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J APPL POULT RES 2007. 16:126-137
© 2007 Poultry Science Association
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Informal Nutrition Symposium

Metabolic Challenges and Early Bone Development

J. J. Dibner1, J. D. Richards, M. L. Kitchell and M. A. Quiroz

Novus International Inc., St. Charles, MO 63304

Correspondence: 1 Corresponding author: Julia.Dibner{at}novusint.com


   SUMMARY
TOP
 SUMMARY
DESCRIPTION OF PROBLEM
 BONE DISORDERS ASSOCIATED WITH...
 BONE DEVELOPMENT
 NUTRITIONAL INTERVENTION AGAINST...
 CONCLUSIONS AND APPLICATIONS
 REFERENCES AND NOTES
 
Lameness is the phenotypic expression of a wide variety of genetic, conformational, nutritional, toxic, and infectious conditions. Poultry selected for rapid growth are susceptible to lameness, and it can be a significant source of mortality in heavy birds. Genetic selection has been successful in providing annual improvements in meat poultry productivity; however, some support systems, such as the cardiovascular and skeletal systems, have not kept up with the increase in body mass, making birds increasingly susceptible to compromise or failure of these systems. Breeders have been selecting for robust support systems in addition to increased productivity, but meat birds are still challenged with keeping structural and supply organs synchronized with the growth of demand tissues such as muscle. The structural system of the bird is comprised of bone, cartilage, ligaments, tendons, and the connective tissue of skin and other organs. Healthy bone growth can be disrupted by developmental, nutritional, environmental, or infectious conditions, with bone problems often being associated with more than one of these causes. A review of recent reports on bone formation and the role of trace minerals in bone development and repair indicate that availability of Zn, Cu, and Mn should be considered by nutritionists who want to enhance the resilience of bone, cartilage, and other structural tissues in their birds.

Key Words: tibial dyschondroplasia • lameness • endochondral ossification • trace mineral • poultry


   DESCRIPTION OF PROBLEM
TOP
 SUMMARY
 DESCRIPTION OF PROBLEM
BONE DISORDERS ASSOCIATED WITH...
 BONE DEVELOPMENT
 NUTRITIONAL INTERVENTION AGAINST...
 CONCLUSIONS AND APPLICATIONS
 REFERENCES AND NOTES
 
Genetic selection for efficient production has improved the performance of meat poultry, particularly broilers and turkey poults, to levels that have not been equaled by any other source of animal protein. This selection has been successful in providing annual improvements in productivity since the 1950s, with resulting increases in BW and feed efficiency that show little sign of reaching their limits. It became evident in the 1980s that some support systems, such as the cardiovascular and skeletal systems, had not kept up with the increase in body mass and that the birds were increasingly susceptible to compromise or failure of these systems associated with various deviations from stress-free conditions. Thus, any one of a variety of situations could provoke a breakdown in support systems. As commercial breeders began to select for robust support systems in addition to increased productivity, the situation has improved, but meat birds are still challenged with keeping structural and supply organs synchronized with the growth of demand tissues such as muscle. One of the most frequently affected systems is the structural bone, joints, tendons and the connective tissue of the legs and feet. This review will describe the most common structural disorders in broilers and turkey poults grown for meat yield and the various stresses that can evoke them. A review of recent reports on the role of trace minerals in bone development will serve to highlight some tactics that the nutritionist can use to enhance the ability of structural tissues to respond to stress.


   BONE DISORDERS ASSOCIATED WITH RAPID GROWTH
TOP
 SUMMARY
 DESCRIPTION OF PROBLEM
 BONE DISORDERS ASSOCIATED WITH...
BONE DEVELOPMENT
 NUTRITIONAL INTERVENTION AGAINST...
 CONCLUSIONS AND APPLICATIONS
 REFERENCES AND NOTES
 
Lameness is the phenotypic expression of a wide variety of conditions. It is common in poultry selected for rapid growth and has been estimated to affect 2 to 6% of turkey flocks [1], in which it is most common in birds older than 14 wk. Within a flock, the incidence can exceed 15% [2], and lameness is a significant source of mortality in heavy birds. It should be noted that many abnormalities in bone development can be initiated early in life, with lameness appearing only later in association with a conformational, environmental, or infectious challenge [3, 4, 5, 6]. In broilers, recent reductions in leg-related condemnations and mortalities are largely due to changes in genetic selection that, along with rigorous attention to health, nutrition, and management, have reduced the susceptibility of broilers to lameness [7]. Nevertheless, bone problems are still among the most costly disorders associated with rapid growth because of their chronicity, their tendency to reduce feed intake, and the frequency of downgrades and condemnations when affected birds are processed. Regardless of the factors provoking it, once lameness has developed, it very rarely resolves, tending to become worse with age and increasing BW. Pododermatitis, a chronic ulcerative dermatitis of the feet and hocks, contributes to progression of lameness and the performance decline associated with it.

