Interrelationships between bone microarchitecture and strength in ovariectomized monkeys treated with teriparatide.
Bone microarchitecture measured at the iliac crest at 6 mo was confirmed to be a reasonable surrogate for, and a predictor of, architecture and strength of the femoral neck and lumbar vertebra after 18 mo of teriparatide treatment. However, the data taken together showed the importance of cortical bone volume for vertebra to assess pharmacological effects on bone quality.


BACKGROUND
Improvements in bone architecture with teriparatide treatment are suggested to contribute to fracture risk reduction in osteoporotic patients. Teriparatide significantly improves microarchitecture in the iliac crest of humans by stimulating bone modeling and remodeling processes that differ dramatically from those induced by antiresorptives. The relationship between improvements of bone microarchitecture and improvements of bone strength with teriparatide treatment has not yet been fully studied.


METHODS
Ovariectomized monkeys were administered vehicle (n = 20); teriparatide 1.0 microg/kg/d (n = 19); or teriparatide 5.0 microg/kg/d (n = 21) for 18 mo. Iliac crest biopsies were obtained at 6 and 15 mo after initiation of treatment. Animals were killed after 18 mo of treatment, and adjacent vertebrae or contralateral proximal femora were processed for biomechanical or histomorphometric analyses. Pearson correlation analyses were performed to assess the relationship between biomechanical and static histomorphometric parameters of lumbar vertebra, femoral neck, and iliac crest biopsies.


RESULTS
Static histomorphometric parameters of the 6- and 15-mo biopsies were significantly correlated with the vertebral and femoral neck parameters obtained at 18 mo of teriparatide treatment. Iliac crest biopsy parameters at 6 and 15 mo also correlated with vertebral and femoral neck strength at 18 mo. Static histomorphometry of the lumbar vertebra and femoral neck at 18 mo also significantly correlated with strength at these sites. However, cortical bone volume of the lumbar vertebrae had the strongest correlation with vertebral and femoral neck strength (r = 0.74 and 0.71, respectively).


CONCLUSIONS
Teriparatide dose dependently improved cortical and trabecular microarchitecture of vertebra and femoral neck, as well as trabecular microarchitecture of the iliac crest. Bone microarchitecture at all sites was significantly correlated with lumbar vertebra and femoral neck strength. Cortical bone volume of vertebra had the strongest correlation with vertebral and femoral neck strength. Therefore, structural improvement seemed to be part of the mechanism for improved strength observed with teriparatide treatment. Trabecular bone architecture of the iliac crest at 6 mo also correlated with vertebral and femoral neck strength, as did femoral neck (cortical and trabecular) histomorphometry and trabecular histomorphometry of vertebra after 18 mo of treatment. Because clinical assessment of cortical bone volume is not readily possible for vertebra noninvasively, these findings confirm the importance of iliac crest biopsies to monitor skeletal health and show that biopsies are a reasonable surrogate to assess spine and femoral neck structure and function.
Chen
Peiqi
P
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. chenpe@lilly.com
Jerome
Christopher P
CP
Burr
David B
DB
Turner
Charles H
CH
Ma
Yanfei L
YL
Rana
Asad
A
Sato
Masahiko
M
D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology*; D019245:Compressive Strength / Q000187:drug effects / Q000502:physiology; D005260:Female; D005272:Femur Neck / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D007085:Ilium / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008159:Lumbar Vertebrae / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008252:Macaca fascicularis; D010052:Ovariectomy; D019379:Teriparatide / Q000494:pharmacology*
D019379:Teriparatide