Weekly teriparatide treatment increases vertebral body strength by improving cortical shell architecture in ovariectomized cynomolgus monkeys

• Published in: Bone (New York, N.Y.) Vol. 121; pp. 80 - 88
• Main Authors: Fujihara, Ryuji, Mashiba, Tasuku, Yoshitake, Shingo, Komatsubara, Satoshi, Iwata, Ken, Takao-Kawabata, Ryoko, Yamamoto, Tetsuji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2019
• Subjects: Animals; Bone Density - drug effects; Bone histomorphometry; Bone mechanical property; Bone Remodeling - drug effects; Compressive Strength - drug effects; Cynomolgus monkey; Female; Lumbar Vertebrae - drug effects; Macaca fascicularis; Ovariectomy; Teriparatide; Teriparatide - therapeutic use; Vertebral cortical bone; Bone histomorphometry; Vertebral cortical bone; Bone mechanical property; Teriparatide; Cynomolgus monkey
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2019.01.006

Weekly teriparatide treatment is reported to reduce the incidence of osteoporotic vertebral fractures. However, the effect of weekly teriparatide on cortical bone has not been clarified. This study aimed to examine the effects of weekly teriparatide treatment on bone mass, intracortical structure, and remodeling of the lumbar vertebral cortical shell and its relation to mechanical properties in ovariectomized cynomolgus monkeys. Female monkeys, aged 9 to 15 years, were divided into four groups: (1) SHAM group, (2) ovariectomized group (OVX group), (3) OVX with 1.2 μg/kg once-weekly teriparatide group (LOW group), (4) OVX with 6.0 μg/kg once-weekly teriparatide group (HIGH group). After 18 months, all animals were double-labeled with calcein, and lumbar vertebrae were analyzed with histomorphometry and compressive mechanical tests. Following ovariectomy, we found reductions in the anterior cortical shell area of the vertebrae and reductions in nearly all of the tested vertebral mechanical properties. Weekly teriparatide significantly preserved the anterior cortical shell area and the energy absorption capacity of the lumbar vertebrae in a dose-dependent manner. Multiple regression analyses indicated that improved mechanical properties were more associated with the increased anterior cortical shell area rather than the cancellous bone volume. The intracortical structure of the Haversian canals was also preserved following teriparatide treatment after ovariectomy. These findings suggest the importance of the cortical shell as a therapeutic target in the treatment of osteoporosis. Weekly teriparatide treatment increases the compressive mechanical strength of the lumbar vertebrae by thickening the anterior cortical shell.
•Ovariectomy led to reduced anterior cortical shell area and vertebral mechanical strength in cynomolgus monkeys.•Weekly teriparatide treatment dose-dependently preserved anterior cortical shell area and mechanical properties of the lumbar vertebrae.•Improved mechanical properties were associated more with increased anterior cortical shell area than with cancellous bone volume.