Bone abnormalities in birds can be initiated by developmental, degenerative, nutritional, environmental, or infectious problems and are often associated with more than one of these causes. The condition advances to lameness in otherwise apparently healthy flocks that are fed high-density diets at high stocking density and that live in environmental conditions that maximize their growth rate [8, 9, 10]. Abnormal bone development can result in varus-valgus disease, tibial dyschondroplasia (TD), and chondrodystrophy. One cause of developmental abnormalities is imbalance – excess or deficiency – of specific hormones, including androgens, estrogens, the growth hormone-insulin-like growth factor-I system, parathyroid and thyroid hormones, and also stress-related hormones such as glucocorticoids [6]. Degenerative diseases include pododermatitis, rupture of the gastrocnemius tendon, and degenerative joint disease [8].

Nutritional stress such as vitamin or mineral deficiency or imbalance is associated with rickets and also with TD. It is important to realize that the presence of oxidized fat in the diet will cause the degradation of all fat-soluble vitamins, including vitamins D, A, and E [11]. This can reduce availability of these vitamins, sometimes resulting in lameness. It is also important to recognize that the osteolytic action of osteoclasts may be enhanced in the presence of free radicals found in poorly stabilized fat samples [12].

Among the most common infectious problems are bacterial chondronecrosis with osteomyelitis (femoral head necrosis) and tenosynovitis. Using dexamethasone injection followed by airsac challenge with Escherichia coli as a model for stress, Huff et al. [4] have shown that turkeys selected for fast growth are more likely to develop turkey osteomyelitis complex than birds from a slow-growing line selected for egg production.

Environmental stresses, which include high stocking density, low brooding temperatures, poor ventilation, and poor litter quality, are associated with lameness due to infected hocks, TD, pododermatitis, and tenosynovitis [8, 13]. It should also be noted that an initially minor problem such as a crack in a foot pad, if not promptly healed, can lead to lameness. An example of this is the frequency with which pododermatitis is associated with joint infections in hocks, knees, and hips [13].

It is clear that lameness is a very complex problem with many components. Genetics plays a contributing role, but lameness is closely related to the extremely rapid bone growth in broilers and turkeys fed and managed to achieve their full potential for growth [8, 9]. The structural support system has very little flexibility to respond to many commonly occurring stresses.

TD
Tibial dyschondroplasia, the most common bone disorder in poultry, was first described by Leach and Nesheim [14]. Avian TD is characterized by an accumulation of the avascular part of the growth plate distal to the zone of proliferation. Figure 1Go shows the histological appearance of a normal (panel A) and TD-affected (panel B) proximal tibia growth plate. Some authors describe TD as a failure of vascularization due to reduction in vascular penetration normally mediated by collagenolytic matrix metalloproteinases [15, 16]. There is also evidence that the defect in thiram-induced TD is related to apoptosis in endothelial cells [17]. Many studies have been done comparing the chondrocytes and extracellular matrix (ECM) of normal and dystrophic cartilage. The chondrocytes in TD do not fully differentiate and hypertrophy; rather, they appear to be arrested in a prehypertrophic state of differentiation [18]. The regulation of chondrocyte differentiation and gene expression is currently under study. Whether differentiation is mediated by Zn, as in other tissues, remains to be determined. Biochemically, growth plate cartilage from TD birds differs in several respects from that of normal birds [19]. Changes in osteogenic proteins such as osteocalcin and osteopontin are often accompanied by reductions in growth factors such as transforming growth factor-ß and collagen type X [18].


Figure 1
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  		Figure 1. Histological appearance of normal (panel A) and tibial dyschondroplastic (TD; panel B) growth plates from 14-wk-old tom turkeys. Residual cartilage and lack of vascular invasion are seen in the dyschondroplastic tibia growth plate. Masson’s trichrome, 10x.

 
There are conflicting data on the proteoglycan content of the ECM of TD lesions, but it has been suggested that higher molecular weight proteoglycans may inhibit vascular invasion and in this way retard ossification [18, 20]. Osteochondrosis is a developmental defect in endochondral ossification in horses and swine. The histopathology of this disorder resembles that of TD in poultry [21]. Among the nutritional conditions associated with osteochondrosis is Cu deficiency [22, 23]. In addition, Cu supplementation can prevent the TD associated with thiram administration in chicks [15, 24]. Tibial dyschondroplasia serves as an example of the leg problems that accompany rapid growth and is the most commonly studied lesion, but not all leg problems in broilers and turkeys arise from this particular pathological process. One interesting fact to note is that the progression of a chondrocyte from the proliferative stage to the hypertrophic stage is estimated at 21 h for rapidly growing meat birds [25]. This can be compared to a 4-d period for rabbit chondrocytes [22], a 2-d period for rat, and 20-d period for human chondrocytes [26]. The selection for rapid growth in meat birds undoubtedly contributes to these differences in growth plate cellular kinetics.


   BONE DEVELOPMENT
TOP
 SUMMARY
 DESCRIPTION OF PROBLEM
 BONE DISORDERS ASSOCIATED WITH...
 BONE DEVELOPMENT
NUTRITIONAL INTERVENTION AGAINST...
 CONCLUSIONS AND APPLICATIONS
 REFERENCES AND NOTES
 
During development in ovo, a hyaline cartilage model of the appendicular skeleton is laid down [27]. The process of converting this model to bone, endochondral ossification, is begun in ovo but primarily occurs after hatch [28]. In addition, growth in the length of the long bones continues to use the endochondral ossification process by the replacement of new hyaline cartilage formed at the epiphyseal plate [29]. Many birds are marketed before epiphyseal plate closure. In this sense, the axial bones of most meat poultry never reach the stage of homeostasis and remodeling characteristic of adult vertebrates but are undergoing development throughout the life of the bird [30]. Indeed, Rath et al. [31] observed that the longitudinal bone growth of broiler breeders continued until 25 wk of age. This is important, because the processes of bone dissolution and reformation are coupled in bone remodeling but uncoupled during initial bone deposition [27].

