Trabecular Bone Microarchitectural Parameters Research Articles

Quantification of bone microarchitecture using photon-counting CT at different radiation doses: A comparison with µCT

PurposeAccurate measurements of trabecular bone microarchitecture are required for a proper assessment of bone fragility. Photon-counting detector CT (PCD-CT) has different technical properties than conventional CT, resulting in higher resolution and thereby potentially enabling in-vivo measurement of trabecular microarchitecture. The purpose of this study was to quantify trabecular bone microarchitectural parameters with PCD-CT at varying radiation doses and compare this to µCT as gold standard. MethodBoth distal radii, distal tibiae, femoral heads, and two vertebrae were dissected from one human. All specimens were scanned ex-vivo on a PCD-CT system (slice increment 0.1 mm; pixel size 0.1042–0.127 mm) and a µCT system (isotropic voxel size 49–68.4 µm). The radiation doses of the PCD-CT scans were varied from 2.5 to 120 mGy based on the volume CT dose index (CTDIvol32). For the PCD-CT scans, contrast-to-noise ratio and trabecular sharpness were calculated and compared between radiation doses. µCT and PCD-CT scans were registered. The trabecular bone was then segmented from all PCD-CT and µCT scans and split into cubes with 6-mm edge length. For each cube, bone volume over total volume, trabecular thickness, trabecular number, and trabecular heterogeneity were calculated and compared between corresponding PCD-CT and µCT cubes. ResultsWith increasing dose, contrast-to-noise ratio and trabecular sharpness values increased for the PCD-CT images. Already at the lowest dose, high correlations between the trabecular microarchitectural parameters between µCT and PCD-CT were found (R2 = 0.55–0.95), which improved with increasing radiation dose (R2 = 0.76–0.96 at 20 mGy). ConclusionsPCD-CT can be used to quantify trabecular bone microarchitecture, with accuracy comparable to µCT and at clinically relevant radiation doses.

Trabecular bone microstructure parameters as predictors for chronological age: a systematic review.

Estimating chronological age is crucial in forensic identification. The increased application of medical imaging in age analysis has facilitated the development of new quantitative methods for the macroscopic evaluation of bones. This study aimed to determine the association of age-related changes in the trabecular microstructure with chronological age for age estimation in forensic science through different non-invasive imaging techniques. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An electronic search was performed with PubMed/MEDLINE, Scopus, and Cochrane databases as well as with a Google Scholar search. Qualitative synthesis was performed using the Anatomical Quality Assessment tool. A detailed literature search yielded 3467 articles. A total of 14 articles were ultimately included in the study. A narrative approach was employed to synthesize the data. Microcomputed tomography, high-resolution peripheral quantitative computed tomography, and cone beam computed tomography have been used for the quantitative estimation of age. These imaging techniques aid in identifying the trabecular bone microarchitectural parameters for chronological age estimation. Age-related changes in trabecular bone included a decrease in the bone volume fraction, trabecular number, and connectivity density and an increase in trabecular separation. This study also revealed that morphometric indices vary with age and anatomical site. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CDRD42023391873.

Freezing does not influence the microarchitectural parameters of the microstructure of the freshly harvested femoral head bone.

The femoral head is one of the most commonly used bones for allografts and biomechanical studies. However, there are few reports on the trabecular bone microarchitectural parameters of freshly harvested trabecular bones. To our knowledge, this is the first study to characterize the microstructure of femoral heads tested immediately after surgery and compare it with the microstructure obtained with conventional freezing. This study aims to investigate whether freezing at -80°C for 6weeks affects the trabecular microstructure of freshly harvested bone tissue. This study was divided into two groups: one with freshly harvested human femoral heads and the other withthe same human femoral heads frozen at -80°C for 6weeks. Each femoral head was scanned using an X-ray microcomputed tomography scanner (µCT) to obtain the microarchitectural parameters, including the bone volume fraction (BV/TV), the mean trabecular thickness (Tb.th), the trabecular separation (Tb.sp), the degree of anisotropy (DA), and the connectivity density (Conn.D). There was no statistically significant difference between the fresh and the frozen groups for any of the parameters measured. This study shows that freezing at -80°C for 6weeks does not alter bone microstructure compared with freshly harvested femoral heads tested immediately after surgery.

