Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice.

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Histomorphometry and µCT scan analysis of osteoporosis in spayed female dogs.

Background: Both humans and small animals suffer from similar metabolic and structural diseases that impact the musculoskeletal system; however, instead of studying animal disease in its own right, animals are more often used as models for research into various human ailments, such as osteoporosis. There are few studies indicating that animals may suffer from osteoporosis, which raises the question of why small animals, which we believe to be equally susceptible, receive so little attention. With this research, we hope to draw the attention of researchers to the fact that the examination of animals for this disease is just as important as the examination of humans; human osteoporosis research receives a great deal of attention, while animals and their health are neglected. Aims: We aimed to analyze the bone volume fraction (BV/TV) and thickness of first (L1) and second (L2) lumbar vertebrae samples from five cadavers using histomorphometric analysis. In addition, we aimed to investigate one cadaver using microcomputed tomography (µCT) imaging. Methods: The L1 and L2 vertebrae from five dog carcasses were used to evaluate the BV/TV and the trabecular thicknesses. We used precise sampling criteria, and also developed a methodological approach to the study of the vertebrae. Using semi-automated methods, we performed histomorphometric analysis and µCT data analysis. Results: We used five dog cadavers in this research. During the histomorphometry study, we observed that the lowest L1 BV/TV ratio was 7.88% and the highest was 23.08%. The L2 vertebrae BV/TV ranged from 11.58% to 23.7%. The L1 and L2 lumbar trabeculae thicknesses were also measured. L1's smallest trabecula was 17.34 microns and its largest was 31.88. The L2 vertebrae trabecula thickness was 18.76-30.75 microns. BV/TV and trabecular thickness were positively correlated (and vice versa). The two-tailed p value was less than 0.00001. This difference is statistically significant. After µCT analysis, we discovered regions in the vertebral body with low porosity; these cavities are usually filled with connective tissue. The bone tissue in these areas is more vulnerable, meaning fracture risk has increased. Conclusions: Animals should not just be considered as models for osteoporosis in humans, but also as potential patients. A single test, such as histomorphometry, may not be sufficient; more advanced technology, such as µCT, is required, since it reveals the pores that make the vertebral column more brittle and susceptible to fracture.

Osteoporosis is the cause of spontaneous humeral fracture in dairy cows from New Zealand.

Outbreaks of humeral fractures in dairy cows have been reported in New Zealand for several years. Gross, histologic, and histomorphometric findings in the humerus from primiparous cows with spontaneous humeral fracture were compared to age-matched control cows. Affected cows had a complete nonarticular spiral fracture of the humerus. Histologically affected humeri had a thicker growth plate with abnormal architecture, thinner cortex with increased abnormal resorption, increased resorption in the distal humerus, decreased trabecular density, abnormal trabecular architecture, presence of growth arrest lines and woven bone formation. Histomorphometry showed reduction in bone volume, trabecular perimeter, and trabecular width. Cows grazed on fodder beet had thicker growth plates with an abnormal appearance compared with cows grazed on pasture, and cows with low/marginal liver copper concentration had more resorption cavities in the distal humerus and thinner cortical bone compared with cows with adequate liver copper concentration. Decreased trabecular density (OR = 249.5), abnormal cortical resorption (OR = 54.2), presence of woven bone formation in the proximal metaphysis (OR = 37.2), and the number of resorption cavities in the distal humerus were significantly associated with a high probability of fracture. Ribs had enlargement of the costochondral junction with fractures in different stages of healing. Histology of the ribs revealed abnormal growth plate appearance, presence of fracture lines, callus tissue, fibrosis, and microfractures. Cows with humeral fracture have osteoporosis due to decreased bone formation and increased bone resorption, likely associated with inadequate feed quality and perhaps copper deficiency leading to a reduction in bone strength and fracture.

Applications of butyric acid in poultry production: the dynamics of gut health, performance, nutrient utilization, egg quality, and osteoporosis.