Endochondral Ossification
The process of endochondral ossification after hatch involves a highly coordinated sequence of events that begins with proliferation of cartilage cells (chondrocytes) in the growth plate. The spatial coordination of this process is reflected in the microscopic anatomy of the epiphyseal plate. At the proximal edge of the plate are resting chondrocytes, below which are the proliferating chondrocytes responsible for new growth. As these cells mature, they secrete the ground substance of hyaline cartilage, including large aggregating sulfated proteoglycans such as aggrecan [32], and the fibers in which they are embedded, primarily type II collagen [33]. The chondrocytes encase themselves in this avascular ECM, through which all nutrients and waste products must diffuse. There are many other components in the ECM, including growth factors, cytokines, prostaglandins, and small molecular weight proteoglycans. The function of many of these smaller molecules is still being described [15, 34, 35, 36]. As the chondrocytes age, their secretory product changes, as does their morphology. The distal end of the growth plate is called the hypertrophic zone, where the chondrocytes enlarge and undergo terminal differentiation [37, 38]. At this time, their secretory products change to include collagen type X as well as type II and other proteins such as annexin and fibronectin [20]. The proteoglycan components are smaller molecular weight molecules such as decorin and byglycan [19, 39]. This zone is also characterized by its high level of alkaline phosphatase activity, which is associated with mineralization. Chondrocytes in the distal hypertrophic zone (the zone of provisional calcification) also synthesize collagen type I, in common with the invading bone precursor cells, osteoblasts [20].

The molecular and cell biology of endochondral ossification are still being described [40]. Mineralization, in particular, is restricted to a small portion of the cartilaginous bone model, the epiphyseal plates, and is controlled both spatially and temporally. Either insufficient or excessive mineralization is associated with significant pathology such as osteoporosis and osteopetrosis. Briefly, as the chondrocytes age and exhaust their supply of glycogen, their mitochondria begin to concentrate Ca [20]. This occurs in conjunction with a shift to anaerobic metabolism accompanied by changes in O2 tension and glycolytic enzymes [33]. The hypertrophic cells begin to shed matrix vesicles, membrane-bound microstructures averaging 30 to 100 nm in diameter [41, 42]. These vesicles contain several specific proteins, including annexins II, V, and VI; alkaline phosphatase; and a core complex of Ca and P that forms before shedding [20]. The complex also includes phosphatidyl serine as a component [43, 44]. These amorphous Ca-P complexes appear to serve as the nucleation site for calcification in endochondral ossification. The annexin mediates Ca2+ influx into the vesicles and also binds directly to types II and X collagen, anchoring the vesicles to the ECM [45]. The matrix vesicle also includes Zn and Cu, and these are thought to have a role in maintaining the amorphous structure of the mineral until the initiation of hydroxyapatite crystallization [46]. Interestingly, a histochemical study of the distribution of Zn in bone tissue detected the mineral at the borderline between calcified and uncalcified material. Zinc staining was associated with the late-stage hypertrophic chondrocytes near the front of vascular invasion, which is consistent with a role for Zn in regulating matrix vesicle mineral crystallization as described above [47]. The membrane and lipid components of the matrix vesicle are not representative of the cell membrane of the hypertrophic chondrocyte [48]. In particular, the matrix vesicle membrane is enriched for phosphatidylserine [41]. The crystallization of hydroxyapatite is initiated in the matrix vesicles. The apatite crystals rupture the vesicle membrane and begin directed growth along the type I collagen fibers synthesized by hypertrophic chondrocytes [20]. Research has suggested a role for type I collagen in hydroxyapatite crystal elongation, orientation, and propagation [49, 50, 51, 52].

As these initial mineralization steps are occurring at the distal edge of the growth plate, invasion of the cartilage model by the vascular system simultaneously delivers bone precursor cells (osteoblasts) to the interior. This initiates the actual process of bone formation [27]. There is evidence that chondrocytes at the chondroosseous junction express angiogenic factors such as vascular endothelial growth factor [53] and transferrin [22] and in this way stimulate the invasion of blood vessels into the model. Degeneration of the cartilage matrix is mediated by collagenase-3, a metalloproteinase containing Zn in the active site [22]. The vessels bring the osteoblasts, which bind to the mineralized cartilage matrix and begin to secrete the components of the bone extracellular matrix, osteoid. The collagen of osteoid is type I. The crosslinking of this collagen provides the structure along which hydroxyapatite crystals grow [45].

These events make it clear that proper bone formation is a highly complex, multistep process that depends on much more than Ca and P. Multiple cell types must act sequentially and in concert for proper development. Each step is governed by transcription factors and signaling polypeptides [54]. It is also important to recognize that this initial ossification does not yield bones that are structurally mature and mechanically robust. Following initial deposition of ECM and mineral, important changes occur that are responsible for the increase in bone breaking strength observed in older birds [55]. For example, although mineral deposition and crystal maturation is essential for compressive strength, the alignment and crosslinking of the collagen in the ECM is highly correlated with bone breaking strength. One interesting thing about bone is that all of these critical posttranslational maturation steps take place outside the cells, within the ECM.

