Genetic background influences cortical bone response to ovariectomy.
Peak bone mass is genetically determined, but little is known about the heritability of bone loss. Inbred mice were ovariectomized at 16 weeks of age and killed at three time-points after surgery. We found that the variation in estrogen deficit-related cortical bone loss is genetically determined.


BACKGROUND
Variability in adult bone morphology and composition among three inbred mouse strains-A/J, C57BL/6J (B6), and C3H/HeJ (C3H)-suggests that they gain bone in different ways during growth. In this study, we tested the hypothesis that these strains would also lose bone differently after estrogen deprivation.


METHODS
Female A/J, B6, and C3H mice (N = 70/strain) were either ovariectomized (OVX) or sham-operated at 16 weeks of age and killed at 4, 8, and 16 weeks after surgery. Cortical bone histomorphometry was performed on right femoral mid-diaphyseal cross-sections. Mechanical properties were determined by loading left femoral mid-diaphyses to failure in four-point bending.


RESULTS
Both OVX-A/J and OVX-B6 mice showed a 7-8% decrease in cortical area and width because of an 8-10% marrow expansion at 16 weeks after OVX. This bone loss did not affect mechanical properties in OVX-A/J femurs, but maximum load and stiffness in OVX-B6 decreased slightly (9%) at 4 and 8 weeks, and markedly (14-19%) at 16 weeks after OVX. In contrast, OVX-C3H showed a significant decrease in cortical area and width (6-7%) at 4 weeks after OVX and a slight decrease in the subperiosteal area (4%) at 8 weeks after OVX, although marrow area remained unchanged. Surprisingly, intracortical resorption spaces, which were present in sham-C3H mice, were greatly increased (+195%) in OVX-C3H mice at 8 weeks after OVX. Bone strength and stiffness in OVX-C3H mice decreased markedly (12-14%) at 4 weeks but slightly (8-10%) at 8 weeks after OVX. All indices except intracortical pore area in OVX-C3H mice returned to sham levels at 16 weeks after OVX.


CONCLUSIONS
The magnitude, timing, and location of cortical bone loss after OVX varied significantly among A/J, B6, and C3H mice. The subsequent changes in mechanical properties after OVX depended on the variable bone patterns as well as the size and shape of the adult bone. Our results suggest that patterns of estrogen deficit-associated cortical bone loss are genetically determined.
Li
Chao Yang
CY
Leni and Peter W. May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York, USA.
Schaffler
Mitchell B
MB
Wolde-Semait
Henock T
HT
Hernandez
Christopher J
CJ
Jepsen
Karl J
KJ
D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000235:genetics; D001846:Bone Development / Q000235:genetics; D016723:Bone Remodeling / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics*; D004548:Elasticity; D005260:Female; D005269:Femur / Q000254:growth & development / Q000378:metabolism; D006253:Haversian System / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000235:genetics; D010052:Ovariectomy; D010521:Periosteum / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D014599:Uterus / Q000254:growth & development; D016474:Weight-Bearing