Ibandronate does not reduce the anabolic effects of PTH in ovariectomized rat tibiae: A microarchitectural and mechanical study

Xiao Yang; Yong Hoow Chan; Padmalosini Muthukumaran; Shamal DasDe; Swee Hin Teoh; Taeyong Lee

doi:10.1016/j.bone.2011.02.007

Ibandronate does not reduce the anabolic effects of PTH in ovariectomized rat tibiae: A microarchitectural and mechanical study

Xiao Yang, Yong Hoow Chan, Padmalosini Muthukumaran, Shamal DasDe, Swee Hin Teoh, Taeyong Lee

Department of Mechanical & Biomedical Engineering

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

24 Scopus citations

Abstract

Osteoporosis remains a challenging problem. Understanding the regulation on osteoclast and osteoblast by drugs has been of great interest. Both anabolic and anti-resorptive drugs yield positive results in the treatment of osteoporosis. However, whether the concurrent administration of parathyroid hormone (1-34) and ibandronate may offer an advantage over monotherapy is still unknown. This study, therefore, attempts to compare the efficacy of two therapeutical approaches and to investigate the beneficial effects in concurrent therapy in a rat model using three-point bending, pQCT and μCT analysis. A total of 60 female Sprague-Dawley rats of age 10 to 12. weeks were divided into 5 groups (SHAM, OVX. +. VEH, OVX. +. PTH, OVX. +. IBAN, OVX. +. PTH. +. IBAN) and subjected to ovariectomy or sham surgery accordingly. Low-dose parathyroid hormone (PTH) and/or ibandronate or its vehicle were administered subcutaneously to the respective groups starting from 4th week post-surgery at weekly intervals. Three rats from each group were euthanized every 2. weeks and their tibiae were harvested. The tibiae were subjected to metaphyseal three-point bending, pQCT and μCT analysis. Serum biomarkers for both bone formation (P1NP) and resorption (CTX) were studied. A total of 11 indices showed a significant difference between SHAM and OVX. +. VEH groups, suggesting the successful establishment of osteoporosis in the rat model. Compared to the previous studies which showed impedance from bisphosphonates in combination therapy with PTH, our study revealed that ibandronate does not block the anabolic effects of PTH in ovariectomized rat tibiae. Maximum load, strength-strain indices and serum bone formation markers of OVX + PTH + IBAN group are significantly higher than both monotherapy groups. With the proper ratio of anabolic and anti-resorptive drugs, the effect could be more pronounced.

Original language	English
Pages (from-to)	1154-1163
Number of pages	10
Journal	Bone
Volume	48
Issue number	5
DOIs	https://doi.org/10.1016/j.bone.2011.02.007
State	Published - 1 May 2011

Bibliographical note

Funding Information:
This work was supported by the Academic Research Funding (AcRF #R397-000-083-112 ) from the Ministry of Education (MoE) , Singapore. The authors wish to acknowledge Dr. Jonnathan Peneyra for performing the OVX surgeries, Dr. Chan Yiong Huak for helping in statistical analysis, Dr. Yeow Chen Hua for his expertise with μCT, Ms. Ally Chan for her assistance in pQCT and Ms. Katrina Wilson for proof-reading the manuscript drafts.

Keywords

Additive effect
Bone morphology
Ibandronate
Micro-CT
PTH

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10.1016/j.bone.2011.02.007

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title = "Ibandronate does not reduce the anabolic effects of PTH in ovariectomized rat tibiae: A microarchitectural and mechanical study",

abstract = "Osteoporosis remains a challenging problem. Understanding the regulation on osteoclast and osteoblast by drugs has been of great interest. Both anabolic and anti-resorptive drugs yield positive results in the treatment of osteoporosis. However, whether the concurrent administration of parathyroid hormone (1-34) and ibandronate may offer an advantage over monotherapy is still unknown. This study, therefore, attempts to compare the efficacy of two therapeutical approaches and to investigate the beneficial effects in concurrent therapy in a rat model using three-point bending, pQCT and μCT analysis. A total of 60 female Sprague-Dawley rats of age 10 to 12. weeks were divided into 5 groups (SHAM, OVX. +. VEH, OVX. +. PTH, OVX. +. IBAN, OVX. +. PTH. +. IBAN) and subjected to ovariectomy or sham surgery accordingly. Low-dose parathyroid hormone (PTH) and/or ibandronate or its vehicle were administered subcutaneously to the respective groups starting from 4th week post-surgery at weekly intervals. Three rats from each group were euthanized every 2. weeks and their tibiae were harvested. The tibiae were subjected to metaphyseal three-point bending, pQCT and μCT analysis. Serum biomarkers for both bone formation (P1NP) and resorption (CTX) were studied. A total of 11 indices showed a significant difference between SHAM and OVX. +. VEH groups, suggesting the successful establishment of osteoporosis in the rat model. Compared to the previous studies which showed impedance from bisphosphonates in combination therapy with PTH, our study revealed that ibandronate does not block the anabolic effects of PTH in ovariectomized rat tibiae. Maximum load, strength-strain indices and serum bone formation markers of OVX + PTH + IBAN group are significantly higher than both monotherapy groups. With the proper ratio of anabolic and anti-resorptive drugs, the effect could be more pronounced.",