Trace Minerals in Bone Development
Although trace minerals are not often considered in the context of bone development, endochondral ossification absolutely depends on trace mineral availability. Manganese is essential for the formation of the mucopolysaccharides that form the ground substance of the cartilage model [27]. Copper is in the amorphous mineral of the matrix vesicles, preventing its premature crystallization [56], and also plays an important role in the crosslinking of collagen and elastin, which gives bone its tensile strength and elasticity [57]. Zinc plays an important role in regulation of hydroxyapatite crystallization [56, 58], collagen synthesis [59], and the cellular invasion of the cartilage matrix by the osteoblasts. This invasion requires the activity of the collagenase-matrix metalloproteinase molecules, particularly collagenase-3, which contain Zn in their active sites [22, 60]. The fact that intracellular Zn fluxes are associated with apoptosis in growth plate chondrocytes [61] suggests that Zn may play a role in endochondral ossification beyond its participation in vascular invasion and hydroxyapatite crystallization [62, 63, 64]. Zinc is also associated with the changes in gene transcription that accompany ossification. Furthermore, recent work indicates that the deficiency of a specific Zn finger protein (the Gli2 transcription factor) is associated with impaired endochondral ossification in mice [65]. In this study, the delayed ossification was associated with aberrant gene expression, including decreased expression of a variety of angiogenic factors in hypertrophic chondrocytes.

Our group has been studying the role of trace mineral availability on bone development and abnormalities associated with rapid growth. The importance of Ca, P, and vitamin D has been so well documented that it is rare to encounter bone abnormalities associated with simple deficiencies in any of these components [66]. What is not as well understood is that the very process of ensuring adequate Ca and P may cause a deficiency in trace minerals. This is due to the tendency of cationic minerals to form insoluble complexes with free P, phytic acid, and other components of the digesta. As more Ca is fed, less Zn, Cu, and Mn are absorbed [66]. This is partly due to the coordinate covalent binding of all of these cations to phytic acid. Phytate is able to form chelates of these minerals that are very stable and highly insoluble [67]. The antagonism is mutual in that the binding of Ca, Zn, and other minerals also reduces the availability of phytin P, even in the presence of exogenous phytase [68]. Antagonisms also occur between one trace mineral and another. For example, high levels of Zn reduce the availability of Cu [69]. The absorbability of Mn, generally low under many circumstances, can be reduced in the presence of supplemental P [70]. Availability of inorganic sources of minerals can also be reduced by other nutrients; for example, Cu availability is reduced by ascorbic acid [71].

Historically, trace minerals have been supplemented in poultry diets using the inorganic salts such as Zn, Cu, and Mn oxide or Zn, Mn, and Cu sulfate. Inorganic minerals have also been used in the development of mineral requirements for poultry diets [72]. However, because of the antagonisms described above, use of inorganic salts can result in variable or low bioavailability of the mineral.

The common denominator in the antagonistic interactions among minerals is the dissociation of the inorganic salt in the relatively low pH of the upper gastrointestinal system. When the mineral reaches the higher pH of more distal gut segments, it can bind to many minerals, nutrients, and nonnutritive components of the digesta, such as phytate and fiber, which render it insoluble. Insoluble forms of minerals are excreted.

The advantage of organic trace minerals is that the binding of the mineral to the organic ligand provides stability of the complex in the upper gastrointestinal system. Organic trace minerals should resist dissociation in the crop, proventriculus, and gizzard, thus allowing the intact complex to be delivered to the absorptive epithelium of the small intestine [73]. The organic forms of many minerals, including Zn, Cu, and Mn, are widely used in animal agriculture. Increased availability of organic Zn and Cu compared to inorganic forms has been demonstrated [74, 75, 76]. Increasing the availability of trace minerals can have significant biological effects, including improved bone mineralization [77, 78, 79]; however, important environmental benefits also accrue from the reduced excretion of those minerals into the environment [80, 81].

Availability of trace minerals, particularly the combination of Zn, Cu, and Mn, plays a critical role in early development because of the integrated function of metalloenzymes in building structural connective tissue. Although collagen synthesis requires Zn, unless sufficient Cu is present, fibrils will not be properly cross-linked, and the resulting structure may be weakened or may fail [31]. The development of appropriate connective tissue requires that compliant organs such as the gut be provided with the capability to accommodate changes in digesta volume at the same time that structural tissues such as tendon be highly resistant to stretching in response to a change in mechanical tension. The ECM of bone contributes tensile strength, whereas the crystalline mineral provides rigidity and compressive strength [31, 39]. Both are essential for bone to be a flexible, strong, and lightweight structural material.