Due to the increasing demand for antibiotic-free livestock products from the consumer side and the ban on the use of antibiotic growth promoters, the poultry feed industry is increasingly interested in developing more alternatives to cope with this problem. Organic acids (butyric acid) have many beneficial effects on poultry health, performance, and egg quality when used in their diet, thus they can be considered for the replacement of antibiotics in livestock production systems. Butyric acid is most efficacious against pathogenic bacteria such as Salmonella spp. and Escherichia coli, and stimulates the population of beneficial gut bacteria. It is a primary energy source for colonocytes and augments the differentiation and maturation of the intestinal cells. Collectively, butyric acid should be considered as an alternative to antibiotic growth promoters, because it reduces pathogenic bacteria and their toxins, enhancing gut health thereby increasing nutrient digestibility, thus leading to improved growth performance and immunity among birds. The possible pathways and mechanisms through which butyric acid enhances gut health and production performance are discussed in this review. Detailed information about the use of butyric acid in poultry and its possible benefits under different conditions are also provided, and the impacts of butyric acid on egg quality and osteoporosis are noted.

Yak (Bos grunniens) milk improves bone mass and microarchitecture in mice with osteoporosis.

The effect of milk on bone health is controversial. In this study, the effects of yak milk in mice with retinoic acid-induced osteoporosis (OP) were evaluated. Yak milk was provided to OP mice as a nutrition supplement for 6 wk. The results showed that yak milk significantly reduced bone turnover markers (tartrate acid phosphatase and alkaline phosphatase). The yak milk treatment was also associated with remarkably increased bone mineral density, bone volume, trabecular thickness, and trabecular number, as well as improved biomechanical properties (maximum load and stress) of the tibia. Furthermore, yak milk mitigated the deterioration of the network and thickness of trabecular bone in treated OP mice compared with the OP model group. The results indicated that yak milk could improve bone mass and microarchitecture through the inhibition of bone resorption in OP mice.

Empirical case report of the mechanical properties of three spayed canine lumbar vertebrae.

Background: Today, animals, like humans, suffer from spinal illnesses, which are aggravated in old age. Much emphasis is placed on diagnosis and treatment, but little focus is given to the spine's mechanical properties. Degenerative spine diseases are a major problem throughout the world. According to the World Health Organization, osteoporosis is a world-class public problem that reduces bone mass, resulting in bone fracturing and increased risk of bone fracturing. Therefore, the mechanical investigation of vertebrae can provide more information about the development of osteoporosis.s. Case Description: For our case report, we used spayed mongrel lumbar vertebrae samples obtained from a canine which was about 8 years old and weighed 28 kg. The dog was diagnosed with a mammary tumor, and its owners decided to euthanize the dog. All consent forms were filled. Conclusion: Mechanical tests were performed on three vertebrae, and a notable difference was observed in the first cycle of the first vertebra (L1). Second-order polynomials for displacement and seventh-order polynomials for pressure were proposed for describing the stress-strain relationship of the vertebrae under the cyclical loads. Our research protocol has been broken down into several parts. After measuring the area of the loaded surface, the largest area was in the L2 vertebra (176 ± 16 mm; 177 ± 3 mm) and the smallest was in the L7 vertebra (156 ± 4 mm; 151 ± 33 mm). The smallest distance was recorded between the first (L1) and seventh (L7) lumbar vertebrae (L1) (15.17 ± 0.93 mm), and the largest distance was recorded between the L3 and L4 vertebrae of the lumbar (19.8 ± 3.7 mm).

A Retrospective Study of Postoperative Development of Implant-Induced Osteoporosis in Radial-Ulnar Fractures in Toy Breed Dogs Treated with Plate Fixation.

OBJECTIVE: This study aimed to evaluate implant-induced osteoporosis (IIO) development in toy breed dogs treated using internal fixation with digital radiographs as the index of pixel values. STUDY DESIGN: There were 226 cases (236 limbs) of toy breed dogs with radial-ulnar fractures. Pixel values were measured on radiographs immediately, 2 weeks and 1 to 12 months after surgery. The ratio of pixel values (PVR) represented the bone mineral areal density based on the humeral condyle in the same image. The dogs were grouped based on the fixation methods, age and status of destabilization. RESULTS: There was a significant decrease in the PVR at 1 to 12 months postoperatively for all cases. There were not any significant differences in PVR of antebrachial fractures between those repaired with plates using locking head screws, cortex screws or a combination of locking and cortex screws. Implant-induced osteoporosis persisted at 1 to 12 months postoperatively in dogs aged ≧6 months, while the PVR increased after 3 months in dogs aged <6 months. Based on the destabilization method, there was a significant increase in the PVR at 3 months in the plate removal group. CONCLUSION: This study suggests that IIO occurs in small dogs treated with plates and screws. Moreover, patients aged < 6 months showed an early postoperative recovery of bone mineral areal density. Further, screw and plate removal could contribute to the recovery of bone mineral areal density.

