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Clodronate prevents osteopenia and loss of trabecular connectivity in estrogen-deficient rats.
J Bone Miner Res. 1998 Feb; 13(2):287-96.JB

Abstract

Daily oral clodronate treatment was evaluated in Sprague-Dawley rats for its ability to inhibit estrogen-deficiency-induced changes in femoral neck, femoral diaphysis, and lumbar vertebrae (L4-L5). Six-month-old ovariectomized (OVX) rats were administered by gavage a vehicle (Veh) or clodronate (100 or 500 mg/kg/day). Sham-operated (SHAM) control rats received the vehicle (n = 15/group). Treatment was started on the day of operation and continued for 3 months. Trabecular bone volume (BV/TV) and structural variables (trabecular number, Tb.N; thickness, Tb.Th; separation, Tb.Sp; and trabecular bone pattern factor, Tb.Pf) were assessed on secondary spongiosa of the right femoral neck Furthermore, cantilever bending test of the left femoral neck and compression test of L4, ash weight of L5, and morphometric studies of femoral diaphysis were carried out, and serum and urinary markers of bone turnover were determined. The OVX/Veh group had higher levels of serum osteocalcin and alkaline phosphatase and higher urinary excretion of deoxypyridinoline/creatinine than the SHAM/Veh group at 3 months postsurgery, and clodronate reduced these changes. BV/TV of femoral neck, bone mass of L5, and the maximum loads of the femoral neck and L4 were lower after OVX than SHAM operation. Although clodronate prevented trabecular bone loss in the femoral neck and preserved Tb.Pf at the SHAM control level, it failed to preserve the mechanical strength at the femoral neck However, in lumbar vertebrae, clodronate prevented the loss of bone mass and mechanical properties. Furthermore, there was a good positive correlation between maximum load of L4 and the ash weight of L5 (n = 58, r = 0.69, p < 0.001). In the femoral neck (n = 55), Tb.Pf correlated negatively with BV/TV and Tb.N (r = -0.59 and r = -0.55;p < 0.001, respectively) and positively with Tb.Sp (r = 0.61, p < 0.001). In femoral mid-diaphysis, there were no significant changes in cortical bone geometry in any of the groups. We conclude that orally administered clodronate suppresses the enhanced bone turnover in adult OVX rats and preserves trabecular bone volume and connectivity in the femoral neck In the axial skeleton, clodronate has a beneficial effect on lumbar vertebral bone mass and strength.

Authors+Show Affiliations

Leiras Oy, Biomedical Research Center, Turku, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

9495523

Citation

Kippo, K, et al. "Clodronate Prevents Osteopenia and Loss of Trabecular Connectivity in Estrogen-deficient Rats." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 13, no. 2, 1998, pp. 287-96.
Kippo K, Hannuniemi R, Isaksson P, et al. Clodronate prevents osteopenia and loss of trabecular connectivity in estrogen-deficient rats. J Bone Miner Res. 1998;13(2):287-96.
Kippo, K., Hannuniemi, R., Isaksson, P., Laurén, L., Osterman, T., Peng, Z., Tuukkanen, J., Kuurtamo, P., Väänänen, H. K., & Sellman, R. (1998). Clodronate prevents osteopenia and loss of trabecular connectivity in estrogen-deficient rats. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 13(2), 287-96.
Kippo K, et al. Clodronate Prevents Osteopenia and Loss of Trabecular Connectivity in Estrogen-deficient Rats. J Bone Miner Res. 1998;13(2):287-96. PubMed PMID: 9495523.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clodronate prevents osteopenia and loss of trabecular connectivity in estrogen-deficient rats. AU - Kippo,K, AU - Hannuniemi,R, AU - Isaksson,P, AU - Laurén,L, AU - Osterman,T, AU - Peng,Z, AU - Tuukkanen,J, AU - Kuurtamo,P, AU - Väänänen,H K, AU - Sellman,R, PY - 1998/3/12/pubmed PY - 1998/3/12/medline PY - 1998/3/12/entrez SP - 287 EP - 96 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 13 IS - 2 N2 - Daily oral clodronate treatment was evaluated in Sprague-Dawley rats for its ability to inhibit estrogen-deficiency-induced changes in femoral neck, femoral diaphysis, and lumbar vertebrae (L4-L5). Six-month-old ovariectomized (OVX) rats were administered by gavage a vehicle (Veh) or clodronate (100 or 500 mg/kg/day). Sham-operated (SHAM) control rats received the vehicle (n = 15/group). Treatment was started on the day of operation and continued for 3 months. Trabecular bone volume (BV/TV) and structural variables (trabecular number, Tb.N; thickness, Tb.Th; separation, Tb.Sp; and trabecular bone pattern factor, Tb.Pf) were assessed on secondary spongiosa of the right femoral neck Furthermore, cantilever bending test of the left femoral neck and compression test of L4, ash weight of L5, and morphometric studies of femoral diaphysis were carried out, and serum and urinary markers of bone turnover were determined. The OVX/Veh group had higher levels of serum osteocalcin and alkaline phosphatase and higher urinary excretion of deoxypyridinoline/creatinine than the SHAM/Veh group at 3 months postsurgery, and clodronate reduced these changes. BV/TV of femoral neck, bone mass of L5, and the maximum loads of the femoral neck and L4 were lower after OVX than SHAM operation. Although clodronate prevented trabecular bone loss in the femoral neck and preserved Tb.Pf at the SHAM control level, it failed to preserve the mechanical strength at the femoral neck However, in lumbar vertebrae, clodronate prevented the loss of bone mass and mechanical properties. Furthermore, there was a good positive correlation between maximum load of L4 and the ash weight of L5 (n = 58, r = 0.69, p < 0.001). In the femoral neck (n = 55), Tb.Pf correlated negatively with BV/TV and Tb.N (r = -0.59 and r = -0.55;p < 0.001, respectively) and positively with Tb.Sp (r = 0.61, p < 0.001). In femoral mid-diaphysis, there were no significant changes in cortical bone geometry in any of the groups. We conclude that orally administered clodronate suppresses the enhanced bone turnover in adult OVX rats and preserves trabecular bone volume and connectivity in the femoral neck In the axial skeleton, clodronate has a beneficial effect on lumbar vertebral bone mass and strength. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/9495523/Clodronate_prevents_osteopenia_and_loss_of_trabecular_connectivity_in_estrogen_deficient_rats_ DB - PRIME DP - Unbound Medicine ER -