The ground substance of tissue, particularly the proteoglycan matrix in which collagen and elastin are embedded, requires Mn for glycosylation of the protein core molecule [66]. Proteoglycans vary in their hydration and aggregation, and these differences are essential to their various structural roles. For example, the highly hydrated proteoglycans of the articular surface of joints provide a cushion to protect the underlying bone [82]. In this example, the expansion of the massive proteoglycans is limited by a collagen network of very high tensile strength that compresses without collapsing. Bone, on the other hand, resists compression even though the organic components of its connective tissue are similar to that of cartilage. It is important to note, however, that the collagen present in the articular cartilage is type II, a network-forming collagen, whereas that of bone is predominantly type I, a fibril-forming collagen [22]. Thus, the large hydrated proteoglycan (aggrecan) is constrained by the collagen network and releases water in response to compressive force. The type I collagen of bone, however, forms large, cross-linked fibers aligned in response to tensile force and in this way reinforces the strength of the hydroxyapatite mineral crystals [82].


   NUTRITIONAL INTERVENTION AGAINST LEG PROBLEMS
TOP
 SUMMARY
 DESCRIPTION OF PROBLEM
 BONE DISORDERS ASSOCIATED WITH...
 BONE DEVELOPMENT
 NUTRITIONAL INTERVENTION AGAINST...
CONCLUSIONS AND APPLICATIONS
 REFERENCES AND NOTES
 
Thousands of studies of the effects of specific nutrients on leg problems in poultry have been reported over the last 40 yr. This body of research, recently reviewed by Whitehead [83] and Oviedo-Rondon and Ferket [84], highlights the importance of the macrominerals Ca and P and their relative ratio on bone development. It has been clearly shown that vitamins D, A, C, K, and most B-vitamins are essential for optimal bone development. High levels of the S amino acids, Met and Cys, as well as the S-containing metabolite homocysteine, particularly associated with marginal vitamin B6 deficiency, are associated with lameness due to abnormal bone collagen [85].

An interesting body of work has demonstrated the effect of fatty acid nutrition on bone mineralization and mechanical properties [86, 87, 88]. Providing fats containing relatively higher levels of n-3 fatty acids to laying hens is associated with increased total n-3 fatty acids in progeny yolk lipid and reduction in progeny tibial prostaglandin E2 production. These changes are associated with increasing tibial shear force, percentage of bone ash, bone collagen pyridinium crosslinks, and diaphyseal cortical thickness in progeny bones [87]. These results add to a growing body of data linking inflammatory cytokines and other immune mediators with bone cell differentiation, both anabolic (chondrocytes and osteoblasts) and catabolic (osteoclasts) [54, 89]. For example, an acute inflammatory response initiated by E. coli lipopolysaccharide can dramatically affect bone metabolism and homeostasis, resulting in decreased tibia Ca and tibia breaking strength [90]. This is perhaps one example of the complex cellular relationships within the bone marrow, i.e., between the hematopoietic stem cells and bone marrow stromal cells of the endosteal surfaces [91], which are providing new insights into the molecular biology governing the relationship between the myeloid and osteogenic lineages [92]. Indeed, the pluripotent stem cell (CD34+ hematopoietic bone marrow cell) of red blood cells, immune cells, and osteoclasts resides near the mesenchymal precursors of bone cells (osteoblasts) [93]. In addition, osteoblasts have been shown to secrete factors that affect the development of hematopoietic stem cells – factors such as granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and interleukin-1 and interleukin-6 [93]. It would be interesting to test whether genetic selection for increased performance has exerted an effect on the common stem cell of the lymphoid and myeloid lineages to result in altered lymphoid, macrophage, and osteoclast differentiation potential [27]. This could yield the tendency to low adaptive immunity, high innate immunity, and poor bone stability phenotype seen in modern meat birds.

Figure 2Go is a micrograph from the tibia of a 14-wk-old turkey. It shows the intimate physical proximity of bone and hematopoietic tissue. Although they reside together and act in coordinated opposition in the bone, the anabolic and catabolic cells of the bone have different origins, one related more to connective tissue and adipose (chondrocytes and osteoblasts), and the other is more related to blood and immune cells (osteoclasts) [27]. The transcription factors and signaling polypeptides of these cells and their precursors are currently being described, and this research is yielding fascinating details about the regulation of bone and immune function. For example, some signaling molecules act in the differentiation of bone and immune cells, including osteoprotegrin, interferon-{gamma}, interleukin-6, tumor necrosis factor-{alpha}, and receptor activator of nuclear factor-{kappa}B ligand [54, 91, 93, 94]. These have begun to reveal the tightly regulated and highly coordinated interactions between the 2 tissues. Such studies may well provide new avenues to approach bone development and the effect of inflammation and infection on bone homeostasis.


Figure 2
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  		Figure 2. Micrograph illustrating cellular relationships in bone marrow of 14-wk-old tom turkeys. New bone (yellow) and the residual cartilage (green) within it create a niche for hematopoietic cell proliferation and differentiation. Mature bone cells (osteocytes) can be seen encased in mineralized matrix, whereas lacunae with remnants of chondrocytes are still visible at the center of bone trabeculae. Cuboidal osteoblasts line the endosteal surface and lay down osteoid for mineralization. Movat’s pentachrome, 300x.

