Assessment of bone turnover and bone quality in type 2 diabetic bone disease： current concepts and future directions

Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes （T2D） and may be predictive of fractures independently of bone mineral density （BMD）. Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score （TBS） and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT （HRpQCT） imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct （AGE） accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk.

Dietary supplementation with calcitriol or quercetin improved eggshell and bone quality by modulating calcium metabolism

This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens.In trial 1,72 Hy-Line Brown layers(80-week-old)with weak-shelled strength(25 to 30 N)were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet(4%calcium level)or basal diets supplemented with 0.5%calcium,5μg/kg calcitriol or 500 mg/kg quercetin for 4 weeks.In trial 2,360 Hy-Line Brown layers(60-week-old)were divided into 3 groups with 8 replicates of 15 birds:control group(basal diet),calcitriol group(basal diet+5μg/kg calcitriol),and quercetin group(basal diet+500 mg/kg quercetin).This trial lasted for 12 weeks.The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials(P<0.05).In trial 2,compared with the control group,both calcitriol and quercetin supplementations improved femoral bone quality,calcium retention of hens and calcium content in uterine fluid at 18.5 h post-oviposition(PO)(P<0.05),along with enhancing uterine morphology.Compared to the control group,supplemental calcitriol or quercetin up-regulated the relative mRNA expression levels of uterine transient receptor potential cation channel,subfamily V,member 6(TRPV6)at 8.5 h PO and plasma membrane calcium-ATPase(PMCA),vitamin D receptor(VDR),estrogen receptor alpha(ERα)at 18.5 h PO(P<0.05),but down-regulated the uterine caspase 3(CASP3)relative mRNA expression level at 8.5 h PO(P<0.05).Meanwhile,the femoral relative mRNA expression levels of tartrate-resistant acid phosphatase(TRAP)(up-regulated at 8.5 and 18.5 h PO)and alkaline phosphatase(ALP)(up-regulated at 8.5 h PO but down-regulated at 18.5 h PO)were also affected by calcitriol or quercetin supplementation(P<0.05).Compared to the calcitriol,quercetin increased hen-day egg production and femoral medullary bone volume/bone tissue volume but reduced femoral stiffness(P<0.05),which were accompanied by increased relative mRNA expression levels of uterine TRPV6,estrogen receptor beta(ERβ)at 18.5 h PO(P<0.05).Overall,both dietary calcitriol and quercetin could improve eggshell and bone quality by modulating calcium metabolism of aged layers.Compared to calcitriol,dietary quercetin up-regulated the expression of uterine calcium transporters,without affecting eggshell quality.

Measurement of Cortical Bone Thickness in Adults by Cone-beam Computerized Tomography for Orthodontic Miniscrews Placement

The purpose of this study was to investigate the cortical bone thickness of the inter-dental area of both jaws for orthodontic miniscrew placement. The cone-beam computerized tomography images of 32 non-orthodontic adults with normal occlusion were taken to measure the cortical bone thick- ness in both.jaws. One-way analysis of variance （ANOVA） was used to analyze the differences in cortical bone thickness. Buccal cortical bone in the mandible was thicker than that in the maxilla. In the maxilla, cortical bone thickness was thicker in the buccal side than in the palatal side. Buccal cortical bone thickness in the mandible was thickest at the site distal to the first molar, and in the maxilla it was thickest at the site mesial to the first molar, while in the palatal side of maxilla it was thickest at the site mesial to the second premolar. The changing pattern of cortical bone thickness varies at different sites. In the buccal side of maxilla, the thinnest cortical bone thickness was lbund to be at 4 mm level from the alveolar crest, while the thickest was at 10 mm level （except for the site mesial to the first premolar）. The buccal cortical bone thickness at the sites mesial or distal to the first molar in the mandible and palatal cortical bone thickness of maxilla tended to increase with increasing distance from the alveolar bone.

