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Reductions in bone mass, structure, and strength in axial and appendicular skeletons associated with increased turnover after ovariectomy in mature cynomolgus monkeys and preventive effects of clodronate.
J Bone Miner Res. 2002 Mar; 17(3):534-43.JB

Abstract

Over 16 months, we evaluated the effects of ovariectomy (OVX) and bisphosphonate clodronate (CLO) on bone in 48 cynomolgus monkeys (9-15 years old) fed a normal calcium diet. We established three OVX groups (oral CLO at 0 [OVX control], 12, or 60 mg/kg per day) and one sham-operated (SHAM) group. At 16 months, the bone mineral density (BMD) values (percentage of group baseline; OVX control vs. SHAM) for lumbar bone (L3-L5), proximal femur, midfemur, radius, and tibia were -2.6% versus 11.2%, -3.5% versus 8.9%, -3.0% versus 9.0%, -5.5% versus 15.7%, and -6.7% versus 13.9%, respectively. In OVX control (i) tibia showed significant loss of bone mineral content (BMC; vs. baseline), (ii) urinary deoxypyridinoline (DPD) and serum osteocalcin (OC) levels increased (peak = 182% and 168%, respectively, of SHAM), (iii) in lumbar bone and midfemur, ultimate load (UL) was reduced (vs. SHAM), (iv) in lumbar bone, trabecular bone-formation rates (BFRs) were not changed significantly, but tibial endocortical and intracortical bone formation rates were significantly raised (vs. SHAM), (v) the volumetric BMD (vBMD) and geometry of the tibial cortex (measured by peripheral quantitative computed tomography [pQCT]) were significantly reduced (vs. SHAM). CLO, 60 mg/kg per day but not 12 mg/kg per day, significantly inhibited OVX-induced changes, age-dependent increases in bone mass, and ability to maintain structure. Thus, in OVX mature cynomolgus monkeys (possibly, a unique model of the cortical bone loss secondary to estrogen deficiency), the post-OVX increases in systemic bone markers were slight, but stimulation of local turnover in the cortical envelope was enough to cause bone loss (more so in tibia than in lumbar trabecular bone). High-dose CLO prevented these changes.

Authors+Show Affiliations

Pharmacology Research, R & D, Kissei Pharmaceutical Company, Ltd., Nagano, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11874245

Citation

Itoh, Fumiaki, et al. "Reductions in Bone Mass, Structure, and Strength in Axial and Appendicular Skeletons Associated With Increased Turnover After Ovariectomy in Mature Cynomolgus Monkeys and Preventive Effects of Clodronate." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 17, no. 3, 2002, pp. 534-43.
Itoh F, Kojima M, Furihata-Komatsu H, et al. Reductions in bone mass, structure, and strength in axial and appendicular skeletons associated with increased turnover after ovariectomy in mature cynomolgus monkeys and preventive effects of clodronate. J Bone Miner Res. 2002;17(3):534-43.
Itoh, F., Kojima, M., Furihata-Komatsu, H., Aoyagi, S., Kusama, H., Komatsu, H., & Nakamura, T. (2002). Reductions in bone mass, structure, and strength in axial and appendicular skeletons associated with increased turnover after ovariectomy in mature cynomolgus monkeys and preventive effects of clodronate. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 17(3), 534-43.
Itoh F, et al. Reductions in Bone Mass, Structure, and Strength in Axial and Appendicular Skeletons Associated With Increased Turnover After Ovariectomy in Mature Cynomolgus Monkeys and Preventive Effects of Clodronate. J Bone Miner Res. 2002;17(3):534-43. PubMed PMID: 11874245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reductions in bone mass, structure, and strength in axial and appendicular skeletons associated with increased turnover after ovariectomy in mature cynomolgus monkeys and preventive effects of clodronate. AU - Itoh,Fumiaki, AU - Kojima,Masami, AU - Furihata-Komatsu,Hanako, AU - Aoyagi,Shigemi, AU - Kusama,Hiroshi, AU - Komatsu,Hidetada, AU - Nakamura,Toshitaka, PY - 2002/3/5/pubmed PY - 2002/9/11/medline PY - 2002/3/5/entrez SP - 534 EP - 43 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 - 17 IS - 3 N2 - Over 16 months, we evaluated the effects of ovariectomy (OVX) and bisphosphonate clodronate (CLO) on bone in 48 cynomolgus monkeys (9-15 years old) fed a normal calcium diet. We established three OVX groups (oral CLO at 0 [OVX control], 12, or 60 mg/kg per day) and one sham-operated (SHAM) group. At 16 months, the bone mineral density (BMD) values (percentage of group baseline; OVX control vs. SHAM) for lumbar bone (L3-L5), proximal femur, midfemur, radius, and tibia were -2.6% versus 11.2%, -3.5% versus 8.9%, -3.0% versus 9.0%, -5.5% versus 15.7%, and -6.7% versus 13.9%, respectively. In OVX control (i) tibia showed significant loss of bone mineral content (BMC; vs. baseline), (ii) urinary deoxypyridinoline (DPD) and serum osteocalcin (OC) levels increased (peak = 182% and 168%, respectively, of SHAM), (iii) in lumbar bone and midfemur, ultimate load (UL) was reduced (vs. SHAM), (iv) in lumbar bone, trabecular bone-formation rates (BFRs) were not changed significantly, but tibial endocortical and intracortical bone formation rates were significantly raised (vs. SHAM), (v) the volumetric BMD (vBMD) and geometry of the tibial cortex (measured by peripheral quantitative computed tomography [pQCT]) were significantly reduced (vs. SHAM). CLO, 60 mg/kg per day but not 12 mg/kg per day, significantly inhibited OVX-induced changes, age-dependent increases in bone mass, and ability to maintain structure. Thus, in OVX mature cynomolgus monkeys (possibly, a unique model of the cortical bone loss secondary to estrogen deficiency), the post-OVX increases in systemic bone markers were slight, but stimulation of local turnover in the cortical envelope was enough to cause bone loss (more so in tibia than in lumbar trabecular bone). High-dose CLO prevented these changes. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/11874245/Reductions_in_bone_mass_structure_and_strength_in_axial_and_appendicular_skeletons_associated_with_increased_turnover_after_ovariectomy_in_mature_cynomolgus_monkeys_and_preventive_effects_of_clodronate_ L2 - https://doi.org/10.1359/jbmr.2002.17.3.534 DB - PRIME DP - Unbound Medicine ER -