 
An example of the interaction between immune challenge and bone homeostasis was observed recently in studies of the effect of an organic source of Zn on the response of birds to coccidiosis vaccination and challenge [95]. In these studies, the organic trace mineral source was Mintrex Zn [96] organic trace mineral, which is a chelated Zn source using 2-hydroxy-4-methylthiobutanoic acid as the organic ligand. In studies comparing this product to inorganic sources of Zn, improvements in tibia Zn deposition over that seen with Zn sulfate were observed in broilers, and the improvement in whole body Zn status was most striking following a coccidiosis challenge [95]. A recent publication by Predieri et al. [97] confirmed the increased availability of Zn from a chelate made with 2-hydroxy-4-methylthiobutanoic acid resulted in a reduction in Zn excretion from the animal.

A recent field trial by Richards et al. [98] tested a blend of organic Zn, Cu, and Mn (Mintrex P organic trace mineral [96]) for the ability to improve leg and foot problems in heavy turkeys. These turkeys were exhibiting lameness that involved pododermatitis, TD, synovitis, and varus-valgus disease. The incidence was typical of that seen in commercial turkeys, with relatively minor foot and leg problems seen early and progressing to overt lameness at 14 wk and above. The treatments in this study consisted of the existing dietary regime and the same diet containing the organic trace mineral blend. The existing regime contained supplemental inorganic trace minerals and 25-hydroxycholecalcif-erol. Birds at ages 0 to 6 wk, 6 to 12 wk, 12 to 16 wk, or 16 to 20 wk were necropsied by selecting 3 lame and 2 normal birds from each of 8 flocks per month for 7 mo. Age and weight of individual birds as well as incidence of TD, rickets, synovitis, and foot pad lesions were recorded. Tibial bones were measured for length, diameter, cortex thickness, bone breaking strength, and ash. Incidence of TD, synovitis, and foot pad lesions increased with age, as did foot pad scores, bone strength, and ash content. Lameness was positively correlated with synovitis (P < 0.05). Bone breaking strength was significantly correlated with width of cortical bone (P < 0.0001). As illustrated in Figure 3Go, the feeding of this organic source of trace minerals significantly (P < 0.05) reduced TD incidence and increased both bone breaking strength and cortical bone thickness in the heaviest birds (> 30 lb). In addition, the organic mineral treatment was also associated with a significant reduction in incidence of synovitis, incidence of foot pad lesions, and also foot pad lesion severity (data not shown). Clearly, in this case, despite the provision of Ca and P, and in the presence of 25-hydroxycholecalciferol, increasing trace mineral bioavailability was able to significantly improve the quality of structural tissues in the heaviest birds.


Figure 3
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  		Figure 3. Effect of an organic trace mineral blend (Mintrex P [96]) added to a diet containing inorganic trace minerals on incidence of tibial dyschondroplasia (TD; left axis), tibia breaking strength (left axis) and cortical bone width (right axis) in 30- to 40-lb tom turkeys. Reduction in TD and increased cortical bone deposition may have contributed to the significant increase in bone breaking strength seen with the organic trace mineral.

 

   CONCLUSIONS AND APPLICATIONS
TOP
 SUMMARY
 DESCRIPTION OF PROBLEM
 BONE DISORDERS ASSOCIATED WITH...
 BONE DEVELOPMENT
 NUTRITIONAL INTERVENTION AGAINST...
 CONCLUSIONS AND APPLICATIONS
REFERENCES AND NOTES
 
  1. Bone development in rapidly growing birds is easily disrupted by deviations in nutrient availability and environmental quality. The structual system in poultry selected for meat yield is only marginally capable of matching the growth rate of the muscle. Thus, management and nutrition must constantly be examined and improved as needed.
  2. Abnormalities in development and metabolic challenges early in life can be manifested later in lameness and poor performance. Once initiated, problems in bone ossification can lead to weakness in legs or in hock, knee, or hip joints that culminates in immobility or condemnation.
  3. There is no one cause of lameness in these birds; the problem is multifactorial. Nevertheless, changes in growth rate, management, or nutrient availability can improve structural performance, resulting in decreases in factors associated with lameness such as TD.
  4. Nutritionists need to consider trace mineral availability, particularly when feeding high levels of Ca and P. Mineral antagonisms can cause a secondary deficiency in Zn, Cu, or Mn, all of which are required for normal bone development and remodeling.


   ACKNOWLEDGMENTS
 
We would like to thank T. Applegate, associate professor, Department of Animal Sciences, Purdue University, West Lafayette, Indiana, for assistance in tibia ash measurement and data interpretation in turkey field trials.


   REFERENCES AND NOTES
TOP
 SUMMARY
 DESCRIPTION OF PROBLEM
 BONE DISORDERS ASSOCIATED WITH...
 BONE DEVELOPMENT
 NUTRITIONAL INTERVENTION AGAINST...
 CONCLUSIONS AND APPLICATIONS
 REFERENCES AND NOTES
 