Targeting FGFR3 signaling and drug repurposing for the treatment of SLC26A2-related chondrodysplasia in mouse model

BackgroundMutations in Slc26a2 cause a spectrum of autosomal-recessive chondrodysplasia with a significant and negligible influence on the quality of life. It has been reported that Slc26a2 deficiency triggers the ATF6 branch of the UPR, which may, in turn, activate the negative regulator of the FGFR3 signaling pathway. However, the correlation between the deletion of Slc26a2 and the augmentation of downstream phosphorylation of FGFR3 has not been investigated in vivo. MethodsFirst, we constructed Slc26a2 and Fgfr3 double knockout mouse lines and observed gross views of the born mice and histological staining of the tibial growth plates. The second approach was to construct tamoxifen-inducible Cre-ERT2 mouse models to replicate SLC26A2-related non-lethal dysplastic conditions. Pharmacological intervention was performed by administering the FGFR3 inhibitor NVP-BGJ398. The effect of NVP-BGJ398 on chondrocytes was assessed by Alcian blue staining, proliferation, apoptosis, and chondrocyte-specific markers and then verified by western blotting for variations in the downstream markers of FGFR3. The growth process was detected using X-rays, micro-CT examination, histomorphometry staining of growth plates, and immunofluorescence. ResultsGenetic ablation of Fgfr3 in embryonic Slc26a2-deficient chondrocytes slightly attenuated chondrodysplasia. Subsequently, in the constructed mild dysplasia model, we found that postnatal intervention with Fgfr3 gene in Slc26a2-deficient chondrocytes partially alleviated chondrodysplasia. In chondrocyte assays, NVP-BGJ398 suppressed the defective phenotype of Slc26a2-deficient chondrocytes and restored the phosphorylation downstream of FGFR3 in a concentration-dependent manner. In addition, in vivo experiments showed significant alleviation of impaired chondrocyte differentiation, and micro-CT analysis showed a clear improvement in trabecular bone microarchitectural parameters. ConclusionOur results suggested that inhibition of FGFR3 signaling pathway overactivation and NVP-BGJ398 has promising therapeutic implications for the development of SLC26A2-related skeletal diseases in humans. The translational potential of this articleOur data provide genetic and pharmacological evidence that targeting FGFR3 signaling via NVP-BGJ398 could be a route for the treatment of SLC26A2-associated skeletal disorders, which promisingly advances translational applications and therapeutic development.

Yeast Hydrolysate and Postmenopausal Osteoporosis

We used an ovariectomy (OVX) rat model to test whether yeast hydrolysate (YH) has therapeutic effects on postmenopausal osteoporosis-induced bone loss. The rats were separated into five treatment groups: the sham group (sham operation); the control group (no treatment after OVX); the estrogen group (estrogen treatment after OVX); YH 0.5% group (drinking water supplementation with 0.5% YH after OVX); and the YH 1% group (drinking water supplementation with 1% YH after OVX). In addition, the YH treatment restored serum testosterone concentration in the OVX rats up to the normal level. Further, YH treatment affected bone markers; a significant increase in serum calcium concentration was observed after adding YH to the diet. The levels of serum alkaline phosphatase, osteocalcin, and cross-linked telopeptides of type I collagen were reduced by YH supplementation, unlike those in the no-treatment control. Although not statistically significant, YH treatment in OVX rats improved trabecular bone microarchitecture parameters. These results show that YH may ameliorate the bone loss caused by postmenopausal osteoporosis because of the normalization of serum testosterone concentration.

Effect of Scanning Resolution on the Prediction of Trabecular Bone Microarchitectures Using Dental Cone Beam Computed Tomography.