Effect of ovariectomy-induced osteoporosis on the amount of orthodontic tooth movement: a systematic review of animal studies.

BACKGROUND: Understanding the impact of osteopenia and osteoporosis on orthodontic tooth movement could be of benefit to the orthodontist, but research in humans presents practical and ethical problems. The ovariectomized animal model could provide useful information on osteoporosis. OBJECTIVE: To compare the amount of tooth movement during or after the application of orthodontic forces between ovariectomized animals and control or sham-operated subjects. SEARCH METHODS: Unrestricted searches in seven databases and manual searching of the reference lists in relevant studies were performed up to February 2021 (PubMed, Central, Cochrane Database of Systematic Reviews, Scopus, Web of Science, Arab World Research Source, ProQuest Dissertations, and Theses Global). SELECTION CRITERIA: We searched for studies quantitatively comparing the amount of tooth movement during or after the application of orthodontic forces between ovariectomized animals and control or sham-operated subjects. DATA COLLECTION AND ANALYSIS: Following study retrieval and selection, relevant data were extracted, and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. Exploratory synthesis and meta-regression were carried out using the random effects model. RESULTS: Thirteen studies were finally selected and no specific concerns regarding bias were identified. During the active period, ovariectomy was associated with a statistically significant acceleratory effect on the rate of orthodontic tooth movement compared to non-treated rats (3 weeks; 4 studies, 0.15 mm more movement in the ovariectomized rats; 95 per cent confidence interval: 0.10-0.19; P = 0.000). Exploratory meta-regression showed that this difference could increase over time. Following force discontinuation, no statistically significant differences were observed [3 weeks; 1 study (median ± SE), Ovariectomy group: 0.30 ± 0.04 mm; Sham operation group: 0.18 ± 0.03; P = 0.1558]. CONCLUSIONS: Ovariectomy-induced osteoporosis may affect the rate of orthodontic tooth movement. Although animal studies should be approached with caution regarding their translational potential, the safe practice would suggest that one should consider potential implications. REGISTRATION: PROSPERO (CRD42018118003).

The effects of eggshell calcium (Biomin H® ) and its combinations with alfacalcidol (1α-hydroxyvitamin D3) and menaquinone-7 (vitamin K2) on ovariectomy-induced bone loss in a rat model of osteoporosis.

The purpose of this study was to investigate the impact of eggshell calcium (Biomin H® dietary supplement) and its combinations with alfacalcidol (1α-hydroxyvitamin D3 ) and menaquinone-7 (vitamin K2 ) on ovariectomy-induced bone loss in rats. Adult female rats (n = 48) were divided into 6 groups of 8 individuals each: sham-operated rats (SHAM); ovariectomized (OVX) rats untreated; OVX rats treated with Biomin H® (BIO); OVX rats simultaneously receiving Biomin H® , vitamin D3 (BIO + D3 ); OVX rats simultaneously treated with Biomin H® , vitamin K2 (BIO + K2 ) and OVX rats treated with Biomin H® , vitamin D3 , vitamin K2 (BIO + D3  + K2 ) during 8 weeks. Biochemical parameters, bone mineral density (BMD), bone mineral content (BMC) and femoral bone microstructure were determined. Plasma calcium and phosphate were increased in BIO + D3 and BIO + D3  + K2 groups as compared to OVX. Alkaline phosphatase was elevated in OVX, BIO versus SHAM, BIO + D3  + K2 groups. When compared to OVX group, decreased urine deoxypyridinoline was observed in all treated groups and femoral BMD, BMC were higher in BIO, BIO + D3 , BIO + D3  + K2 groups. The BIO + K2 rats had similar densitometrical values than OVX individuals. Microcomputed tomography revealed increased trabecular relative bone volume (due to an increase in trabecular number) in BIO + D3 , BIO + D3  + K2 as compared to OVX. The higher relative bone volume in BIO + D3 , BIO + D3  + K2 groups was also accompanied by an increase in bone surface. In the cortical bone, an enhanced periosteal bone apposition was identified in BIO, BIO + D3 , BIO + K2 , BIO + D3  + K2 groups. The rats from BIO + D3  + K2 group had a higher area of primary osteon's vascular canals. In BIO + D3 , BIO + K2 , BIO + D3  + K2 groups, an increased area of secondary osteons was determined in comparison with OVX. Our results indicate the beneficial effect of triple application of Biomin H® , vitamin D3 , vitamin K2 , as well as simultaneous administration of Biomin H® , vitamin D3 on the inhibition of ovariectomy-induced bone loss in a rat model of osteoporosis.

