Browsing by Author "Jepsen, Karl J."

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    Differential changes in bone strength of two inbred mouse strains following administration of a sclerostin-neutralizing antibody during growth
    (PLOS, 2019-04-04) Mathis, Noah J.; Adaniya, Emily N.; Smith, Lauren M.; Robling, Alexander G.; Jepsen, Karl J.; Schlecht, Stephen H.; Anatomy and Cell Biology, IU School of Medicine
    Administration of sclerostin-neutralizing antibody (Scl-Ab) treatment has been shown to elicit an anabolic bone response in growing and adult mice. Prior work characterized the response of individual mouse strains but did not establish whether the impact of Scl-Ab on whole bone strength would vary across different inbred mouse strains. Herein, we tested the hypothesis that two inbred mouse strains (A/J and C57BL/6J (B6)) will show different whole bone strength outcomes following sclerostin-neutralizing antibody (Scl-Ab) treatment during growth (4.5-8.5 weeks of age). Treated B6 femurs showed a significantly greater stiffness (S) (68.8% vs. 46.0%) and maximum load (ML) (84.7% vs. 44.8%) compared to A/J. Although treated A/J and B6 femurs showed greater cortical area (Ct.Ar) similarly relative to their controls (37.7% in A/J and 41.1% in B6), the location of new bone deposition responsible for the greater mass differed between strains and may explain the greater whole bone strength observed in treated B6 mice. A/J femurs showed periosteal expansion and endocortical infilling, while B6 femurs showed periosteal expansion. Post-yield displacement (PYD) was smaller in treated A/J femurs (-61.2%, p < 0.001) resulting in greater brittleness compared to controls; an effect not present in B6 mice. Inter-strain differences in S, ML, and PYD led to divergent changes in work-to-fracture (Work). Work was 27.2% (p = 0.366) lower in treated A/J mice and 66.2% (p < 0.001) greater in treated B6 mice relative to controls. Our data confirmed the anabolic response to Scl-Ab shown by others, and provided evidence suggesting the mechanical benefits of Scl-Ab administration may be modulated by genetic background, with intrinsic growth patterns of these mice guiding the location of new bone deposition. Whether these differential outcomes will persist in adult and elderly mice remains to be determined.
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    Region-specific associations among tissue-level mechanical properties, porosity, and composition in human male femora
    (Elsevier, 2022) Mandair, Gurjit S.; Bigelow, Erin M. R.; Viswanathan, Gowri; Ward, Ferrous S.; Patton, Daniella M.; Schlecht, Stephen H.; Jepsen, Karl J.; Kohn, David H.; Orthopaedic Surgery, School of Medicine
    Region-specific differences in age-related bone remodeling are known to exist. We therefore hypothesized that the decline in tissue-level strength and post-yield strain (PYS) with age is not uniform within the femur, but is driven by region-specific differences in porosity and composition. Four-point bending was conducted on anterior, posterior, medial, and lateral beams from male cadaveric femora (n = 33, 18-89 yrs of age). Mid-cortical porosity, composition, and mineralization were assessed using nano-computed tomography (nanoCT), Raman spectroscopy, and ashing assays. Traits between bones from young and elderly groups were compared, while multivariate analyses were used to identify traits that predicted strength and PYS at the regional level. We show that age-related decline in porosity and mechanical properties varied regionally, with highest positive slope of age vs. Log(porosity) found in posterior and anterior bone, and steepest negative slopes of age vs. strength and age vs. PYS found in anterior bone. Multivariate analyses show that Log(porosity) and/or Raman 1246/1269 ratio explained 46-51% of the variance in strength in anterior and posterior bone. Three out of five traits related to Log(porosity), mineral crystallinity, 1246/1269, mineral/matrix ratio, and/or hydroxyproline/proline (Hyp/Pro) ratio, explained 35-50% of the variance in PYS in anterior, posterior and lateral bones. Log(porosity) and Hyp/Pro ratio alone explained 13% and 19% of the variance in strength and PYS in medial bone, respectively. The predictive performance of multivariate analyses was negatively impacted by pooling data across all bone regions, underscoring the complexity of the femur and that the use of pooled analyses may obscure underlying region-specific differences.
