MRI Quantification of Cortical Bone Porosity, Mineralization, and Morphologic Structure in Postmenopausal Osteoporosis.

Background Preclinical studies have suggested that solid-state MRI markers of cortical bone porosity, morphologic structure, mineralization, and osteoid density are useful measures of bone health. Purpose To explore whether MRI markers of cortical bone porosity, morphologic structure, mineralization, and osteoid density are affected in postmenopausal osteoporosis (OP) and to examine associations between MRI markers and bone mineral density (BMD) in postmenopausal women. Materials and Methods In this single-center study, postmenopausal women were prospectively recruited from January 2019 to October 2020 into two groups: participants with OP who had not undergone treatment, defined as having any dual-energy x-ray absorptiometry (DXA) T-score of -2.5 or less, and age-matched control participants without OP (hereafter, non-OP). Participants underwent MRI in the midtibia, along with DXA in the hip and spine, and peripheral quantitative CT in the midtibia. Specifically, MRI measures of cortical bone porosity (pore water and total water), osteoid density (bound water [BW]), morphologic structure (cortical bone thickness), and mineralization (phosphorous [P] density [31P] and 31P-to-BW concentration ratio) were quantified at 3.0 T. MRI measures were compared between OP and non-OP groups and correlations with BMD were assessed. Results Fifteen participants with OP (mean age, 63 years ± 5 [SD]) and 19 participants without OP (mean age, 65 years ± 6) were evaluated. The OP group had elevated pore water (11.6 mol/L vs 9.5 mol/L; P = .007) and total water densities (21.2 mol/L vs 19.7 mol/L; P = .03), and had lower cortical bone thickness (4.8 mm vs 5.6 mm; P < .001) and 31P density (6.4 mol/L vs 7.5 mol/L; P = .01) than the non-OP group, respectively, although there was no evidence of a difference in BW or 31P-to-BW concentration ratio. Pore and total water densities were inversely associated with DXA and peripheral quantitative CT BMD (P < .001), whereas cortical bone thickness and 31P density were positively associated with DXA and peripheral quantitative CT BMD (P = .01). BW, 31P density, and 31P-to-BW concentration ratio were positively associated with DXA (P < .05), but not with peripheral quantitative CT. Conclusion Solid-state MRI of cortical bone was able to help detect potential impairments in parameters reflecting porosity, morphologic structure, and mineralization in postmenopausal osteoporosis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bae in this issue.

Monocrotophos, an organophosphorus insecticide, induces cortical and trabecular bone loss in Swiss albino mice.

Till now monocrotophos (MCP) has been addressed as a neurotoxic stressor. Limited studies investigate its aftermath on bone pathologies. Given the fact that MCP is a propensely used insecticide in developing countries, this study investigates its potential to mirror osteoporotic features and bone loss incurred in a rodent model. Briefly, Swiss albino mice were orally gavaged daily with varying doses of MCP for 8 weeks. Musculoskeletal changes were analyzed through micro-computed tomography and histology. A series of in vitro and ex vivo cell culture experiments were performed on MC3T3E-1 and primary osteoclast cultures. Results highlight that oral gavaging with MCP causes bone loss from the cortico-trabecular interface by decreasing the osteoblast and increasing the osteoclast number. Results from in vitro studies establish that MCP treatment increases the TRAP-positive multinucleated cell number during osteoclast differentiation. Ex-vivo experiments with MCP-treated animal sera further substantiate the in vivo claims with significant decreases seen in cell viability, proliferation, mineralization and differentiation studies. In conclusion MCP induces osteoclastogenesis (bone loss) on direct stimulation and alters the circulating factors in MCP-treated serum. Holistically, this work would be of potential significance to patients suffering from pesticide induced osteoporosis.

Prospective Study Evaluating Changes in Bone Quality in Premenopausal Women With Breast Cancer Undergoing Adjuvant Chemotherapy.

BACKGROUND: Ovarian suppression from chemotherapy results in bone loss in premenopausal women with breast cancer (BC). Less is known about bone microarchitecture changes. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure volumetric bone density and trabecular and cortical microarchitecture in this population. MATERIALS AND METHODS: The primary endpoint was to assess changes in cortical thickness and trabecular bone density by HR-pQCT. Premenopausal women with stage I to III BC undergoing adjuvant chemotherapy underwent a bone mineral density (BMD) dual energy x-ray absorptiometry scan and HR-pQCT (voxel size, 82 microns) at baseline and 12 months. Paired t tests were used to observe the change over time in bone microarchitecture and areal and volumetric density. RESULTS: Eighteen patients were evaluated, of which 12 patients had baseline and matched 12-month imaging. The mean age was 45.2 years (range, 35-51 years), 17 (94%) patients had hormone receptor-positive BC, and 16 (89%) initiated tamoxifen. At 12 months, there was a significant decrease in femoral neck (P < .05) and lumbar spine and total hip (P < .01) BMD. Changes detected by HR-pQCT at 12 months included significant decreases in cortical thickness and area at the tibia (P < .05), and total and cortical volumetric BMD at the radius and tibia (P < .01), as well as an increase in tibial trabecular area (P < .05). CONCLUSION: Premenopausal women undergoing chemotherapy experience BMD decline and trabecular and cortical bone microarchitecture deterioration. In this population, future efforts should focus on therapy-induced bone loss and optimizing bone density-related management.