Short communication: Dietary bovine milk-derived exosomes improve bone health in an osteoporosis-induced mouse model.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged society with increased life expectancy, the incidence rate of osteoporosis is also rapidly increasing. Inadequate nutrition may negatively influence bone metabolism. Recently, many studies have investigated the functionality of milk-derived exosomes, which play important roles in cell-to-cell communication. However, there are few reports of how milk-derived exosomes influence osteoblast proliferation and differentiation. Here, we determined whether bovine colostrum-derived exosomes promote anti-osteoporosis in vitro and in vivo. Tartrate-resistant acid phosphatase-stained cells were significantly inhibited in Raw264.7 cells treated with exosomes, indicating reduced osteoclast differentiation. We induced osteoporosis in mice using glucocorticoid pellets after orally administering exosomes for 2 mo. Interestingly, the bone mineral density of exosome-fed mouse groups was significantly improved compared with the glucocorticoid-induced osteoporosis group without exosome treatment. In addition, Lactobacillus were decreased in the gut microbiota community of osteoporosis-induced mice, but the gut microbiota community composition was effectively restored by exosome intake. Taken together, we propose that exosomes isolated from bovine colostrum could be a potential candidate for osteoporosis prevention, bone remodeling improvement, and inhibition of bone resorption. To our knowledge, this is the first time that a protective effect of milk exosomes against osteoporosis has been demonstrated in vivo. Our results strongly suggest that bovine colostrum exosomes might be used as a prophylaxis to prevent the onset of osteoporosis. Indeed, our results offer promising alternative strategies in the nutritional management of age-related bone complications.

Effects of low dietary phosphorus on tibia quality and metabolism in caged laying hens.

Osteoporosis is a common bone metabolic disease in caged laying hens. This disease affects animal welfare and economic costs. In this study, a model of osteoporosis induced by low dietary phosphorus was established. A total of sixty 22-week-old Roman white laying hens were randomly divided into two groups, including a control group (group C) and a low dietary phosphorus group (group P). The effects of low dietary phosphorus on the endocrine and tibial osteoprotegerin (OPG)/nuclear factor kappa B receptor activating factor ligand (RANKL) signaling pathways of osteoporosis in caged laying hens were analyzed by serology, bone biomechanics, molecular biology and histopathology. The results showed that low dietary phosphorus decreased the production performance, and egg quality of laying hens and increased the contents of serum calcium (Ca), osteocalcin (OCN), alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRACP). The contents of serum phosphorus, calcitonin (CT), OPG and tibial biomechanics index decreased. The bone mineral density (BMD), cortical bone thickness and the expression level of OPG protein in tibia decreased. The expression of OCN, nuclear factor kappa B receptor activating factor (RANK) and RANKL protein increased. Low dietary phosphorus caused thinning and fracture of the bone trabeculae and enlargement of the bone marrow cavity of tibia. Our results suggest that phosphorus may affect bone metabolism by regulating the OPG/RANKL signaling pathway.

An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens.

BACKGROUND: Skeletal damage is a challenge for laying hens because the physiological adaptations required for egg laying make them susceptible to osteoporosis. Previously, we showed that genetic factors explain 40% of the variation in end of lay bone quality and we detected a quantitative trait locus (QTL) of large effect on chicken chromosome 1. The aim of this study was to combine data from the commercial founder White Leghorn population and the F2 mapping population to fine-map this QTL and understand its function in terms of gene expression and physiology. RESULTS: Several single nucleotide polymorphisms on chromosome 1 between 104 and 110 Mb (galGal6) had highly significant associations with tibial breaking strength. The alternative genotypes of markers of large effect that flanked the region had tibial breaking strengths of 200.4 vs. 218.1 Newton (P < 0.002) and, in a subsequent founder generation, the higher breaking strength genotype was again associated with higher breaking strength. In a subsequent generation, cortical bone density and volume were increased in individuals with the better bone genotype but with significantly reduced medullary bone quality. The effects on cortical bone density were confirmed in a further generation and was accompanied by increased mineral maturity of the cortical bone as measured by infrared spectrometry and there was evidence of better collagen cross-linking in the cortical bone. Comparing the transcriptome of the tibia from individuals with good or poor bone quality genotypes indicated four differentially-expressed genes at the locus, one gene, cystathionine beta synthase (CBS), having a nine-fold higher expression in the genotype for low bone quality. The mechanism was cis-acting and although there was an amino-acid difference in the CBS protein between the genotypes, there was no difference in the activity of the enzyme. Plasma homocysteine concentration, the substrate of CBS, was higher in the poor bone quality genotype. CONCLUSIONS: Validated markers that predict bone strength have been defined for selective breeding and a gene was identified that may suggest alternative ways to improve bone health in addition to genetic selection. The identification of how genetic variants affect different aspects of bone turnover shows potential for translational medicine.

