Effect of strain of layer and age at photostimulation on egg production, egg quality, and bone strength.

PubMed

Silversides, F G; Korver, D R; Budgell, K L

2006-07-01

Bone strength in layers is a concern for economic reasons and animal welfare concerns. Bone characteristics were investigated in 3 strains of hens: Babcock B-300, a small-bodied commercial white-egg layer; ISA-Brown, a commercial brown-egg layer; and an unselected Brown Leghorn line (BL). After being reared together in a single pen with 8 h of light per day, hens were caged with 14 h of light per day. Half of the hens were caged at 18 wk of age and the other half at 20 wk of age, resulting in a 2-wk difference in the age at photostimulation. Body weights, egg production, feed efficiency, and egg quality were measured throughout production. At 15, 25, 50, and 74 wk of age, hens were euthanized for sampling of the radius and the humerus. Breaking strength of the radius and humerus was measured, and the area and density of trabecular (largely medullary bone) and cortical bone were measured using quantitative computed tomography. Egg production and feed conversion of ISA-Brown hens was as good as or better than that of Babcock B-300 hens, and both commercial strains had higher production than the BL. Photostimulation late delayed sexual maturity and improved albumen and shell characteristics but had only minor effects on egg production and did not affect the yolk weight. The delayed photostimulation resulting from caging 2 wk later affected the radius by increasing the area of the trabecular space at 50 wk of age and the density of the bone in the trabecular space at 74 wk of age. Breaking strength of the humerus at 25 wk of age was greater for the birds that were photostimulated late but was not different later in the trial. The humerus, but not the radius, of the BL had a greater breaking strength than that of the commercial strains, suggesting that selection has decreased humeral breaking strength.

MiR-142-5p promotes bone repair by maintaining osteoblast activity.

PubMed

Tu, Manli; Tang, Juanjuan; He, Hongbo; Cheng, Peng; Chen, Chao

2017-05-01

MicroRNAs play important roles in regulating bone regeneration and remodeling. However, the pathophysiological roles of microRNAs in bone repair remain unclear. Here we identify a significant upregulation of miR-142-5p correlated with active osteoblastogenesis during the bone healing process. In vitro, miR-142-5p promoted osteoblast activity and matrix mineralization by targeting the gene encoding WW-domain-containing E3 ubiquitin protein ligase 1. We also found that the expression of miR-142-5p in the callus of aged mice was lower than that in the callus of young mice and directly correlated with the age-related delay in bone healing. Furthermore, treatment with agomir-142-5p in the fracture areas stimulated osteoblast activity which repaired the bone fractures in aged mice. Thus, our study revealed that miR-142-5p plays a crucial role in healing fractures by maintaining osteoblast activity, and provided a new molecular target therapeutic strategy for bone healing.

Bone age detection via carpogram analysis using convolutional neural networks

NASA Astrophysics Data System (ADS)

Torres, Felipe; Bravo, María. Alejandra; Salinas, Emmanuel; Triana, Gustavo; Arbeláez, Pablo

2017-11-01

Bone age assessment is a critical factor for determining delayed development in children, which can be a sign of pathologies such as endocrine diseases, growth abnormalities, chromosomal, neurological and congenital disorders among others. In this paper we present BoneNet, a methodology to assess automatically the skeletal maturity state in pediatric patients based on Convolutional Neural Networks. We train and evaluate our algorithm on a database of X-Ray images provided by the hospital Fundacion Santa Fe de Bogot ´ a with around 1500 images of patients between the ages 1 to 18. ´ We compare two different architectures to classify the given data in order to explore the generality of our method. To accomplish this, we define multiple binary age assessment problems, dividing the data by bone age and differentiating the patients by their gender. Thus, exploring several parameters, we develop BoneNet. Our approach is holistic, efficient, and modular, since it is possible for the specialists to use all the networks combined to determine how is the skeletal maturity of a patient. BoneNet achieves over 90% accuracy for most of the critical age thresholds, when differentiating the images between over or under a given age.

Rap system of stress stimulation can promote bone union after lower tibial bone fracture: a clinical research.

PubMed

Yao, Jian-fei; Shen, Jia-zuo; Li, Da-kun; Lin, Da-sheng; Li, Lin; Li, Qiang; Qi, Peng; Lian, Ke-jian; Ding, Zhen-qi

2012-01-01

Lower tibial bone fracture may easily cause bone delayed union or nonunion because of lacking of dynamic mechanical load. Research Group would design a new instrument as Rap System of Stress Stimulation (RSSS) to provide dynamic mechanical load which would promote lower tibial bone union postoperatively. This clinical research was conducted from January 2008 to December 2010, 92 patients(male 61/female 31, age 16-70 years, mean 36.3 years) who suffered lower tibial bone closed fracture were given intramedullary nail fixation and randomly averagely separated into experimental group and control group(according to the successively order when patients went for the admission procedure). Then researchers analysed the clinical healing time, full weight bearing time, VAS (Visual Analogue Scales) score and callus growth score of Lane-Sandhu in 3,6,12 months postoperatively. The delayed union and nonunion rates were compared at 6 and 12 months separately. All the 92 patients had been followed up (mean 14 months). Clinical bone healing time in experimental group was 88.78±8.80 days but control group was 107.91±9.03 days. Full weight bearing time in experimental group was 94.07±9.81 days but control group was 113.24±13.37 days respectively (P<0.05). The delayed union rate in 6 months was 4.3% in experimental group but 10.9% in control group(P<0.05). The nonunion rate in 12 months was 6.5% in experimental group but 19.6% in control group(P<0.05). In 3, 6, 12 months postoperatively, VAS score and Lane-Sandhu score in experimental group had more significantly difference than them in control group. RSSS can intermittently provide dynamic mechanical load and stimulate callus formation, promote lower tibial bone union, reduce bone delayed union or nonunion rate. It is an adjuvant therapy for promoting bone union after lower tibial bone fracture.

Delay in estrogen commencement is associated with lower bone mineral density in Turner syndrome.

PubMed

Nguyen, H H; Wong, P; Strauss, B J; Jones, G; Ebeling, P R; Milat, F; Vincent, A

2017-10-01

Turner syndrome (TS) is associated with hypogonadism, osteoporosis and fractures. We investigated the prevalence and risk factors for low bone density and fractures in a TS cohort. We included 76 TS patients (median age 28.5 years) attending a tertiary hospital between 1998 and 2015 who underwent dual-energy X-ray absorptiometry. Spine and femoral neck (FN) areal bone mineral density (aBMD) were compared with those of a control group. To adjust for smaller bone size, bone mineral apparent density (BMAD) was calculated. Primary amenorrhea was common (83%) in the TS cohort; the median age of pubertal induction was 15 years (range 11-30 years), and non-continuous estrogen therapy (ET) recorded in 40%. Almost one-third of TS patients reported fractures. TS patients had lower median spinal aBMD (1.026 g/cm 2 vs. 1.221 g/cm 2 ) and BMAD (0.156 g/cm 3 vs. 0.161 g/cm 3 ) than controls, and lower median FN aBMD (0.850 g/cm 2 vs. 1.026 g/cm 2 ) (all p < 0.01). More women with TS had spinal Z-score < -2.0 compared to controls (26.0% vs. 3.6%, p = 0.001). Spine and FN aBMD, BMAD and Z-scores were inversely associated with age commencing ET or years of estrogen deficiency. Delay in ET commencement was an independent risk factor for the lower bone density observed in women with TS. Early pubertal induction and ET compliance are important targets to optimize aBMD.

A large case-control study reveals a positive association between bisphosphonate use and delayed dental healing and osteonecrosis of the jaw.

PubMed

Borromeo, Gelsomina L; Brand, Caroline; Clement, John G; McCullough, Michael; Crighton, Lisa; Hepworth, Graham; Wark, John D

2014-06-01

This study sought to investigate, using a case-control study design, the association between bisphosphonate therapy and delayed dental healing and osteonecrosis of the jaw. Identification of potential cases of delayed dental healing was by consecutive screening of Specialist Oral and Maxillofacial and Special Needs Dentist clinic records for patients aged older than 50 years, during a 6-month window, in Victoria, Australia. Cases were confirmed by a case adjudication panel blinded to bisphosphonate status. Cases associated with malignancy or local radiotherapy were excluded. Controls were matched for age, sex, and source of dental referral (1:4, n = 160 controls). Variables of interest were dental precipitants, dental clinic type, smoking history, and medical comorbidities. A total of 4212 of 22,358 patients met inclusion criteria, of which 69 were potential cases with 40 (0.95%) confirmed cases. The odds ratio (OR) for developing delayed dental healing when taking an oral bisphosphonate was 13.1 (95% confidence interval [CI] 4.4 to 39.3; p < 0.001). There were no cases associated with intravenous bisphosphonate use. There was some evidence of an interaction with age, sex, and clinic type. When adjusted for smoking, the estimated odds ratio was 11.6 (95% CI 1.9 to 69.4; p = 0.01). There was an association between having another illness and delayed dental healing (OR = 2.3; 95% CI 1.0 to 5.2). A dental precipitant was present in 39 of 40 (97.5%) delayed dental healing cases. An important association between bisphosphonate use and delayed dental healing in the setting of benign bone disease, predominately in individuals with a dental precipitant, has been demonstrated. © 2014 American Society for Bone and Mineral Research.

Boys with a simple delayed puberty reach their target height.

PubMed

Cools, B L M; Rooman, R; Op De Beeck, L; Du Caju, M V L

2008-01-01

Final height in boys with delayed puberty is thought to be below target height. This conclusion, however, is based on studies that included patients with genetic short stature. We therefore studied final height in a group of 33 untreated boys with delayed puberty with a target height >-1.5 SDS. Standing height, sitting height, weight and arm span width were measured in each patient. Final height was predicted by the method of Greulich and Pyle using the tables of Bailey and Pinneau for retarded boys at their bone age (PAH1) and the tables of Bailey and Pinneau for average boys plus six months (PAH2). Mean final height (175.8 +/- 6.5 cm) was appropriate for the mean target height (174.7 +/- 4.5 cm). The prediction method of Bailey and Pinneau overestimated the final height by 1.4 cm and the modified prediction method slightly underestimated the final height (-0.15 cm). Boys with untreated delayed puberty reach a final height appropriate for their target height. Final height was best predicted by the method of Bailey and Pinneau using the tables for average boys at their bone age plus six months. Copyright 2008 S. Karger AG, Basel.

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing.

PubMed

Xu, M T; Sun, S; Zhang, L; Xu, F; Du, S L; Zhang, X D; Wang, D W

2016-01-01

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

Variable expressivity of the phenotype in two families with brachydactyly type E, craniofacial dysmorphism, short stature and delayed bone age caused by novel heterozygous mutations in the PTHLH gene.

PubMed

Jamsheer, Aleksander; Sowińska-Seidler, Anna; Olech, Ewelina M; Socha, Magdalena; Kozłowski, Kazimierz; Pyrkosz, Antoni; Trzeciak, Tomasz; Materna-Kiryluk, Anna; Latos-Bieleńska, Anna

2016-05-01

Brachydactyly refers to shortening of digits due to hypoplasia or aplasia of bones forming the hands and/or feet. Isolated brachydactyly type E (BDE), which is characterized by shortened metacarpals and/or metatarsals, results in a small proportion of patients from HOXD13 or PTHLH mutations, although in the majority of cases molecular lesion remains unknown. BDE, like other brachydactylies, shows clinical heterogeneity with highly variable intrafamilial and interindividual expressivity. In this study, we investigated two Polish cases (one familial and one sporadic) presenting with BDE and additional symptoms due to novel PTHLH mutations. Apart from BDE, the affected family showed short stature, mild craniofacial dysmorphism and delayed bone age. Sanger sequencing of PTHLH revealed a novel heterozygous frameshift mutation c.258delC(p.N87Tfs*18) in two affected individuals and one relative manifesting mild brachydactyly. The sporadic patient, in addition to BDE, presented with craniofacial dysmorphism, normal stature and bone age, and was demonstrated to carry a de novo heterozygous c.166C>T(p.R56*) mutation. Our paper reports on the two novel truncating PTHLH variants, resulting in variable combination of BDE and other symptoms. Data shown here expand the knowledge on the phenotypic presentation of PTHLH mutations, highlighting significant clinical variability and incomplete penetrance of the PTHLH-related symptoms.

Minority and Public Insurance Status: Is There a Delay to Alveolar Bone Grafting Surgery?

PubMed

Silvestre, Jason; Basta, Marten N; Fischer, John P; Lowe, Kristen M; Mayro, Rosario; Jackson, Oksana

2017-01-01

  This study sought to determine the timing of alveolar bone grafting (ABG) surgery among children with cleft lip with or without cleft palate (CL±P) with regard to race and insurance status.   A retrospective chart review of consecutive patients receiving ABG surgery was conducted. A multivariate regression model was constructed using predetermined clinical and demographic variables.   A large, urban cleft referral center.   Nonsyndromic patients with CL±P were eligible for study inclusion.   ABG surgery using autogenous bone harvested from the anterior iliac crest.   The primary outcome of interest was age at ABG surgery.   A total of 233 patients underwent ABG surgery at 8.1 ± 2.3 years of age. African American and Hispanic patients received delayed ABG surgery compared with Caucasian patients by approximately 1 year (P < .05). There was no difference in ABG surgery timing by insurance status (P > .05).   The timing of ABG surgery varied by race but not by insurance status. Greater resources may be needed to ensure timely delivery of cleft care to African American and Hispanic children.

Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions.

PubMed

Naderi, Fariba; Eslami, Samira Rajabi; Mirak, Sohrab Afshari; Khak, Mohammad; Amiri, Jalaladin; Beyrami, Bahram; Shekarchi, Babak; Poureisa, Masoud

2015-01-01

Growth hormone deficiency (GHD) is a major problem among children with short stature. In this study, the role of brain magnetic resonance imaging (MRI) in defining the underlying defects among short children with GHD is evaluated. In a cross-sectional study, data of 158 children were evaluated. Growth hormone (GH) levels were measured using stimulating tests and brain MRI with gadolinium contrast was applied, as well. Some 25.3% of patients had GHD with a mean age of 8.01±3.40 years. MRI results showed 35 as normal, four with pituitary hypoplasia, and one with microadenoma. The MRI results were significantly associated with GH levels and presence of other endocrine disorders. There was a significant association between prenatal disorders and patients' bone age delay. In patients with severe GHD and patients with multiple pituitary hormone deficiencies, MRI is more likely to be abnormal, and bone age is much delayed in patients with history of prenatal disorders.

Advanced skeletal maturity in children and adolescents with myelomeningocele.

PubMed

Roiz, Ronald; Mueske, Nicole M; Van Speybroeck, Alexander; Ryan, Deirdre D; Gilsanz, Vicente; Wren, Tishya A L

2017-12-11

Atypical skeletal development is common in youth with myelomeningocele (MM), though the underlying reasons have not been fully elucidated. This study assessed skeletal maturity in children and adolescents with MM and examined the effects of sex, age, sexual development, ethnicity, anthropometrics and shunt status. Forty-three males and 35 females with MM, 6-16 years old, underwent hand radiographs for bone age determination. The difference between bone age and chronological age was evaluated using Wilcoxon sign rank tests. Relationships between age discrepancy (skeletal-chronological) and participant characteristics were assessed using multiple linear regression with forward selection. Overall, forty percent (31/78) of MM participants had an advanced bone age of 1 year or greater (median: 2.5 years), while 47% (37/78) were within 1 year above or below their chronological age (-0.001 years) and 13% (10/78) were delayed by more than 1 year (-1.4 years). Bone age was advanced compared to chronologic age in both males and females (p⩽ 0.024). Advanced bone age was observed in early to late puberty and after maturation (p⩽ 0.07), as well as in Hispanic participants (p= 0.003) and in those with a shunt (p= 0.0004). Advanced bone age was positively correlated with height, weight and body mass index (BMI) percentiles (p= 0.004). In multiple linear regression analysis, advanced bone age was most strongly associated with higher Tanner stage of sexual development, and higher weight, height or BMI percentile. Advanced skeletal maturity is common in children/adolescents with MM over 8 years of age who have reached puberty (65%), particularly those who are overweight (80%). Hormonal effects associated with adiposity and sexual maturity likely influence skeletal maturation. Clinicians may use Tanner stage and weight or BMI to gain insight into skeletal maturity.

Radiographic evaluation for AVN following distal metatarsal Stoffella bunion osteotomy.

PubMed

Klein, Christian; Zembsch, Alexander; Dorn, Ulrich

2009-01-01

Avascular necrosis of the metatarsal head, delayed bone healing and nonunion are complications that may occur after distal first metatarsal osteotomies. Intraoperative damage to the extraosseous blood supply, the location of the osteotomy and postoperative vasospasm have been cited as possible causes of such changes. We evaluated Stoffella's subcapital osteotomies which were performed at our department for the correction of moderate to severe hallux valgus deformities. Standardized radiographs of 300 feet, taken 6weeks, 3 months, and 6 months postoperatively and at the final followup were examined with regard to postoperative AVN or signs of delayed bone healing. Of 228 patients, 202 were women and 26 were men. The patients' mean age was 49 years, and the mean followup was 12 months. In 278 cases the radiographs revealed an unremarkable first metatarsal head. Seventeen cases showed diffuse or localized osteopenia or small cysts in the subchondral bone. These changes fully resolved on subsequent radiographs. The X-rays of two patients revealed progressive narrowing of the joint space, irregular contours on the surface of the joint and an abnormal bone structure. The patients subsequently developed a characteristic picture of avascular necrosis, in one case combined with nonunion. Three patients had delayed bone healing, but ultimately healed successfully. Ischemic changes in bone are known to occur after distal first metatarsal osteotomies. There is a very low incidence of postoperative perfusion problems after Stoffella;s technique, even with lateral soft tissue release.

A safe strategy to decrease fetal lead exposure in a woman with chronic intoxication.

PubMed

Leiba, Adi; Hu, Howard; Zheng, Amin; Kales, Stefanos N

2010-08-01

During pregnancy skeletal lead is mobilized by maternal bone turnover and can threaten fetal development. The exact strategy suggested to women of childbearing age, who were chronically exposed to lead, and, thus, have high bone lead burden, is not well established. We describe 4 years of follow-up of a 29-year-old woman with chronic lead intoxication. We (a) advised her to delay conception until 'toxicological clearance', (b) treated her with multiple courses of lead chelator, DMSA, and (c) prescribed oral calcium. Patient had low blood lead and protoporphyrin level during pregnancy until delivery. Delaying conception, lead chelation, and calcium supplementation can decrease fetal exposure.

Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation

PubMed Central

Nishikawa, Keizo; Nakashima, Tomoki; Takeda, Shu; Isogai, Masashi; Hamada, Michito; Kimura, Ayako; Kodama, Tatsuhiko; Yamaguchi, Akira; Owen, Michael J.; Takahashi, Satoru; Takayanagi, Hiroshi

2010-01-01

Aging leads to the disruption of the homeostatic balance of multiple biological systems. In bone marrow multipotent mesenchymal cells undergo differentiation into various anchorage-dependent cell types, including osteoblasts and adipocytes. With age as well as with treatment of antidiabetic drugs such as thiazolidinediones, mesenchymal cells favor differentiation into adipocytes, resulting in an increased number of adipocytes and a decreased number of osteoblasts, causing osteoporosis. The mechanism behind this differentiation switch is unknown. Here we show an age-related decrease in the expression of Maf in mouse mesenchymal cells, which regulated mesenchymal cell bifurcation into osteoblasts and adipocytes by cooperating with the osteogenic transcription factor Runx2 and inhibiting the expression of the adipogenic transcription factor Pparg. The crucial role of Maf in both osteogenesis and adipogenesis was underscored by in vivo observations of delayed bone formation in perinatal Maf–/– mice and an accelerated formation of fatty marrow associated with bone loss in aged Maf+/– mice. This study identifies a transcriptional mechanism for an age-related switch in cell fate determination and may provide a molecular basis for novel therapeutic strategies against age-related bone diseases. PMID:20877012

Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls.

PubMed

Misra, Madhusmita; Aggarwal, Avichal; Miller, Karen K; Almazan, Cecilia; Worley, Megan; Soyka, Leslie A; Herzog, David B; Klibanski, Anne

2004-12-01

Anorexia nervosa (AN) is an eating disorder that leads to a number of medical sequelae in adult women and has a mortality rate of 5.6% per decade; known complications include effects on hematologic, biochemical, bone density, and body composition parameters. Few data regarding medical and developmental consequences of AN are available for adolescents, in particular for an outpatient community-dwelling population of girls who have this disorder. The prevalence of AN is increasing in adolescents, and it is the third most common chronic disease in adolescent girls. Therefore, it is important to determine the medical effects of this disorder in this young population. We examined clinical characteristics and performed hematologic, biochemical, hormonal, and bone density evaluations in 60 adolescent girls with AN (mean age: 15.8 +/- 1.6 years) and 58 healthy adolescent girls (mean age: 15.2 +/- 1.8 years) of comparable maturity. Nutritional and pubertal status; vital signs; a complete blood count; potassium levels; hormonal profiles; bone density at the lumbar and lateral spine; total body, hip, and femoral neck (by dual-energy x-ray absorptiometry) and body composition (by dual-energy x-ray absorptiometry) were determined. All measures of nutritional status such as weight, percentage of ideal body weight, body mass index, lean body mass, fat mass, and percentage of fat mass were significantly lower in girls with AN than in control subjects. Girls with AN had significantly lower heart rates, lower systolic blood pressure, and lower body temperature compared with control subjects. Total red cell and white cell counts were lower in AN than in control subjects. Among girls with AN, 22% were anemic and 22% were leukopenic. None were hypokalemic. Mean age at menarche did not differ between the groups. However, the proportion of girls who had AN and were premenarchal was significantly higher compared with healthy control subjects who were premenarchal, despite comparable maturity as determined by bone age. Ninety-four percent of premenarchal girls with AN versus 28% of premenarchal control subjects were above the mean age at menarche for white girls, and 35% of premenarchal AN girls versus 0% of healthy adolescents were delayed >2 SD above the mean. The ratio of bone age to chronological age, a measure of delayed maturity, was significantly lower in girls with AN versus control subjects and correlated positively with duration of illness and markers of nutritional status. Serum estradiol values were lower in girls with AN than in control subjects, and luteinizing hormone values trended lower in AN. Levels of insulin-like growth factor-I were also significantly lower in girls with AN. Estradiol values correlated positively with insulin-like growth factor-I, a measure of nutritional status essential for growth (r = 0.28). All measures of bone mineral density (z scores) were lower in girls with AN than in control subjects, with lean body mass, body mass index, and age at menarche emerging as the most important predictors of bone density. Bone density z scores of <-1 at any one site were noted in 41% of girls with AN, and an additional 11% had bone density z scores of <-2. A high prevalence of hemodynamic, hematologic, endocrine, and bone density abnormalities are reported in this large group of community-dwelling adolescent girls with AN. Although a number of these consequences of AN are known to occur in hospitalized adolescents, the occurrence of these findings, including significant bradycardia, low blood pressure, and pubertal delay, in girls who are treated for AN on an outpatient basis is of concern and suggests the need for vigilant clinical monitoring, including that of endocrine and bone density parameters.

The effect of a short-term delay of puberty on trabecular bone mass and structure in female rats: A texture-based and histomorphometric analysis.

PubMed Central

Yingling, Vanessa R; Xiang, Yongqing; Raphan, Theodore; Schaffler, Mitchell; Koser, Karen; Malique, Rumena

2007-01-01

Accrual of bone mass and strength during development is imperative in order to reduce the risk of fracture later in life. Although delayed pubertal onset is associated with an increased incidence of stress fracture, evidence supports the concept of “catch up” growth. It remains unclear if deficits in bone mass associated with delayed puberty have long term effects on trabecular bone structure and strength. The purpose of this study was to use texture-based analysis and histomorphometry to investigate the effect of a delay in puberty on trabecular bone mass and structure immediately post-puberty and at maturity in female rats. Forty-eight female Sprague Dawley rats (25 days) were randomly assigned to one of four groups; 1) short-term control (C-ST), 2) long-term control (C-LT), 3) short-term GnRH antagonist (G-ST) and 4) long-term GnRH antagonist (G-LT). Injections of either saline or gonadotropin-releasing hormone antagonist (GnRH-a) (100 μg/day) (Cetrotide™, Serono, Inc) were given intraperitoneally for 18 days (day 35–42) to both ST and LT. The ST groups were sacrificed after the last injection (day 43) and the LT groups at 6 months of age. Pubertal and gonadal development was retarded by the GnRA antagonist injections as indicated by a delay in vaginal opening, lower ovarian and uterine weights and suppressed estradiol levels in the short-term experimental animals (G-ST). Delayed puberty caused a transient reduction in trabecular bone area as assessed by histomorphometry. Specifically, the significant deficit in bone area resulted from a decreased number of trabecula and an increase in trabecular separation. Texture analysis, a new method to assess bone density and structural anisotropy, correlated well with the standard histomorphometry and measured significant deficits in the density measure (MDensity) in the G-ST group that remained at maturity (6 months). The texture energy deficit in the G-ST group was primarily in the 0° orientation (−13.2 %), which measures the longitudinal trabeculae in the proximal tibia. However, the deficit in the G-LT group was in the 45° and 135° orientations. These results suggest that any “catch-up” growth following the cessation of the GnRH-antagonist injection protocol may be directed in trabeculae oriented perpendicular to 0° at the expense of trabeculae in other orientations. PMID:16979963

Influence of growth hormone therapy on selected dental and skeletal system parameters.

PubMed

Partyka, Małgorzata; Chałas, Renata; Dunin-Wilczyńska, Izabella; Drohomyretska, Myroslava; Klatka, Maria

2018-03-14

Growth hormone deficiency (GHD) is one of the main indications for growth hormone therapy. One characteristic of this disease is bone age delay in relation to the chronological age. Pituitary dysfunction negatively affects the growth and development of the jaws and teeth of the child. The secretion of endocrine glands regulates growth, development, and gender differentiation. It also controls the growth of bones and teeth, regulates metabolism of calcium and phosphate, proteins, lipids and carbohydrates. The primary role in the endocrine system is played by the pituitary gland which is responsible for the production of somatotropin [1]. Dysfunction of the pituitary gland has a negative effect on the growth and development of long bones in the body, and may have an adverse effect on the development of maxilla, mandible and dentition of a child. There is some information in the literature that dental age is delayed in short stature children; the replacement of deciduous teeth by permanent teeth is also delayed, and newly erupted permanent teeth often require orthodontic treatment. Applying hormonal therapy positively affects the process of replacement of dentition [2, 3, 4, 5, 6]. The aim of the study was to assess bone and dental age, as well as analyze the state of dentition in children diagnosed with GH deficiency treated with growth hormone, depending on the duration of treatment. The study material consisted of 110 children (27 males, 83 females), hospitalized for somatotropin hypopituitarism in the Department of Paediatric Endocrinology and Diabetology at the Medical University of Lublin, Poland. The mean birth age was 13 years (156 months) with a standard deviation of 2 years and 6 months (30 months). 47 children (43%) started treatment with the growth hormone (group starting treatment) and 63 children (57%) whose treatment was started 2-3 years previously (group in the course of treatment). The control group consisted of 41 generally healthy children (15males, 25 females) with ENT problems, such as hypoacusis and a condition after nasal injury, hospitalized in the Department of Paediatric Otolaryngology at the Medical University of Lublin, Poland. The mean age was 11 years and 5 months (137 months) with standard deviation of 2 years and 5 months (29 months). Informed consent was obtained from the parents. The study was approved by the Bioethical Committee at the Medical University of Lublin (Resolution No. KE-0254 /216 /2012).

Analysis of Bone Height Changes after Maxillary Sinus Augmentation with Simultaneous and Delayed Placement of Dental Implants: A Clinical and Radiographic Study.

PubMed

Yin, Lihua; Yu, Zhanhai; Chen, Zhuofan; Huang, Baoxin; Zhang, Kailiang; Zhou, Ailing; Li, Xiangxin

2016-08-01

To retrospectively assess the changes of the vertical height of the maxillary sinus floor after augmentation with simultaneous and delayed placement of implants. In total, 38 patients with 76 implants were involved; vertical bone height of the sinus floor was radiographically measured at different stages including preoperation, immediately postsurgery, 6 and 12 months postsurgery, and 6 and 24 months postfunctional loading. Sinus augmentation significantly increased vertical bone height of the sinus floor for both the simultaneous and delayed groups. The survival rate was 100% in the simultaneous group and 95.46% in the delayed group. For simultaneous placement, the vertical bone height of the sinus floor at 6 and 12 months postsurgery was significantly less than that immediately postsurgery. For both groups, augmented bone height of the sinus floor showed significant decrease from 6 months to 24 months postfunctional loading. The mean value of final bone augmentation was 5.85 mm for simultaneous placement and 5.80 mm for delayed placements. Sinus augmentation with simultaneous and delayed placement of implants led to similar survival rates and bone augmentation. Resorption of augmentative bone was evident at 24 months postfunctional loading in both cases. © 2015 by the American College of Prosthodontists.

Effects of immediate and delayed loading on peri-implant trabecular structures: a cone beam CT evaluation.

PubMed

Huang, Yan; Van Dessel, Jeroen; Liang, Xin; Depypere, Maarten; Zhong, Weijian; Ma, Guowu; Lambrichts, Ivo; Maes, Frederik; Jacobs, Reinhilde

2014-12-01

To develop a method for characterizing trabecular bone microarchitecture using cone beam computed tomography (CBCT) and to evaluate trabecular bone changes after rehabilitation using immediate versus delayed implant protocols. Six mongrel dogs randomly received 27 titanium implants in the maxillary incisor or mandibular premolar areas, following one of four protocols: (1) normal extraction socket healing; (2) immediate implant placement and immediate loading; (3) delayed implant placement and delayed loading; (4) delayed implant placement and immediate loading. The animals were euthanized at 8 weeks, and block biopsies were scanned using high resolution CBCT. Standard bone structural variables were assessed in coronal, middle, and apical levels. Coronal and middle regions had more compact, more platelike, and thicker trabeculae. Protocols (2), (3), and (4) had significantly higher values (p < 0.001) than protocol (1) for bone surface density, bone surface volume ratio, and connectivity density, while significantly lower values (p < 0.001) were found for trabecular separation and fractal dimension. However, protocols (2), (3), and (4) did not show significantly different bone remodeling. Compared with normal extraction healing, the implant protocols have an improved bone structural integration. Results do not suggest a different bone remodeling pattern when a delayed versus an immediate implant protocol is used. © 2013 Wiley Periodicals, Inc.

Histological comparison of long-bone cortex between 11-year-old giant cow with dermal dysplasia and the child cow aged 8.5 years.

PubMed

Mori, Ryoichi; Kodaka, Tetsuo; Naito, Yoshihisa

2012-02-01

Young calves are known to be formed with laminar bone in long-bone cortex during growing periods and the osteon formation begins later. Previously, we reported that an 11-year-old giant Holstein cow with dermal dysplasia showed a delayed osteon formation. An 8.5-year-old cow, born from the giant Holstein cow, also showed some dermal dysplasia and the outer-half layer of the child almost retained laminar bone similar to that of the mother, although the body weight was approximately normal. The mother had formed the inner circumferential lamella and the child was going to form the inner circumferential lamella, but their outer circumferential lamellas were not formed yet in both of them, when compared with a 12-years-old cow as a control of the mother. Therefore, we suggest on long-bone formation pattern that the child resembled the mother rather than the control, and that the child had more or less succeeded to the mother genes of delayed osteon formation as well as dermal dysplasia which seemed to be genetic collagen disorder, although there were mild gene appearances.

Effect of age and disease on bone mass in Japanese patients with schizophrenia.

PubMed

Sugawara, Norio; Yasui-Furukori, Norio; Umeda, Takashi; Tsuchimine, Shoko; Fujii, Akira; Sato, Yasushi; Saito, Manabu; Furukori, Hanako; Danjo, Kazuma; Matsuzaka, Masashi; Takahashi, Ippei; Kaneko, Sunao

2012-02-20

There have been a limited number of studies comparing bone mass between patients with schizophrenia and the general population. The aim of this study was to compare the bone mass of schizophrenia patients with that of healthy subjects in Japan. We recruited patients (n = 362), aged 48.8 ± 15.4 (mean ± SD) years who were diagnosed with schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Bone mass was measured using quantitative ultrasound densitometry of the calcaneus. The osteosono-assessment index (OSI) was calculated as a function of the speed of sound and the transmission index. For comparative analysis, OSI data from 832 adults who participated in the Iwaki Health Promotion Project 2009 was used as representative of the general community. Mean OSI values among male schizophrenic patients were lower than those in the general population in the case of individuals aged 40 and older. In females, mean OSI values among schizophrenic patients were lower than those in the general community in those aged 60 and older. In an analysis using the general linear model, a significant interaction was observed between subject groups and age in males. Older schizophrenic patients exhibit lower bone mass than that observed in the general population. Our data also demonstrate gender and group differences among schizophrenic patients and controls with regard to changes in bone mass associated with aging. These results indicate that intervention programs designed to delay or prevent decreased bone mass in schizophrenic patients might be tailored according to gender.

Dietary aspartyl-phenylalanine-1-methyl ester delays osteoarthritis and prevents associated bone loss in STR/ORT mice

PubMed Central

Manion, Carl V.; Hochgeschwender, Ute; Edmundson, Allen B.; Hugli, Tony E.

2011-01-01

Objective. STR/ORT mice provide a well-known model for murine idiopathic OA, with histological joint lesions resembling those of human OA. This model was used to investigate protective effects of the dipeptide aspartyl-phenylalanine-1-methyl ester (Asp-Phe-OMe or aspartame) via the oral route vs a regular diet. Methods. STR/ORT mice were housed individually and fed diets with or without Asp-Phe-OMe (4 mg/kg), after weaning at the age of 3 weeks, until 15 months of age (average of 20 animals per group). The study groups were kept blinded to the investigators, who measured food consumption and body weight and performed gait mobility tests. Radiographic scans were also performed at regular time intervals to evaluate differential radiographic anomalies associated with progress of OA in response to oral Asp-Phe-OMe therapy. Results. The Asp-Phe-OMe-fed animals presented a pattern of significantly delayed disease onset. In addition, their muscle and bone mass were highly preserved, even at later time points after OA was established. Moreover, control animals presented a higher variability in gait motility in comparison with the Asp-Phe-OMe-fed animals, suggesting a protective effect from movement limitations associated with advanced OA. Conclusion. Asp-Phe-OMe, given orally, delays OA in the spontaneous STR/ORT model, improves bone cortical density and muscle mass, and may contribute to a better quality of life for these diseased animals. PMID:21372000

Bone mineralization in childhood and adolescence.

PubMed

Bachrach, L K

1993-08-01

Prevention of osteoporosis depends on establishing adequate peak bone mass in the first two decades of life. Achievement of this goal requires an understanding of factors that promote skeletal health. Genetic factors are important determinants of adult bone mass, but nonheritable variables, including body mass, calcium nutriture, sex steroids, and activity can strongly influence whether maximal bone mineral is achieved. Acquisition of bone mineral continues throughout childhood and adolescence, reaching a lifetime maximum in early adulthood. Adolescence is a particularly critical time for bone mineral accretion as more than half of the bone calcium is normally laid down during the teen years. Chronic illness, malnutrition, or endocrine deficiencies at this age may result in profound deficits in bone mass, which may not be fully reversible. These risk factors contribute to the osteopenia associated with anorexia nervosa, exercise-induced amenorrhea, delayed puberty, Turner's syndrome, and growth hormone deficiency.

Delays in maturation among adolescents with hemophilia and a history of inhibitors

PubMed Central

Lynn, Henry S.; Lail, Alice E.; Hoots, W. Keith; Berntorp, Erik; Gomperts, Edward D.

2007-01-01

Inhibitory antibodies to factors VIII or IX have the potential to affect a broad range of outcomes among people with hemophilia; however, their possible effect on growth and maturation has not been explored. We evaluated skeletal maturation (bone age), pubertal progression, serum testosterone levels, height velocity, and stature in the multicenter Hemophilia Growth and Development Study. A total of 333 children and adolescents (mean age, 12.4 years) were enrolled from 1989 to 1990 and followed for 7 years. Of these, 18% (n = 60) had a history of inhibitors. Bone age among HIV− adolescents with a history of inhibitors lagged 9 or more months behind those without inhibitors at every age from 12 to 15 years. Those with a history of inhibitors were older at every Tanner stage transition, attained a lower maximum growth velocity, and their serum testosterone levels were significantly lower compared with those without inhibitors. Delays were greater among HIV+ patients with a history of inhibitors compared with those without inhibitors; however, the differences were generally small and not statistically significant. The results of this investigation underscore the importance of monitoring the growth and maturation of children and adolescents with hemophilia, particularly those with inhibitors. PMID:17715388

Response to growth hormone treatment in Prader-Willi syndrome: auxological criteria versus genetic diagnosis.

PubMed

Scheermeyer, Elly; Hughes, Ian; Harris, Mark; Ambler, Geoff; Crock, Patricia; Verge, Charles F; Craig, Maria E; Bergman, Phil; Werther, George; van Driel, Mieke; Davies, Peter Sw; Choong, Catherine S Y

2013-12-01

The Australian Prader-Willi Syndrome (PWS) database was established to monitor the efficacy and safety of growth hormone (GH) treatment in PWS. This study aims to compare response to GH based on eligibility criteria. Comparative study: 72 children received GH on the basis of short stature or evidence of GH deficiency (pre-2009: PWS-SS) and 94 on a genetic diagnosis (post-2009: PWS-Dx). We report on mandatory patient data for GH prescription: median and standard deviation score (SDS) for height and body mass index (BMI), waist/height ratio, bone age/chronological age ratio and adverse events. Comparisons were made using non-parametric tests. At baseline, the PWS-SS cohort was shorter (height SDS: -2.6 vs. -1.1, P < 0.001), had a lower BMI (0.6 vs. 1.5 SDS, P < 0.05) and greater bone age delay (bone age/chronological age: 0.7 vs. 0.9, P < 0.05) than the PWS-Dx cohort. PWS-SS parents were shorter (mid-parental height SDS: -0.13 vs. 0.28, P < 0.005). Mean change in height over 2 years was 0.9 SDS and in BMI using PWS reference standards -0.3 SDSPWS (n = 106) (year 2, height SDS: PWS-SS = -1.7, PWS-Dx = 0.1; BMI SDSPWS : PWS-SS = -1.0, PWS-Dx = -0.6). The waist/height ratio reduced (PWS-Dx: 0.60 vs. 0.56, P < 0.05) and bone age delay was unchanged over this period. No serious adverse events were reported. The PWS-SS cohort represents a subgroup of the wider PWS-Dx population; however both cohorts improved height SDS with normalisation of height in the PWS-Dx cohort and lowering of BMI relative to PWS standards supporting the efficacy of treatment under the current Australian GH programme. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

BMP-2/PLGA delayed-release microspheres composite graft, selection of bone particulate diameters, and prevention of aseptic inflammation for bone tissue engineering.

PubMed

Ji, Ye; Xu, Gong Ping; Zhang, Zhi Peng; Xia, Jing Jun; Yan, Jing Long; Pan, Shang Ha

2010-03-01

Autogenous bone grafts are widely used in the repair of bone defects. Growth factors such as bone morphogenetic protein 2 (BMP-2) can induce bone regeneration and enhance bone growth. The combination of an autogenous bone graft and BMP-2 may provide a better osteogenic effect than either treatment alone, but BMP-2 is easily inactivated in body fluid. The objective of this study was to develop a technique that can better preserve the in vivo activity of BMP-2 incorporated in bone grafts. In this study, we first prepared BMP-2/poly(lactic-co-glycolic acid) (PLGA) delayed-release microspheres, and then combined collagen, the delayed-release microspheres, and rat autologous bone particulates to form four groups of composite grafts with different combinations: collagen in group A; collagen combined with bone particulates in group B; collagen combined with BMP-2/PLGA delayed-release microspheres in group C; and collagen combined with both bone particulates and BMP-2/PLGA delayed-release microspheres in group D. The four groups of composite grafts were implanted into the gluteus maximus pockets in rats. The ectopic osteogenesis and ALP level in group D (experimental group) were compared with those in groups A, B, and C (control groups) to study whether it had higher osteogenic capability. Results showed that the composite graft design increased the utility of BMP-2 and reduced the required dose of BMP-2 and volume of autologous bone. The selection of bone particulate diameter had an impact on the osteogenetic potential of bone grafts. Collagen prevented the occurrence of aseptic inflammation and improved the osteoinductivity of BMP-2. These results showed that this composite graft design is effective and feasible for use in bone repair.

Endocrine Disorders in Cystic Fibrosis.

PubMed

Blackman, Scott M; Tangpricha, Vin

2016-08-01

Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. Copyright © 2016 Elsevier Inc. All rights reserved.

Ethnic and sex differences in skeletal maturation among the Birth to Twenty cohort in South Africa

PubMed Central

Cole, Tim J; Rousham, Emily K; Hawley, Nicola L; Cameron, Noel; Norris, Shane A; Pettifor, John M

2015-01-01

Aim To examine ethnic and sex differences in the pattern of skeletal maturity from adolescence to adulthood using a novel longitudinal analysis technique (SuperImposition by Translation And Rotation (SITAR)). Setting Johannesburg, South Africa. Participants 607 boys and girls of black as well as white ethnicity from the Birth to Twenty bone health study, assessed annually from 9 to 20 years of age. Outcome measure Bone maturity scores (Tanner–Whitehouse III radius, ulna, and short bones (TW3 RUS)) assessed longitudinally from hand-wrist radiographs were used to produce individual and mean growth curves of bone maturity and analysed by the SITAR method. Results The longitudinal analysis showed that black boys matured later by 7.0 SE 1.6 months (p<0.0001) but at the same rate as white boys, whereas black girls matured at the same age but at a faster rate than white girls (by 8.7% SE 2.6%, p=0.0007). The mean curves for bone maturity score consistently showed a midpubertal double kink, contrasting with the quadratic shape of the commonly used reference centile curves for bone maturity (TW3). Conclusions Skeletal maturity was reached 1.9 years earlier in girls than boys, and the pattern of maturation differed between the sexes. Within girls, there were no ethnic differences in the pattern or timing of skeletal maturity. Within boys, however, skeletal maturity was delayed by 7 months in black compared with white ethnicity. Skeletal maturation, therefore, varies differentially by sex and ethnicity. The delayed maturity of black boys, but not black girls, supports the hypothesis that boys have greater sensitivity to environmental constraints than girls. PMID:25409981

In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels.

PubMed

Maïmoun, L; Coste, O; Mariano-Goulart, D; Galtier, F; Mura, T; Philibert, P; Briot, K; Paris, F; Sultan, C

2011-12-01

Peripubertal artistic gymnasts display elevated areal bone mineral density at various bone sites, despite delayed menarche and a high frequency of menstrual disorders, factors that may compromise bone health. The concomitant improvement in femoral bone geometry and strength suggested that this type of physical activity might have favourable clinical impact. The purpose of this study is to evaluate the effect of artistic gymnastics (GYM) on areal bone mineral density (aBMD), femoral bone geometry and bone markers and its relationship with the osteoprotegerin (OPG)/rank-ligand (RANKL) system in peripubertal girls. Forty-six girls (age 10-17.2 years) were recruited for this study: 23 elite athletes in the GYM group (training 12-30 h/week, age at start of training 5.3 years) and 23 age-matched (± 6 months; leisure physical activity ≤ 3 h/week) controls (CON). The aBMD at whole body, total proximal femur, lumbar spine, mid-radius and skull was determined using dual-X-ray absorptiometry. Hip structural analysis (HSA software) was applied at the femur to evaluate cross-sectional area (CSA, cm(2)), cross-sectional moment of inertia (CSMI, cm(4)), and the section modulus (Z, cm(3)) and buckling ratio at neck, intertrochanteric region and shaft. Markers of bone turnover and OPG/RANKL levels were also analysed. GYM had higher (5.5-16.4%) non-adjusted aBMD and adjusted aBMD for age, fat-free soft tissue and fat mass at all bone sites, skull excepted and the difference increased with age. In the three femoral regions adjusted for body weight and height, CSA (12.5-18%), CSMI (14-18%), Z (15.5-18.6%) and mean cortical thickness (13.6-21%) were higher in GYM than CON, while the buckling ratio (21-27.1%) was lower. Bone markers decreased with age in both groups and GYM presented higher values than CON only in the postmenarchal period. A similar increase in RANKL with age without OPG variation was observed for both groups. GYM is associated not only with an increase in aBMD but also an improvement in bone geometry associated with an increase in bone remodelling. These adaptations seem to be independent of the OPG/RANKL system.

A comparison of skeletal maturity assessed by radiological and ultrasonic methods.

PubMed

Utczas, Katinka; Muzsnai, Agota; Cameron, Noel; Zsakai, Annamaria; Bodzsar, Eva B

2017-07-08

The estimation of skeletal maturity is a useful tool in pediatric practice to determine the degree of delay or advancement in growth disorders and the effectiveness of treatment in conditions that influence linear growth. Skeletal maturity of children is commonly assessed using either Greulich-Pyle (GP) or Tanner-Whitehouse methods (TW2 and TW3). However, a less invasive ultrasonic method, that does not use ionizing radiation, has been suggested for use in epidemiological studies of skeletal maturity. The main purpose of the present study was to determine the accuracy of an ultrasonic method based on the GP maturity indicators compared to the standard GP radiographic method. Skeletal maturity of 1502 healthy children, aged from 6 to 18 years, was estimated by quantitative ultrasound and compared to GP bone ages estimated from left hand and wrist radiographs of a subsample of 47 randomly selected participants. The ultrasonic bone age estimation demonstrated very strong correlations with all the radiological age estimations. The correlation coefficients ranged between 0.895 and 0.958, and the strongest correlation of ultrasonic skeletal maturity estimation was found with the Tanner-Whitehouse RUS method. The ultrasonic bone age estimation is suggested for use between the chronological ages of 8.5-16.0 years in boys and 7.5-15.0 years in girls. The ultrasonic bone age estimation is suggested for use in epidemiological surveys since the sensitivity for screening for not normal bone development is appropriate, at least within the 8-15 years age interval. © 2017 Wiley Periodicals, Inc.

Open reduction of nasal bone fractures through an intercartilaginous incision.

PubMed

Kim, Ji Heui; Lee, Jun Ho; Hong, Seok Min; Park, Chan Hum

2013-01-01

Open reduction through an intercartilaginous incision was useful for treating delayed-diagnosed nasal bone fractures because it resulted in a successful outcome with minimal complications. Nasal bone fractures are generally managed with closed reduction, which is usually inadequate and results in airway obstruction with a delayed diagnosis of nasal bone fracture when bone healing and fibrotic adhesions around the bone fragment have progressed. This study investigated the surgical outcome of open reduction through an intercartilaginous incision for delayed-diagnosis nasal bone fractures. The study enrolled 18 patients who underwent open reduction through an intercartilaginous incision to correct delayed-diagnosis nasal bone fractures. Three independent otorhinolaryngologists evaluated the outcomes 4-35 months (average 12.7 months) postoperatively as excellent, fair or poor. The time from injury to surgery was 11-39 days (20-39 days in adults and 11-30 days in children). The 18 cases included 16 primary repairs and two revisions. A Kirschner wire was inserted in six (33.3%) patients who had unstable reduced nasal bones. Postoperatively, l5 (83%) patients had excellent results, two (11%) had fair, and one (6%) had a poor outcome. No patient experienced any complication.

N-cadherin Regulation of Bone Growth and Homeostasis is Osteolineage Stage-Specific

PubMed Central

Fontana, Francesca; Hickman-Brecks, Cynthia L.; Salazar, Valerie S.; Revollo, Leila; Abou-Ezzi, Grazia; Grimston, Susan K.; Jeong, Sung Yeop; Watkins, Marcus; Fortunato, Manuela; Alippe, Yael; Link, Daniel C.; Mbalaviele, Gabriel; Civitelli, Roberto

2017-01-01

N-cadherin inhibits osteogenic cell differentiation and canonical Wnt/β-catenin signaling in vitro. However, in vivo both conditional Cdh2 ablation and overexpression in osteoblasts lead to low bone mass. We tested the hypothesis that N-cadherin has different effects on osteolineage cells depending upon their differentiation stage. Embryonic conditional osteolineage Cdh2 deletion in mice results in defective growth, low bone mass and reduced osteoprogenitor number. These abnormalities are prevented by delaying Cdh2 ablation until 1 month of age, thus targeting only committed and mature osteoblasts, suggesting they are the consequence of N-cadherin deficiency in osteoprogenitors. Indeed, diaphyseal trabecularization actually increases when Cdh2 is ablated postnatally. The sclerostin-insensitive Lrp5A214V mutant, associated with high bone mass, does not rescue the growth defect, but it overrides the low bone mass of embryonically Cdh2 deleted mice, suggesting N-cadherin interacts with Wnt signaling to control bone mass. Finally, bone accrual and β-catenin accumulation after administration of an anti-Dkk1 antibody are enhanced in N-cadherin deficient mice. Thus, while lack of N-cadherin in embryonic and perinatal age is detrimental to bone growth and bone accrual, in adult mice loss of N-cadherin in osteolineage cells favors bone formation. Hence, N-cadherin inhibition may widen the therapeutic window of osteoanabolic agents. PMID:28240364

Neglected nonunion of phalangeal neck fractures of the thumb in children: the outcome of delayed bone grafting in adulthood.

PubMed

Al-Qattan, Mohammad M

2012-03-01

Over a 12-year period, the author treated a total of 5 adults (mean age, 23 years) with neglected nonunion of phalangeal neck fractures of the thumb that were sustained in early childhood. Cosmetically, the affected thumb was shorter and smaller than the contralateral thumb. The thumb tip was flail and thumb pinch was weak. X-rays showed a nonunited phalangeal neck fracture with no radiologic evidence of avascular necrosis of the phalangeal head. All patients underwent iliac crest bone grafting. Bone union was obtained in all patients. At final follow-up (mean, 9 months), all patients were satisfied with the cosmetic appearance of the thumb. The thumb length increased by an average of 6 mm (range, 5-8 mm). Pinch improved in the range of 69% to 87% of the power of the contralateral thumb. However, there was restricted range of motion of the interphalangeal joint (mean range of motion of 10 degree only). It was concluded that delayed bone grafting of neglected nonunions of pediatric phalangeal neck fractures of the thumb is a worthwhile procedure and has a high satisfaction rate.

The Effect of Prepubertal Calcium Carbonate Supplementation on Skeletal Development in Gambian Boys—A 12-Year Follow-Up Study

PubMed Central

Cole, T. J.; Laskey, M. A.; Ceesay, M.; Mendy, M. B.; Sawo, Y.; Prentice, A.

2014-01-01

Context: Calcium intake during growth is essential for future bone health but varies widely between individuals and populations. The impact on bone of increasing calcium intake is unknown in a population where low calcium intake, stunting, and delayed puberty are common. Objective: To determine the effect of prepubertal calcium supplementation on mean age at peak velocity for bone growth and mineral accrual. Design and Setting: Prospective follow-up of boys in rural Gambia, West Africa, who had participated in a double-blind, randomized, placebo-controlled trial of calcium supplementation. Participants: Eighty boys, initially aged 8.0–11.9 years, were followed up for 12 years. Interventions: Subjects received 1 year of calcium carbonate supplementation (1000 mg daily, 5 d/wk). Main Outcome Measures: Dual-energy x-ray absorptiometry measurements were carried out for whole body (WB), lumbar spine, and total hip bone mineral content, bone area (BA), and WB lean mass. Super imposition by translation and rotation models was made to assess bone growth. Results: Age at peak velocity was consistently earlier in the calcium group compared to the placebo group, for WB bone mineral content (mean, −6.2 [SE, 3.1]; P = .05), WB BA (mean, −7.0 [SE, 3.2] mo; P = .03), lumbar spine and total hip BA. By young adulthood, supplementation did not change the amount of bone accrued (mineral or size) or the rate of bone growth. Conclusions: Twelve months of prepubertal calcium carbonate supplementation in boys with a low calcium diet advanced the adolescent growth spurt but had no lasting effect on bone mineral or bone size. There is a need for caution when applying international recommendations to different populations. PMID:24762110

5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial.

PubMed

Wagner-Johnston, Nina D; Sloan, Jeff A; Liu, Heshan; Kearns, Ann E; Hines, Stephanie L; Puttabasavaiah, Suneetha; Dakhil, Shaker R; Lafky, Jacqueline M; Perez, Edith A; Loprinzi, Charles L

2015-08-01

Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results. A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of <-2.0 or fracture. The incidence of a 5% decrease in the total lumbar spine bone mineral density at 5 years was 10.2% in the upfront treatment arm versus 41.2% in the delayed treatment arm (P<.0001). A total of 41 patients in the delayed treatment arm were eventually started on ZA. With the exception of increased NCI Common Toxicity Criteria (CTC) grade 1/2 elevated creatinine and fever in the patients treated on the upfront arm and cerebrovascular ischemia among those in the delayed treatment arm, there were no significant differences observed between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront treatment arm (2 vs 8 cumulative cases), although this difference was not found to be statistically significant. Bone fractures occurred in 24 patients in the upfront treatment arm versus 25 patients in the delayed treatment arm. Immediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms. © 2015 American Cancer Society.

Kinetic examination of femoral bone modeling in broilers.

PubMed

Prisby, R; Menezes, T; Campbell, J; Benson, T; Samraj, E; Pevzner, I; Wideman, R F

2014-05-01

Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute to subsequent pathology of the femoral head in fast-growing broilers.

Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing.

PubMed

Correa, Fernanda A; França, Marcela M; Fang, Qing; Ma, Qianyi; Bachega, Tania A; Rodrigues, Andresa; Ozel, Bilge A; Li, Jun Z; Mendonca, Berenice B; Jorge, Alexander A L; Carvalho, Luciani R; Camper, Sally A; Arnhold, Ivo J P

2017-12-01

Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS -3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene.

Absence of bone sialoprotein (BSP) impairs cortical defect repair in mouse long bone.

PubMed

Malaval, Luc; Monfoulet, Laurent; Fabre, Thierry; Pothuaud, Laurent; Bareille, Reine; Miraux, Sylvain; Thiaudiere, Eric; Raffard, Gerard; Franconi, Jean-Michel; Lafage-Proust, Marie-Hélène; Aubin, Jane E; Vico, Laurence; Amédée, Joëlle

2009-11-01

Matrix proteins of the SIBLING family interact with bone cells and with bone mineral and are thus in a key position to regulate bone development, remodeling and repair. Within this family, bone sialoprotein (BSP) is highly expressed by osteoblasts, hypertrophic chondrocytes and osteoclasts. We recently reported that mice lacking BSP (BSP-/-) have very low trabecular bone turnover. In the present study, we set up an experimental model of bone repair by drilling a 1 mm diameter hole in the cortical bone of femurs in both BSP-/- and +/+ mice. A non-invasive MRI imaging and bone quantification procedure was designed to follow bone regeneration, and these data were extended by microCT imaging and histomorphometry on undecalcified sections for analysis at cellular level. These combined approaches revealed that the repair process as reflected in defect-refilling in the cortical area was significantly delayed in BSP-/- mice compared to +/+ mice. Concomitantly, histomorphometry showed that formation, mineralization and remodeling of repair (primary) bone in the medulla were delayed in BSP-/- mice, with lower osteoid and osteoclast surfaces at day 15. In conclusion, the absence of BSP delays bone repair at least in part by impairing both new bone formation and osteoclast activity.

Extracorporeal shock wave therapy in treatment of delayed bone-tendon healing.

PubMed

Wang, Lin; Qin, Ling; Lu, Hong-bin; Cheung, Wing-hoi; Yang, Hu; Wong, Wan-nar; Chan, Kai-ming; Leung, Kwok-sui

2008-02-01

Extracorporeal shock wave therapy is indicated for treatment of chronic injuries of soft tissues and delayed fracture healing and nonunion. No investigation has been conducted to study the effect of shock wave on delayed healing at the bone-tendon junction. Shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling of healing tissue in delayed healing of bone-tendon junction surgical repair. Controlled laboratory study. Twenty-eight mature rabbits were used for establishing a delayed healing model at the patella-patellar tendon complex after partial patellectomy and then divided into control and shock wave groups. In the shock wave group, a single shock wave treatment was given at week 6 postoperatively to the patella-patellar tendon healing complex. Seven samples were harvested at week 8 and 7 samples at week 12 for radiologic, densitometric, histologic, and mechanical evaluations. Radiographic measurements showed 293.4% and 185.8% more new bone formation at the patella-patellar tendon healing junction in the shock wave group at weeks 8 and 12, respectively. Significantly better bone mineral status was found in the week 12 shock wave group. Histologically, the shock wave group showed more advanced remodeling in terms of better alignment of collagen fibers and thicker and more mature regenerated fibrocartilage zone at both weeks 8 and 12. Mechanical testing showed 167.7% and 145.1% higher tensile load and strength in the shock wave group at week 8 and week 12, respectively, compared with controls. Extracorporeal shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling in the delayed bone-to-tendon healing junction in rabbits. These results provide a foundation for future clinical studies toward establishment of clinical indication for treatment of delayed bone-to-tendon junction healing.

Mosaic Trisomy 9p in a Patient with Mild Dysmorphic Features and Normal Intelligence.

PubMed

Brar, Randeep; Basel, Donald G; Bick, David P; Weik, LuAnn; vanTuinen, Peter; Peterson, Jess F

2017-01-01

To the Editor: Partial and whole duplications of the short arm of chromosome 9 have been commonly reported in the literature with characteristic phenotypic features and intellectual disabilities. The clinical features of 9p duplications are broad and can include growth retardation, developmental delay, intellectual disability, microbrachycephaly, deep set eyes, hypertelorism, downslanting palpebral fissures, prominent nasal root, bulbous nasal tip, low-set ears, short fingers and toes with hypoplastic nails, and delayed bone age (Bonaglia et al., 2002; Zou et al., 2009; Guilherme et al., 2014).

The effects of nutrition, puberty and dancing on bone density in adolescent ballet dancers.

PubMed

Burckhardt, Peter; Wynn, Emma; Krieg, Marc-Antoine; Bagutti, Carlo; Faouzi, Mohamed

2011-06-01

Ballet dancers have on average a low bone mineral content (BMC), with elevated fracture-risk, low body mass index (BMI) for age (body mass index, kg/m2), low energy intake, and delayed puberty. This study aims at a better understanding of the interactions of these factors, especially with regard to nutrition. During a competition for pre-professional dancers we examined 127 female participants (60 Asians, 67 Caucasians). They averaged 16.7 years of age, started dancing at 5.8 years, and danced 22 hours/week. Assessments were made for BMI, BMC (DXA), and bone mineral apparent density (BMAD) at the lumbar spine and femoral neck, pubertal stage (Tanner score), and nutritional status (EAT-40 questionnaire and a qualitative three-day dietary record). BMI for age was found to be normal in only 42.5% of the dancers, while 15.7% had a more or less severe degree of thinness (12.6% Grade2 and 3.1% Grade 3 thinness). Menarche was late (13.9 years, range 11 to 16.8 years). Food intake, evaluated by number of consumed food portions, was below the recommendations for a normally active population in all food groups except animal proteins, where the intake was more than twice the recommended amount. In this population, with low BMI and intense exercise, BMC was low and associated with nutritional factors; dairy products had a positive and non-dairy proteins a negative influence. A positive correlation between BMAD and years since menarche confirmed the importance of exposure to estrogens and the negative impact of delayed puberty. Because of this and the probable negative influence of a high intake of non-dairy proteins, such as meat, fish, and eggs, and the positive association with a high dairy intake, ballet schools should promote balanced diets and normal weight and should recognize and help dancers avoid eating disorders and delayed puberty caused by extensive dancing and inadequate nutrition.

Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma.

PubMed

Liu, Hen-Yu; Huang, Chiung-Fang; Lin, Tzu-Chieh; Tsai, Ching-Yu; Tina Chen, Szu-Yu; Liu, Alice; Chen, Wei-Hong; Wei, Hong-Jian; Wang, Ming-Fu; Williams, David F; Deng, Win-Ping

2014-12-01

Aging is related to loss of functional stem cell accompanying loss of tissue and organ regeneration potentials. Previously, we demonstrated that the life span of ovariectomy-senescence accelerated mice (OVX-SAMP8) was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice after platelet rich plasma (PRP)/embryonic fibroblast transplantation. The aim of this study is to investigate the potential of PRP for recovering cellular potential from senescence and then delaying animal aging. We first examined whether stem cells would be senescent in aged mice compared to young mice. Primary adipose derived stem cells (ADSCs) and bone marrow derived stem cells (BMSCs) were harvested from young and aged mice, and found that cell senescence was strongly correlated to animal aging. Subsequently, we demonstrated that PRP could recover cell potential from senescence, such as promote cell growth (cell proliferation and colony formation), increase osteogenesis, decrease adipogenesis, restore cell senescence related markers and resist the oxidative stress in stem cells from aged mice. The results also showed that PRP treatment in aged mice could delay mice aging as indicated by survival, body weight and aging phenotypes (behavior and gross morphology) in term of recovering the cellular potential of their stem cells compared to the results on aged control mice. In conclusion these findings showed that PRP has potential to delay aging through the recovery of stem cell senescence and could be used as an alternative medicine for tissue regeneration and future rejuvenation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prophylactic pamidronate partially protects from glucocorticoid-induced bone loss in the mdx mouse model of Duchenne muscular dystrophy.

PubMed

Yoon, Sung-Hee; Chen, Jinghan; Grynpas, Marc D; Mitchell, Jane

2016-09-01

Glucocorticoids are extensively used to treat patients with Duchenne muscular dystrophy because of their ability to delay muscle damage, prolong ambulation and extend life. However, use of glucocorticoids significantly increases bone loss, fragility and fractures. To determine if antiresorptive bisphosphonates could prevent the effects of glucocorticoids on bone quality, we used dystrophic mdx mice treated with the glucocorticoid prednisone during 8weeks of rapid bone growth from 5 to 13weeks of age and treated some mice with the bisphosphonate pamidronate during the first two weeks of prednisone administration. Prednisone reduced long bone growth, decreased cortical bone thickness and area and decreased the strength of the femurs. Pamidronate treatment protected mice from cortical bone loss but did not increase bone strength. The combination of prednisone and pamidronate inhibited remodeling of metaphyseal trabecular bone with large numbers of trabeculae containing remnants of calcified cartilage. Prednisone improved muscle strength in the mdx mice and decreased serum creatine kinase with evidence of improved muscle histology and these effects were maintained in mice treated with pamidronate. Copyright © 2016. Published by Elsevier Inc.

Reduced COX-2 expression in aged mice is associated with impaired fracture healing.

PubMed

Naik, Amish A; Xie, Chao; Zuscik, Michael J; Kingsley, Paul; Schwarz, Edward M; Awad, Hani; Guldberg, Robert; Drissi, Hicham; Puzas, J Edward; Boyce, Brendan; Zhang, Xinping; O'Keefe, Regis J

2009-02-01

The cellular and molecular events responsible for reduced fracture healing with aging are unknown. Cyclooxygenase 2 (COX-2), the inducible regulator of prostaglandin E(2) (PGE(2)) synthesis, is critical for normal bone repair. A femoral fracture repair model was used in mice at either 7-9 or 52-56 wk of age, and healing was evaluated by imaging, histology, and gene expression studies. Aging was associated with a decreased rate of chondrogenesis, decreased bone formation, reduced callus vascularization, delayed remodeling, and altered expression of genes involved in repair and remodeling. COX-2 expression in young mice peaked at 5 days, coinciding with the transition of mesenchymal progenitors to cartilage and the onset of expression of early cartilage markers. In situ hybridization and immunohistochemistry showed that COX-2 is expressed primarily in early cartilage precursors that co-express col-2. COX-2 expression was reduced by 75% and 65% in fractures from aged mice compared with young mice on days 5 and 7, respectively. Local administration of an EP4 agonist to the fracture repair site in aged mice enhanced the rate of chondrogenesis and bone formation to levels observed in young mice, suggesting that the expression of COX-2 during the early inflammatory phase of repair regulates critical subsequent events including chondrogenesis, bone formation, and remodeling. The findings suggest that COX-2/EP4 agonists may compensate for deficient molecular signals that result in the reduced fracture healing associated with aging.

Stimulant medication effects on growth and bone age in children with attention-deficit/hyperactivity disorder: a prospective cohort study.

PubMed

Poulton, Alison S; Bui, Quoc; Melzer, Elaine; Evans, Richard

2016-03-01

Stimulant medication is known to cause transient weight loss and slowing down of growth, but whether it delays physical maturation is unclear. We studied growth and bone age over the first 3 years of treatment in children with attention-deficit/hyperactivity disorder (patients) compared with healthy siblings (controls). Bone age was estimated blindly by two independent radiologists using Tanner and Whitehouse version 3. Dexamphetamine or methylphenidate was titrated and continued when clinically indicated. Forty out of 73 patients, together with 22 controls, completed the study. There were no significant growth differences between the two groups at baseline. Despite slower growth on treatment [5.1 cm/year, 95% confidence interval (CI): 4.7-5.5, vs. 6.3 cm/year, 95% CI: 5.7-6.8, P=0.002; and 2.7 kg/year, 95% CI: 2.1-3.3, vs. 4.4 kg/year, 95% CI: 3.5-5.3, P=0.005], the patients showed no significant maturational delay (RUS score: 49 U/year, 95% CI: 44-55, vs. 55 U/year, 95% CI: 47-63, P=0.27). A subgroup of patients underwent serial biochemistry and dual-energy X-ray absorptiometry, recording a significant reduction in fat (5.61±3.56-4.22±3.09 kg, P<0.001) and leptin (3.88±2.87-2.57±1.94 ng/ml, P=0.017). The pattern of change in height z-score over time was modified by the dose of medication (P for interaction=0.024). We found no medication effect on the rate of maturation, which was instead predicted by baseline leptin (P=0.035 controlling for age and sex).

Anabolic Steroids as a Novel Therapeutic Strategy for the Prevention of Bone Loss after Spinal Cord Injury: Animal Model and Molecular Mechanism

DTIC Science & Technology

2012-10-01

bone loss. At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common...TERMS- Spinal cord injuries, Nandrolone, Androgens, Hypogonadism , Bone loss, Wnt signaling 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common in men

Ethnic and sex differences in skeletal maturation among the Birth to Twenty cohort in South Africa.

PubMed

Cole, Tim J; Rousham, Emily K; Hawley, Nicola L; Cameron, Noel; Norris, Shane A; Pettifor, John M

2015-02-01

To examine ethnic and sex differences in the pattern of skeletal maturity from adolescence to adulthood using a novel longitudinal analysis technique (SuperImposition by Translation And Rotation (SITAR)). Johannesburg, South Africa. 607 boys and girls of black as well as white ethnicity from the Birth to Twenty bone health study, assessed annually from 9 to 20 years of age. Bone maturity scores (Tanner-Whitehouse III radius, ulna, and short bones (TW3 RUS)) assessed longitudinally from hand-wrist radiographs were used to produce individual and mean growth curves of bone maturity and analysed by the SITAR method. The longitudinal analysis showed that black boys matured later by 7.0 SE 1.6 months (p<0.0001) but at the same rate as white boys, whereas black girls matured at the same age but at a faster rate than white girls (by 8.7% SE 2.6%, p=0.0007). The mean curves for bone maturity score consistently showed a midpubertal double kink, contrasting with the quadratic shape of the commonly used reference centile curves for bone maturity (TW3). Skeletal maturity was reached 1.9 years earlier in girls than boys, and the pattern of maturation differed between the sexes. Within girls, there were no ethnic differences in the pattern or timing of skeletal maturity. Within boys, however, skeletal maturity was delayed by 7 months in black compared with white ethnicity. Skeletal maturation, therefore, varies differentially by sex and ethnicity. The delayed maturity of black boys, but not black girls, supports the hypothesis that boys have greater sensitivity to environmental constraints than girls. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing

PubMed Central

Wang, Xin; Friis, Thor E.; Masci, Paul P.; Crawford, Ross W.; Liao, Wenbo; Xiao, Yin

2016-01-01

The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing. PMID:27767056

Short Stature, Accelerated Bone Maturation, and Early Growth Cessation Due to Heterozygous Aggrecan Mutations

PubMed Central

Nilsson, Ola; Guo, Michael H.; Dunbar, Nancy; Popovic, Jadranka; Flynn, Daniel; Jacobsen, Christina; Lui, Julian C.; Hirschhorn, Joel N.; Baron, Jeffrey

2014-01-01

Context: Many children with idiopathic short stature have a delayed bone age. Idiopathic short stature with advanced bone age is far less common. Objective: The aim was to identify underlying genetic causes of short stature with advanced bone age. Setting and Design: We used whole-exome sequencing to study three families with autosomal-dominant short stature, advanced bone age, and premature growth cessation. Results: Affected individuals presented with short stature [adult heights −2.3 to −4.2 standard deviation scores (SDS)] with histories of early growth cessation or childhood short stature (height SDS −1.9 to −3.5 SDS), advancement of bone age, and normal endocrine evaluations. Whole-exome sequencing identified novel heterozygous variants in ACAN, which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The variants were present in all affected, but in no unaffected, family members. In Family 1, a novel frameshift mutation in exon 3 (c.272delA) was identified, which is predicted to cause early truncation of the aggrecan protein. In Family 2, a base-pair substitution was found in a highly conserved location within a splice donor site (c.2026+1G>A), which is also likely to alter the amino acid sequence of a large portion of the protein. In Family 3, a missense variant (c.7064T>C) in exon 14 affects a highly conserved residue (L2355P) and is strongly predicted to perturb protein function. Conclusions: Our study demonstrates that heterozygous mutations in ACAN can cause a mild skeletal dysplasia, which presents clinically as short stature with advanced bone age. The accelerating effect on skeletal maturation has not previously been noted in the few prior reports of human ACAN mutations. Our findings thus expand the spectrum of ACAN defects and provide a new molecular genetic etiology for the unusual child who presents with short stature and accelerated skeletal maturation. PMID:24762113

Mathematical evaluation of the influence of multiple factors on implant stability quotient values in clinical practice: a retrospective study

PubMed Central

Huang, Hairong; Wismeijer, Daniel; Shao, Xianhong; Wu, Gang

2016-01-01

Objectives The objective of this study is to mathematically evaluate the influence of multiple factors on implant stability quotient values in clinical practice. Patients and methods Resonance frequency analysis was performed at T1 (measured immediately at the time of implant placement) and at T2 (measured before dental restoration) in 177 patients (329 implants). Using a multivariate linear regression model, we analyzed the influence of the following eleven candidate factors: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting (presence or absence), insertion torque, I-/II-stage healing pattern, implant diameter, implant length, and T1–T2 time interval. Results The following factors were identified to significantly influence the implant stability quotient (ISQ) values at T1: insertion torque, bone grafting, I-/II-stage healing pattern, immediate/delayed implantation, maxillary/mandibular location, implant diameter, and sex. In contrast, the ISQ values at T2 were significantly influenced only by three factors: implant diameter, T1–T2 time interval, and insertion torque. Conclusion Among the eleven candidate factors, seven key factors were found to influence the T1-ISQ values, while only three key factors influenced the T2-ISQ values. Both T1 and T2-ISQ values were found to be influenced by implant diameter and insertion torque. T1 was influenced specifically by the sex of the patient, the location (maxillary or mandibular), the implantation mode (immediate/delayed implantation), the healing stage, and the absence or presence of bone graft materials. PMID:27785040

Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flandin, Isabelle; Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon; Hartmann, Olivier

2006-04-01

Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver,more » kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma.« less

Subdural Hematomas in Children under 2 Years. Accidental or Inflicted? A 10-Year Experience.