Nanomechanical Characterization of Bone Quality Depending on Tissue Age via Bimodal Atomic Force Microscopy

Characterization of bone quality during the healing process is crucial for successful implantation procedures and patient comfort.In this study,a bone implant specimen that underwent a 4-week healing period was investigated.Bimodal atomic force microscopy(AFM)was employed to simultaneously obtain the morphology and elastic modulus maps of the newly formed and pre-existing bone regions within the sample.Results indicate that the new bone matrix possessed lower miner-alization levels and presented larger,uneven mineral grains,exhibiting the attributes of a woven bone.On the other hand,the old bone matrix exhibited a more uniform and mineralized structure,which is characteristic of lamellar bones.The new bone had a lower overall elastic modulus than the old bone.Bimodal AFM further confrmed that the new bone displayed three regions comprising unmineralized,partially mineralized,and fully matured sections,which indicate a turbulent change in its composition.Meanwhile,the old bone exhibited two sections comprising partially mineralized and matured bone parts,which denote the fnal phase of mineralization.This study provides valuable insights into the morphological and nanome-chanical diferences between the old and new bone matrixes and presents a novel approach to investigate bone quality at diferent phases of the bone-healing process.

Effects of denosumab treatment in chronic liver disease patients with osteoporosis

BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BMD)and decrease the risk of osteoporotic fracture in the general population.However,there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo.The study period for evaluating efficacy and safety was 12 mo.Changes from baseline in BMD at the lumbar spine,femoral neck,and total hip were evaluated at 12 mo of denosumab treatment.Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b(bone resorption marker),serum total procollagen type I N-terminal propeptide(bone formation maker),and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients,138(34.1%)patients were diagnosed with osteoporosis;among these,78 patients met the exclusion criteria and thus 60 patients were finally included in the present study.The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine,femoral neck,and total hip were+4.44%,+3.71%,and+4.03%,respectively.Denosumab significantly improved BMD,regardless of sex,patient age,and presence of liver cirrhosis.Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P<0.001).Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P=0.010).No patients experienced fractures and moderate-to-severe adverse events,except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD,suppressed bone turnover,and improved bone quality marker levels in CLD patients with osteoporosis,irrespective of differences in baseline characteristics.

Recent advancements in the analysis of bone microstructure: new dimensions in forensic anthropology

Bone is a mechanically active,three-dimensionally(3D)complex,and dynamic tissue that changes in structure over the human lifespan.Bone tissue exists and remodels in 3D and changes over time,introducing a fourth dimension.The products of the remodelling process,secondary and fragmentary osteons,have been studied substantially using traditional two-dimensional(2D)techniques.As a result,much has been learned regarding the biological information encrypted in the histomorphology of bone,yielding a wealth of information relating to skeletal structure and function.Three-dimensional imaging modalities,however,hold the potential to provide a much more comprehensive understanding of bone microarchitecture.The visualization and analysis of bone using high-resolution 3D imaging will improve current understandings of bone biology and have numerous applications in both biological anthropology and biomedicine.Through recent technological advancements,we can hone current anthropological applications of the analysis of bone microstructure and accelerate research into the third and fourth dimensional realms.This review will explore the methodological approaches used historically by anthropologists to assess cortical bone microstructure,spanning from histology to current ex vivo imaging modalities,discuss the growing capabilities of in vivo imaging,and conclude with an introduction of novel nonhistological modalities for investigating bone quality.