Osteoporosis in an Asian small-clawed otter (Aonyx cinereus Illiger, 1815).

Osteoporosis is a skeletal disease that occurs in many mammals. Our report describes osteoporosis in an Asian small-clawed otter (Aonyx cinereus). Gross, histological, and radiographic observations showed that all of the bones had numerous pockmarks on their surfaces. Histologically, the pockmarks were filled with fibrous tissue without inflammation. However, the spongy bone was normal according to the histological and radiographic results. Overall, the results showed that this was a case of osteoporosis that mainly involved external rather than internal surfaces.

Inhibition of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase-2 Facilitates CD31hiEndomucinhi Blood Vessel and Bone Formation in Ovariectomized Mice.

BACKGROUND/AIMS: Recently, we and others showed that the relative abundance of a specific vessel subtype, strongly positive for CD31 and Endomucin (CD31hiEmcnhi), is associated with bone formation and bone loss, and platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces the formation of the specific vessels and thereby stimulates osteogenesis. Inhibition of Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) has been shown to block the fusion of preosteoclasts into mature osteoclasts. However, it is unclear whether inhibition of SHP-2 could promote preosteoclast-induced angiogenesis and then enhance bone formation. This study aimed to determine the effects of a specific SHP-2 inhibitor (NSC-87877) on CD31 hiEmcnhi vessel and bone formation. METHODS: 3-month-old C57BL/6 mice were subjected to either ovariectomy (OVX) or sham operation. OVX mice were intraperitoneally injected with NSC-87877 and the control (sham) mice were treated with an equal volume of diluents (PBS). Two months later, bone samples from mice were collected for µCT, histological, immunohistochemical and immunofluorescent analyses to assess bone mass, osteogenic and osteoclastic acitivities, as well as the densities of CD31hiEmcnhi vessels. A series of angiogenesis- related assays were performed to test the effects of NSC-87877 on the pro-angiogenic activities of preosteoclasts in vitro. RESULTS: We found that NSC-87877 is sufficient to induce bone-sparing effects in OVX-induced osteoporotic mouse model. We also found that NSC-87877 induces higher numbers of preosteoclasts and CD31hiEmcnhi vessels and higher levels of PDGF-BB in bone marrow of osteoporotic mice. In vitro assays showed that NSC-87877 prevents preosteoclast fusion, increases PDGF-BB production, and augments the pro-angiogenic abilities of preosteoclasts. CONCLUSION: Our results suggest that NSC-87877 can be used as a promising therapeutic agent for osteoporosis by inhibiting osteoclast formation and promoting preosteoclast-induced angiogenesis.

Chronic arsenicosis and cadmium exposure in wild snowshoe hares (Lepus americanus) breeding near Yellowknife, Northwest Territories (Canada), part 2: Manifestation of bone abnormalities and osteoporosis.

Various bone abnormalities, including osteoporosis, have been associated with chronic arsenic and cadmium exposure in experimental animal models, but information regarding the bone pathology of wild population of small mammals breeding in contaminated environment is limited. This present study was conducted to comparatively assess the prevalence and pattern of skeletal abnormalities in free ranging snowshoe hares inhabiting an area heavily contaminated by arsenic and other trace metals, near the vicinity of the abandoned Giant mine, and in a reference location approximately 20km from the city of Yellowknife, Northwest Territories, Canada. The femur and vertebrae of snowshoe hares from the mine area and reference location were subjected to bone densitometry examination and biomechanical testing using dual energy X-ray absorptiometry (DXA) and 3-point bending test. t-test results indicated that femoral densitometry parameters such as bone mineral density (BMD) (p=0.5), bone mineral content (BMC) (p=0.675), bone area (BA) (p=0.978) and tissue area (TA) (p=0.549) were not significantly different between locations. All densitometry parameters of the vertebrae (BMD, BA and TA) differed between locations (p<0.05), except for BMC (p=0.951) which showed no significant difference between the two locations. Vertebrae from the mine area also showed relatively lower BA and TA compared to the reference location. A constellation of skeletal abnormalities were also observed along the axial and appendicular bones respectively. Specifically, growth defects, osteoporosis, cortical fractures, sclerosis, and cyst like changes were commonly observed in the femurs and vertebrae of hares from both locations. With respect to biomechanical properties, only bone stiffness and peak load tended to be relatively reduced in specimens from the mine area, whereas work to failure was notably increased in specimens from the reference site compared to those from the mine area. Taken together, the results of this preliminary study suggest that chronic concomitant exposure to arsenic and cadmium may be involved in the etiology of various bone abnormalities, including osteoporosis in wild population of snowshoe hares from the Yellowknife area. The result presented in this study represent the first evaluation of osteological effects in free-ranging furbearers (snowshoe hares) diagnosed with arsenicosis, and concomitantly exposed to environmental levels of cadmium.