keywords = "Additive effect, Bone morphology, Ibandronate, Micro-CT, PTH",

author = "Xiao Yang and Chan, {Yong Hoow} and Padmalosini Muthukumaran and Shamal DasDe and Teoh, {Swee Hin} and Taeyong Lee",

note = "Funding Information: This work was supported by the Academic Research Funding (AcRF #R397-000-083-112 ) from the Ministry of Education (MoE) , Singapore. The authors wish to acknowledge Dr. Jonnathan Peneyra for performing the OVX surgeries, Dr. Chan Yiong Huak for helping in statistical analysis, Dr. Yeow Chen Hua for his expertise with μCT, Ms. Ally Chan for her assistance in pQCT and Ms. Katrina Wilson for proof-reading the manuscript drafts. ",

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AU - Muthukumaran, Padmalosini

AU - DasDe, Shamal

AU - Teoh, Swee Hin

AU - Lee, Taeyong

N1 - Funding Information: This work was supported by the Academic Research Funding (AcRF #R397-000-083-112 ) from the Ministry of Education (MoE) , Singapore. The authors wish to acknowledge Dr. Jonnathan Peneyra for performing the OVX surgeries, Dr. Chan Yiong Huak for helping in statistical analysis, Dr. Yeow Chen Hua for his expertise with μCT, Ms. Ally Chan for her assistance in pQCT and Ms. Katrina Wilson for proof-reading the manuscript drafts.

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N2 - Osteoporosis remains a challenging problem. Understanding the regulation on osteoclast and osteoblast by drugs has been of great interest. Both anabolic and anti-resorptive drugs yield positive results in the treatment of osteoporosis. However, whether the concurrent administration of parathyroid hormone (1-34) and ibandronate may offer an advantage over monotherapy is still unknown. This study, therefore, attempts to compare the efficacy of two therapeutical approaches and to investigate the beneficial effects in concurrent therapy in a rat model using three-point bending, pQCT and μCT analysis. A total of 60 female Sprague-Dawley rats of age 10 to 12. weeks were divided into 5 groups (SHAM, OVX. +. VEH, OVX. +. PTH, OVX. +. IBAN, OVX. +. PTH. +. IBAN) and subjected to ovariectomy or sham surgery accordingly. Low-dose parathyroid hormone (PTH) and/or ibandronate or its vehicle were administered subcutaneously to the respective groups starting from 4th week post-surgery at weekly intervals. Three rats from each group were euthanized every 2. weeks and their tibiae were harvested. The tibiae were subjected to metaphyseal three-point bending, pQCT and μCT analysis. Serum biomarkers for both bone formation (P1NP) and resorption (CTX) were studied. A total of 11 indices showed a significant difference between SHAM and OVX. +. VEH groups, suggesting the successful establishment of osteoporosis in the rat model. Compared to the previous studies which showed impedance from bisphosphonates in combination therapy with PTH, our study revealed that ibandronate does not block the anabolic effects of PTH in ovariectomized rat tibiae. Maximum load, strength-strain indices and serum bone formation markers of OVX + PTH + IBAN group are significantly higher than both monotherapy groups. With the proper ratio of anabolic and anti-resorptive drugs, the effect could be more pronounced.

AB - Osteoporosis remains a challenging problem. Understanding the regulation on osteoclast and osteoblast by drugs has been of great interest. Both anabolic and anti-resorptive drugs yield positive results in the treatment of osteoporosis. However, whether the concurrent administration of parathyroid hormone (1-34) and ibandronate may offer an advantage over monotherapy is still unknown. This study, therefore, attempts to compare the efficacy of two therapeutical approaches and to investigate the beneficial effects in concurrent therapy in a rat model using three-point bending, pQCT and μCT analysis. A total of 60 female Sprague-Dawley rats of age 10 to 12. weeks were divided into 5 groups (SHAM, OVX. +. VEH, OVX. +. PTH, OVX. +. IBAN, OVX. +. PTH. +. IBAN) and subjected to ovariectomy or sham surgery accordingly. Low-dose parathyroid hormone (PTH) and/or ibandronate or its vehicle were administered subcutaneously to the respective groups starting from 4th week post-surgery at weekly intervals. Three rats from each group were euthanized every 2. weeks and their tibiae were harvested. The tibiae were subjected to metaphyseal three-point bending, pQCT and μCT analysis. Serum biomarkers for both bone formation (P1NP) and resorption (CTX) were studied. A total of 11 indices showed a significant difference between SHAM and OVX. +. VEH groups, suggesting the successful establishment of osteoporosis in the rat model. Compared to the previous studies which showed impedance from bisphosphonates in combination therapy with PTH, our study revealed that ibandronate does not block the anabolic effects of PTH in ovariectomized rat tibiae. Maximum load, strength-strain indices and serum bone formation markers of OVX + PTH + IBAN group are significantly higher than both monotherapy groups. With the proper ratio of anabolic and anti-resorptive drugs, the effect could be more pronounced.

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Ibandronate does not reduce the anabolic effects of PTH in ovariectomized rat tibiae: A microarchitectural and mechanical study

Abstract

Bibliographical note

Keywords

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