activity as shown by similar bone formation rates as with PTH alone. Our findings suggest that while risedronate pretreatment may slow the bone anabolic response to PTH, a withdrawal period prior to PTH treatment allows osteoblastic activity to respond normally to PTH stimulation.

AB - The study was designed to investigate if pre-treating rats with a therapeutic equivalent dose of risedronate blunted the anabolic effects of PTH, and whether a withdrawal period prior to PTH treatment would alter any effect of risedronate on PTH treatment. Skeletally mature rats were treated for 18 weeks with vehicle, risedronate, or risedronate for 8 weeks followed by vehicle for 10 weeks (withdrawal period). At the end of this period, animals were treated for a further 12 weeks with PTH or PTH vehicle. Trabecular and cortical bone mass were monitored by serial pQCT, or by DXA and microCT. Bone histomorphometry was performed on the proximal tibiae and tibial shafts for bone turnover parameters at week 40. Risedronate alone moderately increased while PTH alone markedly increased trabecular bone mass at the proximal tibial (35% and 200%, respectively) and lumbar vertebral body (14% and 36%, respectively). The maximum bone gains were similar with and without pretreatment with risedronate as compared to the PTH alone. Continuous administration of risedronate for 18 weeks prior to PTH treatment had lower percentage increases in proximal tibial BMD during the first 8 weeks of PTH treatments, and had lower active bone forming surface and bone formation rates after being treated with PTH 12 weeks as compared to the PTH alone group. However, with the 10-week withdrawal period, risedronate did not blunt the stimulatory effect of PTH on osteoblast activity as shown by similar bone formation rates as with PTH alone. Our findings suggest that while risedronate pretreatment may slow the bone anabolic response to PTH, a withdrawal period prior to PTH treatment allows osteoblastic activity to respond normally to PTH stimulation.

KW - Bone morphology

KW - PTH

KW - Risedronate

KW - Withdrawal

UR - http://www.scopus.com/inward/record.url?scp=35348885488&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348885488&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2007.07.005

DO - 10.1016/j.bone.2007.07.005

M3 - Article

VL - 41

SP - 813

EP - 819

JO - Bone

JF - Bone

SN - 8756-3282

IS - 5

ER -