Human type H vessels are a sensitive biomarker of bone mass.

Vascularization is fundamental for bone formation and bone tissue homeostasis. However, in human subjects, a direct molecular relationship has not been identified between angiogenesis and agents that promote bone disease or factors related to age. Osteopenia is a condition in which bone mineral density is lower than normal, and it represents a sign of normal aging. Here we tested whether the type H vessel, which was recently identified as strongly positive for CD31 and Endomucin (CD31hiEmcnhi) in mice, is an important indicator of aging and osteopenia in human subjects. We found that age-dependent losses of type H vessels in human bone sections conform to the observations in aged mice. The abundance of human type H vessels and osteoprogenitors may be relevant to changes in the skeletal microarchitecture and advanced osteopenia. Furthermore, ovariectomized mice, a widely used model for postmenopausal osteoporosis, exhibited significantly reduced type H vessels accompanied by reduced osteoprogenitors, which is consistent with impaired bone microarchitecture and osteoporosis, suggesting that this feature is an indicator of bone mass independent of aging. More importantly, administration of desferrioxamine led to significantly increased bone mass via enhanced angiogenesis and increased type H vessels in ovariectomized mice. Altogether, these data represent a novel finding that type H vessels are regulated in aged and osteopenia subjects. The abundance of human type H vessels is an early marker of bone loss and represents a potential target for improving bone quality via the induction of type H vessels.

Genetic architecture of bone quality variation in layer chickens revealed by a genome-wide association study.

Skeletal problems in layer chickens are gaining attention due to animal welfare and economic losses in the egg industry. The genetic improvement of bone traits has been proposed as a potential solution to these issues; however, genetic architecture is not well understood. We conducted a genome-wide association study (GWAS) on bone quality using a sample of 1534 hens genotyped with a 600 K Chicken Genotyping Array. Using a linear mixed model approach, a novel locus close to GSG1L, associated with femur bone mineral density (BMD), was uncovered in this study. In addition, nine SNPs in genes were associated with bone quality. Three of these genes, RANKL, ADAMTS and SOST, were known to be associated with osteoporosis in humans, which makes them good candidate genes for osteoporosis in chickens. Genomic partitioning analysis supports the fact that common variants contribute to the variations of bone quality. We have identified several strong candidate genes and genomic regions associated with bone traits measured in end-of-lay cage layers, which accounted for 1.3-7.7% of the phenotypic variance. These SNPs could provide the relevant information to help elucidate which genes affect bone quality in chicken.

Novel Nonsurgical Approach to Stabilization of Bilateral Pathologic Femoral Fractures in an Egg-laying Maroon-bellied Conure (Pyrrhura frontalis).

A 2-year-old, egg-laying maroon-bellied conure (Pyrrhura frontalis) was referred for treatment of bilateral femoral fractures believed to be secondary to recent egg laying and nutritional and husbandry deficiencies. On radiographs, all skeletal components were diffusely osteopenic, precluding surgical fixation. A novel device to stabilize the bilateral femoral fractures was manufactured with polyvinyl chloride piping, which braced the bird's feet at the level of the perch and supported its upper body weight via a breast plate, thus maintaining the bird in a physiologically appropriate perching position. The conure was ambulatory and returned to normal function after 3 weeks of external coaptation with this device. After 6 weeks, callus formation was palpable over both fracture sites even though minimal bone remodeling was visible radiographically. This body splint device may present a viable alternative to euthanasia in select cases of bilateral femoral fractures in companion birds.