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1.
Osteoporos Int ; 33(5): 1125-1136, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35034156

RESUMO

Macro- and microarchitectural, bone material property, dynamic histomorphometric, and bone turnover marker data were studied in normal bone mineral density (BMD) post-menopausal women with fragility fracture. Women with fracture had thinner iliac cortices and more homogeneous bone material properties in cortical bone than age/BMD-matched non-fracture women. Low cortical thickness and bone tissue heterogeneity in normal BMD women are associated with prevalent fragility fracture. INTRODUCTION: Bone mass (bone mineral density, (BMD)) of the spine and hip is today's best single measurement for evaluating future fragility fracture risk. However, the majority of fragility fractures occur in women with BMD T-score above the WHO osteoporotic BMD threshold of - 2.5, indicating that non-BMD endpoints may play a role in their fragility fractures. We hypothesize that in non-osteoporotic women, bone micoarchitecture, bone material properties, dynamic histomorphometric endpoints, and bone turnover markers are related to fragility fracture. METHODS: Two groups (N = 60 each) of post-menopausal women with total hip BMD T-score ranging from + 0.3 to -2.49 were recruited: fragility fracture and age/BMD-matched, non-fragility fracture women. Normal (T-score > - 0.99) and osteopenic (T-score ≤ - 1.0) BMD cohorts were designated within both the fracture and non-fracture groups. Transiliac biopsy specimens were obtained to evaluate dynamic histomorphometric and microarchitectural endpoints and bone material properties by static and dynamic nanoindentation testing. All variables for fracture and non-fracture women within each BMD cohort were compared by the Wilcoxon signed-rank test (P < 0.01). RESULTS: Compared to non-fracture/normal BMD women, fracture/normal BMD women display lower iliac cortical thickness (- 12%, P = 0.0041) and lower heterogeneity of hardness (- 27%, P = 0.0068), elastic modulus (- 35%, P = 0.0009), and storage modulus (- 23%, P = 0.0054) in the cortical bone tissue, and lower heterogeneity of hardness (- 13%, P = 0.0088) in the trabecular bone tissue. Osteopenic women had no abnormalities related to fracture status. CONCLUSION: Post-menopausal women with normal BMD and fragility fracture have low cortical thickness and heterogeneity of several bone material properties in cortical and trabecular mineralized bone tissue. These differences may explain a portion of the excess bone fragility in women with normal BMD and fragility fracture.


Assuntos
Fraturas Ósseas , Fraturas por Osteoporose , Densidade Óssea , Remodelação Óssea , Osso Esponjoso/patologia , Feminino , Humanos , Ílio , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/patologia , Pós-Menopausa
2.
Bone ; 127: 207-214, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31229674

RESUMO

Women with similar areal Bone Mineral Densities (BMD) may show divergent fracture incidence due to differences in bone quality. The hypothesis tested in the present pilot study is that postmenopausal (PM) women who have sustained osteoporotic fractures have altered organic matrix quality compared to those who have not. We used Raman microspectroscopy to analyze transiliac biopsies collected from fracturing (n = 6, mean age 62.5 ±â€¯7.4 yrs; Cases) and non-fracturing PM women (n = 6, age- and BMD-matched; mean age 62.2 ±â€¯7.3 yrs; Controls). Previous results show differences in intrinsic material properties by nanoindentation that are more homogenously distributed and could facilitate microcrack propagation in Cases, along with lower mineral carbonate/phosphate ratio by Fourier transform infrared spectroscopic imaging, and no differences in bone tissue mineralization by digitized microradiography. No differences between groups were seen by conventional histomorphometry. Spectra were acquired 2 µm away from previously performed nanoindents, in cortical and cancellous compartments. The determined parameters were: mineral to matrix ratio (MM), and nanoporosity (a surrogate for tissue water (TW)), glycosaminoglycan (GAG), pyridinoline (Pyd; trivalent enzymatic collagen cross-link), N(6)-carboxymethyllysine (CML; advanced glycation endproduct), and pentosidine (PEN; advanced glycation endproduct) content. ANCOVA indicated no differences in any of the spectroscopic outcomes between cancellous and cortical compartments. On the other hand, Cases had lower nanoporosity (TW) and GAG, and elevated Pyd, and CML content compared to Controls. In conclusion, the results of the present study indicate significant differences in organic matrix quality in PM women that sustain fragility fractures versus age- and BMD-matched controls, highlighting its importance as a potential independent determinant of fracture incidence.


Assuntos
Densidade Óssea , Matriz Óssea/patologia , Fraturas Ósseas/patologia , Fraturas Ósseas/fisiopatologia , Pós-Menopausa/fisiologia , Fatores Etários , Biópsia , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Análise Espectral Raman
3.
Bone ; 97: 233-242, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28132909

RESUMO

Osteoporotic (low-trauma) fractures are a significant public health problem. Over 50% of women over 50yrs. of age will suffer an osteoporotic fracture in their remaining lifetimes. While current therapies reduce skeletal fracture risk by maintaining or increasing bone density, additional information is needed that includes the intrinsic material strength properties of bone tissue to help develop better treatments, since measurements of bone density account for no more than ~50% of fracture risk. The hypothesis tested here is that postmenopausal women who have sustained osteoporotic fractures have reduced bone quality, as indicated with measures of intrinsic material properties compared to those who have not fractured. Transiliac biopsies (N=120) were collected from fracturing (N=60, Cases) and non-fracturing postmenopausal women (N=60, age- and BMD-matched Controls) to measure intrinsic material properties using the nano-indentation technique. Each biopsy specimen was embedded in epoxy resin and then ground, polished and used for the nano-indentation testing. After calibration, multiple indentations were made using quasi-static (hardness, modulus) and dynamic (storage and loss moduli) testing protocols. Multiple indentations allowed the median and variance to be computed for each type of measurement for each specimen. Cases were found to have significantly lower median values for cortical hardness and indentation modulus. In addition, cases showed significantly less within-specimen variability in cortical modulus, cortical hardness, cortical storage modulus and trabecular hardness, and more within-specimen variability in trabecular loss modulus. Multivariate modeling indicated the presence of significant independent mechanical effects of cortical loss modulus, along with variability of cortical storage modulus, cortical loss modulus, and trabecular hardness. These results suggest mechanical heterogeneity of bone tissue may contribute to fracture resistance. Although the magnitudes of differences in the intrinsic properties were not overwhelming, this is the first comprehensive study to investigate, and compare the intrinsic properties of bone tissue in fracturing and non-fracturing postmenopausal women.


Assuntos
Osso e Ossos/patologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/patologia , Ferimentos e Lesões/complicações , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Osso Esponjoso/patologia , Estudos de Casos e Controles , Osso Cortical/patologia , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada
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