Single and simultaneous effects of acrylamide and ethanol on bone microstructure of mice after one remodeling cycle.

BACKGROUND: This study aimed to examine femoral bone microstructure of mice after single and simultaneous administration to acrylamide and ethanol since both substances are often consumed separately and/or together by humans. Interactive effects of these toxins were analysed after one remodeling cycle. METHODS: Twenty clinically healthy adult mice were randomly divided into four groups following 2 weeks administration of toxins: A group - mice were fed with acrylamide (40 mg/kg bw); E group - mice were ethanol-fed (15% ethanol); AE group - mice were simultaneously fed with both toxins, and a C group - control (without acrylamide and/or ethanol supplementation). Generally, 2D and 3D imaging methods were used to determine cortical and trabecular bone tissues microstructure. Biochemical analyses of plasma parameters were also realized using commercially available ELISA tests and spectrophotometrically. RESULTS: Single and simultaneous exposure to acrylamide and ethanol affected only cortical bone microstructure. No significant changes in trabecular bone morphometry were detected among all groups. In mice from the A group, increased endocortical remodeling associated with a higher level of serum calcium and vasoconstriction of primary osteon's vascular canals (POVC) were identified. On the contrary, increased cortical porosity consistent with a decreased relative bone volume, bone mineral density (BMD) and lower levels of alkaline phosphatase (ALP), glutathione (GSH), calcium in plasma and also with vasodilation of POVC were observed in the E group. In the AE group, the highest density of secondary osteons associated with a lower BMD and decreased levels of ALP, GSH were documented. The parameters of POVC and Haversian canals approximated to the C group. In addition, single and simultaneous exposure to both toxins caused liver disease consistent with a higher values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in plasma of all experimental groups. CONCLUSIONS: Single administration to acrylamide and ethanol had negative effects on cortical bone structure of mice after one remodeling cycle. However, we identified possible antagonistic impact of these toxins on the structure of the cortical bone.

Extraction of gray-scale intensity distributions from micro computed tomography imaging for femoral cortical bone differentiation between low-magnesium and normal diets in a laboratory mouse model.

Previous studies have shown that the geometric development of femoral trabecular bone is affected by insufficient dietary intake of magnesium. However, it is not clear whether the development of femoral cortical bone can be quantitatively evaluated according to a diet with inadequate magnesium supplementation. Therefore, we used a micro computed tomography (CT) imaging approach with a laboratory mouse model to explore the potential application of texture analysis for the quantitative assessment of femoral cortical bones. C57BL/6J male mice were divided into two groups, where one group was fed a normal diet and the other group was fed a low-magnesium diet. We used a micro CT scanner for image acquisition, and the subsequent development of cortical bone was examined by texture analysis based on the statistical distribution of gray-scale intensities in which seven essential parameters were extracted from the micro CT images. Our calculations showed that the mean intensity increased by 7.20% (p = 0.000134), sigma decreased by 29.18% (p = 1.98E-12), skewness decreased by 19.52% (p = 0.0000205), kurtosis increased by 9.62% (p = 0.0877), energy increased by 24.19% (p = 3.32E-09), entropy decreased by 6.14% (p = 3.00E-10), and the Nakagami parameter increased by 104.32% (p = 4.13E-12) in the low-magnesium group when compared to the normal group. We found that the statistical parameters extracted from the gray-scale intensity distribution were able to differentiate between femoral cortical bone developments in the two different diet groups.

The effect of hydrochloric acid on microstructure of porcine (Sus scrofa domesticus) cortical bone tissue.