ERIC Educational Resources Information Center

Tzioumi, Dimitra; Oates, R. Kim

1998-01-01

Analysis of 38 children under 2 with subdural hematomas found the most common causes were nonaccidental injury (55%), accidents (39%), and nontraumatic causes (6%). Also, the frequent presence of retinal hemorrhages, bone and rib fractures, delay in presentation, and young age suggests child abuse as the most common cause of these injuries.…

Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs

PubMed Central

Chiaro, Joseph A; Baron, Matthew D; del Alcazar, Chelsea; O’Donnell, Patricia; Shore, Eileen M; Elliott, Dawn M; Ponder, Katherine P; Haskins, Mark E; Smith, Lachlan J

2013-01-01

Introduction Mucopolysaccharidosis I (MPS I) is a lysosomal storage disorder characterized by deficient α-L-iduronidase activity leading to accumulation of poorly degraded dermatan and heparan sulfate glycosaminoglycans (GAGs). MPS I is associated with significant cervical spine disease, including vertebral dysplasia, odontoid hypoplasia, and accelerated disc degeneration, leading to spinal cord compression and kypho-scoliosis. The objective of this study was to establish the nature and rate of progression of cervical vertebral bone disease in MPS I using a canine model. Methods C2 vertebrae were obtained post-mortem from normal and MPS I dogs at 3, 6 and 12 months-of-age. Morphometric parameters and mineral density for the vertebral trabecular bone and odontoid process were determined using micro-computed tomography. Vertebrae were then processed for paraffin histology, and cartilage area in both the vertebral epiphyses and odontoid process were quantified. Results Vertebral bodies of MPS I dogs had lower trabecular bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD) than normals at all ages. For MPS I dogs, BV/TV, Tb.Th and BMD plateaued after 6 months-of-age. The odontoid process appeared morphologically abnormal for MPS I dogs at 6 and 12 months-of-age, although BV/TV and TMD were not significantly different from normals. MPS I dogs had significantly more cartilage in the vertebral epiphyses at both 3 and 6 months-of-age. At 12 months-of-age, epiphyseal growth plates in normal dogs were absent, but in MPS I dogs they persisted. Conclusions In this study we report reduced trabecular bone content and mineralization, and delayed cartilage to bone conversion in MPS I dogs from 3 months-of-age, which may increase vertebral fracture risk and contribute to progressive deformity. The abnormalities of the odontoid process we describe likely contribute to increased incidence of atlanto-axial subluxation observed clinically. Therapeutic strategies that enhance bone formation may decrease incidence of spine disease in MPS I patients. PMID:23563357

Single-blind randomized clinical trial to evaluate clinical and radiological outcomes after one year of immediate versus delayed implant placement supporting full-arch prostheses

PubMed Central

Pellicer-Chover, Hilario; Peñarrocha-Oltra, David; Bagán, Leticia; Fichy-Fernandez, Antonio J.; Canullo, Luigi

2014-01-01

Purpose: To evaluate and compare peri-implant health, marginal bone loss and success of immediate and delayed implant placement for rehabilitation with full-arch fixed prostheses. Material and Methods: The present study was a prospective, randomized, single-blind, clinical preliminary trial. Patients were randomized into two treatment groups. In Group A implants were placed immediately post-extraction and in Group B six months after extraction. The following control time-points were established: one week, six months and twelve months after loading. Measurements were taken of peri-implant crevicular fluid volume, plaque index, gingival retraction, keratinized mucosa, probing depth, modified gingival index and presence of mucositis. Implant success rates were evaluated for the two groups. The study sample included fifteen patients (nine women and six men) with a mean average age of 63.7 years. One hundred and forty-four implants were placed: 76 placed in healed sites and 68 placed immediately. Results: At the moment of prosthetic loading, keratinized mucosa width and probing depth were higher in immediate implants than delayed implants, with statistically significant differences. However, after six and twelve months, differences between groups had disappeared. Bone loss was 0.54 ± 0.39 mm for immediate implants and 0.66 ± 0.25 mm for delayed implants (p=0.201). No implants failed in either group. Conclusions: The present study with a short follow-up and a small sample yielded no statistically significant differences in implant success and peri-implant marginal bone loss between immediate and delayed implants with fixed full-arch prostheses. Peri-implant health showed no statistically significant differences for any of the studied parameters (crevicular fluid volume, plaque index, gingival retraction, keratinized mucosa, probing depth, modified gingival index and presence of mucositis) at the twelve-month follow-up. Key words:Immediate implants, delayed implants, peri-implant health, success rate. PMID:24316712

Apical and marginal bone alterations around implants in maxillary sinus augmentation grafted with autogenous bone or bovine bone material and simultaneous or delayed dental implant positioning.

PubMed

Sbordone, Ludovico; Levin, Liran; Guidetti, Franco; Sbordone, Carolina; Glikman, Ari; Schwartz-Arad, Devorah

2011-05-01

A re-pneumatization phenomenon was recorded in sinuses grafted with different materials. The specific aims of this paper were to assess the dental implant survival rate and the behavior of marginal and apical bone remodeling around dental implants placed following sinus augmentation. A retrospective study was conducted on consecutive patients treated in two surgical centers. Different surgical techniques were adopted for sinus augmentation: simultaneous or delayed dental implant insertion with bovine bone-material augmentation or autologous bone grafting (chin and iliac crest). Survival rates were recorded for the overall number of implants (patients of group A). Apical and marginal bone levels (ABL and MBL, respectively) were radiographically measured, and statistical analysis was performed in implants of a subgroup of patients (group B). A total of 282 dental implants were positioned. Recorded cumulative survival rates (CSRs) were 95.6% and 100% for autogenous and bovine bone material, respectively, while CSRs at 2-year follow-up for immediate and delayed procedures were 99.3% and 96.5%. For the subgroup B, 57 sinus augmentation procedures were performed in 39 patients, with the positioning of 154 implants. Generally, the apical- and marginal-bone resorption of the bovine bone-material group was less than that of the autogenous group. The differences between the ABL values of the bovine bone-material and iliac-crest groups were statistically significant at 1 year, whereas this significance disappeared at the 2-year follow-up; tests showed that a statistical difference was recorded in the bovine bone-material group between the 1- and 2-year follow-ups. With regard to MBL comparisons between simultaneous and delayed implantation, the differences maintained their significance at the 2-year follow-up also. Differences regarding apical bone alteration between autogenous bone from the iliac crest and bovine bone material at the 1- and 2-year follow-ups, as well as in the bovine bone-material group between the 1- and 2-year follow-ups, attested to slower but more prolonged physiologic bone remodeling in the bovine-graft-material group than in the autogenous-bone group. The MBL analysis showed that remodeling in the delayed implant group demonstrated a greater resorption in the cervical portion than was seen in the simultaneous implant group. © 2010 John Wiley & Sons A/S.

Induction of a hypothyroid state during juvenile development delays pubertal reactivation of the neuroendocrine system governing luteinising hormone secretion in the male rhesus monkey (Macaca mulatta).

PubMed

Mann, D R; Bhat, G K; Stah, C D; Pohl, C R; Plant, T M

2006-09-01

The present study aimed to determine the influence of thyroid status on the timing of the pubertal resurgence in gonadotrophin-releasing hormone pulse generator activity [tracked by circulating luteinising hormone (LH) levels] in male rhesus monkeys. Six juvenile monkeys were orchidectomised and then treated with the antithyroid drug, methimazole, from 15-19 months until 36 months of age, at which time thyroxine (T(4)) replacement was initiated. Four additional agonadal monkeys served as controls. Blood samples were drawn weekly for hormonal assessments. Body weight, crown-rump length and bone age were monitored at regular intervals. By 8 weeks of methimazole treatment, plasma T(4) had fallen sharply, and the decline was associated with a plasma thyroid-stimulating hormone increase. In controls, plasma LH levels remained undetectable until the pubertal rise occurred at 29.3 +/- 0.2 months of age. This developmental event occurred in only half of the methimazole-treated animals before 36 months of age when T(4) replacement was initiated. The hypothyroid state was associated with a profound arrest of growth and bone maturation, but increased body mass indices and plasma leptin levels. T(4) replacement in methimazole-treated monkeys was associated with the pubertal rise in LH in the remaining three animals and accelerated somatic development in all six animals. Although pubertal resurgence in LH secretion occurred at a later chronological age in methimazole-treated animals compared to controls, bone age, crown-rump length and body weight at that time did not differ between groups. There were no long-term differences in plasma prolactin between groups. We conclude that juvenile hypothyroidism in male primates causes a marked delay in the pubertal resurgence of LH secretion, probably occasioned at the hypothalamic level. Whether this effect is meditated by an action of thyroid hormone directly on the hypothalamus or indirectly as a result of the concomitant deficit in somatic development remains to be determined.

Clec11a/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton

PubMed Central

Yue, Rui; Shen, Bo; Morrison, Sean J

2016-01-01

Bone marrow stromal cells maintain the adult skeleton by forming osteoblasts throughout life that regenerate bone and repair fractures. We discovered that subsets of these stromal cells, osteoblasts, osteocytes, and hypertrophic chondrocytes secrete a C-type lectin domain protein, Clec11a, which promotes osteogenesis. Clec11a-deficient mice appeared developmentally normal and had normal hematopoiesis but reduced limb and vertebral bone. Clec11a-deficient mice exhibited accelerated bone loss during aging, reduced bone strength, and delayed fracture healing. Bone marrow stromal cells from Clec11a-deficient mice showed impaired osteogenic differentiation, but normal adipogenic and chondrogenic differentiation. Recombinant Clec11a promoted osteogenesis by stromal cells in culture and increased bone mass in osteoporotic mice in vivo. Recombinant human Clec11a promoted osteogenesis by human bone marrow stromal cells in culture and in vivo. Clec11a thus maintains the adult skeleton by promoting the differentiation of mesenchymal progenitors into mature osteoblasts. In light of this, we propose to call this factor Osteolectin. DOI: http://dx.doi.org/10.7554/eLife.18782.001 PMID:27976999

Evaluation of growth hormone treatment efficacy in short Japanese children born small for gestational age: Five-year treatment outcome and impact on puberty

PubMed Central

Horikawa, Reiko; Tanaka, Toshiaki; Nishinaga, Hiromi; Ogawa, Yoshihisa; Yokoya, Susumu

2017-01-01

Abstract. Some children born small for gestational age (SGA) have short stature and are at an increased risk of developing psychosocial or behavioral problems. Here we evaluated the efficacy of GH and its effects on the timing of pubertal onset in a 3-yr extension of our previous 2-yr (total 5 yr) multicenter, randomized, double-blind, parallel-group clinical trial of 65 short Japanese children born SGA. Patients received low or high doses of GH (0.033 or 0.067 mg/kg/day, respectively). Age at onset of puberty was not statistically different for male and female patients receiving high- or low-dose GH. After the onset of puberty, no difference in height gain was observed between the two GH dose groups. At the onset of puberty, height standard deviation scores for chronological age of boys and girls improved significantly in both dose groups with evidence of a dose-response effect. Mean bone age/chronological age ratios in the low- and high-dose groups were significantly increased compared with baseline, being significantly greater in the high-dose group at 5 yr after treatment initiation. Delayed bone age at baseline was close to chronological age following GH treatment. GH treatment, especially high-dose GH, induced advanced bone age in short children born SGA. PMID:28458458

Ligand-Mediated Activation of an Engineered Gs G Protein-Coupled Receptor in Osteoblasts Increases Trabecular Bone Formation

PubMed Central

Hsiao, Edward C.; Millard, Susan M.; Louie, Alyssa; Huang, Yong; Conklin, Bruce R.; Nissenson, Robert A.

2010-01-01

Age-dependent changes in skeletal growth play important roles in regulating skeletal expansion and in the course of many diseases affecting bone. How G protein-coupled receptor (GPCR) signaling affects these changes is poorly understood. Previously, we described a mouse model expressing Rs1, an engineered receptor with constitutive Gs activity. Rs1 expression in osteoblasts from gestation induced a dramatic age-dependent increase in trabecular bone with features resembling fibrous dysplasia; however, these changes were greatly minimized if Rs1 expression was delayed until after puberty. To further investigate whether ligand-induced activation of the Gs-GPCR pathway affects bone formation in adult mice, we activated Rs1 in adult mice with the synthetic ligand RS67333 delivered continuously via an osmotic pump or intermittently by daily injections. We found that osteoblasts from adult animals can be stimulated to form large amounts of bone, indicating that adult mice are sensitive to the dramatic bone- forming actions of Gs signaling in osteoblasts. In addition, our results show that intermittent and continuous activation of Rs1 led to structurally similar but quantitatively different degrees of trabecular bone formation. These results indicate that activation of a Gs-coupled receptor in osteoblasts of adult animals by either intermittent or continuous ligand administration can increase trabecular bone formation. In addition, osteoblasts located at the bone epiphyses may be more responsive to Gs signaling than osteoblasts at the bone diaphysis. This model provides a powerful tool for investigating the effects of ligand-activated Gs-GPCR signaling on dynamic bone growth and remodeling. PMID:20150184

Bone mineral content and density of the lumbar spine of infants and toddlers: influence of age, sex, race, growth, and human milk feeding.

PubMed

Kalkwarf, Heidi J; Zemel, Babette S; Yolton, Kimberly; Heubi, James E

2013-01-01

Little is known about factors that affect bone mass and density of infants and toddlers and the means to assess their bone health owing to challenges in studying this population. The objectives of this study were to describe age, sex, race, growth, and human milk feeding effects on bone mineral content (BMC) and areal density (aBMD) of the lumbar spine, and determine precision of BMC and aBMD measurements. We conducted a cross-sectional study of 307 healthy participants (63 black), ages 1 to 36 months. BMC and aBMD of the lumbar spine were measured by dual-energy X-ray absorptiometry. Duplicate scans were obtained on 76 participants for precision determination. Age-specific Z-scores for aBMD, weight, and length (BMDZ, WAZ, LAZ) were calculated. Information on human milk feeding duration was ascertained by questionnaire. Between ages 1 and 36 months, lumbar spine BMC increased about fivefold and aBMD increased twofold (p < 0.0001). BMC was greater (5.8%) in males than in females (p = 0.001), but there was no difference in aBMD (p = 0.37). There was no difference in BMC or aBMD between whites and blacks (p ≥ 0.16). WAZ and LAZ were positively associated with BMDZ (r = 0.34 and 0.24, p < 0.001). Duration of human milk feeding was negatively associated with BMDZ in infants <12 months of age (r = -0.42, p < 0.001). Precision of BMC and aBMD measurements was good, 2.20% and 1.84%, respectively. Dramatic increases in BMC and aBMD of the lumbar spine occur in the first 36 months of life. We provide age-specific values for aBMD of healthy infants and toddlers that can be used to evaluate bone deficits. Future studies are needed to identify the age when sex and race differences in aBMD occur, and how best to account for delayed or accelerated growth in the context of bone health assessment of infants and toddlers. Copyright © 2013 American Society for Bone and Mineral Research.

Floating-Harbor syndrome: description of a further patient, review of the literature, and suggestion of autosomal dominant inheritance.

PubMed

Lacombe, D; Patton, M A; Elleau, C; Battin, J

1995-08-01

The Floating-Harbor syndrome is a growth retardation syndrome with delayed bone age, speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips. We present an additional patient and review 16 cases from the literature. The possible phenotype in the patient's mother suggests a dominant mode of inheritance for the syndrome. The Floating Harbor syndrome is a growth deficiency syndrome characterized by proportionate short stature, characteristic face and delayed speech development. Inheritance is possibly autosomal dominant.

Growth hormone deficiency: an unusual presentation of floating harbor syndrome.

PubMed

Galli-Tsinopoulou, Assimina; Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Maggana, Ioanna; Kotanidou, Eleni; Kokka, Paraskevi; Stylianou, Charilaos

2011-01-01

Floating-Harbor Syndrome (FHS) is a very rare condition of unknown etiology characterized by short stature, delayed bone age, characteristic facial features, delayed language skills and usually normal motor development. This syndrome has only once been associated with growth hormone deficiency and precocious puberty in the same patient. We describe a 5 4/12 year-old girl with the typical features of FHS in whom growth hormone deficiency was diagnosed and two years later central precocious puberty was noted. The patient showed a good response to human recombinant growth hormone as well as gonadotropin releasing hormone analogue treatment.

Recurrent Proximal Femur Fractures in a Teenager With Osteogenesis Imperfecta on Continuous Bisphosphonate Therapy: Are We Overtreating?

PubMed

Vasanwala, Rashida F; Sanghrajka, Anish; Bishop, Nicholas J; Högler, Wolfgang

2016-07-01

Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment maintenance regimens should be considered on a case-by-case basis. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

High dietary cholesterol masks type 2 diabetes-induced osteopenia and changes in bone microstructure in rats.

PubMed

Lapmanee, Sarawut; Charoenphandhu, Narattaphol; Aeimlapa, Ratchaneevan; Suntornsaratoon, Panan; Wongdee, Kannikar; Tiyasatkulkovit, Wacharaporn; Kengkoom, Kanchana; Chaimongkolnukul, Khuanjit; Seriwatanachai, Dutmanee; Krishnamra, Nateetip

2014-10-01

Type 2 diabetes mellitus (T2DM) often occurs concurrently with high blood cholesterol or dyslipidemia. Although T2DM has been hypothesized to impair bone microstructure, several investigations showed that, when compared to age-matched healthy individuals, T2DM patients had normal or relatively high bone mineral density (BMD). Since cholesterol and lipids profoundly affect the function of osteoblasts and osteoclasts, it might be cholesterol that obscured the changes in BMD and bone microstructure in T2DM. The present study, therefore, aimed to determine bone elongation, epiphyseal histology, and bone microstructure in non-obese T2DM Goto-Kakizaki rats treated with normal (GK-ND) and high cholesterol diet. We found that volumetric BMD was lower in GK-ND rats than the age-matched wild-type controls. In histomorphometric study of tibial metaphysis, T2DM evidently suppressed osteoblast function as indicated by decreases in osteoblast surface, mineral apposition rate, and bone formation rate in GK-ND rats. Meanwhile, the osteoclast surface and eroded surface were increased in GK-ND rats, thus suggesting an activation of bone resorption. T2DM also impaired bone elongation, presumably by retaining the chondrogenic precursor cells in the epiphyseal resting zone. Interestingly, several bone changes in GK rats (e.g., increased osteoclast surface) disappeared after high cholesterol treatment as compared to wild-type rats fed high cholesterol diet. In conclusion, high cholesterol diet was capable of masking the T2DM-induced osteopenia and changes in several histomorphometric parameters that indicated bone microstructural defect. Cholesterol thus explained, in part, why a decrease in BMD was not observed in T2DM, and hence delayed diagnosis of the T2DM-associated bone disease.

[Jaw osteosarcomas].

PubMed

Steve, M; Ernenwein, D; Chaine, A; Bertolus, C; Goudot, P; Ruhin-Poncet, B

2011-11-01

Osteosarcoma (OS) is the most frequent bone malignant tumor. It is usually found on long bones, 5 to 10% are located on jaws, accounting for 0.5 to 1% of all facial tumors. There is little published data which concerns only few patients. Our aim was to study retrospectively cases of facial bone OS in adults, and to compare our results with published data to suggest an optimal management scheme. Thirty-three patients were managed for an OS, from January 1997 to January 2007. Fourteen patients with a maxillary and mandibular OS, treated in first-intention in our unit, were included. The following data were analyzed: age; personal history; circumstance of discovery; clinical, functional, and physical signs; loco-regional extension and metastasis radiological investigation. The histological slides were systematically reviewed. The protocol, therapeutic outcome, and follow-up were studied. The mean age at diagnosis was 43. Swelling was the most frequent functional sign. The mean delay before management was 3.4 months. The most frequent radiological presentation was a lytic and hyperdense image. The diagnosis was suggested after CT scan in 57.1% of cases. The biopsy was correlated to the anatomopathological analysis in 78.6% of cases. The most common treatment was surgical exeresis completed by chemotherapy. The 5-year survival rate was 50%. Jaw OS are specific because of their localization and specific bone ultrastructure. Their management remains controversial: should they be managed like limb OS or treated more specifically? Neoadjuvant chemotherapy, even if it delays exeresis for 3 months, seems to stop the growth or reduce the tumor. An early anatomopathological analysis of the surgical piece determines adjuvant therapy. The negative prognostic factors are: maxillary localization because of limited exeresis margins, tumoral size, and osteoblastic sub-type. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Dietary Approaches that Delay Age-Related Diseases

PubMed Central

Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

2006-01-01

Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2–15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet—disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood and even in the fetus may influence the later development of aging diseases and lifespan. PMID:18047254

A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability.

PubMed

Yuan, Haiming; Meng, Zhe; Zhang, Lina; Luo, Xiangyang; Liu, Liping; Chen, Mengfan; Li, Xinwei; Zhao, Weiwei; Liang, Liyang

2016-01-01

Interstitial duplications distal to 15q13 are very rare. Here, we reported a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay and intellectual disability. His had distinctive facial features including macrocephaly, broad forehead, deep-set and widely spaced eyes, broad nose bridge, shallow philtrum and thick lips. A de novo 6.4 Mb interstitial duplication of 15q15.3q21.2 was detected by chromosomal microarray analysis. We compared our patient's clinical phenotypes with those of several individuals with overlapping duplications and several candidate genes responsible for the phenotypes were identified as well. The results suggest a novel contiguous gene duplication syndrome characterized with shared features including short stature, hypogonadism, global developmental delay and other congenital anomalies.

Is bisphosphonate therapy for benign bone disease associated with impaired dental healing? A case-controlled study

PubMed Central

2011-01-01

Background Bisphosphonates are common first line medications used for the management of benign bone disease. One of the most devastating complications associated with bisphosphonate use is osteonecrosis of the jaws which may be related to duration of exposure and hence cumulative dose, dental interventions, medical co-morbidities or in some circumstances with no identifiable aggravating factor. While jaw osteonecrosis is a devastating outcome which is currently difficult to manage, various forms of delayed dental healing may be a less dramatic and, therefore, poorly-recognised complications of bisphosphonate use for the treatment of osteoporosis. It is hypothesised that long-term (more than 1 year's duration) bisphosphonate use for the treatment of post-menopausal osteoporosis or other benign bone disease is associated with impaired dental healing. Methods/Design A case-control study has been chosen to test the hypothesis as the outcome event rate is likely to be very low. A total of 54 cases will be recruited into the study following review of all dental files from oral and maxillofacial surgeons and special needs dentists in Victoria where potential cases of delayed dental healing will be identified. Potential cases will be presented to an independent case adjudication panel to determine if they are definitive delayed dental healing cases. Two hundred and fifteen controls (1:4 cases:controls), matched for age and visit window period, will be selected from those who have attended local community based referring dental practices. The primary outcome will be the incidence of delayed dental healing that occurs either spontaneously or following dental treatment such as extractions, implant placement, or denture use. Discussion This study is the largest case-controlled study assessing the link between bisphosphonate use and delayed dental healing in Australia. It will provide invaluable data on the potential link between bisphosphonate use and osteonecrosis of the jaws. PMID:21477374

Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

PubMed Central

Foster, B.L.; Ao, M.; Willoughby, C.; Soenjaya, Y.; Holm, E.; Lukashova, L.; Tran, A. B.; Wimer, H.F.; Zerfas, P.M.; Nociti, F.H.; Kantovitz, K.R.; Quan, B.D.; Sone, E.D.; Goldberg, H.A.; Somerman, M.J.

2015-01-01

Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in endochondral ossification in the cranial base, and craniofacial morphology was unaffected in Bsp−/− mice. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp−/− molar teeth. Dissimilar effects of loss of BSP on mineralization of dental and craniofacial tissues suggest local differences in the role of BSP and/or yet to be defined interactions with site-specific factors. PMID:25963390

Clinical and Radiographic Assessment of Three-Implant-Supported Fixed-Prosthesis Rehabilitation of the Edentulous Mandible: Immediate Versus Delayed Loading.

PubMed

Primo, Bruno Tochetto; Mezzari, Leonardo Marcos; da Fontoura Frasca, Luís Carlos; Linderman, Raquel; Rivaldo, Elken Gomes

To evaluate and compare the clinical and radiographic outcomes of mandibular rehabilitation with fixed prostheses on three implants with immediate versus delayed loading. The sample comprised 21 patients who underwent treatment with immediate loading and 23 who received delayed loading. All had worn their prostheses for at least 18 months. Radiographic evaluation of bone loss was carried out in Adobe Photoshop CS5 by a single calibrated examiner using digitized panoramic radiographs. Clinical examination of the technical conditions of the prosthetic device assessed the condition of the acrylic resin base, dental occlusion, metal framework, presence of cover screws, screw fixation of the prosthesis and abutments, length of cantilever (effort) and resistance arms, presence of plaque on prosthetic abutments, and hygiene of the prosthesis. One implant failed in each group, resulting in a 95.23% treatment success rate with immediate loading and 95.65% with delayed loading (no statistically significant between-group difference). In the immediate-loading group, the mean bone loss was 1.96 ± 0.73 mm around central implants and 1.64 ± 0.84 mm at distal implants. In the delayed-loading group, the mean bone loss was 1.85 ± 0.67 mm around central implants and 1.70 ± 0.77 mm at distal implants. According to Student t test, there was no significant within-group difference in bone loss and no difference between the immediate-loading and delayed-loading groups. The only prosthesis-related complications that differed significantly between groups were "condition of the acrylic base," "occlusion," and "presence of right cover screw." There was no statistically significant association of lever arm ratio with peri-implant bone loss or bone loss on the mesial surfaces compared to the distal surfaces of the distal implants. The three-implant-supported fixed prosthesis protocol tested in this study proved to be a viable therapeutic strategy for mandibular edentulous patients with maxillary complete dentures, regardless of whether loading was immediate or delayed, with no difference in peri-implant bone loss.

Medial joint line bone bruising at MRI complicating acute ankle inversion injury: what is its clinical significance?

PubMed

Chan, V O; Moran, D E; Shine, S; Eustace, S J

2013-10-01

To assess the incidence and clinical significance of medial joint line bone bruising following acute ankle inversion injury. Forty-five patients who underwent ankle magnetic resonance imaging (MRI) within 2 weeks of acute ankle inversion injury were included in this prospective study. Integrity of the lateral collateral ligament complex, presence of medial joint line bone bruising, tibio-talar joint effusion, and soft-tissue swelling were documented. Clinical follow-up at 6 months was carried out to determine the impact of injury on length of time out of work, delay in return to normal walking, delay in return to sports activity, and persistence of medial joint line pain. Thirty-seven patients had tears of the anterior talofibular ligament (ATFL). Twenty-six patients had medial joint line bone bruising with altered marrow signal at the medial aspect of the talus and congruent surface of the medial malleolus. A complete ATFL tear was seen in 92% of the patients with medial joint line bone bruising (p = 0.05). Patients with an ATFL tear and medial joint line bone bruising had a longer delay in return to normal walking (p = 0.0002), longer delay in return to sports activity (p = 0.0001), and persistent medial joint line pain (p = 0.0003). There was no statistically significant difference in outcome for the eight patients without ATFL tears. Medial joint line bone bruising following an acute ankle inversion injury was significantly associated with a complete ATFL tear, longer delay in the return to normal walking and sports activity, as well as persistent medial joint line pain. Its presence should prompt detailed assessment of the lateral collateral ligament complex, particularly the ATFL. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Delayed osteon formation in long-bone diaphysis of an 11-year-old giant cow with dermal dysplasia.

PubMed

Mori, R; Kodaka, T; Naito, Y

1999-02-01

The transverse sections of radius diaphysis in an 11-year-old giant Holstein cow with dermal dysplasia of a collagen disorder-related skin fragility (Cow 1), probably based on increasing turnover of the dermal collagen as reported previously, were morphologically and physico-chemically investigated. Cow 1 had about one and a half times as much as the body weight of normal Holstein cows, aged 5 to 6.5 years with stabilized growth. The bone samples were compared with those of a 12-year-old Holstein cow as controls (Cow 2). It has been reported that the long-bone diaphysis of young calves and some herbivorous dinosaurs are occupied with laminar bone showing a concentric appositional formation, and that such a laminar bone is characteristically seen during the growing period of some farm animals and large dogs that show very rapid growth rates. Cow 1 had a smaller number of osteons than Cow 2 in the outer-half layer of the diaphysis, and showed an intermediate type between Cow 2 and a 1-year-old Holstein ox in the entire layers, although their bone volumes were similar among them. There were no significant differences in Ca and P concentrations and the Vickers microhardness values between the bone matrix of Cow 1 and Cow 2. The bone-collagen fibrils of Cow 1 showed uneven diameters and a disordered arrangement. Thus, there may be some relation in collagen formation between the bone matrix of Cow 1 and the dermis. From the remaining volume of laminar bone, Cow 1, aged 11 years, had probably shown growth until quite recently, so that we consider that Cow 1 became a giant animal, in the same way as some herbivorous dinosaurs.

Prevalence of metabolic bone disease in children with celiac disease is independent of symptoms at diagnosis.

PubMed

Turner, Justine; Pellerin, Genevieve; Mager, Diana

2009-11-01

: Given dietary gluten exposure, growing children with celiac disease may experience malabsorption of nutrients, negatively affecting bone health. The purpose of this study was to determine the prevalence of low bone mass in children with celiac disease, according to the presence of symptoms at diagnosis. : A retrospective chart review of the Stollery Children's Hospital Celiac Clinic charts (April 1989-September 2007) was conducted. Bone mineral density (BMD) of the spine was measured using dual energy x-ray absorptiometry. Demographics, symptoms at presentation, and anthropometric and biochemical data relevant to bone health were recorded. : Seventy-four children (9.6 +/- 3.7 years; range 3.3-16.0 years) were included. Lumbar BMD z scores more than or equal to -1 were observed in 58 cases (65%), z scores below -1 but above -2 were observed in 14 cases (19%) and z scores less than or equal to -2 were observed in 12 cases (16%). There was no significant difference in mean lumbar BMD z scores between symptomatic and asymptomatic children (P = 0.34). When adjusted for bone age and bone surface area, BMD lumbar z score was inversely correlated with age at diagnosis (P < 0.05). : An equivalent reduction in spine bone mass was observed in children with celiac disease at diagnosis regardless of the presence of symptoms. Delayed diagnosis of children with celiac disease may increase the risk of adult osteoporosis. Appropriate screening of children at risk of celiac disease for the purpose of early diagnosis, as well as routine evaluation of bone mineral density in such children, are important to prevent long-term complications associated with poor bone health.

Effect of healing time on bone-implant contact of orthodontic micro-implants: a histologic study.

PubMed

Ramazanzadeh, Barat Ali; Fatemi, Kazem; Dehghani, Mahboobe; Mohtasham, Nooshin; Jahanbin, Arezoo; Sadeghian, Hamed

2014-01-01

Objectives. This study aimed to evaluate the effect of immediate and delayed loading of orthodontic micro-implants on bone-implant contact. Materials and Methods. Sixty four micro-implants were implanted in dog's jaw bone. The micro-implants were divided into loaded and unloaded (control) groups. The control group had two subgroups: four and eight weeks being implanted. The loaded group had two subgroups of immediate loading and delayed (after four weeks healing) loading. Loaded samples were subjected to 200g load for four weeks. After sacrificing the animals micro-implants and surrounding tissues were observed histologically. Bone-implant contact ratios (BIC) were calculated and different groups' results were compared by three-way ANOVA. Results. Mean survival rate was 96.7% in general. Survival rates were 96.7%, 94.4% and 100% for control, immediate and delayed loaded groups, respectively. BIC values were not significantly different in loaded and control groups, immediate and delayed loading groups, and pressure and tension sides. Mandibular micro-implants had significantly higher BIC than maxillary ones in immediate loading, 4-weeks control, and 8-weeks control groups (P = 0.021, P = 0.009, P = 0.003, resp.). Conclusion Immediate or delayed loading of micro-implants in dog did not cause significant difference in Bone-implant contact which could be concluded that healing time had not significant effect on micro-implant stability.

Effect of Healing Time on Bone-Implant Contact of Orthodontic Micro-Implants: A Histologic Study

PubMed Central

Ramazanzadeh, Barat Ali; Fatemi, Kazem; Dehghani, Mahboobe; Mohtasham, Nooshin; Jahanbin, Arezoo; Sadeghian, Hamed

2014-01-01

Objectives. This study aimed to evaluate the effect of immediate and delayed loading of orthodontic micro-implants on bone-implant contact. Materials and Methods. Sixty four micro-implants were implanted in dog's jaw bone. The micro-implants were divided into loaded and unloaded (control) groups. The control group had two subgroups: four and eight weeks being implanted. The loaded group had two subgroups of immediate loading and delayed (after four weeks healing) loading. Loaded samples were subjected to 200g load for four weeks. After sacrificing the animals micro-implants and surrounding tissues were observed histologically. Bone-implant contact ratios (BIC) were calculated and different groups' results were compared by three-way ANOVA. Results. Mean survival rate was 96.7% in general. Survival rates were 96.7%, 94.4% and 100% for control, immediate and delayed loaded groups, respectively. BIC values were not significantly different in loaded and control groups, immediate and delayed loading groups, and pressure and tension sides. Mandibular micro-implants had significantly higher BIC than maxillary ones in immediate loading, 4-weeks control, and 8-weeks control groups (P = 0.021, P = 0.009, P = 0.003, resp.). Conclusion Immediate or delayed loading of micro-implants in dog did not cause significant difference in Bone-implant contact which could be concluded that healing time had not significant effect on micro-implant stability. PMID:25006463

Body mass index and bone loss among postmenopausal women: the 10-year follow-up of the OSTPRE cohort.

PubMed

Saarelainen, Jarmo; Kiviniemi, Vesa; Kröger, Heikki; Tuppurainen, Marjo; Niskanen, Leo; Jurvelin, Jukka; Honkanen, Risto

2012-03-01

Obesity protects against osteoporosis, but the magnitude of this association has been difficult to assess from cross-sectional or short term studies. We examined the time course of bone loss as a function of body mass index (BMI) in early and late postmenopausal women. Our study population (n = 300) was a random sample of the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study, Finland. We excluded women without complete BMD results, premenopausal women during the second bone densitometry and women who had used hormone replacement therapy, bisphosphonates or calcitonin. BMI along with femoral neck and spinal bone mineral density (BMD) were assessed three times by dual-energy X-ray absorptiometry during a mean follow-up of 10.5 years (SD 0.5). The mean baseline age was 53.6 years (SD 2.8), time since menopause 2.9 years (SD 4.3) and BMI 27.3 kg/m(2) (SD 4.4). The data was analyzed by linear mixed models. Thus, we were able to approximate the bone loss up to 20 postmenopausal years. To illustrate, a woman with a baseline BMI of 20 kg/m(2) became osteopenic 2 (spine) and 4 (femoral neck) years after menopause, while obesity (BMI of 30 kg/m(2)) delayed the incidence of osteopenia by 5 (spine) and 9 (femoral neck) years, respectively. The delay was due to high baseline BMD of the obese, while bone loss rate was similar for both lean and obese subjects. This lean versus obese difference may also be partly due to altered X-ray attenuation due to fat mass.

Usefulness of magnetic resonance findings of the hypothalamic-pituitary region in the management of short children with growth hormone deficiency: evidence from a longitudinal study.

PubMed

Kalina, Maria A; Kalina-Faska, Barbara; Gruszczyńska, Katarzyna; Baron, Jan; Małecka-Tendera, Ewa

2012-01-01

The purpose of this study is to assess the relationship between magnetic resonance images (MRI) of the hypothalamic-pituitary (H-P) region and response to recombinant human growth hormone (rhGH) treatment in short children with growth hormone deficiency, basing on changes of auxologic parameters, as well as to answer the question if MRI may serve for selecting and monitoring the rhGH responders. The study group comprised 85 children treated with rhGH, aged 7.3-18.7 years, followed for the mean period of 3.2 years (range, 2.1-9.5 years). Auxologic parameters (height deficit hSDS, deviation from the mid-parental height hSDS-mpSDS, bone delay index bone age/chronological age ratio (BA/CA)) were assessed before, during and at the end of rhGH treatment; growth velocity was calculated before and during rhGH therapy. Parameters were correlated with the MRI of the H-P region. Structural anomalies of the H-P region were found in 22 (25.9%) children: empty sella syndrome (ESS) in 12 (14.1%) patients, ectopic posterior pituitary (EPP) in ten (11.8%). Patients' height deficit and their deviation from parental height before rhGH therapy was significantly greater in the EPP group (median hSDS = -3.8; hSDS-mpSDS = -2.5), bone age delay was the greatest in the ESS group (median BA/CA = 0.69), after therapy - in the EPP group (median BA/CA = 0.82). Growth velocity improved in the first year of the rhGH therapy in all groups; however, the most significant acceleration was observed in the EPP group (median delta hSDS = 0.9), then stabilised and was comparable in all groups. MRI may be helpful in predicting response to the rhGH treatment, providing midline abnormalities are taken into account.

[Comparative study on graft of autogeneic iliac bone and tissue engineered bone].

PubMed

Shen, Bing; Xie, Fu-lin; Xie, Qing-fang

2002-11-01

To compare the clinical results of repairing bone defect of limbs with tissue engineering technique and with autogeneic iliac bone graft. From July 1999 to September 2001, 52 cases of bone fracture were randomly divided into two groups (group A and B). Open reduction and internal fixation were performed in all cases as routine operation technique. Autogeneic iliac bone was implanted in group A, while tissue engineered bone was implanted in group B. Routine postoperative treatment in orthopedic surgery was taken. The operation time, bleeding volume, wound healing and drainage volume were compared. The bone union was observed by the X-ray 1, 2, 3, and 5 months after operation. The sex, age and disease type had no obvious difference between groups A and B. all the wounds healed with first intention. The swelling degree of wound and drainage volume had no obvious difference. The operation time in group A was longer than that in group B (25 minutes on average) and bleeding volume in group A was larger than that in group B (150 ml on average). Bone union completed within 3 to 7 months in both groups. But there were 2 cases of delayed union in group A and 1 case in group B. Repair of bone defect with tissue engineered bone has as good clinical results as that with autogeneic iliac bone graft. In aspect of operation time and bleeding volume, tissue engineered bone graft is superior to autogeneic iliac bone.

Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae: A mouse model of premature aging.

PubMed

Yang, Haisheng; Albiol, Laia; Chan, Wing-Lee; Wulsten, Dag; Seliger, Anne; Thelen, Michael; Thiele, Tobias; Spevak, Lyudmila; Boskey, Adele; Kornak, Uwe; Checa, Sara; Willie, Bettina M

2017-12-08

Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (Gorab Prx1 ) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the Gorab Prx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that Gorab Prx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared (FTIR) imaging indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the Gorab Prx1 tibiae (p < .05), suggesting delayed mineralization. In vivo strain gauge measurement and finite element analysis showed ∼two times higher tissue-level strains within the Gorab Prx1 tibiae relative to LC tibiae when subjected to axial compressive loads of the same magnitude. Three-point bending tests suggested that Gorab Prx1 tibiae were weaker and more brittle, as indicated by decreasing whole-bone strength (46%), stiffness (55%), work-to-fracture (61%) and post-yield displacement (47%). Many of these morphological and biomechanical characteristics of the Gorab Prx1 tibia recapitulated changes in other animal models of skeletal aging. Future studies are necessary to confirm how our observations might guide the way to a better understanding and treatment of GO. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Study of bone mass with dual energy x-ray absorptiometry in a population of 99 lower limb amputees].

PubMed

Leclercq, M M; Bonidan, O; Haaby, E; Pierrejean, C; Sengler, J

2003-02-01

Osteopenia in lower extremity amputation is described with an increased risk of fracture and it seems to be interesting to study bone mass in a population of 99 amputees of limb. We studied the bone mass with Dual Energy Xray Absorptiometry in patients with limb amputation, above and under knee and who have been treated in the rehabilitation department of Mulhouse's hospital and more specifically the percentage of the difference of the mesure between amputed and non amputed side and the influence on this mesure of several factors like sexe; age; diabetes mellitus; delay of amputation; aetiology and use of prosthesis. For all the population, we find lower values of BMD (Bone mineral density) for femoral neck -10.4% +/- 12.2 (P < 0,001) and trochanter -14.9% +/- 14.5 (P < 0,001) between amputated and non amputated side, and also comparing with normal population -19.9% +/- 18.8 (P < 0,001) for femoral neck and -8.8% +/- 22 (P < 0,001) for trochanter.There is no influence of sexe, age, and time since amputation on BMD. The study of sub-groupes shows that the loss of bone mass is depending on traumatic amputation, the level of amputation (above knee) and when prothetis doesn't fit. Arteritis or diabetis are not pejoratif factors. This work confirms the mechanical factors as an important parameter of bone loss in the limb amputation.

Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition

PubMed Central

2013-01-01

Background In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. Methods Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. Conclusions Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair. PMID:23324433

Psychosocial predictors of immune response following bone marrow transplantation.

PubMed

Pulgar, Ángeles; Garrido, Sergio; Alcalá, Antonio; Reyes del Paso, Gustavo A

2012-01-01

This study analyzed the relationship between some psychosocial variables (depression, anxiety, stress, coping strategies, social support, optimism, rationality, and need for harmony) and clinical parameters indicative of immunological response after bone marrow transplantation (BMT; day of engraftment, number of infections and hemoglobin level) while controlling for demographic variables (age, educative level, civil state, and time from cancer diagnosis). Thirty-one post BMT hematological cancer patients were evaluated. Results show that higher educative levels are associated to lower number of infections, while age is associated with a delay in the time of engraftment; coping strategies, specially redefinition of the situation, relaxation, stoicism and passivity, are positively associated with the three clinical indices; depression is positively associated to number of infections during the hospitalization period; and rationality is associated with lower hemoglobin levels. These results suggest that psychosocial variables, especially coping strategies, play an important role in determining the immunological response after BMT.

Blood-pool SPECT in addition to bone SPECT in the viability assessment in mandibular reconstruction.

PubMed

Aydogan, F; Akbay, E; Cevik, C; Kalender, E

2014-01-01

The assessment of the postoperative viability of vascularized and non-vascularized grafts used in the reconstruction of mandibular defects due to trauma and surgical reasons is a major problem in maxillofacial surgery. In the present study, we evaluated the feasibility and image quality of blood-pool SPECT, which is used for the first time in the literature here in the assessment of mandibular reconstruction, in addition to non-invasive bone scintigraphy and bone SPECT. We also evaluated whether it would be useful in clinical prediction. Micro-vascularized and non-vascularized bone grafts were used in 12 Syrian men with maxillofacial trauma. Between days 5-7 after surgery, three-phase bone scintigraphy, blood-pool SPECT and delayed bone SPECT scans were performed. After month 6, the patients were assessed by control CT scans. Of the non-vascularized grafts, one graft was reported as non-viable at week one. At month 6, graft resorption was demonstrated on the CT images. The remaining non-vascularized grafts and all of the micro-vascularized grafts were considered to be viable according to delayed bone SPECT and blood-pool SPECT images. However, only the anterior and posterior ends could be clearly assessed on delayed SPECT images, while blood-pool SPECT images allowed the clear assessment of the entire graft. The combined use of blood-pool and delayed SPECT scans could allow for better assessment of graft viability in the early period, and can provide more detailed information to clinicians about prognosis in the follow-up of patients undergoing mandibular graft reconstruction.

Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial.

PubMed

Hero, Matti; Norjavaara, Ensio; Dunkel, Leo

2005-12-01

In males as well as in females, estrogen is an essential regulator of bone maturation, growth plate fusion, and cessation of longitudinal growth. Therefore, an increase in predicted adult height (PAH) may be achieved in short boys by blocking estrogen biosynthesis. We tested the hypothesis that a decrease in the rate of bone maturation and an increase in PAH can be achieved in boys with idiopathic short stature (ISS) by the method of blocking estrogen biosynthesis with an aromatase inhibitor. Secondarily, we investigated the effects of aromatase inhibition on bone mineralization. This was a prospective, double-blind, randomized, placebo (Pl)-controlled clinical study. The study was performed at a university hospital out-patient clinic. Thirty-one boys, aged 9.0-14.5 yr, with ISS were studied. The boys were treated with the aromatase inhibitor letrozole (Lz; 2.5 mg/d) or Pl for 2 yr. The main outcome measure was the change in PAH after 24 months of treatment. PAH increased by 5.9 cm (P < 0.0001), and height SD score for bone age increased by 0.7 SD score (P < 0.0001) in the Lz-treated boys, whereas no changes occurred in the respective measures in Pl-treated boys. Areal bone mineral density of the lumbar spine and femoral neck, assessed by dual-energy x-ray absorptiometry, increased in a similar fashion in both groups during the treatment, whereas bone mineral apparent density increased only in those taking Lz (median increase, 4.3%; P = 0.009). Treatment with the aromatase inhibitor Lz delays bone maturation and improves PAH in boys with ISS. No adverse effects on bone mineralization were evident after 2 yr of treatment.

Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures

PubMed Central

Kague, Erika; Roy, Paula; Asselin, Garrett; Hu, Gui; Stanley, Alexandra; Albertson, Craig; Simonet, Jacqueline; Fisher, Shannon

2017-01-01

During growth, individual skull bones overlap at sutures, where osteoblast differentiation and bone deposition occur. Mutations causing skull malformations have revealed some required genes, but many aspects of suture regulation remain poorly understood. We describe a zebrafish mutation in osterix/sp7, which causes a generalized delay in osteoblast maturation. While most of the skeleton is patterned normally, mutants have specific defects in the anterior skull and upper jaw, and the top of the skull comprises a random mosaic of bones derived from individual initiation sites. Osteoblasts at the edges of the bones are highly proliferative and fail to differentiate, consistent with global changes in gene expression. We propose that signals from the bone itself are required for orderly recruitment of precursor cells and growth along the edges. The delay in bone maturation caused by loss of Sp7 leads to unregulated bone formation, revealing a new mechanism for patterning the skull and sutures. PMID:26992365

Effects of Immediate and Delayed Loading on the Outcomes of All-on-4 Treatment: A Prospective Study

PubMed Central

Najafi, Hossein; Siadat, Hakimeh; Rokn, Amirreza

2016-01-01

Objectives: The purpose of this study was to compare the outcomes of immediate and delayed rehabilitation of edentulous jaws by means of two straight and two tilted implants after one year of function. Materials and Methods: Thirty consecutive patients (16 males, 14 females) were enrolled in this study. Two anterior straight and two posterior tilted implants were placed in each patient. According to the implant insertion torque and the need for bone grafting, implants were loaded immediately (at 72 hours) or delayed (after four months) using a fixed metal resin prosthesis. Results: One axial implant failed in the delayed group after one year of loading, resulting in cumulative implant survival rate of 99.3%. The mean marginal bone loss was 0.84mm. No significant difference was found between axial and tilted implants in the two groups (P>0.05) Conclusions: Based on the results, immediate or delayed fabrication of final prosthesis on two tilted and two axial implants did not result in significant differences in survival rates or marginal bone loss. PMID:28243303

Characterization of the Correct Mandibular Premolar Region for Delayed Dental Implantation in Beagle Dogs.

PubMed

Xie, Chenxi; Fu, Xiaoming; Xu, Ling; Xu, Sheng

2018-05-01

For delayed dental implantation into the mandible, the implant size should be chosen according to the characteristics of that bone. This study investigated anatomic features of the mandible in beagle dogs, to develop recommendations regarding the correct implantation region and available bone area for delayed dental implantation surgery. We used 20 healthy male beagle dogs to create delayed dental implantation models. The dogs' mandibles underwent cone beam CT (CBCT) imaging; the locations of the middle mental foramen and canine root apex were measured on CBCT images. The dogs then were euthanized and their mandibles measured by using a digital vernier caliper. In addition, the correct implantation region and available bone areas were evaluated. The data obtained by using the 2 measuring methods were compared statistically. The results showed that the positions of the middle mental foramen and canine root apex were relatively fixed, with little variation. The implantation and available bone regions showed little variation among dogs and did not differ significantly between the 2 measuring methods. In conclusion, the correct implantation region (mean ± 1 SD) in the beagle mandible for delayed dental implantation surgery was 17.53 ± 0.46 mm in width. The recommended available bone areas (height × width) were 7.22 ± 0.68 mm × 5.32 ± 0.49 mm (P2), 8.21 ± 0.71 mm × 5.81 ± 0.56 mm (P3), and 9.17 ± 0.65 mm × 6.39 ± 0.56 mm (P4) in the premolar region.

Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy

PubMed Central

Greenspan, Susan L.; Nelson, Joel B.; Trump, Donald L.; Wagner, Julie M.; Miller, Megan E.; Perera, Subashan; Resnick, Neil M.

2008-01-01

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health. PMID:18802155

Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia.

PubMed

Brooks, Elizabeth Drake; Little, Dianne; Arumugam, Ramamani; Sun, Baodong; Curtis, Sarah; Demaster, Amanda; Maranzano, Michael; Jackson, Mark W; Kishnani, Priya; Freemark, Michael S; Koeberl, Dwight D

2013-06-01

Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (-/-) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (-/-) mice. Untreated G6pase (-/-) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia. Copyright © 2013 Elsevier Inc. All rights reserved.

Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia

PubMed Central

Brooks, Elizabeth Drake; Little, Dianne; Arumugam, Ramamani; Sun, Baodong; Curtis, Sarah; DeMaster, Amanda; Maranzano, Michael; Jackson, Mark W.; Kishnani, Priya; Freemark, Michael S.; Koeberl, Dwight D.

2013-01-01

Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (−/−) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (−/−) mice. Untreated G6pase (−/−) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia. PMID:23623482

Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

PubMed Central

Decker, Celeste; Yu, Zi-Fan; Giugliani, Roberto; Schwartz, Ida Vanessa D.; Guffon, Nathalie; Teles, Elisa Leão; Miranda, M. Clara Sá; Wraith, J. Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Ketteridge, David; Hopwood, John J.; Plecko, Barbara; Steiner, Robert; Whitley, Chester B.; Kaplan, Paige; Swiedler, Stuart J.; Conrad, Susan; Harmatz, Paul

2010-01-01

Background and Methods Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16 years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96 weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation. PMID:20634905

Tailoring the excitation of fundamental flexural guide waves in coated bone by phase-delayed array: two-dimensional simulations.

PubMed

Kilappa, Vantte; Moilanen, Petro; Salmi, Ari; Haeggström, Edward; Zhao, Zuomin; Myllylä, Risto; Timonen, Jussi

2015-03-01

The fundamental flexural guided wave (FFGW) enables ultrasonic assessment of cortical bone thickness. In vivo, it is challenging to detect this mode, as its power ratio with respect to disturbing ultrasound is reduced by soft tissue covering the bone. A phase-delayed ultrasound source is proposed to tailor the FFGW excitation in order to improve its power ratio. This situation is analyzed by 2D finite-element simulations. The soft tissue coating (7-mm thick) was simulated as a fluid covering an elastic plate (bone, 2-6 mm thick). A six-element array of emitters on top of the coating was excited by 50-kHz tone bursts so that each emitter was appropriately delayed from the previous one. Response was recorded by an array of receivers on top of the coating, 20-50 mm away from the closest emitter. Simulations predicted that such tailored/phase-delayed excitations should improve the power ratio of FFGW by 23 ± 5 dB, independent of the number of emitters (N). On the other hand, the FFGW magnitude should increase by 5.8 ± 0.5 dB for each doubling of N. This suggests that mode tailoring based on phase-delayed excitation may play a key role in the development of an in vivo FFGW assessment.

Effect of Immediate and Delayed High-Strain Loading on Tendon-to-Bone Healing After Anterior Cruciate Ligament Reconstruction

PubMed Central

Packer, Jonathan D.; Bedi, Asheesh; Fox, Alice J.; Gasinu, Selom; Imhauser, Carl W.; Stasiak, Mark; Deng, Xiang-Hua; Rodeo, Scott A.

2014-01-01

Background: We previously demonstrated, in a rat anterior cruciate ligament (ACL) graft reconstruction model, that the delayed application of low-magnitude-strain loading resulted in improved tendon-to-bone healing compared with that observed after immediate loading and after prolonged immobilization. The purpose of this study was to determine the effect of higher levels of strain loading on tendon-to-bone healing. Methods: ACL reconstruction was carried out in a rat model in three randomly assigned groups: high-strain daily loading beginning on either (1) postoperative day one (immediate-loading group; n = 7) or (2) postoperative day four (delayed-loading group; n = 11) or (3) after prolonged immobilization (immobilized group; n = 8). Animals were killed two weeks after surgery and micro-computed tomography (micro-CT) and biomechanical testing of the bone-tendon-bone complex were carried out. Results: The delayed-loading group had greater tissue mineral density than either the immediate-loading or immobilized group (mean [and standard deviation], 813.0 ± 24.9 mg/mL compared with 778.4 ± 32.6 mg/mL and 784.9 ± 26.4 mg/mL, respectively; p < 0.05). There was a trend toward greater bone volume per total volume fraction in both the immobilized and the delayed-loading group compared with the immediate-loading group (0.24 ± 0.03 and 0.23 ± 0.06 compared with 0.20 ± 0.05; p = 0.06). Trabecular thickness was greater in the immobilized group compared with the immediate-loading group (106.5 ± 23.0 μm compared with 72.6 ± 10.6 μm; p < 0.01). There were no significant differences in failure load or stiffness between the immobilized group and either high-strain cyclic-loading group. Conclusions: Immediate application of high-strain loading appears to have a detrimental effect on healing in this rat model. Any beneficial effects of delayed loading on the healing tendon-bone interface (after a brief period of immobilization) may be offset by the detrimental effects of excessive strain levels or by the detrimental effects of stress deprivation on the graft. Clinical Relevance: The timing and magnitude of mechanical load on a healing rat ACL reconstruction graft may have important implications for postoperative rehabilitation. Avoidance of exercises that cause high graft strain in the early postoperative period may lead to improved tendon-to-bone healing in humans. PMID:24806014

Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair

PubMed Central

Yu, Yan Yiu; Lieu, Shirley; Hu, Diane; Miclau, Theodore; Colnot, Céline

2012-01-01

Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate (N-BP), is the most potent bisphosphonate among the clinically approved bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis does not occur in long bones. The aim of this study was to compare the effects of zoledronate on long bone and cranial bone regeneration using a previously established model of non-stabilized tibial fractures and a new model of mandibular fracture repair. Contrary to tibial fractures, which heal mainly through endochondral ossification, mandibular fractures healed via endochondral and intramembranous ossification with a lesser degree of endochondral ossification compared to tibial fractures. In the tibia, ZA reduced callus and cartilage formation during the early stages of repair. In parallel, we found a delay in cartilage hypertrophy and a decrease in angiogenesis during the soft callus phase of repair. During later stages of repair, ZA delayed callus, cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and bone remodeling in correlation with a decrease in osteoclast number during the soft and hard callus phases of repair. These results reveal a more profound impact of ZA on cartilage and bone remodeling in the mandible compared to the tibia. This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones. PMID:22359627

Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration.

PubMed

Inoue, Yuji; Iriyama, Aya; Ueno, Shuji; Takahashi, Hidenori; Kondo, Mineo; Tamaki, Yasuhiro; Araie, Makoto; Yanagi, Yasuo

2007-08-01

Because there is no effective treatment for this retinal degeneration, potential application of cell-based therapy has attracted considerable attention. Several investigations support that bone marrow mesenchymal stem cells (MSCs) can be used for a broad spectrum of indications. Bone marrow MSCs exert their therapeutic effect in part by secreting trophic factors to promote cell survival. The current study investigates whether bone marrow MSCs secrete factor(s) to promote photoreceptor cell survival and whether subretinal transplantation of bone marrow MSCs promotes photoreceptor survival in a retinal degeneration model using Royal College of Surgeons (RCS) rats. In vitro, using mouse retinal cell culture, it was demonstrated that the conditioned medium of the MSCs delays photoreceptor cell apoptosis, suggesting that the secreted factor(s) from the MSCs promote photoreceptor cell survival. In vivo, the MSCs were injected into the subretinal space of the RCS rats and histological analysis, real-time RT-PCR and electrophysiological analysis demonstrated that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function in the RCS rats. These results suggest that MSC is a useful cell source for cell-replacement therapy for some forms of retinal degeneration.

Triple-phase bone image abnormalities in Lyme arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, S.J.; Dadparvar, S.; Slizofski, W.J.

1989-10-01

Arthritis is a frequent manifestation of Lyme disease. Limited triple-phase Tc-99m MDP bone imaging of the wrists and hands with delayed whole-body images was performed in a patient with Lyme arthritis. This demonstrated abnormal joint uptake in the wrists and hands in all three phases, with increased activity seen in other affected joints on delayed whole-body images. These findings are nonspecific and have been previously described in a variety of rheumatologic conditions, but not in Lyme disease. Lyme disease should be considered in the differential diagnosis of articular and periarticular bone scan abnormalities.

Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing.

PubMed

Monfoulet, Laurent; Malaval, Luc; Aubin, Jane E; Rittling, Susan R; Gadeau, Alain P; Fricain, Jean-Christophe; Chassande, Olivier

2010-02-01

Bone healing is a complex multi-step process, which depends on the position and size of the lesion, and on the mechanical stability of the wounded area. To address more specifically the mechanisms involved in cortical bone healing, we created drill-hole defects in the cortex of mouse femur, a lesion that triggers intramembranous repair, and compared the roles of bone sialoprotein (BSP) and osteopontin (OPN), two proteins of the extracellular matrix, in the repair process. Bone regeneration was analyzed by ex vivo microcomputerized X-ray tomography and histomorphometry of bones of BSP-deficient, OPN-deficient and wild-type mice. In all mouse strains, the cortical gap was bridged with woven bone within 2 weeks and no mineralized tissue was observed in the marrow. Within 3 weeks, lamellar cortical bone filled the gap. The amount and degree of mineralization of the woven bone was not affected by OPN deficiency, but cortical bone healing was delayed in BSP-deficient mice due to delayed mineralization. Gene expression studies showed a higher amount of BSP transcripts in the repair bone of OPN-deficient mice, suggesting a possible compensation of OPN function by BSP in OPN-null mice. Our data suggest that BSP, but not OPN, plays a role in primary bone formation and mineralization of newly formed bone during the process of cortical bone healing. (c) 2009 Elsevier Inc. All rights reserved.

Osteoporotic risk and physeal closure in prepubertal ovariohysterectomized cats.

PubMed

Uçmak, Melih; Yılmaz, Özge Turna; Gündüz, Mehmet Can; Uçmak, Zeynep Günay; Duzgun, Oktay; Eskiyurt, Nurten; Oruç, Coşkun Umut; Genç, Sema; Erzengin, Ömer Mehmet; Karaçam, Esra

2015-10-01

We aimed to examine the early effects of prepubertal ovariohysterectomy (P-OHE) on bone loss and proximal physeal closure in cats. Fourteen kittens randomly underwent P-OHE or sham operations (S-OP) at three months (mo) of age and were allocated to group I and group II. Each mo between four and nine mo of age, dual-energy X-ray absorptiometry (DEXA) scans were performed to determine the total body bone mineral density (BMD) and bone mineral content (BMC). Proximal radial physeal closure and radial length were determined by radiography. Bone-specific alkaline phosphatase (BAP), carboxy-terminal collagen teleopeptide (CTX), 17-β estradiol, progesterone, calcium (Ca) and phosphorus (P) were measured in the serum samples. No significant differences were observed between the groups in terms of BMD, BMC, BAP, BAP/CTX, P, progesterone and body weight (BW) (between 4 and 9mo) and for Ca (between 5 and 9mo) and for CTX levels (between 4 and 8mo). The 17-β estradiol was significantly higher at 6, 8 and 9mo of age in the S-OP group due to puberty (P=0.02, P=0.03 and P=0.02 respectively). Although there was a significant difference (P=0.0002) between the P-OHE and S-OP groups in terms of the proximal radial physeal closure times (7.43±0.20mo and 6.14±0.14mo, respectively), no significant difference was observed for the mean radius length (10.59±0.10cm and 10.06±0.27cm, respectively) at the last evaluation time. In conclusion, prepubertal ovariohysterectomized cats do not have any osteoporotic risks until nine mo of age and exhibit a delayed physeal closure time without a change in radius length. Copyright © 2015. Published by Elsevier B.V.

PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3

PubMed Central

Chen, Hangang; Sun, Xianding; Yin, Liangjun; Chen, Shuai; Zhu, Ying; Huang, Junlan; Jiang, Wanling; Chen, Bo; Zhang, Ruobin; Chen, Lin; Nie, Mao; Xie, Yangli; Deng, Zhongliang

2017-01-01

Bone fracture healing is processed through multiple stages including the cartilaginous callus formation and its transition to bony callus. FGFR3 negatively regulates chondrogenesis and enhances osteogenesis during skeleton development. We previously found in mice carrying gain-of-function mutation of FGFR3 that FGFR3 delays the healing of un-stabilized fracture that heals mainly through endochondral ossification. Since fracture is regularly treated in clinics with rigid fixation, and stabilized fracture is healed largely through intramembranous ossification, we asked whether FGFR3, a key regulator of osteogenesis, also affect the regeneration of stabilized fracture. We found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis and the subsequent bone formation. We further studied whether PTH1-34 can improve the osteopenia and delayed healing of the stabilized tibia fracture in mice with achondroplasia. Fracture healing was evaluated by radiography, micro-CT, biomechanical tests, histology, and real-time polymerase chain reaction (RT-PCR) analysis. We found that PTH 1-34 can alleviate the decreased bone mass and compromised architecture in ACH mice. Histological analysis revealed that administration of PTH1-34 increased the size of both the total callus and cartilaginous callus at 14 days after the surgery in ACH mice. RT-PCR data suggested that systemic PTH1-34 accelerated the initiation of chondrogenesis and chondrocyte maturation (earlier and higher levels of expression of chondrogenesis related markers) and enhanced the osteogenic differentiation in the fracture callus in ACH mice. These results indicate that the PTH1-34 administration resulted in an enhanced callus formation during bone fracture healing in ACH mice, which is at least in part mediated by an increase of cartilaginous callus at early stage and the promotion of bone formation in bony callus. In summary, in this study we revealed that FGFR3 delays the regeneration of stabilized fracture by inhibiting both the chondrogenesis and osteogenesis, and PTH1-34 treatment can improve the dysregulated bone metabolism and delayed bone injury healing resulting from gain-of-function mutation of FGFR3. PMID:29104492

Mechanical induction of critically delayed bone healing in sheep: radiological and biomechanical results.

PubMed

Schell, Hanna; Thompson, Mark S; Bail, Hermann J; Hoffmann, Jan-Erik; Schill, Alexander; Duda, Georg N; Lienau, Jasmin

2008-10-20

This study aimed to mechanically produce a standardized ovine model for a critically delayed bone union. A tibial osteotomy was stabilized with either a rigid (group I) or mechanically critical (group II) external fixator in sheep. Interfragmentary movements and ground reaction forces were monitored throughout the healing period of 9 weeks. After sacrifice at 6 weeks, 9 weeks and 6 months, radiographs were taken and the tibiae were examined mechanically. Interfragmentary movements were considerably larger in group II throughout the healing period. Unlike group I, the operated limb in group II did not return to full weight bearing during the treatment period. Radiographic and mechanical observations showed significantly inferior bone healing in group II at 6 and 9 weeks compared to group I. After 6 months, five sheep treated with the critical fixator showed radiological bridging of the osteotomy, but the biomechanical strength of the repair was still inferior to group I at 9 weeks. The remaining three animals had even developed a hypertrophic non-union. In this study, mechanical instability was employed to induce a critically delayed healing model in sheep. In some cases, this approach even led to the development of a hypertrophic non-union. The mechanical induction of critical bone healing using an external fixation device is a reasonable attempt to investigate the patho-physiological healing cascade without suffering from any biological intervention. Therefore, the presented ovine model provides the basis for a comparative evaluation of mechanisms controlling delayed and standard bone healing.

Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs

PubMed Central

Peck, Sun H.; O'Donnell, Philip J.M.; Kang, Jennifer L.; Malhotra, Neil R.; Dodge, George R.; Pacifici, Maurizio; Shore, Eileen M.; Haskins, Mark E.; Smith, Lachlan J.

2015-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients. PMID:26422116

Calorie restriction in rhesus monkeys.

PubMed

Mattison, Julie A; Lane, Mark A; Roth, George S; Ingram, Donald K

2003-01-01

Calorie restriction (CR) extends lifespan and reduces the incidence and age of onset of age-related disease in several animal models. To determine if this nutritional intervention has similar actions in a long-lived primate species, the National Institute on Aging (NIA) initiated a study in 1987 to investigate the effects of a 30% CR in male and female rhesus macaques (Macaca mulatta) of a broad age range. We have observed physiological effects of CR that parallel rodent studies and may be predictive of an increased lifespan. Specifically, results from the NIA study have demonstrated that CR decreases body weight and fat mass, improves glucoregulatory function, decreases blood pressure and blood lipids, and decreases body temperature. Juvenile males exhibited delayed skeletal and sexual maturation. Adult bone mass was not affected by CR in females nor were several reproductive hormones or menstrual cycling. CR attenuated the age-associated decline in both dehydroepiandrosterone (DHEA) and melatonin in males. Although 81% of the monkeys in the study are still alive, preliminary evidence suggests that CR will have beneficial effects on morbidity and mortality. We are now preparing a battery of measures to provide a thorough and relevant analysis of the effectiveness of CR at delaying the onset of age-related disease and maintaining function later into life.

Animal models for osteoporosis

NASA Technical Reports Server (NTRS)

Turner, R. T.; Maran, A.; Lotinun, S.; Hefferan, T.; Evans, G. L.; Zhang, M.; Sibonga, J. D.

2001-01-01

Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

Delayed Expression of Circulating TGF-β1 and BMP-2 Levels in Human Nonunion Long Bone Fracture Healing.

PubMed

Hara, Yoshiaki; Ghazizadeh, Mohammad; Shimizu, Hajime; Matsumoto, Hisashi; Saito, Nobuyuki; Yagi, Takanori; Mashiko, Kazuki; Mashiko, Kunihiro; Kawai, Makoto; Yokota, Hiroyuki

2017-01-01

The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-β1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition. We performed a comprehensive analysis of plasma TGF-β1 and BMP-2 levels in blood samples from 10 patients with proved nonunion and 10 matched patients with normal union following a predetermined time schedule. The concentrations of TGF-β1 and BMP-2 were measured at each time point using a solid-phase ELISA. TGF-β1 and BMP-2 levels were detectable in all patients. For all patients, a maximal peak for TGF-β1 was found at 3-week. In normal union group, TGF-β1 showed a maximal peak at 2-week while nonunion group had a delayed maximal peak at 3-week. Plasma levels of BMP-2 for all patients and for normal union group reached a maximal peak at 1-week, but nonunion group showed a delayed maximal peak at 2-week. In general, plasma TGF-β1 or BMP-2 level was not significantly different between normal union and nonunion groups. The expression levels of TGF-β1 and BMP-2 appeared to be delayed in nonunion patients which could play an important role in developing an early marker of fracture union condition and facilitate improved patient's management.

Can Time of Implant Placement influence Bone Remodeling?

PubMed

Rafael, Caroline F; Passoni, Bernardo; Araúio, Carlos; de Araúio, Maria A; Benfatti, César; Volpato, Claudia

2016-04-01

Since the alveolar process is tissue "dental dependent," after the extraction of the dental element, this process suffers some degree of atrophy during the healing process, which can be reduced with the installation of immediate implants, aiming to maintain the original bone architecture. The aim of this study was to investigate the influence of the time of implant placement on bone formation around them. Seven dogs were selected and randomly divided into two groups: Group 1, where implants were placed immediately after extraction of two lower premolars without flap elevation, and group 2, where implants were delayed by 4 months after extractions. Each group received 14 implants, and 4 months after the second surgery, the samples were processed and analyzed histomorphometrically. A mean average analysis and the Kruskal-Wallis test (p < 0.05) were performed. The buccal bone-implant contact (BIC) mean average was found larger in immediate implants (42.61%) compared with delayed implants (37.69%). Group 1 had statistically higher outcomes in bone formation and BIC on the buccal bone wall. It was concluded that performing immediate implants with the palatal approach technique and leaving a buccal GAP enables a higher or at least equal rate to BIC and bone area around them, when compared with delayed implants. Actually, the patients and dentists want to do a shorter treatment with satisfactory results, but it is necessary to understand whether different times of implant placement can influence the results and longevity of the treatment.

Bone augmentation of the osteo-odonto alveolar lamina in MOOKP--will it delay laminar resorption?

PubMed

Iyer, Geetha; Srinivasan, Bhaskar; Agarwal, Shweta; Rishi, Ekta; Rishi, Pukhraj; Rajan, Gunaseelan; Shanmugasundaram, Shanmugasundaram

2015-07-01

We aimed to describe a new technique and analyse the early outcomes of augmenting the canine tooth using a mandibular bone graft in an attempt to delay or retard the process of laminar resorption following the modified osteo odonto keratoprosthesis (MOOKP) procedure. This was a retrospective case series. Eyes that underwent the bone augmentation procedure between December 2012 and February 2014 were retrospectively analysed. The procedure, performed by the oromaxillofacial surgeon, involved securing a mandibular bone graft beneath the periosteum on the labial aspect of the canine tooth chosen to be harvested for the MOOKP procedure. This procedure was performed simultaneously with the Stage 1 A of the MOOKP. Three months later, the tooth was harvested and fashioned into the osteo-odonto alveolar lamina similar to the method described in the Rome-Vienna Protocol. The bone augmentation procedure was performed in 11 eyes (five SJS/ six chemical injuries). The mean follow-up after Stage 2 of MOOKP procedure in these eyes was 7.45 months (2 to 20 months). Complications noted were peripheral laminar exposure (three eyes-SJS) and bone graft exposure and necrosis in the mouth (nine-SJS). No evidence of clinical laminar resorption was noted in any of the eyes. Laminar resorption in MOOKP can lead to vision and globe threatening complications due to the consequent cylinder instability and chances of extrusion. Augmenting the bone on the labial aspect of the canine tooth might have a role to play in delaying or preventing laminar resorption.

Bone Mineral Density and Growth in Children Having Undergone Liver Transplantation With Corticosteroid-Free Immunosuppressive Protocol.

PubMed

Mager, Diana; Al-Zaben, Abeer Salman; Robert, Cheri; Gilmour, Susan; Yap, Jason

2017-05-01

Children post-liver transplantation (post-LTX) are at risk of growth delay and decreased bone mineral density (BMD) secondary to corticosteroid (CS) therapy and suboptimal intake of nutrients important for bone health. The pediatric LTX program at Stollery Children's Hospital introduced a CS-free LTX regimen in 2003. This retrospective study investigated whether the implementation of a CS-free protocol resulted in improvements in BMD (dual x-ray absorptiometry) and growth following LTX. A retrospective chart review of all children undergoing LTX was conducted. The parameters included repeated measures of anthropometric (weight, weight z score, height, height z score), BMD/bone mineral content (BMC), laboratory variables, graft function (number/severity of rejection), and CS therapy (dose, duration). A total of 39 patients met study inclusion (20 male; n = 28 on CS; n = 11 CS-free). Mean duration of follow-up was 5.5 ± 3.3 years. The mean weight and height z scores were -0.31 ± 0.14 (CS) and 0.22 ± 0.23 (CS-free; P = .09) and -0.71 ± 0.13 (CS) and 0.23 ± 0.22 (CS-free; P = .002), respectively. Lumbar and whole-body BMD z score less than -2 were present in 15% and 8% of the cohort, respectively. There were no significant differences between CS and CS-free in lumbar BMC (22.2 ± 1.4 and 23.4 ± 2.02 g; P = .165) and lumbar BMD (0.57 ± 0.02 and 0.80 ± 0.22 g/cm 2 ; P = .152), respectively. Lumbar BMC ( r 2 = 0.89, P < .05) and whole-body BMC ( r 2 = 0.93, P < .05) were inversely related to CS dose >0.2 mg/kg/d and positively related to bone age ( P < .01). CS therapy in children post-LTX is associated with reduced BMC and delayed linear growth. Understanding the clinical and nutrition factors influencing bone health is important to optimizing growth and bone health in children post-LTX.

The first Korean patient with Potocki-Shaffer syndrome: a rare cause of multiple exostoses.

PubMed

Sohn, Young Bae; Yim, Shin-Young; Cho, Eun-Hae; Kim, Ok-Hwa

2015-02-01

Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)×1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered.

Alveolar ridge preservation with deproteinized bovine bone graft and collagen membrane and delayed implants.

