Validation of a novel microradiography device for characterization of bone mineralization

Montagner, Florian; Kaftandjian, Valérie; Farlay, Delphine; Brau, Daniel; Boivin, Georges; Follet, Hélène

doi:10.3233/xst-150481

Cited by 13 publications

(14 citation statements)

References 20 publications

(18 reference statements)

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“…Microradiography-based matrix mineralization data were previously shown to correlate with tissue-level bone strength ( 39 ). The digital microradiography method used in the current study was validated and used in previous clinical studies ( 31 , 40 , 41 ). As expected for a potent remodeling inhibitor, denosumab increased the overall degree of mineralization ( i.e., DMB), and reduced the heterogeneity of mineralization (HI), compared with placebo.…”

Section: Discussionmentioning

confidence: 99%

“…Section thickness was measured with a precision micrometric thickness comparator (precision of 1 μm; Compac, Geneva, Switzerland). Bone sections were analyzed for matrix mineralization by digitized quantitative microradiography in a blinded manner, using code from a MATLAB program, as previously described ( 31 ). With this method, quantitative X-ray absorption by bone tissue is reflected in grayscale values that are converted at the pixel level into a DMB, expressed in grams of mineral per cm 3 of bone tissue.…”

Section: Methodsmentioning

confidence: 99%

“…In most cases, both cortices were analyzed, and results for each cortex were averaged. DMB was measured for each bone region and subregion, as was the heterogeneity index (HI), which reflects the width of the DMB distribution curve at one-half of its maximum height ( 25 , 31 ). Limited data on total bone DMB and HI for the denosumab years 2/3, 5, and 10 groups were reported previously ( 9 ).…”

Section: Methodsmentioning

confidence: 99%

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Effects of Long-Term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis

Dempster

Brown

Fahrleitner‐Pammer

et al. 2018

The Journal of Clinical Endocrinology &Amp; Metabolism

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ContextDenosumab is a potent antiresorptive agent that reduces fractures in postmenopausal women with osteoporosis.ObjectiveDetermine effects of up to 10 years of denosumab on bone histology, remodeling, and matrix mineralization characteristics.Design and SettingInternational, multicenter, randomized, double-blind trial [Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM)] with a long-term open-label extension.PatientsPostmenopausal women with osteoporosis (92 women in FREEDOM, 46 in extension) who provided iliac bone biopsies, including 11 who provided biopsies at multiple time points.InterventionsFREEDOM subjects were randomized 1:1 to subcutaneous denosumab 60 mg or placebo every 6 months for 3 years. Long-term extension subjects continued receiving denosumab, open-label, for 7 additional years.OutcomesBone histology, histomorphometry, matrix mineralization.ResultsTen-year denosumab biopsies showed normal histology. Bone histomorphometry indicated normal bone structure and reduced bone remodeling after 10 years of denosumab, similar to levels after 2 and/or 3 and 5 years of denosumab. The degree of mineralization of bone was increased and mineralization heterogeneity was reduced in the denosumab years 2/3 group vs placebo. Changes in these mineralization variables progressed from years 2/3 to year 5 of denosumab, but not thereafter.ConclusionsDenosumab for 2/3, 5, and 10 years was associated with normal histology, low bone remodeling rate, increased matrix mineralization, and lower mineralization heterogeneity compared with placebo. These variables were unchanged from year 5 to year 10. These data, in combination with the maintenance of low fracture rates for up to 10 years as previously reported with denosumab therapy, suggest that strong, prolonged remodeling inhibition does not impair bone strength.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Long-Term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis

Dempster

Brown

Fahrleitner‐Pammer

et al. 2018

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Degree (DMB) and heterogeneity index (HI) of mineralization (grams of mineral/cm 3 of bone) were assessed by digitized methodology with a Microfocus Hammamatsu L9421‐02X‐ray tube equipped with a copper anode, recently described …”

Section: Methodsmentioning

confidence: 99%

“…(18) Digitized microradiography Degree (DMB) and heterogeneity index (HI) of mineralization (grams of mineral/cm 3 of bone) were assessed by digitized methodology with a Microfocus Hammamatsu L9421-02X-ray tube equipped with a copper anode, recently described. (19) Microindentation Microhardness was measured using a Micromet 5104 (Buehler, Lake Bluff, IL, USA) equipped with a Vickers indenter. (20) For each sample, 60 indents (20 in cortical 1, 20 in cortical 2, and 20 in trabecular bone) were randomly performed on the surfaced blocks.…”