  1. Lilburn, M. 1994. Skeletal growth of commercial poultry species. Poult. Sci. 73:897–903.[ISI][Medline]
  2. Vaillancourt, P., L. Ivy, J. Barnes, D. Wages, and L. Baucom. 1999. Causes of mortality in male turkeys during the last part of grow-out. Pages 87–88 in 48th West. Poult. Dis. Conf. Vancouver, Canada. AAAP, Kennett, PA.
  3. Farquharson, C. 2003. Bone growth. Pages 170–185 in Biology of Growth of Domestic Animals. C. Scanes, ed. Blackwell Publishing Co., Ames, IA.
  4. Huff, G. R., W. E. Huff, N. C. Rath, J. M. Balog, N. Anthony, and K. Nestor. 2006. Stress-induced Colibacillosis and turkey osteomyelitis complex in turkeys selected for increased body weight. Poult. Sci. 85:266–272.[Abstract/Free Full Text]
  5. Moraes, V., R. Malheiros, R. Furlan, L. Bruno, E. Malheiros, and M. Macari. 2002. Effect of environmental temperature during the first week of brooding on broiler chick body weight, viscera and bone development. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-635X2002000100003&lng=pt&nrm=iso&tlng=en Accessed Jan. 2007.
  6. van der Eerden, B., M. Karperien, and J. Wit. 2003. Systemic and local regulation of the growth plate. Endocr. Rev. 24:782–801.[Abstract/Free Full Text]
  7. Whitehead, C. C., R. H. Fleming, R. Julian, and P. Sorensen. 2003. Skeletal problems associated with selection for increased productions. Pages 29–52 in Poultry Genetics, Breeding and Biotechnology. W. Muir and S. Aggrey, ed. CABI, Wallingford, Oxfordshire, UK.
  8. Bradshaw, R., R. Kirkden, and D. Broom. 2002. A review of the aetiology and pathology of leg weakness in broilers in relation to welfare. Avian Poult. Biol. Rev. 13:45–103.
  9. Julian, R. 2005. Production and growth related disorders and other metabolic diseases of poultry — A review. Vet. J. 169:350–369.[ISI][Medline]
  10. Newman, S., and S. Leeson. 1998. Effect of housing birds in cages or an aviary system on bone characteristics. Poult. Sci. 77:1492–1496.[Abstract/Free Full Text]
  11. Leeson, S., G. Diaz, and J. Summers. 1995. Skeletal disorders. Pages 124–175 in Poultry Metabolic Disorders and Mycotoxins. Univ. Books, Guelph, Ontario, Canada.
  12. Garret, I., R. Boyce, L. Oreffo, J. Bonewald, J. Poser, and G. Mundy. 1990. Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J. Clin. Invest. 85:632–639.[ISI][Medline]
  13. Mayne, R. 2005. A review of the aetiology and possible causative factors of foot pad dermatitis in growing turkeys and broilers. World’s Poult. Sci. J. 61:256–267.[ISI]
  14. Leach, R. J., and M. Nesheim. 1965. Nutritional, genetic and morphological studies of an abnormal cartilage formation in young chicks. J. Nutr. 86:236–244.[Abstract/Free Full Text]
  15. Pines, M., A. Hasdai, and E. Monsonego-Ornan. 2005. Tibial dyschondroplasia—tools, new insights and future prospects. World’s Poult. Sci. J. 61:285–297.[ISI]
  16. Rath, N. C., W. E. Huff, J. M. Balog, G. Bayyari, and R. Reddy. 1997. Matrix metalloproteinase activities in avian tibial dyschondroplasia. Poult. Sci. 76:501–505.[Abstract/Free Full Text]
  17. Rath, N. C., M. Richards, G. R. Huff, W. E. Huff, and J. M. Balog. 2005. Changes in the tibial growth plates of chickens with thiram-induced dyschondroplasia. J. Comp. Pathol. 133:41–52.[ISI][Medline]
  18. Farquharson, C., and D. Jefferies. 2000. Chondrocytes and longitudinal bone growth: The development of tibial dyschondroplasia. Poult. Sci. 79:994–1004.[Abstract/Free Full Text]
  19. Tselepis, C., A. P. Kwan, D. Thornton, and J. Sheehan. 2000. The biochemical characterization of aggrecan from normal and tibial-dyschondroplastic chicken growth-plate cartilage. Biochem. J. 351:517–525.[ISI][Medline]
  20. Kirsch, T., H.-D. Nah, I. M. Shapiro, and M. Pacifici. 1997. Regulated production of mineralization-competent matrix vesicles in hypertrophic chondrocytes. J. Cell. Biol. 137:1149–1160.[Abstract/Free Full Text]
  21. Palmer, N. 1993. Bone diseases of unknown cause. Pages 118–125 in Bone Diseases of Unknown Cause. Vol. 1. K. Jubb, P. Kennedy, and N. Palmer, ed. Acad. Press, San Diego, CA.
  22. Orth, M. W. 1999. The regulation of growth plate cartilage turnover. J. Anim. Sci. 77(Suppl. 2):183–189.[Abstract/Free Full Text]
  23. Bridges, C., and E. Harris. 1988. Experimentally induced cartilaginous fractures (osteochondritis dissecans) in foals fed low-copper diets. J Am. Vet. Med. Assoc. 193:215–221.[ISI][Medline]
  24. Hargest, T., R. M. Leach, and C. V. Gay. 1985. Avian tibial dyschondroplasia. I. Ultrastructure. Am. J. Vet. Pathol. 119:175–190.