PubMed

Pang, Chaoyuan; Ding, Yuxiang; Zhou, Hongzhi; Qin, Ruifeng; Hou, Rui; Zhang, Guoliang; Hu, Kaijin

2014-09-01

To evaluate clinically and radiographically an alveolar ridge, preservation technique with deproteinized bovine bone graft and absorbable collagen membrane and then restoration with delayed implants were done. The study included 30 patients. The trial group's sockets were filled with deproteinized bovine bone graft (Bio-Oss) and covered with absorbable collagen membrane (Bio-Gide). The control group's sockets healed without any treatment. Panoramic radiograph and computed tomography were taken immediately after graft and 3 and 6 months later to evaluate the height, width, and volume change of the alveolar ridge bone. Dental implants were inserted in all sockets at 6 months, and osseointegration condition was evaluated in the following 12 months. All sockets healed uneventfully. In the trial group, the mean (SD) height reduction of the alveolar ridge bone was 1.05 (0.24) mm at 3 months and 1.54 (0.25) mm at 6 months. The width reduction was 1.11 (0.13) mm at 3 months and 1.84 (0.35) mm at 6 months. Bone volume reduction was 193.79 (21.47) mm at 3 months and 262.06 (33.08) mm at 6 months. At the same trend, in the control group, the bone height reduction was 2.12 (0.15) mm at 3 months and 3.26 (0.29) mm at 6 months. The width reduction was 2.72 (0.19) mm at 3 months and 3.56 (0.28) mm at 6 months. Bone volume reduction was 252.19 (37.21) mm at 3 months and 342.32 (36.41) mm at 6 months. There was a significant difference in alveolar ridge bone height, width, and volume reduction in the 2 groups. The osseointegration condition had no significant difference between the 2 groups. This study suggested that the deproteinized bovine bone graft and absorbable collagen membrane were beneficial to preserve the alveolar ridge bone and had no influence on the osseointegration of delayed implant.

Delayed Union of a Sacral Fracture: Percutaneous Navigated Autologous Cancellous Bone Grafting and Screw Fixation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huegli, R. W.; Messmer, P.; Jacob, A. L.

2003-09-15

Delayed or non-union of a sacral fracture is a serious clinical condition that may include chronic pain, sitting discomfort, gait disturbances, neurological problems, and inability to work. It is also a difficult reconstruction problem. Late correction of the deformity is technically more demanding than the primary treatment of acute pelvic injuries. Open reduction, internal fixation (ORIF), excision of scar tissue, and bone grafting often in a multi-step approach are considered to be the treatment of choice in delayed unions of the pelvic ring. This procedure implies the risk of neurological and vascular injuries, infection, repeated failure of union, incomplete correctionmore » of the deformity, and incomplete pain relief as the most important complications. We report a new approach for minimally invasive treatment of a delayed union of the sacrum without vertical displacement. A patient who suffered a Malgaigne fracture (Tile C1.3) was initially treated with closed reduction and percutaneous screw fixation (CRPF) of the posterior pelvic ring under CT navigation and plating of the anterior pelvic ring. Three months after surgery he presented with increasing hip pain caused by a delayed union of the sacral fracture. The lesion was successfully treated percutaneously in a single step procedure using CT navigation for drilling of the delayed union, autologous bone grafting, and screw fixation.« less

Dysosteosclerosis Presents as an “Osteoclast-Poor” Form of Osteopetrosis: Comprehensive Investigation of a 3-Year-Old Girl and Literature Review

PubMed Central

Whyte, Michael P; Wenkert, Deborah; McAlister, William H; Novack, Deborah V; Nenninger, Angie R; Zhang, Xiafang; Huskey, Margaret; Mumm, Steven

2010-01-01

Dysosteosclerosis (DSS), an extremely rare dense bone disease, features short stature and fractures and sometimes optic atrophy, cranial nerve palsy, developmental delay, and failure of tooth eruption in infancy or early childhood consistent with osteopetrosis (OPT). Bone histology during childhood shows unresorbed primary spongiosa from deficient osteoclast action. Additionally, there is remarkable progressive flattening of all vertebrae and, by adolescence, paradoxical metaphyseal osteopenia with thin cortical bone. Reports of consanguinity indicate autosomal recessive inheritance, yet more affected males than females suggest X-linked recessive inheritance. We investigated a nonconsanguineous girl with DSS. Osteosclerosis was discovered at age 7 months. Our studies, spanning ages 11 to 44 months, showed weight at approximately 50th percentile, and length diminishing from approximately 30th percentile to –2.3 SD. Head circumference was +4 SD. The patient had frontal bossing, blue sclera, normal teeth, genu valgum, and unremarkable joints. Radiographs showed orbital and facial sclerosis, basilar thickening, bone-in-bone appearance of the pelvis, sclerotic long bone ends, and fractures of ribs and extremities. Progressive metaphyseal widening occurred as vertebrae changed from ovoid to flattened and became beaked anteriorly. A hemogram was normal. Consistent with OPT, serum parathyroid hormone (PTH) concentrations reflected dietary calcium levels. Serum bone alkaline phosphatase, osteocalcin, and TRACP-5b were subnormal. The iliac crest contained excessive primary spongiosa and no osteoclasts. No mutations were identified in the splice sites or exons for the genes encoding chloride channel 7, T-cell immune regulator 1, OPT-associated transmembrane protein 1, and monocyte colony-stimulating factor (M-CSF) and its receptor C-FMS, ANKH, OPG, RANK, and RANKL. Genomic copy-number microarray was unrevealing. Hence, DSS is a distinctive OPT of unknown etiology featuring osteoclast deficiency during early childhood. How osteopenia follows is an enigma of human skeletal pathobiology. © 2010 American Society for Bone and Mineral Research. PMID:20499338

Whole body BMC in pediatric Crohn disease: independent effects of altered growth, maturation, and body composition.

PubMed

Burnham, Jon M; Shults, Justine; Semeao, Edisio; Foster, Bethany; Zemel, Babette S; Stallings, Virginia A; Leonard, Mary B

2004-12-01

Whole body BMC was assessed in 104 children and young adults with CD and 233 healthy controls. CD was associated with significant deficits in BMC and lean mass, relative to height. Adjustment for lean mass eliminated the bone deficit in CD. Steroid exposure was associated with short stature but not bone deficits relative to height. Children with Crohn disease (CD) have multiple risk factors for impaired bone accrual. The confounding effects of poor growth and delayed maturation limit the interpretation of prior studies of bone health in CD. The objective of this study was to assess BMC relative to growth, body composition, and maturation in CD compared with controls. Whole body BMC and lean mass were assessed by DXA in 104 CD subjects and 233 healthy controls, 4-26 years of age. Multivariable linear regression models were developed to sequentially adjust for differences in skeletal size, pubertal maturation, and muscle mass. BMC-for-height z scores were derived to determine CD-specific covariates associated with bone deficits. Subjects with CD had significantly lower height z score, body mass index z score, and lean mass relative to height compared with controls (all p < 0.0001). After adjustment for group differences in age, height, and race, the ratio of BMC in CD relative to controls was significantly reduced in males (0.86; 95% CI, 0.83, 0.94) and females (0.91; 95% CI, 0.85, 0.98) with CD. Adjustment for pubertal maturation did not alter the estimate; however, addition of lean mass to the model eliminated the bone deficit. Steroid exposure was associated with short stature but not bone deficits. This study shows the importance of considering differences in body size and composition when interpreting DXA data in children with chronic inflammatory conditions and shows an association between deficits in muscle mass and bone in pediatric CD.

Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing.

PubMed

Jäger, Marten; Ott, Claus-Eric; Grünhagen, Johannes; Hecht, Jochen; Schell, Hanna; Mundlos, Stefan; Duda, Georg N; Robinson, Peter N; Lienau, Jasmin

2011-03-24

The sheep is an important model organism for many types of medically relevant research, but molecular genetic experiments in the sheep have been limited by the lack of knowledge about ovine gene sequences. Prior to our study, mRNA sequences for only 1,556 partial or complete ovine genes were publicly available. Therefore, we developed a composite de novo transcriptome assembly method for next-generation sequence data to combine known ovine mRNA and EST sequences, mRNA sequences from mouse and cow, and sequences assembled de novo from short read RNA-Seq data into a composite reference transcriptome, and identified transcripts from over 12 thousand previously undescribed ovine genes. Gene expression analysis based on these data revealed substantially different expression profiles in standard versus delayed bone healing in an ovine tibial osteotomy model. Hundreds of transcripts were differentially expressed between standard and delayed healing and between the time points of the standard and delayed healing groups. We used the sheep sequences to design quantitative RT-PCR assays with which we validated the differential expression of 26 genes that had been identified by RNA-seq analysis. A number of clusters of characteristic expression profiles could be identified, some of which showed striking differences between the standard and delayed healing groups. Gene Ontology (GO) analysis showed that the differentially expressed genes were enriched in terms including extracellular matrix, cartilage development, contractile fiber, and chemokine activity. Our results provide a first atlas of gene expression profiles and differentially expressed genes in standard and delayed bone healing in a large-animal model and provide a number of clues as to the shifts in gene expression that underlie delayed bone healing. In the course of our study, we identified transcripts of 13,987 ovine genes, including 12,431 genes for which no sequence information was previously available. This information will provide a basis for future molecular research involving the sheep as a model organism.

Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing

PubMed Central

2011-01-01

Background The sheep is an important model organism for many types of medically relevant research, but molecular genetic experiments in the sheep have been limited by the lack of knowledge about ovine gene sequences. Results Prior to our study, mRNA sequences for only 1,556 partial or complete ovine genes were publicly available. Therefore, we developed a composite de novo transcriptome assembly method for next-generation sequence data to combine known ovine mRNA and EST sequences, mRNA sequences from mouse and cow, and sequences assembled de novo from short read RNA-Seq data into a composite reference transcriptome, and identified transcripts from over 12 thousand previously undescribed ovine genes. Gene expression analysis based on these data revealed substantially different expression profiles in standard versus delayed bone healing in an ovine tibial osteotomy model. Hundreds of transcripts were differentially expressed between standard and delayed healing and between the time points of the standard and delayed healing groups. We used the sheep sequences to design quantitative RT-PCR assays with which we validated the differential expression of 26 genes that had been identified by RNA-seq analysis. A number of clusters of characteristic expression profiles could be identified, some of which showed striking differences between the standard and delayed healing groups. Gene Ontology (GO) analysis showed that the differentially expressed genes were enriched in terms including extracellular matrix, cartilage development, contractile fiber, and chemokine activity. Conclusions Our results provide a first atlas of gene expression profiles and differentially expressed genes in standard and delayed bone healing in a large-animal model and provide a number of clues as to the shifts in gene expression that underlie delayed bone healing. In the course of our study, we identified transcripts of 13,987 ovine genes, including 12,431 genes for which no sequence information was previously available. This information will provide a basis for future molecular research involving the sheep as a model organism. PMID:21435219

In vivo quantification of bone-fluorine by delayed neutron activation analysis: a pilot study of hand-bone-fluorine levels in a Canadian population.

PubMed

Chamberlain, Mike; Gräfe, James L; Aslam; Byun, Soo-Hyun; Chettle, David R; Egden, Lesley M; Webber, Colin E; McNeill, Fiona E

2012-03-01

Humans can be exposed to fluorine (F) through their diet, occupation, environment and oral dental care products. Fluorine, at proper dosages, is believed to have positive effects by reducing the incidence of dental caries, but fluorine toxicity can occur when people are exposed to excessive quantities of fluorine. In this paper we present the results of a small pilot in vivo study on 33 participants living in Southwestern Ontario, Canada. The mean age of participants was 45 ± 18 years with a range of 20-87 years. The observed calcium normalized hand-bone-fluorine concentrations in this small pilot study ranged from 1.1 to 8.8 mg F/g Ca. Every person measured in this study had levels of fluorine in bone above the detection limit of the system. The average fluorine concentration in bone was found to be 3.5 ± 0.4 mg F/g Ca. No difference was observed in average concentration for men and women. In addition, a significant correlation (r(2) = 0.55, p < 0.001) was observed between hand-bone-fluorine content and age. The amount of fluorine was found to increase at a rate of 0.084 ± 0.014 mg F/g Ca per year. There was no significant difference observed in this small group of subjects between the accumulation rates in men and women. To the best of our knowledge, this is the first time data from in vivo measurement of fluorine content in humans by neutron activation analysis have been presented. The data determined by this technique were found to be consistent with results from ex vivo studies from other countries. We suggest that the data demonstrate that this low risk non-invasive diagnostic technique will permit the routine assessment of bone-fluorine content with potential application in the study of clinical bone-related diseases. This small study demonstrated that people in Southern Ontario are exposed to fluoride in measureable quantities, and that fluoride can be seen to accumulate in bone with age. However, all volunteers were found to have levels below those expected with clinical fluorosis, and only one older subject was found to have levels comparable with preclinical exposure.

The role of calcium in osteoporosis.

PubMed

Arnaud, C D; Sanchez, S D

1990-01-01

Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25-30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. The RDA for age 10-25 is 1200 mg/day. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years old). Starting at age 40-45, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D3. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Available evidence suggests that the impairments of intestinal calcium absorption observed during the menopause and aging can be overcome only by inordinately large calcium intakes (1500 to 2500 mg/day). Since this amount is difficult to derive from the diet, can cause constipation, and may not prevent trabecular bone loss, it should not be used as a substitute for sex hormone replacement. Women taking estrogen replacement should be provided the RDA for calcium of 800 mg/day at a minimum. Those who cannot or will not take estrogen should be asked to ingest at least 1000 to 1500 mg/day of calcium to delay cortical bone loss and prevent secondary hyperparathyroidism. It should be emphasized that up to 2000 mg/day of calcium is safe in teenaged children and adults. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. It is also possible that excessive intakes of phosphate could have a deleterious effect on calcium balance in populations whose need for calcium is great (e.g. growing children) or whose ability to produce 1,25(OH)2D3 is impaired (e.g. the elderly). Moderation in the intake of these nutrients is urged. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g. sex, age, and race) or less controllable (e.g. disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

Extracorporeal shockwave enhanced regeneration of fibrocartilage in a delayed tendon-bone insertion repair model.

PubMed

Chow, Dick Ho Kiu; Suen, Pui Kit; Huang, Le; Cheung, Wing-Hoi; Leung, Kwok-Sui; Ng, Chun; Shi, San Qiang; Wong, Margaret Wan Nar; Qin, Ling

2014-04-01

Fibrous tissue is often formed in delayed healing of tendon bone insertion (TBI) instead of fibrocartilage. Extracorporeal shockwave (ESW) provides mechanical cues and upregulates expression of fibrocartilage-related makers and cytokines. We hypothesized that ESW would accelerate fibrocartilage regeneration at the healing interface in a delayed TBI healing model. Partial patellectomy with shielding at the TBI interface was performed on 32 female New Zealand White Rabbits for establishing this delayed TBI healing model. The rabbits were separated into the control and ESW group for evaluations at postoperative week 8 and 12. Shielding was removed at week 4 and a single ESW treatment was applied at week 6. Fibrocartilage regeneration was evaluated histomorphologically and immunohistochemically. Vickers hardness of the TBI matrix was measured by micro-indentation. ESW group showed higher fibrocartilage area, thickness, and proteoglycan deposition than the control in week 8 and 12. ESW increased expression of SOX9 and collagen II significantly in week 8 and 12, respectively. ESW group showed a gradual transition of hardness from bone to fibrocartilage to tendon, and had a higher Vickers hardness than the control group at week 12. In conclusion, ESW enhanced fibrocartilage regeneration at the healing interface in a delayed TBI healing model. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Testosterone treatment and arginine-induced growth hormone stimulation in male delayed puberty: effects on serum calcium, phosphate and vitamin D metabolites.

PubMed

Hyldstrup, L; Christiansen, C; Nielsen, M D; Transbøl, I

1984-06-01

Hormonal changes after arginine-induced growth hormone stimulation and subsequent testosterone treatment were examined in 5 patients classified as having male delayed puberty. All the patients responded well to growth hormone stimulation and a significant negative correlation was found between the delay in height age and the maximal growth hormone response, r = 0.80, P less than 0.05. The testosterone treatment did not alter this pattern. Changes in PTH, 25OHD, 24.25(OH)2D, and 1.25(OH)2D were examined at 24 h after the infusion. The results showed significant reductions in PTH (P less than 0.05) and 24.25 (OH)2D (P less than 0.05) and a possible increase in 1.25(OH)2D, whereas 25OHD remained unchanged. These results may support the conception of growth hormone as a common denominator of growth and bone metabolism.

Long-Term Retrospective Clinical and Radiographic Follow-up of 205 Brånemark System Mk III TiUnite Implants Submitted to Either Immediate or Delayed Loading.

PubMed

Imburgia, Mario; Del Fabbro, Massimo

2015-10-01

Studies are needed to evaluate long-term performance of immediately loaded implants with moderately rough surface. This retrospective study evaluated long-term survival and periimplant soft and hard tissue conditions in patients treated with TiUnite implants. Forty-one consecutive patients (mean age, 52.6 years) received 205 Brånemark System Mk III TiUnite implants (145 maxillary, 60 mandibular). The indication was single tooth (n = 7 implants), partial (n = 94), or full arches (n = 104). One hundred thirteen implants were immediately loaded. Cumulative survival rate (CSR) of implants was assessed. Long-term marginal bone remodeling, probing pocket depth (PPD), and periimplant mucosa conditions were assessed. Follow-up averaged 8.8 years (range, 6.6-10.6 years). Eight implants in 5 patients failed. CSR was 96.1% (implant basis) and 87.8% (patient basis) up to 10 years. At the longest follow-up, bone loss averaged 0.43 ± 1.15 mm (n = 173), PPD averaged 3.64 ± 0.74 mm, and periimplant mucosa was healthy in 74.6% of cases. Furthermore, 50.3% and 35.5% of implants scored negative for plaque and bleeding, respectively. No significant difference in CSR and hard and soft tissue conditions was found in the long term between immediately and delayed loaded implants. Implants with TiUnite surface demonstrated excellent long-term survival, marginal bone response, and soft tissue conditions, despite a nonoptimal level of oral hygiene.

Extended exposure to alkylator chemotherapy: delayed appearance of myelodysplasia.

PubMed

Chamberlain, Marc C; Raizer, Jeffrey

2009-06-01

A case series of gliomas treated with alkylator-based chemotherapy who subsequently developed myelodysplastic syndrome (tMDS) or acute myelocytic leukemia (AML). Alkylator-based chemotherapy is recognized to be leukemogenic; however, it is infrequently described as a delayed consequence of anti-glioma treatment. Seven patients (4 men; 3 women) ages 34-69 years (median 44), with gliomas (3 Grade 2; 4 Grade 3) were treated with surgery, all but one with involved-field radiotherapy and all with alkylator-based chemotherapy (temozolomide; 6 patients, nitrosoureas; 5 patients, both agents; 5 patients). Exposure to alkylator-based chemotherapy ranged from 8 to 30 months (median 24). The diagnosis of tMDS was determined by bone marrow biopsy in 7 patients. Seven patients showed chromosomal abnormalities consistent with chemotherapy induced MDS. Three patients were diagnosed with AML as well (in two determined by bone marrow and one at autopsy). Interval from last chemotherapy exposure to diagnosis of tMDS/AML ranged from 3 to 31 months (median 24 months). Two patients were treated with bone marrow transplantation and 5 received supportive care only. Five patients have died, 2 as a consequence of recurrent brain tumor, 1 as a complication of transplantation, and 2 due to AML. Although rare, induction of tMDS/AML following extended use of alkylator-based chemotherapy may become more relevant with the evolving practice to treat gliomas for protracted periods. Future work to determine at risk patients would be important.

Immediate Versus Delayed Loading of Implant for Replacement of Missing Mandibular First Molar: A Randomized Prospective Six Years Clinical Study.

PubMed

Chidagam, Prudhvi Raj Lakshmi Venkata; Gande, Vijaya Chandra; Yadlapalli, Sravanthi; Venkata, Ramani Yarlagadda; Kondaka, Sudheer; Chedalawada, Sravya

2017-04-01

Emergence of dental implants made the replacement of missing tooth easy. During the early days of introduction, implants were loaded three to six months after implant insertion, but understanding of healing cascade and improved production technology has changed the phase of restoration from delayed to immediate loading. To evaluate and compare the clinical outcome of immediate and delayed loaded implant supported prosthesis for missing mandibular first molar. The objectives were bleeding on probing, probing depth, implant mobility, marginal bone level and peri-implant radiolucency were evaluated during follow up period. Twenty patients were included in this study who were in the need of fixed implant supported prosthesis for missing mandibular first molar. Single tooth implant with immediate loading done within two days of implant insertion in one group and another group were loaded after three months of implant insertion. These groups were evaluated clinically and radiographically over a period of 72 months after loading using Wilcoxon matched pairs test and Mann-Whitney U test. The study consists of 14 male and six female patients with the age range of 19 to 31 years. There was no bleeding on probing and probing depth remained well within the normal range even after 72 months of loading among both the groups. Minimal marginal bone loss observed with no mobility and peri-implant radiolucency. Implant supported prosthesis for missing mandibular first molar with immediate loading can be used as a successful treatment modality. It reduces treatment time, provides early function and prevents undue migration of adjacent tooth. Immediate loading showed similar clinical and radiographic results as that of delayed loading, indicating it as an equally efficient technique for implant supported prosthesis.

Papineau debridement, Ilizarov bone transport, and negative-pressure wound closure for septic bone defects of the tibia.

PubMed

Karargyris, Orestis; Polyzois, Vasilios D; Karabinas, Panayiotis; Mavrogenis, Andreas F; Pneumaticos, Spyros G

2014-08-01

Ilizarov pioneered bone transport using a circular external fixator. Papineau described a staged technique for the treatment for infected pseudarthrosis of the long bones. This article presents a single-stage Papineau technique and Ilizarov bone transport, and postoperative negative-pressure wound dressing changes for septic bone defects of the tibia. We studied the files of seven patients (mean age, 32 years) with septic bone defects of the tibia treated with a Papineau technique and Ilizarov bone transport in a single stage, followed by postoperative negative-pressure wound dressing changes. All patients had septic pseudarthrosis and skin necrosis of the tibia. The technique included a single-stage extensive surgical debridement of necrotic bone, open bone grafting with cancellous bone autograft and bone transport, and postoperative negative-pressure wound dressing changes for wound closure. The mean time from the initial injury was 6 months (range, 4-8 months). The mean follow-up was 14 months (range, 10-17 months). All patients experienced successful wound healing at a mean of 29 days. Six patients experienced successful bone regeneration and union at the docking side at a mean of 6 months. One patient experienced delayed union at the docking site, which was treated with autologous cancellous bone grafting. Two patients experienced pin track infection, which was successfully treated with antibiotics and pin site dressing changes. All patients were able to return to their work and previous levels of activity, except one patient who had a stiff ankle joint and had to change his job. No patient experienced recurrence of infection, or fracture of the regenerated or transported bone segment until the period of this study. The combined Papineau and Ilizarov bone transport technique with negative-pressure wound closure provides for successful eradication of the infection, reconstruction of the bone defect, and soft-tissue closure. A single-stage surgical treatment is feasible, without any complications.

Acute changes in biochemical markers of bone resorption and formation after Thai traditional massage.

PubMed

Saetung, Sunee; Chailurkit, La-or; Ongphiphadhanakul, Boonsong

2010-07-01

Mechanical loadings by active exercise or passive low amplitude vibration have been demonstrated to enhance bone mass or delay bone loss. Traditional Thai massage can be anabolic to bone due to the application of physical loading on the body in a rhythmic fashion. To explore the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover immediately after the massage. Subjects consisted of 30 healthy females aged 20-40 years. Each subject received Thai traditional massage for 2 hours by a single masseuse. Bone mineral density (BMD) at baseline was measured by dual-energy X-ray absorptiometry (DEXA). C-terminal telopeptide of type 1 collagen (CTx-I) and total procollagen type 1 amino-terminal propeptide (P1NP) were determined by electrochemiluminescence immunoassay. There was a 4.8% increase in serum P1NP concentrations after massage (median 43.4 ng/ml vs. 41.3 ng/ml, p < 0.05). Serum CTx-I also decreased after massage (median 2-hour vs. baseline 0.29 ng/ml vs. 0.31 ng/ml, p < 0.05). There was a nearly significant negative correlation between the percentage change in serum P1NP and BMD at the total femur (r = -0.37, p = 0.056) whereas the statistically significant correlation disappeared between percentage change in bone turnover and the other sites of BMD. Thai traditional massage induces acute changes in bone formation and resorption markers. Study on the more prolonged effects of Thai traditional massage is warranted to explore its implication in the enhancement of bone health.

Characterizing the composition of bone formed during fracture healing using scanning electron microscopy techniques.

PubMed

Perdikouri, Christina; Tägil, Magnus; Isaksson, Hanna

2015-01-01

About 5-10% of all bone fractures suffer from delayed healing, which may lead to non-union. Bone morphogenetic proteins (BMPs) can be used to induce differentiation of osteoblasts and enhance the formation of the bony callus, and bisphosphonates help to retain the newly formed callus. The aim of this study was to investigate if scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) can identify differences in the mineral composition of the newly formed bone compared to cortical bone from a non-fractured control. Moreover, we investigate whether the use of BMPs and bisphosphonates-alone or combined-may have an effect on bone mineralization and composition. Twelve male Sprague-Dawley rats at 9 weeks of age were randomly divided into four groups and treated with (A) saline, (B) BMP-7, (C) bisphosphonates (Zoledronate), and (D) BMP-7 + Zoledronate. The rats were sacrificed after 6 weeks. All samples were imaged using SEM and chemically analyzed with EDS to quantify the amount of C, N, Ca, P, O, Na, and Mg. The Ca/P ratio was the primary outcome. In the fractured samples, two areas of interest were chosen for chemical analysis with EDS: the callus and the cortical bone. In the non-fractured samples, only the cortex was analyzed. Our results showed that the element composition varied to a small extent between the callus and the cortical bone in the fractured bones. However, the Ca/P ratio did not differ significantly, suggesting that the mineralization at all sites is similar 6 weeks post-fracture in this rat model.

Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I.

PubMed

Pievani, Alice; Azario, Isabella; Antolini, Laura; Shimada, Tsutomu; Patel, Pravin; Remoli, Cristina; Rambaldi, Benedetta; Valsecchi, Maria Grazia; Riminucci, Mara; Biondi, Andrea; Tomatsu, Shunji; Serafini, Marta

2015-03-05

Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in mucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-l-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPS IH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring α-l-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear. © 2015 by The American Society of Hematology.

Genetically engineered flavonol enriched tomato fruit modulates chondrogenesis to increase bone length in growing animals.

PubMed

Choudhary, Dharmendra; Pandey, Ashutosh; Adhikary, Sulekha; Ahmad, Naseer; Bhatia, Chitra; Bhambhani, Sweta; Trivedi, Prabodh Kumar; Trivedi, Ritu

2016-02-26

Externally visible body and longitudinal bone growth is a result of proliferation of chondrocytes. In growth disorder, there is delay in the age associated increase in height. The present study evaluates the effect of extract from transgenic tomato fruit expressing AtMYB12 transcription factor on bone health including longitudinal growth. Constitutive expression of AtMYB12 in tomato led to a significantly enhanced biosynthesis of flavonoids in general and the flavonol biosynthesis in particular. Pre-pubertal ovary intact BALB/c mice received daily oral administration of vehicle and ethanolic extract of wild type (WT-TOM) and transgenic AtMYB12-tomato (MYB12-TOM) fruits for six weeks. Animal fed with MYB12-TOM showed no inflammation in hepatic tissues and normal sinusoidal Kupffer cell morphology. MYB12-TOM extract significantly increased tibial and femoral growth and subsequently improved the bone length as compared to vehicle and WT-TOM. Histomorphometry exhibited significantly wider distal femoral and proximal tibial growth plate, increased number and size of hypertrophic chondrocytes in MYB12-TOM which corroborated with micro-CT and expression of BMP-2 and COL-10, marker genes for hypertrophic cells. We conclude that metabolic reprogramming of tomato by AtMYB12 has the potential to improve longitudinal bone growth thus helping in achievement of greater peak bone mass during adolescence.

High energy focused shock wave therapy accelerates bone healing. A blinded, prospective, randomized canine clinical trial.

PubMed

Kieves, N R; MacKay, C S; Adducci, K; Rao, S; Goh, C; Palmer, R H; Duerr, F M

2015-01-01

To evaluate the influence of shock wave therapy (SWT) on radiographic evidence of bone healing after tibial plateau leveling osteotomy (TPLO). Healthy dogs between two to nine years of age that underwent TPLO were randomly assigned to receive either electro-hydraulic SWT (1,000 shocks) or sham treatment (SHAM). Treatment or SHAM was administered to the osteotomy site immediately postoperatively and two weeks postoperatively. Three blinded radiologists evaluated orthogonal radiographs performed eight weeks postoperatively with both a 5-point and a 10-point bone healing scale. Linear regression analysis was used to compare median healing scores between groups. Forty-two dogs (50 stifles) were included in the statistical analysis. No major complications were observed and all osteotomies healed uneventfully. The median healing scores were significantly higher at eight weeks postoperatively for the SWT group compared to the SHAM group for the 10-point (p <0.0002) and 5-point scoring systems (p <0.0001). Shock wave therapy applied immediately and two weeks postoperatively led to more advanced bone healing at the eight week time point in this study population. The results of this study support the use of electro-hydraulic SWT as a means of accelerating acute bone healing of canine osteotomies. Additional studies are needed to evaluate its use for acceleration of bone healing following fracture, or with delayed union.

Bone Marrow Aspirate Concentrate in Animal Long Bone Healing: An Analysis of Basic Science Evidence.

PubMed

Gianakos, Arianna; Ni, Amelia; Zambrana, Lester; Kennedy, John G; Lane, Joseph M

2016-01-01

Long bone fractures that fail to heal or show a delay in healing can lead to increased morbidity. Bone marrow aspirate concentrate (BMAC) containing bone mesenchymal stem cells (BMSCs) has been suggested as an autologous biologic adjunct to aid long bone healing. The purpose of this study was to systematically review the basic science in vivo evidence for the use of BMAC with BMSCs in the treatment of segmental defects in animal long bones. The PubMed/MEDLINE and EMBASE databases were screened in July 14-25, 2014. The following search criteria were used: [("bmac" OR "bone marrow aspirate concentrate" OR "bmc" OR "bone marrow concentrate" OR "mesenchymal stem cells") AND ("bone" OR "osteogenesis" OR "fracture healing" OR "nonunion" OR "delayed union")]. Three authors extracted data and analyzed for trends. Quality of evidence score was given to each study. Results are presented as Hedge G standardized effect sizes with 95% confidence intervals. The search yielded 35 articles for inclusion. Of studies reporting statistics, 100% showed significant increase in bone formation in the BMAC group on radiograph. Ninety percent reported significant improvement in earlier bone healing on histologic/histomorphometric assessment. Eighty-one percent reported a significant increase in bone area on micro-computed tomography. Seventy-eight percent showed a higher torsional stiffness for the BMAC-treated defects. In the in vivo studies evaluated, BMAC confer beneficial effects on the healing of segmental defects in animal long bone models when compared with a control. Proof-of-concept has been established for BMAC in the treatment of animal segmental bone defects.

Multivariate linear regression analysis to identify general factors for quantitative predictions of implant stability quotient values

PubMed Central

Huang, Hairong; Xu, Zanzan; Shao, Xianhong; Wismeijer, Daniel; Sun, Ping; Wang, Jingxiao

2017-01-01

Objectives This study identified potential general influencing factors for a mathematical prediction of implant stability quotient (ISQ) values in clinical practice. Methods We collected the ISQ values of 557 implants from 2 different brands (SICace and Osstem) placed by 2 surgeons in 336 patients. Surgeon 1 placed 329 SICace implants, and surgeon 2 placed 113 SICace implants and 115 Osstem implants. ISQ measurements were taken at T1 (immediately after implant placement) and T2 (before dental restoration). A multivariate linear regression model was used to analyze the influence of the following 11 candidate factors for stability prediction: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting, insertion torque, I-stage or II-stage healing pattern, implant diameter, implant length and T1-T2 time interval. Results The need for bone grafting as a predictor significantly influenced ISQ values in all three groups at T1 (weight coefficients ranging from -4 to -5). In contrast, implant diameter consistently influenced the ISQ values in all three groups at T2 (weight coefficients ranging from 3.4 to 4.2). Other factors, such as sex, age, I/II-stage implantation and bone type, did not significantly influence ISQ values at T2, and implant length did not significantly influence ISQ values at T1 or T2. Conclusions These findings provide a rational basis for mathematical models to quantitatively predict the ISQ values of implants in clinical practice. PMID:29084260

Parathyroid hormone and bone healing.

PubMed

Ellegaard, M; Jørgensen, N R; Schwarz, P

2010-07-01

Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.

A variant microcephalic osteodysplastic slender-bone disorder with growth hormone deficiency and a pigmentary retinopathy.

PubMed

Maclean, K; Ambler, G; Flaherty, M; Kozlowski, K; Adès, L C

2002-10-01

We present the case of a 3-year-old boy with post-natal growth failure, microcephaly, developmental delay, facial dysmorphism, an evolving pigmentary retinopathy, pituitary hypoplasia, micropenis, and growth hormone (GH) deficiency. He has a microcephalic osteodysplastic slender-bone disorder with disharmonic delayed osseous maturation, most closely resembling patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). Intrauterine growth retardation, a universal finding in the MOPD II, was absent in our patient.

Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development

NASA Technical Reports Server (NTRS)

Simske, Steven J.; Bateman, Ted A.; Smith, Erin E.; Ferguson, Virginia L.; Chapes, Stephen K.

2002-01-01

We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.

Delayed Implants Outcome in Maxillary Molar Region.

PubMed

Crespi, Roberto; Capparè, Paolo; Crespi, Giovanni; Gastaldi, Giorgio; Gherlone, Enrico F

2017-04-01

The aim of the present study was to assess bone volume changes in maxillary molar regions after delayed implants placement. Patients presented large bone defects after tooth extractions. Reactive soft tissue was left into the defects. No grafts were used. Cone beam computed tomography (CBCT) scans were performed before tooth extractions, at implant placement (at 3 months from extraction) and 3 years after implant placement, bone volume measurements were assessed. Bucco-lingual width showed a statistically significant decrease (p = .013) at implant placement, 3 months after extraction. Moreover, a statistically significant increase (p < .01) was measured 3 years after implant placement. No statistically significant differences (p > .05) were found between baseline values (before extraction) and at 3 years from implant placement. Vertical dimension showed no statistically significant differences (p > .05) at implant placement, 3 months after extraction. Statistically significant differences (p < .0001) were found between baseline values (before extraction) and at 3 months from implant placement as well as between implant placement values and 3 years later. CT scans presented successful outcome of delayed implants placed in large bone defects at 3-year follow-up. © 2016 Wiley Periodicals, Inc.

Coupled external fixator and skin flap transposition for treatment of exposed and nonunion bone.

PubMed

Zhao, Yong-gang; Ding, Jing; Wang, Neng

2011-02-01

To discuss the effect of coupled external fixator and skin flap transposition on exposed and nonunion bones. The data of 12 cases of infected nonunion and exposed bone following open fracture treated in our hospital during the period of March 1998 to June 2008 were analysed. There were 10 male patients, 2 female patients, whose age were between 19-52 years and averaged 28 years. There were 10 tibial fractures and 2 femoral fractures. The course of diseases lasted for 12-39 months with the mean period of 19 months. All the cases were treated by the coupled external fixator and skin flap transposition. Primary healing were achieved in 10 cases and delayed healing in 2 cases in whom the tibia was exposed due to soft tissue defect and hence local flap transposition was performed. All the 12 cases had bony union within 6-12 months after operation with the average time of 8 months. They were followed up for 1-3 years and all fractures healed up with good function and no infection recurrence. The coupled external fixator and skin flap transposition therapy have shown optimal effects on treating infected, exposed and nonunion bones.

Factors associated with nonunion, delayed union, and malunion in foot and ankle surgery in diabetic patients.

PubMed

Shibuya, Naohiro; Humphers, Jon M; Fluhman, Benjamin L; Jupiter, Daniel C

2013-01-01

The incidence of bone healing complications in diabetic patients is believed to be high after foot and ankle surgery. Although the association of hyperglycemia with bone healing complications has been well documented, little clinical information is available to show which diabetes-related comorbidities directly affect bone healing. Our goal was to better understand the risk factors associated with poor bone healing in the diabetic population through an exploratory, observational, retrospective, cohort study. To this end, 165 diabetic patients who had undergone arthrodesis, osteotomy, or fracture reduction were enrolled in the study to assess the risk factors associated with nonunion, delayed union, and malunion after elective and nonelective foot and/or ankle surgery. Bivariate analyses showed that a history of foot ulcer, peripheral neuropathy, and surgery duration were statistically significantly associated with bone healing complications. After adjusting for other covariates, only peripheral neuropathy, surgery duration, and hemoglobin A1c levels >7% were significantly associated statistically with bone healing complications. Of the risk factors we considered, peripheral neuropathy had the strongest association with bone healing complications. Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Treatment of type II and type III open tibia fractures in children.

PubMed

Bartlett, C S; Weiner, L S; Yang, E C

1997-07-01

To determine whether severe open tibial fractures in children behave like similar fractures in adults. A combined retrospective and prospective review evaluated treatment protocol for type II and type III open tibial fractures in children over a ten-year period from 1984 to 1993. Twenty-three fractures were studied in children aged 3.5 to 14.5 (18 boys and 5 girls). There were six type II, eight type IIIA, and nine type IIIB fractures. Type I fractures were not included. Seven fractures were comminuted with significant butterfly fragments or segmental patterns. Treatment consisted of adequate debridement of soft tissues, closure of dead space, and stabilization with external fixation. Bone debridement only included contaminated devitalized bone or devitalized bone without soft tissue coverage. Bone that could be covered despite periosteal stripping was preserved. Clinical and roentgenographic examinations were used to determine time to union. All fractures in this series healed between eight and twenty-six weeks. Wound coverage included two flaps, three skin grafts, and two delayed primary closures. No bone grafts were required. There were no deep infections, growth arrests, or malunions. Follow-up has ranged from six months to four years. Open tibia fractures in children differ from similar fractures in adults in the following ways: soft tissues have excellent healing capacity, devitalized bone that is not contaminated or exposed can be saved and will become incorporated, and external fixation can be maintained until the fracture has healed. Periosteum in young children can form bone even in the face of bone loss.

Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging

PubMed Central

Youm, Yun-Hee; Grant, Ryan W.; McCabe, Laura R.; Albarado, Diana C.; Nguyen, Kim Yen; Ravussin, Anthony; Pistell, Paul; Newman, Susan; Carter, Renee; Laque, Amanda; Münzberg, Heike; Rosen, Clifford J.; Ingram, Donald K.; Salbaum, J. Michael; Dixit, Vishwa Deep

2014-01-01

SUMMARY Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related ‘sterile’ inflammation in both periphery and brain independently of the non-canonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome and astrogliosis. Consistent with the hypothesis that systemic low grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases. PMID:24093676

Bone healing in 2016

PubMed Central

Buza, John A.; Einhorn, Thomas

2016-01-01

Summary Delayed fracture healing and nonunion occurs in up to 5–10% of all fractures, and can present a challenging clinical scenario for the treating physician. Methods for the enhancement of skeletal repair may benefit patients that are at risk of, or have experienced, delayed healing or nonunion. These methods can be categorized into either physical stimulation therapies or biological therapies. Physical stimulation therapies include electrical stimulation, low-intensity pulsed ultrasonography, or extracorporeal shock wave therapy. Biological therapies can be further classified into local or systemic therapy based on the method of delivery. Local methods include autologous bone marrow, autologous bone graft, fibroblast growth factor-2, platelet-rich plasma, platelet-derived growth factor, and bone morphogenetic proteins. Systemic therapies include parathyroid hormone and bisphosphonates. This article reviews the current applications and supporting evidence for the use of these therapies in the enhancement of fracture healing. PMID:27920804

Osteoclasts prefer aged bone.

PubMed

Henriksen, K; Leeming, D J; Byrjalsen, I; Nielsen, R H; Sorensen, M G; Dziegiel, M H; Martin, T John; Christiansen, C; Qvist, P; Karsdal, M A

2007-06-01

We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of aged bones. Osteoclasts resorb aging bone in order to repair damage and maintain the quality of bone. The mechanism behind the targeting of aged bone for remodeling is not clear. We investigated whether bones endogenously possess the ability to control osteoclastic resorption. To biochemically distinguish aged and young bones; we measured the ratio between the age-isomerized betaCTX fragment and the non-isomerized alphaCTX fragment. By measurement of TRACP activity, CTX release, number of TRACP positive cells and pit area/pit number, we evaluated osteoclastogenesis as well as osteoclast resorption on aged and young bones. We found that the alphaCTX/betaCTX ratio is 3:1 in young compared to aged bones, and we found that both alpha and betaCTX are released by osteoclasts during resorption. Osteoclastogenesis was augmented on aged compared to young bones, and the difference was enhanced under low serum conditions. We found that mature osteoclasts resorb more on aged than on young bone, despite unchanged adhesion and morphology. These data indicate that the age of the bone plays an important role in controlling osteoclast-mediated resorption, with significantly higher levels of osteoclast differentiation and resorption on aged bones when compared to young bones.

Use of fibular bone graft and cancellous screw fixation in the management of neglected femur neck fractures in young patients.

PubMed

Khani, Ghulam Mustafa Kaim; Hafeez, Kamran; Bux, Muhammad; Rasheed, Nusrat; Ahmed, Naveed; Anjum, M Perwez

2017-01-01

To present the clinical outcome of patients with neglected femur neck fracture treated with fibular bone graft. During May 2010-February 2013, 15 patients younger than 35 years of age with neglected fracture neck of femur were managed with non-vascularized fibular graft and cannulated screws. Fractures were classified according to Sandhu Classification. Hip function was assessed using Harris hip score. Fifteen patients with mean age of 28.67 years were managed. Mean period of delay from injury to presentation was 3.07 months. Mean follow-up was 18.5 months. Union was achieved in 13 cases. 2 patients developed nonunion with progression of avascular necrosis (AVN). Patients with healed fracture did not show radiological signs of AVN till the past follow-up. Functional status was evaluated at 6 months according to Harris hip score and was poor in 2 patients, fair in 2 patients, good in 6 patients, and excellent in 5 patients. Fibular graft along with two cancellous screws proved to be an effective technique in our cases with neglected femur neck fractures.

In Vivo Hypobaric Hypoxia Performed During the Remodeling Process Accelerates Bone Healing in Mice

PubMed Central

Durand, Marjorie; Collombet, Jean-Marc; Frasca, Sophie; Begot, Laurent; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2014-01-01

We investigated the effects of respiratory hypobaric hypoxia on femoral bone-defect repair in mice because hypoxia is believed to influence both mesenchymal stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb immobilization in patients suffering from bone trauma, our hypoxic mouse model was further subjected to hind-limb unloading. A hole was drilled in the right femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected to hind-limb unloading for 1 week. Seven days after surgery, mice were either housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic conditions. Unsuspended control mice were housed in either hypobaric or normoxic conditions. Animals were sacrificed on postsurgery day 11 to allow for collection of both contralateral and lesioned femurs, blood, and spleen. As assessed by microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect and the newly synthesized bone volume in the cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric data suggested that bone-repair improvement likely results from the acceleration of the natural bone-healing process rather than from extended mobilization of MSC-derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond delayed hypoxia-enhanced bone-healing efficiency. PMID:24944208

Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair.

PubMed

Scanlon, Vanessa; Soung, Do Yu; Adapala, Naga Suresh; Morgan, Elise; Hansen, Marc F; Drissi, Hicham; Sanjay, Archana

2015-01-01

Mice in which Cbl is unable to bind PI3K (YF mice) display increased bone volume due to enhanced bone formation and repressed bone resorption during normal bone homeostasis. We investigated the effects of disrupted Cbl-PI3K interaction on fracture healing to determine whether this interaction has an effect on bone repair. Mid-diaphyseal femoral fractures induced in wild type (WT) and YF mice were temporally evaluated via micro-computed tomography scans, biomechanical testing, histological and histomorphometric analyses. Imaging analyses revealed no change in soft callus formation, increased bony callus formation, and delayed callus remodeling in YF mice compared to WT mice. Histomorphometric analyses showed significantly increased osteoblast surface per bone surface and osteoclast numbers in the calluses of YF fractured mice, as well as increased incorporation of dynamic bone labels. Furthermore, using laser capture micro-dissection of the fracture callus we found that cells lacking Cbl-PI3K interaction have higher expression of Osterix, TRAP, and Cathepsin K. We also found increased expression of genes involved in propagating PI3K signaling in cells isolated from the YF fracture callus, suggesting that the lack of Cbl-PI3K interaction perhaps results in enhanced PI3K signaling, leading to increased bone formation, but delayed remodeling in the healing femora.

Therapeutic Strategies for Bone Metastases and Their Clinical Sequelae in Prostate Cancer

PubMed Central

Autio, Karen A.; Scher, Howard I.

2013-01-01

Opinion statement Skeletal metastases threaten quality of life, functionality, and longevity in patients with metastatic castration-resistant prostate cancer (mCRPC). Therapeutic strategies for bone metastases in prostate cancer can palliate pain, delay/prevent skeletal complications, and prolong survival. Pharmacologic agents representing several drug classes have demonstrated the ability to achieve these treatment goals in men with mCRPC. Skeletal-related events such as fracture and the need for radiation can be delayed using drugs that target the osteoclast/osteoblast pathway. Cancer-related bone pain can be palliated using beta-emitting bone-seeking radiopharmaceuticals such as samarium-153 EDTMP and strontium-89. Also, prospective randomized studies have demonstrated that cytotoxic chemotherapy can palliate bone pain. For the first time, bone-directed therapy has been shown to prolong survival using the novel alpha-emitting radiopharmaceutical radium-223. Given these multifold clinical benefits, treatments targeting bone metabolism, tumor-bone stromal interactions, and bone metastases themselves are now central elements of routine clinical care. Decisions about which agents, alone or in combination, will best serve the patient’s and clinician’s clinical goals is contingent on the treatment history to date, present disease manifestations, and symptomatology. Clinical trials exploring novel agents such as those targeting c-Met and Src are under way, using endpoints that directly address how patients feel, function, and survive. PMID:22528368

Sotos Syndrome. Clinical Exchange.

ERIC Educational Resources Information Center

Shuey, Elaine M.; Jamison, Kristen

1996-01-01

Sotos syndrome is characterized by high birth length, rapid bone growth, distinctive facial features, and possible verbal and motor delays. It is more common in males than females. Developmental deficits, specific learning problems, and speech/language delays may also occur. (DB)

The effect of carprofen on selected markers of bone metabolism in dogs with chronic osteoarthritis.

PubMed

Liesegang, A; Limacher, S; Sobek, A

2007-08-01

The purpose of this study was to investigate the effect of the nonsteroidal anti-inflammatory drug carprofen on bone turnover and to monitor the progress of chronic osteoarthritic dogs by measuring different bone markers and radiographic evalutation of the corresponding joints. For this purpose 20 dogs of different ages and weight were devided into 2 groups. Ten dogs were assigned to Group R, treated with carprofen, and ten dogs to Group C, which had no treatment. Radiographs of the affected joints were reviewed initially and six months later at the end of the experiment. Blood was taken 8 times from each dog. Four bone markers (Osteocalcin (OC), bone-specific alkaline phosphatase (bAP), carboxyterminal telopeptide of type I collagen (ICTP), serum CrossLaps (CTX) as well as 1,25-(OH)2-Vitamin D and parathyroid hormone (PTH) were monitored for 6 months. No significant group effects on bone markers were notied. In Group R a decrease in ICTP concentrations during the first three months and a significant decrease in CTX concentrations in the first two months of the study were observed. The bone formation marker bAP revealed a significant decrease throughout the experiment. Three dogs of Group C and one dog of Group R showed osteoarthritic progression in the radiographs. The significant decrease of CTX indicates that carprofentreatment could have a retarding effect on the progression of osteoarthritis. Radiological findings suggest that carprofen may delay osteophyte formation. The monitoring of focal metabolic processes as in bone of a osteoarthrotic joint is difficult, since the bone mass is very active and metabolic processes may have an influence on the monitoring.

[Progressive bone lengthening of the hand in congenital malformations. 41 cases].

PubMed

Foucher, G; Pajardi, G; Lamas, C; Medina, J; Navarro, R

2001-09-01

We retrospectively reviewed the experience of two Hand Units with progressive bone distraction lengthening, collecting 41 cases of hand skeleton lengthening for congenital malformations. The Ilizarov callostasis method was used in 31 cases and in 10 cases bone union was reestablished at a second stage with an iliac graft (2 cases), vascularized metacarpal bone graft (one case), and vascularized (one case) or nonvascularized (3 cases) toe epiphysis. In the last three cases of index lengthening, the distal part was translocated to the tip of the third, deepening at the same stage the first web. The most frequently treated malformation was symbrachydactyly (22 cases). Mean lengthening was 2.3 cm (0.9 to 3.5) with a mean treatment duration of 3.8 months (1.5 - 8.2). The "lengthening index" was 0.59. There was a significant difference between phalanx and metacarpal lengthening, but the amount of lengthening or treatment duration were not affected by technique (Ilizarov vs bone grafting) or age. The complication rate was 32%. There were two complete failures, one extensor tendon tear, 3 pin tract infections (one requiring interruption of the lengthening), 2 cases of relevant pain, 2 delayed unions, 2 angulations and 1 callus fracture, 1 metacarpophalangeal dislocation and 1 joint stiffness. Despite advances in micorsurgical toe transfer, there are still indications for bone lengthening in congenital malformations. The apparent simplicity of the technique can mask a certain number of complications, emphasizing the need for surgical experience. Progressive bone lengthening in congenital deformity has the advantage of preserving sensitivity and avoiding bone resorption. Callostasis does not increase the duration of treatment compared to bone graft.

Operative stabilization of open long bone fractures: A tropical tertiary hospital experience

PubMed Central

Ifesanya, Adeleke O.; Alonge, Temitope O.

2012-01-01

Background: Operative treatment of open fractures in our environment is fraught with problems of availability of theater space, appropriate hardware, and instrumentation such that high complication rates may be expected. Materials and Methods: We evaluated all open long bone fractures operatively stabilized at our center to determine the outcome of the various treatment modalities as well as the determinant factors. Result: A total of 160 patients with 171 fractures treated between December 1995 and December 2008 were studied. There were twice as many males; mean age was 35.0 years. About half were open tibia fractures. Gustilo IIIa and IIIb fractures each accounted for 56 cases (45.2%). Fifty-three percent were stabilized within the first week of injury. Interval between injury and operative fixation averaged 11.1 days. Anderson-Hutchin's technique was employed in 27 cases (21.8%), external fixation in 21 (16.9%), plate osteosynthesis in 50 (40.3%), and intramedullary nail 15 cases (12.1%). Mean time to union was 24.7 weeks. Fifty-two complications occurred in 50 fractures (40.3%) with joint stiffness and chronic osteomyelitis each accounting for a quarter of the complications. Union was delayed in grade IIIb open fractures and those fractures treated with external fixation. Conclusion: A significant proportion of open long bone fractures we operatively treated were severe. Severe open fractures (type IIIb) with concomitant stabilization using external fixation delayed fracture union. While we recommend intramedullary devices for open fractures, in our setting where locking nails are not readily available, external fixation remains the safest choice of skeletal stabilization particularly when contamination is high. PMID:23271839

Changes in biomechanical strain and morphology of rat calvarial sutures and bone after Tgf-β3 inhibition of posterior interfrontal suture fusion.

PubMed

Shibazaki-Yorozuya, Reiko; Wang, Qian; Dechow, Paul C; Maki, Koutaro; Opperman, Lynne A

2012-06-01

Craniofacial sutures are bone growth fronts that respond and adapt to biomechanical environments. Little is known of the role sutures play in regulating the skull biomechanical environment during patency and fusion conditions, especially how delayed or premature suture fusion will impact skull biomechanics. Tgf-β3 has been shown to prevent or delay suture fusion over the short term in rat skulls, yet the long-term patency or its consequences in treated sutures is not known. It was therefore hypothesized that Tgf-β3 had a long-term impact to prevent suture fusion and thus alter the skull biomechanics. In this study, collagen gels containing 3 ng Tgf-β3 were surgically placed superficial to the posterior interfrontal suture (IFS) and deep to the periosteum in postnatal day 9 (P9) rats. At P9, P24, and P70, biting forces and strains over left parietal bone, posterior IFS, and sagittal suture were measured with masticatory muscles bilaterally stimulated, after which the rats were sacrificed and suture patency analyzed histologically. Results demonstrated that Tgf-β3 treated sutures showed less fusion over time than control groups, and strain patterns in the skulls of the Tgf-β3-treated group were different from that of the control group. Although bite force increased with age, no alterations in bite force were attributable to Tgf-β3 treatment. These findings suggest that the continued presence of patent sutures can affect strain patterns, perhaps when higher bite forces are present as in adult animals. Copyright © 2012 Wiley Periodicals, Inc.

Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing.

PubMed

Rodriguez-Menocal, Luis; Shareef, Shahjahan; Salgado, Marcela; Shabbir, Arsalan; Van Badiavas, Evangelos

2015-03-13

Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.

[Decline in renal function in old age : Part of physiological aging versus age-related disease].

PubMed

Braun, F; Brinkkötter, P T

2016-08-01

The incidence and prevalence of chronic renal disease (CKD) in elderly patients are continuously increasing worldwide. Loss of renal function is not only considered to be part of the aging process itself but also reflects the multimorbidity of many geriatric patients. Calculating the glomerular filtration rate using specific algorithms validated for the elderly population and measuring the amount of proteinuria allow an estimation of renal function in elderly patients with high accuracy. Chronic renal failure has many clinical consequences and not only results in a delayed excretion of toxins cleared by the kidneys but also affects hematogenesis, water and electrolyte balance as well as mineral bone metabolism. Furthermore, CKD directly leads to and aggravates geriatric syndromes and in particular the onset of frailty. Therapeutic strategies to halt progression of CKD not only comprise treatment of the underlying disease but also efficient blood pressure and diabetic control and the avoidance of nephrotoxic medications.

Cancer-associated bone disease.

PubMed

Rizzoli, R; Body, J-J; Brandi, M-L; Cannata-Andia, J; Chappard, D; El Maghraoui, A; Glüer, C C; Kendler, D; Napoli, N; Papaioannou, A; Pierroz, D D; Rahme, M; Van Poznak, C H; de Villiers, T J; El Hajj Fuleihan, G

2013-12-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations.

Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis.

PubMed

Fang, Fang; Peters, Tracy L; Beard, John D; Umbach, David M; Keller, Jean; Mariosa, Daniela; Allen, Kelli D; Ye, Weimin; Sandler, Dale P; Schmidt, Silke; Kamel, Freya

2017-11-01

Blood lead and bone turnover may be associated with the risk of amyotrophic lateral sclerosis (ALS). We aimed to assess whether these factors were also associated with time from ALS diagnosis to death through a survival analysis of 145 ALS patients enrolled during 2007 in the National Registry of Veterans with ALS. Associations of survival time with blood lead and plasma biomarkers of bone resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay, site of onset, and score on the Revised ALS Functional Rating Scale. Hazard ratios were calculated for each doubling of biomarker concentration. Blood lead, plasma CTX, and plasma PINP were mutually adjusted for one another. Increased lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival, whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42, 0.83), after ALS diagnosis. No interactions were observed between lead or bone turnover and other prognostic indicators. Lead toxicity and bone metabolism may be involved in ALS pathophysiology. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Clinical Features and Risk Factors of Skeletal-Related Events in Genitourinary Cancer Patients with Bone Metastasis: A Retrospective Analysis of Prostate Cancer, Renal Cell Carcinoma, and Urothelial Carcinoma.

PubMed

Owari, Takuya; Miyake, Makito; Nakai, Yasushi; Morizawa, Yosuke; Itami, Yoshitaka; Hori, Shunta; Anai, Satoshi; Tanaka, Nobumichi; Fujimoto, Kiyohide

2018-06-06

The objective of the present study was to report the incidence of skeletal-related events (SREs) and identify risk factors for SREs in patients with genitourinary cancer with newly diagnosed bone metastasis. This retrospective study included 180 patients with bone metastasis from prostate cancer (PCa; n = 111), renal cell carcinoma (RCC; n = 43), and urothelial carcinoma (UC; n = 26). Clinical factors at the time of diagnosis of bone metastasis were evaluated with Cox proportional hazards regression analysis to identify independent risk factors for SREs. During follow-up, 29 (26%) patients with PCa, 30 (70%) with RCC, and 15 (58%) with UC developed SREs. Treatment with bone-modifying agents (BMAs) before the development of SREs and within 6 months from the diagnosis of bone metastasis significantly delayed the time to first SRE as compared to nonuse of BMAs. Multivariate analysis identified type of primary cancer (PCa vs. RCC, PCa vs. UC), performance status, and bone pain as significant independent predictive risk factors for SREs. Treatment with BMAs significantly delayed the development of first SREs. The identified predictors of SREs might be useful to select patients who would benefit most from early treatment with BMAs. © 2018 S. Karger AG, Basel.

Computerized Bone Age Estimation Using Deep Learning Based Program: Evaluation of the Accuracy and Efficiency.

PubMed

Kim, Jeong Rye; Shim, Woo Hyun; Yoon, Hee Mang; Hong, Sang Hyup; Lee, Jin Seong; Cho, Young Ah; Kim, Sangki

2017-12-01

The purpose of this study is to evaluate the accuracy and efficiency of a new automatic software system for bone age assessment and to validate its feasibility in clinical practice. A Greulich-Pyle method-based deep-learning technique was used to develop the automatic software system for bone age determination. Using this software, bone age was estimated from left-hand radiographs of 200 patients (3-17 years old) using first-rank bone age (software only), computer-assisted bone age (two radiologists with software assistance), and Greulich-Pyle atlas-assisted bone age (two radiologists with Greulich-Pyle atlas assistance only). The reference bone age was determined by the consensus of two experienced radiologists. First-rank bone ages determined by the automatic software system showed a 69.5% concordance rate and significant correlations with the reference bone age (r = 0.992; p < 0.001). Concordance rates increased with the use of the automatic software system for both reviewer 1 (63.0% for Greulich-Pyle atlas-assisted bone age vs 72.5% for computer-assisted bone age) and reviewer 2 (49.5% for Greulich-Pyle atlas-assisted bone age vs 57.5% for computer-assisted bone age). Reading times were reduced by 18.0% and 40.0% for reviewers 1 and 2, respectively. Automatic software system showed reliably accurate bone age estimations and appeared to enhance efficiency by reducing reading times without compromising the diagnostic accuracy.

Delayed surgical treatment for neglected or mal-reduced talar fractures.

PubMed

Huang, Peng-Ju; Cheng, Yuh-Min

2005-10-01

From 1993 to 2002, we treated nine patients for neglected or mal-reduced talar fractures. Average patient age was 39 (20-64) years and average follow-up 53 months. The time interval between injury and index operation ranged from 4 weeks to 4 years. Surgical procedures included open reduction with or without bone grafting in six cases, open reduction combined with ankle fusion in one case, talar neck osteotomy in one case, and talar neck osteotomy combined with subtalar fusion in one case. All cases had solid bone union. One patient developed avascular necrosis of the talus needing subsequent ankle arthrodesis. In six patients, adjacent hindfoot arthrosis occurred. The overall AOFAS ankle-hindfoot score was in average 77.4. We conclude that in neglected and mal-reduced talar fractures, surgical treatment can lead to a favourable outcome if the hindfoot joints are not arthritic.

Socket preservation.

PubMed

Fee, L

2017-04-21

Socket preservation maintains bone volume post-extraction in anticipation of an implant placement or fixed partial denture pontic site. This procedure helps compensate for the resorption of the facial bone wall. Socket preservation should be considered when implant placement needs to be delayed for patient or site-related reasons. The ideal healing time before implant placement is six months. Socket preservation can reduce the need for later bone augmentation. By reducing bone resorption and accelerating bone formation it increases implant success and survival. Biomaterials for socket grafting including autograft, allograft, xenograft and alloplast. A bone substitute with a low substitution rate is recommended.

Singer's preferred acoustic condition in performance in an opera house and self-perception of the singer's voice

NASA Astrophysics Data System (ADS)

Noson, Dennis; Kato, Kosuke; Ando, Yoichi

2004-05-01

Solo singers have been shown to over estimate the relative sound pressure level of a delayed, external reproduction of their own voice, singing single syllables, which, in turn, appears to influence the preferred delay of simulated stage reflections [Noson, Ph.D. thesis, Kobe University, 2003]. Bone conduction is thought to be one factor separating singer versus instrumental performer judgments of stage acoustics. Using a parameter derived from the vocal signal autocorrelation function (ACF envelope), the changes in singer preference for delayed reflections is primarily explained by the ACF parameter, rather than internal bone conduction. An auditory model of a singer's preferred reflection delay is proposed, combining the effects of acoustical environment (reflection amplitude), bone conduction, and performer vocal overestimate, which may be applied to the acoustic design of reflecting elements in both upstage and forestage environments of opera stages. For example, soloists who characteristically underestimate external voice levels (or overestimate their own voice) should be provided shorter distances to reflective panels-irrespective of their singing style. Adjustable elements can be deployed to adapt opera houses intended for bel canto style performances to other styles. Additional examples will also be discussed. a)Now at Kumamoto Univ., Kumamoto, Japan. b)Now at: 1-10-27 Yamano Kami, Kumamoto, Japan.

Models of tibial fracture healing in normal and Nf1-deficient mice.

PubMed

Schindeler, Aaron; Morse, Alyson; Harry, Lorraine; Godfrey, Craig; Mikulec, Kathy; McDonald, Michelle; Gasser, Jürg A; Little, David G

2008-08-01

Delayed union and nonunion are common complications associated with tibial fractures, particularly in the distal tibia. Existing mouse tibial fracture models are typically closed and middiaphyseal, and thus poorly recapitulate the prevailing conditions following surgery on a human open distal tibial fracture. This report describes our development of two open tibial fracture models in the mouse, where the bone is broken either in the tibial midshaft (mid-diaphysis) or in the distal tibia. Fractures in the distal tibial model showed delayed repair compared to fractures in the tibial midshaft. These tibial fracture models were applied to both wild-type and Nf1-deficient (Nf1+/-) mice. Bone repair has been reported to be exceptionally problematic in human NF1 patients, and these patients can also spontaneously develop tibial nonunions (known as congenital pseudarthrosis of the tibia), which are recalcitrant to even vigorous intervention. pQCT analysis confirmed no fundamental differences in cortical or cancellous bone in Nf1-deficient mouse tibiae compared to wild-type mice. Although no difference in bone healing was seen in the tibial midshaft fracture model, the healing of distal tibial fractures was found to be impaired in Nf1+/- mice. The histological features associated with nonunited Nf1+/- fractures were variable, but included delayed cartilage removal, disproportionate fibrous invasion, insufficient new bone anabolism, and excessive catabolism. These findings imply that the pathology of tibial pseudarthrosis in human NF1 is complex and likely to be multifactorial.

Pyogenic Sacroiliitis in a 13-Month-Old Child: A Case Report and Literature Review.

PubMed

Leroux, Julien; Julien, Leroux; Bernardini, Isabelle; Isabelle, Bernardini; Grynberg, Lucie; Lucie, Grynberg; Grandguillaume, Claire; Claire, Grandguillaume; Michelin, Paul; Paul, Michelin; Ould Slimane, Mourad; Slimane, Ould Slimane; Nectoux, Eric; Eric, Nectoux; Deroussen, François; François, Deroussen; Gouron, Richard; Richard, Gouron; Angelliaume, Audrey; Audrey, Angelliaume; Ilharreborde, Brice; Brice, Ilharreborde; Renaux-Petel, Mariette; Mariette, Renaux-Petel

2015-10-01

Pyogenic sacroiliitis is exceptional in very young children. Diagnosis is difficult because clinical examination is misleading. FABER test is rarely helpful in very young children. Inflammatory syndrome is frequent. Bone scintigraphy and MRI are very sensitive for the diagnosis. Joint fluid aspiration and blood cultures are useful to identify the pathogen. Appropriate antibiotic therapy provides rapid regression of symptoms and healing. We report the case of pyogenic sacroiliitis in a 13-month-old child.Clinical, biological, and imaging data of this case were reviewed and reported retrospectively.A 13-month-old girl consulted for decreased weight bearing without fever or trauma. Clinical examination was not helpful. There was an inflammatory syndrome. Bone scintigraphy found a sacroiliitis, confirmed on MRI. Aspiration of the sacroiliac joint was performed. Empiric intravenous biantibiotic therapy was started. Patient rapidly recovered full weight bearing. On the 5th day, clinical examination and biological analysis returned to normal. Intravenous antibiotic therapy was switched for oral. One month later, clinical examination and biological analysis were normal and antibiotic therapy was stopped.Hematogenous osteoarticular infections are common in children but pyogenic sacroiliitis is rare and mainly affects older children. Diagnosis can be difficult because clinical examination is poor. Moreover, limping and decreased weight bearing are very common reasons for consultation. This may delay the diagnosis or refer misdiagnosis. Bone scintigraphy is useful to locate a bone or joint disease responsible for limping. In this observation, bone scintigraphy located the infection at the sacroiliac joint. Given the young age, MRI was performed to confirm the diagnosis. Despite the very young age of the patient, symptoms rapidly disappeared with appropriate antibiotic therapy.We report the case of pyogenic sacroiliitis in a 13-month-old child. It reminds the risk of misdiagnosing pyogenic sacroiliitis in children because it is exceptional and clinical examination is rarely helpful. It also highlights the usefulness of bone scintigraphy and MRI in osteoarticular infections in children.

Dental implants typically help retain peri-implant vertical bone height: evidence-based analysis.

PubMed

Greenstein, Gary; Cavallaro, John

2013-01-01

The dental literature is assessed regarding the ability of dental implants to maintain vertical bone height after various implant placement scenarios: immediate, delayed, insertion into partially and fully edentate healed ridges, and under overdentures. Studies are also reviewed to determine if bone loss after implant insertion is continuous. Numerous investigations that support the concept that implants preserve bone height are identified. In addition, the data indicate that a minuscule amount of annual bone loss usually persists after implant placement, but it is often clinically imperceptible.

De morseir syndrome presenting as ambiguous genitalia.

PubMed

Thukral, Anubhav; Chitra, S; Chakraborty, Partho P; Roy, Ajitesh; Goswami, Soumik; Bhattacharjee, Rana; Dutta, Deep; Maisnam, Indira; Ghosh, Sujoy; Mukherjee, Satinath; Chowdhury, Subhankar

2012-12-01

A 10-year-old boy presented with genital ambiguity, poor linear growth, and delayed milestones. The aim and to highlight that although rare but congenital, hypogonadotropic hypogonadism may rarely present as ambiguity. The patient was found to have bilateral cryptorchidism with proximal penile hypospadias, microphallus with a proportionate dwarfism with mildly delayed bone age, and karyotype 46XY. Euthyroid with normal steroid axis, growth hormone insufficient as suggested by auxology, low IGF1, and poor response to clonidine stimulation. MRI brain shows hypoplastic corpus callosum, hypoplastic anterior pituitary, and ectopic posterior pituitary bright spot. The patient underwent laparoscopic removal of right intrabdominal testis and orchidoplexy was performed on the left one. Testicular biopsy revealed no malignancy and growth hormone replacement was initiated. The patient awaits definitive repair of hypospadias. As a provisional diagnosis of combined growth hormone and gonadotropin deficiency, most probable diagnosis is septo-optic dysplasia or de moseir syndrome leading to genital ambiguity.

Plasma concentrations of osteocalcin are associated with the timing of pubertal progress in boys.

PubMed

Schündeln, Michael M; Bäder, Lena; Kiewert, Cordula; Herrmann, Ralf; Führer, Dagmar; Hauffa, Berthold P; Grasemann, Corinna

2017-02-01

Animal models have shown that the skeletal hormone osteocalcin stimulates testicular testosterone synthesis. To assess whether osteocalcin might be a useful marker to detect pubertal development disorders, we examined osteocalcin plasma concentrations in children and adolescents with and without disorders of pubertal development. Osteocalcin concentrations were investigated in a total of 244 patients with endocrine disorders (122 males, mean age: 11.87+3.77 years), including patients with precocious puberty and constitutional delay of puberty. Osteocalcin concentrations were highest among adolescents with precocious puberty and advanced pubertal development (120.60±45.22 ng/mL), while the concentrations were lowest among patients with constitutional delay of puberty (102.20±37.13 ng/mL). Overall, osteocalcin concentrations were strongly correlated with markers of bone metabolism. Although plasma osteocalcin concentrations are associated with pubertal development in boys, it does not appear to be a useful diagnostic marker for altered pubertal development.

[Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual association. Clinical case].

PubMed

Mora-Bautista, Víctor M; Mendoza-Rojas, Víctor; Contreras-García, Gustavo A

2017-06-01

Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients. Sociedad Argentina de Pediatría.

Application of Local Vibrations in Delayed and Non-Union Fractures: a Case Study

NASA Astrophysics Data System (ADS)

Trombetta, Chiara; Abundo, Paolo; Foti, Calogero; Rosato, Nicola

2011-02-01

The aim of the study was to assess the efficacy of local vibration treatments (LV) in delayed-union and non-union fractures, through therapeutic exercise vibration (TEV) practice, analysing the radiological trend. The Medical Engineering Service of the Fondazione Policlinico Tor Vergata in collaboration with the Chair-Department of Rehabilitation Medicine of the University of Rome Tor Vergata and the Boscosystem company, is developing a device dedicated to LV application, to favour bone regeneration and muscle strengthening. This case report analyses the bone activity of a male patient presenting a right tibial fracture, treated with TEV. At the end of the TEV program, clinical results confirmed independent ambulation with disappearance of perimalleolar edema, while radiographic images revealed the presence of bone repair activity around the fracture line.

Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia

PubMed Central

Horiki, Mitsuru; Imamura, Takeshi; Okamoto, Mina; Hayashi, Makoto; Murai, Junko; Myoui, Akira; Ochi, Takahiro; Miyazono, Kohei; Yoshikawa, Hideki; Tsumaki, Noriyuki

2004-01-01

Biochemical experiments have shown that Smad6 and Smad ubiquitin regulatory factor 1 (Smurf1) block the signal transduction of bone morphogenetic proteins (BMPs). However, their in vivo functions are largely unknown. Here, we generated transgenic mice overexpressing Smad6 in chondrocytes. Smad6 transgenic mice showed postnatal dwarfism with osteopenia and inhibition of Smad1/5/8 phosphorylation in chondrocytes. Endochondral ossification during development in these mice was associated with almost normal chondrocyte proliferation, significantly delayed chondrocyte hypertrophy, and thin trabecular bone. The reduced population of hypertrophic chondrocytes after birth seemed to be related to impaired bone growth and formation. Organ culture of cartilage rudiments showed that chondrocyte hypertrophy induced by BMP2 was inhibited in cartilage prepared from Smad6 transgenic mice. We then generated transgenic mice overexpressing Smurf1 in chondrocytes. Abnormalities were undetectable in Smurf1 transgenic mice. Mating Smad6 and Smurf1 transgenic mice produced double-transgenic pups with more delayed endochondral ossification than Smad6 transgenic mice. These results provided evidence that Smurf1 supports Smad6 function in vivo. PMID:15123739

Moore-Federman syndrome and acromicric dysplasia: are they the same entity?

PubMed Central

Winter, R M; Patton, M A; Challener, J; Mueller, R F; Baraitser, M

1989-01-01

Four unrelated patients are reported with short stature, stiffness of the joints, short fingers, inability to make a fist, and thickened skin on the forearms. Investigations have failed to show a lysosomal storage disorder and radiographs show non-specific changes with a delayed carpal bone age. The clinical features in the four children are very similar to the recently described acromicric dysplasia. There are also similarities to Moore-Federman syndrome which has only been described in one family. The case is made that acromicric dysplasia and Moore-Federman syndrome are the same entity. Images PMID:2732993

Congenital hypothyroidism and concurrent renal insufficiency in a kitten.

PubMed

Lim, Chee Kin; Rosa, Chantal T; de Witt, Yolanda; Schoeman, Johan P

2014-11-14

A 3-month-old male domestic short-hair kitten was presented with chronic constipation and disproportionate dwarfism. Radiographs of the long bones and spine revealed delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of congenital primary hypothyroidism was confirmed by low serum total thyroxine and high thyroid stimulating hormone concentrations. Appropriate supplementation of levothyroxine was instituted. The kitten subsequently developed mild renal azotaemia and renal proteinuria, possibly as a consequence of treatment or an unmasked congenital renal developmental abnormality. Early recognition, diagnosis and treatment are vital as alleviation of clinical signs may depend on the cat's age at the time of diagnosis.

