Understanding bone strength: size isn’t everything

Meulen, Marjolein C. H. van der; Jepsen, Karl J.; Mikic, Borjana

doi:10.1016/s8756-3282(01)00491-4

Cited by 253 publications

(175 citation statements)

References 22 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…Bone biomechanical integrity can be partitioned into the following contributing components: the amount, architecture and distribution, and bone material composition and strength [32,33]. The experimental approach we took was to examine bone biomechanical integrity of femurs from two distinct mouse strains and three genotypes at three age points.…”

Section: Discussionmentioning

confidence: 99%

Role of genetic background in determining phenotypic severity throughout postnatal development and at peak bone mass in Col1a2 deficient mice (oim)

Carleton¹,

McBride²,

Carson³

et al. 2008

Bone

View full text Add to dashboard Cite

Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disease characterized by extreme bone fragility. Although fracture numbers tend to decrease post-puberty, OI patients can exhibit significant variation in clinical outcome, even among related individuals harboring the same mutation. OI most frequently results from mutations in type I collagen genes, yet how genetic background impacts phenotypic outcome remains unclear. Therefore, we analyzed the phenotypic severity of a known proα2(I) collagen gene defect (oim) on two genetic backgrounds (congenic C57BL/6J and outbred B6C3Fe) throughout postnatal development to discern the phenotypic contributions of the Col1a2 locus relative to the contribution of the genetic background.To this end, femora and tibiae were isolated from wildtype (Wt) and homozygous (oim/oim) mice of each strain at 1, 2 and 4 months of age. Femoral geometry was determined via µCT prior to torsional loading to failure to assess bone structural and material biomechanical properties. Changes in mineral composition, collagen content and bone turnover were determined using neutron activation analyses, hydroxyproline content and serum pyridinoline crosslinks.Corresponding Author: Charlotte L. Phillips, Ph.D., Associate Professor, Departments of Biochemistry and Child Health, University of Missouri-Columbia, 1 Hospital Dr., M743 Medical Sciences Bldg., Columbia, MO 65212, Phone: (573) 882-5122, Fax: (573) 884-4597, Email: PhillipsCL@missouri.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. µCT analysis demonstrated genotype-, strain-and age-associated changes in femoral geometry as well as a marked decrease in the amount of bone in oim/oim mice of both strains. Oim/oim mice of both strains, as well as C57BL/6J (B6) mice of all genotypes, had reduced femoral biomechanical strength properties compared to Wt at all ages, although they improved with age. Mineral levels of fluoride, magnesium and sodium were associated with biomechanical strength properties in both strains and all genotypes at all ages. Oim/oim animals also had reduced collagen content as compared to Wt at all ages. Serum pyridinoline crosslinks were highest at two months of age, regardless of strain or genotype. NIH Public AccessStrain differences in bone parameters exist throughout development, implicating a role for genetic background in determining biomechanical strength. Age-associated improvements indicate that oim/ oim animals partially compensate for their weaker bone material, but never attain Wt levels. These studies indicate the importance of genetic back...

show abstract

Section: Discussionmentioning

confidence: 99%

Role of genetic background in determining phenotypic severity throughout postnatal development and at peak bone mass in Col1a2 deficient mice (oim)

Carleton¹,

McBride²,

Carson³

et al. 2008

Bone

View full text Add to dashboard Cite

show abstract

“…Bone strength has been shown to depend on both its density and structure [9], which may or may not be interdependent. Density measures alone, although widely used clinically, cannot identify osteoporotic subjects who will sustain fractures, due to the large overlap in bone mass measures in individuals with fractures and those without fractures [10].…”

Section: Introductionmentioning

confidence: 99%

“…Density measures alone, although widely used clinically, cannot identify osteoporotic subjects who will sustain fractures, due to the large overlap in bone mass measures in individuals with fractures and those without fractures [10]. Other factors including bone size, architecture and material properties must be considered [9]. Multiple approaches such as Mean Intercept Lengths (MIL) [10] and the Fourier power spectrum [11,12,13,14] have been used to characterize the structure of trabecular bone, particularly in describing orientation disparity or anisotropy.…”

Section: Introductionmentioning

confidence: 99%

The effect of a short-term delay of puberty on trabecular bone mass and structure in female rats: A texture-based and histomorphometric analysis

Yingling

Xiang

Raphan

et al. 2007

Bone

View full text Add to dashboard Cite

Accrual of bone mass and strength during development is imperative in order to reduce the risk of fracture later in life. Although delayed pubertal onset is associated with an increased incidence of stress fracture, evidence supports the concept of "catch up" growth. It remains unclear if deficits in bone mass associated with delayed puberty have long term effects on trabecular bone structure and strength. The purpose of this study was to use texture-based analysis and histomorphometry to investigate the effect of a delay in puberty on trabecular bone mass and structure immediately postpuberty and at maturity in female rats. Forty-eight female Sprague Dawley rats (25 days) were randomly assigned to one of four groups; 1) short-term control (C-ST), 2) long-term control (C-LT), 3) short-term GnRH antagonist (G-ST) and 4) long-term GnRH antagonist (G-LT). Injections of either saline or gonadotropin-releasing hormone antagonist (GnRH-a) (100 μg/day) (Cetrotide™, Serono, Inc) were given intraperitoneally for 18 days (day 35-42) to both ST and LT. The ST groups were sacrificed after the last injection (day 43) and the LT groups at 6 months of age. Pubertal and gonadal development was retarded by the GnRA antagonist injections as indicated by a delay in vaginal opening, lower ovarian and uterine weights and suppressed estradiol levels in the short-term Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptBone. Author manuscript; available in PMC 2007 April 10. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript experimental animals (G-ST). Delayed puberty caused a transient reduction in trabecular bone area as assessed by histomorphometry. Specifically, the significant deficit in bone area resulted from a decreased number of trabecula and an increase in trabecular separation. Texture analysis, a new method to assess bone density and structural anisotropy, correlated well with the standard histomorphometry and measured significant deficits in the density measure (M Density ) in the G-ST group that remained at maturity (6 months). The texture energy deficit in the G-ST group was primarily in the 0° orientation (−13.2 %), which measures the longitudinal trabeculae in the proximal tibia. However, the deficit in the G-LT group was in the 45° and 135° orientations. These results suggest that any "catch-up" growth following the cessation of the GnRH-antagonist injection protocol may be directed in trabeculae oriented perpendicular to 0° at the expense of trabeculae in other orientations.

show abstract

“…Regardless of the test, appropriate measurements of bone size and length must be reported so that data can be normalized for geometric differences. To understand bone structural performance, structural measurements must be accompanied either by cross-sectional geometry or tissue material properties [20]. For example, whole femora of A/J mice are significantly stronger but more brittle than C57BL/6J when tested in four-point bending [lo].…”

Section: Mechunicul Propertiesmentioning

confidence: 99%