Assessing bone quality and quantity at the location of dental implants before dental implantation is crucial. In recent years, dental cone-beam computed tomography (dental CBCT) has often been used to assess bone quality and quantity prior to dental implant. However, the effect of scanning resolution on the prediction of trabecular bone microarchitectural parameters (TBMPs) remains unclear. The objective of this study was to examine how dental CBCT with various scanning resolution differs with regard to predicting TBMPs. This study used micro-computed tomography (micro-CT) with 18 μm resolution and dental CBCT with 100 μm and 150 μm resolutions on 28 fresh bovine vertebrae cancellous bone specimens. Subsequently, all images were input into the ImageJ software to measure four TBMPs: bone volume total volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp). One-way analysis of variance and Tukey’s test were subsequently used to assess the differences between three scanning modes for the four TBMPs. In addition, correlations between measurement results obtained from micro-CT and dental CBCT with two resolutions were measured. The experimental results indicated that significant differences in four TBMPs were observed between micro-CT and dental CBCT (p < 0.05). The correlation coefficients between BV/TV, Tb.N, and Tb.Sp obtained from micro-CT and from dental CBCT with 100 μm resolution (0.840, 0.739, and 0.820, respectively) were greater than the correlation coefficients between BV/TV, Tb.N, and Tb.Sp obtained from micro-CT and from dental CBCT with 150 μm resolution (0.758, 0.367, and 0.724, respectively). The experimental results revealed that the TBMPs measured with dental CBCT with two resolutions differed from ideal values, but a higher resolution could provide more accurate prediction results, particularly for BV/TV, Tb.N, and Tb.Sp.

SUN-455 Abnormalities in Bone Microarchitecture of Women with Active Acromegaly Using HR-pQCT

Acromegaly has been associated with high bone turnover rate and frequency of vertebral fractures, findings mainly observed in patients with active disease and untreated hypogonadism. However, DXA measurements of bone mineral density (BMD) in acromegaly are controversial, and may be normal, low or even high when compared with normal controls. Therefore, the use of alternative diagnostic tools that evaluate bone quality, such as HR-pQCT, as well as the selection of a population of patients without risk factors for osteoporosis can improve the assessment of excess GH on bone microarchitecture. To evaluate BMD and bone microarchitecture in women with acromegaly in comparison with healthy subjects, we conducted a cross-sectional study, including twenty six women with acromegaly (11 active/15 controlled) with sixty female healthy controls matched by age and body mass index (BMI kg/m2). Areal BMD (aBMD) was measured at lumbar spine(L1-L4), femoral neck and total hip by DXA. Bone microarchitecture was assessed by HR-pQCT at the distal radius and tíbia. We enrolled twenty six women with acromegaly (40.3± 5.8years,30.2 kg/m2) and 60 control subjects (40.6 ± 5.8 years, 28.4 ± 4.6 kg/m2), none of whom had hypopituitarism. Acromegaly patients and controls were comparable for age (40.3 ± 5.8 vs 40.5 ± 5.8 years; P=0.83); and BMI (28.3 ± 5.0 vs 28.3 ± 4.6 kg/m2; P=0.12). Patients with active acromegaly showed higher IGF-1 levels than controlled patients (375.2 ± 122.6 vs 160.7 ± 44.8 ng/mL, respectively). Compared to healthy controls,patients with acromegaly showed significantly higher aBMD at lumbar L1-L4 (1.000 ± 0.11 vs 1.130 ± 0.11; P<0.01), total Hip (0.93 ± 0.11 vs 1.040 ± 0.15; P<0.001) and femoral neck (0.82 ± 0.12 vs 0.900 ± 0.16; P=0.01.). HR-pQCT at the radius, showed significantly reduced trabecular BMD (TbBMD); (P<0.01); trabecular number (TbN); (P<0.001) and increased trabecular separation (TbSp) (P<0.001). On the other hand, patients with acromegaly had increased cortical BDM(Ct.BMD); (P<0,001) and cortical thickness (CtTh); (P<0.001). At the tibia, only trabecular thickness was significantly decreased (P<0.01). No differences in BMD and bone microstructure were observed between patients with active and controlled acromegaly. Conclusions: The current study demonstrates that women with acromegaly without associated hormonal deficiencies had reduced trabecular bone microarchitecture parameters and increased cortical parameters at peripheral sites using HR-pQCT. This finding provides additional evidence for the role of GH/IGF-1 levels in establishing and regulating skeletal microstructure. The limitations of this study include the cross-sectional design and relatively small numbers of patients. Longitudinal studies are needed to confirm our findings. Funding: This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) #2016/23765-0

Improving the prediction of the trabecular bone microarchitectural parameters using dental cone-beam computed tomography