Timing of cranioplasty after decompressive craniectomy for trauma.

PubMed

Piedra, Mark P; Nemecek, Andrew N; Ragel, Brian T

2014-01-01

The optimal timing of cranioplasty after decompressive craniectomy for trauma is unknown. The aim of this study was to determine if early cranioplasty after decompressive craniectomy for trauma reduces complications. Consecutive cases of patients who underwent autologous cranioplasty after decompressive craniectomy for trauma at a single Level I Trauma Center were studied in a retrospective 10 year data review. Associations of categorical variables were compared using Chi-square test or Fisher's exact test. A total of 157 patients were divided into early (<12 weeks; 78 patients) and late (≥12 weeks; 79 patients) cranioplasty cohorts. Baseline characteristics were similar between the two cohorts. Cranioplasty operative time was significantly shorter in the early (102 minutes) than the late (125 minutes) cranioplasty cohort (P = 0.0482). Overall complication rate in both cohorts was 35%. Infection rates were lower in the early (7.7%) than the late (14%) cranioplasty cohort as was bone graft resorption (15% early, 19% late), hydrocephalus rate (7.7% early, 1.3% late), and postoperative hematoma incidence (3.9% early, 1.3% late). However, these differences were not statistically significant. Patients <18 years of age were at higher risk of bone graft resorption than patients ≥18 years of age (OR 3.32, 95% CI 1.25-8.81; P = 0.0162). After decompressive craniectomy for trauma, early (<12 weeks) cranioplasty does not alter the incidence of complication rates. In patients <18 years of age, early (<12 weeks) cranioplasty increases the risk of bone resorption. Delaying cranioplasty (≥12 weeks) results in longer operative times and may increase costs.

Automated bone age assessment of older children using the radius

NASA Astrophysics Data System (ADS)

Tsao, Sinchai; Gertych, Arkadiusz; Zhang, Aifeng; Liu, Brent J.; Huang, Han K.

2008-03-01

The Digital Hand Atlas in Assessment of Skeletal Development is a large-scale Computer Aided Diagnosis (CAD) project for automating the process of grading Skeletal Development of children from 0-18 years of age. It includes a complete collection of 1,400 normal hand X-rays of children between the ages of 0-18 years of age. Bone Age Assessment is used as an index of skeletal development for detection of growth pathologies that can be related to endocrine, malnutrition and other disease types. Previous work at the Image Processing and Informatics Lab (IPILab) allowed the bone age CAD algorithm to accurately assess bone age of children from 1 to 16 (male) or 14 (female) years of age using the Phalanges as well as the Carpal Bones. At the older ages (16(male) or 14(female) -19 years of age) the Phalanges as well as the Carpal Bones are fully developed and do not provide well-defined features for accurate bone age assessment. Therefore integration of the Radius Bone as a region of interest (ROI) is greatly needed and will significantly improve the ability to accurately assess the bone age of older children. Preliminary studies show that an integrated Bone Age CAD that utilizes the Phalanges, Carpal Bones and Radius forms a robust method for automatic bone age assessment throughout the entire age range (1-19 years of age).

Bone density and brain atrophy in early Alzheimer's disease.

PubMed

Loskutova, Natalia; Honea, Robyn A; Vidoni, Eric D; Brooks, William M; Burns, Jeffrey M

2009-01-01

Studies suggest a link between bone loss and Alzheimer's disease. To examine bone mineral density (BMD) in early Alzheimer's disease (AD) and its relationship to brain structure and cognition, we evaluated 71 patients with early stage AD (Clinical Dementia Rating (CDR) 0.5 and 1) and 69 non-demented elderly control participants (CDR 0). Measures included whole body BMD by dual energy x-ray absorptiometry (DXA) and normalized whole brain volumes computed from structural MRI scans. Cognition was assessed with a standard neuropsychological test battery. Mean BMD was lower in the early AD group (1.11 +/- 0.13) compared to the non-demented control group (1.16 +/- 0.12, p = 0.02), independent of age, gender, habitual physical activity, smoking, depression, estrogen replacement, and apolipoprotein E4 carrier status. In the early AD group, BMD was related to whole brain volume (b = 0.18, p = 0.03). BMD was also associated with cognitive performance, primarily in tests of memory (logical memory [b = 0.15, p = 0.04], delayed logical memory [b = 0.16, p = 0.02], and the selective reminding task - free recall [b = 0.18, p = 0.009]). BMD is reduced in the earliest clinical stages of AD and associated with brain atrophy and memory decline, suggesting that central mechanisms may contribute to bone loss in early AD.

Use of cervical vertebral dimensions for assessment of children growth.

PubMed

Caldas, Maria de Paula; Ambrosano, Gláucia Maria Bovi; Haiter-Neto, Francisco

2007-04-01

The purpose of this study was to investigate whether skeletal maturation using cephalometric radiographs could be used in a Brazilian population. The study population was selected from the files of the Oral Radiological Clinic of the Dental School of Piracicaba, Brazil and consisted of 128 girls and 110 boys (7.0 to 15.9 years old) who had cephalometric and hand-wrist radiographs taken on the same day. Cervical vertebral bone age was evaluated using the method described by Mito and colleagues in 2002. Bone age was assessed by the Tanner-Whitehouse (TW3) method and was used as a gold standard to determine the reliability of cervical vertebral bone age. An analysis of variance and Tukey's post-hoc test were used to compare cervical vertebral bone age, bone age and chronological age at 5% significance level. The analysis of the Brazilian female children data showed that there was a statistically significant difference (p<0.05) between cervical vertebral bone age and chronological age and between bone age and chronological age. However no statistically significant difference (p>0.05) was found between cervical vertebral bone age and bone age. Differently, the analysis of the male children data revealed a statistically significant difference (p<0.05) between cervical vertebral bone age and bone age and between cervical vertebral bone age and chronological age (p<0.05). The findings of the present study suggest that the method for objectively evaluating skeletal maturation on cephalometric radiographs by determination of vertebral bone age can be applied to Brazilian females only. The development of a new method to objectively evaluate cervical vertebral bone age in males is needed.

Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome.

PubMed

Van Hulle, Severine; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J; De Schepper, Jean

2016-03-05

Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency.

Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome

PubMed Central

Hulle, Severine Van; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J.; Schepper, Jean De

2016-01-01

Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency. PMID:26757742

Bone-Targeting Radiopharmaceuticals for the Treatment of Bone-Metastatic Castration-Resistant Prostate Cancer: Exploring the Implications of New Data

PubMed Central

Saylor, Philip J.; Everly, Jason J.; Sartor, Oliver

2014-01-01

Background. Clinical features of patients with castration-resistant prostate cancer (CRPC) are characterized by a high incidence of bone metastases, which are associated with impairment of quality of life, pain, skeletal-related events (SREs), and a negative impact on prognosis. Advances in the understanding of cancer cell-bone stroma interactions and molecular mechanisms have recently permitted the development of new agents. Purpose. We review the merits, applications, and limitations of emerging data sets on bone-metastatic CRPC with a focus on radium-223, an α-emitting radiopharmaceutical, and its use in therapy for this disease. Methods. References for this review were identified through searches of PubMed and Medline databases, and only papers published in English were considered. Related links in the databases were reviewed, along with relevant published guidelines, recently published abstracts from major medical meetings, and transcripts from a recent round table of clinical investigators. Results. Prior to radium-223, available bone-targeted therapies demonstrated the ability to delay SREs and palliate bone pain in patients with metastatic CRPC but without evidence of improvement in overall survival (OS). In a randomized controlled phase III trial, radium-223 demonstrated the ability to improve OS and delay SREs in docetaxel-pretreated or docetaxel-unfit men with symptomatic bone-metastatic CRPC and was not associated with significantly more grade 3 or 4 adverse events than placebo. Conclusion. Radium-223 has a targeted effect on bone metastases in CRPC and has an important role in docetaxel-pretreated or docetaxel-unfit men with symptomatic bone-metastatic CRPC. PMID:25232039

Ovariectomy-Induced Osteopenia Influences the Middle and Late Periods of Bone Healing in a Mouse Femoral Osteotomy Model.

PubMed

Pang, Jian; Ye, Meina; Gu, Xinfeng; Cao, Yuelong; Zheng, Yuxin; Guo, Hailing; Zhao, Yongfang; Zhan, Hongsheng; Shi, Yinyu

2015-08-01

It is known that bone healing is delayed in the presence of osteoporosis in humans. However, due to the complexities of the healing of osteoporotic fractures, animal models may be more appropriate for studying the effects of osteoporosis in more detail and for testing drugs on the fracture repair process. The purpose of this study was to investigate the influence of ovariectomy-induced osteopenia in bone healing in an open femoral osteotomy model, and to test the feasibility of this model for evaluating the healing process under osteopenic conditions. Ovariectomized (OVX) mouse models were employed to assess the effects of osteopenia on fracture healing, A mid-shaft femur osteotomy model was also established 3 weeks after ovariectomy as an osteopenic fracture group (OVX group). Femurs were then harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT), histology, and biomechanical analysis. A sham-operated group (sham group) was used for comparison. The OVX mice had significantly lower bone volume density (BVF), volumetric bone mineral density (vBMD), and tissue mineral density (TMD) in the fracture calluses at 6 weeks (p<0.05), and similar trend was observed in 2 weeks. Additionally, larger calluses in OVX animals were observed via micro-CT and X-ray, but these did not result in better healing outcomes, as determined by biomechanical test at 6 weeks. Histological images of the healing fractures in the OVX mice found hastening of broken end resorption and delay of hard callus remodeling. The impaired biomechanical measurements in the OVX group (p<0.05) were consistent with micro-CT measurements and radiographic scoring, which also indicated delay in fracture healing of the OVX group. This study provided evidence that ovariectomy-induced osteopenia impair the middle and late bone healing process. These data also supported the validity of the mouse femoral osteotomy model in evaluating the process of bone healing under osteopenic conditions.

In situ accumulation of advanced glycation endproducts (AGEs) in bone matrix and its correlation with osteoclastic bone resorption.

PubMed

Dong, X Neil; Qin, An; Xu, Jiake; Wang, Xiaodu

2011-08-01

Advanced glycation end products (AGEs) have been observed to accumulate in bone with increasing age and may impose effects on bone resorption activities. However, the underlying mechanism of AGEs accumulation in bone is still poorly understood. In this study, human cortical bone specimens from young (31±6years old), middle-aged (51±3years old) and elderly (76±4years old) groups were examined to determine the spatial-temporal distribution of AGEs in bone matrix and its effect on bone resorption activities by directly culturing osteoclastic cells on bone slices. The results of this study indicated that the fluorescence intensity (excitation wave length 360nm and emission wave length 470±40nm) could be used to estimate the relative distribution of AGEs in bone (pentosidine as its marker) under an epifluorescence microscope. Using the fluorescence intensity as the relative measure of AGEs concentration, it was found that the concentration of AGEs varied with biological tissue ages, showing the greatest amount in the interstitial tissue, followed by the old osteons, and the least amount in newly formed osteons. In addition, AGEs accumulation was found to be dependent on donor ages, suggesting that the younger the donor the less AGEs were accumulated in the tissue. Most interestingly, AGEs accumulation appeared to initiate from the region of cement lines, and spread diffusively to the other parts as the tissue aged. Finally, it was observed that the bone resorption activities of osteoclasts were positively correlated with the in situ concentration of AGEs and such an effect was enhanced with increasing donor age. These findings may help elucidate the mechanism of AGEs accumulation in bone and its association with bone remodeling process. Copyright © 2011 Elsevier Inc. All rights reserved.

IN SITU ACCUMULATION OF ADVANCED GLYCATION ENDPRODUCTS (AGES) IN BONE MATRIX AND ITS CORRELATION WITH OSTEOCLASTIC BONE RESORPTION

PubMed Central

Dong, X. Neil; Qin, An; Xu, Jiake; Wang, Xiaodu

2011-01-01

Advanced glycation end products (AGEs) have been observed to accumulate in bone with increasing age and may impose effects on bone resorption activities. However, the underlying mechanism of AGEs accumulation in bone is still poorly understood. In this study, human cortical bone specimens from young (31±6 years old), middle-aged (51±3 years old) and elderly (76±4 years old) groups were examined to determine the spatial-temporal distribution of AGEs in bone matrix and its effect on bone resorption activities by directly culturing osteoclastic cells on bone slices. The results of this study indicated that the fluorescence intensity (excitation wave length 360 nm and emission wave length 470±40 nm) could be used to estimate the relative distribution of AGEs in bone (pentosidine as its marker) under an epifluorescence microscope. Using the fluorescence intensity as the relative measure of AGEs concentration, it was found that the concentration of AGEs varied with biological tissue ages, showing the greatest amount in the interstitial tissue, followed by the old osteons, and the least amount in newly formed osteons. In addition, AGEs accumulation was found to be dependent on donor ages, suggesting that the younger the donor the less AGEs were accumulated in the tissue. Most interestingly, AGEs accumulation appeared to initiate from the region of cement lines, and spread diffusively to the other parts as the tissue aged. Finally, it was observed that the bone resorption activities of osteoclasts were positively correlated with the in situ concentration of AGEs and such an effect was enhanced with increasing donor age. These findings may help elucidate the mechanism of AGEs accumulation in bone and its association with bone remodeling process. PMID:21530698

Short- and long-term (final height) growth responses to growth hormone (GH) therapy in patients with Turner syndrome: correlation of growth response to stimulated GH levels, spontaneous GH secretion, and karyotype.

PubMed

Schmitt, K; Haeusler, G; Blümel, P; Plöchl, E; Frisch, H

1997-01-01

In 41 girls with Turner syndrome, the growth hormone (GH) peak values during stimulation tests and parameters of spontaneous nocturnal GH secretion were studied and compared with respect to different karyotypes, short-term growth response to GH therapy, and final height. 22.0% of the girls tested had a subnormal (peak < 11 ng/ml) and 9.7% a pathological (< 7 ng/ml) GH response. The spontaneous GH secretion showed a good correlation with the data of the provocation tests, providing no further information regarding GH capacity. Short-term growth response to GH treatment could not be predicted by any of the investigated parameters. Although patients with isochromosomes had frequent subnormal GH tests, their growth response to GH treatment after 1 year was comparable to that of girls with XO karyotype and mosaicism. In 18 patients who had reached final height, the height gain during treatment (calculated as final height minus projected adult height) was not different among patients with normal, subnormal, or pathological GH tests. In contrast, final height minus projected adult height in 4 girls with isochromosomes was 15.7 +/- 5.1 versus 7.6 +/- 3.3 cm in 14 patients with other karyotypes (p < 0.01). These girls had a more pronounced bone age delay (3.3 +/- 0.3 vs. 1.8 +/- 1.2 years) at the start of therapy and thus a better growth potential. We conclude that short- and long-term growth responses to GH treatment in Turner syndrome could not be predicted by GH testing. Patients with isochromosomes might represent a subpopulation which is more frequently GH deficient and shows a marked bone age delay.

Cancer-associated bone disease

PubMed Central

Body, J.-J.; Brandi, M.-L.; Cannata-Andia, J.; Chappard, D.; El Maghraoui, A.; Glüer, C.C.; Kendler, D.; Napoli, N.; Papaioannou, A.; Pierroz, D.D.; Rahme, M.; Van Poznak, C.H.; de Villiers, T.J.; El Hajj Fuleihan, G.

2016-01-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations. PMID:24146095

Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis.

PubMed

Ding, Qingfeng; Sun, Peng; Zhou, Hao; Wan, Bowen; Yin, Jian; Huang, Yao; Li, Qingqing; Yin, Guoyong; Fan, Jin

2018-07-01

Intermittent low‑dose injections of parathyroid hormone (PTH) have been reported to exert bone anabolic effects and to promote fracture healing. As an important proangiogenic cytokine, vascular endothelial growth factor (VEGF) is secreted by bone marrow mesenchymal stem cells (BMSCs) and osteoblasts, and serves a crucial regulatory role in the process of vascular development and regeneration. To investigate whether lack of endogenous PTH causes reduced angiogenic capacity and thereby delays the process of fracture healing by downregulating the VEGF signaling pathway, a PTH knockout (PTHKO) mouse fracture model was generated. Fracture healing was observed using X‑ray and micro‑computerized tomography. Bone anabolic and angiogenic markers were analyzed by immunohistochemistry and western blot analysis. The expression levels of VEGF and associated signaling pathways in murine BMSC‑derived osteoblasts were measured by quantitative polymerase chain reaction and western blot analysis. The expression levels of protein kinase A (PKA), phosphorylated‑serine/threonine protein kinase (pAKT), hypoxia‑inducible factor‑1α (HIF1α) and VEGF were significantly decreased in BMSC‑derived osteoblasts from PTHKO mice. In addition, positive platelet endothelial cell adhesion molecule staining was reduced in PTHKO mice, as determined by immunohistochemistry. The expression levels of HIF1α, VEGF, runt‑related transcription factor 2, osteocalcin and alkaline phosphatase were also decreased in PTHKO mice, and fracture healing was delayed. In conclusion, lack of endogenous PTH may reduce VEGF expression in BMSC‑derived osteoblasts by downregulating the activity of the PKA/pAKT/HIF1α/VEGF pathway, thus affecting endochondral bone formation by causing a reduction in angiogenesis and osteogenesis, ultimately leading to delayed fracture healing.

Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas-Deficient (lpr) Mouse Model of Lupus†

PubMed Central

Al-Sebaei, Maisa O; Daukss, Dana M; Belkina, Anna C; Kakar, Sanjeev; Wigner, Nathan A; Cusher, Daniel; Graves, Dana; Einhorn, Thomas; Morgan, Elise; Gerstenfeld, Louis C

2014-01-01

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas-deficient B6.MRL/Faslpr/J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Faslpr/J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Faslpr/J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Faslpr/J mice had elevated Treg cells in both spleens and bones of B6.MRL/Faslpr/J but decreased percentage of activated T cells in bone tissues. Fracture led to ∼30% to 60% systemic increase in Treg cells in both wild-type and B6.MRL/Faslpr/J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Faslpr/J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings suggest that retention of viable chondrocytes locally inhibits osteoclast activity or matrix proteolysis during cartilage resorption. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. PMID:24677136

Differences in Non-Enzymatic Glycation and Collagen Crosslinks between Human Cortical and Cancellous Bone

PubMed Central

Karim, Lamya; Tang, Simon Y.; Sroga, Grażyna E.; Vashishth, Deepak

2015-01-01

Purpose Accumulation of collagen crosslinks (advanced glycation end products [AGEs]) produced by non-enzymatic glycation deteriorates bone's mechanical properties and fracture resistance. Although a single AGE, pentosidine, is commonly used as a representative marker, it is unclear whether it quantitatively reflects total fluorescent AGEs in bone. The goal of this study was to establish the relationship between pentosidine and total AGEs in cancellous and cortical bone. Methods Pentosidine and total AGEs were quantified in 170 human bone samples. Total fluorescent AGEs were measured in 28 additional cancellous and cortical bone specimens of the same apparent volume that were incubated in control or in vitro glycation solutions. Correlations between pentosidine and total AGEs and differences between cortical and cancellous groups were determined. Results Pentosidine was correlated with total AGEs in cancellous bone (r=0.53, p<0.0001) and weakly correlated in cortical bone (r=0.23, p<0.05). There was more pentosidine (p<0.01) and total AGEs (p<0.001) in cancellous than in cortical bone. The in vitro glycation sub-study showed that cancellous bone accumulated more AGEs than cortical bone (p<0.05). Conclusion The relationship between pentosidine and total AGEs and their magnitude of accumulation differed in cancellous and cortical bone of the same apparent volume, and were dependent on the surface-to-volume ratios of each sample. It is important to consider the bone types as two separate entities, and it is crucial to quantify total AGEs in addition to pentosidine to allow for more comprehensive analysis of the effects of non-enzymatic glycation in bone. PMID:23471564

Evaluation of hearing and speech-language in preschool children: how important, why we should perform?

PubMed

Tokgöz-Yılmaz, Suna; Özcebe, Esra; Türkyılmaz, Meral Didem; Köse, Aysen; Sennaroğlu, Gonca; Orhon, Filiz; Ulukol, Betül

2013-01-01

The aim of the study was to present the hearing and speech-language findings of preschool children. The children in this study were aged 3-5 years. Sixtyseven of 239 children (28.0%) had been referred to a physician because of possible middle ear problems, and 25 of the 67 children had slight and mild conduction type hearing loss with air-bone gaps. One of 239 children had profound sensorineural hearing loss. Speech-language problems were found in 70 of 239 children (29.3%). Necessary attention should be paid to the evaluation of hearing and speech-language skills in preschool-aged children to avoid delayed detection and to give these children the opportunity for timely intervention for hearing and speech-language problems.

Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo.

PubMed

Yang, Xiao; Mostafa, Ahmed Jenan; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

2016-10-01

Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

An Essential Physiological Role for MCT8 in Bone in Male Mice

PubMed Central

Leitch, Victoria D.; Di Cosmo, Caterina; Liao, Xiao-Hui; O’Boy, Sam; Galliford, Thomas M.; Evans, Holly; Croucher, Peter I.; Boyde, Alan; Dumitrescu, Alexandra; Weiss, Roy E.; Refetoff, Samuel; Williams, Graham R.

2017-01-01

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance. PMID:28637283

Bone morphogenetic protein 2 and decorin expression in old fracture fragments and surrounding tissues.

PubMed

Han, X G; Wang, D K; Gao, F; Liu, R H; Bi, Z G

2015-09-21

Bone morphogenetic protein 2 (BMP-2) can promote fracture healing. Although the complex role BMP-2 in bone formation is increasingly understood, the role of endogenous BMP-2 in nonunion remains unclear. Decorin (DCN) can promote the formation of bone matrix and calcium deposition to control bone morphogenesis. In this study, tissue composition and expression of BMP-2 and DCN were detected in different parts of old fracture zones to explore inherent anti-fibrotic ability and osteogenesis. Twenty-three patients were selected, including eight cases of delayed union and 15 cases of nonunion. Average duration of delayed union or nonunion was 15 months. Fracture fragments and surrounding tissues, including bone grafts, marrow cavity contents, and sticking scars, were categorically sampled during surgery. Through observation and histological testing, component comparisons were made between fracture fragments and surrounding tissue. The expression levels of DCN and BMP-2 in different tissues were detected by immunohistochemical staining and real-time polymerase chain reaction. The expression of DCN and BMP- 2 in different parts of the nonunion area showed that, compared with bone graft and marrow cavity contents, sticking scars had the highest expression of BMP-2. Compared with the marrow cavity contents and sticking scars, bone grafts had the highest expression of DCN. The low antifibrotic and osteogenic activity of the nonunion area was associated with non-co-expression of BMP-2 and DCN. Therefore, the co-injection of osteogenic factor BMP and DCN into the nonunion area can improve the induction of bone formation and enhance the conversion of the old scar, thereby achieving better nonunion treatment.

Effects of coffee intake and intraperitoneal caffeine on bone repair process--a histologic and histometric study.

PubMed

Macedo, Rander Moreira; Brentegani, Luiz Guilherme; Lacerda, Suzie Aparecida de

2015-01-01

Studies have suggested that caffeine acts on bone promoting an increase of calcium excretion, inhibition of osteoblast proliferation and delay in tissue repair process, raising the risk of fractures, osteoporosis, periodontal disease and affecting the success of bone reconstructive procedures. The aim of this study was to analyze histomorphometrically the process of alveolar bone healing after tooth extraction in rats subjected to daily intake of boiled coffee or intraperitoneal administration of caffeine. Forty-five male rats were divided according to the treatment in Control group (C); Coffee group (CO) - treated with coffee since birth; and Caffeine (CAF) - intraperitoneal injection of aqueous solution of caffeine 1.5% (0.2 mL/100g body weight) for 30 days. When weighing between 250-300 g they were anesthetized, subjected to extraction of the maxillary right incisor, and euthanized 7, 21 and 42 days after surgery for histological assessments of bone volume and the quality of formed bone in the dental socket. The qualitative results demonstrated larger amounts of blood clot and immature bone in animals under treatment of pure caffeine compared to coffee and control. Histometric analysis revealed that coffee treatment led to a 40% drop in bone formation, and caffeine a 60% drop in comparison to control animals (ANOVA p≤0.01). It was concluded that both the daily ingestion of coffee and the intraperitoneal administration of caffeine in rats delayed the alveolar bone reparative process after tooth extraction, and this effect was more aggressive when pure caffeine was used.

Fracture healing in osteoporotic bone.

PubMed

Cheung, Wing Hoi; Miclau, Theodore; Chow, Simon Kwoon-Ho; Yang, Frank F; Alt, Volker

2016-06-01

As the world population rises, osteoporotic fracture is an emerging global threat to the well-being of elderly patients. The process of fracture healing by intramembranous ossification or/and endochondral ossification involve many well-orchestrated events including the signaling, recruitment and differentiation of mesenchymal stem cells (MSCs) during the early phase; formation of a hard callus and extracellular matrix, angiogenesis and revascularization during the mid-phase; and finally callus remodeling at the late phase of fracture healing. Through clinical and animal research, many of these factors are shown to be impaired in osteoporotic bone. Animal studies related to post-menopausal estrogen deficient osteoporosis (type I) have shown healing to be prolonged with decreased levels of MSCs and decreased levels of angiogenesis. Moreover, the expression of estrogen receptor (ER) was shown to be delayed in ovariectomy-induced osteoporotic fracture. This might be related to the observed difference in mechanical sensitivity between normal and osteoporotic bones, which requires further experiments to elucidate. In mice fracture models related to senile osteoporosis (type II), it was observed that chondrocyte and osteoblast differentiation were impaired; and that transplantation of juvenile bone marrow would result in enhanced callus formation. Other factors related to angiogenesis and vasculogenesis have also been noted to be impaired in aged models, affecting the degradation of cartilaginous matrixes and vascular invasion; the result is changes in matrix composition and growth factors concentrations that ultimately impairs healing during age-related osteoporosis. Most osteoporotic related fractures occur at metaphyseal sites clinically, and reports have indicated that differences exist between diaphyseal and metaphyseal fractures. An animal model that satisfies three main criteria (metaphyseal region, plate fixation, osteoporosis) is suggested for future research for more comprehensive understanding of the impairment in osteoporotic fractures. Therefore, a metaphyseal fracture or osteotomy that achieves complete discontinuity fixed with metal implants is suggested on ovariectomized aged rodent models. © 2016 Elsevier Ltd. All rights reserved.

Early effects of zoledronic acid and teriparatide on bone microarchitecture, remodeling and collagen crosslinks: comparison between iliac crest and lumbar vertebra in ewes.

PubMed

Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D

2012-10-01

Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 μg/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (p<0.0001). This was associated with a trend of higher Tb.N, Tb.Th, DA, an inferior Conn.D and a lower bone turnover as shown by the decreases of osteoid parameters, MS/BS, Ac.f in LV1 when compared to IC. In addition, the ratio PYD/DPD was 4 times higher in LV1 than IC. After 3 months, significant decreases of sALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly only in LV1 (p<0.05) with a trend of increases in MS/BS and BFR/BS, compared to LV1-CTRL. In conclusion, in adult ewes, the bone mass, microarchitecture, remodeling and collagen crosslink content differ according to the bone site (iliac crest and vertebra). Furthermore, after 3 months, the responses to ZOL and TPTD were of different magnitude and delay between the two bone sites. The distinction of bone sites to study the early effects of anti-osteoporotic therapies appears meaningful in order to approach their site-specific anti-fracture efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

Reverse distal femoral locking compression plate a salvage option in nonunion of proximal femoral fractures.

PubMed

Dumbre Patil, Sampat S; Karkamkar, Sachin S; Patil, Vaishali S Dumbre; Patil, Shailesh S; Ranaware, Abhijeet S

2016-01-01

When primary fixation of proximal femoral fractures with implants fails, revision osteosynthesis may be challenging. Tracts of previous implants and remaining insufficient bone stock in the proximal femur pose unique problems for the treatment. Intramedullary implants like proximal femoral nail (PFN) or surface implants like Dynamic Condylar Screw (DCS) are few of the described implants for revision surgery. There is no evidence in the literature to choose one implant over the other. We used the reverse distal femur locking compression plate (LCP) of the contralateral side in such cases undergoing revision surgery. This implant has multiple options of fixation in proximal femur and its curvature along the length matches the anterior bow of the femur. We aimed to evaluate the efficacy of this implant in salvage situations. Twenty patients of failed primary proximal femoral fractures who underwent revision surgery with reverse distal femoral locking plate from February 2009 to November 2012 were included in this retrospective study. There were 18 subtrochanteric fractures and two ipsilateral femoral neck and shaft fractures, which exhibited delayed union or nonunion. The study included 14 males and six females. The mean patient age was 43.6 years (range 22-65 years) and mean followup period was 52.1 months (range 27-72 months). Delayed union was considered when clinical and radiological signs of union failed to progress at the end of four months from initial surgery. All fractures exhibited union without any complications. Union was assessed clinically and radiologically. One case of ipsilateral femoral neck and shaft fracture required bone grafting at the second stage for delayed union of the femoral shaft fracture. Reverse distal femoral LCP of the contralateral side can be used as a salvage option for failed fixation of proximal femoral fractures exhibiting nonunion.

Evaluation of the Reliability and Validity of the Crawford Classification of Congenital Tibial Dysplasia

DTIC Science & Technology

2007-12-01

Month 1): a. Train a research coordinator to identify potential radiographs at pediatric orthopedic hospital. b. Have conference call with...JR. Delayed autogenous bone graft in the treatment of congenital pseudarthrosis. J Bone Joint Surg Am 1949;31:23. 8. Rudicel S. The orthopaedic

Long-term outcome of free fibula osteocutaneous flap and massive allograft in the reconstruction of long bone defect.

PubMed

Halim, Ahmad Sukari; Chai, Siew Cheng; Wan Ismail, Wan Faisham; Wan Azman, Wan Sulaiman; Mat Saad, Arman Zaharil; Wan, Zulmi

2015-12-01

Reconstruction of massive bone defects in bone tumors with allografts has been shown to have significant complications including infection, delayed or nonunion of allograft, and allograft fracture. Resection compounded with soft tissue defects requires skin coverage. A composite osteocutaneous free fibula offers an optimal solution where the allografts can be augmented mechanically and achieve biological incorporation. Following resection, the cutaneous component of the free osteocutaneous fibula flaps covers the massive soft tissue defect. In this retrospective study, the long-term outcome of 12 patients, who underwent single-stage limb reconstruction with massive allograft and free fibula osteocutaneous flaps instead of free fibula osteal flaps only, was evaluated. This study included 12 consecutive patients who had primary bone tumors and had follow-up for a minimum of 24 months. The mean age at the time of surgery was 19.8 years. A total of eight patients had primary malignant bone tumors (five osteosarcomas, two chondrosarcomas and one synovial sarcoma), and four patients had benign bone tumors (two giant-cell tumors, one aneurysmal bone cyst, and one neurofibromatosis). The mean follow-up for the 12 patients was 63 months (range 24-124 months). Out of the 10 patients, nine underwent lower-limb reconstruction and ambulated with partial weight bearing and full weight bearing at an average of 4.2 months and 8.2 months, respectively. In conclusion, augmentation of a massive allograft with free fibula osteocutaneous flap is an excellent alternative for reducing the long-term complication of massive allograft and concurrently addresses the soft tissue coverage. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Osteoporosis-related life habits and knowledge about osteoporosis among women in El Salvador: A cross-sectional study

PubMed Central

Hernandez-Rauda, Roberto; Martinez-Garcia, Sandra

2004-01-01

Background Osteoporosis is a systemic skeletal disorder, characterized by reduced bone mass, deterioration of bone structure, increased bone fragility, and increased fracture risk. It is more frequent to find among women than men at a 4:1 ratio. Evidence suggests that to adopt changes on some life habits can prevent or delay development of osteoporosis. Several osteoporosis-risk factors have been confirmed in the US and western Europe, but in El Salvador there are neither reliable epidemiological statistics about this skeletal disorder nor studies addressing osteoporosis-risk factors in women. The aim of this study was to determinate the extent of osteoporosis knowledge, the levels of both daily calcium intake and weight-bearing physical activity, and the influence of several osteoporosis-risk factors on these variables in three age groups of Salvadorean women. Methods In this exploratory cross-sectional study, an osteoporosis knowledge assessment questionnaire incluiding a food frequency and a physical activity record section were used to collect data and it was delivered through a face-to-face interview. A convenience sample (n = 197) comprised of three groups of women aged 25–35 years, 36–49 years, and over 49 years was taken. Among-group comparisons of means were analyzed by two-way ANOVA. To determinate the overall influence of osteoporosis-risk factors, the multivariate analysis was used. Results Study results indicated that better educated women had more knowledge about osteoporosis than women with a low education level, regardless of age, even though this knowledge was rather fair. Older women got more weight-bearing physical activity at home and less at place of employment than reported by the younger women; however, neither group performed sufficient high-intensity WBPA to improve bone mass. Regardless of age, the most women consumed 60% or less than the Dietary Reference Intake of calcium and depend on household income, lactose intolerance and coffee rather than milk consumption. Conclusion In summary, the majority of women in this study have modest knowledge on osteoporosis. The knowledge base is not linked to preventive health habits, including sufficient calcium intake and performance of weight-bearing physical activities. They are thus at increased risk for low bone mass. PMID:15329150

Mitogen‐inducible gene‐6 partly mediates the inhibitory effects of prenatal dexamethasone exposure on endochondral ossification in long bones of fetal rats

PubMed Central

Shang‐Guan, Yangfan; Ma, Jing; Hu, Hang; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin

2016-01-01

Abstract Background and Purpose Prenatal exposure to dexamethasone slows down fetal linear growth and bone mineralization but the regulatory mechanism remains unknown. Here we assessed how dexamethasone regulates bone development in the fetus. Experimental Approach Dexamethasone (1 mg·kg−1·day−1) was injected subcutaneously every morning in pregnant rats from gestational day (GD)9 to GD20. Fetal femurs and tibias were harvested at GD20 for histological and gene expression analysis. Femurs of 12‐week‐old female offspring were harvested for microCT (μCT) measurement. Primary chondrocytes were treated with dexamethasone (10, 50, 250 and 1000 nM). Key Results Prenatal dexamethasone exposure resulted in accumulation of hypertrophic chondrocytes and delayed formation of the primary ossification centre in fetal long bone. The retardation was accompanied by reduced maturation of hypertrophic chondrocytes, decreased osteoclast number and down‐regulated expression of osteocalcin and bone sialoprotein in long bone. In addition, the mitogen‐inducible gene‐6 (Mig6) and osteoprotegerin (OPG) expression were stimulated, and the receptor activator of NF‐κB ligand (RANKL) expression was repressed. Moreover, dexamethasone activated OPG and repressed RANKL expression in both primary chondrocytes and primary osteoblasts, and the knockdown of Mig6 abolished the effect of dexamethasone on OPG expression. Further, μCT measurement showed loss of bone mass in femur of 12‐week‐old offspring with prenatal dexamethasone exposure. Conclusions and Implications Prenatal dexamethasone exposure delays endochondral ossification by suppressing chondrocyte maturation and osteoclast differentiation, which may be partly mediated by Mig6 activation in bone. Bone development retardation in the fetus may be associated with reduced bone mass in later life. PMID:27128203

Congenital cutis laxa with ligamentous laxity and delayed development, Dandy-Walker malformation and minor heart and osseous defects.

PubMed

Biver, A; De Rijcke, S; Toppet, V; Ledoux-Corbusier, M; Van Maldergem, L

1994-06-01

We present a female infant exhibiting congenital cutis laxa with retardation of growth and motor development, ligamentous laxity and congenital dislocation of the hips. This connective tissue disorder was associated with Dandy-Walker malformation, atrial and ventricular defect and minor bone abnormalities including multiple wormian bones, abnormal tubulation of long bones and absent twelfth pair of ribs. This association is believed to be unique.

Composite Bone and Soft Tissue Loss Treated with Distraction Histiogenesis

DTIC Science & Technology

2010-01-01

their frames removed had healed docking sites, and the fourth whose frame remained in place had a healing fracture without evidence of delayed union ...interventions (3–8). The goals of limb salvage surgery in this setting are to restore length and alignment, regenerate bone loss, obtain fracture union ...angulation to manage composite bone and soft tissue loss associated with combat-related type IIIB open tibia fractures . Four patients underwent placement

Accumulation of carboxymethyl-lysine (CML) in human cortical bone.

PubMed

Thomas, Corinne J; Cleland, Timothy P; Sroga, Grazyna E; Vashishth, Deepak

2018-05-01

Advanced glycation end-products (AGEs) are a category of post translational modification associated with the degradation of the structural properties of multiple different types of tissues. Typically, AGEs are the result of a series of post-translational modification reactions between sugars and proteins through a process known as non-enzymatic glycation (NEG). Increases in the rate of NEG of bone tissue are associated with type 2 diabetes and skeletal fragility. Current methods of assessing NEG and its impact on bone fracture risk involve measurement of pentosidine or total fluorescent AGEs (fAGEs). However, pentosidine represents only a small fraction of possible fAGEs present in bone, and neither pentosidine nor total fAGE measurement accounts for non-fluorescent AGEs, which are known to form in significant amounts in skin and other collagenous tissues. Carboxymethyl-lysine (CML) is a non-fluorescent AGE that is often measured and has been shown to accumulate in tissues such as skin, heart, arteries, and intervertebral disks, but is currently not assessed in bone. Here we show the localization of CML to collagen I using mass spectrometry for the first time in human bone. We then present a new method using demineralization followed by heating and trypsin digestion to measure CML content in human bone and demonstrate that CML in bone is 40-100 times greater than pentosidine (the current most commonly used marker of AGEs in bone). We then establish the viability of CML as a measurable AGE in bone by showing that levels of CML, obtained from bone using this technique, increase with age (p<0.05) and are correlated with previously reported measures of bone toughness. Thus, CML is a viable non-fluorescent AGE target to assess AGE accumulation and fragility in bone. The method developed here to extract and measure CML from human bone could facilitate the development of a new diagnostic assay to evaluate fracture risk and potentially lead to new therapeutic approaches to address bone fragility. Copyright © 2018 Elsevier Inc. All rights reserved.

Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone

PubMed Central

Balseanu, Adrian Tudor; Buga, Ana-Maria; Catalin, Bogdan; Wagner, Daniel-Christoph; Boltze, Johannes; Zagrean, Ana-Maria; Reymann, Klaus; Schaebitz, Wolf; Popa-Wagner, Aurel

2014-01-01

Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the stem cell mobilizer granulocyte colony-stimulating factor (G-CSF). We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs) in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 μg/kg) or in combination with a single dose (106 cells) of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min) of the middle cerebral artery. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration.” However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time. PMID:25002846

Prader-Willi Critical Region, a Non-Translated, Imprinted Central Regulator of Bone Mass: Possible Role in Skeletal Abnormalities in Prader-Willi Syndrome.

PubMed

Khor, Ee-Cheng; Fanshawe, Bruce; Qi, Yue; Zolotukhin, Sergei; Kulkarni, Rishikesh N; Enriquez, Ronaldo F; Purtell, Louise; Lee, Nicola J; Wee, Natalie K; Croucher, Peter I; Campbell, Lesley; Herzog, Herbert; Baldock, Paul A

2016-01-01

Prader-Willi Syndrome (PWS), a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR), including a set of small non-translated nucleolar RNA's (snoRNA). Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health and disease.

Multiple Low Energy Long Bone Fractures in the Setting of Rothmund-Thomson Syndrome.

PubMed

Beckmann, Nicholas

2015-01-01

Rothmund-Thomson syndrome is a rare autosomal recessive genodermatosis characterized by a poikilodermatous rash starting in infancy as well as various skeletal anomalies, juvenile cataracts, and predisposition to certain cancers. Although Rothmund-Thomson syndrome is associated with diminished bone mineral density in addition to multiple skeletal abnormalities, there are few reports of the association with stress fractures or pathologic fractures in low energy trauma or delayed healing of fractures. Presented is a case of a young adult male with Rothmund-Thomson syndrome presenting with multiple episodes of long bone fractures caused by low energy trauma with one of the fractures exhibiting significantly delayed healing. The patient was also found to have an asymptomatic stress fracture of the lower extremity, another finding of Rothmund-Thomson syndrome rarely reported in the literature. A thorough review of the literature and comprehensive presentation of Rothmund-Thomson syndrome is provided in conjunction with our case.

Computer-assisted analysis of cervical vertebral bone age using cephalometric radiographs in Brazilian subjects.

PubMed

Caldas, Maria de Paula; Ambrosano, Gláucia Maria Bovi; Haiter Neto, Francisco

2010-01-01

The aims of this study were to develop a computerized program for objectively evaluating skeletal maturation on cephalometric radiographs, and to apply the new method to Brazilian subjects. The samples were taken from the patient files of Oral Radiological Clinics from the North, Northeast, Midwest and South regions of the country. A total of 717 subjects aged 7.0 to 15.9 years who had lateral cephalometric radiographs and hand-wrist radiographs were selected. A cervical vertebral computerized analysis was created in the Radiocef Studio 2 computer software for digital cephalometric analysis, and cervical vertebral bone age was calculated using the formulas developed by Caldas et al.17 (2007). Hand-wrist bone age was evaluated by the TW3 method. Analysis of variance (ANOVA) and the Tukey test were used to compare cervical vertebral bone age, hand-wrist bone age and chronological age (P < 0.05). No significant difference was found between cervical vertebral bone age and chronological age in all regions studied. When analyzing bone age, it was possible to observe a statistically significant difference between cervical vertebral bone age and hand-wrist bone age for female and male subjects in the North and Northeast regions, as well as for male subjects in the Midwest region. No significant difference was observed between bone age and chronological age in all regions except for male subjects in the North and female subjects in the Northeast. Using cervical vertebral bone age, it might be possible to evaluate skeletal maturation in an objective manner using cephalometric radiographs.

Bone mineral density in periodontally healthy and edentulous postmenopausal women.

PubMed

Bando, K; Nitta, H; Matsubara, M; Ishikawa, I

1998-07-01

(Osteoporosis is the most common metabolic disease among postmenopausal women. Reduced masticatory function caused by tooth loss may be a contributing risk factor of osteoporosis. The present study examined the effect of dentate state on skeletal bone mineral density (BMD) in postmenopausal women. Fourteen periodontally healthy dentate subjects (group H; mean age: 64.0 + 5.5 years) and 12 edentulous subjects (group E; mean age: 67.1 + 2.9 years) were randomly selected from the clinics of the departments of Periodontology and Gerodontology, respectively. Informed consent was obtained from all participants. BMD of the lumbar spine (L2-L4) was measured by dual energy x-ray absorptiometry. In addition, occlusal force was measured in 11 group H subjects and 8 group E subjects by using an occlusal diagnostic system. Risk factors associated with osteoporosis including age, calcium intake, physical activity, and cigarette smoking and causes of tooth loss were assessed by interview and questionnaire sent to all participants. The BMD of group H was 1.07 t 0.21 g/cm2 and that of group E was 0.89 + 0.17 g/cm2, which was significantly different(P< 0.05). The occlusal force of group H and E patients was 312.4 + 148 Nand 56.3 + 36 N, respectively, which was significantly different (P< 0.05). Risk factors such as calcium intake, physical activity, and smoking did not differ significantly between the 2 groups. Thus, the periodontally healthy dentate women, who showed about 6 times higher occlusal force than edentulous women, maintained significantly higher BMD of the lumbar spine than edentulous women. Our results suggest that sufficient masticatory function with periodontally healthy dentition may inhibit or delay the progress of osteoporotic change in skeletal bone or that edentulous women may be more susceptible to osteoporosis.

Denosumab for the management of bone disease in patients with solid tumors.

PubMed

Body, Jean-Jacques

2012-03-01

Many patients with advanced cancer develop bone metastases, which reduces their quality of life. Bone metastases are associated with an increased risk of skeletal-related events, which can lead to increased morbidity and mortality. In patients with bone metastases, tumor cells disrupt the normal process of bone remodeling, leading to increased bone destruction. Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL), a key regulatory factor in bone remodeling. By binding to RANKL, denosumab disrupts the cycle of bone destruction. In clinical studies in patients with prostate or breast cancer and bone metastases, denosumab was superior to the current standard of care, zoledronic acid, for delaying skeletal-related events, while in patients with other solid tumors or multiple myeloma, denosumab was noninferior to zoledronic acid. This article examines the pharmacokinetics, efficacy, and safety and tolerability of denosumab for the management of bone events in patients with cancer.

A multi-method assessment of bone maintenance and loss in an Imperial Roman population: Implications for future studies of age-related bone loss in the past.

PubMed

Beauchesne, Patrick; Agarwal, Sabrina C

2017-09-01

One of the hallmarks of contemporary osteoporosis and bone loss is dramatically higher prevalence of loss and fragility in females post-menopause. In contrast, bioarchaeological studies of bone loss have found a greater diversity of age- and sex-related patterns of bone loss in past populations. We argue that the differing findings may relate to the fact that most studies use only a single methodology to quantify bone loss and do not account for the heterogeneity and complexity of bone maintenance across the skeleton and over the life course. We test the hypothesis that bone mass and maintenance in trabecular bone sites versus cortical bone sites will show differing patterns of age-related bone loss, with cortical bone sites showing sex difference in bone loss that are similar to contemporary Western populations, and trabecular bone loss at earlier ages. We investigated this hypothesis in the Imperial Roman population of Velia using three methods: radiogrammetry of the second metacarpal (N = 71), bone histology of ribs (N = 70), and computerized tomography of trabecular bone architecture (N = 47). All three methods were used to explore sex and age differences in patterns of bone loss. The suite of methods utilized reveal differences in the timing of bone loss with age, but all methods found no statistically significant differences in age-related bone loss. We argue that a multi-method approach reduces the influence of confounding factors by building a reconstruction of bone turnover over the life cycle that a limited single-method project cannot provide. The implications of using multiple methods beyond studies of bone loss are also discussed. © 2017 Wiley Periodicals, Inc.

Diaphyseal forearm fractures, 20 years after surgical treatment. Is there still an indication for percutaneous fixation?

PubMed

Fernández-Marín, M R; Hidalgo-Pérez, M; Arias-Rodríguez, G; García-Mendoza, A; Prada-Chamorro, E; Domecq-Fernández de Bobadilla, G

This is a retrospective study of 98 diaphyseal forearm fractures in adults, treated by a percutaneous technique with intramedullar Kirchner wires. We reviewed 64 patients with 98 forearm fractures with a radiographic follow-up, assessing the presence of pseudarthrosis or delayed bone union and evaluating functional outcomes with the Anderson and the Disability of the Arm, Shoulder and Hand scale. Clinical and radiological bone union was achieved in an average of 12 weeks. We obtained 77% of excellent and good results following Anderson's scale. There were 4 cases of pseudarthrosis and 6 cases of delayed bone union. This surgical technique provides several advantages, such as a low incidence of complications and a total absence of infections, refractures and iatrogenic neurovascular injuries. It allows a lower hospital stay and a shortening of the surgery time compared with other techniques such as plates and intramedullary nails, that have similar results, in terms of bone union and functional outcomes, as we have verified from the published literature. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

PubMed

Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

2011-12-01

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing.

PubMed

Lu, Xuanyu; Li, Wenjin; Fukumoto, Satoshi; Yamada, Yoshihiko; Evans, Carla A; Diekwisch, Tom; Luan, Xianghong

2016-01-01

The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBN(Δ5-6) truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

The Ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing

PubMed Central

Lu, Xuanyu; Li, Wenjin; Fukumoto, Satoshi; Yamada, Yoshihiko; Evans, Carla; Diekwisch, Thomas G.H.; Luan, Xianghong

2016-01-01

The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBNΔ5-6 truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing. PMID:26899203

Diaphyseal long bone nonunions - types, aetiology, economics, and treatment recommendations.

PubMed

Rupp, Markus; Biehl, Christoph; Budak, Matthäus; Thormann, Ulrich; Heiss, Christian; Alt, Volker

2018-02-01

The intention of the current article is to review the epidemiology with related socioeconomic costs, pathophysiology, and treatment options for diaphyseal long bone delayed unions and nonunions. Diaphyseal nonunions in the tibia and in the femur are estimated to occur 4.6-8% after modern intramedullary nailing of closed fractures with an even much higher risk in open fractures. There is a high socioeconomic burden for long bone nonunions mainly driven by indirect costs, such as productivity losses due to long treatment duration. The classic classification of Weber and Cech of the 1970s is based on the underlying biological aspect of the nonunion differentiating between "vital" (hypertrophic) and "avital" (hypo-/atrophic) nonunions, and can still be considered to represent the basis for basic evaluation of nonunions. The "diamond concept" units biomechanical and biological aspects and provides the pre-requisites for successful bone healing in nonunions. For humeral diaphyseal shaft nonunions, excellent results for augmentation plating were reported. In atrophic humeral shaft nonunions, compression plating with stimulation of bone healing by bone grafting or BMPs seem to be the best option. For femoral and tibial diaphyseal shaft fractures, dynamization of the nail is an atraumatic, effective, and cheap surgical possibility to achieve bony consolidation, particularly in delayed nonunions before 24 weeks after initial surgery. In established hypertrophic nonunions in the tibia and femur, biomechanical stability should be addressed by augmentation plating or exchange nailing. Hypotrophic or atrophic nonunions require additional biological stimulation of bone healing for augmentation plating.

Artistic versus rhythmic gymnastics: effects on bone and muscle mass in young girls.

PubMed

Vicente-Rodriguez, G; Dorado, C; Ara, I; Perez-Gomez, J; Olmedillas, H; Delgado-Guerra, S; Calbet, J A L

2007-05-01

We compared 35 prepubertal girls, 9 artistic gymnasts and 13 rhythmic gymnasts with 13 nonphysically active controls to study the effect of gymnastics on bone and muscle mass. Lean mass, bone mineral content and areal density were measured by dual energy X-ray absorptiometry, and physical fitness was also assessed. The artistic gymnasts showed a delay in pubertal development compared to the other groups (p<0.05). The artistic gymnasts had a 16 and 17 % higher aerobic power and anaerobic capacity, while the rhythmic group had a 14 % higher anaerobic capacity than the controls, respectively (all p<0.05). The artistic gymnasts had higher lean mass (p<0.05) in the whole body and the extremities than both the rhythmic gymnasts and the controls. Body fat mass was 87.5 and 61.5 % higher in the controls than in the artistic and the rhythmic gymnasts (p<0.05). The upper extremity BMD was higher (p<0.05) in the artistic group compared to the other groups. Lean mass strongly correlated with bone mineral content (r=0.84, p<0.001), and multiple regression analysis showed that total lean mass explained 64 % of the variability in whole body bone mineral content, but only 20 % in whole body bone mineral density. Therefore, recreational artistic gymnastic participation is associated with delayed pubertal development, enhanced physical fitness, muscle mass, and bone density in prepubertal girls, eliciting a higher osteogenic stimulus than rhythmic gymnastic.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.

PubMed

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-04-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.

Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence.

PubMed

Kulin, H E; Finkelstein, J W; D'Arcangelo, M R; Susman, E J; Chinchilli, V; Kunselman, S; Schwab, J; Demers, L; Lookingbill, G

1997-01-01

In a group of 22 boys with constitutional delay in growth and/or adolescence, intermittent testosterone enanthate treatment was employed in a randomized clinical trial at multiple doses ranging from 25-100 mg every two weeks for three month periods extending over 15-21 months. Twelve of the patients displayed a prompt increase in endogenous testosterone levels during the study period, reaching levels in the adult male range (> 250 ng/dl). The remaining 10 boys showed sluggish changes in endogenous testosterone during the investigation, ranging from 35-177 ng/dl. The bone ages and testicular sizes of the two groups at study initiation did not differ though urine LH was significantly less at study entry in the slowly maturing group. The data reveal a great diversity in the pace and pattern of endogenous testosterone changes in the study population. The results also suggest that exogenous sex steroid treatment of such patients does not speed up the central nervous system processes controlling the onset and progression of puberty. Boys with delayed puberty should be followed until endogenous testosterone levels reach the adult male range in order to rule out mild gonadotropin deficits.

Immediate versus Delayed Treatment in the Anterior Maxilla Using Single Implants with a Laser-Microtextured Collar: 3-Year Results of a Case Series on Hard- and Soft-Tissue Response and Esthetics.

PubMed

Guarnieri, Renzo; Belleggia, Fabrizio; Grande, Maurizio

2016-02-01

To compare peri-implant marginal bone loss, soft tissue response, and esthetics following single immediate implant treatment (IIT) and delayed implant treatment (DIT) in the esthetic zone of the maxilla in well-selected patients. Adequate bone volume and ideal soft tissue level/contour were considered requirements for implant therapy, with additional prerequisites for IIT of residual alveolar bone wall integrity and a thick gingival biotype. IIT included immediate placement and provisionalization, while DIT included extraction socket preservation followed by implant placement and provisionalization 4 months later. Cortical bone levels and peri-implant mucosal conditions were evaluated at regular intervals. The esthetic outcome was objectively rated after 3 years using the pink esthetic score (PES) and white esthetic score (WES). Twelve patients received an immediate Laser-Lok® implant, and 13 patients received a delayed Laser-Lok® implant. No significant differences were found between the study groups regarding survival rate (100%). The mean bone level from the implant/abutment interface was 0.35 ± 0.18 mm for IIT and 0.42 ± 0.21 mm for DIT after 3 years (p > 0.05). Mesial and distal papillae remained stable over time in DIT. A tendency for regrowth of mesial and distal papillae was found following IIT (p < 0.05). Midfacial soft tissues remained stable over time following DIT and IIT. Within the limitations of this study (e.g., small sample size, short follow-up duration), the results suggest that regarding success rate, hard/soft tissue responses, and esthetics, DIT and IIT with single Laser-Lok® implants in the anterior maxilla are comparable and predictable options for well-selected patients. © 2015 by the American College of Prosthodontists.

External fixation of tibial pilon fractures and fracture healing.

PubMed

Ristiniemi, Jukka

2007-06-01

Distal tibial fractures are rare and difficult to treat because the bones are subcutaneous. External fixation is commonly used, but the method often results in delayed union. The aim of the present study was to find out the factors that affect fracture union in tibial pilon fractures. For this purpose, prospective data collection of tibial pilon fractures was carried out in 1998-2004, resulting in 159 fractures, of which 83 were treated with external fixation. Additionally, 23 open tibial fractures with significant > 3 cm bone defect that were treated with a staged method in 2000-2004 were retrospectively evaluated. The specific questions to be answered were: What are the risk factors for delayed union associated with two-ring hybrid external fixation? Does human recombinant BMP-7 accelerate healing? What is the role of temporary ankle-spanning external fixation? What is the healing potential of distal tibial bone loss treated with a staged method using antibiotic beads and subsequent autogenous cancellous grafting compared to other locations of the tibia? The following risk factors for delayed healing after external fixation were identified: post-reduction fracture gap of >3 mm and fixation of the associated fibula fracture. Fracture displacement could be better controlled with initial temporary external fixation than with early definitive fixation, but it had no significant effect on healing time, functional outcome or complication rate. Osteoinduction with rhBMP-7 was found to accelerate fracture healing and to shorten the sick leave. A staged method using antibiotic beads and subsequent autogenous cancellous grafting proved to be effective in the treatment of tibial bone loss. Healing potential of the bone loss in distal tibia was at least equally good as in other locations of the tibia.

Effects of Growth Hormone and Nutritional Therapy in Boys with Constitutional Growth Delay: A Randomized Controlled Trial

PubMed Central

Han, Joan C.; Damaso, Ligeia; Welch, Susan; Balagopal, Prabhakaran; Hossain, Jobayer; Mauras, Nelly

2010-01-01

Objective To examine whether supplemental nutrition augments the anabolic actions of growth hormone (GH) in boys with constitutional delay of growth and maturation (CDGM). Study design We conducted a randomized, controlled trial at an outpatient clinical research center. Subjects were 20 prepubertal boys (age 9.3±1.3y) with CDGM (height-SDS -2.0±0.5, bone age delay 1.8±0.8y, BMI-SDS -1.2±1.0, peak stimulated GH 15.7±7.7ng/mL), who were randomized (N=10/group) to 6 months observation or daily nutritional supplementation, followed by additional daily GH therapy in all for another 12 months. T-tests and repeated measures ANOVAs compared energy intake, total energy expenditure (TEE), growth, hormones and nutrition markers. Results Energy intake was increased at 6 months within the Nutrition (p=0.04) but not the Observation group, and TEE was not statistically different within either group at 6 months. Addition of 6 months GH resulted in higher energy intake and TEE in the GH/Nutrition group at 12 months (p<0.01), but not in the GH group vs. baseline. Height, weight, lean body mass, hormones and nutrition markers increased comparably in both groups throughout 18 months. Conclusions Boys with CDGM utilize energy at an accelerated rate, an imbalance not overcome with added nutrition. GH therapy increases growth comparably with or without added nutrition in these patients. PMID:20961566

Coexisting diseases modifying each other’s presentation - lack of growth failure in Turner syndrome due to the associated pituitary gigantism.

PubMed

Dragović, Tamara; Đuran, Zorana; Jelić, Svetlana; Marinković, Dejan; Kiković, Saša; Kuzmić-Janković, Snežana; Hajduković, Zoran

2016-10-01

Turner syndrome presents with one of the most frequent chromosomal aberrations in female, typically presented with growth retardation, ovarian insufficiency, facial dysmorphism, and numerous other somatic stigmata. Gigantism is an extremely rare condition resulting from an excessive growth hormone (GH) secretion that occurs during childhood before the fusion of epiphyseal growth plates. The major clinical feature of gigantism is growth acceleration, although these patients also suffer from hypogonadism and soft tissue hypertrophy. We presented a girl with mosaic Turner syndrome, delayed puberty and normal linear growth for the sex and age, due to the simultaneous GH hypersecretion by pituitary tumor. In the presented case all the typical phenotypic stigmata related to Turner syndrome were missing. Due to excessive pituitary GH secretion during the period while the epiphyseal growth plates of the long bones are still open, characteristic stagnation in longitudinal growth has not been demonstrated. The patient presented with delayed puberty and primary amenorrhea along with a sudden appearance of clinical signs of hypersomatotropinism, which were the reasons for seeking medical help at the age of 16. Physical examination of children presenting with delayed puberty but without growth arrest must include an overall hormonal and genetic testing even in the cases when typical clinical presentations of genetic disorder are absent. To the best of our knowledge, this is the first reported case of simultaneous presence of Turner syndrome and gigantism in the literature.

Development of controlled drug delivery systems for bone fracture-targeted therapeutic delivery: A review.

PubMed

Wang, Yuchen; Newman, Maureen R; Benoit, Danielle S W

2018-06-01

Impaired fracture healing is a major clinical problem that can lead to patient disability, prolonged hospitalization, and significant financial burden. Although the majority of fractures heal using standard clinical practices, approximately 10% suffer from delayed unions or non-unions. A wide range of factors contribute to the risk for nonunions including internal factors, such as patient age, gender, and comorbidities, and external factors, such as the location and extent of injury. Current clinical approaches to treat nonunions include bone grafts and low-intensity pulsed ultrasound (LIPUS), which realizes clinical success only to select patients due to limitations including donor morbidities (grafts) and necessity of fracture reduction (LIPUS), respectively. To date, therapeutic approaches for bone regeneration rely heavily on protein-based growth factors such as INFUSE, an FDA-approved scaffold for delivery of bone morphogenetic protein 2 (BMP-2). Small molecule modulators and RNAi therapeutics are under development to circumvent challenges associated with traditional growth factors. While preclinical studies has shown promise, drug delivery has become a major hurdle stalling clinical translation. Therefore, this review overviews current therapies employed to stimulate fracture healing pre-clinically and clinically, including a focus on drug delivery systems for growth factors, parathyroid hormone (PTH), small molecules, and RNAi therapeutics, as well as recent advances and future promise of fracture-targeted drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Parathyroid hormone-related protein is required for tooth eruption

PubMed Central

Philbrick, William M.; Dreyer, Barbara E.; Nakchbandi, Inaam A.; Karaplis, Andrew C.

1998-01-01

Parathyroid hormone (PTH)-related protein (PTHrP)-knockout mice die at birth with a chondrodystrophic phenotype characterized by premature chondrocyte differentiation and accelerated bone formation, whereas overexpression of PTHrP in the chondrocytes of transgenic mice produces a delay in chondrocyte maturation and endochondral ossification. Replacement of PTHrP expression in the chondrocytes of PTHrP-knockout mice using a procollagen II-driven transgene results in the correction of the lethal skeletal abnormalities and generates animals that are effectively PTHrP-null in all sites other than cartilage. These rescued PTHrP-knockout mice survive to at least 6 months of age but are small in stature and display a number of developmental defects, including cranial chondrodystrophy and a failure of tooth eruption. Teeth appear to develop normally but become trapped by the surrounding bone and undergo progressive impaction. Localization of PTHrP mRNA during normal tooth development by in situ hybridization reveals increasing levels of expression in the enamel epithelium before the formation of the eruption pathway. The type I PTH/PTHrP receptor is expressed in both the adjacent dental mesenchyme and in the alveolar bone. The replacement of PTHrP expression in the enamel epithelium with a keratin 14-driven transgene corrects the defect in bone resorption and restores the normal program of tooth eruption. PTHrP therefore represents an essential signal in the formation of the eruption pathway. PMID:9751753

Contrasting skeletal phenotypes in mice with an identical mutation targeted to thyroid hormone receptor alpha1 or beta.

PubMed

O'Shea, Patrick J; Bassett, J H Duncan; Sriskantharajah, Srividya; Ying, Hao; Cheng, Sheue-yann; Williams, Graham R

2005-12-01

Thyroid hormone (T(3)) regulates bone turnover and mineralization in adults and is essential for skeletal development. Surprisingly, we identified a phenotype of skeletal thyrotoxicosis in T(3) receptor beta(PV) (TRbeta(PV)) mice in which a targeted frameshift mutation in TRbeta results in resistance to thyroid hormone. To characterize mechanisms underlying thyroid hormone action in bone, we analyzed skeletal development in TRalpha1(PV) mice in which the same PV mutation was targeted to TRalpha1. In contrast to TRbeta(PV) mice, TRalpha1(PV) mutants exhibited skeletal hypothyroidism with delayed endochondral and intramembranous ossification, severe postnatal growth retardation, diminished trabecular bone mineralization, reduced cortical bone deposition, and delayed closure of the skull sutures. Skeletal hypothyroidism in TRalpha1(PV) mutants was accompanied by impaired GH receptor and IGF-I receptor expression and signaling in the growth plate, whereas GH receptor and IGF-I receptor expression and signaling were increased in TRbeta(PV) mice. These data indicate that GH receptor and IGF-I receptor are physiological targets for T(3) action in bone in vivo. The divergent phenotypes observed in TRalpha1(PV) and TRbeta(PV) mice arise because the pituitary gland is a TRbeta-responsive tissue, whereas bone is TRalpha responsive. These studies provide a new understanding of the complex relationship between central and peripheral thyroid status.

Histologic and histomorphometric evaluation of peri-implant bone of immediate or delayed occlusal-loaded non-splinted implants in the posterior mandible--an experimental study in monkeys.

PubMed

Stokholm, Rie; Isidor, Flemming; Nyengaard, Jens R

2014-11-01

The primary aim of this study was to compare the bone reaction around immediate-loaded non-splinted single implants vs. delayed loaded non-splinted single implants placed in healed ridges in the posterior mandible. Six adult Macaca Fascicularis monkeys were used in this study. The first and second premolars and the first molar were extracted in both sides of the mandible. After 3 months of healing, four implants (Replace Select Tapered; Nobel Biocare, Gothenburg, Sweden) with a moderately rough surface (TiUnite, Nobel Biocare) were placed in the edentulous areas of each monkey, two in each side. The implants had a length of 10 mm and a diameter of 3.5 mm. Four groups of varying time and occlusal loading aspects were created: (i) control group: implant placed non-loaded for 3 months; (ii) immediate loaded: implant placed and loaded immediately for 3 months; (iii) immediate loaded: implant placed and loaded immediately for 6 months; and (iv) delayed loaded: implant placed submerged for 3 months and then loaded for 3 months. At the loaded implants, after a second stage surgery, a composite crown was made directly on an abutment mounted on the implant reinsuring simultaneous occlusal contact on the implant crown and the neighboring teeth. After euthanization of the animals, histologic specimens were quantified in the light microscope. All implants were clinically, radiographically, and histologically osseointegrated at the time of euthanization and with only mild signs of inflammation in the peri-implant mucosa. The histologic marginal bone level was located on average 1.14-1.74 mm apical to the margin of the implants in the various groups. The average bone-to-implant contact (BIC) varied between 55% and 65% and the average bone density (i.e., the proportion of mineralized bone tissue from the implant surface and to a distance of 1 mm lateral to the implant) varied between 30.6% and 34.2%. No statistical significant differences between groups were observed in the above-stated histomorphometric parameters. Similar histologic and histomorphometric findings were observed in immediately and delayed loaded non-splinted implants placed in the posterior mandible of macaque monkeys. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

PubMed

Passeron, Thierry; Salhi, Aicha; Mazer, Jean-Michel; Lavogiez, Céline; Mazereeuw-Hautier, Juliette; Galliot, Chrystèle; Collet-Villette, Anne-Marie; Labreze, Christine; Boon, Laurence; Hardy, Jean-Philippe; Fayard, Virginie; Livideanu, Cristina Bulai; Toubel, Gérard; Georgescou, Gabriela; Gral, Nathalie; Maza, Aude; Lacour, Jean-Philippe

2016-07-01

There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). We sought to characterize patients with hypertrophic PWS presenting during childhood. Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Aging Versus Postmenopausal Osteoporosis: Bone Composition and Maturation Kinetics at Actively-Forming Trabecular Surfaces of Female Subjects Aged 1 to 84 Years.

PubMed

Paschalis, Eleftherios P; Fratzl, Peter; Gamsjaeger, Sonja; Hassler, Norbert; Brozek, Wolfgang; Eriksen, Erik F; Rauch, Frank; Glorieux, Francis H; Shane, Elizabeth; Dempster, David; Cohen, Adi; Recker, Robert; Klaushofer, Klaus

2016-02-01

Bone strength depends on the amount of bone, typically expressed as bone mineral density (BMD), determined by dual-energy X-ray absorptiometry (DXA), and on bone quality. Bone quality is a multifactorial entity including bone structural and material compositional properties. The purpose of the present study was to examine whether bone material composition properties at actively-forming trabecular bone surfaces in health are dependent on subject age, and to contrast them with postmenopausal osteoporosis patients. To achieve this, we analyzed by Raman microspectroscopy iliac crest biopsy samples from healthy subjects aged 1.5 to 45.7 years, paired biopsy samples from females before and immediately after menopause aged 46.7 to 53.6 years, and biopsy samples from placebo-treated postmenopausal osteoporotic patients aged 66 to 84 years. The monitored parameters were as follows: the mineral/matrix ratio; the mineral maturity/crystallinity (MMC); nanoporosity; the glycosaminoglycan (GAG) content; the lipid content; and the pyridinoline (Pyd) content. The results indicate that these bone quality parameters in healthy, actively-forming trabecular bone surfaces are dependent on subject age at constant tissue age, suggesting that with advancing age the kinetics of maturation (either accumulation, or posttranslational modifications, or both) change. For most parameters, the extrapolation of models fitted to the individual age dependence of bone in healthy individuals was in rough agreement with their values in postmenopausal osteoporotic patients, except for MMC, lipid, and Pyd content. Among these three, Pyd content showed the greatest deviation between healthy aging and disease, highlighting its potential to be used as a discriminating factor. © 2015 American Society for Bone and Mineral Research.

Lifelong physical activity in maintaining bone strength in older men and women of the Age, Gene/Environment Susceptibility-Reykjavik Study.

PubMed

Rianon, N J; Lang, T F; Sigurdsson, G; Eiriksdottir, G; Sigurdsson, S; Garcia, M; Pajala, S; Koster, A; Yu, B; Selwyn, B J; Taylor, W C; Kapadia, A S; Gudnason, V; Launer, L J; Harris, T B

2012-09-01

We examined if lifelong physical activity is important for maintaining bone strength in the elderly. Associations of quantitative computerized tomography-acquired bone measures (vertebral and femoral) and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES-Reykjavik Study. Results conclude lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health later in life. Skeletal loading is thought to modulate the loss of bone in later life, and physical activity is a chief means of affecting bone strength by skeletal loading. Despite much discussion regarding lifelong versus early adulthood physical activity for preventing bone loss later in life, inconsistency still exists regarding how to maintain bone mass later in life (≥65 years). We examined if lifelong physical activity is important for maintaining bone strength in the elderly. The associations of quantitative computerized tomography-acquired vertebral and femoral bone measures and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES-Reykjavik Study. Our findings conclude that lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health in the elderly.

A Review and Proposed Rationale for the use of Ultrasonography as a Diagnostic Modality in the Identification of Bone Stress Injuries.

PubMed

Fukushima, Yaeko; Ray, Jeremiah; Kraus, Emily; Syrop, Isaac P; Fredericson, Michael

2018-04-14

Bone stress injuries are common in military personnel and athletes. The delayed diagnosis of a bone stress injury can lead to a more severe injury that requires a longer period of treatment. The early detection of bone stress injuries is a central part of management. Currently, the reference standard for detecting bone stress injuries is magnetic resonance imaging. However, the expanding use of point-of-care ultrasonography (US) may enable the early detection of bone stress injuries in the clinical setting. In this article, we review the US detection of bone stress injuries, as well as discuss the rationale for the use of US in the diagnosis of these injuries. © 2018 by the American Institute of Ultrasound in Medicine.

Effect of periodontitis on the development of osteoporosis: results from a nationwide population-based cohort study (2003-2013).

PubMed

Choi, Jung-Kyu; Kim, Young-Taek; Kweon, Hye-In; Park, Eun-Cheol; Choi, Seong-Ho; Lee, Jae-Hong

2017-09-11

The prevalence of osteoporosis associated with the aging process is anticipated to increase along with the rising aging population. Periodontitis that the most common chronic infections of humankind is considered the risk factor for osteoporosis. The aim of this study was to identify the association between osteoporosis and periodontitis using a population-based cohort. The case group was defined as patients diagnosed with periodontitis and treated with subgingival curettage, root conditioning, periodontal flap operation, bone grafting for alveolar bone defects, and guided tissue regeneration. Case and control groups matched for gender, age, household income, type of social security, disability, and residential area were generated. A Cox proportional hazard model was constructed to examine the difference in the development of osteoporosis between the case and control groups. The final sample included 13,464 participants. The incidence of osteoporosis was 1.1% in males and 15.8% in females during a 10-year period. The risk factors for osteoporosis in males were increasing age and Charlson Comorbidity Index score. Periodontitis was not associated with the development of osteoporosis in males. The risk factors for osteoporosis in females were increasing age, body mass index, Charlson Comorbidity Index score, diabetes, and periodontitis. Women with periodontitis were more likely to also develop osteoporosis (HR: 1.22, 95% CI: 1.01-1.48). Periodontitis has an effect on the development of osteoporosis in females. Managing good teeth is required for the prevention and delay of osteoporosis. This includes dental examinations, regular cleanings and gum treatment.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory.

PubMed

Jones, W; Roberts, R E

1933-05-01

(1) Pathology of calcification and ossification.-The Leriche-Policard theories. Hyperaemia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. "Myositis ossificans."(2) Radiological significance of density of bone shadows.-Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular.(3) Hyperaemic decalcification of bone.-Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperaemic dislocation of the atlas. Hyperaemic decalcification and nephrolithiasis.(4) Anaemic sclerosis of bone.-Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone-Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases.(5) Pathological calcification.-Calcification of supraspinatus tendon. Calcification of tumours-angioma, haematoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs.(6) Pathological ossification.-Ossification of tendons. Ossification of semilunar cartilages.

Identification of osteocalcin as a permanent aging constituent of the bone matrix: basis for an accurate age at death determination.