Use of 25-hydroxyvitamin D_(3) in diets for sows:A review

Dietary supplementation with 25-hydroxyvitamin D_(3)(25OHD_(3)),as an alternative source of vitamin D,is becoming increasingly popular due to its commercialization and more efficient absorbability.The addition of 25OHD_(3)rather than its precursor vitamin D_(3)can circumvent the 25-hydroxylation reaction in the liver,indicating that supplementation of 25OHD_(3)can rapidly improve the circulating vitamin D status of animals.Emerging experiments have reported that maternal 25OHD_(3)supplementation could increase sow performances and birth outcomes and promote circulating vitamin D status of sows and their offspring.Increased milk fat content was observed in many experiments;however,others demonstrated that adding 25OHD_(3)to lactating sow diets increased the contents of milk protein and lactose.Although an inconsistency between the results of different experiments exists,these studies suggested that maternal 25OHD_(3)supplementation could alter milk composition via its effects on the mammary gland.Previous studies have demonstrated that adding 25OHD_(3)to sow diets could improve the mRNA expressions of insulin-induced gene 1(INSIG1)and sterol regulatory element-binding protein 1(SREBP1)in the mammary gland cells from milk and increase the mRNA expressions of acetyl-CoA carboxylaseα(ACCα)and fatty acid synthase(FAS)in the mammary gland tissue.Maternal 25OHD_(3)supplementation promotes skeletal muscle development of piglets before and after parturition,and improves bone properties including bone density and bone breaking force in lactating sows and their piglets.Interestingly,25OHD_(3)supplementation in sow diets could improve neonatal bone development via regulation of milk fatty acid composition related to bone metabolism and mineralization.In this review,we also discuss the effects of adding 25OHD_(3)to sow diets on the gut bacterial metabolites of suckling piglets,and propose that butyrate production may be associated with bone health.Therefore,to better understand the nutritional functions of maternal 25OHD_(3)supplementation,this paper reviews advances in the studies of 25OHD_(3)for sow nutrition and provides references for practical application.

Cage type and mineral nutrition had independent impact on skeletal development in Lohmann LSL-Lite pullets from hatch to 16 weeks of age

The effects of rearing cage type and dietary Ca,available P and vitamin D_(3)(VitD_(3))on body and skeletal development were studied.A total of 3,420 Lohmann LSL-Lite day-old chicks were reared in conventional(CON)or furnished cages(FUR)to 16 wk of age.Initially,40 and 150 chicks/cage were placed in CON and FUR and transitioned to 20 and 75 chicks/cage at 8 wk of age,respectively.Three diets:Diet 1,Diet 1.5 and Diet 2 were formulated to meet nutrient specifications with Diet 1.5 and Diet 2 containing 1.5 and 2 times more Ca,P and VitD_(3)than Diet 1,respectively.Diets were allocated within cage type to give 6 replicates and fed in 3 feeding programs:starter,grower and developer.At 4,12 and 16 wk of age,BW was recorded,and femur,tibia and blood samples for bone quality and related parameters.There were no interactions(P>0.05)of cage type,diet and pullet age on BW,plasma Ca and inorganic P,femur and tibia morphometry,mineral density(MD),breaking strength(BS)and ash concentration(AC).Concentration of Ca,P and VitD_(3)linearly decreased BW(P<0.001),relative femur(P=0.010)and tibia weight(P=0.013).A quadratic increase on femur MD(P=0.03)and BS(P=0.026)was observed with dietary concentration of Ca,P and VitD_(3).Femur(P=0.031)was longer for CON than FUR pullets,however,femur for FUR pullets had higher(P=0.003)AC.Cage had no effect(P≥0.415)femoral MD and BS.Pullets reared in FUR cages exhibited higher tibial MD(P=0.015),BS(P=0.071),AC(P<0.01)and whole-body mineral content(P<0.01).In conclusion,cage type and diets showed independent effect on femur and tibia quality with FUR pullets exhibiting enhanced indices of mineralization.Feeding pullets twice the recommended Ca,P and VitD_(3)decreased BW,relative weight of leg bone but enhanced femoral strength with no effects on tibia attributes.

Mechanisms for increased systemic fracture risk after index fracture

The single best predictor of future fracture risk is a prior fracture at any skeletal site.However,the mechanisms underlying this relationship remain incompletely understood.Here we review three potential mechanisms underlying increased risk.An index fracture may reflect preexisting deficits in bone quality or impairments in physical function.Second,fracture may cause biomechanical changes that increase future fracture risk.Third,fracture induces a period of systemic bone loss that is never fully recovered.Further investigation into these mechanisms can inform treatments that prevent future fractures for individuals with a prior history of fracture.