BackgroundIn this study, we explored how various preprocessing approaches can be employed to enhance the capability of dental CBCT to accurately estimate trabecular bone microarchitectural parameters.MethodsIn total, 30 bovine vertebrae cancellous bone specimens were used for in study. Voxel resolution 18-μm micro-computed tomography (micro-CT) and 100-μm dental CBCT were used to scan each specimen. Micro-CT images were used to calculate trabecular bone microarchitectural parameters; the results were set as the gold standard. Subsequently, before the dental CBCT images were converted into binary images to calculate trabecular bone microarchitectural parameters, three preprocessing approaches were used to process the dental CBCT images. For Group 1, no preprocessing approach was applied. For Group 2, images were sharpened and despeckable noises were removed. For Group 3, the function of local thresholding was added to Group 2 to form Group 3. For Group 4, the air pixels was removed from Group 3 to form Group 4. Subsequently, all images were imported into a software package to estimate trabecular bone microarchitectural parameters (bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular number (TbN), and trabecular separation (TbSp)). Finally, a paired t-test and a Pearson correlation test were performed to compare the capability of micro-CT with the capability of dental CBCT for estimating trabecular bone microarchitectural parameters.ResultsRegardless of whether dental CBCT images underwent image preprocessing (Groups 1 to 4), the four trabecular bone microarchitectural parameters measured using dental CBCT images were significantly different from those measured using micro-CT images. However, after three image preprocessing approaches were applied to the dental CBCT images (Group 4), the BV/TV obtained using dental CBCT was highly positively correlated with that obtained using micro-CT (r = 0.87, p < 0.001); the correlation coefficient was greater than that of Group 1 (r = −0.15, p = 0.412), Group 2 (r = 0.16, p = 0.386), and Group 3 (r = 0.47, p = 0.006). After dental CBCT images underwent image preprocessing, the efficacy of using dental CBCT for estimating TbN and TbSp was enhanced.ConclusionsImage preprocessing approaches can be used to enhance the efficacy of using dental CBCT for predicting trabecular bone microarchitectural parameters.

Tetrahydroxy stilbene glucoside protected against diabetes‐induced osteoporosis in mice with streptozotocin‐induced hyperglycemia

Tetrahydroxy stilbene glucoside (TSG), an active component from medicinal herb Polygonum multiflorum Thunb, could block the activity of the tissue renin-angiotensin system (RAS), which plays a critical role in development of diabetic osteoporosis. This study aimed to determine if TSG therapy could alleviate bone deteriorations in diabetic mouse model induced by streptozotocin. The diabetic mice showed the loss of trabecular bone mass and the changes of trabecular bone microarchitectural parameters as well as the increase in amount of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts at the distal metaphysis of femur when compared with those of nondiabetic mice. Treatment with TSG significantly elevated calcium content in serum and bone and improved biological parameters of trabecular bone, accompanied by increasing messenger RNA (mRNA) expression of RUNX-2, COL-I, and OCN and protein expression of β-catenin as well as down-regulating protein expression of RAS components including renin and AT1R. In addition, TSG repressed diabetes-induced decrease in ratio of OPG/RANKL expression and increase in sclerostin expression in bone. The similar effects of TSG on osteoblasts-specific genes were found in MC3T3-E1 cells. Taken together, the present study demonstrated the osteopreserve effects of TSG in diabetic mice, and the underlying mechanism might be attributed to its regulation on osteogenesis and osteoclastogenesis.

A neoflavonoid dalsissooal isolated from heartwood of Dalbergia sissoo Roxb. has bone forming effects in mice model for osteoporosis

Dalbergia sissoo Roxb. is a well known medicinal plant of India, enriched with various flavonoids used for treating multiple diseases. Earlier, we have shown that extract of Dalbergia sissoo Roxb. leaves mitigate ovariectomy induced bone loss and pure compounds (neoflavonoids) isolated from it, promote osteoblastogenesis in primary calvarial osteoblasts cells in vitro. Here, we hypothesize that dalsissooal (DSL), a novel neoflavonoid isolated from the heartwood of Dalbergia sissoo Roxb. is an important constituent of the extract that imparts bone forming effects. Treatment with DSL enhanced trabecular bone micro-architecture parameters, biomechanical strength, increased bone formation rate and mineral apposition rate in OVx mice comparable to 17β-estradiol. It increased bone formation by enhancing osteoblast gene expression and reduced bone turnover by decreasing osteoclastic gene expressions. Interestingly, we observed that DSL has no uterine estrogenic effects. At cellular levels, DSL promoted differentiation of bone marrow cells as well as calvaria osteoblast cells towards osteoblast lineage by enhancing differentiation and mineralizing ability to form mineralizing nodules via stimulating BMP-2 and RunX-2 expressions. Overall, our data suggest that oral supplementation of a novel neoflavonoid dalsissooal isolated from heartwood of Dalbergia sissoo Roxb. exhibited bone anabolic action by improving structural property of bone, promoting new bone formation and reducing bone turnover rate in post-menopausal model for osteoporosis with no uterine hyperplasia.