PubMed

Ritz, S; Turzynski, A; Schütz, H W; Hollmann, A; Rochholz, G

1996-01-12

Age at death determination based on aspartic acid racemization in dentin has been applied successfully in forensic odontology for several years now. An age-dependent accumulation of D-aspartic acid has also recently been demonstrated in bone osteocalcin, one of the most abundant noncollagenous proteins of the organic bone matrix. Evaluation of these initial data on in vivo racemization of aspartic acid in bone osteocalcin was taken a step further. After purification of osteocalcin from 53 skull bone specimens, the extent of aspartic acid racemization in this peptide was determined. The D-aspartic acid content of purified bone osteocalcin exhibited a very close relationship to age at death. This confirmed identification of bone osteocalcin as a permanent, 'aging' peptide of the organic bone matrix. Its D-aspartic acid content may be used as a measure of its age and hence that of the entire organism. The new biochemical approach to determination of age at death by analyzing bone is complex and demanding from a methodologic point of view, but appears to be superior in precision and reproducibility to most other methods applicable to bone.

Marginal Bone Loss after Ten Years in an Adult Danish Population: A Radiographic Study.

PubMed

Bahrami, Golnosh; Vaeth, Michael; Wenzel, Ann; Isidor, Flemming

To evaluate marginal bone loss over a 10-year period in individuals and in tooth groups in relation to age and level of marginal bone. In 1997, 616 randomly selected individuals (mean age: 42 years, range: 21-63 years) underwent a full-mouth radiographic survey. In 2008, the survey was repeated in 362 of the same individuals (182 women and 180 men). The marginal bone level of each tooth was measured in mm from the cementoenamel junction to the marginal bone. These measurements were used to calculate marginal bone loss during the 10-year period for individuals and tooth groups in relation to age and to baseline marginal bone level, calculated as the average between measurements in 1997 and 2008 to circumvent regression towards the mean. The average annual marginal bone loss was 0.09 mm (SD ± 0.04 mm) during the 10-year study period. The association between marginal bone loss and baseline marginal bone level was more pronounced in the youngest age group, compared to the other age groups. Molars displayed the most severe bone loss during the study period. Marginal bone loss over a 10-year period is associated with age and baseline marginal bone level. Younger individuals with a reduced marginal bone level were at higher risk for further bone loss. Molars lose marginal bone more rapidly than other tooth groups.

Case Report: The Specter of Untreated Congenital Hypothyroidism in Immigrant Families

PubMed Central

Hamdoun, Elwaseila; Karachunski, Peter; Nathan, Brandon; Fischer, Melissa; Torkelson, Jane L.; Drilling, Amy

2016-01-01

Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was –7.5 SDs with a very delayed bone age of –13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (–5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. PMID:27244801

Case Report: The Specter of Untreated Congenital Hypothyroidism in Immigrant Families.

PubMed

Hamdoun, Elwaseila; Karachunski, Peter; Nathan, Brandon; Fischer, Melissa; Torkelson, Jane L; Drilling, Amy; Petryk, Anna

2016-05-01

Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was -7.5 SDs with a very delayed bone age of -13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (-5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. Copyright © 2016 by the American Academy of Pediatrics.

Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

PubMed Central

Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

2016-01-01

Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

Age related changes in the bone tissue under conditions of hypokinesia

NASA Technical Reports Server (NTRS)

Podrushnyak, E. P.; Suslov, E. I.

1980-01-01

Microroentgenography of nine young people, aged 24-29, before and after hypokinesia (16-37 days strict bed rest), showed that the heel bone density of those with initially high bone density generally decreased and that of those with initially low bone density generally increased. X-ray structural analysis of the femurs of 25 corpses of accidentally killed healthy people, aged 18-70, data are presented and discussed, with the conclusion that the bone hydroxyapatite crystal structure stabilizes by ages 20 to 25, is stable from ages 25 to 60 and decreases in density after age 60. It is concluded that bone tissue structure changes, both with age, and in a comparatively short time in hypokinesia.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation

PubMed Central

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-01-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra–bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss. PMID:25751060

State of the mineral component of rat bone tissue during hypokinesia and the recovery period

NASA Technical Reports Server (NTRS)

Volozhin, A. I.; Stupakov, G. P.; Pavlova, M. N.; Muradov, I. S.

1980-01-01

Experiments were conducted on young growing rats. Hypokinesia lasting from 20 to 200 days caused retarded gain in weight and volume of the femur and delayed development of the cortical layer of the diaphysis. In contrast, the density of the cortical layer of the femoral diaphysis increased due to elevation of the mineral saturation of the bone tissue microstructures. Incorporation of Ca into the bone tissue in hypokinesia had a tendency to reduce. Partial normalization of the bone tissue mineral component occurred during a 20 day recovery period following hypokinesia.

The effects of a CO2 laser on the healing of a bone defect.

PubMed

Corsair, A

1997-03-01

This case report illustrates a potentially valuable application of the CO2 laser in periodontal surgery. An intrabony defect was treated with a bone allograft. During the 28-day postsurgical period, epithelialization of the wound was delayed by lasing the soft tissue over the bony defect at weekly intervals for 4 weeks. This procedure resulted in complete regeneration of the bone defect in this case. Controlled studies need to be carried out to determine if the use of the laser to retard epithelial downgrowth has a clinically significant effect on bone regeneration.

Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae

PubMed Central

Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

2012-01-01

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20–40 years) and a group of elderly women (n = 5, age: 70–95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (−2.374 vs. −2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. PMID:22946475

Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae.

PubMed

Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

2012-11-01

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20-40 years) and a group of elderly women (n = 5, age: 70-95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (-2.374 vs. -2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

Effect of Age and Caponization on Blood Parameters and Bone Development of Male Native Chickens in Taiwan

PubMed Central

Lin, Cheng-Yung; Hsu, Jenn-Chung; Wan, Tien-Chun

2012-01-01

An experiment was carried out to determine the effect of age and caponization on the development blood and bone characteristics development in male country chickens in Taiwan. A total of two hundred 8-wk-old LRI native chicken cockerels, Taishi meat No.13 from LRI-COA, were used as experimental animals. Cockerels were surgically caponized at 8 wks of age. Twelve birds in each group were bled and dressed from 8 wks to 35 wks of age at 1 to 5 wk intervals. The results indicated that the plasma testosterone concentration was significantly (p<0.05) lower in capons after 12 wks of age (caponized treatment after 4 wks) than that of the intact males. The relative tibia weight, bone breaking strength, cortical thickness, bone ash, bone calcium, bone phosphorus and bone magnesium contents were significantly (p<0.05) higher in intact males, while capons had higher (p<0.05) plasma ionized calcium, inorganic phosphorus and alkaline phosphatase concentration. The plasma testosterone concentration, relative tibia weight, tibia length, breaking strength, cortical thickness, bone ash, calcium, and phosphorus contents of intact males chickens increased significantly (p<0.05) with the advance of age. In addition, the relative tibia weight of capons peaked at 18 wks of age, and declined at 35 wks of age. The bone ash, calcium and phosphorus content increased most after 14 wks of age in male native chickens in Taiwan. Also, tibia length and cortical thickness peaked at 22 wks of age. However, the peak of bone strength was found at 26 wks of age. These findings support the assertion that androgens can directly influence bone composition fluxes in male chickens. Caponization caused a significant increase in bone loss at 4 wks post treatment, which reflected bone cell damage, and demonstrated reductions in the relative tibia weight, breaking strength, cortical thickness, bone ash, calcium, phosphorus and magnesium contents, and increases in plasma ionized calcium, inorganic phosphorus and alkaline phosphatase concentration. PMID:25049655

X-Ray Exam: Bone Age Study (For Parents)

MedlinePlus

... for Educators Search English Español X-Ray Exam: Bone Age Study KidsHealth / For Parents / X-Ray Exam: Bone Age Study What's in this article? What It ... de la edad ósea What It Is A bone age study helps doctors estimate the maturity of ...

Segmenting Bone Parts for Bone Age Assessment using Point Distribution Model and Contour Modelling

NASA Astrophysics Data System (ADS)

Kaur, Amandeep; Singh Mann, Kulwinder, Dr.

2018-01-01

Bone age assessment (BAA) is a task performed on radiographs by the pediatricians in hospitals to predict the final adult height, to diagnose growth disorders by monitoring skeletal development. For building an automatic bone age assessment system the step in routine is to do image pre-processing of the bone X-rays so that features row can be constructed. In this research paper, an enhanced point distribution algorithm using contours has been implemented for segmenting bone parts as per well-established procedure of bone age assessment that would be helpful in building feature row and later on; it would be helpful in construction of automatic bone age assessment system. Implementation of the segmentation algorithm shows high degree of accuracy in terms of recall and precision in segmenting bone parts from left hand X-Rays.

Clinical Results and Complications of Lower Limb Lengthening for Fibular Hemimelia: A Report of Eight Cases.

PubMed

Mishima, Kenichi; Kitoh, Hiroshi; Iwata, Koji; Matsushita, Masaki; Nishida, Yoshihiro; Hattori, Tadashi; Ishiguro, Naoki

2016-05-01

Fibular hemimelia is a rare but the most common congenital long bone deficiency, encompassing a broad range of anomalies from isolated fibular hypoplasia up to substantial femoral and tibial shortening with ankle deformity and foot deficiency. Most cases of fibular hemimelia manifest clinically significant leg length discrepancy (LLD) with time that requires adequate correction by bone lengthening for stable walking. Bone lengthening procedures, especially those for pathological bones, are sometimes associated with severe complications, such as delayed consolidation, fractures, and deformities of the lengthened bones, leading to prolonged healing time and residual LLD at skeletal maturity. The purpose of this study was to review our clinical results of lower limb lengthening for fibular hemimelia.This study included 8 Japanese patients who diagnosed with fibular hemimelia from physical and radiological findings characteristic of fibular hemimelia and underwent single or staged femoral and/or tibial lengthening during growth or after skeletal maturity. LLD, state of the lengthened callus, and bone alignment were evaluated with full-length radiographs of the lower limb. Previous interventions, associated congenital anomalies, regenerate fractures were recorded with reference to medical charts and confirmed on appropriate radiographs. Successful lengthening was defined as the healing index <50 days/cm without regenerate fractures.A significant difference was observed in age at surgery between successful and unsuccessful lengthening. The incidence of regenerate fractures was significantly correlated with callus maturity before frame removal. LLD was corrected within 11 mm, whereas mechanical axis deviated laterally.Particular attention should be paid to the status of callus maturation and the mechanical axis deviation during the treatment period in fibular hemimelia.

Wrapping grafting for congenital pseudarthrosis of the tibia

PubMed Central

Yan, An; Mei, Hai-Bo; Liu, Kun; Wu, Jiang-Yan; Tang, Jin; Zhu, Guang-Hui; Ye, Wei-Hua

2017-01-01

Abstract Objective: Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. The autogenic iliac bone graft is important consistent of treatment for CPT. The purpose of this study was to investigate the role of wrapping autogenic iliac bone graft in improvement of the curing opportunities of CPT. Methods: We combined Ilizarov fixator with intramedullary rodding of the tibia and wrapping autogenic iliac bone graft for treatment 51 cases of CPT between 2007 and 2010. The mean age is 3.2 years at index operation, of which 31 patients (61%) were below 3 years old. According to Crawford classification, 5 tibia had type-II morphology; 3, type-III; 43, type-IV. Results: In the postoperative follow-up of 3.5 months (range from 3 to 4.5 months), all cases were found that the bone graft sites of pseudarthrosis of the tibia showed a significant augmentation and spindle-shaped expansion as obvious change. All cases of this series have been followed-up, average followed-up time were 1.6 years (range from 7 to 3.1 years), of which 19 cases were more than 2 years. The average time of removed the Ilizarov ring fixator was 3.5 months (range from 3 to 4.5 months). According to Johnston Clinical evaluation system, 26 cases had grade I, 21 cases, grade II, 4 cases, grade III. Following the Ohnishi X-ray evaluation criteria, union of pseudarthrosis of the tibia were 42 cases, delayed union 5 cases, nonunion 4 cases. Conclusion: Autogenic iliac bone graft is able to offer the activity of osteoblasts and osteogenesis induced by bone morphogenetic protein (BMP) and glycoprotein, meanwhile enclosing bone graft could help keep cancellous bone fragments in close contact around pseudarthrosis of the tibia, allowing the formation of high concentration of glycoprotein and BMP induced by chemical factors because of established the sealing environment in location, all of which could enhance the healing of pseudarthrosis of the tibia. PMID:29310362

Radionuclide Imaging of Musculoskeletal Injuries in Athletes with Negative Radiographs.

PubMed

Nagle, C E; Freitas, J E

1987-06-01

In brief: Radionuclide bone scans can be useful in the diagnostic evaluation of musculoskeletal injuries in athletes. Bone scans can detect shinsplints, stress fractures, and muscle injuries before they are detectable on radiographs. Prognosis can be accurately assessed, allowing appropriate treatment to proceed without delay. The authors discuss the use of bone scans and identify musculoskeletal injuries that are associated with specific sports, such as stress fracture of the femur (soccer), tibia (running), scapula (gymnastics), and pars interarticularis (football or lacrosse).

Bone scanning in the detection of occult fractures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batillas, J.; Vasilas, A.; Pizzi, W.F.

1981-07-01

The potential role of bone scanning in the early detection of occult fractures following acute trauma was investigated. Technetium 99m pyrophosphate bone scans were obtained in patients with major clinical findings and negative or equivocal roentgenograms following trauma. Bone scanning facilitated the prompt diagnosis of occult fractures in the hip, knee, wrist, ribs and costochondral junctions, sternum, vertebrae, sacrum, and coccyx. Several illustrative cases are presented. Roentgenographic confirmation occurred following a delay of days to weeks and, in some instances, the roentgenographic findings were subtle and could be easily overlooked. This study demonstrates bone scanning to be invaluable and definitivemore » in the prompt detection of occult fractures.« less

DYSAPOPTOSIS OF OSTEOBLASTS AND OSTEOCYTES INCREASES CANCELLOUS BONE FORMATION BUT EXAGGERATES BONE POROSITY WITH AGE

PubMed Central

Jilka, Robert L.; O’Brien, Charles A.; Roberson, Paula K.; Bonewald, Lynda F.; Weinstein, Robert S.; Manolagas, Stavros C.

2013-01-01

Skeletal aging is accompanied by decreased cancellous bone mass and increased formation of pores within cortical bone. The latter accounts for a large portion of the increase in non-vertebral fractures after age 65 in humans. We selectively deleted Bak and Bax, two genes essential for apoptosis, in two types of terminally differentiated bone cells: the short-lived osteoblasts that elaborate the bone matrix, and the long-lived osteocytes that are immured within the mineralized matrix and choreograph the regeneration of bone. Attenuation of apoptosis in osteoblasts increased their working lifespan and thereby cancellous bone mass in the femur. In long-lived osteocytes, however, it caused dysfunction with advancing age and greatly magnified intracortical femoral porosity associated with increased production of receptor activator of nuclear factor-κB ligand and vascular endothelial growth factor. Increasing bone mass by artificial prolongation of the inherent lifespan of short-lived osteoblasts, while exaggerating the adverse effects of aging on long-lived osteocytes, highlights the seminal role of cell age in bone homeostasis. In addition, our findings suggest that distress signals produced by old and/or dysfunctional osteocytes are the culprits of the increased intracortical porosity in old age. PMID:23761243

Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption.

PubMed

Yang, Xiao; Gandhi, Chintan; Rahman, Md Mizanur; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

2015-12-01

Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Previous studies have shown controversial results regarding the role of in situ AGEs accumulation in osteoclastic resorption. To address this issue, this study cultured human osteoclast cells directly on human cadaveric bone slices from different age groups (young and elderly) to warrant its relevance to in vivo conditions. The cell culture was terminated on the 3rd, 7th, and 10th day, respectively, to assess temporal changes in the number of differentiated osteoclasts, the number and size of osteoclastic resorption pits, the amount of bone resorbed, as well as the amount of matrix AGEs released in the medium by resorption. In addition, the in situ concentration of matrix AGEs at each resorption pit was also estimated based on its AGEs autofluorescent intensity. The results indicated that (1) osteoclastic resorption activities were significantly correlated with the donor age, showing larger but shallower resorption pits on the elderly bone substrates than on the younger ones; (2) osteoclast resorption activities were not significantly dependent on the in situ AGEs concentration in bone matrix, and (3) a correlation was observed between osteoclast activities and the concentration of AGEs released by the resorption. These results suggest that osteoclasts tend to migrate away from initial anchoring sites on elderly bone substrate during resorption compared to younger bone substrates. However, such behavior is not directly related to the in situ concentration of AGEs in bone matrix at the resorption sites.

Correlation between word recognition score and intracochlear new bone and fibrous tissue after cochlear implantation in the human.

PubMed

Kamakura, Takefumi; Nadol, Joseph B

2016-09-01

Cochlear implantation is an effective, established procedure for patients with profound deafness. Although implant electrodes have been considered as biocompatible prostheses, surgical insertion of the electrode induces various changes within the cochlea. Immediate changes include insertional trauma to the cochlea. Delayed changes include a tissue response consisting of inflammation, fibrosis and neo-osteogenesis induced by trauma and an immunologic reaction to a foreign body. The goal of this study was to evaluate the effect of these delayed changes on the word recognition scores achieved post-operatively. Seventeen temporal bones from patients who in life had undergone cochlear implantation were prepared for light microscopy. We digitally calculated the volume of fibrous tissue and new bone within the cochlea using Amira(®) three-dimensional reconstruction software and assessed the correlations of various clinical and histologic factors. The postoperative CNC word score was positively correlated with total spiral ganglion cell count. Fibrous tissue and new bone were found within the cochlea of all seventeen specimens. The postoperative CNC word score was negatively correlated with the % volume of new bone within the scala tympani, scala media/vestibuli and the cochlea, but not with the % volume of fibrous tissue. The % volume of new bone in the scala media/vestibuli was positively correlated with the degree of intracochlear insertional trauma, especially trauma to the basilar membrane. Our results revealed that the % volume of new bone as well as residual total spiral ganglion cell count are important factors influencing post-implant hearing performance. New bone formation may be reduced by limiting insertional trauma and increasing the biocompatibility of the electrodes. Copyright © 2016 Elsevier B.V. All rights reserved.

Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

PubMed

Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

2018-05-01

GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Correlation between word recognition score and intracochlear new bone and fibrous tissue after cochlear implantation in the human

PubMed Central

Kamakura, Takefumi; Nadol, Joseph B

2016-01-01

Cochlear implantation is an effective, established procedure for patients with profound deafness. Although implant electrodes have been considered as biocompatible prostheses, surgical insertion of the electrode induces various changes within the cochlea. Immediate changes include insertional trauma to the cochlea. Delayed changes include a tissue response consisting of inflammation, fibrosis and neo-osteogenesis induced by trauma and an immunologic reaction to a foreign body. The goal of this study was to evaluate the effect of these delayed changes on the word recognition scores achieved post-operatively. Seventeen temporal bones from patients who in life had undergone cochlear implantation were prepared for light microscopy. We digitally calculated the volume of fibrous tissue and new bone within the cochlea using Amira® three-dimensional reconstruction software and assessed the correlations of various clinical and histologic factors. The postoperative CNC word score was positively correlated with total spiral ganglion cell count. Fibrous tissue and new bone were found within the cochlea of all seventeen specimens. The postoperative CNC word score was negatively correlated with the % volume of new bone within the scala tympani, scala media/vestibuli and the cochlea, but not with the % volume of fibrous tissue. The % volume of new bone in the scala media/vestibuli was positively correlated with the degree of intracochlear insertional trauma, especially trauma to the basilar membrane. Our results revealed that the % volume of new bone as well as residual total spiral ganglion cell count are important factors influencing post-implant hearing performance. New bone formation may be reduced by limiting insertional trauma and increasing the biocompatibility of the electrodes. PMID:27371868

CD133: Enhancement of Bone Healing by Local Transplantation of Peripheral Blood Cells in a Biologically Delayed Rat Osteotomy Model

PubMed Central

Preininger, Bernd; Duda, Georg; Gerigk, Hinnerk; Bruckner, Jonas; Ellinghaus, Agnes; Sass, F. Andrea; Perka, Carsten; Schmidt-Bleek, Katharina; Dienelt, Anke

2013-01-01

Sufficient angiogenesis is crucial during tissue regeneration and therefore also pivotal in bone defect healing. Recently, peripheral blood derived progenitor cells have been identified to have in addition to their angiogenic potential also osteogenic characteristics, leading to the hypothesis that bone regeneration could be stimulated by local administration of these cells. The aim of this study was to evaluate the angiogenic potential of locally administered progenitor cells to improve bone defect healing. Cells were separated from the peripheral blood of donor animals using the markers CD34 and CD133. Results of the in vitro experiments confirmed high angiogenic potential in the CD133(+) cell group. CD34(+) and CD133(+) cells were tested in an in vivo rat femoral defect model of delayed healing for their positive effect on the healing outcome. An increased callus formation and higher bone mineral density of callus tissue was found after the CD133(+) cell treatment compared to the group treated with CD34(+) cells and the control group without cells. Histological findings confirmed an increase in vessel formation and mineralization at day 42 in the osteotomy gap after CD133(+) cell transplantation. The higher angiogenic potential of CD133(+) cells from the in vitro experients therefore correlates with the in vivo data. This study demonstrates the suitability of angiogenic precursors to further bone healing and gives an indication that peripheral blood is a promising source for progenitor cells circumventing the problems associated with bone marrow extraction. PMID:23457441

Cooperative hunting and meat sharing 400–200 kya at Qesem Cave, Israel

PubMed Central

Stiner, Mary C.; Barkai, Ran; Gopher, Avi

2009-01-01

Zooarchaeological research at Qesem Cave, Israel demonstrates that large-game hunting was a regular practice by the late Lower Paleolithic period. The 400- to 200,000-year-old fallow deer assemblages from this cave provide early examples of prime-age-focused ungulate hunting, a human predator–prey relationship that has persisted into recent times. The meat diet at Qesem centered on large game and was supplemented with tortoises. These hominins hunted cooperatively, and consumption of the highest quality parts of large prey was delayed until the food could be moved to the cave and processed with the aid of blade cutting tools and fire. Delayed consumption of high-quality body parts implies that the meat was shared with other members of the group. The types of cut marks on upper limb bones indicate simple flesh removal activities only. The Qesem cut marks are both more abundant and more randomly oriented than those observed in Middle and Upper Paleolithic cases in the Levant, suggesting that more (skilled and unskilled) individuals were directly involved in cutting meat from the bones at Qesem Cave. Among recent humans, butchering of large animals normally involves a chain of focused tasks performed by one or just a few persons, and butchering guides many of the formalities of meat distribution and sharing that follow. The results from Qesem Cave raise new hypotheses about possible differences in the mechanics of meat sharing between the late Lower Paleolithic and Middle Paleolithic. PMID:19666542

Effects of a laughter and exercise program on physiological and psychological health among community-dwelling elderly in Japan: randomized controlled trial.

PubMed

Hirosaki, Mayumi; Ohira, Tetsuya; Kajiura, Mitsugu; Kiyama, Masahiko; Kitamura, Akihiko; Sato, Shinichi; Iso, Hiroyasu

2013-01-01

To examine the effects of a once-weekly laughter and exercise program on physical and psychological health among elderly people living in the community. As a regular exercise program can be difficult to maintain, we provided a more enjoyable program to enhance adherence to exercise. A total of 27 individuals aged 60 years or older, without disabilities, were randomly assigned to either an immediate treatment group (n=14) or a delayed treatment group (n=13). The intervention was a 120-min session consisting of laughter and exercise, carried out once a week for 10 consecutive weeks. Measurements taken at baseline, 3 and 6 months included bodyweight, height, body fat, lean mass, bone mineral density, hemoglobin A1c (HbA(1c)), glucose, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides, as well as self-rated health and psychological factors. All participants completed the 3-month program. Bone mineral density increased significantly in the immediate treatment group compared with the delayed treatment group during the first 3 months (P<0.001). In addition, HbA(1c) decreased significantly (P=0.001), and self-rated health increased significantly (P=0.012). The combination of a laughter and exercise program might have physiological and psychological health benefits for the elderly. Laughter might be an effective strategy to motivate the elderly to participate in physical activity. © 2012 Japan Geriatrics Society.

Cooperative hunting and meat sharing 400-200 kya at Qesem Cave, Israel.

PubMed

Stiner, Mary C; Barkai, Ran; Gopher, Avi

2009-08-11

Zooarchaeological research at Qesem Cave, Israel demonstrates that large-game hunting was a regular practice by the late Lower Paleolithic period. The 400- to 200,000-year-old fallow deer assemblages from this cave provide early examples of prime-age-focused ungulate hunting, a human predator-prey relationship that has persisted into recent times. The meat diet at Qesem centered on large game and was supplemented with tortoises. These hominins hunted cooperatively, and consumption of the highest quality parts of large prey was delayed until the food could be moved to the cave and processed with the aid of blade cutting tools and fire. Delayed consumption of high-quality body parts implies that the meat was shared with other members of the group. The types of cut marks on upper limb bones indicate simple flesh removal activities only. The Qesem cut marks are both more abundant and more randomly oriented than those observed in Middle and Upper Paleolithic cases in the Levant, suggesting that more (skilled and unskilled) individuals were directly involved in cutting meat from the bones at Qesem Cave. Among recent humans, butchering of large animals normally involves a chain of focused tasks performed by one or just a few persons, and butchering guides many of the formalities of meat distribution and sharing that follow. The results from Qesem Cave raise new hypotheses about possible differences in the mechanics of meat sharing between the late Lower Paleolithic and Middle Paleolithic.

Computational segmentation of collagen fibers in bone matrix indicates bone quality in ovariectomized rat spine.

PubMed

Daghma, Diaa Eldin S; Malhan, Deeksha; Simon, Paul; Stötzel, Sabine; Kern, Stefanie; Hassan, Fathi; Lips, Katrin Susanne; Heiss, Christian; El Khassawna, Thaqif

2018-05-01

Bone loss varies according to disease and age and these variations affect bone cells and extracellular matrix. Osteoporosis rat models are widely investigated to assess mechanical and structural properties of bone; however, bone matrix proteins and their discrepant regulation of diseased and aged bone are often overlooked. The current study considered the spine matrix properties of ovariectomized rats (OVX) against control rats (Sham) at 16 months of age. Diseased bone showed less compact structure with inhomogeneous distribution of type 1 collagen (Col1) and changes in osteocyte morphology. Intriguingly, demineralization patches were noticed in the vicinity of blood vessels in the OVX spine. The organic matrix structure was investigated using computational segmentation of collagen fibril properties. In contrast to the aged bone, diseased bone showed longer fibrils and smaller orientation angles. The study shows the potential of quantifying transmission electron microscopy images to predict the mechanical properties of bone tissue.

* Calvarial Bone Regeneration Is Enhanced by Sequential Delivery of FGF-2 and BMP-2 from Layer-by-Layer Coatings with a Biomimetic Calcium Phosphate Barrier Layer.

PubMed

Gronowicz, Gloria; Jacobs, Emily; Peng, Tao; Zhu, Li; Hurley, Marja; Kuhn, Liisa T

2017-12-01

A drug delivery coating for synthetic bone grafts has been developed to provide sequential delivery of multiple osteoinductive factors to better mimic aspects of the natural regenerative process. The coating is composed of a biomimetic calcium phosphate (bCaP) layer that is applied to a synthetic bone graft and then covered with a poly-l-Lysine/poly-l-Glutamic acid polyelectrolyte multilayer (PEM) film. Bone morphogenetic protein-2 (BMP-2) was applied before the coating process directly on the synthetic bone graft and then, bCaP-PEM was deposited followed by adsorption of fibroblast growth factor-2 (FGF-2) into the PEM layer. Cells access the FGF-2 immediately, while the bCaP-PEM temporally delays the cell access to BMP-2. In vitro studies with cells derived from mouse calvarial bones demonstrated that Sca-1 and CD-166 positive osteoblast progenitor cells proliferated in response to media dosing with FGF-2. Coated scaffolds with BMP-2 and FGF-2 were implanted in mouse calvarial bone defects and harvested at 1 and 3 weeks. After 1 week in vivo, proliferation of cells, including Sca-1+ progenitors, was observed with low dose FGF-2 and BMP-2 compared to BMP-2 alone, indicating that in vivo delivery of FGF-2 activated a similar population of cells as shown by in vitro testing. At 3 weeks, FGF-2 and BMP-2 delivery increased bone formation more than BMP-2 alone, particularly in the center of the defect, confirming that the proliferation of the Sca-1 positive osteoprogenitors by FGF-2 was associated with increased bone healing. Areas of bone mineralization were positive for double fluorochrome labeling of calcium and alkaline phosphatase staining of osteoblasts, along with increased TRAP+ osteoclasts, demonstrating active bone formation distinct from the bone-like collagen/hydroxyapatite scaffold. In conclusion, the addition of a bCaP layer to PEM delayed access to BMP-2 and allowed the FGF-2 stimulated progenitors to populate the scaffold before differentiating in response to BMP-2, leading to improved bone defect healing.

Rapid restoration of bone mass after surgical management of hyperthyroidism: A prospective case control study in Southern India.

PubMed

Karunakaran, Poongkodi; Maharajan, Chandrasekaran; Mohamed, Kamaludeen N; Rachamadugu, Suresh V

2016-03-01

The rate and the extent of bone remineralization at cancellous versus cortical sites after treatment of hyperthyroidism is unclear. Few studies have examined the effect of operative management of hyperthyroidism on recovery of bone mass. To evaluate prospectively the bone mineral density (BMD), bone mineral content (BMC), and bone areal size at the spine, hip, and forearm before and after total thyroidectomy. A prospective case control observational study from August 2011 to July 2014 in a single center. This study evaluated 40 overt hyperthyroid patients and 31 age-matched euthyroid controls who were operative candidates. Bone indices were measured at baseline and 6-month postoperatively using dual energy x-ray absorptiometry. Serum levels of alkaline phosphatase and 25-hydroxy vitamin D3 (25OHD) were assessed. Baseline BMD of hyperthyroid subjects at the spine, hip, and forearm were less than euthyroid controls (P = .001) with concomitant increases in serum alkaline phosphatase (mean ± SD, 143 ± 72 vs 72 ± 23 IU/L control; P < .001). The 25OHD level was 24.3 ± 10.6 and 26.1 ± 14.6 ng/mL in patients and controls, respectively. Among hyperthyroid patients, posttreatment BMD expressed as g/cm(2) were 0.97 ± 0.12 (vs pretreatment 0.91 ± 0.14; P = .001) at the spine, 0.87 ± 0.12 (vs pretreatment 0.80 ± 0.13; P = .001) at the hip, and 0.67 ± 0.09 (vs pretreatment 0.64 ± 0.11; P = .191) at the forearm. The percent change in BMD was greatest at spine (8.3%) followed by the hip (7.6%) and forearm (3.0%). Operative management with total thyroidectomy improved the bone loss associated with hyperthyroidism as early as 6 months postoperatively at the hip and spine despite concomitant vitamin D deficiency. Delayed recovery of bone indices at the forearm, a cortical bone, requires further long-term evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacotherapy of bone metastases in breast cancer patients.

PubMed

Petrut, Bianca; Simmons, Christine; Broom, Reuben; Trinkaus, Mateya; Clemons, Mark

2008-04-01

A diagnosis of bone metastases is often a devastating occurrence in breast cancer patients. Bone metastases are associated with increased morbidity as reflected through pain, reduced quality of life and skeletal-related events. This paper reviews the role of different pharmacotherapeutic agents in the treatment of bone metastases from breast cancer. Randomised controlled trials of osteoclast-inhibiting agents, that is the bisphosphonates, have shown significant patient benefit. The aims of bisphosphonates are to prevent and delay skeletal-related events, reduce bone pain and improve quality of life. However, there are some limitations with bisphosphonate treatment. Biochemical markers of bone turnover seem to be a promising tool in guiding bisphosphonate treatment and future research directions. Hopefully, patient management will be further improved as new agents become available such as denosumab, osteoprotegerin analogues and anti-angiogenic agents.

Advanced Glycation End-products and Bone Fractures.

PubMed

Vashishth, Deepak

2009-08-01

Bone does not turn over uniformly, and becomes susceptible to post-translational modification by non-enzymatic glycation (NEG). NEG of bone causes the formation of advanced glycation end-products (AGEs) and this process is accelerated with aging, diabetes and antiresorptive postmenopausal osteoporosis therapy. Due to the elevated incidence of fracture associated with aging and diabetes, several studies have attempted to measure and evaluate AGEs as biomarkers for fracture risk. Here current methods of estimating AGEs in bone by liquid chromatography and fluorometric assay are summarized and the relationships between AGEs and fracture properties at whole bone, apparent tissue and matrix levels are discussed.

An uncommon clinical feature of IAN injury after third molar removal: a delayed paresthesia case series and literature review.

PubMed

Borgonovo, Andrea; Bianchi, Albino; Marchetti, Andrea; Censi, Rachele; Maiorana, Carlo

2012-05-01

After an inferior alveolar nerve (IAN) injury, the onset of altered sensation usually begins immediately after surgery. However, it sometimes begins after several days, which is referred to as delayed paresthesia. The authors considered three different etiologies that likely produce inflammation along the nerve trunk and cause delayed paresthesia: compression of the clot, fibrous reorganization of the clot, and nerve trauma caused by bone fragments during clot organization. The aim of this article was to evaluate the etiology of IAN delayed paresthesia, analyze the literature, present a case series related to three different causes of this pathology, and compare delayed paresthesia with the classic immediate symptomatic paresthesia.

Expansion of myeloid-derived suppressor cells with aging in the bone marrow of mice through a NF-κB-dependent mechanism.

PubMed

Flores, Rafael R; Clauson, Cheryl L; Cho, Joonseok; Lee, Byeong-Chel; McGowan, Sara J; Baker, Darren J; Niedernhofer, Laura J; Robbins, Paul D

2017-06-01

With aging, there is progressive loss of tissue homeostasis and functional reserve, leading to an impaired response to stress and an increased risk of morbidity and mortality. A key mediator of the cellular response to damage and stress is the transcription factor NF-κB. We demonstrated previously that NF-κB transcriptional activity is upregulated in tissues from both natural aged mice and in a mouse model of a human progeroid syndrome caused by defective repair of DNA damage (ERCC1-deficient mice). We also demonstrated that genetic reduction in the level of the NF-κB subunit p65(RelA) in the Ercc1 -/∆ progeroid mouse model of accelerated aging delayed the onset of age-related pathology including muscle wasting, osteoporosis, and intervertebral disk degeneration. Here, we report that the largest fraction of NF-κB -expressing cells in the bone marrow (BM) of aged (>2 year old) mice (C57BL/6-NF-κB EGFP reporter mice) are Gr-1 + CD11b + myeloid-derived suppressor cells (MDSCs). There was a significant increase in the overall percentage of MDSC present in the BM of aged animals compared with young, a trend also observed in the spleen. However, the function of these cells appears not to be compromised in aged mice. A similar increase of MDSC was observed in BM of progeroid Ercc1 -/∆ and BubR1 H/H mice. The increase in MDSC in Ercc1 -/∆ mice was abrogated by heterozygosity in the p65/RelA subunit of NF-κB. These results suggest that NF-κB activation with aging, at least in part, drives an increase in the percentage of MDSCs, a cell type able to suppress immune cell responses. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Maternal Nutrition during Pregnancy Affects Testicular and Bone Development, Glucose Metabolism and Response to Overnutrition in Weaned Horses Up to Two Years

PubMed Central

Mendoza, Luis; Peugnet, Pauline; Dubois, Cédric; Dahirel, Michèle; Lejeune, Jean-Philippe; Caudron, Isabelle; Guenon, Isabelle; Camous, Sylvaine; Tarrade, Anne; Wimel, Laurence; Serteyn, Didier; Bouraima-Lelong, Hélène; Chavatte-Palmer, Pascale

2017-01-01

Introduction Pregnant mares and post-weaning foals are often fed concentrates rich in soluble carbohydrates, together with forage. Recent studies suggest that the use of concentrates is linked to alterations of metabolism and the development of osteochondrosis in foals. The aim of this study was to determine if broodmare diet during gestation affects metabolism, osteoarticular status and growth of yearlings overfed from 20 to 24 months of age and/or sexual maturity in prepubertal colts. Material and methods Twenty-four saddlebred mares were fed forage only (n = 12, group F) or cracked barley and forage (n = 12, group B) from mid-gestation until foaling. Colts were gelded at 12 months of age. Between 20 and 24 months of age, all yearlings were overfed (+140% of requirements) using an automatic concentrate feeder. Offspring were monitored for growth between 6 and 24 months of age, glucose homeostasis was evaluated via modified frequently sampled intra veinous glucose tolerance test (FSIGT) at 19 and 24 months of age and osteoarticular status was investigated using radiographic examinations at 24 months of age. The structure and function of testicles from prepubertal colts were analyzed using stereology and RT-qPCR. Results Post-weaning weight growth was not different between groups. Testicular maturation was delayed in F colts compared to B colts at 12 months of age. From 19 months of age, the cannon bone was wider in B vs F yearlings. F yearlings were more insulin resistant at 19 months compared to B yearlings but B yearlings were affected more severely by overnutrition with reduced insulin sensitivity. The osteoarticular status at 24 months of age was not different between groups. Conclusion In conclusion, nutritional management of the pregnant broodmare and the growing foal may affect sexual maturity of colts and the metabolism of foals until 24 months of age. These effects may be deleterious for reproductive and sportive performances in older horses. PMID:28081146

Age determination in manatees using growth-layer-group counts in bone

USGS Publications Warehouse

Marmontel, M.; O'Shea, T.J.; Kochman, H.I.; Humphrey, S.R.

1996-01-01

Growth layers were observed in histological preparations of bones of known-age, known minimum-age, and tetracycline-marked free-ranging and captive Florida manatees (Trichechus manatus latirostris), substantiating earlier preliminary findings of other studies. Detailed analysis of 17 new case histories showed that growth-layer group (GLG) counts in the periotic bone were consistent with known age, or time since tetracycline administration, but were less reliable in other bones. GLG counts were also made in periotic bones of 1,196 Florida manatees of unknown age found dead from 1974 through 1991. These counts were conducted in order to assess variability and to determine relationships among estimated age, size, sex, and degree of bone resorption. Resorption can interfere with accuracy of GLG counts. This effect does not occur until ages greater than about 15 yr and body lengths greater than 300 cm are attained. GLGs were also observed in periotic bones of Antillean manatees (Trichechus manatus manatus) but were not validated against known-age specimens. Use of GLG counts in the periotic bone is suitable for application to studies of population dynamics and other age-related aspects of manatee biology.

Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis.

PubMed

Schmidt-Bleek, Katharina; Kwee, Brian J; Mooney, David J; Duda, Georg N

2015-08-01

Delayed healing or nonhealing of bone is an important clinical concern. Although bone, one of the two tissues with scar-free healing capacity, heals in most cases, healing is delayed in more than 10% of clinical cases. Treatment of such delayed healing condition is often painful, risky, time consuming, and expensive. Tissue healing is a multistage regenerative process involving complex and well-orchestrated steps, which are initiated in response to injury. At best, these steps lead to scar-free tissue formation. At the onset of healing, during the inflammatory phase, stationary and attracted macrophages and other immune cells at the fracture site release cytokines in response to injury. This initial reaction to injury is followed by the recruitment, proliferation, and differentiation of mesenchymal stromal cells, synthesis of extracellular matrix proteins, angiogenesis, and finally tissue remodeling. Failure to heal is often associated with poor revascularization. Since blood vessels mediate the transport of circulating cells, oxygen, nutrients, and waste products, they appear essential for successful healing. The strategy of endogenous regeneration in a tissue such as bone is interesting to analyze since it may represent a blueprint of successful tissue formation. This review highlights the interdependency of the time cascades of inflammation, angiogenesis, and tissue regeneration. A better understanding of these inter-relations is mandatory to early identify patients at risk as well as to overcome critical clinical conditions that limit healing. Instead of purely tolerating the inflammatory phase, modulations of inflammation (immunomodulation) might represent a valid therapeutic strategy to enhance angiogenesis and foster later phases of tissue regeneration.

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

PubMed Central

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes.

PubMed

Nabeshima, Yoko; Washida, Miwa; Tamura, Masaru; Maeno, Akiteru; Ohnishi, Mutsuko; Shiroishi, Toshihiko; Imura, Akihiro; Razzaque, M Shawkat; Nabeshima, Yo-ichi

2014-08-01

Taking good care of elderly is a major challenge of our society, and thus identification of potential drug targets to reduce age-associated disease burden is desirable. α-klotho(-/-) (α-kl) is a short-lived mouse model that displays multiple phenotypes resembling human aging-related syndromes. Such ageing phenotype of α-kl(-/-) mice is associated with activation of a proteolytic enzyme, Calpain-1. We hypothesized that uncontrolled activation of calpain-1 might be causing age-related phenotypes in α-kl-deficient mice. We found that daily administration of BDA-410, a calpain-1 inhibitor, strikingly ameliorated multiple aging-related phenotypes. Treated mice showed recovery of reproductive ability, increased body weight, reduced organ atrophy, and suppression of ectopic calcifications, bone mineral density reduction, pulmonary emphysema and senile atrophy of skin. We also observed ectopic expression of FGF23 in calcified arteries of α-kl(-/-) mice, which might account for the clinically observed association of increased FGF23 level with increased risk of cardiovascular mortality. These findings allow us to propose that modulation of calpain-1 activity is a potential therapeutic option for delaying age-associated organ pathology, particularly caused by the dysregulation of mineral ion homeostasis.

Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes

PubMed Central

Nabeshima, Yoko; Washida, Miwa; Tamura, Masaru; Maeno, Akiteru; Ohnishi, Mutsuko; Shiroishi, Toshihiko; Imura, Akihiro; Razzaque, M. Shawkat; Nabeshima, Yo-ichi

2014-01-01

Taking good care of elderly is a major challenge of our society, and thus identification of potential drug targets to reduce age-associated disease burden is desirable. α-klotho-/- (α-kl) is a short-lived mouse model that displays multiple phenotypes resembling human aging-related syndromes. Such ageing phenotype of α-kl-/- mice is associated with activation of a proteolytic enzyme, Calpain-1. We hypothesized that uncontrolled activation of calpain-1 might be causing age-related phenotypes in α-kl-deficient mice. We found that daily administration of BDA-410, a calpain-1 inhibitor, strikingly ameliorated multiple aging-related phenotypes. Treated mice showed recovery of reproductive ability, increased body weight, reduced organ atrophy, and suppression of ectopic calcifications, bone mineral density reduction, pulmonary emphysema and senile atrophy of skin. We also observed ectopic expression of FGF23 in calcified arteries of α-kl-/- mice, which might account for the clinically observed association of increased FGF23 level with increased risk of cardiovascular mortality. These findings allow us to propose that modulation of calpain-1 activity is a potential therapeutic option for delaying age-associated organ pathology, particularly caused by the dysregulation of mineral ion homeostasis. PMID:25080854

Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

NASA Technical Reports Server (NTRS)

Bloomfield, Susan A.; Hogan, Harry A.; Delp, Michael D.

2002-01-01

The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats.

PubMed

El Khassawna, Thaqif; Böcker, Wolfgang; Brodsky, Katharina; Weisweiler, David; Govindarajan, Parameswari; Kampschulte, Marian; Thormann, Ulrich; Henss, Anja; Rohnke, Marcus; Bauer, Natali; Müller, Robert; Deutsch, Andreas; Ignatius, Anita; Dürselen, Lutz; Langheinrich, Alexander; Lips, Katrin S; Schnettler, Reinhard; Heiss, Christian

2015-11-01

Bone loss is a symptom related to disease and age, which reflects on bone cells and ECM. Discrepant regulation affects cell proliferation and ECM localization. Rat model of osteoporosis (OVX) was investigated against control rats (Sham) at young and old ages. Biophysical, histological and molecular techniques were implemented to examine the underlying cellular and extracellular matrix changes and to assess the mechanisms contributing to bone loss in the context of aging and the widely used osteoporotic models in rats. Bone loss exhibited a compromised function of bone cells and infiltration of adipocytes into bone marrow. However, the expression of genes regulating collagen catabolic process and adipogenesis was chronologically shifted in diseased bone in comparison with aged bone. The data showed the involvement of Wnt signaling inhibition in adipogenesis and bone loss due to over-expression of SOST in both diseased and aged bone. Further, in the OVX animals, an integrin-mediated ERK activation indicated the role of MAPK in osteoblastogenesis and adipogenesis. The increased PTH levels due to calcium and estrogen deficiency activated osteoblastogenesis. Thusly, RANKL-mediated osteoclastogenesis was initiated. Interestingly, the data show the role of MEPE regulating osteoclast-mediated resorption at late stages in osteoporotic bone. The interplay between ECM and bone cells change tissue microstructure and properties. The involvement of Wnt and MAPK pathways in activating cell proliferation has intriguing similarities to oncogenesis and myeloma. The study indicates the importance of targeting both pathways simultaneously to remedy metabolic bone diseases and age-related bone loss.

ASSOCIATION BETWEEN NON-ENZYMATIC GLYCATION, RESORPTION, AND MICRODAMAGE IN HUMAN TIBIAL CORTICES

PubMed Central

Karim, Lamya; Diab, Tamim; Vashishth, Deepak

2015-01-01

Purpose/Introduction Changes in the quality of bone material contribute significantly to bone fragility. In order to establish a better understanding of the interaction of the different components of bone quality and their influence on bone fragility we investigated the relationship between non-enzymatic glycation, resorption, and microdamage generated in vivo in cortical bone using bone specimens from the same donors. Methods Total fluorescent advanced glycation end-products (AGEs) were measured in 96 human cortical bone samples from 83 donors. Resorption pit density, average resorption pit area, and percent resorption area were quantified in samples from 48 common donors with AGE measurements. Linear microcrack density and diffuse damage were measured in 21 common donors with AGE and resorption measurements. Correlation analyses were performed between all measured variables to establish the relationships among them and their variation with age. Results We found that average resorption pit area and percent resorption area decreased with increasing AGEs independently of age. Resorption pit density and percent resorption area demonstrated negative age-adjusted correlation with diffuse damage. Furthermore, average resorption pit area, resorption pit density, and percent resorption area were found to decrease significantly with age. Conclusions The current study demonstrated the in vivo interrelationship between the organic constituents, remodeling, and damage formation in cortical bone. In addition to the age-related reduction in resorption, there is a negative correlation between AGEs and resorption independent of age. This inverse relationship indicates that AGEs alter the resorption process and/or accumulate in the tissue as a result of reduced resorption and may lead to bone fragility by adversely affecting fracture resistance through altered bone matrix properties. PMID:25326375

Delayed hypersensitivity and neutrophil chemotaxis: effect of trauma.

PubMed

Meakins, J L; McLean, A P; Kelly, R; Bubenik, O; Pietsch, J B; MacLean, L D

1978-04-01

To investigate alterations in host defense produced by trauma, skin testing with five standard recall antigens was done on admission and weekly on 53 patients with blunt trauma and seven with penetrating missile injuries, who then were classified as normal (N), 2 or more positive responses; relatively anergic (RA), one positive response; or anergic (A), no response. Neutrophil chemotaxis was tested 145 times in 32 patients. Degree of injury was assessed by assigning one point to pelvic fracture, long-bone fracture, head, chest, or abdominal injury, to a maximum of five. The A and RA patients had greater trauma, 3 vs. 1.6 for N, and a significantly increased rate of sepsis (p less than 0.005) and mortality (p less than 0.05). Incidence of anergy depended upon age and extent of trauma. Neutrophil chemotaxis in A and RA patients was significantly (p less than 0.001) worse at 96.7 +/- 2.4 mu and 99.8 +/- 1.7 mu compared to N, 113.2 +/- 1.7 mu, and controls 121 +/- 4 mu. With recovery, chemotaxis returned to normal. It is concluded that failure of delayed hypersensitivity responses follows trauma, is related to the severity of injury and age of patient, and is associated with an abnormality of neutrophil chemotaxis and increased rate of sepsis.

Assessment and management of nutrition in older people and its importance to health.

PubMed

Ahmed, Tanvir; Haboubi, Nadim

2010-08-09

Nutrition is an important element of health in the older population and affects the aging process. The prevalence of malnutrition is increasing in this population and is associated with a decline in: functional status, impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, higher hospital readmission rates, and mortality. Older people often have reduced appetite and energy expenditure, which, coupled with a decline in biological and physiological functions such as reduced lean body mass, changes in cytokine and hormonal level, and changes in fluid electrolyte regulation, delay gastric emptying and diminish senses of smell and taste. In addition pathologic changes of aging such as chronic diseases and psychological illness all play a role in the complex etiology of malnutrition in older people. Nutritional assessment is important to identify and treat patients at risk, the Malnutrition Universal Screening Tool being commonly used in clinical practice. Management requires a holistic approach, and underlying causes such as chronic illness, depression, medication and social isolation must be treated. Patients with physical or cognitive impairment require special care and attention. Oral supplements or enteral feeding should be considered in patients at high risk or in patients unable to meet daily requirements.

Determinants of utilization of traditional bone setters in Ilorin, north central Nigeria.

PubMed

Aderibigbe, S A; Agaja, S R; Bamidele, J O

2013-03-01

Traditional bone setting (TBS) practice is an important part of health care delivery in many developing countries and has been in Nigeria for long. Despite the complications that arise from the cultural practice, TBS services is still in high demand by a significant number of people. This study was conducted to determine the factors that influence the utilization of TBS practice. A descriptive cross-sectional study was carried out using a semi structured questionnaire to gather information from 400 randomly selected residents of ilorin West LGA in north central Nigeria. Multistage sampling technique was used in selecting the respondents. The respondents were between the ages of 18-72 years with a mean age of 36.3 +/- 12.3. Three hundred and three (77.3%) of the respondents know of TBS practice as a way of getting treatment for bone injuries. More than two third 210 (69.3%) of the respondents who know TBS practice as a form of treatment for bone injuries think that TBS therapy is preferable to Orthodox medicine in handling bone injuries. Reasons for preference are that it is cheap 134 (63.8%), acceptable 123 (58.6%) and accessible 109 (51.9%) to them. More than half(52.3%) of the respondents had patronized TBS treatment at one time or the other. Main reason for patronage of TBS was influence from family members and friends (53.6%). However, factors that influence the respondents decision to utilize TBS treatment include attitude of health workers 310 (77.5%), delay in hospitals 284(71.0%) fear of amputation 272 (54.35) and fear of operation 217(54.3%) in hospitals. There was a statistically significant (p < 0.05) relationship between respondents age, sex, marital status, occupation, ethnicity as well as the income level of the respondents and the utilization of TBS. Utilisation of TBS is quite popular among the studied population because it is believed to be cheap, acceptable and accessible to them and a high proportion of the respondents utilize TBS notwithstanding that they live in a community where they have better access to orthodox medical care. Influence from family and friends is the main reason for consulting TBS. Regulations should be made concerning the advertisement of TBS practice by relevant agencies and the public should be made aware through health education on the dangers of TBS treatment.

Bone Area Histomorphometry.

PubMed

Andronowski, Janna M; Crowder, Christian

2018-05-21

Quantifying the amount of cortical bone loss is one variable used in histological methods of adult age estimation. Measurements of cortical area tend to be subjective and additional information regarding bone loss is not captured considering cancellous bone is disregarded. We describe whether measuring bone area (cancellous + cortical area) rather than cortical area may improve histological age estimation for the sixth rib. Mid-shaft rib cross-sections (n = 114) with a skewed sex distribution were analyzed. Ages range from 16 to 87 years. Variables included: total cross-sectional area, cortical area, bone area, relative bone area, relative cortical area, and endosteal area. Males have larger mean total cross-sectional area, bone area, and cortical area than females. Females display a larger mean endosteal area and greater mean relative measure values. Relative bone area significantly correlates with age. The relative bone area variable will provide researchers with a less subjective and more accurate measure than cortical area. © 2018 American Academy of Forensic Sciences.

[Fat embolism syndrome after bone fractures].

PubMed

Campo-López, C; Flors-Villaverde, P; Calabuig-Alborch, J R

2012-11-01

To review the incidence, clinical features, diagnosis, therapy and mortality rates of fat embolism syndrome (FES) in a tertiary referral hospital in the last decade. Retrospective and descriptive study of patients diagnosed with post-traumatic FES between january 2001 and december 2011. A total of 19 patients, 16 men and 3 women, with an average age of 27 years were evaluated. All had long bone fractures, multiple in 78.9%, as a result of multiple injuries. Respiratory symptoms were the most frequent (89.5%), followed by neurological symptoms (68.4%) and petechial rash (63.2%). The average time of presentation of the syndrome after admission was 42 hours. All patients underwent early stabilisation of the fracture prior to the embolic event. Steroids prophylaxis was not used in any of the cases. Definitive surgical treatment had mean delay of 7 days. The mean hospital stay was 34 days. The overall incidence of FES was 0.14%, and mortality was 10.5%. Post-traumatic FES mainly affected young patients with multiple injuries and long bone fractures. They all had symptoms of the classic clinical triad (respiratory, neurological, rash) after an initial asymptomatic period of less than 2 days. The overall incidence was low. Copyright © 2012 Elsevier España, S.L. All rights reserved.

A double-plating approach to distal femur fracture: A clinical study.

PubMed

Steinberg, Ely L; Elis, Jacov; Steinberg, Yohai; Salai, Moshe; Ben-Tov, Tomer

2017-10-01

Locked plating is one of the latest innovative options for treating supracondylar femur fractures with relatively low failure rates. Single lateral plating was often found to have a relative higher failure rate. No clinical studies of double-plating distal femur fixation have thus far been reported. The aim of this study is to present our clinical experience with this surgical approach. Thirty-two patients (26 females and 6 males, mean age 76 years, range 44-101) were included in the study. Eight of them patients had a periprosthetic stable implant fracture and two patients were treated for a nonunion. All fractures, excluding one that needed bone grafting and one refracture, healed within 12 weeks. One patient needed bone grafting for delayed union and one patient needed fixation exchange due to femur re-fracture at the site of the most proximal screw. Two patients developed superficial wound infection and one patient required medial plate removal after union due to deep infection. Based on these promising results, we propose that the double-plating technique should be considered in the surgeon's armamentarium for the treatment of supracondylar femur fractures, particularly in patients with poor bone quality, comminuted fractures and very low periprosthetic fractures. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Direct Role of Collagen Glycation in Bone Fracture

PubMed Central

Poundarik, Atharva A.; Wu, Ping-Cheng; Evis, Zafer; Sroga, Grazyna E.; Ural, Ani; Rubin, Mishaela; Vashishth, Deepak

2015-01-01

Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bone’s organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales. Through atomic force spectroscopy, we established that NEG impairs collagen’s ability to dissipate energy. Mechanical testing of in vitro glycated human bone specimen revealed that AGE accumulation due to NEG dramatically reduces the capacity of organic and mineralized matrix to creep and caused bone to fracture under impact at low levels of strain (3000–5000 μstrain) typically associated with fall. Fracture mechanics tests of NEG modified human cortical bone of varying ages, and their age-matched controls revealed that NEG disrupted microcracking based toughening mechanisms and reduced bone propagation and initiation fracture toughness across all age groups. A comprehensive mechanistic model, based on experimental and modeling data, was developed to explain how NEG and AGEs are causal to, and predictive of bone fragility. Furthermore, fracture mechanics and indentation testing on diabetic mice bones revealed that diabetes mediated NEG severely disrupts bone matrix quality in vivo. Finally, we show that AGEs are predictive of bone quality in aging humans and have diagnostic applications in fracture risk. PMID:26530231

A prospective study of change in bone mass with age in postmenopausal women.

PubMed

Hui, S L; Wiske, P S; Norton, J A; Johnston, C C

1982-01-01

For the first time a model for age-related bone loss has been developed from prospective data utilizing a new weighted least squares method. Two hundred and sixty-eight Caucasian women ranging in age from 50 to 95 were studied. A quadratic function best fit the data, and correcting for body weight and bone width reduced variance. The derived equation is: bone mass = (0.6032) (bone width) (cm) + (0.003059) (body weight) (kg) - (0.0163) (age - 50) + (0.0002249) (age - 50)2. Analysis of cross-sectional data on 583 Caucasian women of similar age showed a quadratic function with very similar coefficients. This quadratic function predicts an increase in bone mass after age 86, therefore 42 women over age 70 who had been followed for at least 2.5 yr were identified to test for this effect. of these, 13 had significantly positive regression coefficients of bone mass on age, and rate of change in bone width was positive in 40 of 42 individuals, of which 5 were significant. Since photon absorptiometry measures net changes on all bone envelopes, the most likely explanation for the observed changes is an early exponential loss of endosteal bone which ultimately slows or perhaps stops. There is a positive balance on the periosteal envelope which only becomes apparent in later years when the endosteal loss stops. These new statistical methods allow the development of models utilizing data collected at irregular intervals. The methods used are applicable to other biological data collected prospectively.

Age-related Changes in the Fracture Resistance of Male Fischer F344 Rat Bone

PubMed Central

Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J.; Does, Mark D.; Nyman, Jeffry S.

2015-01-01

In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Both Raman spectroscopy and reference point indentation detected differences in tissue properties with age, though the trends did not necessarily match observations from human tissue. PMID:26610688

Age-related changes in the fracture resistance of male Fischer F344 rat bone.

PubMed

Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J; Does, Mark D; Nyman, Jeffry S

2016-02-01

In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue. Published by Elsevier Inc.

Use of postoperative steroids to reduce pain and inflammation.

PubMed

Fleischli, J W; Adams, W R

1999-01-01

Postoperative injection of a steroid is used by many podiatric surgeons to reduce pain and inflammation after foot surgery. The authors present a review of the literature on postoperative steroid use from many medical specialties as well as a review of wound and bone healing. The literature indicates that using a steroid is a safe and effective means to reduce postoperative pain and edema. Studies have shown steroids to delay healing, inhibit collagen synthesis, and increase the risk of postoperative infection. No author reported a delay in wound or bone healing or increased infection rate in patients in which a steroid was used. Although there is literature to support this practice, many questions remain and further investigation is needed.

Callus remodelling model

NASA Astrophysics Data System (ADS)

Miodowska, Justyna; Bielski, Jan; Kromka-Szydek, Magdalena

2018-01-01

The objective of this paper is to investigate the healing process of the callus using bone remodelling approach. A new mathematical model of bone remodelling is proposed including both underload and overload resorption, as well as equilibrium and bone growth states. The created model is used to predict the stress-stimulated change in the callus density. The permanent and intermittent loading programs are considered. The analyses indicate that obtaining a sufficiently high values of the callus density (and hence the elasticity) modulus is only possible using time-varying load parameters. The model predictions also show that intermittent loading program causes delayed callus healing. Understanding how mechanical conditions influence callus remodelling process may be relevant in the bone fracture treatment and initial bone loading during rehabilitation.

Prevalence of low bone mass among adolescents with nontransfusion-dependent hemoglobin E/β-thalassemia and its relationship with anemia severity.

PubMed

Nakavachara, Pairunyar; Petchkul, Jaturat; Jeerawongpanich, Krittha; Kiattisakthavee, Pornpimol; Manpayak, Teerarat; Netsakulnee, Parichat; Chaichanwattanakul, Katharee; Pooliam, Julaporn; Srichairatanakool, Somdet; Viprakasit, Vip

2018-01-01

Low bone mass is common among adolescents with transfusion-dependent β-thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion-dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion-dependent (NTD) β-thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/β-thalassemia. To determine the prevalence of low bone mass among adolescents with NTD Hb E/β-thalassemia and factors relating to low bone mass. We investigated BMD of lumbar spine (L2-L4; BMDLS) and total body (BMDTB), as measured by dual-energy X-ray absorptiometry, in 22 adolescents (aged 13.2-20 years) with NTD Hb E/β-thalassemia. Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z-score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z-score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z-scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z-scores adjusted for bone age. We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/β-thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long-term bone health. © 2017 Wiley Periodicals, Inc.

Mean alveolar bone crest height decrement in subjects with an osteoporosis risk

NASA Astrophysics Data System (ADS)

Effrianto, H. P. S.; Priminiarti, M.; Makes, B. N.

2017-08-01

People 40-75 years of age have an osteoporosis risk that may be signaled by a decrease in alveolar bone crest height. Thus, this measure can be used as an indicator of osteoporosis risk. This study was conducted to provide a database of decreased alveolar bone crest heights in ages at risk of osteoporosis by using intraoral radiographs. Forty periapical radiographs of the posterior region of tooth 36 (or 46) were measured twice at different times by two different observers. The interproximal decrease in alveolar bone crest height was measured from the alveolar bone crest to the cementoenamel junction (CEJ) for each tooth on the mesial and distal sides using a ruler (mm). The mean decrease in alveolar bone crest height in at-risk ages for osteoporosis was 3.50±1.085 mm, with a mean of 3.15±0.864 mm for those 45-59 years of age, and 3.90±1.156 mm for those aged 60-75 years. The mean decrease in alveolar bone crest height in people 60-75 years of age was larger than in people 45-59 years of age. There was a medium correlation between age and decreased alveolar bone crest height.

Aging and the 4 kHz Air-bone Gap

PubMed Central

Nondahl, David M.; Tweed, Ted S.; Cruickshanks, Karen J.; Wiley, Terry L.; Dalton, Dayna S.

2011-01-01

Purpose To assess age- and gender-related patterns in the prevalence and 10-year incidence of 4 kHz air-bone gaps, and associated factors. Method Data were obtained as part of the longitudinal, population-based Epidemiology of Hearing Loss Study. An air-bone gap at 4 kHz was defined as an air-conduction threshold ≥15 dB higher than the bone-conduction threshold in the right ear. Results Among 3,553 participants aged 48 to 92 years at baseline (1993-1995), 3.4% had a 4 kHz air-bone gap in the right ear. The prevalence increased with age. Among the 120 participants with an air-bone gap, 60.0% did not have a flat tympanogram or an air-bone gap at .5 kHz. Ten years later we assessed 2093 participants who did not have a 4 kHz air-bone gap at baseline; 9.2% had developed a 4 kHz air-bone gap in the right ear. The incidence increased with age. Among the 192 participants who had developed an air-bone gap, 60.9% did not have a flat tympanogram or air-bone gaps at other frequencies. Conclusions These results suggest that a finding of a 4 kHz air-bone gap may reflect a combination of aging and other factors and not necessarily exclusively abnormal middle ear function. PMID:22232408

S-Ketoprofen Inhibits Tenotomy-Induced Bone Loss and Dynamics in Weanling Rats

NASA Technical Reports Server (NTRS)

Zeng, Q. Q.; Jee, W. S. S.; Ke, H. Z.; Wechter, W. J.

1993-01-01

The objects of this study were to determine whether S-ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats. Forty five 4 week-old Sprague-Dawley female rats were either sham-operated or subjected to knee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluorescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancellous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This was due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-ketoprofen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resorption. In the tibial shaft, tenotomy inhibited the enlargement of total tissue area by depressing periosteal bone formation, and thus inhibited age-related cortical bone gain. S-ketoprofen treatment did not prevent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose levels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenotomy inhibited age-related bone gain and stimulated bone loss in cancellous bone sites, and only inhibited age-related bone gain in cortical bone sites. S-ketoprofen treatment at the highest dose levels prevented the changes in cancellous bone, and reduced marrow area to increase cortical bone in the tibial shafts.

Three-phase bone scan in osteomyelitis and other musculoskeletal disorders.

PubMed

Sutter, C W; Shelton, D K

1996-10-01

The three-phase bone scan is very sensitive and is the study of choice in the evaluation of patients with suspected osteomyelitis and normal radiographs. If the underlying bone pathology, such as a healing fracture or degenerative disease, is detected on radiographs of the bone, the indium-111-labeled autologous leukocyte scan is the most cost-effective second study. When fracture of the long bones is clinically suspected but radiographs are normal and a delay in definitive diagnosis is acceptable, it is practical and economical to take follow-up films in 10 to 14 days. In cases requiring prompt diagnosis or when follow-up radiographic films are not diagnostic, the three-phase bone scan is the most cost-effective study. The three-phase bone scan is also used in the evaluation of occupational and sports injuries, including shin splints, stress and occult fractures, enthesiopathies and reflex sympathetic dystrophy.

Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

NASA Technical Reports Server (NTRS)

Morukov, B. V.; Zaychik, V. YE.; Ivanov, V. M.; Orlov, O. I.

1988-01-01

Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone.

PubMed

Sroga, Grażyna E; Wu, Ping-Cheng; Vashishth, Deepak

2015-01-01

Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones.

Insulin-Like Growth Factor 1, Glycation and Bone Fragility: Implications for Fracture Resistance of Bone

PubMed Central

Sroga, Grażyna E.; Wu, Ping-Cheng; Vashishth, Deepak

2015-01-01

Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones. PMID:25629402

Genetics Home Reference: SADDAN

MedlinePlus

... CLOSE navigation Home Page Search Home Health ... delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities. All people with this ...

Immediate implant placement into fresh extraction sockets versus delayed implants into healed sockets: A systematic review and meta-analysis.

PubMed

Mello, C C; Lemos, C A A; Verri, F R; Dos Santos, D M; Goiato, M C; Pellizzer, E P

2017-09-01

The aim of this systematic review and meta-analysis was to compare the survival rate of the implants and the peri-implant tissue changes associated with implants inserted in fresh extraction sockets and those inserted in healed sockets. This review has been registered at PROSPERO under the number CRD42016043309. A systematic search was conducted by two reviewers independently in the databases PubMed/MEDLINE, Embase, and the Cochrane Library using different search terms; articles published until November 2016 were searched for. The searches identified 30 eligible studies. A total of 3,049 implants were installed in a total of 1,435 patients with a mean age of 46.68 years and a minimum of 6 months of follow-up. The survival rate of delayed implants (98.38%) was significantly greater than immediate implants (95.21%) (p=.001). For the marginal bone loss (p=.32), implant stability quotients values (p=.44), and pocket probing depth (p=.94) there was no significant difference between the analysed groups. The immediate implants placed in fresh sockets should be performed with caution because of the significantly lower survival rates than delayed implants inserted in healed sockets. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Pseudofracture: an acute peripheral tissue trauma model.

PubMed

Darwiche, Sophie S; Kobbe, Philipp; Pfeifer, Roman; Kohut, Lauryn; Pape, Hans-Christoph; Billiar, Timothy

2011-04-18

Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; this response is often accompanied by a delayed immunosuppression that adds the clinical complications of infection and can also increase mortality. Many studies have begun to assess these changes in the reactivity of the immune system following trauma. Immunologic studies are greatly supported through the wide variety of transgenic and knockout mice available for in vivo modeling; these strains aid in detailed investigations to assess the molecular pathways involved in the immunologic responses. The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible. This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone. The pseudofracture model consists of two parts: a bilateral muscle crush injury to the hindlimbs, followed by injection of a bone solution into these injured muscles. The bone solution is prepared by harvesting the long bones from both hindlimbs of an age- and weight-matched syngeneic donor. These bones are then crushed and resuspended in phosphate buffered saline to create the bone solution. Bilateral femur fracture is a commonly used and well-established model of extremity trauma, and was the comparative model during the development of the pseudofracture model. Among the variety of available fracture models, we chose to use a closed method of fracture with soft tissue injury as our comparison to the pseudofracture, as we wanted a sterile yet proportionally severe peripheral tissue trauma model. Hemorrhagic shock is a common finding in the setting of severe trauma, and the global hypoperfusion adds a very relevant element to a trauma model. The pseudofracture model can be easily combined with a hemorrhagic shock model for a multiple trauma model of high severity.

The relative contributions of non-enzymatic glycation and cortical porosity on the fracture toughness of aging bone

PubMed Central

Tang, S.Y.; Vashishth, D.

2010-01-01

The risk of fracture increases with age due to the decline of bone mass and bone quality. One of the age-related changes in bone quality occurs through the formation and accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation (NEG). However as a number of other changes including increased porosity occur with age and affect bone fragility, the relative contribution of AGEs on the fracture resistance of aging bone is unknown. Using a high-resolution nonlinear finite element model that incorporate cohesive elements and micro-computed tomography-based 3d meshes, we investigated the contribution of AGEs and cortical porosity on the fracture toughness of human bone. The results show that NEG caused a 52% reduction in propagation fracture toughness (R-curve slope). The combined effects of porosity and AGEs resulted in an 88% reduction in propagation toughness. These findings are consistent with previous experimental results. The model captured the age-related changes in the R-curve toughening by incorporating bone quantity and bone quality changes, and these simulations demonstrate the ability of the cohesive models to account for the irreversible dynamic crack growth processes affected by the changes in post-yield material behavior. By decoupling the matrix-level effects due to NEG and intracortical porosity, we are able to directly determine the effects of NEG on fracture toughness. The outcome of this study suggests that it may be important to include the age-related changes in the material level properties by using finite element analysis towards the prediction of fracture risk. PMID:21056419

Trisacryl Gelatin Microspheres Versus Polyvinyl Alcohol Particles in the Preoperative Embolization of Bone Neoplasms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basile, Antonio; Rand, Thomas; Lomoschitz, Fritz

2004-09-15

The aim of this study was to compare the efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles (PVA) in the preoperative embolization of bone neoplasms, on the basis of intraoperative blood loss quantified by the differences in preoperative and postoperative hematic levels of hemoglobin, hematocrit and erythrocytes count. From January 1997 to December 2002, preoperative embolization of bone tumors (either primary or secondary) was carried out in 49 patients (age range 12/78), 20 of whom were treated with trysacril gelatin microspheres (group A) and 29 with PVA particles (group B). The delay between embolization and surgery ranged from 1more » to 13 days in group A and 1 to 4 days in group B. As used in international protocols, we considered hematic levels of hemoglobin, hematocrit and erythrocytes count for the measurement of intraoperative blood loss then the differences in pre- and postoperative levels were used as statistical comparative parameters. We compared the values of patients treated with embospheres (n = 10) and PVA (n = 18) alone, and patients treated with (group A = 10; group B = 11) versus patients treated without other additional embolic materials in each group (group A = 10; group B = 18). According to the Student's t-test (p < 0.05), the difference of hematic parameters between patients treated by embospheres and PVA alone were significant; otherwise there was no significant difference between patients treated with only one embolic material (embospheres and PVA) versus those treated with other additional embolic agents in each group. The patients treated with microspheres had a minor quantification of intraoperative blood loss compared to those who received PVA particles. Furthermore, they had a minor increase of bleeding related to the delay time between embolization and surgery. The use of additional embolic material did not improve the efficacy of the procedure in either group of patients.« less

Ovariectomy-induced osteopenia influences the middle and late periods of bone healing in a mouse femoral osteotomy model.

PubMed

Pang, Jian; Ye, Meina; Cao, Yuelong; Zheng, Yuxin; Guo, Hailing; Zhao, Yongfang; Zhan, Hongsheng; Shi, Yinyu

2014-10-09

Objective It is known that bone healing was delayed in the presence of osteoporosis in humans. However, due to the complexities of the healing of osteoporotic fractures, animal models may be more appropriate to study the effects of osteoporosis in more details and to test drugs on the fracture repair process. The purpose of this study was to investigate the influence of ovariectomy-induced osteopenia in bone healing in an open femoral osteotomy model, and to test the feasibility of this model for evaluating the healing process under osteopenic conditions. Methods In assessing the effects of osteopenia on fracture healing, ovariectomized mouse models were employed. A mid-shaft femur osteotomy model was also established 3 weeks after ovariectomy as an osteopenic fracture group (OVX group). Femurs were then harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT), histology and biomechanical analysis. A sham-operated group (Sham group) was used for comparison. Results The OVX mice had significantly lower BVF, vBMD and TMD in the fracture calluses at 6 weeks (P < 0.05), and similar trend was observed in 2 weeks. Additionally, larger calluses in OVX animals were observed via micro-CT and X-ray, but these did not result in better healing outcomes as determined by biomechanical test at 6 weeks. Histological images of the healing fractures in the OVX mice found forward of broken end resorption and delay of hard callus remodeling. The impaired biomechanical measurements in the OVX group (P < 0.05) were consistent with micro-CT measurements and radiographic scoring, which also indicated delay in fracture healing of the OVX group. Conclusions This study provided evidences that ovariectomy-induced osteopenia impair the middle and late bone healing process once more. These data also supported the validity of the mouse femoral osteotomy model in evaluating the process of bone healing under osteopenic conditions.