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    Sex and External Size Specific Limitations in Assessing Bone Health From Adult Hand Radiographs
    (Wiley, 2022-06-29) Bigelow, Erin M.R.; Goulet, Robert W.; Ciarelli, Antonio; Schlecht, Stephen H.; Kohn, David H.; Bredbenner, Todd L.; Harlow, Sioban D.; Karvonen-Gutierrez, Carrie A.; Jepsen, Karl J.; Orthopaedic Surgery, School of Medicine
    Morphological parameters measured for the second metacarpal from hand radiographs are used clinically for assessing bone health during growth and aging. Understanding how these morphological parameters relate to metacarpal strength and strength at other anatomical sites is critical for providing informed decision-making regarding treatment strategies and effectiveness. The goals of this study were to evaluate the extent to which 11 morphological parameters, nine of which were measured from hand radiographs, relate to experimentally measured whole-bone strength assessed at multiple anatomical sites and to test whether these associations differed between men and women. Bone morphology and strength were assessed for the second and third metacarpals, radial diaphysis, femoral diaphysis, and proximal femur for 28 white male donors (18-89 years old) and 35 white female donors (36-89+ years old). The only morphological parameter to show a significant correlation with strength without a sex-specific effect was cortical area. Dimensionless morphological parameters derived from hand radiographs correlated significantly with strength for females, but few did for males. Males and females showed a significant association between the circularity of the metacarpal cross-section and the outer width measured in the mediolateral direction. This cross-sectional shape variation contributed to systematic bias in estimating strength using cortical area and assuming a circular cross-section. This was confirmed by the observation that use of elliptical formulas reduced the systematic bias associated with using circular approximations for morphology. Thus, cortical area was the best predictor of strength without a sex-specific difference in the correlation but was not without limitations owing to out-of-plane shape variations. The dependence of cross-sectional shape on the outer bone width measured from a hand radiograph may provide a way to further improve bone health assessments and informed decision making for optimizing strength-building and fracture-prevention treatment strategies.
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    State of the mineralized tissue comprising the femoral ACL enthesis in young women with an ACL failure
    (Wiley, 2021) Patton, Daniella M.; Ochocki, Danielle N.; Martin, Colin T.; Casden, Michael; Jepsen, Karl J.; Ashton-Miller, James A.; Wojtys, Edward M.; Schlecht, Stephen H.; Orthopaedic Surgery, School of Medicine
    Despite poor graft integration among some patients that undergo an ACL reconstruction, there has been little consideration of the bone quality into which the ACL femoral tunnel is drilled and the graft is placed. Bone mineral density of the knee decreases following ACL injury. However, trabecular and cortical architecture differences between injured and non-injured femoral ACL entheses have not been reported. We hypothesize that injured femoral ACL entheses will show significantly less cortical and trabecular mass compared to non-injured controls.Femoral ACL enthesis explants from 54 female patients (13 – 25 years) were collected during ACL reconstructive surgery. Control explants (n = 12) were collected from 7 donors (18 - 36 years). Injured (I) femoral explants differed from those of non-injured (NI) controls with significantly less (p ≤ 0.001) cortical volumetric bone mineral density (vBMD) (NI: 736.1 – 867.6 mg/cc; I: 451.2 – 891.9 mg/cc), relative bone volume (BV/TV) (NI: 0.674 – 0.867; I: 0.401 – 0.792) and porosity (Ct.Po) (NI: 0.133 – 0.326; I: 0.209 – 0.600). Injured explants showed significantly lesstrabecular vBMD (p = 0.013) but not trabecular BV/TV (p = 0.314), thickness (p = 0.412), or separation (p = 0.828). We found significantly less cortical bone within injured femoral entheses compared to non-injured controls.Lower cortical and trabecular bone mass within patient femoral ACL entheses may help explain poor ACL graft osseointegration outcomes in the young and may be a contributor to the osteolytic phenomenon that often occurs within the graft tunnel following ACL reconstruction.
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    Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes
    (Springer, 2016-12) Aref, Mohammad W.; McNerny, Erin M.B.; Brown, Drew; Jepsen, Karl J.; Allen, Matthew R.; Anatomy and Cell Biology, School of Medicine
    Aref, M. W., McNerny, E. M. B., Brown, D., Jepsen, K. J., & Allen, M. R. (2016). Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes. Osteoporosis International : A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 27(12), 3637–3643. https://doi.org/10.1007/s00198-016-3701-9