Cortical Bone Morphological and Trabecular Bone Microarchitectural Changes in the Mandible and Femoral Neck of Ovariectomized Rats.

ObjectiveThis study used microcomputed tomography (micro-CT) to evaluate the effects of ovariectomy on the trabecular bone microarchitecture and cortical bone morphology in the femoral neck and mandible of female rats.Materials and MethodsTwelve female Wister rats were divided into two groups: the control and ovariectomized groups. The rats in the ovariectomized group received ovariectomy at 8 weeks of age; all the rats were sacrificed at 20 weeks of age, and their mandibles and femurs were removed and scanned using micro-CT. Four microstructural trabecular bone parameters were measured for the region below the first mandibular molar and the femoral neck region: bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp), and trabecular number (TbN). In addition, four cortical bone parameters were measured for the femoral neck region: total cross-sectional area (TtAr), cortical area (CtAr), cortical bone area fraction (CtAr/TtAr), and cortical thickness (CtTh). The CtTh at the masseteric ridge was used to assess the cortical bone morphology in the mandible. The trabecular bone microarchitecture and cortical bone morphology in the femoral necks and mandibles of the control group were compared with those of the ovariectomized group. Furthermore, Spearman’s correlation (rs) was conducted to analyze the correlation between the osteoporosis conditions of the mandible and femoral neck.ResultsRegarding the trabecular bone microarchitectural parameters, the BV/TV of the trabecular bone microarchitecture in the femoral necks of the control group (61.199±11.288%, median ± interquartile range) was significantly greater than that of the ovariectomized group (40.329±5.153%). Similarly, the BV/TV of the trabecular bone microarchitecture in the mandibles of the control group (51.704±6.253%) was significantly greater than that of the ovariectomized group (38.486±9.111%). Furthermore, the TbSp of the femoral necks in the ovariectomized group (0.185±0.066 mm) was significantly greater than that in the control group (0.130±0.026mm). Similarly, the TbSp of the mandibles in the ovariectomized group (0.322±0.047mm) was significantly greater than that in the control group (0.285±0.041mm). However, the TbTh and TbN trends for the mandibles and femoral necks were inconsistent between the control and ovariectomized groups. Regarding the cortical bone morphology parameters, the TtAr of the femoral necks in the ovariectomized group was significantly smaller than that in the control group. There was no significant difference in the TtAr, CtAr, or CtTh of the femoral necks between the control and ovariectomized groups, and no significant difference in the CtTh of the mandibles between the control and ovariectomized groups. Moreover, the BV/TV and TbSp of the mandibles were highly correlated with those of the femurs (rs = 0.874 and rs = 0.755 for BV/TV and TbSp, respectively). Nevertheless, the TbTh, TbN, and CtTh of the mandibles were not correlated with those of the femoral necks.ConclusionAfter the rats were ovariectomized, osteoporosis of the trabecular bone microarchitecture occurred in their femurs and mandibles; however, ovariectomy did not influence the cortical bone morphology. In addition, the parametric values of the trabecular bone microarchitecture in the femoral necks were highly correlated with those of the trabecular bone microarchitecture in the mandibles.