Alteraciones puberales en adolescentes con leucemia en fase de vigilancia.

PubMed

Arriaga-Cázares, Héctor Eliud; Cázares-Bellazetin, Mara Alejandra; Sánchez-Sánchez, Luz María; Bahena-García, Ana Laura; Palacios-Saucedo, Gerardo Del Carmen

2017-01-01

To evaluate which factors are associated with alterations in pubertal development in pediatric patients with leukemia in the surveillance phase. A case-control study was carried out, including patients aged 8-14 years with diagnosis of acute lymphoblastic leukemia under surveillance. Demographic data were collected, age at diagnosis, type of leukemia, risk of leukemia, duration and type of treatment received, time of surveillance phase; and pubertal development was assessed by Tanner stage, bone age, pelvic ultrasound for women, and LH levels. Fisher's exact test and Mann-Whitney U-test were used. Twenty-five pediatric patients with a diagnosis of acute lymphoblastic leukemia between 8 and 14 years of age with a median of 8 were included, only 4 (16%) presented pubertal alterations, 1 had pubertal delay and 3 advanced puberty. The history of radiotherapy was related to pubertal alterations (p = 0.03). The antecedent of having received radiotherapy as part of the treatment in patients with acute lymphoblastic leukemia is a risk factor for developing pubertal abnormalities. Copyright: © 2017 SecretarÍa de Salud

Immediate loading of subcrestally placed dental implants in anterior and premolar sites.

PubMed

Henningsen, Anders; Smeets, Ralf; Köppen, Kai; Sehner, Susanne; Kornmann, Frank; Gröbe, Alexander; Heiland, Max; Gerlach, Till

2017-11-01

Immediate loading of dental implants has been evolving into an appropriate procedure for the treatment of partially edentulous jaws. The purpose of this study was to evaluate the clinical success and radiological outcome of immediately and delayed loaded dental implants in anterior and premolar sites. In this retrospective study, data of 163 individuals requiring tooth removal with subsequent implant placement in anterior and premolar sites were analyzed. Implants were immediately loaded by provisional acrylic resin bridges or loaded with delay. Implants were followed up annually for up to 9 years including intraoral radiographs. A total of 285 implants in 163 patients were placed. 218 implants were immediately loaded and 67 implants with delay. Fifteen implants failed during the follow-up period resulting in survival rates of 94.5% for immediate loading and 95.5% for delayed loading. After an initial decrease of 0.3 mm in the first 12 months the marginal bone level remained stable. No statistically significant differences were found in marginal bone loss between immediately and delayed loaded implants (P = 0.518, 95% CI). Within the limits of this study, immediate loading of immediately subcrestally placed dental implants in anterior and premolar sites is a reliable treatment option for dental rehabilitation. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Delayed healing of lower limb fractures with bisphosphonate therapy.

PubMed

Yue, B; Ng, A; Tang, H; Joseph, S; Richardson, M

2015-07-01

Bisphosphonate therapy (BT) is used commonly in the management of osteoporosis. A systematic review was conducted investigating delayed union of lower limb, long bone fractures in patients on BT. We specifically assessed whether BT increases the risk of delayed union or non-union in lower limb, long bone fractures. A literature search was conducted in the PubMed and Embase™ on 4 November 2014. Articles that investigated lower limb fractures, history of BT and fracture union were included in the review. A total of 9,809 papers were retrieved and 14 were deemed suitable for this review. The mean time to union in patients on BT was 8.5 months. A longer time to union was reported in a study investigating BT users versus controls (6.5 vs 4.8 months respectively). The mean rate of delayed or non-union for BT associated atypical fractures was 20% per fracture. Specifically in one study, delayed union was more common in the cohort with more than three years of BT (67%) than in the group with less than three years of BT (26%). Surgical fixation was associated with improved outcomes compared with non-operative management. BT has been described to be associated with multiple adverse outcomes related to atypical fractures. Current evidence recommends operative management for this patient group. Further investigation is required to evaluate the exact effects of BT on lower limb fractures, in particular typical femoral fractures.

End-threaded intramedullary positive profile screw ended self-tapping pin (Admit pin) - A cost-effective novel implant for fixing canine long bone fractures.

PubMed

Chanana, Mitin; Kumar, Adarsh; Tyagi, Som Prakash; Singla, Amit Kumar; Sharma, Arvind; Farooq, Uiase Bin

2018-02-01

The current study was undertaken to evaluate the clinical efficacy of end-threaded intramedullary pinning for management of various long bone fractures in canines. This study was conducted in two phases, managing 25 client-owned dogs presented with different fractures. The technique of application of end-threaded intramedullary pinning in long bone fractures was initially standardized in 6 clinical patients presented with long bone fractures. In this phase, end-threaded pins of different profiles, i.e., positive and negative, were used as the internal fixation technique. On the basis of results obtained from standardization phase, 19 client-owned dogs clinically presented with different fractures were implanted with end-threaded intramedullary positive profile screw ended self-tapping pin in the clinical application phase. The patients, allocated randomly in two groups, when evaluated postoperatively revealed slight pin migration in Group-I (negative profile), which resulted in disruption of callus site causing delayed union in one case and large callus formation in other two cases whereas no pin migration was observed in Group-II (positive profile). Other observations in Group-I was reduced muscle girth and delayed healing time as compared to Group-II. In clinical application, phase 21 st and 42 nd day post-operative radiographic follow-up revealed no pin migration in any of the cases, and there was no bone shortening or fragment collapse in end-threaded intramedullary positive profile screw ended self-tapping pin. The end-threaded intramedullary positive profile screw ended self-tapping pin used for fixation of long bone fractures in canines can resist pin migration, pin breakage, and all loads acting on the bone, i.e., compression, tension, bending, rotation, and shearing to an extent with no post-operative complications.

Size Does Matter: An Integrative In Vivo-In Silico Approach for the Treatment of Critical Size Bone Defects

PubMed Central

Carlier, Aurélie; van Gastel, Nick; Geris, Liesbet; Carmeliet, Geert; Van Oosterwyck, Hans

2014-01-01

Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non-union. In this work, we use an integrative in vivo - in silico approach to investigate the occurrence of non-unions, as well as to design possible treatment strategies thereof. The gap size of the domain geometry of a previously published mathematical model was enlarged in order to study the complex interplay of blood vessel formation, oxygen supply, growth factors and cell proliferation on the final healing outcome in large bone defects. The multiscale oxygen model was not only able to capture the essential aspects of in vivo non-unions, it also assisted in understanding the underlying mechanisms of action, i.e., the delayed vascularization of the central callus region resulted in harsh hypoxic conditions, cell death and finally disrupted bone healing. Inspired by the importance of a timely vascularization, as well as by the limited biological potential of the fracture hematoma, the influence of the host environment on the bone healing process in critical size defects was explored further. Moreover, dependent on the host environment, several treatment strategies were designed and tested for effectiveness. A qualitative correspondence between the predicted outcomes of certain treatment strategies and experimental observations was obtained, clearly illustrating the model's potential. In conclusion, the results of this study demonstrate that due to the complex non-linear dynamics of blood vessel formation, oxygen supply, growth factor production and cell proliferation and the interactions thereof with the host environment, an integrative in silico-in vivo approach is a crucial tool to further unravel the occurrence and treatments of challenging critical sized bone defects. PMID:25375821

Degeneration of the osteocyte network in the C57BL/6 mouse model of aging.

PubMed

Tiede-Lewis, LeAnn M; Xie, Yixia; Hulbert, Molly A; Campos, Richard; Dallas, Mark R; Dusevich, Vladimir; Bonewald, Lynda F; Dallas, Sarah L

2017-10-26

Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte parameters determined using novel multiplexed-3D-confocal imaging techniques. Age-related bone changes analogous to those in humans were observed, including increased cortical diameter, decreased cortical thickness, reduced trabecular BV/TV and cortical porosities. This was associated with a dramatic reduction in osteocyte dendrite number and cell density, particularly in females, where osteocyte dendricity decreased linearly from 5, 12, 18 to 22mo and correlated significantly with cortical bone parameters. Reduced dendricity preceded decreased osteocyte number, suggesting dendrite loss may trigger loss of viability. Age-related degeneration of osteocyte networks may impair bone anabolic responses to loading and gender differences in osteocyte cell body and lacunar fluid volumes we observed in aged mice may lead to gender-related differences in mechanosensitivity. Therapies to preserve osteocyte dendricity and viability may be beneficial for bone health in aging.

Phrenic Arterial Injury Presenting as Delayed Hemothorax Complicating Simple Rib Fracture.

PubMed

Ahn, Hong Joon; Lee, Jun Wan; Kim, Kun Dong; You, In Sool

2016-04-01

Delayed hemothorax after blunt torso injury is rare, but might be associated with significant morbidity and mortality. We present a case of delayed hemothorax bleeding from phrenic artery injury in a 24-year-old woman. The patient suffered from multiple rib fractures on the right side, a right hemopneumothorax, thoracic vertebral injury and a pelvic bone fracture after a fall from a fourth floor window. Delayed hemothorax associated with phrenic artery bleeding, caused by a stab injury from a fractured rib segment, was treated successfully by a minimally invasive thoracoscopic surgery. Here, we have shown that fracture of a lower rib or ribs might be accompanied by delayed massive hemothorax that can be rapidly identified and promptly managed by thoracoscopic means.

Phrenic Arterial Injury Presenting as Delayed Hemothorax Complicating Simple Rib Fracture

PubMed Central

2016-01-01

Delayed hemothorax after blunt torso injury is rare, but might be associated with significant morbidity and mortality. We present a case of delayed hemothorax bleeding from phrenic artery injury in a 24-year-old woman. The patient suffered from multiple rib fractures on the right side, a right hemopneumothorax, thoracic vertebral injury and a pelvic bone fracture after a fall from a fourth floor window. Delayed hemothorax associated with phrenic artery bleeding, caused by a stab injury from a fractured rib segment, was treated successfully by a minimally invasive thoracoscopic surgery. Here, we have shown that fracture of a lower rib or ribs might be accompanied by delayed massive hemothorax that can be rapidly identified and promptly managed by thoracoscopic means. PMID:27051252

Testosterone supplementation, glucocorticoid milieu and bone homeostasis in the ageing male.

PubMed

Ajdžanović, Vladimir Z; Filipović, Branko R; Šošić Jurjević, Branka T; Milošević, Verica Lj

2017-08-01

Male ageing is entwined with a continuous fall in free testosterone levels, which contributes to the pathogenesis of bone loss. Glucocorticoid excess, either dependent on the ageing process or iatrogenically induced, was found to additionally impair the bone structure and metabolism. Cautious testosterone supplementation in this respect may positively affect the glucocorticoid milieu and bone homeostasis, while testosterone-induced changes in the glucocorticoid output could serve as a determinant of bone-related therapeutic outcome. Namely, bone mineral content/density, the parameters of trabecular bone structure as well as bone strength are enhanced, serum calcitonin levels tend to increase, while serum osteocalcin, serum parathyroid hormone and urinary calcium decrease, all upon testosterone administration to the ageing male. In parallel, testosterone application decreases glucocorticoid secretion in the animal models of male ageing, while clinical data in this field are still inconsistent. Importantly, a physiological link exists between testosterone-induced changes in glucocorticoid levels and the tendency of bone status improvement in the ageing male. We believe that the assessment of circulating adrenocorticotropic hormone concentrations together with glucocorticoid levels, reflecting the hypothalamic-pituitary-adrenal axis feedback loop operativeness during testosterone supplementation, represents a well-balanced bone-related therapeutic update. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Later Age at Onset of Independent Walking Is Associated With Lower Bone Strength at Fracture-Prone Sites in Older Men.

PubMed

Ireland, Alex; Muthuri, Stella; Rittweger, Joern; Adams, Judith E; Ward, Kate A; Kuh, Diana; Cooper, Rachel

2017-06-01

Later age at onset of independent walking is associated with lower leg bone strength in childhood and adolescence. However, it is unknown whether these associations persist into older age or whether they are evident at axial (central) or upper limb sites. Therefore, we examined walking age obtained at age 2 years and bone outcomes obtained by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at ages 60 to 64 years in a nationally representative cohort study of British people, the MRC National Survey of Health and Development. It was hypothesized that later walking age would be associated with lower bone strength at all sites. Later independent walking age was associated with lower height-adjusted hip (standardized regression coefficients with 95% confidence interval [CI] -0.179 [-0.251 to -0.107]), spine (-0.157 [-0.232 to -0.082]), and distal radius (-0.159 [-0.245 to -0.073]) bone mineral content (BMC, indicating bone compressive strength) in men (all p < 0.001). Adjustment for covariates partially attenuated these associations, primarily because of lower lean mass and adolescent sporting ability in later walkers. These associations were also evident for a number of hip geometric parameters (including cross-sectional moment of inertia [CSMI], indicating bone bending/torsional strength) assessed by hip structural analysis (HSA) from DXA scans. Similar height-adjusted associations were also observed in women for several hip, spine, and upper limb outcomes, although adjustment for fat or lean mass led to complete attenuation for most outcomes, with the exception of femoral shaft CSMI and spine bone area (BA). In conclusion, later independent walking age appears to have a lifelong association with bone strength across multiple skeletal sites in men. These effects may result from direct effects of early life loading on bone growth and mediation by adult body composition. Results suggest that late walking age may represent a novel risk factor for subsequent low bone strength. Existing interventions effective in hastening walking age may have positive effects on bone across life. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

[Scintigraphic detection of osteoblast activity after implantation of BAS-0 bioactive glass-ceramic material into long bone defects].

PubMed

Sponer, P; Urban, K; Urbanová, E

2006-06-01

The aim of the study was to demonstrate, by three-phase bone scintigraphy, radionuclide uptake at the site of defects in long bones filled with the non-resorbable bioactive glass-ceramic material BAS-0 at a long follow-up. Twenty patients, 14 men and 6 women, operated on between 1990 and 2000 for benign bone tumors or tumor-like lesions localized in the femur, tibia or humerus were comprised in the study. Their average age at the time of operation was 14 years (range, 8 to 24). The diagnoses based on histological examination included juvenile bone cysts in 11, aneurysmal bone cyst in five, non-ossifying fibroma in two, and fibrous dysplasia in two patients. The lesions were localized in the femur, humerus and tibia in 11, five and four patients, respectively. The metaphysis was affected in eight and the diaphysis in 12 patients. Clinical, radiological and scintigraphic examinations were carried out at 2 to 12 years (7 years on average) after surgery. The clinical evaluation included subjective complaints and objective findings. Radiographs were made in standard projections and the osteo-integration of glass-ceramic material was investigated. Three-phase bone scans were made and the healthy and the affected limbs in each patient were compared by means of an index. Radionuclide uptake was considered normal when the index value was equal to 1.0, mildly increased at an index value of 1.2, moderately increased at 1.2-1.5 and markedly increased at an index value higher than 1.5. The clinical evaluation showed that, in the patients with glass-ceramic filling of metaphyses, six had no subjective complaints and two reported transient pain. In the patients with implants in diaphyses, subjective complaints were recorded in nine and no complaints in three patients. No inflammatory changes in soft tissues were found. No restriction in weightbearing of the limb treated was reported by any of the patients. On radiography, 18 patients were free from any disease residue or recurrence. Two patients had a residual defect. The bioactive glass-ceramic material BAS-0 was completely incorporated in all patients. On three-phase bone scans, radionuclide distribution on the flow phase and soft tissue phase was symmetrical in both limbs of all patients. For the metaphyseal location of implants, the delayed images demonstrated physiological radionuclide distribution in one patient, mildly increased distribution (index up to 1.2) in four, increased uptake (index up to 1.5) in two patients, and highly increased uptake (index above 1.5) in one patient. For the diaphyseal location of implants, the delayed scans demonstrated slightly increased radionuclide distribution in two, markedly increased in two and highly increased uptake in eight patients. The tissue during incorporation of a non-resorbable synthetic material is influenced by stress-shielding. This changes local mechanical signals, which has a negative effect on the adjacent bone tissue. Stress accumulating at the interface of a rigid implant and bone tissue may result in pain, and is detected by scintigraphy as an increased nucleotide uptake, particularly in diaphyseal grafts. This paper presents problems associated with implantation of the non-resorbable bioactive glass-ceramic material BAS-0 in the treatment of diaphyseal defects of long bones. The results show that, for filling of the defects described herein, non-resorbable glass-ceramic materials are not suitable.

Estrogen-Related Receptors and the control of bone cell fate.

PubMed

Carnesecchi, Julie; Vanacker, Jean-Marc

2016-09-05

Bone loss is naturally occurring in aging males and females and exacerbated in the latter after menopause, altogether leading to cumulative skeleton fragility and increased fracture risk. Two types of therapeutic strategies can be envisioned to counteract age- or menopause-associated bone loss, aiming at either reducing bone resorption exerted by osteoclasts or, alternatively, promoting bone formation by osteoblasts. We here summarize data suggesting that inhibition of the Estrogen-Related Receptors α and/or γ could promote bone formation and compensate for bone loss induced by ageing or estrogen-deficiency. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Rehabilitation of neglected Monteggia fracture: Dislocations in children.

PubMed

Yıldırım, Azad; Nas, Kemal

2017-11-06

There are limited studies related to the rehabilitation of neglected Monteggia fracture-dislocations. This study reports the results of the rehabilitation of neglected Monteggia fractures and dislocations and the best treatment options available. Thirteen children were rehabilitated between 2009 and 2012. A retrospective chart review was conducted to record the following: age, gender, anatomic region of fractures, time delay from symptom onset to fracture, Bado classification, Mayo Elbow Performance Index (MEPI) which includes pain, range of motion and daily life comfort, surgeries, length of hospitalization, location and pattern of fracture, length of follow-up and complications. The study group included thirteen children and adolescents; eleven males and two females with a mean age of 8.5 (range 2-15) years. According to the Bado classification, 11 patients had type 1, one had type 3 and one had type 4 fracture-dislocations. For Mayo Elbow Performance Index (MEPI) scales, patients that were less than ten years old had greater mean scores. Two patients had superficial infection, one had subluxation, one had osteoarthritis, one had delayed bone union and two had rigidity at the elbow. The goals of elbow rehabilitation following Neglected Monteggia cases include restoring function by restoring motion and muscle performance; influencing scar remodeling and preventing joint contracture; and restoring or maintaining joint stability. Patients aged younger than 10 years and intervals of less than one-year, between trauma and diagnosis, as well as early and effective rehabilitation were found as important parameters regarding favorable outcomes.

Ankle fractures have features of an osteoporotic fracture.

PubMed

Lee, K M; Chung, C Y; Kwon, S S; Won, S H; Lee, S Y; Chung, M K; Park, M S

2013-11-01

We report the bone attenuation of ankle joint measured on computed tomography (CT) and the cause of injury in patients with ankle fractures. The results showed age- and gender-dependent low bone attenuation and low-energy trauma in elderly females, which suggest the osteoporotic features of ankle fractures. This study was performed to investigate the osteoporotic features of ankle fracture in terms of bone attenuation and cause of injury. One hundred ninety-four patients (mean age 51.0 years, standard deviation 15.8 years; 98 males and 96 females) with ankle fracture were included. All patients underwent CT examination, and causes of injury (high/low-energy trauma) were recorded. Mean bone attenuations of the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis were measured on CT images. Patients were divided into younger age (<50 years) and older age (≥50 years) groups, and mean bone attenuation and causes of injury were compared between the two groups in each gender. Proportion of low-energy trauma was higher in the older age group than in the younger age group, but the difference was only significant in female gender (p = 0.011). The older age group showed significantly lower bone attenuation in the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis than the younger age group in both genders. The older age group showed more complex pattern of fractures than the younger age group. With increasing age, bone attenuations tended to decrease and the difference of bone attenuation between the genders tended to increase in the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis. Ankle fracture had features of osteoporotic fracture that is characterized by age- and gender-dependent low bone attenuation. Ankle fracture should not be excluded from the clinical and research interest as well as from the benefit of osteoporosis management.

Bone microarchitecture, biomechanical properties, and advanced glycation end-products in the proximal femur of adults with type 2 diabetes.

PubMed

Karim, Lamya; Moulton, Julia; Van Vliet, Miranda; Velie, Kelsey; Robbins, Ann; Malekipour, Fatemeh; Abdeen, Ayesha; Ayres, Douglas; Bouxsein, Mary L

2018-05-29

Skeletal fragility is a major complication of type 2 diabetes mellitus (T2D), but there is a poor understanding of mechanisms underlying T2D skeletal fragility. The increased fracture risk has been suggested to result from deteriorated bone microarchitecture or poor bone quality due to accumulation of advanced glycation end-products (AGEs). We conducted a clinical study to determine whether: 1) bone microarchitecture, AGEs, and bone biomechanical properties are altered in T2D bone, 2) bone AGEs are related to bone biomechanical properties, and 3) serum AGE levels reflect those in bone. To do so, we collected serum and proximal femur specimens from T2D (n = 20) and non-diabetic (n = 33) subjects undergoing total hip replacement surgery. A section from the femoral neck was imaged by microcomputed tomography (microCT), tested by cyclic reference point indentation, and quantified for AGE content. A trabecular core taken from the femoral head was imaged by microCT and subjected to uniaxial unconfined compression tests. T2D subjects had greater HbA 1 c (+23%, p ≤ 0.0001), but no difference in cortical tissue mineral density, cortical porosity, or trabecular microarchitecture compared to non-diabetics. Cyclic reference point indentation revealed that creep indentation distance (+18%, p ≤ 0.05) and indentation distance increase (+20%, p ≤ 0.05) were greater in cortical bone from T2D than in non-diabetics, but no other indentation variables differed. Trabecular bone mechanical properties were similar in both groups, except for yield stress, which tended to be lower in T2D than in non-diabetics. Neither serum pentosidine nor serum total AGEs were different between groups. Cortical, but not trabecular, bone AGEs tended to be higher in T2D subjects (21%, p = 0.09). Serum AGEs and pentosidine were positively correlated with cortical and trabecular bone AGEs. Our study presents new data on biomechanical properties and AGEs in adults with T2D, which are needed to better understand mechanisms contributing to diabetic skeletal fragility. Copyright © 2017. Published by Elsevier Inc.

IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

PubMed

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-02-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. © 2015 American Society for Bone and Mineral Research.

Aging and bone loss: new insights for the clinician

PubMed Central

Demontiero, Oddom; Vidal, Christopher

2012-01-01

It is well known that the underlying mechanisms of osteoporosis in older adults are different than those associated with estrogen deprivation. Age-related bone loss involves a gradual and progressive decline, which is also seen in men. Markedly increased bone resorption leads to the initial fall in bone mineral density. With increasing age, there is also a significant reduction in bone formation. This is mostly due to a shift from osteoblastogenesis to predominant adipogenesis in the bone marrow, which also has a lipotoxic effect that affects matrix formation and mineralization. We review new evidence on the pathophysiology of age-related bone loss with emphasis upon the mechanism of action of current osteoporosis treatments. New potential treatments are also considered, including therapeutic approaches to osteoporosis in the elderly that focus on the pathophysiology and potential reversal of adipogenic shift in bone. PMID:22870496

A Meta-Analysis of Experiments Linking Incubation Conditions with Subsequent Leg Weakness in Broiler Chickens

PubMed Central

Groves, Peter J.; Muir, Wendy I.

2014-01-01

A series of incubation and broiler growth studies were conducted using one strain of broiler chicken (fast feathering dam line) observing incubation effects on femoral bone ash % at hatch and the ability of the bird to remain standing at 6 weeks of age (Latency-To-Lie). Egg shell temperatures during incubation were consistently recorded. Parsimonious models were developed across eight studies using stepwise multiple linear regression of egg shell temperatures over 3-day periods and both bone ash at hatch and Latency-To-Lie. A model for bone ash at hatch explained 70% of the variation in this factor and revealed an association with lower egg shell temperatures during days 4–6 and 13–15 and higher egg shell temperatures during days 16–18 of incubation. Bone ash at hatch and subsequent Latency-To-Lie were positively correlated (r = 0.57, P<0.05). A model described 66% of the variation Latency-To-Lie showing significant association of the interaction of femoral ash at hatch and lower average egg shell temperatures over the first 15 days of incubation. Lower egg shell temperature in the early to mid incubation process (days 1–15) and higher egg shell temperatures at a later stage (days 16–18) will both tend to delay the hatch time of incubating eggs. Incubation profiles that resulted in later hatching chicks produced birds which could remain standing for a longer time at 6 weeks of age. This supports a contention that the effects of incubation observed in many studies may in fact relate more to earlier hatching and longer sojourn of the hatched chick in the final stage incubator. The implication of these outcomes are that the optimum egg shell temperature during incubation for broiler leg strength development may be lower than that regarded as ideal (37.8°C) for maximum hatchability and chick growth. PMID:25054636

A meta-analysis of experiments linking incubation conditions with subsequent leg weakness in broiler chickens.

PubMed

Groves, Peter J; Muir, Wendy I

2014-01-01

A series of incubation and broiler growth studies were conducted using one strain of broiler chicken (fast feathering dam line) observing incubation effects on femoral bone ash % at hatch and the ability of the bird to remain standing at 6 weeks of age (Latency-To-Lie). Egg shell temperatures during incubation were consistently recorded. Parsimonious models were developed across eight studies using stepwise multiple linear regression of egg shell temperatures over 3-day periods and both bone ash at hatch and Latency-To-Lie. A model for bone ash at hatch explained 70% of the variation in this factor and revealed an association with lower egg shell temperatures during days 4-6 and 13-15 and higher egg shell temperatures during days 16-18 of incubation. Bone ash at hatch and subsequent Latency-To-Lie were positively correlated (r = 0.57, P<0.05). A model described 66% of the variation Latency-To-Lie showing significant association of the interaction of femoral ash at hatch and lower average egg shell temperatures over the first 15 days of incubation. Lower egg shell temperature in the early to mid incubation process (days 1-15) and higher egg shell temperatures at a later stage (days 16-18) will both tend to delay the hatch time of incubating eggs. Incubation profiles that resulted in later hatching chicks produced birds which could remain standing for a longer time at 6 weeks of age. This supports a contention that the effects of incubation observed in many studies may in fact relate more to earlier hatching and longer sojourn of the hatched chick in the final stage incubator. The implication of these outcomes are that the optimum egg shell temperature during incubation for broiler leg strength development may be lower than that regarded as ideal (37.8°C) for maximum hatchability and chick growth.

RhBMP-7 for the treatment of nonunion of fractures of long bones.

PubMed

Papanagiotou, M; Dailiana, Z H; Karachalios, T; Varitimidis, S; Vlychou, M; Hantes, M; Malizos, K N

2015-07-01

We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients' quality of life was estimated using the Short Form (SF) 12 score. A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year. Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union. ©2015 The British Editorial Society of Bone & Joint Surgery.

Vertebral Compression Fractures

MedlinePlus

... and monitored to avoid putting pressure on the ribs that can cause new fractures. Surgical Procedures • When there is severe incapacitating pain • When healing is delayed or when bone fragments ...

Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss.

PubMed

Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

2009-04-01

Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of aging in vivo, leading to decreased ability to form and maintain bone homeostasis with age. In this review we summarize evidence of MSC involvement in age related bone loss and suggest new emerging targets for intervention.

Non-canonical Wnt4 prevents skeletal aging and inflammation by inhibiting NF-κB

PubMed Central

Yu, Bo; Chang, Jia; Liu, Yunsong; Li, Jiong; Kevork, Kareena; Al-Hezaimi, Khalid; Graves, Dana T; Park, No-Hee; Wang, Cun-Yu

2014-01-01

Aging-related bone loss and osteoporosis affect millions of patients worldwide. Chronic inflammation associated with aging and arthritis promotes bone resorption and impairs bone formation. Here we show that Wnt4 attenuated bone loss in osteoporosis and skeletal aging by inhibiting nuclear factor-kappa B (NF-κB) via non-canonical Wnt signaling. Transgenic mice expressing Wnt4 from osteoblasts were significantly protected from bone loss and chronic inflammation induced by ovariectomy, tumor necrosis factor or natural aging. In addition to promoting bone formation, Wnt4 could inhibit osteoclast formation and bone resorption. Mechanistically, Wnt4 inhibited transforming growth factor beta-activated kinase 1-mediated NF-κB activation in macrophages and osteoclast precursors independent of β-catenin. Moreover, recombinant Wnt4 proteins were able to alleviate osteoporotic bone loss and inflammation by inhibiting NF-κB in vivo. Taken together, our results suggest that Wnt4 might be used as a therapeutic agent for treating osteoporosis by attenuating NF-κB. PMID:25108526

Aging mechanisms in bone

PubMed Central

Almeida, Maria

2012-01-01

Advancing age and loss of bone mass and strength are closely linked. Elevated osteoblast and osteocyte apoptosis and decreased osteoblast number characterize the age-related skeletal changes in humans and rodents. Similar to other tissues, oxidative stress increases in bone with age. This article reviews current knowledge on the effects of the aging process on bone and its cellular constituents, with particular emphasis on the role of reactive oxygen species (ROS). FoxOs, sirtuins and the p53/p66shc signaling cascade alter osteoblast number and bone formation via ROS-dependent and -independent mechanisms. Specifically, activation of the p53/p66shc signaling increases osteoblast/osteocyte apoptosis in the aged skeleton and decreases bone mass. FoxO activation in osteoblasts prevents oxidative stress to preserve skeletal homeostasis. However, while defending against stress FoxOs bind to β-catenin and attenuate Wnt/T-cell cell factor transcriptional activity and osteoblast generation. Thus, pathways that impact longevity and several diseases of ageing might also contribute to age-related osteoporosis. PMID:23705067

Suppression of Autophagy in Osteocytes Mimics Skeletal Aging*

PubMed Central

Onal, Melda; Piemontese, Marilina; Xiong, Jinhu; Wang, Yiying; Han, Li; Ye, Shiqiao; Komatsu, Masaaki; Selig, Martin; Weinstein, Robert S.; Zhao, Haibo; Jilka, Robert L.; Almeida, Maria; Manolagas, Stavros C.; O'Brien, Charles A.

2013-01-01

Bone mass declines with age but the mechanisms responsible remain unclear. Here we demonstrate that deletion of a conditional allele for Atg7, a gene essential for autophagy, from osteocytes caused low bone mass in 6-month-old male and female mice. Cancellous bone volume and cortical thickness were decreased, and cortical porosity increased, in conditional knock-out mice compared with control littermates. These changes were associated with low osteoclast number, osteoblast number, bone formation rate, and wall width in the cancellous bone of conditional knock-out mice. In addition, oxidative stress was higher in the bones of conditional knock-out mice as measured by reactive oxygen species levels in the bone marrow and by p66shc phosphorylation in L6 vertebra. Each of these changes has been previously demonstrated in the bones of old versus young adult mice. Thus, these results demonstrate that suppression of autophagy in osteocytes mimics, in many aspects, the impact of aging on the skeleton and suggest that a decline in autophagy with age may contribute to the low bone mass associated with aging. PMID:23645674

Effect of Anti-Sclerostin Therapy and Osteogenesis Imperfecta on Tissue-level Properties in Growing and Adult Mice While Controlling for Tissue Age

PubMed Central

Sinder, Benjamin P.; Lloyd, William R.; Salemi, Joseph D.; Marini, Joan C.; Caird, Michelle S.; Morris, Michael D.; Kozloff, Kenneth M.

2016-01-01

Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as Osteogenesis Imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly→Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5 weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2–4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages >3wk) and rapidly growing Brtl/+ (at tissue ages > 4wk) mice compared to WT. At identical tissue ages defined by fluorescent labels adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and animal age on bone quality. PMID:26769006

Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

PubMed

Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

2016-03-01

Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and animal age on bone quality. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimisation of composite bone plates for ulnar transverse fractures.

PubMed

Chakladar, N D; Harper, L T; Parsons, A J

2016-04-01

Metallic bone plates are commonly used for arm bone fractures where conservative treatment (casts) cannot provide adequate support and compression at the fracture site. These plates, made of stainless steel or titanium alloys, tend to shield stress transfer at the fracture site and delay the bone healing rate. This study investigates the feasibility of adopting advanced composite materials to overcome stress shielding effects by optimising the geometry and mechanical properties of the plate to match more closely to the bone. An ulnar transverse fracture is characterised and finite element techniques are employed to investigate the feasibility of a composite-plated fractured bone construct over a stainless steel equivalent. Numerical models of intact and fractured bones are analysed and the mechanical behaviour is found to agree with experimental data. The mechanical properties are tailored to produce an optimised composite plate, offering a 25% reduction in length and a 70% reduction in mass. The optimised design may help to reduce stress shielding and increase bone healing rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recombinant human bone morphogenetic protein-2 for grade III open segmental tibial fractures from combat injuries in Iraq.

PubMed

Kuklo, T R; Groth, A T; Anderson, R C; Frisch, H M; Islinger, R B

2008-08-01

This is a retrospective consecutive case series of 138 Gustillo-Anderson type IIIB and IIIC segmental tibial fractures treated at Walter Reed Army Medical Center in soldiers injured in Iraq between March 2003 and March 2005. Five patients with a head injury and four who were lost to follow-up were excluded. The patients were treated definitively with either a ringed external fixator or a reamed intramedullary nail, evaluated in terms of supplementary bone grafting with either autogenous bone (group 1, 67 patients) or recombinant human bone morphogenetic protein-2 at 1.50 mg/ml applied to an absorbable collagen sponge (group 2, 62 patients). The mechanism of injury, defect size and classification, associated injuries, presence of infection, preliminary treatment/fixation, number of procedures before definitive management, time to and details of definitive management, subsequent infection, re-operation, smoking history and other complications were noted. Radiographs were assessed for union, delayed union or nonunion by an independent investigator. All the patients were male. Their mean age was 26.6 years (20 to 42) and the mean follow-up was for 15.6 months (12 to 32). Group 2 had a slightly higher profile of concomitant injuries and a slightly worse fracture classification, but these were not significant. The rate of union was 76% (51 of 67) for group 1 and 92% for group 2 (57 of 62; p = 0.015). There was also a higher rate of subsequent infection in group 1 (14.9%) compared with group 2 (3.2%; p = 0.001) and a higher rate of re-operation (28%) in group 1 (p = 0.003). There were no observed hypersensitivity reactions to the recombinant human bone morphogenetic protein-2 implant.

A Phase I Study of Zoledronic Acid and Low Dose Cyclophosphamide in Recurrent/Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) Study

PubMed Central

Russell, Heidi V.; Groshen, Susan G.; Ara, Tasnim; DeClerck, Yves A.; Hawkins, Randy; Jackson, Hollie A.; Daldrup-Link, Heike E.; Marachelian, Araz; Skerjanec, Andrej; Park, Julie R.; Katzenstein, Howard; Matthay, Katherine K.; Blaney, Susan M.; Villablanca, Judith G.

2010-01-01

Background Zoledronic acid, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone is a common metastatic site of advanced neuroblastoma. We previously reported efficacy of zoledronic acid in a murine model of neuroblastoma bone invasion prompting this Phase I trial of zoledronic acid with cyclophosphamide in children with neuroblastoma and bone metastases. The primary objective was to determine recommended dosing of zoledronic acid for future trials. Procedure Escalating doses of intravenous zoledronic acid were given every 28 days with oral metronomic cyclophosphamide (25 mg/m2/day). Toxicity, response, zoledronic acid pharmacokinetics, bone turnover markers, serum IL-6, and sIL-6R were evaluated. Results Twenty-one patients, median age 7.5 (range 0.8 - 25.6) years were treated with 2 mg/m2 (n=4), 3 mg/m2 (n=3), or 4 mg/m2 (n=14) zoledronic acid. Fourteen patients were evaluable for dose escalation. A median of one (range 1-18) courses was given. Two dose limiting toxicities (Grade 3 hypophosphatemia) occurred at 4 mg/m2 zoledronic acid. Other Grade 3-4 toxicities included hypocalcemia (n=2), elevated transaminases (n=1), neutropenia (n=2), anemia (n=1), lymphopenia (n=1), and hypokalemia (n=1). Osteosclerosis contributed to fractures in one patient after 18 courses. Responses in evaluable patients included 1 partial response, 9 stable disease (median 4.5 courses, range 3-18), and 10 progressions. Zoledronic acid pharmacokinetics were similar to adults. Markers of osteoclast activity and serum IL-6 levels decreased with therapy. Conclusions Zoledronic acid with metronomic cyclophosphamide is well tolerated with clinical and biologic responses in recurrent/refractory neuroblastoma. The recommended dose of zoledronic acid is 4 mg/m2 every 28 days. PMID:21671363

Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: relative contributions of bone size and volumetric bone mineral density.

PubMed

Henry, Yvette M; Fatayerji, Diana; Eastell, Richard

2004-04-01

The age at which peak bone mineral content (peak BMC) is reached remains controversial and the mechanism underlying bone mass "consolidation" is still undefined. The aims of this study were to investigate; (1) the timing of peak BMC by studying bone size and volumetric BMD (vBMD) as separate entities and (2) to determine the relative contributions of bone size and vBMD to bone mass "consolidation". A total of 132 healthy Caucasian children (63 boys and 69 girls, ages 11-19 years) and 134 healthy Caucasian adults (66 men and 68 women, ages 20-50 years) were studied. BMC was measured by DXA at the AP and lateral lumbar spine (LS) femoral neck (FN) and ultradistal radius (UDR). vBMD and bone volume (size) were estimated. Bone mass "consolidation" was examined between age 16 years to the age peak bone values were attained. During growth, BMC and bone size increased steeply with age and approximately 80-90% of peak values were achieved by late adolescence. vBMD at the spine and UDR (in women) increased gradually, but vBMD at the FN and UDR in men remained almost constant. During "consolidation", bone size continued to increase with little change in vBMD. Peak vBMD at the lumbar spine was reached at 22 and 29 years in men and women, respectively, but earlier at the FN at 12 years. At the UDR peak vBMD was achieved at age 19 years in women, with little change in men. In conclusion, peak vBMD and bone size are almost fully attained during late adolescence. Although speculative, the lack of change in vBMD during consolidation implies that the continued increase in bone mass may primarily be due to increases in bone size rather than increases in either trabecular volume, cortical thickness or the degree of mineralisation of existing bone matrix (vBMD). Skeletal growth and maturation is heterogeneous, but crucial in understanding how the origins of osteoporosis may begin during childhood and young adulthood.

PROLONGED PERFORMANCE OF A HIGH REPETITION LOW FORCE TASK INDUCES BONE ADAPTATION IN YOUNG ADULT RATS, BUT LOSS IN MATURE RATS

PubMed Central

Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

2015-01-01

We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14–18 mo of age) and 14 young adult (2.5–6.5 mo of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes. PMID:26517953

Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD.

PubMed

Havill, Lorena M; Mahaney, Michael C; L Binkley, Teresa; Specker, Bonny L

2007-05-01

Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age- and sex-specific bone effects of activity. Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8-85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. Accounting for effects of age, sex, and activity levels, genes explained 40-62% of the residual variation in BMC and BMD and 27-75% in bone size (all p<0.001). Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater among women than men (age-by-sex interaction; all p

Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

PubMed

Lopes, Noella; Vachon, Hortense; Marie, Julien; Irla, Magali

2017-06-01

Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 + thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Immediate Single-Tooth Implant Placement in Bony Defects in the Esthetic Zone: A 1-Year Randomized Controlled Trial.

PubMed

Slagter, Kirsten W; Meijer, Henny J A; Bakker, Nicolaas A; Vissink, Arjan; Raghoebar, Gerry M

2016-06-01

This study aims to assess, with regard to marginal bone level (MBL), whether the outcome of immediate implant placement in bony defects in the esthetic zone was non-inferior to delayed implant placement after 1 year. Forty patients with a failing tooth in the esthetic zone and a labial bony defect of ≥5 mm after removal of a tooth were randomly assigned for immediate (n = 20) or delayed (n = 20) implant placement. Second-stage surgery and provisionalization occurred after 3 months of healing. Follow-up was at 1 month and 1 year after definitive crown placement. The study was powered to detect a difference in MBL of >0.9 mm. Buccal bone thickness, soft tissue peri-implant parameters, esthetic indices, and patient satisfaction were also assessed. One year after definitive crown placement, MBL loss was 0.56 ± 0.39 mm mesially and 0.74 ± 0.51 mm distally for the immediate placement group and 0.51 ± 0.43 mesially and 0.54 ± 0.45 distally mm for the delayed placement group, respectively (not significant). Regarding differences in means, non-inferiority was observed after 1 year (difference in mean for immediate versus delayed: mesially 0.04 mm [95% confidence interval (CI) = -0.22 to 0.30 mm, P = 0.40]; distally 0.21 mm [95% CI = -0.10 to 0.51 mm, P = 0.58]). No significant differences in the other outcome variables were observed. Immediate implant placement with delayed provisionalization was non-inferior to delayed implant placement with delayed provisionalization in labial bony defects of ≥5 mm regarding change in MBL. Although not powered for other outcome variables, no clinically relevant differences were observed in these variables.

Effect of type 2 diabetes-related non-enzymatic glycation on bone biomechanical properties

PubMed Central

Karim, Lamya; Bouxsein, Mary L.

2015-01-01

There is clear evidence that patients with type 2 diabetes mellitus (T2D) have increased fracture risk, despite having high bone mineral density (BMD) and body mass index (BMI). Thus, poor bone quality has been implicated as a mechanism contributing to diabetic skeletal fragility. Poor bone quality in T2D may result from the accumulation of advanced glycation end-products (AGEs), which are post-translational modifications of collagen resulting from a spontaneous reaction between extracellular sugars and amino acid residues on collagen fibers. This review discusses what is known and what is not known regarding AGE accumulation and diabetic skeletal fragility, examining evidence from in vitro experiments to simulate a diabetic state, ex vivo studies in normal and diabetic human bone, and diabetic animal models. Key findings in the literature are that AGEs increase with age, affect bone cell behavior, and are altered with changes in bone turnover. Further, they affect bone mechanical properties and microdamage accumulation, and can be inhibited in vitro by various inhibitors and breakers (e.g. aminoguanidine, N-Phenacylthiazolium Bromide, vitamin B6). While a few studies report higher AGEs in diabetic animal models, there is little evidence of AGE accumulation in bone from diabetic patients. There are several limitations and inconsistencies in the literature that should be noted and studied in greater depth including understanding the discrepancies between glycation levels across reported studies, clarifying differences in AGEs in cortical versus cancellous bone, and improving the very limited data available regarding glycation content in diabetic animal and human bone, and its corresponding effect on bone material properties in T2D. PMID:26211993

Delayed Union of a Jones Fracture in a Patient With Rothmund-Thomson Syndrome: A Case Report and Review of the Literature.

PubMed

Barisonek, Kirsten L; Protzman, Nicole M; Wobst, Garrett M; Brigido, Stephen A

2016-01-01

Rothmund-Thomson syndrome is a rare autosomal recessive genodermatosis, characterized by poikiloderma, small stature, juvenile cataracts, sparse hair, skeletal abnormalities, and a predisposition to osteogenic sarcomas and skin cancers. Although numerous skeletal abnormalities have been described in patients with Rothmund-Thomson syndrome, to our knowledge, only 1 study has shown evidence of delayed fracture healing in a patient with Rothmund-Thomson syndrome. We present the case of a 13-year-old female diagnosed with Rothmund-Thomson syndrome who demonstrated delayed union of her fifth metatarsal after a Jones fracture. She was treated conservatively for 6 weeks with non-weightbearing cast immobilization and was then transitioned to a controlled ankle motion walker for an additional 4 weeks. Two months later, however, she continued to experience pain, and, on radiographic examination, the fracture remained unchanged. Therefore, with her guardian's consent, the patient elected to undergo open reduction and internal fixation of the fifth metatarsal fracture. At 8 weeks postoperatively, the patient reported a subsidence of symptoms and had returned to normal activity. With our report, we hope to increase practitioner awareness that delayed bone healing could be a possibility in patients with Rothmund-Thomson syndrome and encourage consideration of routine imaging and supplementation with calcium and vitamin D. Additionally, the present findings suggest that patients with Rothmund-Thomson syndrome could benefit from early surgical intervention, given their poor bone healing capacity and high likelihood of nonunion. Although the association between impaired bone healing and Rothmund-Thomson syndrome is rational, additional studies are needed to determine the prevalence of chronic nonunion in this patient population. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Effects of Untreated Periodontitis on Osseointegration of Dental Implants in a Beagle Dog Model.

PubMed

Lee, Daehyun; Sohn, Byungjin; Kim, Kyoung Hwa; Kim, Sungtae; Koo, Ki-Tae; Kim, Tae-Il; Seol, Yang-Jo; Lee, Yong-Moo; Rhyu, In-Chul; Ku, Young

2016-10-01

There have been previous studies on the relationship between periodontitis and peri-implantitis, but limited information is available on how periodontitis affects osseointegration and wound healing of newly placed dental implants adjacent to natural teeth. The objective of the present experiment is to evaluate healing around dental implants adjacent to teeth with untreated experimental periodontitis. The study included six male beagle dogs. Scaling and plaque control procedures were performed on three dogs (control group). In the other three dogs (experimental group), retraction cords and ligature wires were placed subgingivally around all premolars and the first molars. Induced experimental periodontitis was confirmed after 3 months. Each control or experimental group was divided into two subgroups depending on the timing of implant placement (immediate/delayed). Twelve dental implants (two implants for each dog) were placed immediately, and the other 12 dental implants (two implants for each dog) were placed 2 months after extraction. The animals were sacrificed 2 months after implant placement. Histologic and histometric analyses were performed. Four implants (three from the immediate placement group and one from the delayed placement group) failed in the experimental group. There were significant differences in the percentage of bone-to-implant contact and marginal bone volume density between the control and experimental groups. Both parameters were significantly lower in the experimental group than in the control group (P <0.05). There was a tendency toward more marginal bone loss in the experimental group than the control group. Immediate placement of implants is associated with a higher failure rate compared with delayed placement. Untreated experimental periodontitis was correlated with compromised osseointegration in the implants with delayed placement.

Sex-specific patterns in cortical and trabecular bone microstructure in the Kirsten Skeletal Collection, South Africa.

PubMed

Beresheim, Amy C; Pfeiffer, Susan K; Grynpas, Marc D; Alblas, Amanda

2018-02-07

The purpose of this study was to provide bone histomorphometric reference data for South Africans of the Western Cape who likely dealt with health issues under the apartheid regime. The 206 adult individuals ( n female = 75, n male = 131, mean = 47.9 ± 15.8 years) from the Kirsten Skeletal Collection, U. Stellenbosch, lived in the Cape Town metropole from the late 1960s to the mid-1990s. To study age-related changes in cortical and trabecular bone microstructure, photomontages of mid-thoracic rib cross-sections were quantitatively examined. Variables include relative cortical area (Rt.Ct.Ar), osteon population density (OPD), osteon area (On.Ar), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp). All cortical variables demonstrated significant relationships with age in both sexes, with women showing stronger overall age associations. Peak bone mass was compromised in some men, possibly reflecting poor nutritional quality and/or substance abuse issues throughout adolescence and early adulthood. In women, greater predicted decrements in On.Ar and Rt.Ct.Ar suggest a structural disadvantage with age, consistent with postmenopausal bone loss. Age-related patterns in trabecular bone microarchitecture are variable and difficult to explain. Except for Tb.Th, there are no statistically significant relationships with age in women. Men demonstrate significant negative correlations between BV/TV, Tb.N, and age, and a significant positive correlation between Tb.Sp and age. This research highlights sex-specific differences in patterns of age-related bone loss, and provides context for discussion of contemporary South African bone health. While the study sample demonstrates indicators of poor bone quality, osteoporosis research continues to be under-prioritized in South Africa. © 2018 Wiley Periodicals, Inc.

Age-related changes in bone turnover in men.

PubMed

Fatayerji, D; Eastell, R

1999-07-01

Biochemical markers of bone turnover can be used to study the pathophysiology of osteoporosis. So far there have been few such studies in men. The aims of this study were to determine the effect of aging on bone turnover and to identify which hormones might regulate bone turnover in men. We studied 178 healthy Caucasian men, ages 20-79 years (30 per decade). The data for the effect of age on bone turnover was best fit by a quadratic function (nadirs at age 56, 57, 53, 39, and 58 years for intact propeptide of type I procollagen, osteocalcin, bone alkaline phosphatase, free deoxypyridinoline, and cross-linked N-telopeptides of type I collagen, respectively). For most markers, bone turnover tended to be highest in the third decade, lowest in the fifth and sixth decade, with a small increase in some markers in the eighth decade. Insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3, dehydroepiandrosterone sulfate, testosterone, estradiol, and free androgen index all decreased significantly with age (54, 17, 76, 26, 33, and 57%, respectively), while sex hormone binding globulin and parathyroid hormone increased significantly with age (62% and 43%). IGF-I and sex hormones were positively correlated with bone turnover, and this association was stronger in young men than older men. In conclusion, increased IGF-I and sex hormones may be associated with increased bone turnover in young men, with less influence on bone turnover in older men.

Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis.

PubMed

Yamaguchi, Masayoshi

2006-11-01

Aging induces a decrease in bone mass, and osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Bone loss with increasing age may be due to decreased bone formation and increased bone resorption. Pharmacologic and nutritional factors may prevent bone loss with aging, although chemical compounds in food and plants which act on bone metabolism are poorly understood. We have found that isoflavones (including genistein and daidzein), which are contained in soybeans, have a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption, thereby increasing bone mass. Menaquinone-7, an analogue of vitamin K(2) which is abundant in fermented soybeans, has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption. Of various carotenoids, beta-cryptoxanthin, which is abundant in Satsuma mandarin (Citrus unchiu MARC), has a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. The supplementation of these factors has a preventive effect on bone loss induced by ovariectomy in rats, which are an animal model of osteoporosis, and their intake has been shown to have a stimulatory effect on bone mass in humans. Factors with an anabolic effect on bone metabolism were found in extracts obtained from wasabi leafstalk (Wasabi japonica MATSUM), the marine alga Sargassum horneri, and bee pollen Cistus ladaniferus. Phytocomponent p-hydroxycinnamic acid was also found to have an anabolic effect on bone metabolism. Food chemical factors thus play a role in bone health and may be important in the prevention of bone loss with increasing age.

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

PubMed

Hung, V W Y; Zhu, T Y; Cheung, W-H; Fong, T-N; Yu, F W P; Hung, L-K; Leung, K-S; Cheng, J C Y; Lam, T-P; Qin, L

2015-06-01

In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.

Bone morphogenetic protein (BMP)1-3 enhances bone repair.

PubMed

Grgurevic, Lovorka; Macek, Boris; Mercep, Mladen; Jelic, Mislav; Smoljanovic, Tomislav; Erjavec, Igor; Dumic-Cule, Ivo; Prgomet, Stefan; Durdevic, Dragan; Vnuk, Drazen; Lipar, Marija; Stejskal, Marko; Kufner, Vera; Brkljacic, Jelena; Maticic, Drazen; Vukicevic, Slobodan

2011-04-29

Members of the astacin family of metalloproteinases such as human bone morphogenetic protein 1 (BMP-1) regulate morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFβ, BMP2, BMP4 and GFD8. We have recently discovered that BMP1-3 isoform of the Bmp-1 gene circulates in the human plasma and is significantly increased in patients with acute bone fracture. We hypothesized that circulating BMP1-3 might have an important role in bone repair and serve as a novel bone biomarker. When administered systemically to rats with a long bone fracture and locally to rabbits with a critical size defect of the ulna, recombinant human BMP1-3 enhanced bone healing. In contrast, neutralization of the endogenous BMP1-3 by a specific polyclonal antibody delayed the bone union. Invitro BMP1-3 increased the expression of collagen type I and osteocalcin in MC3T3-E(1) osteoblast like cells, and enhanced the formation of mineralized bone nodules from bone marrow mesenchymal stem cells. We suggest that BMP1-3 is a novel systemic regulator of bone repair. Copyright © 2011 Elsevier Inc. All rights reserved.

Bone mineral content in the senescent rat femur: an assessment using single photon absorptiometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiebzak, G.M.; Smith, R.; Howe, J.C.

1988-06-01

The single photon absorptiometry technique was evaluated for measuring bone mineral content (BMC) of the excised femurs of the rat, and the system was used to examine the changes in cortical and trabecular bone from young adult (6 mo), mature adult (12 mo), and senescent (24 mo) male and female animals. BMC of the femur midshaft, representing cortical bone, apparently increased progressively with advancing age. The width of the femur at the scan site also increased with age. Normalizing the midshaft BMC by width partially compensated for the age-associated increase. However, when bone mineral values were normalized by the corticalmore » area at the scan site, to take into account the geometric differences in the femurs of different aged animals, maximum bone densities were found in the mature adult and these values decreased slightly in the femurs from senescent rats. In contrast, the BMC of the femur distal metaphysis, representing trabecular bone, decreased markedly in the aged rat. The loss of trabecular bone was also evident from morphological examination of the distal metaphysis. These findings indicated that bone mineral loss with age was site specific in the rat femur. These studies provided additional evidence that the rat might serve as a useful animal model for specific experiments related to the pathogenesis of age-associated osteopenia.« less

Targeted delivery of mesenchymal stem cells to the bone.

PubMed

Yao, Wei; Lane, Nancy E

2015-01-01

Osteoporosis is a disease of excess skeletal fragility that results from estrogen loss and aging. Age related bone loss has been attributed to both elevated bone resorption and insufficient bone formation. We developed a hybrid compound, LLP2A-Ale in which LLP2A has high affinity for the α4β1 integrin on mesenchymal stem cells (MSCs) and alendronate has high affinity for bone. When LLP2A-Ale was injected into mice, the compound directed MSCs to both trabecular and cortical bone surfaces and increased bone mass and bone strength. Additional studies are underway to further characterize this hybrid compound, LLP2A-Ale, and how it can be utilized for the treatment of bone loss resulting from hormone deficiency, aging, and inflammation and to augment bone fracture healing. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

IGF-1 REGULATES VERTEBRAL BONE AGING THROUGH SEX-SPECIFIC AND TIME-DEPENDENT MECHANISMS

PubMed Central

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L.; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-01-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, while others report that loss of IGF-1 is beneficial as it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igff/f mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan- early in postnatal development (crossing albumin-Cre mice with Igff/f mice), or early adulthood, and late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using microCT and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NFkB-ligand levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2 fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. PMID:26260312

Impairment of Bony Crypt Development Associated With Hexavalent Chromium Exposure During Tooth Eruption.

PubMed

Sánchez, Luciana M; Lewicki, Marianela; De Lucca, Romina C; Ubios, Ángela M

2015-12-01

Improperly treated hexavalent chromium-containing industrial wastes contaminate drinking water, potentially affecting children taking breast milk or baby bottles prepared with infant formula. Thus, the aim of the present work was to determine the effect of this toxic on bone activity in the developing alveolus during tooth eruption of suckling Wistar rats intoxicated with potassium dichromate. Experimental animals received a daily dose of 12.5mg/kg body weight of potassium dichromate by gavage for 10 days; controls received an equivalent volume of saline solution. Histologic and histomorphometric studies of the mandible were performed. The data were statistically analyzed using Student's t test; statistical significance was set at a value of p <0.05. Experimental animals exhibited delayed tooth eruption, decreased periodontal width and bone volume, a lower percentage of bone formation surfaces, and higher percentage of quiescent surfaces (p<0.05) compared to controls. The delay in tooth eruption observed after exposure to hexavalent chromium is the result of a lower rate of bone remodeling in the developing alveolus. The obtained results show the importance of controlling toxic substances in drinking water, since their effects may alter the growth and development of subjects who were exposed during early infancy. Sociedad Argentina de Investigación Odontológica.

Persistent Low Level of Osterix Accelerates Interleukin-6 Production and Impairs Regeneration after Tissue Injury

PubMed Central

Baek, Wook-Young; Park, Seung-Yoon; Kim, Yeo Hyang; Lee, Min-A; Kwon, Tae-Hwan; Park, Kwon-Moo; de Crombrugghe, Benoit; Kim, Jung-Eun

2013-01-01

Osterix (Osx) is an essential transcription factor for osteoblast differentiation and bone formation. Osx knockout show a complete absence of bone formation, whereas Osx conditional knockout in osteoblasts produce an osteopenic phenotype after birth. Here, we questioned whether Osx has a potential role in regulating physiological homeostasis. In Osx heterozygotes expressing low levels of Osx in bones, the expression levels of pro-inflammatory cytokines were significantly elevated, indicating that reduced Osx expression may reflect an inflammatory-prone state. In particular, the expression of interleukin-6, a key mediator of chronic inflammation, was increased in Osx heterozygotes and decreased in Osx overexpressing osteoblasts, and transcriptionally down-regulated by Osx. Although no significant differences were revealed in renal morphology and function between Osx heterozygotes and wild-type under normoxic conditions, recovery of kidneys after ischemic damage was remarkably delayed in Osx heterozygotes, as indicated by elevated blood urea nitrogen and creatinine levels, and by morphological alterations consistent with acute tubular necrosis. Eventually, protracted low Osx expression level caused an inflammatory-prone state in the body, resulting in the enhanced susceptibility to renal injury and the delayed renal repair after ischemia/reperfusion. This study suggests that the maintenance of Osx expression in bone is important in terms of preventing the onset of an inflammatory-prone state. PMID:23922826

Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

PubMed

Takahashi, Kuniyuki; Morita, Yuka; Ohshima, Shinsuke; Izumi, Shuji; Kubota, Yamato; Horii, Arata

2017-12-01

The temporal bone shows regional differences in bone development. The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.

Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia.

PubMed

Zuna, Jan; Moericke, Anja; Arens, Mari; Koehler, Rolf; Panzer-Grümayer, Renate; Bartram, Claus R; Fischer, Susanna; Fronkova, Eva; Zaliova, Marketa; Schrauder, André; Stanulla, Martin; Zimmermann, Martin; Trka, Jan; Stary, Jan; Attarbaschi, Andishe; Mann, Georg; Schrappe, Martin; Cario, Gunnar

2016-06-01

Minimal residual disease (MRD) at the end of induction therapy is important for risk stratification of acute lymphoblastic leukaemia (ALL), but bone marrow (BM) aspiration is often postponed or must be repeated to fulfil qualitative and quantitative criteria for morphological assessment of haematological remission and/or MRD analysis. The impact of BM aspiration delay on measured MRD levels and resulting risk stratification is currently unknown. We analysed paired MRD data of 289 paediatric ALL patients requiring a repeat BM aspiration. MRD levels differed in 108 patients (37%) with a decrease in the majority (85/108). This would have resulted in different risk group allocation in 64 of 289 patients (23%) when applying the ALL-Berlin-Frankfurt-Münster 2000 criteria. MRD change was associated with the duration of delay; 40% of patients with delay ≥7 days had a shift to lower MRD levels compared to only 18% after a shorter delay. Patients MRD-positive at the original but MRD-negative at the repeat BM aspiration (n = 50) had a worse 5-year event-free survival than those already negative at first aspiration (n = 115) (86 ± 5% vs. 94 ± 2%; P = 0·024). We conclude that BM aspirations should be pursued as scheduled in the protocol because delayed MRD sampling at end of induction may result in false-low MRD load and distort MRD-based risk assessment. © 2016 John Wiley & Sons Ltd.

Alveolar ridge preservation of an extraction socket using autogenous tooth bone graft material for implant site development: prospective case series

PubMed Central

Yun, Pil-Young; Um, In-Woong; Lee, Hyo-Jung; Yi, Yang-Jin; Bae, Ji-Hyun; Lee, Junho

2014-01-01

This case series evaluated the clinical efficacy of autogenous tooth bone graft material (AutoBT) in alveolar ridge preservation of an extraction socket. Thirteen patients who received extraction socket graft using AutoBT followed by delayed implant placements from Nov. 2008 to Aug. 2010 were evaluated. A total of fifteen implants were placed. The primary and secondary stability of the placed implants were an average of 58 ISQ and 77.9 ISQ, respectively. The average amount of crestal bone loss around the implant was 0.05 mm during an average of 22.5 months (from 12 to 34 months) of functional loading. Newly formed tissues were evident from the 3-month specimen. Within the limitations of this case, autogenous tooth bone graft material can be a favorable bone substitute for extraction socket graft due to its good bone remodeling and osteoconductivity. PMID:25551013

A review of the physiological and histological effects of laser osteotomy.

PubMed

Rajitha Gunaratne, G D; Khan, Riaz; Fick, Daniel; Robertson, Brett; Dahotre, Narendra; Ironside, Charlie

2017-01-01

Osteotomy is the surgical cutting of bone. Some obstacles to laser osteotomy have been melting, carbonisation and subsequent delayed healing. New cooled scanning techniques have resulted in effective bone cuts without the strong thermal side effects, which were observed by inappropriate irradiation techniques with continuous wave and long pulsed lasers. With these new techniques, osteotomy gaps histologically healed with new bone formation without any noticeable or minimum thermal damage. No significant cellular differences in bone healing between laser and mechanical osteotomies were noticed. Some studies even suggest that the healing rate may be enhanced following laser osteotomy compared to conventional mechanical osteotomy. Additional research is necessary to evaluate different laser types with appropriate laser setting variables to increase ablation rates, with control of depth, change in bone type and damage to adjacent soft tissue. Laser osteotomy has the potential to become incorporated into the armamentarium of bone surgery.

T1 correlates age: A short-TE MR relaxometry study in vivo on human cortical bone free water at 1.5T.

PubMed

Akbari, Atena; Abbasi-Rad, Shahrokh; Rad, Hamidreza Saligheh

2016-02-01

Large pores of human cortical bone (>30μm) are filled with fluids, essentially consisting of water, suggesting that cortical bone free water can be considered as a reliable surrogate measure of cortical bone porosity and hence quality. Signal from such pores can be reliably captured using Short Echo Time (STE) pulse sequence with echo-time in the range of 1-1.5msec (which should be judiciously selected correspond to T2(⁎) value of free water molecules). Furthermore, it is well-known that cortical bone T1-relaxivity is a function of its geometry, suggesting that cortical bone free water increases with age. In this work, we quantified cortical bone free water longitudinal relaxation time (T1) by a Dual-TR technique using STE pulse sequence. In the sequel, we investigated relationship between STE-derived cortical bone free water T1-values and age in a group of healthy volunteers (thirty subjects covering the age range of 20-70years) at 1.5T. Preliminary results showed that cortical bone free water T1 highly correlates with age (r(2)=0.73, p<0.0001), representing cortical bone free water T1 as a reliable indicator of cortical bone porosity and age-related deterioration. It can be concluded that STE-MRI can be utilized as proper alternative in quantifying cortical bone porosity parameters in-vivo, with the advantages of widespread clinical availability and being cost-effective. Copyright © 2015 Elsevier Inc. All rights reserved.

Spontaneous mutation of Dock7 results in lower trabecular bone mass and impaired periosteal expansion in aged female Misty mice.

PubMed

Le, Phuong T; Bishop, Kathleen A; Maridas, David E; Motyl, Katherine J; Brooks, Daniel J; Nagano, Kenichi; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

2017-12-01

Misty mice (m/m) have a loss of function mutation in Dock7 gene, a guanine nucleotide exchange factor, resulting in low bone mineral density, uncoupled bone remodeling and reduced bone formation. Dock7 has been identified as a modulator of osteoblast number and in vitro osteogenic differentiation in calvarial osteoblast culture. In addition, m/m exhibit reduced preformed brown adipose tissue innervation and temperature as well as compensatory increase in beige adipocyte markers. While the low bone mineral density phenotype is in part due to higher sympathetic nervous system (SNS) drive in young mice, it is unclear what effect aging would have in mice homozygous for the mutation in the Dock7 gene. We hypothesized that age-related trabecular bone loss and periosteal envelope expansion would be altered in m/m. To test this hypothesis, we comprehensively characterized the skeletal phenotype of m/m at 16, 32, 52, and 78wks of age. When compared to age-matched wild-type control mice (+/+), m/m had lower areal bone mineral density (aBMD) and areal bone mineral content (aBMC). Similarly, both femoral and vertebral BV/TV, Tb.N, and Conn.D were decreased in m/m while there was also an increase in Tb.Sp. As low bone mineral density and decreased trabecular bone were already present at 16wks of age in m/m and persisted throughout life, changes in age-related trabecular bone loss were not observed highlighting the role of Dock7 in controlling trabecular bone acquisition or bone loss prior to 16wks of age. Cortical thickness was also lower in the m/m across all ages. Periosteal and endosteal circumferences were higher in m/m compared to +/+ at 16wks. However, endosteal and periosteal expansion were attenuated in m/m, resulting in m/m having lower periosteal and endosteal circumferences by 78wks of age compared to +/+, highlighting the critical role of Dock7 in appositional bone expansion. Histomorphometry revealed that osteoblasts were nearly undetectable in m/m and marrow adipocytes were elevated 3.5 fold over +/+ (p=0.014). Consistent with reduced bone formation, osteoblast gene expression of Alp, Col1a1, Runx-2, Sp7, and Bglap was significantly decreased in m/m whole bone. Furthermore, markers of osteoclasts were either unchanged or suppressed. Bone marrow stromal cell migration and motility were inhibited in culture and changes in senescence markers suggest that osteoblast function may also be inhibited with loss of Dock7 expression in m/m. Finally, increased Oil Red O staining in m/m ear mesenchymal stem cells during adipogenesis highlights a potential shift of cells from the osteogenic to adipogenic lineages. In summary, loss of Dock7 in the aging m/m resulted in an impairment of periosteal and endocortical envelope expansion, but did not alter age-related trabecular bone loss. These studies establish Dock7 as a critical regulator of both cortical and trabecular bone mass, and demonstrate for the first time a novel role of Dock7 in modulating compensatory changes in the periosteum with aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone microstructure in men assessed by HR-pQCT: Associations with risk factors and differences between men with normal, low, and osteoporosis-range areal BMD.

PubMed

Okazaki, Narihiro; Burghardt, Andrew J; Chiba, Ko; Schafer, Anne L; Majumdar, Sharmila

2016-12-01

The primary objective of this study was to analyze the relationships between bone microstructure and strength, and male osteoporosis risk factors including age, body mass index, serum 25-hydroxyvitamin D level, and testosterone level. A secondary objective was to compare microstructural and strength parameters between men with normal, low, and osteoporosis-range areal bone mineral density (aBMD). Seventy-eight healthy male volunteers (mean age 62.4 ± 7.8 years, range 50-84 years) were recruited. The participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultra-distal radius and tibia. From the HR-pQCT images, volumetric bone mineral density (BMD) and cortical and trabecular bone microstructure were evaluated, and bone strength and cortical load fraction (Ct.LF) were estimated using micro-finite element analysis (μFEA). Age was more strongly correlated with bone microstructure than other risk factors. Age had significant positive correlations with cortical porosity at both ultra-distal radius and tibia ( r  = 0.36, p  = 0.001, and r  = 0.47, p  < 0.001, respectively). At the tibia, age was negatively correlated with cortical BMD, whereas it was positively correlated with trabecular BMD. In μFEA, age was negatively correlated with Ct.LF, although not with bone strength. Compared with men with normal aBMD, men with low or osteoporosis-range aBMD had significantly poor trabecular bone microstructure and lower bone strength at the both sites, while there was no significant difference in cortical bone. Cortical bone microstructure was negatively affected by aging, and there was a suggestion that the influence of aging may be particularly important at the weight-bearing sites.

Van Wyk Grumbach Syndrome: A Rare Consequence of Hypothyroidism.

PubMed

Reddy, Pavan; Tiwari, Kritika; Kulkarni, Abhishek; Parikh, Ketan; Khubchandani, Raju

2018-05-19

Long standing hypothyroidism presenting as an ovarian mass has been well described in literature as the Van Wyk Grumbach syndrome (hypothyroidism, isosexual precocious puberty and ovarian mass). Here, authors report this entity in a 11 y 7 mo old girl child who was referred to a surgeon in view of intestinal obstruction along with a multiloculated ovarian cyst. On evaluation, she was found to have raised serum creatinine, short stature, delayed bone age and pituitary enlargement. She was diagnosed with autoimmune thyroiditis and was started on replacement therapy with thyroxine, after which the ovarian cysts regressed. This entity should be kept in mind in cases of ovarian cysts, especially those with isosexual precocity, to prevent unnecessary evaluation and surgical misadventures.

EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma.

PubMed

Ferrari, Stefano; Bielack, Stefan S; Smeland, Sigbjørn; Longhi, Alessandra; Egerer, Gerlinde; Sundby Hall, Kirsten; Donati, Davide; Kevric, Matthias; Brosjö, Otte; Comandone, Alessandro; Werner, Mathias; Monge, Odd; Palmerini, Emanuela; Berdel, Wolfgang E; Bjerkehagen, Bodil; Paioli, Anna; Lorenzen, Sylvie; Eriksson, Mikael; Gambarotti, Marco; Tunn, Per-Ulf; Jebsen, Nina L; Cesari, Marilena; von Kalle, Thekla; Ferraresi, Virginia; Schwarz, Rudolf; Bertulli, Rossella; Kasparek, Anne-Katrin; Grignani, Giovanni; Krasniqi, Fatime; Sorg, Benjamin; Hecker-Nolting, Stefanie; Picci, Piero; Reichardt, Peter

2018-01-01

The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study. The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

Salvage of infected craniotomy bone flaps with the wash-in, wash-out indwelling antibiotic irrigation system. Technical note and case series of 12 patients.

PubMed

Auguste, Kurtis I; McDermott, Michael W

2006-10-01

When complicated by infection, craniotomy bone flaps are commonly removed, discarded, and delayed cranioplasty is performed. This treatment paradigm is costly, carries the risks associated with additional surgery, and may cause cosmetic deformities. The authors present their experience with an indwelling antibiotic irrigation system used for the sterilization and salvage of infected bone flaps as an alternative to their removal and replacement. The authors retrospectively reviewed the medical records for 12 patients with bone flap infections following craniotomy who received treatment with the wash-in, wash-out indwelling antibiotic irrigation system. Infected flaps were removed and scrubbed with povidone-iodine solution and soaked in 1.5% hydrogen peroxide while the wound was debrided. The bone flaps were returned to the skull and the irrigation system was installed. Antibiotic medication was infused through the system for a mean of 5 days. Intravenous antibiotic therapy was continued for 2 weeks and oral antibiotics for 3 months postoperatively. Wound checks were performed at clinic follow-up visits, and there was a mean follow-up period of 13 months. Eleven of the 12 patients who had undergone placement of the bone flap irrigation system experienced complete resolution of the infection. In five patients there was involvement of the nasal sinus cavities, and in four there was a history of radiation treatment. In the one patient whose infection recurred, there was both involvement of the nasal sinuses and a history of extensive radiation treatment. Infected bone flaps can be salvaged, thus avoiding the cost, risk, and possible disfigurement associated with flap removal and delayed cranioplasty. Although prior radiation treatment and involvement of the nasal sinuses may interfere with wound healing and clearance of the infection, these factors should not preclude the use of irrigation with antibiotic agents for bone flap salvage.

Inhibition of GSK-3β Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice

PubMed Central

Loiselle, Alayna E.; Lloyd, Shane A. J.; Paul, Emmanuel M.; Lewis, Gregory S.; Donahue, Henry J.

2013-01-01

Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair. PMID:24260576

Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice

PubMed Central

McGee-Lawrence, Meghan E.; Carpio, Lomeli R.; Bradley, Elizabeth W.; Dudakovic, Amel; Lian, Jane B.; van Wijnen, Andre J.; Kakar, Sanjeev; Hsu, Wei; Westendorf, Jennifer J.

2014-01-01

Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/− mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/− mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2−/−:Runx2+/− mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/− mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2−/−:Runx2+/− calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/− and double mutant Axin2−/−:Runx2+/− mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/− mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2−/− mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. PMID:24973690

Mastoid bone fracture presenting as unusual delayed onset of facial nerve palsy.

PubMed

Hsu, Ko-Chiang; Wang, Ann-Ching; Chen, Shyi-Jou

2008-03-01

Delayed-onset facial nerve paralysis is a rather uncommon complication of a mastoid bone fracture for children younger than 10 years. We routinely arrange a cranial computed tomography (CT) for patients encountering initial loss of consciousness, severe headache, intractable vomiting, and/or any neurologic deficit arising from trauma to the head. However, minor symptomatic cranial nerve damage may be missed and the presenting symptom diagnosed as being a peripheral nerve problem. Herein, we report a case of a young boy who presented at our emergency department (ED) 3 days subsequent to his accident, complaining of hearing loss in the right ear and paralysis of the ipsilateral face. Unpredictably, we observed his cranial CT scan revealing a linear fracture of the skull over the right temporal bone involving the right mastoid air cells. The patient was treated conservatively and recovered well without any adverse neurologic consequences. We emphasize that ED physicians should arrange a cranial CT scan for a head-injured child with symptomatic facial nerve palsy, even if there are no symptoms such as severe headache, vomiting, Battle sign, and/or initial loss of consciousness.