We evaluated the degradation of cortical bone tissue by hydrochloric acid (HCl) since intentional bone decalcification in a forensic context has not been studied on a histomorphological level. We used 70 pig metatarsal bones split into subsamples and immersed in one of three concentrations of acidic solutions (0.5M, 1M, 2M HCl) for two and four hours. We analyzed the cortical thicknesses on transversal cross-sections, thicknesses of the three histomorphologically distinct zones present in acid-immersed bones, and number and area of crystals present in one of the zones. Furthermore, we analyzed the ratio of calcium to phosphorus (Ca:P). We observed a division of the cortical bone cross section into three distinctive zones: demineralized matrix (DM) in the periosteal part of bone, middle contact zone (CZ), and mineralized matrix (MM) in the endosteal part of bone. With increasing acid concentration and time of immersion (from 0.5M HCl for 2h to 2M HCl for 4h), the thickness of DM increased by 67%, the thickness of CZ increased by 56%, and the thickness of MM decreased by 32%. The Ca:P ratio in the contact zone of acid-treated samples did not change significantly with changing acid concentration and time of immersion. The Ca:P ratio of the CZ decreased by 10% when compared to the Ca:P ratio of MM in acid-treated samples. Moreover, we observed crystals on the outer periosteal border of the DM zone, in the CZ, and in the MM Haversian/Volkmann's canals. The size and number of the crystals in the CZ of acid-treated bones increased with acid concentration and time of acid immersion. Moreover, we also observed significant differences in all analyzed properties between anatomical regions. Due to varying reactions to acid immersion among anatomical regions, bone micro-degradation should be observed separately for each region.

Fluoride intake and cortical and trabecular bone characteristics in adolescents at age 17: A prospective cohort study.

OBJECTIVE: To investigate the associations between period-specific and cumulative fluoride (F) intakes from birth to age 17 years, and radial and tibial bone measures obtained using peripheral quantitative computed tomography (pQCT). METHODS: Participants (n = 380) were recruited from hospitals at birth and continued their participation in the ongoing Iowa Fluoride Study/Iowa Bone Development Study until age 17. Fluoride intakes from water, other beverages, selected foods, dietary fluoride supplements and dentifrice were determined every 1.5-6 months using detailed questionnaires. Associations between F intake and bone measures (cortical and trabecular bone mineral content [BMC], density and strength) were determined in bivariate and multivariable analyses adjusted for height, weight, maturity offset, physical activity, and daily calcium and protein intake using robust regression analysis. RESULTS: Fluoride intake ranged from 0.7 to 0.8 mg F/d for females and from 0.7 to 0.9 mg F/d for males. Spearman correlations between daily F intake and pQCT bone measures were weak. For females, Spearman correlations ranged from r = -.08 to .21, and for males, they ranged from r = -.03 to .30. In sex-specific, height-, weight- and maturity offset- partially adjusted regression analyses, associations between females' fluoride intake and bone characteristics were almost all negative; associations for males were mostly positive. In the fully adjusted models, which also included physical activity, and protein and calcium intakes, no significant associations were detected for females; significant positive associations were detected between F intake from 14 to 17 years and tibial cortical bone content (ß = 21.40, P < .01) and torsion strength (ß = 175.06, P < .01) for males. CONCLUSION: In this cohort of 17-year-old adolescents, mostly living in optimally fluoridated areas, lifelong F intake from combined sources was weakly associated with bone pQCT measures.

Cortical Thinning and Structural Bone Changes in Non-Human Primates after Single-Fraction Whole-Chest Irradiation.

Stereotactic body radiation therapy (SBRT) is associated with an increased risk of vertebral compression fracture. While bone is typically considered radiation resistant, fractures frequently occur within the first year of SBRT. The goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. Sixteen male rhesus macaque non-human primates (NHPs) were analyzed after whole-chest irradiation to a midplane dose of 10 Gy. Ages at the time of exposure varied from 45-134 months. Computed tomography (CT) scans were taken 2 months prior to irradiation and 2, 4, 6 and 8 months postirradiation for all animals. Bone mineral density (BMD) and cortical thickness were calculated longitudinally for thoracic (T) 9, lumbar (L) 2 and L4 vertebral bodies; gross morphology and histopathology were assessed per vertebra. Greater mortality (related to pulmonary toxicity) was noted in NHPs <50 months at time of exposure versus NHPs >50 months ( P = 0.03). Animals older than 50 months at time of exposure lost cortical thickness in T9 by 2 months postirradiation ( P = 0.0009), which persisted to 8 months. In contrast, no loss of cortical thickness was observed in vertebrae out-of-field (L2 and L4). Loss of BMD was observed by 4 months postirradiation for T9, and 6 months postirradiation for L2 and L4 ( P < 0.01). For NHPs younger than 50 months at time of exposure, both cortical thickness and BMD decreased in T9, L2 and L4 by 2 months postirradiation ( P < 0.05). Regions that exhibited the greatest degree of cortical thinning as determined from CT scans also exhibited increased porosity histologically. Rapid loss of cortical thickness was observed after high-dose chest irradiation in NHPs. Younger age at time of exposure was associated with increased pneumonitis-related mortality, as well as greater loss of both BMD and cortical thickness at both in- and out-of-field vertebrae. Older NHPs exhibited rapid loss of BMD and cortical thickness from in-field vertebrae, but only loss of BMD in out-of-field vertebrae. Bone is sensitive to high-dose radiation, and rapid loss of bone structure and density increases the risk of fractures.