Associations Between Physical Activity And Lower‐Limb Strength With Bone Parameters In Healthy Young Women: A Pilot Study

BackgroundMechanical loading‐induced strain provided from physical activity plays an essential role in promoting bone modeling. Furthermore, muscle contraction is an important factor in maintaining bone mass. Therefore, the study aimed to investigate the relationship between physical activity level and lower‐limb strength with bone mineral density (BMD), bone microarchitecture and body composition in young women.MethodsHealthy young women (age: 29.0±6.2 yrs, BMI: 22.46±2.26 kg/m2, n=14), not engaged in systematic exercise training programs, participated in this cross‐sectional study. Moderate‐to‐vigorous physical activity (MVPA) was assessed by accelerometry (ActiGraph GT3X+) for seven consecutive days. Leg press one repetition maximum (1‐RM) test was conducted in order to evaluate lower‐limb strength. BMD (i.e. assessed in four different skeletal sites, as follows: whole body, total femur, femur neck and lumbar spine) and body composition (i.e. lean mass and bone mineral content [BMC]) were measured by dual‐energy x‐ray absorptiometry. Trabecular bone microarchitecture parameters were measured by high‐resolution peripheral quantitative computed tomography in left tibia.ResultsThere was a positive correlation between MVPA and some skeletal sites, such as: total femur BMD (r=0.62, p=0.041) and femur neck BMD (r=0.63, p=0.038). No significant correlation was observed between MVPA and trabecular bone microarchitecture parameters. MVPA was significant correlated with lean mass (r=0.90, p&lt;0.001) and BMC (r=0.78, p=0.004). Lower‐limb strength was positively correlated with whole body BMD (r=0.66, p=0.009), total femur BMD (r=0.76, p=0.001), femur neck BMD (r=0.69, p=0.006), lumbar spine BMD (r=0.74, p=0.002), as well as tibial trabecular number (Tb.N) (r=0.63, p=0.021), and a negative correlation between tibial trabecular separation (Tb.Sp) (r=−0.55, p=0.050). With regard to body composition, lower‐limb strength was significantly associated with lean mass (r=0.73, p=0.002) and BMC (r=0.83, p&lt;0.001).ConclusionsThese preliminary data show that both lower‐limb strength and physical activity level are positively associated with measurements of BMD in young women, especially in lower‐limb sites. Furthermore, lower‐limb strength, but not physical activity level, is positively associated with tibial trabecular number and negatively associated with tibial trabecular separation.Support or Funding InformationFAPESP (process: 2015/02833‐5)

A comparison of micro-CT and dental CT in assessing cortical bone morphology and trabecular bone microarchitecture.

ObjectiveThe objective of this study was to evaluate the relationship between the trabecular bone microarchitecture and cortical bone morphology by using micro-computed tomography (micro-CT) and dental cone-beam computed tomography (dental CT).Materials and MethodsSixteen femurs and eight fifth lumbar vertebrae were collected from eight male Sprague Dawley rats. Four trabecular bone microarchitecture parameters related to the fifth lumbar vertebral body (percent bone volume [BV/TV], trabecular thickness [TbTh], trabecular separation [TbSp], and trabecular number [TbN]) were calculated using micro-CT. In addition, the volumetric cancellous bone grayscale value (vCanGrayscale) of the fifth lumbar vertebral body was measured using dental CT. Furthermore, four cortical bone morphology parameters of the femoral diaphysis (total cross-sectional area [TtAr], cortical area [CtAr], cortical bone area fraction [CtAr/TtAr], and cortical thickness [CtTh]) were calculated using both micro-CT and dental CT. Pearson analysis was conducted to calculate the correlation coefficients (r) of the micro-CT and dental CT measurements. Paired-sample t tests were used to compare the differences between the measurements of the four cortical bone morphology parameters obtained using micro-CT and dental CT.ResultsHigh correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV [r = 0.84] and TbTh [r = 0.84]) measured using micro-CT were observed. The absolute value of the four cortical bone morphology parameters may be different between the dental CT and micro-CT approaches. However, high correlations (r ranged from 0.71 to 0.90) among these four cortical bone morphology parameters measured using the two approaches were obtained.ConclusionWe observed high correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV and TbTh) measured using micro-CT, in addition to high correlations between the cortical bone morphology measured using micro-CT and dental CT. Further experiments are necessary to validate the use of dental CT on human bone.