Effects of Age on Bone mRNA Levels of Sclerostin and Other Genes Relevant to Bone Metabolism in Humans

PubMed Central

Roforth, Matthew M.; Fujita, Koji; McGregor, Ulrike I.; Kirmani, Salman; McCready, Louise K.; Peterson, James M.; Drake, Matthew T.; Monroe, David G.; Khosla, Sundeep

2013-01-01

Although aging is associated with a decline in bone formation in humans, the molecular pathways contributing to this decline remain unclear. Several previous clinical studies have shown that circulating sclerostin levels increase with age, raising the possibility that increased production of sclerostin by osteocytes leads to the age-related impairment in bone formation. Thus, in the present study, we examined circulating sclerostin levels as well as bone mRNA levels of sclerostin using quantitative polymerase chain reaction (QPCR) analyses in needle bone biopsies from young (mean age, 30.0 years) versus old (mean age, 72.9 years) women. In addition, we analyzed the expression of genes in a number of pathways known to be altered with skeletal aging, based largely on studies in mice. While serum sclerostin levels were 46% higher (p < 0.01) in the old as compared to the young women, bone sclerostin mRNA levels were no different between the two groups (p = 0.845). However, genes related to notch signaling were significantly upregulated (p = 0.003 when analyzed as a group) in the biopsies from the old women. In an additional analysis of 118 genes including those from genome-wide association studies related to bone density and/or fracture, BMP/TGFβ family genes, selected growth factors and nuclear receptors, and Wnt/Wnt-related genes, we found that mRNA levels of the Wnt inhibitor, SFRP1, were significantly increased (by 1.6-fold, p = 0.0004, false discovery rate [q] = 0.04) in the biopsies from the old as compared to the young women. Our findings thus indicate that despite increases in circulating sclerostin levels, bone sclerostin mRNA levels do not increase in elderly women. However, aging is associated with alterations in several key pathways and genes in humans that may contribute to the observed impairment in bone formation. These include notch signaling, which represents a potential therapeutic target for increasing bone formation in humans. Our studies further identified mRNA levels of SFRP1 as being increased in aging bone in humans, suggesting that this may also represent a viable target for the development of anabolic therapies for age-related bone loss and osteoporosis. PMID:24184314

Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

DTIC Science & Technology

2012-07-01

Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

Utilization of bone impedance for age estimation in postmortem cases.

PubMed

Ishikawa, Noboru; Suganami, Hideki; Nishida, Atsushi; Miyamori, Daisuke; Kakiuchi, Yasuhiro; Yamada, Naotake; Wook-Cheol, Kim; Kubo, Toshikazu; Ikegaya, Hiroshi

2015-11-01

In the field of Forensic Medicine the number of unidentified cadavers has increased due to natural disasters and international terrorism. The age estimation is very important for identification of the victims. The degree of sagittal closure is one of such age estimation methods. However it is not widely accepted as a reliable method for age estimation. In this study, we have examined whether measuring impedance value (z-values) of the sagittal suture of the skull is related to the age in men and women and discussed the possibility to use bone impedance for age estimation. Bone impedance values increased with aging and decreased after the age of 64.5. Then we compared age estimation through the conventional visual method and the proposed bone impedance measurement technique. It is suggested that the bone impedance measuring technique may be of value to forensic science as a method of age estimation. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells

PubMed Central

Bowser, Matthew; Herberg, Samuel; Arounleut, Phonepasong; Shi, Xingming; Fulzele, Sadanand; Hill, William D.; Isales, Carlos M.; Hamrick, Mark W.

2013-01-01

The activin A-myostatin-follistatin system is thought to play an important role in the regulation of muscle and bone mass throughout growth, development, and aging; however, the effects of these ligands on progenitor cell proliferation and differentiation in muscle and bone are not well understood. In addition, age-associated changes in the relative expression of these factors in musculoskeletal tissues have not been described. We therefore examined changes in protein levels of activin A, follistatin, and myostatin (GDF-8) in both muscle and bone with age in C57BL6 mice using ELISA. We then investigated the effects of activin A, myostatin and follistatin on the proliferation and differentiation of primary myoblasts and mouse bone marrow stromal cells (BMSCs) in vitro. Myostatin levels and the myostatin:follistatin ratio increased with age in the primarily slow-twitch mouse soleus muscle, whereas the pattern was reversed with age in the fast-twitch extensor digitorum longus muscle. Myostatin levels and the myostatin: follistatin ratio increased significantly (+75%) in mouse bone marrow with age, as did activin A levels (+17%). Follistatin increased the proliferation of primary myoblasts from both young and aged mice, whereas myostatin increased proliferation of younger myoblasts but decreased proliferation of older myoblasts. Myostatin reduced proliferation of both young and aged BMSCs in a dose-dependent fashion, and activin A increased mineralization in both young and aged BMSCs. Together these data suggest that aging in mice is accompanied by changes in the expression of activin A and myostatin, as well as changes in the response of bone and muscle progenitor cells to these factors. Myostatin appears to play a particularly important role in the impaired proliferative capacity of muscle and bone progenitor cells from aged mice. PMID:23178301

Osteocalcin and bone-specific alkaline phosphatase in Asian elephants (Elephas maximus) at different ages.

PubMed

Arya, Nlin; Moonarmart, Walasinee; Cheewamongkolnimit, Nareerat; Keratikul, Nutcha; Poon-Iam, Sawinee; Routh, Andrew; Bumpenpol, Pitikarn; Angkawanish, Taweepoke

2015-11-01

Bone turnover markers could offer a potential alternative means for the early diagnosis of metabolic bone disease in young growing elephants although the baseline of bone turnover markers in elephant is not well established. The aim of this study was to determine any relationship between the age of captive Asian elephants (Elephas maximus) and markers of bone formation. Serum samples from 24 female Asian elephants were collected to evaluate levels of two bone formation markers, namely, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Both intact and N-terminal midfragment OC and BAP were negatively correlated with age. The findings demonstrate that younger elephants have a higher rate of bone turnover than older elephants. Use of these and additional bone markers could lead to the establishment of validated protocols for the monitoring of bone disease in elephants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Age-related variation in limb bone diaphyseal structure among Inuit foragers from Point Hope, northern Alaska.

PubMed

Wallace, I J; Nesbitt, A; Mongle, C; Gould, E S; Grine, F E

2014-01-01

Age-related deterioration of limb bone diaphyseal structure is documented among precontact Inuit foragers from northern Alaska. These findings challenge the concept that bone loss and fracture susceptibility among modern Inuit stem from their transition away from a physically demanding traditional lifestyle toward a more sedentary Western lifestyle. Skeletal fragility is rare among foragers and other traditional-living societies, likely due to their high physical activity levels. Among modern Inuit, however, severe bone loss and fractures are apparently common. This is possibly because of recent Western influences and increasing sedentism. To determine whether compromised bone structure and strength among the Inuit are indeed aberrant for a traditional-living group, data were collected on age-related variation in limb bone diaphyseal structure from a group predating Western influences. Skeletons of 184 adults were analyzed from the Point Hope archaeological site. Mid-diaphyseal structure was measured in the humerus, radius, ulna, femur, and tibia using CT. Structural differences were assessed between young, middle-aged, and old individuals. In all bones examined, both females and males exhibited significant age-related reductions in bone quantity. With few exceptions, total bone (periosteal) area did not significantly increase between young and old age in either sex, nor did geometric components of bending rigidity (second moments of area). While the physically demanding lifestyles of certain traditional-living groups may protect against bone loss and fracture susceptibility, this is not the case among the Inuit. It remains possible, however, that Western characteristics of the modern Inuit lifestyle exacerbate age-related skeletal deterioration.

[Endocrine complications of cystic fibrosis in childhood].

PubMed

Castanet, M; Wieliczko, M-C

2012-05-01

Since the 20 last years, the median age of survival has dramatically improved in children suffering from cystic fibrosis and complications such as growth retardation, pubertal delay and low bone mineral density are now more often than not observed in affected adolescents. The severity of the disease and the poor nutritional status due to pancreatic insufficiency and malabsorption are commonly implicated but recent data suggest that the disease could also play a role though the alteration of the chlore chanel (CFTR). Furthermore an increase prevalence of glucose intolerance and diabetes due to the progressive β cells destruction is observed in these children that make the life sometimes difficult for these adolescents already affected by an heavy chronic disease. The monitoring of the children should thus now become pluridisciplinary and include regular clinical evaluation of height and pubertal status, mineral bone density by DEXA and OGTT every two years since 10 years of age. Therefore, in addition to the standard treatment of cystic fibrosis is now added the vitamin D supplementation, the subcutaneous insulin therapy and may be the growth hormone that could be a new therapeutic demonstrating beneficial effects in these chronic disease. However further studies need to be performed to improve the management of these new endocrine complications more and more frequent in children and adolescents suffering from cystic fibrosis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Experimentally induced, synergistic late effects of a single dose of radiation and aging: significance in LKS fraction as compared with mature blood cells.

PubMed

Hirabayashi, Yoko; Tsuboi, Isao; Nakachi, Kei; Kusunoki, Yoichiro; Inoue, Tohru

2015-03-01

The number of murine mature blood cells recovered within 6 weeks after 2-Gy whole-body irradiation at 6 weeks of age, whereas in the case of the undifferentiated hematopoietic stem/progenitor cell (HSC/HPC) compartment [cells in the lineage-negative, c-kit-positive and stem-cell-antigen-1-positive (LKS) fraction], the numerical differences between mice with and without irradiation remained more than a year, but conclusively the cells showed numerical recovery. When mice were exposed to radiation at 6 months of age, acute damages of mature blood cells were rather milder probably because of their maturation with age; but again, cells in the LKS fraction were specifically damaged, and their numerical recovery was significantly delayed probably as a result of LKS-specific cellular damages. Interestingly, in contrast to the recovery of the number of cells in the LKS fraction, their quality was not recovered, which was quantitatively assessed on the basis of oxidative-stress-related fluorescence intensity. To investigate why the recovery in the number of cells in the LKS fraction was delayed, expression levels of genes related to cellular proliferation and apoptosis of cells in the bone marrow and LKS fraction were analyzed by real-time polymerase chain reaction (RT-PCR). In the case of 21-month-old mice after radiation exposure, Ccnd1, PiK3r1 and Fyn were overexpressed solely in cells in the LKS fraction. Because Ccnd1and PiK3r1 upregulated by aging were further upregulated by radiation, single-dose radiation seemed to induce the acceleration of aging, which is related to the essential biological responses during aging based on a lifetime-dependent relationship between a living creature and xenobiotic materials. Copyright © 2014 John Wiley & Sons, Ltd.

History of amenorrhoea compromises some of the exercise-induced benefits in cortical and trabecular bone in the peripheral and axial skeleton: a study in retired elite gymnasts.

PubMed

Ducher, G; Eser, P; Hill, B; Bass, S

2009-10-01

Female gymnasts frequently present with overt signs of hypoestrogenism, such as late menarche or menstrual dysfunction. The objective was to investigate the impact of history of amenorrhoea on the exercise-induced skeletal benefits in bone geometry and volumetric density in retired elite gymnasts. 24 retired artistic gymnasts, aged 17-36 years, who had been training for at least 15 h/week at the peak of their career and had been retired for 3-18 years were recruited. They had not been engaged in more than 2 h/week of regular physical activity since retirement. Former gymnasts who reported history of amenorrhoea ('AME', n=12: either primary or secondary amenorrhoea) were compared with former gymnasts ('NO-AME', n=12) and controls ('C', n=26) who did not report history of amenorrhoea. Bone mineral content (BMC), total bone area (ToA) and total volumetric density (ToD) were measured by pQCT at the radius and tibia (4% and 66%). Trabecular volumetric density (TrD) and bone strength index (BSI) were measured at the 4% sites. Cortical area (CoA), cortical thickness (CoTh), medullary area (MedA), cortical volumetric density (CoD), stress-strain index (SSI) and muscle and fat area were measured at the 66% sites. Spinal BMC, areal BMD and bone mineral apparent density (BMAD) were measured by DXA. Menarcheal age was delayed in AME when compared to NO-AME (16.4+/-0.5 years vs. 13.3+/-0.4 years, p<0.001). No differences were detected between AME and C for height-adjusted spinal BMC, aBMD and BMAD, TrD and BSI at the distal radius and tibia, CoA at the proximal radius, whereas these parameters were greater in NO-AME than C (p<0.05-0.005). AME had lower TrD and BSI at the distal radius, and lower spinal BMAD than NO-AME (p<0.05) but they had greater ToA at the distal radius (p<0.05). Greater spinal BMC, aBMD and BMAD as well as trabecular volumetric density and bone strength in the peripheral skeleton were found in former gymnasts without a history of menstrual dysfunction but not in those who reported either primary or secondary amenorrhoea. History of amenorrhoea may have compromised some of the skeletal benefits associated with high-impact gymnastics training.

AGE-RELATED EFFECT ON THE CONCENTRATION OF COLLAGEN CROSSLINKS IN HUMAN OSTEONAL AND INTERSTITIAL BONE TISSUE

PubMed Central

Nyman, Jeffry S.; Roy, Anuradha; Acuna, Rae L.; Gayle, Heather J.; Reyes, Michael J.; Tyler, Jerrod H.; Dean, David D.; Wang, Xiaodu

2007-01-01

Collagen crosslinks are important to the quality of bone and may be contributors to the age-related increase in bone fracture. This study was performed to investigate whether age and gender effects on collagen crosslinks are similar in osteonal and interstitial bone tissues. Forty human cadaveric femurs were collected and divided into two age groups: Middle aged (42–63 years of age) and Elderly (69–90 years of age) with ten males and ten females in each group (n = 10). Micro-cores of bone tissue from both secondary osteons (newly formed) and interstitial regions (biologically old) in the medial quadrant of the diaphysis were extracted using a custom-modified, computer numerical controlled machine. The bone specimens were then analyzed using high performance liquid chromatography to determine the effects of age and gender on the concentration of mature, enzymatic crosslinks (hydroxylysyl-pyridinoline – HP and lysylpyridinoline – LP) and a non-enzymatic crosslink (pentosidine – PE) at these two bony sites. The results indicate that age has a significant effect on the concentration of LP and PE, while gender has a significant effect on HP and LP. In addition, the concentration of the crosslinks in the secondary osteons is significantly different from that in the interstitial bone regions. These results suggest that the rate of non-enzymatic crosslinking may increase while the formation of maturate enzymatic crosslinks may decrease with age. Such changes could potentially reduce the inherent quality of the bone tissue in the elderly skeleton. PMID:16962838

[Aging and homeostasis. Management of disorders in bone and calcium metabolism associated with ageing.

PubMed

Takeuchi, Yasuhiro

Disorders in bone and calcium metabolism associated with aging are based on secondary hyperparathyroidism due to impaired intestinal calcium absorption caused by insufficient vitamin D actions and augmented bone resorption due to sex hormone deficiency. Both of them are involved in the development of osteoporosis that increases risk of fractures. Therefore, the most important thing for management of disorders in bone and calcium metabolism associated with aging is to prevent fractures with appropriate drugs for osteoporosis.

Physical activity effects on bone metabolism.

PubMed

Smith, E L; Gilligan, C

1991-01-01

The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

Age-related decrements in bone mineral density in women over 65

NASA Technical Reports Server (NTRS)

Steiger, P.; Cummings, S. R.; Black, D. M.; Spencer, N. E.; Genant, H. K.

1992-01-01

Age-related changes in bone density contribute to the risk of fractures. To describe the relationship between age and bone mass in elderly women, we studied a large cohort of women over age 65 years who were recruited from population-based lists in four cities in the United States. Bone density in g/cm2 was measured by single-photon absorptiometry (SPA) and dual x-ray absorptiometry (DXA) at the distal and proximal radius, the calcaneus, the lumbar spine, and the proximal femur. Centralized data collection was used to control data quality and consistency. We found a strong inverse relationship between bone density and age for most sites. Decrements in bone density between women aged 65-69 years and women 85 years and older exceeded 16% in all regions except the spine, where the difference between the two age groups was 6%. Ward's triangle and the calcaneus exhibited the largest decrements, with 26 and 21%, respectively. The estimates of annual changes in bone mineral density by linear regression at sites other than the spine ranged from -0.82% at the femoral neck and trochanter to -1.30% at Ward's triangle. Correlations between the different regions ranged from r = 0.51 between the proximal radius and Ward's triangle to r = 0.66 between the distal radius and calcaneus. We conclude that the inverse relationship between age and bone mass measured by absorptiometry techniques in white women continues into the ninth decade of life. The relationship is strongest for bone density of Ward's triangle and the calcaneus and weakest for the spine.

Childhood growth predicts higher bone mass and greater bone area in early old age: findings among a subgroup of women from the Helsinki Birth Cohort Study.

PubMed

Mikkola, T M; von Bonsdorff, M B; Osmond, C; Salonen, M K; Kajantie, E; Cooper, C; Välimäki, M J; Eriksson, J G

2017-09-01

We examined the associations between childhood growth and bone properties among women at early old age. Early growth in height predicted greater bone area and higher bone mineral mass. However, information on growth did not improve prediction of bone properties beyond that predicted by body size at early old age. We examined the associations between body size at birth and childhood growth with bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) in early old age. A subgroup of women (n = 178, mean 60.4 years) from the Helsinki Birth Cohort Study, born 1934-1944, participated in dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and hip. Height and weight at 0, 2, 7, and 11 years, obtained from health care records, were reconstructed into conditional variables representing growth velocity independent of earlier growth. Weight was adjusted for corresponding height. Linear regression models were adjusted for multiple confounders. Birth length and growth in height before 7 years of age were positively associated with femoral neck area (p < 0.05) and growth in height at all age periods studied with spine bone area (p < 0.01). Growth in height before the age of 7 years was associated with BMC in the femoral neck (p < 0.01) and birth length and growth in height before the age of 7 years were associated with BMC in the spine (p < 0.05). After entering adult height into the models, nearly all associations disappeared. Weight gain during childhood was not associated with bone area or BMC, and aBMD was not associated with early growth. Optimal growth in height in girls is important for obtaining larger skeleton and consequently higher bone mass. However, when predicting bone mineral mass among elderly women, information on early growth does not improve prediction beyond that predicted by current height and weight.

Pseudohypoparathyroidism

MedlinePlus

... one parent needs to pass you the faulty gene for you to have the condition. It is also called Albright hereditary osteodystrophy. The condition causes short stature, round face, obesity, developmental delay, and short hand bones. Symptoms depend ...

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis.

PubMed

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D; Davies, John E; Stanford, William L

2016-05-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance--replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. ©AlphaMed Press.

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis

PubMed Central

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D.

2016-01-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance—replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. Significance This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. PMID:26987353

Setup of a bone aging experimental model in the rabbit comparing changes in cortical and trabecular bone: Morphological and morphometric study in the femur.

PubMed

Pazzaglia, Ugo E; Sibilia, Valeria; Congiu, Terenzio; Pagani, Francesca; Ravanelli, Marco; Zarattini, Guido

2015-07-01

Bone aging was studied in an experimental model (rabbit femur) in three populations aged 0.5, 1.5, and 7.5 years. Cortical bone histology was compared with a data set from a 1.5-month-old population of an earlier published paper. From 0.5-year-old onward, the mean femur length did not increase further. Thereafter, the mean marrow area increased and the cortical area decreased significantly with aging. This was associated with a structural pattern transformation from plexiform to laminar and then Haversian-like type. The distal meta-epiphysis bone trabecular density of the oldest populations also was significantly lower in specific regions of interest (ROI). Percentage sealed primary vascular canals in laminar bone significantly increased with aging without variation of percentage sealed secondary osteons. Remodeling rate reflected by the density of cutting cones did not significantly change among the age populations. These data suggest that laminar bone vascular pattern is more functional in the fast diaphyseal expansion but not much streamlined with the renewal of blood flow during secondary remodeling. Bone aging was characterized by: 1) secondary remodeling subendosteally; 2) increment of sealed primary vascular canals number; 3) increased calcium content of the cortex; 4) cortical and trabecular bone mass loss in specific ROIs. Taken together, the present data may give a morphological and morphometric basis to perform comparative studies on experimental models of osteoporosis in the rabbit. © 2015 Wiley Periodicals, Inc.

Osteosarcopenic obesity in women: impact, prevalence, and management challenges

PubMed Central

JafariNasabian, Pegah; Inglis, Julia E; Kelly, Owen J; Ilich, Jasminka Z

2017-01-01

Osteosarcopenic obesity syndrome (OSO) has recently been identified as a condition encompassing osteopenia/osteoporosis, sarcopenia and obesity. OSO is especially deleterious in older adults (even if they are not obese by conventional measures), due to age-related redistribution of fat and its infiltration into bone and muscle. Osteoporosis and bone fractures in elderly increase the risk of sarcopenia, which, through decreased mobility, increases the risk of more falls and fractures, creating a vicious cycle. Obesity plays a dual role: to a certain extent, it promotes bone and muscle gains through mechanical loading; in contrast, increased adiposity is also a source of pro-inflammatory cytokines and other endocrine factors that impair bone and muscle. As the elderly population increases, changes in lifestyle to delay the onset of OSO, or prevent OSO, are warranted. Among these changes, dietary patterns and physical activity modifications are the first ones to be implemented. The typical Western diet (and lifestyle) promotes several chronic diseases including OSO, by facilitating a pro-inflammatory state, largely via the imbalance in omega-6/omega-3 fatty acid ratio and low-fiber and high-processed food consumption. Nutritional modifications to prevent and/or alleviate the OSO syndrome include adequate intake of protein, calcium, magnesium and vitamin D and increasing consumptions of foods containing omega-3 polyunsaturated fatty acids and fiber. Certain types of physical activity, often decreased in overweight/obese women and in elderly, might preserve bone and muscle, as well as help in reducing body fat accrual and fat infiltration. Habitual daily activities and some alternative modes of exercise may be more appropriate for older adults and play a crucial role in preventing bone and muscle loss and maintaining optimal weight. In conclusion, older adults who suffer from OSO syndrome may benefit from combined efforts to improve diet and physical activity, and such recommendations should be fostered as part of public health programs. PMID:28144165

Osteosarcopenic obesity in women: impact, prevalence, and management challenges.

PubMed

JafariNasabian, Pegah; Inglis, Julia E; Kelly, Owen J; Ilich, Jasminka Z

2017-01-01

Osteosarcopenic obesity syndrome (OSO) has recently been identified as a condition encompassing osteopenia/osteoporosis, sarcopenia and obesity. OSO is especially deleterious in older adults (even if they are not obese by conventional measures), due to age-related redistribution of fat and its infiltration into bone and muscle. Osteoporosis and bone fractures in elderly increase the risk of sarcopenia, which, through decreased mobility, increases the risk of more falls and fractures, creating a vicious cycle. Obesity plays a dual role: to a certain extent, it promotes bone and muscle gains through mechanical loading; in contrast, increased adiposity is also a source of pro-inflammatory cytokines and other endocrine factors that impair bone and muscle. As the elderly population increases, changes in lifestyle to delay the onset of OSO, or prevent OSO, are warranted. Among these changes, dietary patterns and physical activity modifications are the first ones to be implemented. The typical Western diet (and lifestyle) promotes several chronic diseases including OSO, by facilitating a pro-inflammatory state, largely via the imbalance in omega-6/omega-3 fatty acid ratio and low-fiber and high-processed food consumption. Nutritional modifications to prevent and/or alleviate the OSO syndrome include adequate intake of protein, calcium, magnesium and vitamin D and increasing consumptions of foods containing omega-3 polyunsaturated fatty acids and fiber. Certain types of physical activity, often decreased in overweight/obese women and in elderly, might preserve bone and muscle, as well as help in reducing body fat accrual and fat infiltration. Habitual daily activities and some alternative modes of exercise may be more appropriate for older adults and play a crucial role in preventing bone and muscle loss and maintaining optimal weight. In conclusion, older adults who suffer from OSO syndrome may benefit from combined efforts to improve diet and physical activity, and such recommendations should be fostered as part of public health programs.

Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children

PubMed Central

Gozes, I; Van Dijck, A; Hacohen-Kleiman, G; Grigg, I; Karmon, G; Giladi, E; Eger, M; Gabet, Y; Pasmanik-Chor, M; Cappuyns, E; Elpeleg, O; Kooy, R F; Bedrosian-Sermone, S

2017-01-01

A major flaw in autism spectrum disorder (ASD) management is late diagnosis. Activity-dependent neuroprotective protein (ADNP) is a most frequent de novo mutated ASD-related gene. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Adnp haploinsufficiency results in cognitive and social deficiencies coupled to sex- and age-dependent deficits in the key microtubule and ion channel pathways. Here, collaborating with parents/caregivers globally, we discovered premature tooth eruption as a potential early diagnostic biomarker for ADNP mutation. The parents of 44/54 ADNP-mutated children reported an almost full erupted dentition by 1 year of age, including molars and only 10 of the children had teeth within the normal developmental time range. Looking at Adnp-deficient mice, by computed tomography, showed significantly smaller dental sacs and tooth buds at 5 days of age in the deficient mice compared to littermate controls. There was only trending at 2 days, implicating age-dependent dysregulation of teething in Adnp-deficient mice. Allen Atlas analysis showed Adnp expression in the jaw area. RNA sequencing (RNAseq) and gene array analysis of human ADNP-mutated lymphoblastoids, whole-mouse embryos and mouse brains identified dysregulation of bone/nervous system-controlling genes resulting from ADNP mutation/deficiency (for example, BMP1 and BMP4). AKAP6, discovered here as a major gene regulated by ADNP, also links cognition and bone maintenance. To the best of our knowledge, this is the first time that early primary (deciduous) teething is related to the ADNP syndrome, providing for early/simple diagnosis and paving the path to early intervention/specialized treatment plan. PMID:28221363

Do biodegradable magnesium alloy intramedullary interlocking nails prematurely lose fixation stability in the treatment of tibial fracture? A numerical simulation.

PubMed

Wang, Haosen; Hao, Zhixiu; Wen, Shizhu

2017-01-01

Intramedullary interlocking nailing is an effective technique used to treat long bone fractures. Recently, biodegradable metals have drawn increased attention as an intramedullary interlocking nailing material. In this study, numerical simulations were implemented to determine whether the degradation rate of magnesium alloy makes it a suitable material for manufacturing biodegradable intramedullary interlocking nails. Mechano-regulatory and bone-remodeling models were used to simulate the fracture healing process, and a surface corrosion model was used to simulate intramedullary rod degradation. The results showed that magnesium alloy intramedullary rods exhibited a satisfactory degradation rate; the fracture healed and callus enhancement was observed before complete dissolution of the intramedullary rod. Delayed magnesium degradation (using surface coating techniques) did not confer a significant advantage over the non-delayed degradation process; immediate degradation also achieved satisfactory healing outcomes. However, delayed degradation had no negative effect on callus enhancement, as it did not cause signs of stress shielding. To avoid risks of individual differences such as delayed union, delayed degradation is recommended. Although the magnesium intramedullary rod did not demonstrate rapid degradation, its ability to provide high fixation stiffness to achieve earlier load bearing was inferior to that of the conventional titanium alloy and stainless steel rods. Therefore, light physiological loads should be ensured during the early stages of healing to achieve bony healing; otherwise, with increased loading and degraded intramedullary rods, the fracture may ultimately fail to heal. Copyright © 2016 Elsevier Ltd. All rights reserved.

Delayed healing of lower limb fractures with bisphosphonate therapy

PubMed Central

Ng, A; Tang, H; Joseph, S; Richardson, M

2015-01-01

Introduction Bisphosphonate therapy (BT) is used commonly in the management of osteoporosis. A systematic review was conducted investigating delayed union of lower limb, long bone fractures in patients on BT. We specifically assessed whether BT increases the risk of delayed union or non-union in lower limb, long bone fractures. Methods A literature search was conducted in the PubMed and Embase™ on 4 November 2014. Articles that investigated lower limb fractures, history of BT and fracture union were included in the review. Results A total of 9,809 papers were retrieved and 14 were deemed suitable for this review. The mean time to union in patients on BT was 8.5 months. A longer time to union was reported in a study investigating BT users versus controls (6.5 vs 4.8 months respectively). The mean rate of delayed or non-union for BT associated atypical fractures was 20% per fracture. Specifically in one study, delayed union was more common in the cohort with more than three years of BT (67%) than in the group with less than three years of BT (26%). Surgical fixation was associated with improved outcomes compared with non-operative management. Conclusions BT has been described to be associated with multiple adverse outcomes related to atypical fractures. Current evidence recommends operative management for this patient group. Further investigation is required to evaluate the exact effects of BT on lower limb fractures, in particular typical femoral fractures. PMID:26264082

[Scintigraphic findings in a patient with sickle-cell thalassemia and recurrent pain attacks].

PubMed

Mikosch, Peter; Jauk, Barbara; Kaulfersch, Wilhelm; Gallowitsch, Hans-Jürgen; Lind, Peter

2003-01-01

The case of an eight years old African boy who suffers from sickle cell-thalassemia is presented. In the course of the disease frequent pain attacks occurred within the abdomen and extremities, recently also within the trunk. Local pain, at some occasions in combination with local swelling and always positive laboratory parameters for inflammation, hindered a solely clinical differentiation between bone infarcts and osteomyelitis. Bone scintigraphy, eventually in combination with bone marrow scintigraphy, can assist the clinician in the differentiation of aseptic bone infarcts versus secondary osteomyelitis. Based on the presented case scintigraphic results for bone infarcts, osteomyelitis and special scintigraphic pattern seen in sickle cell disease are presented. Furthermore, problems regarding the interpretation of the scintigraphies in relation to the delayed time after the beginning of pain attacks are discussed.

Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone.

PubMed

Smith, Christopher A; Board, Tim N; Rooney, Paul; Eagle, Mark J; Richardson, Stephen M; Hoyland, Judith A

2017-01-01

To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC) osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC). BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP) enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1) concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors.

Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

PubMed

Solomon, P R; Groccia-Ellison, M E

1996-06-01

Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

Physiological Stresses Related to Hypercapnia during Patrols on Submarines

DTIC Science & Technology

1975-12-01

Acid- base balance, CO., storage, and calcium homeostasis | I am trying to show that this delayed renal response in low level chronic hypercapnia is 1...C02 Co, P BONE 4 1 BLOOD Fig. 11. Cycles in acid- base balance, bone buffering, and renal regulation during prolonged exposure to 0.7...patrols on submarines K. E. SCHAEFER Naval Submarine Medical Research Laboratory, Naval Submarine Base . Groton. CT 06340 Schaefer, K. E. 1979

Skeletal maturity and growth of adolescent mothers: relationship to pregnancy outcome.

PubMed

Stevens-Simon, C; McAnarney, E R

1993-09-01

The purpose of this study was to evaluate the relationship between postpartum maternal bone age and the incidence of obstetric and neonatal complications in adolescent pregnancies. Bone age determinations were obtained on 93 poor, black 12- through 18-year-old adolescents during the puerperium. Results showed maternal bone ages ranging from 15 to 18 years; bone age was less than 18 years in 64 (68.8%) of the 93 adolescent mothers we studied. Maternal bone age correlated significantly with maternal chronologic age (r = 0.70) and prepregnant body size (r = 0.25) but did not correlate with total maternal weight gain and growth during pregnancy, the incidence of obstetric and neonatal complications, or infant birth weight and gestational age. Our findings suggest that many young, pregnant adolescents have the potential to grow during and after pregnancy, but do not support the hypothesis that ongoing maternal growth is an obstetric risk factor during adolescence.

Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones.

PubMed

Ishihara, Akikazu; Weisbrode, Steve E; Bertone, Alicia L

2015-10-01

Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Emergency ultrasound in the detection of pediatric long-bone fractures.

PubMed

Barata, Isabel; Spencer, Robert; Suppiah, Ara; Raio, Christopher; Ward, Mary Frances; Sama, Andrew

2012-11-01

Long-bone fractures represent one of the most commonly sustained injuries following trauma and account for nearly 4% of emergency department visits in the United States each year. These fractures are associated with a significant risk of bleeding and neurovascular compromise. Delays in their identification and treatment can lead to loss of limb and even death. Although emergency physicians currently rely predominantly on radiography for the examination of long-bone injuries, emergency ultrasound has several advantages over radiography and may be useful in the identification of long-bone fractures. Ultrasound is rapid, noninvasive, and cost-effective. Unlike radiography, ultrasound does not expose children to ionizing radiation, which has been linked to cancer. The goal of this study was to assess the agreement between emergency physicians' and radiologists' final assessments of suspected long-bone fractures using emergency ultrasound and radiography, respectively, in the pediatric population. This is a prospective study involving a convenience sample of pediatric patients (<18 years of age) who presented to the emergency department of a university-affiliated, level I trauma center between March 2008 and January 2009 with at least 1 suspected long-bone fracture. Suspected fractures were characterized by swelling, erythema, and localized pain. Patients who had a history of fracture, extremity deformity, orthopedic hardware in the traumatized area, or an open fracture were excluded from this study. Each investigator received limited, focused training in the use of ultrasonography for fracture identification and localization. This training consisted of a brief didactic session and video review of normal and fractured long-bones. A total of 53 subjects (mean age, 10.2 [SD, 3.8] years; 56.6% were male) were enrolled, which corresponded to 98 ultrasound examinations. Sixty-nine scans (70.4%) involved bones of the upper extremity, and 29 (29.6%) the lower extremity. Radiography identified a total of 43 fractures. The sensitivity and specificity of ultrasound in the detection of long-bone fractures were 95.3% (95% confidence interval [CI], 82.9%-99.2%) and 85.5% (95% CI, 72.8%-93.1%), respectively, and the positive and negative predictive values were 83.7% (95% CI, 68.8%-92.2%) and 96% (95% CI, 84.9%-99.3%), respectively. Overall, ultrasound detected 100.0% of diaphyseal fractures and 27 (93.1%) of 29 end-of-bone or near-joint fractures.Radiography revealed 6 displacements that met the published criteria for reduction, all of which were also revealed by ultrasound. The overall sensitivity and specificity for ultrasound identifying the need for reduction were 100.0% (95% CI, 51.7%-100.0%) and 97.3% (95% CI, 84.2%-99.9%), respectively, and positive and negative predictive values were 85.7% (95% CI, 42.0%-99.2%) and 100.0% (95% CI, 88.0%-100.0%), respectively. Emergency department physician-performed focused ultrasound was more accurate in detecting diaphyseal fractures than in detecting fractures in the metaphysis and/or epiphysis. The high sensitivity and specificity of ultrasound in the detection of long-bone fractures and the need for reduction support the use of ultrasound in the evaluation of suspected long-bone fractures in children.

Age-associated bone loss and intraskeletal variability in the Imperial Romans.

PubMed

Cho, Helen; Stout, Sam Darrel

2011-01-01

An Imperial Roman sample from the Isola Sacra necropolis (100-300 A.D.) offered an opportunity to histologically examine bone loss and intraskeletal variability in an urban archaeological population. Rib and femur samples were analyzed for static indices of bone remodeling and measures of bone mass. The Imperial Romans experienced normal age-associated bone loss via increased intracortical porosity and endosteal expansion, with females exhibiting greater bone loss and bone turnover rates than in males. Life events such as menopause and lactation coupled with cultural attitudes and practices regarding gender and food may have led to increased bone loss in females. Remodeling dynamics differ between the rib and femur and the higher remodeling rates in the rib may be attributed to different effective age of the adult compacta or loading environment. This study demonstrates that combining multiple methodologies to examine bone loss is necessary to shed light on the biocultural factors that influence bone mass and bone loss.

Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers.

PubMed

Bacchetta, Justine; Fargue, Sonia; Boutroy, Stéphanie; Basmaison, Odile; Vilayphiou, Nicolas; Plotton, Ingrid; Guebre-Egziabher, Fitsum; Dohin, Bruno; Kohler, Rémi; Cochat, Pierre

2010-06-01

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds.

PubMed

Solchaga, Luis A; Temenoff, Johnna S; Gao, Jizong; Mikos, Antonios G; Caplan, Arnold I; Goldberg, Victor M

2005-04-01

The natural repair of osteochondral defects can be enhanced with biocompatible, biodegradable materials that support the repair process. It is our hypothesis that hyaluronan-based scaffolds are superior to synthetic scaffolds because they provide biological cues. We tested this thesis by comparing two hyaluronan-based scaffolds [auto cross-linked polysaccharide polymer (ACP) and HYAFF-11] to polyester-based scaffolds [poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA)] with similar pore size, porosity and degradation times. Fifty-four rabbits received bilateral osteochondral defects. One defect received a hyaluronan-based scaffold and the contralateral defect received the corresponding polyester-based scaffold. Rabbits were euthanized 4, 12 and 20 weeks after surgery and the condyles dissected and processed for histology. Only ACP-treated defects presented bone at the base of the defect at 4 weeks. At 12 weeks, only defects treated with rapidly dissolving implants (ACP and PLGA) presented bone reconstitution consistently, while bone was present in only one third of those treated with slowly dissolving scaffolds (HYAFF-11 and PLLA). After 20 weeks, the articular surface of PLGA-treated defects presented fibrillation more frequently than in ACP-treated defects. The surface of defects treated with slowly dissolving scaffolds presented more cracks and fissures. The degradation rate of the scaffolds is critical for the repair process. Slowly dissolving scaffolds sustain thicker cartilage at the surface but, it frequently presents cracks and discontinuities. These scaffolds also delay bone formation at the base of the defects. Hyaluronan-based scaffolds appear to allow faster cell infiltration leading to faster tissue formation. The degradation of ACP leads to rapid bone formation while the slow degradation of HYAFF-11 prolongs the presence of cartilage and delays endochondral bone formation.

Bone and fat connection in aging bone.

PubMed

Duque, Gustavo

2008-07-01

The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study.

PubMed

Farooqui, Zishaan; Bakulski, Kelly M; Power, Melinda C; Weisskopf, Marc G; Sparrow, David; Spiro, Avron; Vokonas, Pantel S; Nie, Linda H; Hu, Howard; Park, Sung Kyun

2017-01-01

Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. In a 1993-2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25. Among men 51-98 at baseline, higher patella Pb concentration (IQR: 21μg/g) was associated with -0.13 lower baseline MMSE (95% CI: -0.25, -0.004) and faster longitudinal MMSE decline (-0.016 units/year, 95% CI: -0.032, -0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: -0.026, -0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: -0.027, -0.002). We found weaker associations with tibia Pb. Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Segmentation of bone pixels from EROI Image using clustering method for bone age assessment

NASA Astrophysics Data System (ADS)

Bakthula, Rajitha; Agarwal, Suneeta

2016-03-01

The bone age of a human can be identified using carpal and epiphysis bones ossification, which is limited to teen age. The accurate age estimation depends on best separation of bone pixels and soft tissue pixels in the ROI image. The traditional approaches like canny, sobel, clustering, region growing and watershed can be applied, but these methods requires proper pre-processing and accurate initial seed point estimation to provide accurate results. Therefore this paper proposes new approach to segment the bone from soft tissue and background pixels. First pixels are enhanced using BPE and the edges are identified by HIPI. Later a K-Means clustering is applied for segmentation. The performance of the proposed approach has been evaluated and compared with the existing methods.

Basic Biology of Skeletal Aging: Role of Stress Response Pathways

PubMed Central

2013-01-01

Although a decline in bone formation and loss of bone mass are common features of human aging, the molecular mechanisms mediating these effects have remained unclear. Evidence from pharmacological and genetic studies in mice has provided support for a deleterious effect of oxidative stress in bone and has strengthened the idea that an increase in reactive oxygen species (ROS) with advancing age represents a pathophysiological mechanism underlying age-related bone loss. Mesenchymal stem cells and osteocytes are long-lived cells and, therefore, are more susceptible than other types of bone cells to the molecular changes caused by aging, including increased levels of ROS and decreased autophagy. However, short-lived cells like osteoblast progenitors and mature osteoblasts and osteoclasts are also affected by the altered aged environment characterized by lower levels of sex steroids, increased endogenous glucocorticoids, and higher oxidized lipids. This article reviews current knowledge on the effects of the aging process on bone, with particular emphasis on the role of ROS and autophagy in cells of the osteoblast lineage in mice. PMID:23825036

Gradual downhill running improves age-related skeletal muscle and bone weakness: implication of autophagy and bone morphogenetic proteins.

PubMed

Kim, Jeong-Seok; Lee, Young-Hee; Yi, Ho-Keun

2016-12-01

What is the central question of this study? Exercise training by running has an effect on age-related muscle and bone wasting that improves physical activity and quality of life in the elderly. However, the effect of downhill running on age-related muscle and bone wasting, and its mechanisms, are unclear. What is the main finding and its importance? Gradual downhill running can improve skeletal muscle growth and bone formation by enhancing autophagy and bone morphogenetic protein signalling in aged rats. Therefore, downhill running exercise might be a practical intervention to improve skeletal muscle and bone protection in the elderly. Recent evidence suggests that autophagy and the bone morphogenetic protein (BMP) signalling pathway regulate skeletal muscle growth and bone formation in aged rats. However, the effect of downhill running on muscle growth and bone formation is not well understood. Thus, we investigated the effect of downhill and uphill running on age-related muscle and bone weakness. Young and late middle-aged rats were randomly assigned to control groups (young, YC; and late middle-aged, LMC) and two types of running training groups (late middle-aged downhill, LMD; and late middle-aged uphill, LMU). Training was progressively carried out on a treadmill at a speed of 21 m min -1 with a slope of +10 deg for uphill training versus 16 m min -1 with a slope of -16 deg for downhill training, both for 60 min day -1 , 5 days week -1 for 8 weeks. Downhill and uphill training increased autophagy-related protein 5, microtubule-associated protein light chain, Beclin-1 and p62 proteins in aged rats. In addition, superoxide dismutase, haem oxygenase-1 and the BMP signalling pathway were elevated. Phosphorylation of mammalian target of rapamycin and myogenic differentiation were increased significantly in the LMD and LMU groups. Consequently, in the femur, BMP-2, BMP-7 and autophagy molecules were highly expressed in the LMD and LMU groups. These results suggest that both downhill and uphill training appear to have a positive effect on expression of autophagy molecules and BMPs. In particular, these physiological adaptations from gradual downhill exercise have an effect on bone morphological changes and muscle quality similar to gradual uphill training interventions in ageing. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Effect of recombinant insulin-like growth factor-1 treatment on short-term linear growth in a child with Majewski osteodysplastic primordial dwarfism type II and hepatic insufficiency.

PubMed

Faienza, Maria Felicia; Acquafredda, Angelo; D'Aniello, Mariangela; Soldano, Lucia; Marzano, Flaviana; Ventura, Annamaria; Cavallo, Luciano

2013-01-01

We report the case of a boy affected by severe intrauterine and postnatal growth retardation, microcephaly, facial dysmorphisms and postnecrotic cirrhosis, diagnosed at birth as having Seckel syndrome, and subsequently confirmed as Majewski osteodysplastic primordial dwarfism type II (MOPD II) on the basis of clinical and radiological features of skeletal dysplasia. At our observation (6 years 7 months) he presented height -10.3 standard deviation score (SDS), weight -22.1 SDS, head circumference -8 SDS, delayed bone age of 4 years with respect to chronological age. In consideration of the low levels of insulin-like growth factor-1 (IGF-1) as well as of hepatic insufficiency, we started the treatment with recombinant human IGF-1 (rhIGF-1) at the dose of 0.04 mg/kg in 2 doses/day, with an increase of 0.04 mg/kg after 1 week until the maximum dose of 0.12 mg/kg. We observed an early response to rhIGF-1 treatment, with a shift of height velocity from 1.8 cm/year (-4.6 SDS) at 4 cm/year (-1.9 SDS), and an increase in bone age of 1.5 years during the first 6 months. rhIGF-1 treatment does not seem to be able to replace the physiological action of IGF-1 in patients with MOPD II and hepatic insufficiency, however, it seems to preserve the typical growth pattern of MOPD II patients, avoiding a further widening of the growth deficiency in these subjects.

[Treatment of adult avascular necrosis of femoral head by transplanting iliac bone flap with deep iliac circumflex vessels and cancellous bone].

PubMed

Yu, Zhiliang; Zhang, Ning; Yang, Yi; Wang, Bin; Gao, Shuo; Zhao, Xiaoyong

2013-07-01

To investigate the effectiveness of transplanting iliac bone flap with deep iliac circumflex vessels and cancellous bone for the treatment of adult avascular necrosis of the femoral head (ANFH). A retrospective analysis was made on the clinical data of 685 patients (803 hips) with ANFH, who underwent iliac bone flap transplantation with deep iliac circumflex vessels and cancellous bone between March 2002 and January 2010. There were 489 males (580 hips) and 196 females (223 hips) with a mean age of 40.4 years (range, 18-63 years), including 567 unilateral cases (303 left hips and 264 right hips) and 118 bilateral cases. The causes of ANFH included alcohol-induced in 223 cases, steroid-induced in 179 cases, alcohol + steroid-induced in 21 cases, traumatic in 136 cases, acetabular dysplasia in 8 cases, bone cyst in 5 cases, septic arthritis in 2 cases, joint tuberculosis in 3 cases, rheumatoid arthritis in 5 cases, and idiopathic in 103 cases. According to Steinberg staging, 211 hips were rated as stage II, 513 hips as stage III, and 79 hips as stage IV. The preoperative Harris hip score was 60.30 +/- 7.02. Fat necrosis occurred in 2 cases after operation, primary healing of incision was obtained in the other cases; delayed infection, lower extremity deep vein thrombosis, and pulmonary embolism occurred in 2 cases, respectively. All patients were followed up 36-60 months (mean, 49 months). Harris hip score at last follow-up (83.50 +/- 7.31) was significantly higher than that at preoperation (t= -2 266.980, P=0.000), and the scores were significantly higher than those at preoperation in different stages (P < 0.05). The results were excellent in 523 hips, good in 185 hips, fair in 65 hips, and poor in 30 hips, and the excellent and good rate was 88.2%. X-ray examination showed bone fusion of transplanted bone flap and bone graft with an average of 4.2 months (range, 3-6 months); according to Steinberg staging, imaging stable rate was 78.3% (629/803) at last follow-up. Iliac bone flap transplantion with deep iliac circumflex vessels and cancellous bone has the advantages of complete decompression of the femoral head, exact flap blood supply, improved blood supply of the femoral head, new support for the femoral head, and participation of osteoinductive effect for the treatment of adult ANFH, so it is an effective treatment for the retention of the femoral head.

Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

PubMed

Langdahl, Bente; Ferrari, Serge; Dempster, David W

2016-12-01

The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that rediscovering a phenomenon that was first observed more half a century ago will have an important impact on our understanding of how new antifracture treatments work.

Low bone mineral mass is associated with decreased bone formation and diet in girls with Rett syndrome.

PubMed

Motil, Kathleen J; Barrish, Judy O; Neul, Jeffrey L; Glaze, Daniel G

2014-09-01

The aim of the present study was to characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of girls with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Total body bone mineral content (BMC) and bone mineral density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and sex, showed significant positive associations with total body BMD z scores. The present study suggests decreased bone formation instead of increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium, and phosphorus intakes may offer an opportunity to improve bone health in RTT.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory

PubMed Central

Jones, Watson; Roberts, R. E.

1933-01-01

(1) Pathology of calcification and ossification.—The Leriche-Policard theories. Hyperæmia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. “Myositis ossificans.” (2) Radiological significance of density of bone shadows.—Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular. (3) Hyperæmic decalcification of bone.—Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperæmic dislocation of the atlas. Hyperæmic decalcification and nephrolithiasis. (4) Anæmic sclerosis of bone.—Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone—Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases. (5) Pathological calcification.—Calcification of supraspinatus tendon. Calcification of tumours—angioma, hæmatoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs. (6) Pathological ossification.—Ossification of tendons. Ossification of semilunar cartilages. PMID:19989304

Osteosynthesis of ununited femoral neck fracture by internal fixation combined with iliac crest bone chips and muscle pedicle bone grafting

PubMed Central

Baksi, D D; Pal, A K; Baksi, D P

2016-01-01

Background: Ununited femoral neck fracture is seen commonly in developing countries due to delayed presentation or failure of primary internal fixation. Such fractures, commonly present with partial or total absorption of femoral neck, osteonecrosis of femoral head in 8–30% cases with upward migration of trochanter posing problem for osteosynthesis, especially in younger individuals. Several techniques for treatment of such conditions are described like osteotomies or nonvascularied cortical or cancellous bone grafting provided varying degrees of success in terms of fracture union but unsatisfactory long term results occurred due to varying incidence of avascular necrosis (AVN) of femoral head. Moreover, in presence of AVN of femoral head neither free fibular graft nor cancellous bone graft is satisfactory. The vascularied bone grafting by deep circumflex iliac artery based on iliac crest bone grafting, free vascularied fibular grafting and muscle pedicle periosteal grafting showed high incidence of success rate. Osteosynthesis is the preferred treatment of choice in ununited femoral neck fracture in younger individuals. Materials and Methods: Of the 293 patients operated during the period from June 1977 to June 2009, 42 were lost to followup. Seven patients with gluteus medius muscle pedicle bone grafting (MPBG) were excluded. Thus, out of 244 patients, 208 (85.3%) untreated nonunion and 36 (14.7%) following failure of primary internal fixation were available for studies. Time interval between the date of injury and operation in untreated nonunion cases was mean 6.5 months and in failed internal fixation cases was mean 11.2 months. Ages of the patients varied from 16 to 55 years. Seventy patients had partial and 174 had subtotal absorption of the femoral neck. Evidence of avascular necrosis (AVN) femoral head was found histologically in 135 (54.3%) and radiologically in 48 (19.7%) patients. The patients were operated by open reduction of fracture, cannulated hip screw fixation, iliac crest bone chips and quadratus femoris MPBG. Results: The mean followup is 12.5 years (range 3-35). The union of fractures occurred in 202 (82.8%), delayed union in 18 (7.3%), and established nonunion in 24 (9.8%) patients. Full weight bearing was permitted at 16–22 weeks after union of fractures. Mean Harris hip score at the longest followup was 85.5. Among the complications, superficial wound infection occurred in 20 (8.2%), deep infection in seven (2.9%), and coxa vara in 39 (16%) patients. Preoperative radiodensity of femoral head disappeared mostly after the union of fracture whereas fresh radiodensity of femoral head appeared in 20 (8%) patients; nine (45%) of them developed segmental collapse. Conclusion: Ununited femoral neck fractureis characterized by absorption of femoral neck, posterior cortical defect, smoothening and overriding of fracture surfaces with intervening fibrous tissues associated with or without AVN of femoral head. The above method of osteosynthesis rectified the above pathology and provided satisfactory results with union of fractures in 90.1% patients at long term followup. PMID:27512217

Comparison of two kinds of bovine bone in maxillary sinus augmentation: a histomorphometric study.

PubMed

Moon, Jee-Won; Sohn, Dong-Seok; Heo, Jeung-Uk; Kim, Jin Sun

2015-02-01

The purpose of this study was to compare the histomorphometric from sinus augmentation with calcium-phosphate nanocrystal-coated bovine bone (Biocera) and anorganic bovine bone matrix (Bio-Oss). Bilateral maxillary sinus augmentations were performed on 5 patients with delayed placement of implants. The lateral bony window was created using a piezoelectric saw, and the sinus membrane was elevated to make a new compartment. Bio-Oss was grafted in one sinus as the control group and Biocera was grafted in the opposite sinus as the test group. The bony window was repositioned over the bone graft. In all cases, samples were taken for biopsy at the time of implant placement, 6 to 8 months after the grafting procedure. Independent t tests were used to examine between-group differences. None of the 5 patients had complications during healing period. Histomorphometrically, the Bio-Oss group showed 28.46% (±5.28%) of newly formed bone. Biocera group showed 29.94% (±8.72%) of newly formed bone. Newly formed bone along inner surface of repositioned bony window area showed more mature and dense bone structure than new bone formed along bone graft. This study revealed that both bovine bone grafts were considered as suitable bone graft materials for maxillary sinus augmentation.

Influence of irradiation on the osteoinductive potential of demineralized bone matrix.

PubMed

Wientroub, S; Reddi, A H

1988-04-01

Samples of demineralized bone matrix (DBM) were exposed to graduated doses of radiation (1-15 Megarad) (Mrad) utilizing a linear accelerator and then implanted into the thoracic region of Long-Evans rats. Subcutaneous implantation of DBM into allogenic rats induces endochondral bone. In response to matrix implantation, a cascade of events ensues; mesenchymal cell proliferation on day 3 postimplantation, chondrogenesis on day 7, calcification of the cartilagenous matrix and chondrolysis on day 9, and osteogenesis on day 11 resulting in formation of an ossicle containing active hemopoietic tissue. Bone formation was assessed by measuring alkaline phosphatase activity, the rate of mineralization was determined by measuring 45Ca incorporation to bone mineral, and 40Ca content measured the extent of mineralization; acid phosphatase activity was used as a parameter for bone resorption. The dose of radiation (2.5 Mrad) currently used by bone banks for sterilization of bone tissue did not destroy the bone induction properties of DBM. Furthermore, radiation of 3-5 Mrad even enhanced bone induction, insofar as it produced more bone at the same interval of time than was obtained from unirradiated control samples. None of the radiation doses used in these experiments abolished bone induction, although the response induced by matrix irradiated with doses higher than 5 Mrad was delayed.

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis.

PubMed

Junbo, Wang; Sijia, Liu; Hongying, Chen; Lei, Liu; Pu, Wang

2017-06-15

Whole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritisrabbit model. Ninety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed. After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group. Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Overexpression of Insulin-Like Growth Factor 1 Enhanced the Osteogenic Capability of Aging Bone Marrow Mesenchymal Stem Cells.

PubMed

Chen, Ching-Yun; Tseng, Kuo-Yun; Lai, Yen-Liang; Chen, Yo-Shen; Lin, Feng-Huei; Lin, Shankung

2017-01-01

Many studies have indicated that loss of the osteoblastogenic potential in bone marrow mesenchymal stem cells (bmMSCs) is the major component in the etiology of the aging-related bone deficit. But how the bmMSCs lose osteogenic capability in aging is unclear. Using 2-dimentional cultures, we examined the dose response of human bmMSCs, isolated from adult and aged donors, to exogenous insulin-like growth factor 1 (IGF-1), a growth factor regulating bone formation. The data showed that the mitogenic activity and the osteoblastogenic potential of bmMSCs in response to IGF-1 were impaired with aging, whereas higher doses of IGF-1 increased the proliferation rate and osteogenic potential of aging bmMSCs. Subsequently, we seeded IGF-1-overexpressing aging bmMSCs into calcium-alginate scaffolds and incubated in a bioreactor with constant perfusion for varying time periods to examine the effect of IGF-1 overexpression to the bone-forming capability of aging bmMSCs. We found that IGF-1 overexpression in aging bmMSCs facilitated the formation of cell clusters in scaffolds, increased the cell survival inside the cell clusters, induced the expression of osteoblast markers, and enhanced the biomineralization of cell clusters. These results indicated that IGF-1 overexpression enhanced cells' osteogenic capability. Thus, our data suggest that the aging-related loss of osteogenic potential in bmMSCs can be attributed in part to the impairment in bmMSCs' IGF-1 signaling, and support possible application of IGF-1-overexpressing autologous bmMSCs in repairing bone defect of the elderly and in producing bone graft materials for repairing large scale bone injury in the elderly.

NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

PubMed Central

Yao, Zhenqiang; Li, Yanyun; Yin, Xiaoxiang; Dong, Yufeng; Xing, Lianping; Boyce, Brendan F.

2013-01-01

RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through non-canonical signaling, but they involved a complex knockout mouse model and the molecular mechanisms involved were not investigated. Here, we report that RelB−/− mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB−/− bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runx2. In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB−/− bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. PMID:24115294

SATB2-Nanog axis links age-related intrinsic changes of mesenchymal stem cells from craniofacial bone

PubMed Central

Xu, Rongyao; Ge, Jie; Fu, Yu; Zhang, Yuchao; Du, Yifei; Ye, Jinhai; Cheng, Jie; Jiang, Hongbing

2016-01-01

Bone mesenchymal stem cells (BMSCs) senescence contributes to age-related bone loss. The alveolar bone in jaws originates from neural crest cells and possesses significant site- and age-related properties. However, such intrinsic characteristics of BMSCs from alveolar bone (AB-BMSCs) and the underlying regulatory mechanisms still remain unknown. Here, we found that the expression of special AT-rich binding protein 2 (SATB2) in human AB-BMSCs significantly decreased with aging. SATB2 knockdown on AB-BMSCs from young donors displayed these aging-related phenotypes in vitro. Meanwhile, enforced SATB2 overexpression could rejuvenate AB-BMSCs from older donors. Importantly, satb2 gene- modified BMSCs therapy could prevent the alveolar bone loss during the aging of rats. Mechanistically, the stemness regulator Nanog was identified as the direct transcriptional target of SATB2 in BMSCs and functioned as a downstream mediator of SATB2. Collectively, our data reveal that SATB2 in AB-BMSCs associates with their age-related properties, and prevents AB-BMSCs senescence via maintaining Nanog expression. These findings highlight the translational potential of transcriptional factor-based cellular reprogramming for anti-aging therapy. PMID:27632702

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting: approval and efficacy

PubMed Central

Navari, Rudolph M

2009-01-01

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient characteristics (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV. This review provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The chemistry and pharmacology of palonosetron are described, as well as the initial and recent clinical trials. Palonosetron has a longer half-life and a higher binding affinity than the first-generation 5-HT3 receptor antagonists. Palonosetron has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared to the first-generation 5-HT3 receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy. There were no clinically relevant adverse reactions reported in the palonosetron clinical trials which were different from the common reactions reported for the 5-HT3 receptor antagonist class. Due to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation. PMID:21188135

Brief communication: a proposed method for the assessment of pubertal stage in human skeletal remains using cervical vertebrae maturation.

PubMed

Shapland, Fiona; Lewis, Mary E

2014-01-01

The assessment of age-at-death in non-adult skeletal remains is under constant review. However, in many past societies an individual's physical maturation may have been more important in social terms than their exact age, particularly during the period of adolescence. In a recent article (Shapland and Lewis: Am J Phys Anthropol 151 (2013) 302-310) highlighted a set of dental and skeletal indicators that may be useful in mapping the progress of the pubertal growth spurt. This article presents a further skeletal indicator of adolescent development commonly used by modern clinicians: cervical vertebrae maturation (CVM). This method is applied to a collection of 594 adolescents from the medieval cemetery of St. Mary Spital, London. Analysis reveals a potential delay in ages of attainment of the later CVM stages compared with modern adolescents, presumably reflecting negative environmental conditions for growth and development. The data gathered on CVM is compared to other skeletal indicators of pubertal maturity and long bone growth from this site to ascertain the usefulness of this method on archaeological collections. Copyright © 2013 Wiley Periodicals, Inc.

Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp; Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp; Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp

In diabetes mellitus (DM), high glucose (HG) and advanced glycation end products (AGEs) are involved in bone quality deterioration. Osteocytes produce sclerostin and receptor activator of nuclear factor-kB ligand (RANKL) and regulate osteoblast and osteoclast function. However, whether HG or AGEs directly affect osteocytes and regulate sclerostin and RANKL production is unknown. Here, we examined the effects of HG, AGE2, and AGE3 on the expression of sclerostin and RANKL and on apoptosis in osteocyte-like MLO-Y4-A2 cells. Treatment of the cells with 22 mM glucose, 100 μg/mL either AGE2 or AGE3 significantly increased the expression of sclerostin protein and mRNA; however, both AGEs,more » but not glucose, significantly decreased the expression of RANKL protein and mRNA. Moreover, treatment of the cells with HG, AGE2, or AGE3 for 72 h induced significant apoptosis. These detrimental effects of HG, AGE2, and AGE3 on sclerostin and RANKL expressions and on apoptosis were antagonized by pretreatment of the cells with 10{sup −8} M human parathyroid hormone (PTH)-(1–34). Thus, HG and AGEs likely suppress bone formation by increasing sclerostin expression in osteocytes, whereas AGEs suppress bone resorption by decreasing RANKL expression. Together, these processes may cause low bone turnover in DM. In addition, HG and AGEs may cause cortical bone deterioration by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function. - Highlights: • AGEs are involved in bone quality deterioration in diabetes mellitus (DM). • AGEs increased sclerostin as well as apoptosis, and decreased RANKL in osteocytes. • The effects of AGEs on osteocyte function were antagonized by human PTH-(1–34). • AGEs may cause low bone turnover and cortical porosity in DM. • PTH may be effective in bone quality deterioration by improving osteocyte function.« less

Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage

PubMed Central

Singh, Lakshman; Brennan, Tracy A.; Russell, Elizabeth; Kim, Jung-Hoon; Chen, Qijun; Johnson, F. Brad; Pignolo, Robert J.

2016-01-01

Bone marrow derived mesenchymal progenitor cells (MPCs) play an important role in bone homeostasis. Age-related changes occur in bone resulting in a decrease in bone density and a relative increase in adipocity. Although in vitro studies suggest the existence of an age-related lineage switch between osteogenic and adipogenic fates, stem cell and microenvironmental contributions to this process have not been elucidated in vivo. In order to study the effects of MPC and microenvironmental aging on functional engraftment and lineage switching, transplantation studies were performed under non-myeloablative conditions in old recipients, with donor MPCs derived from young and old green fluorescent protein (GFP) transgenic mice. Robust engraftment by young MPCs or their progeny was observed in the marrow, bone-lining region and in the matrix of young recipients; however, significantly lower engraftment was seen at the same sites in old recipients transplanted with old MPCs. Differentiation of transplanted MPCs strongly favored adipogenesis over osteogenesis in old recipients irrespective of MPC donor age, suggesting that microenvironmental alterations that occur with in vivo aging are predominately responsible for MPC lineage switching. These data indicate that aging alters bone-fat reciprocity and differentiation of mesenchymal progenitors toward an adipogenic fate. PMID:26805026

Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage.

PubMed

Singh, Lakshman; Brennan, Tracy A; Russell, Elizabeth; Kim, Jung-Hoon; Chen, Qijun; Brad Johnson, F; Pignolo, Robert J

2016-04-01

Bone marrow derived mesenchymal progenitor cells (MPCs) play an important role in bone homeostasis. Age-related changes occur in bone resulting in a decrease in bone density and a relative increase in adipocity. Although in vitro studies suggest the existence of an age-related lineage switch between osteogenic and adipogenic fates, stem cell and microenvironmental contributions to this process have not been elucidated in vivo. In order to study the effects of MPC and microenvironmental aging on functional engraftment and lineage switching, transplantation studies were performed under non-myeloablative conditions in old recipients, with donor MPCs derived from young and old green fluorescent protein (GFP) transgenic mice. Robust engraftment by young MPCs or their progeny was observed in the marrow, bone-lining region and in the matrix of young recipients; however, significantly lower engraftment was seen at the same sites in old recipients transplanted with old MPCs. Differentiation of transplanted MPCs strongly favored adipogenesis over osteogenesis in old recipients irrespective of MPC donor age, suggesting that microenvironmental alterations that occur with in vivo aging are predominately responsible for MPC lineage switching. These data indicate that aging alters bone-fat reciprocity and differentiation of mesenchymal progenitors towards an adipogenic fate. Copyright © 2016 Elsevier Inc. All rights reserved.

Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender.

PubMed

Schwartz, Z; Somers, A; Mellonig, J T; Carnes, D L; Dean, D D; Cochran, D L; Boyan, B D

1998-04-01

Demineralized freeze-dried bone allografts (DFDBA) have been used extensively in periodontal therapy. DFDBA is used because it contains bone morphogenetic protein (BMP), which induces new bone formation during the healing process. Most commercial bone banks do not verify the presence or activity of BMP in DFDBA nor the ability of DFDBA to induce new bone. Recently, we showed that different bone bank preparations of DFDBA, even from the same bank, varied considerably in their ability to induce new bone, suggesting inherent differences in the quality of the material. Therefore, we examined whether donor age or gender contributed to the variability seen with these preparations. Twenty-seven batches of DFDBA from different donors were donated by one bone bank which had been shown previously to supply DFDBA that was consistently able to induce new bone formation. Each batch was implanted bilaterally in the thigh muscle of nude mice. After 56 days, the implants were excised and examined by light microscopy and histomorphometry. Seventy percent of the preparations tested induced new bone formation. Most of these preparations produced ossicles containing cortical bone surrounding bone marrow-like tissue. The ability to induce bone appears to be age-dependent, with DFDBA from older donors being less likely to have strong bone-inducing activity. By contrast, no difference in ability to induce new bone was noticed between male or female donors. The results of this study confirm that commercial preparations of DFDBA differ in their ability to induce new bone formation. In fact, some of the batches had no activity at all. The ability of DFDBA to induce new bone formation is suggested to be age-dependent, but not gender-dependent by our study. These results indicate that commercial bone banks need to verify the ability of DFDBA to induce new bone formation and should reconsider the advisability of using bone from older donors.

Age-related changes in vertebral and iliac crest 3D bone microstructure--differences and similarities.

PubMed

Thomsen, J S; Jensen, M V; Niklassen, A S; Ebbesen, E N; Brüel, A

2015-01-01

Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes. The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between the bone microstructure at these skeletal sites. Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19-96 years) and 39 men (23-95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified. For both women and men, bone volume per total volume (BV/TV), connectivity density (CD), and trabecular number (Tb.N) decreased significantly, while structure model index (SMI) and trabecular separation (Tb.Sp) increased significantly with age at either skeletal site. Vertebral trabecular thickness (Tb.Th) was independent of age for both women and men, while iliac Tb.Th decreased significantly with age for men, but not for women. In general, the vertebral and iliac age-related changes were similar. The 95th percentile of the Tb.Th distribution increased significantly with age for women but was independent of age for men at the vertebral body, while it was independent of age for either sex at the iliac crest. The Tb.Th probability density functions at the two skeletal sites became significantly more similar with age for women, but not for men. The microstructural parameters at the iliac crest and the vertebral bodies were only moderately correlated from r = 0.38 for SMI in women to r = 0.75 for Tb.Sp in men. Age-related changes in vertebral and iliac bone microstructure were in general similar. The iliac and vertebral Tb.Th distributions became more similar with age for women. Despite the overall similar age-related changes in trabecular bone microstructure, the vertebral and iliac bone microstructural measures were only weakly correlated (r = 0.38 to 0.75).

Analysis of the effects of growth hormone, exercise and food restriction on cancellous bone in different bone sites in middle-aged female rats.

PubMed

Banu, J; Orhii, P B; Okafor, M C; Wang, L; Kalu, D N

2001-06-01

The aim of this study is to determine the effects of growth hormone (GH), exercise (EX), GH+EX and food restriction on cancellous bone in middle-aged female rats. Female F344 rats aged 13 months were divided into (1) age-matched controls; (2) GH treated (2.5 mg/kg. 5 day/week); (3) EX (voluntary wheel running); (4) GH+EX; and (5) food restricted (FR) (fed 60% of the ad libitum food intake). The animals were treated for 18 weeks, at the end of which they were sacrificed. Cancellous bone and cortical bone in the fourth lumbar vertebra, proximal tibial metaphysis (PTM), distal femoral metaphysis (DFM) and femoral neck (NF) were analyzed using peripheral quantitative computerized tomography (pQCT) densitometry. Growth hormone increased cancellous bone area, cancellous bone mineral content, cortical bone area and cortical bone mineral content in the vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased significantly after GH treatment. Exercise increased the cancellous bone area in the vertebra, PTM and DFM. Cortical bone area and cortical bone mineral content increased after EX in the vertebra, PTM, DFM and NF. No significant change was seen in the tibial muscle wet weight after EX. Growth hormone+EX increased cancellous bone area in the vertebra PTM and DFM but had no effect in neck of the femur. Cancellous bone mineral content, cortical bone area and cortical bone mineral content increased with GH+EX in the vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased significantly with GH+EX. Food restriction decreased cancellous bone area and cancellous bone mineral content in all the bones studied. The decrease was statistically significant only at the distal femoral metaphysis. The tibial muscle wet weight decreased when compared with the age-matched control, but this decrease was not statistically significant. We conclude that the effect of the dose of GH used and the levels of voluntary wheel running EX used increased cancellous bone in intact rats; the effect of GH is much greater and different bones respond with varying intensities. The effects of combined treatment of GH and EX on cancellous bone are not always significantly higher than those of GH alone. FR at the level studied has a mostly negative effect on cancellous bone.

Effect of cisplatin on bone transport osteogenesis in dogs.

PubMed

Ehrhart, Nicole; Eurell, Jo Ann C; Tommasini, Matteo; Constable, Peter D; Johnson, Ann L; Feretti, Antonio

2002-05-01

To document effects of cisplatin on regenerate bone formation during the distraction and consolidation phases of bone transport osteogenesis. 10 skeletally mature hounds. Bone transport osteogenesis was performed to reconstruct a 3-cm defect in the radius of each dog. Five dogs were randomly selected to receive cisplatin (70 mg/m2, IV, q 21 d for 4 cycles), and 5 were administered saline (0.9% NaCl) solution. Bone mineral density was measured by use of dual-energy x-ray absorptiometry (DEXA) on days 24, 55, and 90 after surgery. Dogs were euthanatized 90 days after surgery. Histomorphometry was performed on nondecalcified sections of regenerate bone. Bone mineral density and histomorphometric indices of newly formed bone were compared between groups. Densitometric differences in regenerate bone mineral density were not detected between groups at any time period. Cisplatin-treated dogs had decreased mineralized bone volume, decreased percentage of woven bone volume, decreased percentage of osteoblast-covered bone, increased porosity, and increased percentage of osteoblast-covered surfaces, compared with values for control dogs. Lamellar bone volume and osteoid volume did not differ significantly between groups. Regenerate bone will form and remodel during administration of cisplatin. Results of histomorphometric analysis suggest that bone formation and resorption may be uncoupled in cisplatin-treated regenerate bone as a result of increased osteoclast activity or delayed secondary bone formation during remodeling. These histomorphometric differences were modest in magnitude and did not result in clinically observable complications or decreased bone mineral density as measured by use of DEXA.

Novel NR2F1 variants likely disrupt DNA binding: molecular modeling in two cases, review of published cases, genotype–phenotype correlation, and phenotypic expansion of the Bosch–Boonstra–Schaaf optic atrophy syndrome

PubMed Central

Zimmermann, Michael T.; Ferber, Matthew J.; Niu, Zhiyv; Urrutia, Raul A.; Klee, Eric W.; Babovic-Vuksanovic, Dusica

2017-01-01

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the NR2F1 gene. There are presently 28 cases of BBSOAS described in the literature. Its common features include developmental delay, intellectual disability, hypotonia, optic nerve atrophy, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, and thinning of the corpus callosum. Here we report two unrelated probands with novel, de novo, missense variants in NR2F1. The first is a 14-yr-old male patient with hypotonia, intellectual disability, optic nerve hypoplasia, delayed bone age, short stature, and altered neurotransmitter levels on cerebrospinal fluid testing. The second is a 5-yr-old female with severe developmental delay, motor and speech delay, and repetitive motion behavior. Whole-exome sequencing identified a novel missense NR2F1 variant in each case, Cys86Phe in the DNA-binding domain in Case 1, and a Leu372Pro in the ligand-binding domain in Case 2. The presence of clinical findings compatible with BBSOAS along with structural analysis at atomic resolution using homology-based molecular modeling and molecular dynamic simulations, support the pathogenicity of these variants for BBSOAS. Short stature, abnormal CNS neurotransmitters, and macrocephaly have not been previously reported for this syndrome and may represent a phenotypic expansion of BBSOAS. A review of published cases along with new evidence from this report support genotype–phenotype correlations for this disorder. PMID:28963436

Exercise and Bone Density: Meta-Analysis.