Milk Basic Protein Facilitates Increased Bone Mass in Growing Mice.

Milk basic protein (MBP) comprises a group of basic whey proteins and is effective in preventing bone loss by promoting bone deposition (bone formation) and suppressing withdrawn (bone resorption). We previously revealed the bone protective effects of MBP during life phases involving excessive bone resorption, such as in adults and postmenopausal women, and in animal models (ovariectomized rats and mice). However, it was unclear whether MBP increases bone mass during the growth stage, when there is more bone formation than resorption. We therefore investigated the effect of MBP supplementation on bone mass in 6-wk-old mice provided water supplemented with MBP [0.01%, 0.1%, 1.0% (w/w)] or deionized water (control) ad libitum for 10 wk. Analysis by micro-computerized tomography showed that MBP significantly increased tibia cortical bone mineral density and femur trabecular bone volume to tissue volume compared with mice provided deionized water. Next, the function of MBP in bone remodeling (bone formation and resorption) was evaluated using an in vitro system and the results demonstrated that MBP directly promoted osteoblast proliferation and inhibited osteoclastogenesis. Moreover, the plasma level of insulin-like growth factor-1 was increased by MBP supplementation, suggesting that MBP indirectly promoted osteoblast proliferation/differentiation. These effects enhance bone formation and/or inhibit bone resorption, resulting in increased bone mass in growing mice.

Pueraria mirifica alleviates cortical bone loss in naturally menopausal monkeys.

Since the in vitro and in vivo anti-osteoporotic effects of Pueraria mirifica (PM) in rodents have been verified, its activity in menopausal monkeys was evaluated as required before it can be applicable for human use. In this study, postmenopausal osteoporotic monkeys were divided into two groups (five per group), and fed daily with standard diet alone (PMP0 group) or diet mixed with 1000 mg/kg body weight (BW) of PM powder (PMP1000 group) for 16 months. Every 2 months, the bone mineral density (BMD), bone mineral content (BMC) and bone geometry parameters (cortical area and thickness and periosteal and endosteal circumference) at the distal radius and proximal tibia were determined using peripheral quantitative computed tomography together with plasma and urinary bone markers. Compared with the baseline (month 0) values, the cortical, but not trabecular, BMDs and BMCs and the cortical area and thickness at the metaphysis and diaphysis of the radius and tibia of the PMP0 group continuously decreased during the 16-month study period. In contrast, PMP1000 treatment ameliorated the bone loss mainly at the cortical diaphysis by decreasing bone turnover, as indicated by the lowered plasma bone-specific alkaline phosphatase and osteocalcin levels. Generally, changes in the cortical bone geometry were in the opposite direction to the cortical bone mass after PMP1000 treatment. This study indicated that postmenopausal monkeys continuously lose their cortical bone compartment, and they have a higher possibility for long bone fractures. Oral PMP treatment could improve both the bone quantity (BMC and BMD) and quality (bone geometry).

Feasibility of cone beam computed tomography radiomorphometric analysis and fractal dimension in assessment of postmenopausal osteoporosis in correlation with dual X-ray absorptiometry.

OBJECTIVES: The aim of the present study was to assess the feasibility of using mandibular CBCT radiomorphometric indices and box-counting fractal dimension (FD) to detect osteoporosis in post-menopausal females, compare them with the healthy control group and to correlate the findings with the bone mineral density measured by dual X-ray absorptiometry (DXA). METHODS: This study consisted of 50 post-menopausal females, with age ranging from 55 to 70 years. Based on their DXA results, they were classified into osteoporotic and control groups. Mandibular CBCT radiomorphomertic indices and FD analysis were measured. RESULTS: Significant differences were found for the CT cortical index scores (CTCI), CT mental index (CTMI) and CT mandibular index (CTI) between the control and osteoporotic groups. The control group showed higher mean values than the osteoporotic group. For FD values, no significant differences were found between the two groups. CONCLUSIONS: CBCT radiomorphometric indices could be used as an adjuvant tool to refer patients at risk of osteoporosis for further assessment.

Low serum vitamin D is associated with higher cortical porosity in elderly men.

BACKGROUND: Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. OBJECTIVE: To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. METHODS: A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. RESULTS: Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L-1 ) or insufficiency [25-49 nmol L-1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L-1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized ß = -0.110, R2 = 1.1%, P = 0.024), area (ß = 0.123, R2 = 1.4%, P = 0.007) and cortical volumetric BMD (ß = 0.125, R2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (ß = 0.102, R2 = 0.9%, P = 0.04). CONCLUSION: Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry.