TY - JOUR
T1 - Ibandronate does not reduce the anabolic effects of PTH in ovariectomized rat tibiae
T2 - A microarchitectural and mechanical study
AU - Yang, Xiao
AU - Chan, Yong Hoow
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.
PY - 2011/5/1
Y1 - 2011/5/1
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.
KW - Additive effect
KW - Bone morphology
KW - Ibandronate
KW - Micro-CT
KW - PTH
UR - http://www.scopus.com/inward/record.url?scp=79954614496&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2011.02.007
DO - 10.1016/j.bone.2011.02.007
M3 - Article
C2 - 21334474
AN - SCOPUS:79954614496
SN - 8756-3282
VL - 48
SP - 1154
EP - 1163
JO - Bone
JF - Bone
IS - 5
ER -