Associations of plasma osteocalcin and fetuin‐A with bone mineral density in post‐menopausal women (867.16)

In postmenopausal women, decreases in estrogen disrupt the normal balance of bone turnover, increasing bone resorption relative to bone formation. This study investigated the effects of menopausal hormone treatment (MHT) on volumetric bone mineral density (vBMD) and markers of bone turnover in plasma of healthy, recently‐menopausal women. Women (age 52.3±2.3 yrs; n=115) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) were randomized to either: oral conjugated equine estrogen (oCEE), transdermal 17β estradiol (tE2) each with intermittent oral micronized progesterone or placebo (Pl), for 48 months. vBMD was assessed by quantitative computed tomography of the wrist, and plasma levels of osteocalcin (OCN; a bone turnover marker), and of Fetuin‐A, a hepatocyte‐derived modulator of osteogenesis, were quantified by ELISA. At 48 months, cortical vBMD at the distal radius had decreased by 2.9% in the Pl group, correspondent with an increase above initial plasma OCN (15.0 ng/ml) of 38.5%. MHT attenuated the vBMD decrease (0.9% in both treatment groups combined; P=0.015), and the OCN increase (8.8 and 4.3% in oCEE and tE2, respectively). Plasma Fetuin‐A levels did not differ significantly among groups at 48 mo. Unexpectedly, Fetuin‐A was negatively associated (r=‐0.50 to ‐0.62; P &lt;0.05) with changes in trabecular bone microarchitectural parameters at the distal radius in the Pl group, whereas both oCEE and tE2 attenuated this effect (all P‐values &gt;0.05). As expected, MHT attenuated bone turnover in postmenopausal women. However, the relationship between processes regulated by OCN and Fetuin‐A require further evaluation.Grant Funding Source: Supported by Aurora Foundation, HL90639 and AG44170

Abnormal bone quality versus low bone mineral density in adolescent idiopathic scoliosis: a case-control study with in vivo high-resolution peripheral quantitative computed tomography

Background contextAdolescent idiopathic scoliosis (AIS) is associated with low bone mass that could persist into early adulthood and is an important prognostic factor for curve progression. Previous studies were confined to areal bone mineral density measurement that was a two-dimensional investigation for a three-dimensional structure. Evaluation of volumetric BMD (vBMD) and other bone quality parameters are important for gaining in-depth understanding of the etiopathogenesis of AIS. PurposeThe objective of this study was to carry out direct in vivo measurement of bone quality in AIS using high-resolution peripheral quantitative computed tomography (HR-pQCT) and compare the correlation of bone quality with osteopenia between AIS and control subjects. Study design/settingA case-control study. Patient sampleNewly diagnosed AIS girls (n=112) and non-AIS girls (n=115) between 11 and 13 years. Outcome measuresAreal bone mineral density of bilateral femoral necks and HR-pQCT of the nondominant distal radius were performed. MethodsAreal bone mineral density of femoral necks was measured by dual-energy X-ray absorptiometry. Subjects were classified into the osteopenic (Z score less than or equal to −1) and nonosteopenic (Z score more than −1) groups. Bone quality parameters, including bone morphometry, trabecular bone microarchitecture, and vBMD, were measured by HR-pQCT (XtremeCT; Scanco Medical, Zurich, Switzerland). ResultsIn AIS, the osteopenic group had lower measurements in cortical area, cortical thickness, average vBMD, compact bone vBMD, trabecular vBMD, trabecular bone volume to tissue volume ratio, and trabecular thickness compared with nonosteopenic AIS subjects. In contrast, among the non-AIS controls, the osteopenic group had lower measurements only in bone morphometry, average vBMD, and compact bone vBMD but not in trabecular vBMD and all other trabecular bone microarchitecture parameters. ConclusionsThis is the first study using HR-pQCT to compare the correlation of bone quality with osteopenia in AIS and non-AIS subjects. It provides new insights and highlights the unique bone quality profile with predominant changes in the trabecular compartment in association with osteopenia being notably only detected in the AIS subjects. Further studies in this area are warranted for defining the metabolic nature and biomechanical sequelae of derangement in bone mass and bone quality and their roles in the etiopathogenesis of AIS.