DTIC Science & Technology

1999-09-01

1998, (4) changes in bone mineral density (regional, total) reported in adults ages 18 years and older . Disagreements between the Principal...individual patient data. C. So What? Our work to date suggests that exercise helps to increase and maintain bone mineral density in older (>31 years of age ...between January 1962 and December 1998, (4) changes in bone mineral density (regional, total) reported in adults ages 18 years and older . If you have any

Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone

PubMed Central

Smith, Christopher A.; Board, Tim N.; Rooney, Paul; Eagle, Mark J.; Richardson, Stephen M.

2017-01-01

To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC) osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC). BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP) enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1) concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors. PMID:28505164

Good things come to those who wait: attenuated discounting of delayed rewards in aged Fischer 344 rats

PubMed Central

Simon, Nicholas W.; LaSarge, Candi L.; Montgomery, Karienn S.; Williams, Matthew T.; Mendez, Ian A.; Setlow, Barry; Bizon, Jennifer

2010-01-01

The ability to make advantageous choices among outcomes that differ in magnitude, probability, and delay until their arrival is critical for optimal survival and well-being across the lifespan. Aged individuals are often characterized as less impulsive in their choices than their young adult counterparts, demonstrating an increased ability to forgo immediate in favor of delayed (and often more beneficial) rewards. Such “wisdom” is usually characterized as a consequence of learning and life experience. However, aging is also associated with prefrontal cortical dysfunction and concomitant impairments in advantageous choice behavior. Animal models afford the opportunity to isolate the effects of biological aging on decision making from experiential factors. To model one critical component of decision making, young adult and aged Fischer 344 rats were trained on a two-choice delay discounting task in which one choice provided immediate delivery of a small reward and the other provided a large reward delivered after a variable delay period. Whereas young adult rats showed a characteristic pattern of choice behavior (choosing the large reward at short delays and shifting preference to the small reward as delays increased), aged rats maintained a preference for the large reward at all delays (i.e. – attenuated “discounting” of delayed rewards). This increased preference for the large reward in aged rats was not due to perceptual, motor, or motivational factors. The data strongly suggest that, independent of life experience, there are underlying neurobiological factors that contribute to age-related changes in decision making, and particularly the ability to delay gratification. PMID:18657883

Application of statistical shape analysis for the estimation of bone and forensic age using the shapes of the 2nd, 3rd, and 4th cervical vertebrae in a young Japanese population.

PubMed

Rhee, Chang-Hoon; Shin, Sang Min; Choi, Yong-Seok; Yamaguchi, Tetsutaro; Maki, Koutaro; Kim, Yong-Il; Kim, Seong-Sik; Park, Soo-Byung; Son, Woo-Sung

2015-12-01

From computed tomographic images, the dentocentral synchondrosis can be identified in the second cervical vertebra. This can demarcate the border between the odontoid process and the body of the 2nd cervical vertebra and serve as a good model for the prediction of bone and forensic age. Nevertheless, until now, there has been no application of the 2nd cervical vertebra based on the dentocentral synchondrosis. In this study, statistical shape analysis was used to build bone and forensic age estimation regression models. Following the principles of statistical shape analysis and principal components analysis, we used cone-beam computed tomography (CBCT) to evaluate a Japanese population (35 males and 45 females, from 5 to 19 years old). The narrowest prediction intervals among the multivariate regression models were 19.63 for bone age and 2.99 for forensic age. There was no significant difference between form space and shape space in the bone and forensic age estimation models. However, for gender comparison, the bone and forensic age estimation models for males had the higher explanatory power. This study derived an improved objective and quantitative method for bone and forensic age estimation based on only the 2nd, 3rd and 4th cervical vertebral shapes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Delayed Effects of Acute Radiation Syndrome: Evidence of Long-Term Functional Changes in the Clonogenic Cells of the Small Intestine.

PubMed

Booth, Catherine; Tudor, Gregory L; Katz, Barry P; MacVittie, Thomas J

2015-11-01

Long term or residual damage post-irradiation has been described for many tissues. In hematopoietic stem cells (HSC), this is only revealed when the HSC are stressed and required to regenerate and repopulate a myeloablated host. Such an assay cannot be used to assess the recovery potential of previously irradiated intestinal stem cells (ISC) due to their incompatibility with transplantation. The best approximation to the HSC assay is the crypt microcolony assay, also based on clonogen survival. In the current study, the regenerative capacity of intestinal clonogenic cells in mice that had survived 13 Gy irradiation (with 5% bone marrow shielding to allow survival through the hematopoietic syndrome) and were then aged for 200 d was compared to previously unirradiated age-matched controls. Interestingly, at 200 d following 13 Gy, there remained a statistically significant reduction in crypts present in the various small intestinal regions (illustrating that the gastrointestinal epithelium had not fully recovered despite the 200-d interval). However, upon re-irradiation on day 196, those mice previously irradiated had improved crypt survival and regeneration compared to the age-matched controls. This was evident in all regions of the small intestine following 11-13 Gy re-exposure. Thus, there were either more clonogens per crypt within those previously irradiated and/or those that were present were more radioresistant (possibly because a subpopulation was more quiescent). This is contrary to the popular belief that previously irradiated animals may have an impaired/delayed regenerative response and be more radiosensitive.

The treatment of an unstable slipped capital femoral epiphysis by either intracapsular cuneiform osteotomy or pinning in situ: a comparative study.

PubMed

Walton, R D M; Martin, E; Wright, D; Garg, N K; Perry, D; Bass, A; Bruce, C

2015-03-01

We undertook a retrospective comparative study of all patients with an unstable slipped capital femoral epiphysis presenting to a single centre between 1998 and 2011. There were 45 patients (46 hips; mean age 12.6 years; 9 to 14); 16 hips underwent intracapsular cuneiform osteotomy and 30 underwent pinning in situ, with varying degrees of serendipitous reduction. No patient in the osteotomy group was lost to follow-up, which was undertaken at a mean of 28 months (11 to 48); four patients in the pinning in situ group were lost to follow-up, which occurred at a mean of 30 months (10 to 50). Avascular necrosis (AVN) occurred in four hips (25%) following osteotomy and in 11 (42%) following pinning in situ. AVN was not seen in five hips for which osteotomy was undertaken > 13 days after presentation. AVN occurred in four of ten (40%) hips undergoing emergency pinning in situ, compared with four of 15 (47%) undergoing non-emergency pinning. The rate of AVN was 67% (four of six) in those undergoing pinning on the second or third day after presentation. Pinning in situ following complete reduction led to AVN in four out of five cases (80%). In comparison, pinning in situ following incomplete reduction led to AVN in 7 of 21 cases (33%). The rate of development of AVN was significantly higher following pinning in situ with complete reduction than following intracapsular osteotomy (p = 0.048). Complete reduction was more frequent in those treated by emergency pinning and was strongly associated with AVN (p = 0.005). Non-emergency intracapsular osteotomy may have a protective effect on the epiphyseal vasculature and should be undertaken with a delay of at least two weeks. The place of emergency pinning in situ in these patients needs to be re-evaluated, possibly in favour of an emergency open procedure or delayed intracapsular osteotomy. Non-emergency pinning in situ should be undertaken after a delay of at least five days, with the greatest risk at two and three days after presentation. Intracapsular osteotomy should be undertaken after a delay of at least 14 days. In our experience, closed epiphyseal reduction is harmful. Cite this article: Bone Joint J 2015;97-B:412-19. ©2015 The British Editorial Society of Bone & Joint Surgery.

Histomorphometric reference data of transiliac bone biopsy in children from 8 to 17 years old.

PubMed

Velásquez-Forero, Francisco H; Jiménez-Brau, Daniel A; Esparza-García, Mariela

2018-01-01

Histomorphometric analysis of bone samples is a key tool for studying bone metabolism; however, only a few pediatric reference data exist. The aim of the present study is to report more reference data and to investigate if histomorphometric differences exist between age and gender. We obtained 19 transiliac bone samples previously marked with tetracycline, from children between 8 and 17 years (13 were male), with normal blood test results and urine biochemical bone markers. We evaluated bone histomorphometric parameters using a digitalizing table with osteomeasure to obtain normative data of means and standard deviations, as well as median and range. Due to the small sample, a Monte Carlo simulation was applied. Structural, static, dynamic, and resorptic histomorphometric parameters were evaluated by age and gender following the American Society for Bone and Mineral Research recommendations. Bone volume (in the older children) and mineral apposition rate (in the younger children), the eroded surface (in boys), and the new bone wall thickness (in girls) were significantly increased. On the trabecular area of mineralization front, the modeling and the remodeling bone formation were similar (16 and 18%). The rest of the histomorphometric bone parameters by age and gender showed no significant difference. In healthy children, these bone histomorphometric findings, with these techniques and for this ages could be used as reference values. Copyright: © 2018 Permanyer.

Low Bone Mineral Mass Is Associated with Decreased Bone Formation and Diet in Females with Rett Syndrome

PubMed Central

Motil, Kathleen J.; Barrish, Judy O.; Neul, Jeffrey L.; Glaze, Daniel G.

2014-01-01

Objective To characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of females with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Methods Total body bone mineral content (BMC) and density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Results Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z-scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and gender, showed significant positive associations with total body BMD z-scores. Conclusion This study suggests decreased bone formation rather than increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium and phosphorus intakes may offer an opportunity to improve bone health in RTT. PMID:25144778

Methods and application of bone densitometry in clinical diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wahner, H.W.; Riggs, B.L.

1986-01-01

With the awareness of osteoporosis as a major health problem for an aging population, there is great interest in early recognition and treatment of abnormal bone loss. Effective prevention of bone loss has to occur prior to the occurrence of irreparable damage. Standard radiographic procedures are not sensitive enough for the task. Therefore, a number of alternative procedures to estimate bone loss have been developed over the years, ranging from efforts to quantitate information obtained from radiographic images to sophisticated procedures such as neutron activation analysis or procedures based on the Compton scatter phenomenon. Only two procedures, photon absorptiometry andmore » computed tomography (CT), have emerged as applicable for routine clinical use. In photon absorptiometry the entire bone mineral (cortical and trabecular bone) of a specific skeletal site is measured. CT allows measuring of bone mineral of trabecular or cortical bone alone. Normally, bone mass reaches a maximum in the third decade and then continuously declines. This age-related bone loss is greater in women in whom an accelerated rate of loss occurs at the menopause. When bone density reaches a critical fracture threshold, skeletal fractures occur (spine, hip, and distal long bones). The age at which this critical fracture threshold is reached depends on the maximal bone mass achieved in early adulthood and the rate of loss with increasing age. With the exception of NaF, present-day therapeutic efforts only retard or prevent bone loss but do not significantly add bone mineral to the skeleton. Recognition of high-risk groups and early treatment are therefore required. 79 references.« less

Aging changes in the bones - muscles - joints

MedlinePlus

... ency/article/004015.htm Aging changes in the bones - muscles - joints To use the sharing features on ... to the body. Joints are the areas where bones come together. They allow the skeleton to be ...

Differences of bone mineral mass, volumetric bone mineral density, geometrical and structural parameters and derived strength of the tibia between premenopausal and postmenopausal women of different age groups: a peripheral Quantitative Computed Tomography (pQCT) study

PubMed Central

Stathopoulos, K.D.; Zoubos, A.B.; Papaioannou, N.A.; Mastrokalos, D.; Galanos, A.; Papagelopoulos, P.J.; Skarantavos, G.

2016-01-01

Menopause constitutes a significant cause of bone loss, and it is currently debated whether bone mass is preserved or begins to decline substantially before that time in women. We used pQCT of the tibia to estimate differences of bone mineral mass, bone geometry and derived strength between premenopausal and postmenopausal Caucasian women of different age-groups per decade of age (20-79y). For each individual, we assessed total, trabecular and cortical bone mineral content (BMC, mg) and volumetric bone mineral density (BMD, mg/cm3); total and cortical cross-sectional areas (CSA, mm2); periosteal circumference (PERI_C, mm); endosteal circumference (ENDO_C, mm); mean cortical thickness (CRT_THK, mm); and Stress-Strain Index (SSI). Comparisons were made both between premenopausal (N=84) and postmenopausal (N=231) women as distinct groups, and among women of the different age-groups. Our results indicated that premenopausal women had significantly higher trabecular and cortical BMC and vBMD, with higher cortical CSA, CRT_THK and SSI than postmenopausal women. Moreover, significant differences of trabecular but not cortical BMC, vBMD or SSI were found between women of the younger (<48y) age-groups. PERI_C, ENDO_C displayed lower values in the 20-29y group and higher values in the 70-79y group, denoting significant differences of bone geometry with aging. PMID:27282455

In vivo loss of function study reveals the short stature homeobox-containing (shox) gene plays indispensable roles in early embryonic growth and bone formation in zebrafish.

PubMed

Sawada, Rie; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shimizu, Toshiaki

2015-02-01

Congenital loss of the SHOX gene is considered to be a genetic cause of short stature phenotype in Turner syndrome and Leri-Weill dyschondrosteosis patients. Though SHOX expression initiates during early fetal development, little is known about the embryonic roles of SHOX. The evolutionary conservation of the zebrafish shox gene and the convenience of the early developmental stages for analyses make zebrafish a preferred model. Here, we characterized structure, expression, and developmental roles of zebrafish shox through a loss-of-function approach. We found a previously undiscovered Shox protein that has both a homeodomain and an OAR-domain in zebrafish. The shox transcript emerged during the segmentation period and it increased in later stages. The predominant domains of shox expression were mandibular arch, pectoral fin, anterior notochord, rhombencephalon, and mesencephalon, suggesting that Shox is involved in bone and neural development. Translational blockade of Shox mRNA by an antisense morpholino oligo delayed embryonic growth, which was restored by the co-overexpression of morpholino-resistant Shox mRNA. At later stages, impaired Shox expression markedly delayed the calcification process in the anterior vertebral column and craniofacial bones. Our data demonstrate evolutionarily conserved Shox plays roles in early embryonic growth and in later bone formation. © 2014 Wiley Periodicals, Inc.

Clinical Epidemiology of Buruli Ulcer from Benin (2005-2013): Effect of Time-Delay to Diagnosis on Clinical Forms and Severe Phenotypes.

PubMed

Capela, Carlos; Sopoh, Ghislain E; Houezo, Jean G; Fiodessihoué, René; Dossou, Ange D; Costa, Patrício; Fraga, Alexandra G; Menino, João F; Silva-Gomes, Rita; Ouendo, Edgard M; Rodrigues, Fernando; Pedrosa, Jorge

2015-01-01

Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (>15 cm diameter) or WHO Category (WHO Category 3 lesions). There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time-delay on the emergence of lesions classified as severe has not been addressed. To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory-confirmed cohort, we validated previous observations, demonstrating that time-delay is statistically related to the clinical form of BU. Indeed, for non-ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter >15 cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter ≤15 cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively. Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal/multi-focal progression. Therefore, in future studies on BU epidemiology, severe clinical forms should be systematically considered as distinct phenotypes of the same disease and thus subjected to specific risk factor investigation.

Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose.

PubMed

Sroga, Grażyna E; Siddula, Alankrita; Vashishth, Deepak

2015-01-01

To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs) at the levels that corresponded to approx. 25-30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation) or ribose (ribosylation). Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN) in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women). More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples). Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar supplementation in food and drinks.

Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

PubMed Central

Sroga, Grażyna E.; Siddula, Alankrita; Vashishth, Deepak

2015-01-01

To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs) at the levels that corresponded to approx. 25–30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation) or ribose (ribosylation). Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN) in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women). More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples). Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar supplementation in food and drinks. PMID:25679213

Healing of rabbit calvarial critical-sized defects using autogenous bone grafts and fibrin glue.

PubMed

Lappalainen, Olli-Pekka; Korpi, Riikka; Haapea, Marianne; Korpi, Jarkko; Ylikontiola, Leena P; Kallio-Pulkkinen, Soili; Serlo, Willy S; Lehenkari, Petri; Sándor, George K

2015-04-01

This study aimed to evaluate ossification of cranial bone defects comparing the healing of a single piece of autogenous calvarial bone representing a bone flap as in cranioplasty compared to particulated bone slurry with and without fibrin glue to represent bone collected during cranioplasty. These defect-filling materials were then compared to empty control cranial defects. Ten White New Zealand adult male rabbits had bilateral critical-sized calvarial defects which were left either unfilled as control defects or filled with a single full-thickness piece of autogenous bone, particulated bone, or particulated bone combined with fibrin glue. The defects were left to heal for 6 weeks postoperatively before termination. CT scans of the calvarial specimens were performed. Histomorphometric assessment of hematoxylin-eosin- and Masson trichrome-stained specimens was used to analyze the proportion of new bone and fibrous tissue in the calvarial defects. There was a statistically significant difference in both bone and soft tissue present in all the autogenous bone-grafted defect sites compared to the empty negative control defects. These findings were supported by CT scan findings. While fibrin glue combined with the particulated bone seemed to delay ossification, the healing was more complete compared to empty control non-grafted defects. Autogenous bone grafts in various forms such as solid bone flaps or particulated bone treated with fibrin glue were associated with bone healing which was superior to the empty control defects.

Platelet-rich plasma for the treatment of bone defects: from pre-clinical rational to evidence in the clinical practice. A systematic review.

PubMed

Roffi, Alice; Di Matteo, Berardo; Krishnakumar, Gopal Shankar; Kon, Elizaveta; Filardo, Giuseppe

2017-02-01

The treatment of large bone defects represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have also been used to further improve bone healing. Among these, platelet-rich plasma (PRP) is the most exploited strategy. The aim of the present study was to systematically review the available literature to identify: 1) preclinical in-vivo results supporting the rational of PRP use for bone healing; 2) evidence from the clinical practice on the actual clinical benefit of PRP for the treatment of fractures and complications such as delayed unions and non-unions. A systematic review of the literature was performed on the application of PRP in bone healing, using the following inclusion criteria: pre-clinical and clinical reports of any level of evidence, written in English language, published in the last 20 years (1996-2016), on the use of PRP to stimulate long-bone defect treatment, with focus on fracture and delayed/non-unions healing. The search in the Pubmed database identified 64 articles eligible for inclusion: 45 were preclinical in-vivo studies and 19 were clinical studies. Despite the fact that the overall pre-clinical results seem to support the benefit of PRP in 91.1 % of the studies, a more in depth analysis underlined a lower success rate, with a positive outcome of 84.4 % in terms of histological analysis, and even lower values considering radiological and biomechanical results (75.0 % and 72.7 % positive outcome respectively). This was also mirrored in the clinical literature, where the real benefit of PRP use to treat fractures and non-unions is still under debate. Overall, the available literature presents major limitations in terms of low quality and extreme heterogeneity, which hamper the possibility to optimize PRP treatment and translate it into a real clinical benefit despite positive preclinical findings on its biological potential to favour bone healing.

Biochemical Bone Turnover Markers and Osteoporosis in Older Men: Where Are We?

PubMed Central

Szulc, Pawel

2011-01-01

In men aged less than 60, the association of serum and urinary levels of biochemical bone turnover markers (BTMs) and bone mineral density (BMD) is weak or not significant. After this age, higher BTM levels are correlated weakly, but significantly, with lower BMD and faster bone loss. Limited data from the cohort studies suggest that BTM measurement does not improve the prediction of fragility fractures in older men in comparison with age, BMD, history of falls and fragility fractures. Testosterone replacement therapy (TRT) decreases bone resorption. During TRT, bone formation markers slightly increase (direct effect on osteoblasts), then decrease (slowdown of bone turnover). Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate) induce a rapid decrease in bone resorption followed by a milder decrease in bone formation. In men receiving antiresorptive therapy for prostate cancer, zoledronate, denosumab and toremifene decrease significantly levels of bone resorption and bone formation markers. Teriparatide induced a rapid increase in serum concentrations of bone formation markers followed by an increase in bone resorption. We need more studies on the utility of BTM measurement for the improvement of the persistence and adherence to the anti-osteoporotic treatment in men. PMID:22220284

Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling.

PubMed

Mishina, Yuji; Starbuck, Michael W; Gentile, Michael A; Fukuda, Tomokazu; Kasparcova, Viera; Seedor, J Gregory; Hanks, Mark C; Amling, Michael; Pinero, Gerald J; Harada, Shun-ichi; Behringer, Richard R

2004-06-25

Bone morphogenetic proteins (BMPs) function during various aspects of embryonic development including skeletogenesis. However, their biological functions after birth are less understood. To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice. Mutant mice were smaller than controls up to 6 months after birth. Irregular calcification and low bone mass were observed, but there were normal numbers of osteoblasts. The ability of the mutant osteoblasts to form mineralized nodules in culture was severely reduced. Interestingly, bone mass was increased in aged mutant mice due to reduced bone resorption evidenced by reduced bone turnover. The mutant mice lost more bone after ovariectomy likely resulting from decreased osteoblast function which could not overcome ovariectomy-induced bone resorption. In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption. These results demonstrate essential and age-dependent roles for BMP signaling mediated by BMPRIA (a type IA receptor for BMP) in osteoblasts for bone remodeling.

Open tibial fractures grade IIIC treated successfully with external fixation, negative-pressure wound therapy and recombinant human bone morphogenetic protein 7.

PubMed

Babiak, Ireneusz

2014-10-01

The aim of the therapy in open tibial fractures grade III was to cover the bone with soft tissue and achieve healed fracture without persistent infection. Open tibial fractures grade IIIC with massive soft tissue damage require combined orthopaedic, vascular and plastic-reconstructive procedures. Negative-pressure wound therapy (NPWT), used in two consecutive cases with open fracture grade IIIC of the tibia diaphysis, healed extensive soft tissue defect with exposure of the bone. NPWT eventually allowed for wound closure by split skin graft within 21-25 days. Ilizarov external fixator combined with application of recombinant human bone morphogenetic protein-7 at the site of delayed union enhanced definitive bone healing within 16-18 months. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Characterization of bone marrow-derived mesenchymal stem cells in aging.

PubMed

Baker, Natasha; Boyette, Lisa B; Tuan, Rocky S

2015-01-01

Adult mesenchymal stem cells are a resource for autologous and allogeneic cell therapies for immune-modulation and regenerative medicine. However, patients most in need of such therapies are often of advanced age. Therefore, the effects of the aged milieu on these cells and their intrinsic aging in vivo are important considerations. Furthermore, these cells may require expansion in vitro before use as well as for future research. Their aging in vitro is thus also an important consideration. Here, we focus on bone marrow mesenchymal stem cells (BMSCs), which are unique compared to other stem cells due to their support of hematopoietic cells in addition to contributing to bone formation. BMSCs may be sensitive to age-related diseases and could perpetuate degenerative diseases in which bone remodeling is a contributory factor. Here, we review (1) the characterization of BMSCs, (2) the characterization of in vivo-aged BMSCs, (3) the characterization of in vitro-aged BMSCs, and (4) potential approaches to optimize the performance of aged BMSCs. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

The dawn of computer-assisted robotic osteotomy with ytterbium-doped fiber laser.

PubMed

Sotsuka, Yohei; Nishimoto, Soh; Tsumano, Tomoko; Kawai, Kenichiro; Ishise, Hisako; Kakibuchi, Masao; Shimokita, Ryo; Yamauchi, Taisuke; Okihara, Shin-ichiro

2014-05-01

Currently, laser radiation is used routinely in medical applications. For infrared lasers, bone ablation and the healing process have been reported, but no laser systems are established and applied in clinical bone surgery. Furthermore, industrial laser applications utilize computer and robot assistance; medical laser radiations are still mostly conducted manually nowadays. The purpose of this study was to compare the histological appearance of bone ablation and healing response in rabbit radial bone osteotomy created by surgical saw and ytterbium-doped fiber laser controlled by a computer with use of nitrogen surface cooling spray. An Ytterbium (Yb)-doped fiber laser at a wavelength of 1,070 nm was guided by a computer-aided robotic system, with a spot size of 100 μm at a distance of approximately 80 mm from the surface. The output power of the laser was 60 W at the scanning speed of 20 mm/s scan using continuous wave system with nitrogen spray level 0.5 MPa (energy density, 3.8 × 10(4) W/cm(2)). Rabbits radial bone osteotomy was performed by an Yb-doped fiber laser and a surgical saw. Additionally, histological analyses of the osteotomy site were performed on day 0 and day 21. Yb-doped fiber laser osteotomy revealed a remarkable cutting efficiency. There were little signs of tissue damage to the muscle. Lased specimens have shown no delayed healing compared with the saw osteotomies. Computer-assisted robotic osteotomy with Yb-doped fiber laser was able to perform. In rabbit model, laser-induced osteotomy defects, compared to those by surgical saw, exhibited no delayed healing response.

Knee arthrodesis with lengthening: experience of using Ilizarov techniques to salvage large asymmetric defects following infected peri-articular fractures.

PubMed

Barwick, Thomas W; Montgomery, Richard J

2013-08-01

We present four patients with large bone defects due to infected internal fixation of knee condylar fractures. All were treated by debridement of bone and soft tissue and stabilisation with flap closure if required, followed by bone transport arthrodesis of the knee with simultaneous lengthening. Four patients (three male and one female), mean age 46.5 years (37-57 years), with posttraumatic osteomyelitis at the knee (three proximal tibia and one distal femur) were treated by debridement of infected tissue and removal of internal fixation. Substantial condylar bone defects resulted on the affected side of the knee joint (6-10 cm) with loss of the extensor mechanism in all tibial cases. Two patients required muscle flaps after debridement. All patients received intravenous antibiotics for at least 6 weeks. Bone transport with a circular frame was used to achieve an arthrodesis whilst simultaneously restoring a functional limb length. In three cases a 'peg in socket' docking technique was fashioned to assist stability and subsequent consolidation of the arthrodesis. Arthrodesis of the knee, free of recurrent infection, was successfully achieved in all cases. None has since required further surgery. Debridement to union took an average of 25 months (19-31 months). The median number of interventions undertaken was 9 (8-12). Two patients developed deep vein thrombosis (DVT), one complicated by PE, which delayed treatment. Two required surgical correction of pre-existent equinus contracture using frames. The median limb length discrepancy (LLD) at the end of treatment was 3 cm (3-4 cm). None has required subsequent amputation. Bone loss and infection both reduce the success rate of any arthrodesis. However, by optimising the host environment with eradication of infection by radical debridement, soft-tissue flaps when necessary and bone transport techniques to close the defect, one can achieve arthrodesis and salvage a useful limb. The residual LLD can result from not accounting for later impaction at peg and socket sites, which had the effect of increasing LLD beyond the desirable amount. We therefore recommend continuing the lengthening for an additional 1-2 cm to allow for this. Copyright © 2013 Elsevier Ltd. All rights reserved.

Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing.

PubMed

Wang, Tao; Wang, Yongmei; Menendez, Alicia; Fong, Chak; Babey, Muriel; Tahimic, Candice G T; Cheng, Zhiqiang; Li, Alfred; Chang, Wenhan; Bikle, Daniel D

2015-09-01

Insulin-like growth factors (IGFs) are important local regulators during fracture healing. Although IGF1 deficiency is known to increase the risk of delayed union or non-union fractures in the elderly population, the underlying mechanisms that contribute to this defect remains unclear. In this study, IGF1 signaling during fracture healing was investigated in an osteoblast-specific IGF1 receptor (IGF1R) conditional knockout (KO) mouse model. A closed tibial fracture was induced in IGF1R(flox/flox) /2.3-kb α1(1)-collagen-Cre (KO) and IGF1R(flox/flox) (control) mice aged 12 weeks. Fracture callus samples and nonfractured tibial diaphysis were collected and analyzed by μCT, histology, immunohistochemistry, histomorphometry, and gene expression analysis at 10, 15, 21, and 28 days after fracture. A smaller size callus, lower bone volume accompanied by a defect in mineralization, bone microarchitectural abnormalities, and a higher cartilage volume were observed in the callus of these KO mice. The levels of osteoblast differentiation markers (osteocalcin, alkaline phosphatase, collagen 1α1) were significantly reduced, but the early osteoblast transcription factor runx2, as well as chondrocyte differentiation markers (collagen 2α1 and collagen 10α1) were significantly increased in the KO callus. Moreover, increased numbers of osteoclasts and impaired angiogenesis were observed during the first 15 days of fracture repair, but decreased numbers of osteoclasts were found in the later stages of fracture repair in the KO mice. Although baseline nonfractured tibias of KO mice had decreased trabecular and cortical bone compared to control mice, subsequent studies with mice expressing the 2.3-kb α1(1)-collagen-Cre ERT2 construct and given tamoxifen at the time of fracture and so starting with comparable bone levels showed similar impairment in fracture repair at least initially. Our data indicate that not only is the IGF1R in osteoblasts involved in osteoblast differentiation during fracture repair, but it plays an important role in coordinating chondrocyte, osteoclast, and endothelial responses that all contribute to the endochondral bone formation required for normal fracture repair. © 2015 American Society for Bone and Mineral Research.

Anti-Aging Effects of the Hanwoo Leg Bone, Foot and Tail Infusions (HLI, HFI and HTI) on Skin Fibroblast.

PubMed

Seol, Ja Young; Yoon, Ji Young; Jeong, Hee Sun; Joo, Nami; Choi, Soon Young

2016-01-01

Many researchers revealed that collagen contribute to maintaining the skin's elasticity and inhibit wrinkling of skin. Korean native cattle (Hanwoo) bone (leg bone, foot and tail) infusion contains the various inorganic materials, collagen and chondroitin sulfate. All of this, a large quantity of collagen is included in Hanwoo infusion. Therefore, this study emphasized on the effects of collagen in the Hanwoo bone infusion. For the first time, Hanwoo bone infusions were directly added to the media of Human Dermal Fibroblast (NHDF-c) to test anti-aging effects. First, it was identified that growth rate of skin fibroblast was increased. Furthermore, the Hanwoo bone infusion increased a 50% of fibroblast collagen synthesis. Also, suppression of skin fibroblast aging was confirmed by treatment Hanwoo bone infusion. In conclusion, this study demonstrates the effects of infusion made from Hanwoo leg bone, foot and tail on anti-aging, wrinkle inhibiting and skin fibroblast elasticity maintaining. Therefore, this study identified that traditional infusion has effects that are good for skin elasticity.

Abnormalities of the axial and proximal appendicular skeleton in adults with Laron syndrome (growth hormone insensitivity).

PubMed

Kornreich, L; Konen, O; Schwarz, M; Siegel, Y; Horev, G; Hershkovitz, I; Laron, Z

2008-02-01

To investigate abnormalities in the skeleton (with the exclusion of the skull, cervical spine, hands and feet) in patients with Laron syndrome, who have an inborn growth hormone resistance and congenital insulin-like growth factor-1 (IGF-1) deficiency. The study group was composed of 15 untreated patients with Laron syndrome (seven male and eight female) aged 21-68 years. Plain films of the axial and appendicular skeleton were evaluated retrospectively for abnormalities in structure and shape. The cortical width of the long bones was evaluated qualitatively and quantitatively (in the upper humerus and mid-femur), and the cortical index was calculated and compared with published references. Measurements were taken of the mid-anteroposterior and cranio-caudal diameters of the vertebral body and spinous process at L3, the interpedicular distance at L1 and L5, and the sacral slope. Thoracic and lumbar osteophytes were graded on a 5-point scale. Values were compared with a control group of 20 healthy persons matched for age. The skeleton appeared small in all patients. No signs of osteopenia were visible. The cortex of the long bones appeared thick in the upper limbs in 11 patients and in the lower limbs in four. Compared with the reference values, the cortical width was thicker than average in the humerus and thinner in the femur. The vertebral diameters at L3 and the interpedicular distances at L1 and L5 were significantly smaller in the patients than in the control subjects (P<0.001); however, at L5 the canal was wider, relative to the vertebral body. The study group had a higher rate of anterior osteophytes in the lumbar spine than the controls had, and their osteophytes were also significantly larger. In the six patients for whom radiographs of the upper extremity in its entirety were available on one film, the ulna appeared to be rotated. In one 22-year-old man, multiple epiphyses were still open. Congenital IGF-1 deficiency leads to skeletal abnormalities characterized by small bones, narrow spinal canal, and delayed bone age. The limitation in elbow distensibility common to patients with Laron syndrome may be related to a marked retroversion of the humeral head.

The effect of patient age on bone formation using a fully synthetic nanocrystalline bone augmentation material in maxillary sinus grafting.

PubMed

Wolf, Michael; Wurm, Alexander; Heinemann, Friedhelm; Gerber, Thomas; Reichert, Christoph; Jäger, Andreas; Götz, Werner

2014-01-01

Maxillary sinus floor augmentation is a treatment that has been proposed for patients in whom the alveolar bone height is insufficient. This procedure is commonly used in patients aged 40 to 70 years and older. However, little information exists whether the factor of age might influence the outcome of augmentation procedures. The aim of this study was to investigate whether the patient's age has an effect on bone formation and incorporation in maxillary sinus floor augmentation procedures. A fully synthetic nanocrystalline bone augmentation material (NanoBone, Artoss) was used for sinus floor augmentation in patients with a subantral vertical bone height of at least 3 mm and maximum of 7 mm. After 7 months healing time, biopsy specimens were taken and were divided into two groups according to the patient's age. Exclusion criteria were poor general health (eg, severe renal/and or liver disease), history of a radiotherapy in the head region, chemotherapy at the time of surgical procedure, noncompensated diabetes mellitus, symptoms of a maxillary sinus disease, active periodontal or systemic diseases, smoking, and poor oral hygiene. Histologic analyses with hematoxylin-eosin stain were performed. Multinucleated osteoclast-like cells were identified by histochemical staining (tartrate-resistant acid phosphatase [TRAP]). Quantitative and age-dependent assessment of bone formation, residual bone grafting material, and soft tissue formation following sinus augmentation was performed using histomorphometric analysis and the Bonferroni adjustment of the Student t test. Twenty biopsy specimens from 17 patients were taken and divided into two groups according to age (group 1: 41 to 52 years; group 2: 66 to 71 years) containing 10 specimens each, which were analyzed in triplicate resulting in a total of 30 specimens per group. A regeneration process with varying amounts of newly formed bone surrounded by marrow-like tissue was present in all augmented regions. No signs of inflammation or immune reactions were visible. Residual particles of the augmentation material could be observed within the specimens. An age-dependent difference in investigated parameters between the two age groups could not be documented. The histologic examinations confirm that the fully synthetic nanocrystalline bone augmentation material used in this study is biocompatible and allows maxillary sinus augmentation in patients aged 41 to 70 years.

Determinants of Microdamage in Elderly Human Vertebral Trabecular Bone

PubMed Central

Follet, Hélène; Farlay, Delphine; Bala, Yohann; Viguet-Carrin, Stéphanie; Gineyts, Evelyne; Burt-Pichat, Brigitte; Wegrzyn, Julien; Delmas, Pierre; Boivin, Georges; Chapurlat, Roland

2013-01-01

Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54–95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types. PMID:23457465

Pathophysiology and new strategies for the treatment of Legg-Calvé-Perthes disease.

PubMed

Kim, Harry K W

2012-04-04

Legg-Calvé-Perthes disease is a juvenile form of idiopathic osteonecrosis of the femoral head that can lead to permanent femoral head deformity and premature osteoarthritis. According to two recent multicenter, prospective cohort studies, current nonoperative and operative treatments have modest success rates of producing a good outcome with a spherical femoral head in older children with Legg-Calvé-Perthes disease. Experimental studies have revealed that the immature femoral head is mechanically weakened following ischemic necrosis. Increased bone resorption and delayed new bone formation, in combination with continued mechanical loading of the hip, contribute to the pathogenesis of the femoral head deformity. Biological treatment strategies to improve the healing process by decreasing bone resorption and stimulating bone formation appear promising in nonhuman preclinical studies.

The Relationships between Two Different Drinking Water Fluoride Levels, Dental Fluorosis and Bone Mineral Density of Children

PubMed Central

Grobler, S.R; Louw, A.J; Chikte, U.M.E; Rossouw, R.J; van W Kotze, T.J.

2009-01-01

This field study included the whole population of children aged 10–15 years (77 from a 0.19 mg/L F area; 89 from a 3.00 mg/L F area), with similar nutritional, dietary habits and similar ethnic and socioeconomic status. The fluoride concentration in the drinking water, the bone mineral content, the bone density and the degree of dental fluorosis were determined. The left radius was measured for bone width, bone mineral content, and bone mineral density. The mean fluorosis score was 1.3 in the low fluoride area and 3,6 in the high fluoride area. More than half the children in the low fluoride area had no fluorosis (scores 0 and 1) while only 5% in the high fluoride area had none. Severe fluorosis (30%) was only observed in the high fluoride area. The Wilcoxon Rank Sum Test indicated that fluorosis levels differed significantly (p < 0.05) between the two areas. No relationships were found between dental fluorosis and bone width or between fluorosis and bone mineral density in the two areas (Spearment Rank correlations). A significant increase in bone width was found with age but no differences amongst and boys and girls. A significant positive correlation was found in the high fluoride area between bone mineral density over age. In the 12-13 and 13-14 year age groups in the high fluoride area, girls had higher bone mineral densities. However, a significant negative correlation (p<0.02) was found for the low fluoride area (0.19 mg/L F) over age. PMID:19444344

Gender differences in bone turnover in 2-year-old Thoroughbreds.

PubMed

Jackson, B F; Lonnell, C; Verheyen, K; Wood, J L N; Pfeiffert, D U; Price, J S

2003-11-01

Injuries to the skeleton are a major cause of morbidity and mortality in racehorses and age, gender and season have all been shown to influence risk of injury. To use biochemical markers of bone cell activity to establish to whether cellular processes in bone underlie these described effects. Blood samples were collected monthly from 2-year-old horses in race training between November 1998 and September 1999. Mean age at the start of the study was 20 months (range 18-23 months), with no significant difference in average age between colts (n = 84) and fillies (n = 63). Three markers were measured; osteocalcin (OC, bone formation), the carboxyterminal cross-linked telopeptide of type I collagen (ICTP, bone resorption) and the carboxyterminal propeptide of type I collagen (PICP), which is less 'bone-specific' than the other 2 markers. Colts had, on average, 3.62 ng/ml higher OC concentrations (P = 0.044) and 0.68 mg/l higher ICTP concentrations (P = 0.01) than fillies. The effect of gender was not statistically significant for PICP. However, in May, PICP concentrations were on average 157 mg/l higher in fillies than colts. There was no effect of age or season on marker concentrations. This study has shown that there are gender differences in bone turnover markers in 2-year-old Thoroughbreds; however, age, within the limited range studied, did not have a significant effect on bone cell activity. Lower bone marker concentrations may reflect smaller bone size and/or earlier skeletal maturation in fillies. An increase in concentrations of PICP in fillies in spring and early summer may relect an influence of sex hormones on collagen turnover. Gender differences in bone cell activity in 2-year-old colts and fillies may influence bone's adaptive responses to training and risk of injury.

Velo-facio-skeletal syndrome in a mother and daughter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teebi, A.S.; Meyn, M.S.; Meyers-Seifer, C.H.

We present a woman and her daughter with an apparently new short stature syndrome associated with facial and skeletal anomalies and hypernasality. Manifestations included hypertelorism with broad and high nasal bridge, epicanthal folds, narrow and high arched palate, mild mesomelic brachymelia, short broad hands, prominent finger pads, hyperextensibility of hand joints, small feet, nasal voice, and normal intelligence. The mother had short stubby thumbs and the daughter had posteriorly angulated ears and delayed bone age. The morphology of the nose and the hypernasality are reminiscent to those in the velo-cardio-facial syndrome. High resolution banding and fluorescent in situ hybridization studiesmore » showed no evidence of 22q11 deletions. Differentiation from Aarskog syndrome and Robinow syndrome is discussed. 9 refs., 5 figs., 3 tabs.« less

Repeated irradiation from micro-computed tomography scanning at 2, 4 and 6 months of age does not induce damage to tibial bone microstructure in male and female CD-1 mice.

PubMed

Sacco, Sandra M; Saint, Caitlin; Longo, Amanda B; Wakefield, Charles B; Salmon, Phil L; LeBlanc, Paul J; Ward, Wendy E

2017-01-01

Long-term effects of repeated i n vivo micro-computed tomography (μCT) scanning at key stages of growth and bone development (ages 2, 4 and 6 months) on trabecular and cortical bone structure, as well as developmental patterns, have not been studied. We determined the effect of repetitive μCT scanning at age 2, 4 and 6 months on tibia bone structure of male and female CD-1 mice and characterized developmental changes. At 2, 4 and 6 months of age, right tibias were scanned using in vivo μCT (Skyscan 1176) at one of three doses of radiation per scan: 222, 261 or 460 mGy. Left tibias of the same mice were scanned only at 6 months to serve as non-irradiated controls to determine whether recurrent radiation exposure alters trabecular and cortical bone structure at the proximal tibia. In males, eccentricity was lower ( P <0.05) in irradiated compared with non-irradiated tibias (222 mGy group). Within each sex, all other structural outcomes were similar between irradiated and non-irradiated tibias regardless of dose. Trabecular bone loss occurred in all mice due to age while cortical development continued to age 6 months. In conclusion, repetitive μCT scans at various radiation doses did not damage trabecular or cortical bone structure of proximal tibia in male and female CD-1 mice. Moreover, scanning at 2, 4 and 6 months of age highlight the different developmental time course between trabecular and cortical bone. These scanning protocols can be used to investigate longitudinal responses of bone structures to an intervention.

Age-related changes in mouse bone permeability.

PubMed

Rodriguez-Florez, Naiara; Oyen, Michelle L; Shefelbine, Sandra J

2014-03-21

The determination of lacunar-canalicular permeability is essential for understanding local fluid flow in bone, which may indicate how bone senses changes in the mechanical environment to regulate mechano-adaptation. The estimates of lacunar-canalicular permeability found in the literature vary by up to eight orders of magnitude, and age-related permeability changes have not been measured in non-osteonal mouse bone. The objective of this study is to use a poroelastic approach based on nanoindentation data to characterize lacunar-canalicular permeability in murine bone as a function of age. Nine wild type C57BL/6 mice of different ages (2, 7 and 12 months) were used. Three tibiae from each age group were embedded in epoxy resin, cut in half and indented in the longitudinal direction in the mid-cortex using two spherical fluid indenter tips (R=238 μm and 500 μm). Results suggest that the lacunar-canalicular intrinsic permeability of mouse bone decreases from 2 to 7 months, with no significant changes from 7 to 12 months. The large indenter tip imposed larger contact sizes and sampled larger ranges of permeabilities, particularly for the old bone. This age-related difference in the distribution was not seen for indents with the smaller radius tip. We conclude that the small tip effectively measured lacunar-canalicular permeability, while larger tip indents were influenced by vascular permeability. Exploring the age-related changes in permeability of bone measured by nanoindentation will lead to a better understanding of the role of fluid flow in mechano-transduction. This understanding may help indicate alterations in bone adaptation and remodeling. Copyright © 2013 Elsevier Ltd. All rights reserved.

Severe rickets in a young girl caused by celiac disease: the tragedy of delayed diagnosis: a case report.

PubMed

Al-Sharafi, Butheinah A; Al-Imad, Shafiq A; Shamshair, Amani M; Al-Faqeeh, Derhim H

2014-10-08

Celiac disease is a systemic immune mediated disease which usually presents with gastrointestinal symptoms, but it may present with extra gastrointestinal manifestations such as metabolic bone disease and failure to thrive. This may lead to a delay in the diagnosis. We present a 13 year old female from the middle east with an 8 year history of severe rickets causing multiple bone deformities leaving the child crippled with bowing of both of her arms and legs. The patient was also found to have growth failure, anemia and on further workup she was found to have celiac disease. We are presenting this case because it shows a severe case of rickets after malabsorption for many years. Celiac disease should be kept in mind as a cause of rickets in patients not responding to usual forms of treatment or when associated with other manifestations of malabsorption.

Chronic Effects of Fluoride Exposure on Growth, Metamorphosis, and Skeleton Development in Bufo gargarizans Larvae.

PubMed

Chai, Lihong; Wang, Hongyuan; Zhao, Hongfeng; Dong, Suiming

2017-04-01

Bufo gargarizans tadpoles were chronically exposed to waterborne fluoride at measured concentrations ranging from 0.4 to 61.2 mg F - /L for 70 days from Gosner stage 26 to completion of metamorphosis. The chronic exposure caused a concentration-dependent mortality in all tested fluoride concentrations. Total length, snout-to-vent length (SVL), body mass, and developmental stage of tadpoles were significantly inhibited at 42.6 mg F - /L. In addition, significant metamorphic delay and increase in size at completion of metamorphosis occurred after exposure to 19.8 mg F - /L. Moreover, 19.8 mg F - /L suppressed the bone mineralization of larvae at completion of metamorphosis. However, the bone mineralization could be enhanced by 4.1 mg F - /L. In conclusion, our results suggested that the presence of high concentrations of fluoride could increase mortality risk, delay metamorphosis, and suppress skeletal ossification in B. gargarizans larvae.

The Gambian Bone and Muscle Ageing Study: Baseline Data from a Prospective Observational African Sub-Saharan Study

PubMed Central

Zengin, Ayse; Fulford, Anthony J.; Sawo, Yankuba; Jarjou, Landing M.; Schoenmakers, Inez; Goldberg, Gail; Prentice, Ann; Ward, Kate A.

2017-01-01

The Gambian Bone and Muscle Ageing Study is a prospective observational study investigating bone and muscle ageing in men and women from a poor, subsistence farming community of The Gambia, West Africa. Musculoskeletal diseases, including osteoporosis and sarcopenia, form a major part of the current global non-communicable disease burden. By 2050, the vast majority of the world’s ageing population will live in low- and middle-income countries with an estimated two-fold rise in osteoporotic fracture. The study design was to characterise change in bone and muscle outcomes and to identify possible preventative strategies for fracture and sarcopenia in the increasing ageing population. Men and women aged ≥40 years from the Kiang West region of The Gambia were recruited with stratified sampling by sex and age. Baseline measurements were completed in 488 participants in 2012 who were randomly assigned to follow-up between 1.5 and 2 years later. Follow-up measurements were performed on 465 participants approximately 1.7 years after baseline measurements. The data set comprises a wide range of measurements on bone, muscle strength, anthropometry, biochemistry, and dietary intake. Questionnaires were used to obtain information on health, lifestyle, musculoskeletal pain, and reproductive status. Baseline cross-sectional data show preliminary evidence for bone mineral density and muscle loss with age. Men had greater negative differences in total body lean mass with age than women following adjustments for body size. From peripheral quantitative computed tomography scans, greater negative associations between bone outcomes and age at the radius and tibia were shown in women than in men. Ultimately, the findings from The Gambian Bone and Muscle Ageing Study will contribute to the understanding of musculoskeletal health in a transitioning population and better characterise fracture and sarcopenia incidence in The Gambia with an aim to the development of preventative strategies against both. PMID:28912754

Exercise for Your Bone Health

MedlinePlus

... Exercise for Your Bone Health Exercise for Your Bone Health Vital at every age for healthy bones, ... who have been diagnosed with osteoporosis. The Best Bone Building Exercise The best exercise for your bones ...

Early changes in the distal intertarsal joint of Dutch Warmblood foals and the influence of exercise on bone density in the third tarsal bone.

PubMed

Barneveld, A; van Weeren, P R

1999-11-01

It was hypothesised that imposition of different exercise levels at a young age would lead to differences in bone density in the third tarsal bone and to difference in the prevalence of pathological lesions that might contribute to the development of bone spavin later in life. Furthermore, based on earlier literature, it was hypothesised that such lesions could be classified as a manifestation of osteochondrosis. Changes in bone density in the third tarsal bone and early pathological changes in the articular cartilage of the distal intertarsal joint were studied in the offspring of sires with radiographic evidence of osteochondrosis in either stifle or hock. Twenty-four foals were studied at age 5 months after having been subjected to different exercise programmes (box-rest, box-rest with sprint training, pasture exercise) from age one week. Nineteen other foals that originally belonged to the same exercise groups were studied at age 11 months, after they had been weaned, housed together and subjected to an identical low level exercise regimen for an additional 6 months. Bone density was quantified using a microscopic technique. Histomorphological analysis was performed semiquantitatively and using high detail radiography techniques. At age 5 months, mean +/- s.d. bone density in the compact bone of the third tarsal bone was significantly lower in the box-rested foals (37 +/- 4%) than in both the trained and pastured foals (48 +/- 7% and 52 +/- 11%, respectively). After 6 months of identical exercise the previously box-rested foals showed an increase in bone density (53 +/- 12%) which became similar to the value found in the formerly pastured foals (52 +/- 8%). Major pathological lesions (chondrocyte necrosis, fragmentation and chondrone formation) of the articular cartilage of the third and central tarsal bones were already present at age 5 months, but were significantly more numerous at 11 months. There was no relation between the number of cartilage lesions and the osteochondrosis status of the foals. Only 2 lesions in 11-month-old foals had histological characteristics compatible with osteochondrosis, all other lesions were degenerative in nature. It is concluded that bone density of the compact bone of the subchondral bone plate in the third tarsal bone reacts strongly to variations in exercise at a very young age. Low bone density, caused by lack of exercise, can be compensated for when exercise is later increased. Pathological changes in the distal intertarsal joint are common at 5 months and increase to 11 months. These lesions are degenerative in nature and seem not to be related to osteochondrosis. Although the clinical relevance of these abnormalities is uncertain, they may be relevant for the development of osteoarthritic processes in this region later in life.

Bone age assessment by dual-energy X-ray absorptiometry in children: an alternative for X-ray?

PubMed

Heppe, D H M; Taal, H R; Ernst, G D S; Van Den Akker, E L T; Lequin, M M H; Hokken-Koelega, A C S; Geelhoed, J J M; Jaddoe, V W V

2012-02-01

The aim of the study was to validate dual-energy X-ray absorptiometry (DXA) as a method to assess bone age in children. Paired dual-energy X-ray absorptiometry (DXA) scans and X-rays of the left hand were performed in 95 children who attended the paediatric endocrinology outpatient clinic of University Hospital Rotterdam, the Netherlands. We compared bone age assessments by DXA scan with those performed by X-ray. Bone age assessment was performed by two blinded observers according to the reference method of Greulich and Pyle. Intra-observer and interobserver reproducibility were investigated using the intraclass correlation coefficient (ICC), and agreement was tested using Bland and Altman plots. The intra-observer ICCs for both observers were 0.997 and 0.991 for X-ray and 0.993 and 0.987 for DXA assessments. The interobserver ICC was 0.993 and 0.991 for X-ray and DXA assessments, respectively. The mean difference between bone age assessed by X-ray and DXA was 0.11 years. The limits of agreement ranged from -0.82 to 1.05 years, which means that 95% of all differences between the methods were covered by this range. Results of bone age assessment by DXA scan are similar to those obtained by X-ray. The DXA method seems to be an alternative for assessing bone age in a paediatric hospital-based population.

Ultra-Deep Bone Diagnostics with Fat-Skin Overlayers Using New Pulsed Photothermal Radar

NASA Astrophysics Data System (ADS)

Sreekumar, K.; Mandelis, A.

2013-09-01

The constraints imposed by the laser safety (maximum permissible exposure) ceiling on pump laser energy and the strong attenuation of thermal-wave signals in tissues significantly limit the photothermally active depth in most biological specimens to a level which is normally insufficient for practical applications (a few mm below the skin surface). A theoretical approach for improvement of the signal-to-noise ratio (SNR), minimizing the static (dc) component of the photothermal (PT) signal and making use of the PT radiometric nonlinearity has been introduced. At low frequencies fixed-pulse-width chirps of large peak power were found to be superior to all other equal energy modalities, with an SNR improvement by up to two orders of magnitude. Compared to radar peak delay and amplitude, the long-delayed radar output amplitude is found to be more sensitive to subsurface conditions. Two-dimensional spatial plots of this parameter depicting the back-surface conditions of bones with and without fat tissue overlayers are presented. Pulsed-chirp radar thermography has been demonstrated to monitor the degree of demineralization in goat rib bone with a substantial SNR and spatial resolution that is not practicable with harmonic radars of the same energy density.

Preventing painful age-related bone fractures: Anti-sclerostin therapy builds cortical bone and increases the proliferation of osteogenic cells in the periosteum of the geriatric mouse femur.

PubMed

Thompson, Michelle L; Chartier, Stephane R; Mitchell, Stefanie A; Mantyh, Patrick W

2016-01-01

Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient's functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures. © The Author(s) 2016.

The Changing Sensory and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur.

PubMed

Chartier, Stephane R; Mitchell, Stefanie A T; Majuta, Lisa A; Mantyh, Patrick W

2018-02-10

Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. With aging, the total number of sensory and sympathetic nerve fibers clearly declines as the cambium layer of the periosteum dramatically thins. Yet even in the aging femur, there remains a dense sensory and sympathetic innervation of the periosteum. In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

IL-12p40 impairs mesenchymal stem cell-mediated bone regeneration via CD4+ T cells

PubMed Central

Xu, Jiajia; Wang, Yiyun; Li, Jing; Zhang, Xudong; Geng, Yiyun; Huang, Yan; Dai, Kerong; Zhang, Xiaoling

2016-01-01

Severe or prolonged inflammatory response caused by infection or biomaterials leads to delayed healing or bone repair failure. This study investigated the important roles of the proinflammatory cytokines of the interleukin-12 (IL-12) family, namely, IL-12 and IL-23, in the inflammation-mediated inhibition of bone formation in vivo. IL-12p40−/− mice lacking IL-12 and IL-23 exhibited enhanced bone formation. IL-12 and IL-23 indirectly inhibited bone marrow mesenchymal stem cell (BMMSC) differentiation by stimulating CD4+ T cells to increase interferon γ (IFN-γ) and IL-17 levels. Mechanistically, IL-17 synergistically enhanced IFN-γ-induced BMMSC apoptosis. Moreover, INF-γ and IL-17 exerted proapoptotic effects by upregulating the expression levels of Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as by activating the caspase cascade in BMMSCs. IL-12p40 depletion in mice could promote ectopic bone formation. Thus, IL-12p40 is an attractive therapeutic target to overcome the inflammation-mediated inhibition of bone formation in vivo. PMID:27472064

Tibial and Femoral Tunnel Changes After ACL Reconstruction: A Prospective 2-Year Longitudinal MRI Study.

PubMed

Weber, Alexander E; Delos, Demetris; Oltean, Hanna N; Vadasdi, Katherine; Cavanaugh, John; Potter, Hollis G; Rodeo, Scott A

2015-05-01

Tunnel widening after anterior cruciate ligament reconstruction (ACL-R) is a well-accepted and frequent phenomenon, yet little is known regarding its origin or natural history. To prospectively evaluate the cross-sectional area (CSA) changes in tibial and femoral bone tunnels after ACL-R with serial MRI. Case series; Level of evidence, 4. Patients underwent arthroscopic ACL-R with the same surgeon, surgical technique, and rehabilitation protocol. Each patient underwent preoperative dual-energy x-ray absorptiometry and clinical evaluation, as well as postoperative time zero MRI followed by subsequent MRI and clinical examination, including functional and subjective outcome tests, at 6, 12, 24, 52, and 104 weeks. Tibial and femoral tunnel CSA was measured on each MRI at tunnel aperture (ttA and ftA), midsection (ttM and ftM), and exit (ttE and ftE). Logistic regression modeling was used to examine the predictive value of demographic data and preoperative bone quality (as measured by dual-energy x-ray absorptiometry) on functional outcome scores, manual and instrumented laxity measurements, and changes in tunnel area over time. Eighteen patients (including 12 men), mean age 35.5±8.7 years, underwent ACL-R. There was significant tunnel expansion at ttA and ftA sites 6 weeks postoperatively (P=.024 and .0045, respectively). Expansion continued for 24 weeks, with progressive tunnel narrowing thereafter. Average ttA CSA was significantly larger than ftA CSA at all times. The ttM significantly expanded after 6 weeks (P=.06); continued expansion to week 12 was followed by 21 months of reduction in tunnel diameter. The ftM and both ttE and ftE sites decreased in CSA over the 2 years. Median Lysholm and International Knee Documentation Committee scores significantly improved at final follow-up (P=.0083 and <.0001, respectively), and patients returned to preoperative activity levels. Pivot shift significantly decreased (P<.0001). Younger age (<30 years), male sex, and delayed ACL-R (>1 year from time of injury) predicted increased tunnel widening and accelerated expansion in CSA (P<.005). Tunnel expansion after ACL-R occurs early and primarily at the tunnel apertures. Expansion may not affect clinical outcome. Younger age, male sex, and delay from injury to ACL-R may be potential risks for enlargement. © 2015 The Author(s).

Screening and validation of serum protein biomarkers for early postmenopausal osteoporosis diagnosis.

PubMed

Wang, Long; Hu, Ya-Qian; Zhao, Zhuo-Jie; Zhang, Hong-Yang; Gao, Bo; Lu, Wei-Guang; Xu, Xiao-Long; Lin, Xi-Sheng; Wang, Jin-Peng; Jie, Qiang; Luo, Zhuo-Jing; Yang, Liu

2017-12-01

Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro‑computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array‑based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases‑1 and monocyte chemotactic protein‑1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.

Harvesting the free fibular graft: A modified approach

PubMed Central

Mukherjee, Amitava Narayan; Pal, Ananda Kisor; Singharoy, Debashis; Baksi, Debadyuti; Nath, Chinmoy

2011-01-01

Background: The conventional technique of free non-vascularized fibular grafting is attended with some amount of morbidity and a long scar. We report a technique with little interference to the surrounding soft tissues to harvest more than one-third of whole length fibula. Patients and Methods: Thirty four patients of average age 23.5 years (range 8 to 51 years) having various pathologies like simple bone cysts (n=9), fibrous dysplasias (n=6), giant cell tumors (n=7), fracture non-union (n=10) and aneurysmal bone cysts (n=2) were taken up for the study. The fibula were harvested by two separate incisions, 1 cm each at proximal and distal extent of proposed donor site for taking out of graft after elevating the periosteum circumferentially using a periosteum stripper. Compression bandage and above knee plaster immobilization was applied to reduce the dead space collection. Results: The mean followup is 34 months. The patients were evaluated clinicoradiology. Thirty three patients showed good results. One patient had fair result due to delayed wound healing from hematoma which was treated surgically. Conclusion: The approach of harvesting fibula suggested by author reduces donor site morbidity and is safer than conventional approach. PMID:21221224

Bone Health and Osteoporosis: A Guide for Asian Women Aged 50 and Older

MedlinePlus

... Guide for Asian Women Aged 50 and Older Bone Health and Osteoporosis: A Guide for Asian Women ... you drink alcoholic beverages, do so in moderation. Bone Density Testing If you are at high risk ...

The Nature of Expansion of Paget’s Disease of Bone

DTIC Science & Technology

2013-04-01

SQSTM1 mutant PDB samples. Two exogenous stimulators of the TLR signaling pathway are shown: MV – measles virus and LPS – Lipopolysaccharide. A...stimulation by Interleukins (ILs), LPS or measles , leads to ubiquitination of TRAF6 and binding of the ubiquitinated TRAF6 to the TAB2/TAK1 complex, which... measles virus in the delay of onset of PDB. 11 Conclusion Our laboratory has shown that SQSTM1 mutations also occur in the affected bone of PDB

Osteoid osteoma of the scaphoid: magnetic resonance imaging vessel sign.

PubMed

Kussman, Steven R; Thompson, Michael; Chang, Eric Y

2015-01-01

Osteoid osteomas can be a challenging diagnosis, especially in smaller bones and, particularly, in the carpus. Clinical and imaging diagnosis may both be delayed due to other, more common, post-traumatic or inflammatory pathology in the same area. We present a case of a pathologically proven scaphoid osteoid osteoma with a feeding vessel sign on magnetic resonance imaging, previously described in long bones with computed tomography, as a helpful sign for accurate diagnosis in the scaphoid. Copyright © 2015 Elsevier Inc. All rights reserved.

Two hit hypothesis: an unusual complication following supra-pubic catheter insertion.

PubMed

Nason, G J; Looney, A T; Kelly, M E; McGuire, B B; Mulvin, D W

2014-01-01

Osteomyelitis is an inflammation of the bone caused by an infection. Though bone is normally resistant to bacterial infection, events including trauma, presence of foreign bodies including prosthesis can act as a nidus for infection. Osteomyelitis is a rare but recognised complication of radiotherapy. Osteomyelitis of the pubis has scarcely been reported as a complication following urological procedures- prostatectomy, sling surgery and catheterisation. We report a rare complication of a gentleman post radiotherapy presenting with delayed osteomyelitis of the pubis following supra-pubic catheterisation.

[Lead poisoning: towards a paleo-epidemiologic re-interpretation?].

PubMed

Bourdieu, Anne

2014-01-01

Lead is a major public health issue. Its use has been increasing since Neolithic times, climaxing in the Ancient Rome and the nineteenth century. Defining the frequency of plumbism before modern times proves to be a difficult matter because of its various and delayed symptoms, and of diagenetic processes affecting bones. After reviewing various methods of lead measurement in bone and tooth, we will expose ways to ascertain lead measurement interpretation in order to estimate the epidemiology of plumbism in ancient times.

Headache of a diagnosis: frontotemporal pain and inflammation associated with osteolysis.

PubMed

Tacon, Lyndal J; Parkinson, Jonathon F; Hudson, Bernard J; Brewer, Janice M; Little, Nicholas S; Clifton-Bligh, Roderick J

2008-11-17

A 62-year-old woman presented with left frontotemporal pain, scalp tenderness and raised levels of inflammatory markers. Temporal arteritis was considered likely, and symptoms resolved with prednisone therapy. This delayed diagnostic bone biopsy until a soft tissue abscess formed, and Pott's puffy tumour associated with Prevotella osteomyelitis of the frontal bone was diagnosed. This case highlights the value of early histopathological examination, and is a reminder of a condition seen frequently in the pre-antibiotic era.

Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls.

PubMed

Tournis, S; Michopoulou, E; Fatouros, I G; Paspati, I; Michalopoulou, M; Raptou, P; Leontsini, D; Avloniti, A; Krekoukia, M; Zouvelou, V; Galanos, A; Aggelousis, N; Kambas, A; Douroudos, I; Lyritis, G P; Taxildaris, K; Pappaioannou, N

2010-06-01

Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. We conducted a cross-sectional study at a tertiary center. We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry.

Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

NASA Astrophysics Data System (ADS)

Dant, James T.; Richardson, Richard B.; Nie, Linda H.

2013-05-01

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient radiopharmaceutical for the treatment of bone metastases than 153Sm and 89Sr, if the diffusion of 219Rn to the bone marrow is insignificant.

Lateral approach for maxillary sinus membrane elevation without bone materials in maxillary mucous retention cyst with immediate or delayed implant rehabilitation: case reports.

PubMed

Han, Ji-Deuk; Cho, Seong-Ho; Jang, Kuk-Won; Kim, Seong-Gwang; Kim, Jung-Han; Kim, Bok-Joo; Kim, Chul-Hun

2017-08-01

This case series study demonstrates the possibility of successful implant rehabilitation without bone augmentation in the atrophic posterior maxilla with cystic lesion in the sinus. Sinus lift without bone graft using the lateral approach was performed. In one patient, the cyst was aspirated and simultaneous implantation under local anesthesia was performed, whereas the other cyst was removed under general anesthesia, and the sinus membrane was elevated in a second process, followed by implantation. In both cases, tapered 11.5-mm-long implants were utilized. With all of the implants, good stability and appropriate bone height were achieved. The mean bone level gain was 5.73 mm; adequate bone augmentation around the implants was shown, the sinus floor was moved apically, and the cyst was no longer radiologically detected. Completion of all of the treatments required an average of 12.5 months. The present study showed that sufficient bone formation and stable implantation in a maxilla of insufficient bone volume are possible through sinus lift without bone materials. The results serve to demonstrate, moreover, that surgical treatment of mucous retention cyst can facilitate rehabilitation. These techniques can reduce the risk of complications related to bone grafts, save money, and successfully treat antral cyst.

Lateral approach for maxillary sinus membrane elevation without bone materials in maxillary mucous retention cyst with immediate or delayed implant rehabilitation: case reports

PubMed Central

2017-01-01

This case series study demonstrates the possibility of successful implant rehabilitation without bone augmentation in the atrophic posterior maxilla with cystic lesion in the sinus. Sinus lift without bone graft using the lateral approach was performed. In one patient, the cyst was aspirated and simultaneous implantation under local anesthesia was performed, whereas the other cyst was removed under general anesthesia, and the sinus membrane was elevated in a second process, followed by implantation. In both cases, tapered 11.5-mm-long implants were utilized. With all of the implants, good stability and appropriate bone height were achieved. The mean bone level gain was 5.73 mm; adequate bone augmentation around the implants was shown, the sinus floor was moved apically, and the cyst was no longer radiologically detected. Completion of all of the treatments required an average of 12.5 months. The present study showed that sufficient bone formation and stable implantation in a maxilla of insufficient bone volume are possible through sinus lift without bone materials. The results serve to demonstrate, moreover, that surgical treatment of mucous retention cyst can facilitate rehabilitation. These techniques can reduce the risk of complications related to bone grafts, save money, and successfully treat antral cyst. PMID:28875144

Bone mineral density and correlation factor analysis in normal Taiwanese children.

PubMed

Shu, San-Ging

2007-01-01

Our aim was to establish reference data and linear regression equations for lumbar bone mineral density (BMD) in normal Taiwanese children. Several influencing factors of lumbar BMD were investigated. Two hundred fifty-seven healthy children were recruited from schools, 136 boys and 121 girls, aged 4-18 years were enrolled on a voluntary basis with written consent. Their height, weight, blood pressure, puberty stage, bone age and lumbar BMD (L2-4) by dual energy x-ray absorptiometry (DEXA) were measured. Data were analyzed using Pearson correlation and stepwise regression tests. All measurements increased with age. Prior to age 8, there was no gender difference. Parameters such as height, weight, and bone age (BA) in girls surpassed boys between ages 8-13 without statistical significance (p> or =0.05). This was reversed subsequently after age 14 in height (p<0.05). BMD difference had the same trend but was not statistically significant either. The influencing power of puberty stage and bone age over BMD was almost equal to or higher than that of height and weight. All the other factors correlated with BMD to variable powers. Multiple linear regression equations for boys and girls were formulated. BMD reference data is provided and can be used to monitor childhood pathological conditions. However, BMD in those with abnormal bone age or pubertal development could need modifications to ensure accuracy.

The Effects of Aging on Time Reproduction in Delayed Free-Recall

ERIC Educational Resources Information Center

Rakitin, B.C.; Stern, Y.; Malapani, C.

2005-01-01

The experiments presented here demonstrate that normal aging amplifies differences in time production occurring in delayed free-recall testing. Experiment 1 compared the time production ability of two healthy aged groups as well as college-aged participants. During the test session, which followed a 24-h delay and omitted all feedback and examples…

Pharmacologically targeting beta-catenin for NF1 associated deficiencies in fracture repair.

PubMed

Baht, Gurpreet S; Nadesan, Puviindran; Silkstone, David; Alman, Benjamin A

2017-05-01

Patients with Neurofibromatosis type 1 display delayed fracture healing and the increased deposition of fibrous tissue at the fracture site. Severe cases can lead to non-union and even congenital pseudarthrosis. Neurofibromatosis type 1 is caused by a mutation in the NF1 gene and mice lacking the Nf1 gene show a fracture repair phenotype similar to that seen in patients. Tissue from the fracture site of patients with Neurofibromatosis type 1 and from mice deficient in the Nf1 gene both show elevated levels of β-catenin protein and activation of β-catenin mediated signaling. Constitutively elevated β-catenin leads to a delayed and fibrous fracture repair process, and (RS)-5-methyl-1-phenyl-1,3,4,6-tetrahydro-2,5-benzoxazocine (Nefopam, a centrally-acting, non-narcotic analgesic agent) inhibits β-catenin mediated signaling during skin wound repair. Here we investigate Nefopam's potential as a modulator of bone repair in mice deficient in Nf1. Mice were treated with Nefopam and investigated for bone fracture repair. Bone marrow stromal cells flushed from the long bones of unfractured mice were treated with Nefopam and investigated for osteogenic potential. Treatment with Nefopam was able to lower the β-catenin level and the Axin2 transcript level in the fracture calluses of Nf1 deficient mice. Cultures from the bone marrow of Nf1 -/- mice had significantly lower osteoblastic colonies and mineralized nodules, which was increased when cells were cultured in the presence of Nefopam. Fracture calluses were harvested and analyzed 14days and 21days after injury. Nf1 -/- calluses had less bone, less cartilage, and higher fibrous tissue content than control calluses. Treatment with Nefopam increased the bone and cartilage content and decreased the fibrous tissue content in Nf1 -/- calluses. These findings present a potential treatment for patients with Neurofibromatosis 1 in the context of bone repair. Since Nefopam is already in use in patient care, it could be rapidly translated to the clinical setting. Copyright © 2017 Elsevier Inc. All rights reserved.

A longitudinal study of bone area, content, density, and strength development at the radius and tibia in children 4-12 years of age exposed to recreational gymnastics.

PubMed

Jackowski, S A; Baxter-Jones, A D G; Gruodyte-Raciene, R; Kontulainen, S A; Erlandson, M C

2015-06-01

This study investigated the long-term relationship between the exposure to childhood recreational gymnastics and bone measures and bone strength parameters at the radius and tibia. It was observed that individuals exposed to recreational gymnastics had significantly greater total bone content and area at the distal radius. No differences were observed at the tibia. This study investigated the relationship between exposure to early childhood recreational gymnastics with bone measures and bone strength development at the radius and tibia. One hundred twenty seven children (59 male, 68 female) involved in either recreational gymnastics (gymnasts) or other recreational sports (non-gymnasts) between 4 and 6 years of age were recruited. Peripheral quantitative computed tomography (pQCT) scans of their distal and shaft sites of the forearm and leg were obtained over 3 years, covering the ages of 4-12 years at study completion. Multilevel random effects models were constructed to assess differences in the development of bone measures and bone strength measures between those exposed and not exposed to gymnastics while controlling for age, limb length, weight, physical activity, muscle area, sex, and hours of training. Once age, limb length, weight, muscle area, physical activity, sex, and hours of training effects were controlled, it was observed that individuals exposed to recreational gymnastics had significantly greater total bone area (18.0 ± 7.5 mm(2)) and total bone content (6.0 ± 3.0 mg/mm) at the distal radius (p < 0.05). This represents an 8-21 % benefit in ToA and 8-15 % benefit to ToC from 4 to 12 years of age. Exposure to recreational gymnastics had no significant effect on bone measures at the radius shaft or at the tibia (p > 0.05). Exposure to early life recreational gymnastics provides skeletal benefits to distal radius bone content and area. Thus, childhood recreational gymnastics exposure may be advantageous to bone development at the wrist.

The functional muscle-bone unit in children with cerebral palsy.

PubMed

Duran, I; Schütz, F; Hamacher, S; Semler, O; Stark, C; Schulze, J; Rittweger, J; Schoenau, E

2017-07-01

Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using only age- and height-adjusted bone mineral content (BMC) and areal bone mineral density (aBMD). When applying the functional muscle-bone unit diagnostic algorithm (FMBU-A), the prevalence of positive results decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP. The prevalence of bone health deficits in children with cerebral palsy (CP) might be overestimated because age- and height-adjusted reference percentiles for bone mineral content (BMC) and areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry (DXA) do not consider reduced muscle activity. The aim of this study was to compare the prevalence of positive DXA-based indicators for bone health deficits in children with CP to the prevalence of positive findings after applying a functional muscle-bone unit diagnostic algorithm (FMBU-A) considering reduced muscle activity. The present study was a monocentric retrospective analysis of 297 whole body DXA scans of children with CP. The prevalence of positive results of age- and height-adjusted BMC and aBMD defined as BMC and aBMD below the P3 percentile and of the FMBU-A was calculated. In children with CP, the prevalence of positive results of age-adjusted BMC were 33.3% and of aBMD 50.8%. Height-adjusted results for BMC and aBMD were positive in 16.8 and 36.0% of cases. The prevalence of positive results applying the FMBU-A regarding BMC and aBMD were significantly (p < 0.001) lower than using age- and height-adjusted BMC and aBMD (8.8 and 14.8%). Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using age- and height-adjusted BMC and aBMD. When applying the FMBU-A, the prevalence decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP.

Role of inflammation in the aging bones.

PubMed

Abdelmagid, Samir M; Barbe, Mary F; Safadi, Fayez F

2015-02-15

Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging. Copyright © 2014 Elsevier Inc. All rights reserved.