Cortical and trabecular morphology is altered in the limb bones of mice artificially selected for faster skeletal growth

Saira Farooq,Marta Marchini,Campbell Rolian,Sarah L Manske,Leah M Sparrow,Shannon Leussink,Hayley M Britz

doi:10.1038/s41598-017-10317-x

Saira Farooq, Marta Marchini + Show 5 more

Open Access

https://doi.org/10.1038/s41598-017-10317-x

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Abstract

Bone strength is influenced by mineral density and macro- and microstructure. Research into factors that contribute to bone morphology and strength has focused on genetic, environmental and morphological factors (e.g., body mass index), but little is known regarding the impact of rates of skeletal elongation on adult skeletal morphology and strength. Using micro-CT, we examined the impact of rates of skeletal elongation on bone cortical and trabecular morphology, and on rates of estrogen-dependent bone loss in the tibia in CD-1 mice, and in mice with accelerated skeletal growth (Longshanks). Groups of adult mice (n = 7/group) were subjected to ovariectomy or sham surgeries, scanned for 6 weeks, and indices of bone morphology were collected. Results show that Longshanks mice had significantly less trabecular bone at skeletal maturity, characterized by fewer, thinner trabeculae, and furthermore lost trabecular bone more slowly in response to ovariectomy. Artificial selection for rapid skeletal growth relative to somatic growth thus had a significant impact on trabecular bone morphology in Longshanks. Our data do not unequivocally demonstrate a causal relationship between rapid bone growth and reduced trabecular bone quality, but suggest that rapid linear bone growth may influence the risk of cancellous bone fragility.

Highlights

Bone strength is a major determinant of fracture risk in osteoporosis and other skeletal conditions such as osteopenia[1,2,3]
Comparing Longshanks to CD-1 mice allows us to emphasize the potential impact of limb bone linear growth and length at skeletal maturity over other factors known to contribute to skeletal morphology, such as nutrition and environmental factors, rate and duration of somatic growth, and body mass at skeletal maturity
We sought to answer the following questions: (1) is rapid linear growth associated with changes in cortical and trabecular bone morphology that could compromise a bone’s strength? (2) how does rapid linear bone growth correlate with changes in trabecular vs. cortical morphology? (3) are the changes in cortical and trabecular morphology, if any, similar between the two independently bred Longshanks lines?

Summary

Introduction

Bone strength is a major determinant of fracture risk in osteoporosis and other skeletal conditions such as osteopenia[1,2,3]. We investigated the relationship between accelerated skeletal growth and bone morphology and rates of estrogen-dependent bone loss, in Longshanks mice These mice were selectively bred for increases in tibia length relative to body mass[25, 26]. Comparing Longshanks to CD-1 mice allows us to emphasize the potential impact of limb bone linear growth and length at skeletal maturity over other factors known to contribute to skeletal morphology, such as nutrition and environmental factors, rate and duration of somatic growth, and body mass at skeletal maturity. We used longitudinal micro-CT scans in ovariectomized and sham-operated Longshanks and random-bred control mice to test the overall hypothesis that accelerated bone growth and increased bone length are associated with altered bone morphology and inferred strength at skeletal maturity in the two Longshanks lines. We sought to answer the following questions: (1) is rapid linear growth associated with changes in cortical and trabecular bone morphology that could compromise a bone’s strength? (2) how does rapid linear bone growth correlate with changes in trabecular vs. cortical morphology? (3) are the changes in cortical and trabecular morphology, if any, similar between the two independently bred Longshanks lines?

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