Yeast-Incorporated Gallium Attenuates Glucocorticoid-Induced Bone Loss in Rats by Inhibition of Bone Resorption

Glucocorticoids (GC) are potent anti-inflammatory agents and widely used for the treatment of many immune-mediated and inflammatory diseases, whereas GC-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis and significantly increases the patients' morbidity and mortality. GIOP is characterized as diminished osteogenesis and accelerated bone resorption. Yeast-incorporated gallium (YG) as an organic compound not only reduces elements-associated toxicity, but also maintains its therapeutic effect on improving bone loss or promoting fracture healing in ovariectomized female rats. The aim of this study was to examine whether YG could prevent GC-induced bone loss. Five-month-old male Sprague-Dawley rats were randomly divided into three groups (n = 6): two groups were administered dexamethasone (0.1mg/kg/day) or vehicle (PBS) subcutaneously for 5weeks; one other group was received dexamethasone subcutaneously and YG (120μg/kg/day) orally. Trabecular bone microarchitectural parameters, bone mineral density (BMD), bone strength, body weight, and serum biochemical markers of bone resorption and formation were examined. Compared to the GC alone group, treatment with YG not only prevented microarchitectural deterioration of trabecular bone volume relative to tissue volume, trabecular number, and trabecular separation, but also significantly improved BMD, mechanical strength, and body weight in GC-treated rats. Moreover, YG decreased tartrate-resistant acid phosphatase 5b level but failed to change alkaline phosphatase level in GC-treated rats. This is the first study to show that YG prominently attenuates bone loss and microarchitectural deterioration and inhibits the increased bone resorption in GIOP. It implies that YG might be an alternative therapy for prevention of GC-induced bone loss in humans.

Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long‐term calorie restriction with adequate nutrition

Calorie restriction (CR) reduces bone quantity but not bone quality in rodents. Nothing is known regarding the long-term effects of CR with adequate intake of vitamin and minerals on bone quantity and quality in middle-aged lean individuals. In this study, we evaluated body composition, bone mineral density (BMD), and serum markers of bone turnover and inflammation in 32 volunteers who had been eating a CR diet (approximately 35% less calories than controls) for an average of 6.8 ± 5.2 years (mean age 52.7 ± 10.3 years) and 32 age- and sex-matched sedentary controls eating Western diets (WD). In a subgroup of 10 CR and 10 WD volunteers, we also measured trabecular bone (TB) microarchitecture of the distal radius using high-resolution magnetic resonance imaging. We found that the CR volunteers had significantly lower body mass index than the WD volunteers (18.9 ± 1.2 vs. 26.5 ± 2.2 kg m(-2) ; P = 0.0001). BMD of the lumbar spine (0.870 ± 0.11 vs. 1.138 ± 0.12 g cm(-2) , P = 0.0001) and hip (0.806 ± 0.12 vs. 1.047 ± 0.12 g cm(-2) , P = 0.0001) was also lower in the CR than in the WD group. Serum C-terminal telopeptide and bone-specific alkaline phosphatase concentration were similar between groups, while serum C-reactive protein (0.19 ± 0.26 vs. 1.46 ± 1.56 mg L(-1) , P = 0.0001) was lower in the CR group. Trabecular bone microarchitecture parameters such as the erosion index (0.916 ± 0.087 vs. 0.877 ± 0.088; P = 0.739) and surface-to-curve ratio (10.3 ± 1.4 vs. 12.1 ± 2.1, P = 0.440) were not significantly different between groups. These findings suggest that markedly reduced BMD is not associated with significantly reduced bone quality in middle-aged men and women practicing long-term calorie restriction with adequate nutrition.

Effect of specimen conditioning on the microarchitectural parameters of trabecular bone assessed by micro-computed tomography

The best way to preserve the mechanical properties of bone specimens is hydration in NaCl, whereas the reference process in µCT analysis is defatting. However, for finite element modelling (FEM) it is necessary to use the same bone specimens for biomechanical testing and 3D imaging. This study aimed to evaluate the effect of sample conditioning on trabecular bone microarchitectural parameters. Trabecular bones were analysed by µCT under three successive conditions: first, the fatted samples were analysed immersed in NaCl (process N); second, they were hydrated for 24 h then imaged without immersion (process H); third, the samples were defatted before analysis (process D). The microarchitectural parameters bone volume/tissue volume (BV/TV), trabecular spacing (Tb.Sp), number (Tb.N) and thickness (Tb.Th) were calculated. Except for BV/TV, there was no significant difference between the processes N and D. In process H, BV/TV, Tb.Th and Tb.N were higher and BS/BV and Tb.Sp were lower than in process D. Results showed that the process D may be replaced by the process N. The process H induced significant differences in microarchitectural parameters when compared to process D. Nevertheless, this sample conditioning should be used to develop FEM when µCT images are to be acquired during compressive testing.