Section: Cross-link Measurements By High-performance Liquid Chromatogmentioning

confidence: 99%

Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus

Farlay

Armas

Gineyts

et al. 2015

Journal of Bone and Mineral Research

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108

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Objective Low-energy fractures are frequent complications in Type 1 Diabetes Mellitus patients (T1DM). Modifications of bone intrinsic composition might be a potential cause of fragility observed in diabetic subjects. Advanced Glycation End-products (AGEs) were found in numerous connective tissues from T1DM patients. However, whether AGEs are present at high levels in bone matrix from diabetic subjects is unknown. Moreover, whether elevated AGEs in the bone matrix impair mineralization has not been addressed in humans. The purposes of this study were 1) to determine whether bone matrix from fracturing and non-fracturing T1DM contained more AGEs than bone from healthy patients (CTL), and 2) to compare the degree of mineralization of bone and hardness between fracturing and non-fracturing T1DM versus CTL. Design and methods We analyzed iliac crest bone biopsies from 5 fracturing (Type 1 Diabetes Mellitus) T1DM patients, 5 non-fracturing T1DM patients and 5 healthy subjects, all age- and sex-matched. AGEs (Pentosidine) in bone matrix was measured by high performance liquid chromatography separately in trabecular and cortical bone. The degree of mineralization of bone (DMB) was assessed by digitized microradiography, and mechanical properties by micro- and nanohardness tests. Results Trabecular bone from fracturing T1DM exhibited significantly higher levels of Pentosidine than CTL (p=0.04) and was more mineralized than non-fracturing T1DM (p=0.04) and CTL (p=0.04). Trabecular bone was not significantly different in pentosidine between non-fracturing T1DM and CTL. Cortical bone from non-fracturing T1DM was not significantly different from CTL. Positive correlations were found between HbA1c and Pentosidine (r′=0.79, p<0.003), and between HbA1c and DMB (r′=0.64, p<0.02). Conclusion Both modifications could lead to less flexible bone (reduced modulus of elasticity), and a tendency toward low-energy fractures in T1DM patients.

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Variables Reflecting the Mineralization of Bone Tissue From Fracturing Versus Nonfracturing Postmenopausal Nonosteoporotic Women

et al. 2018

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Women with equivalent areal bone mineral densities may show a different fracture incidence due to differences in bone intrinsic quality. Previously, Fourier transform infrared spectroscopic imaging (FTIRI) on the same iliac bone biopsies reported here, showed that the only significantly different variable was the carbonate/phosphate ratio, which was decreased in the fracturing group. Nanoindentation showed that fracturing bone was less mechanically heterogeneous than nonfracturing bone and could propagate damage (microcracks) more easily. The hypothesis is that fracturing women have reduced mineralization of bone tissue compared to nonfracturing women. Transiliac bone biopsies were collected from fracturing (n = 60, 62.5 ± 7.4 years old) and nonfracturing (n = 60, 62.3 ± 7.3 years old) postmenopausal women, to assess the mineralization of bone tissue using digitized microradiography. The degree of mineralization of bone (DMB, g/cm3) and the heterogeneity index (HI, g/cm3) of the DMB were calculated for cancellous (canc), cortical (cort) and total bone. Results were compared to variables from nanoindentation, FTIRI, and histomorphometry. DMB and HI were not significantly different between fracturing and nonfracturing groups. In the nonfracturing group, cort and canc HI were weakly negatively associated with cort and canc DMB (r′ = −0.388, p < 0.003; r′ = −0.532, p < 0.0001, respectively). In the fracturing group, DMB and HI were negatively correlated only in canc (r′ = −0.295, p = 0.024). DMB and HI were not associated with nanoindentation variables. Cort and canc DMB were positively associated with mineral‐to‐matrix ratio measured by FTIRI (ratio between mineral and organic matrix representing the relative mineralization of the collagen matrix), and negatively associated with carbonate/phosphate ratio. None of the DMB variables were strongly associated with any of the histomorphometric variables. In conclusion, bone mineralization was not significantly different between fracturing and nonfracturing postmenopausal women, suggesting that bone fragility could be partly due to other variables, such as changes in hydration of bone matrix or an increase of non‐enzymatic crosslinks in bone collagen. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Validation of a novel microradiography device for characterization of bone mineralization

Cited by 13 publications

References 20 publications

Effects of Long-Term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis

Effects of Long-Term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis

Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus

Variables Reflecting the Mineralization of Bone Tissue From Fracturing Versus Nonfracturing Postmenopausal Nonosteoporotic Women

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