  25. Thorp, B. H. 1988. Relationship between the rate of longitudinal bone growth and physeal thickness in the growing fowl. Res. Vet. Sci. 45:83–85.[ISI][Medline]
  26. Kember, N. F., and H. A. Sissons. 1976. Quantitative histology of the human growth plate. J. Bone Joint Surg. 58B:426–435.
  27. Gilbert, S. F. 1997. Early vertebrate development: Mesoderm and endoderm. Pages 341–357 in Developmental Biology. 5th ed. Sinauer Assoc. Inc., Sunderland, MA.
  28. Bain, S. D., and B. A. Watkins. 1993. Local modulation of skeletal growth and bone modeling in poultry. J. Nutr. 123:317–322.[Abstract/Free Full Text]
  29. Marks, S. C., Jr., and S. N. Popoff. 1988. Bone cell biology: The regulation of development, structure, and function in the skeleton. Am. J. Anat. 183:1–44.[Medline]
  30. Roberson, K. D., R. Klunzinger, R. Charbeneau, and M. W. Orth. 2005. Evaluation of phytase concentration needed for growing-finishing commercial turkey toms. Br. Poult. Sci. 46:470–477.[ISI][Medline]
  31. Rath, N. C., G. R. Huff, W. Huff, and J. M. Balog. 2000. Factors regulating bone maturity and strength in poultry. Poult. Sci. 79:1024–1032.[Abstract/Free Full Text]
  32. Tselepis, C., J. A. Hoyland, R. E. Barber, B. H. Thorp, and A. P. Kwan. 1996. Expression and distribution of cartilage matrix macromolecules in avian tibial dyschondroplasia. Avian Pathol. 25:305–324.[Medline]
  33. Brighton, C. T. 1984. The growth plate. Orthop. Clin. North Am. 15:571–595.[ISI][Medline]
  34. Denhardt, D. T., M. Noda, A. W. O’Regan, D. Pavlin, and J. S. Berman. 2001. Osteopontin as a means to cope with environmental insults: Regulation of inflammation, tissue remodeling, and cell survival. J. Clin. Invest. 107:1055–1061.[ISI][Medline]
  35. Reddi, A. H. 2000. Initiation and promotion of endochondral bone formation by bone morphogenetic proteins: Potential implications for avian tibial dyschondroplasia. Poult. Sci. 79:978–981.[Abstract/Free Full Text]
  36. Wu, L. N., Y. Ishikawa, B. R. Genge, T. Sampath, T. Kuber, and R. E. Wuthier. 1997. Effect of osteogenic protein-1 on the development and mineralization of primary cultures of avian growth plate chondrocytes: Modulation by retinoic acid. J. Cell. Biochem. 67:498–513.[ISI][Medline]
  37. St-Jacques, B., M. Hammerschmidt, and A. P. McMahon. 1999. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev. 13:2072–2086.[Abstract/Free Full Text]
  38. Wu, L. N., M. Lu, B. R. Gengee, G. Y. Guo, D. Nie, and R. E. Wuthier. 2002. Discovery of sonic hedgehog expression in postnatal growth plate chondrocytes: Differential regulation of sonic and Indian hedgehog by retinoic acid. J. Cell. Biochem. 87:173–187.[ISI][Medline]
  39. Velleman, S. G. 2000. The role of the extracellular matrix in skeletal development. Poult. Sci. 79:985–989.[Abstract/Free Full Text]
  40. Colnot, C. 2005. Cellular and molecular interactions regulating skeletogenesis. J. Cell. Biochem. 95:688–697.[ISI][Medline]
  41. Wuthier, R. E. 1975. Lipid composition of isolated epiphyseal cartilage cells, membranes and matrix vesicles. Biochim. Biophys. Acta 409:128–143.[Medline]
  42. Wuthier, R. E., and S. Gore. 1977. Partition of inorganic ions and phospholipids in isolated cell, membrane and matrix vesicle fractions: Evidence of Ca-Pi-acidic phospholipid complexes. Calcif. Tissue Int. 24:163–171.
  43. Boskey, A. L. 1996. Matrix proteins and mineralization: An overview. Connect. Tissue Res. 35:357–363.[ISI][Medline]
  44. Wuthier, R. E. 1976. Lipids of matrix vesicles. Fed Proc. 35:117–121.[ISI][Medline]
  45. Wu, L. N., B. R. Genge, and R. E. Wuthier. 1991. Association between proteoglycans and matrix vesicles in the extracellular matrix of growth plate cartilage. J. Biol. Chem. 266:1187–1194.[Abstract/Free Full Text]
  46. Litchfield, T. M., Y. Ishikawa, L. N. Wu, R. E. Wuthier, and G. R. Sauer. 1998. Effect of metal ions on calcifying growth plate cartilage chondrocytes. Calcif. Tissue Int. 62:341–349.[ISI][Medline]
  47. Haumont, S. 1960. Distribution of zinc in bone tissue. J Histochem. Cytochem. 9:141–145.[ISI]
  48. Watkins, B. A., C. L. Shen, J. P. McMurtry, H. Xu, S. D. Bain, G. D. Allen, and M. F. Seifert. 1997. Dietary lipids modulate bone prostaglandin E2, insulin-like growth factor-I concentration and formation rate in chicks. J. Nutr. 127:1084–1091.[Abstract/Free Full Text]
  49. Arsenault, A. L. 1988. Crystal-collagen relationships in calcified turkey leg tendons visualized by selected-area dark field electron microscopy. Calcif. Tissue Int. 43:202–212.[ISI][Medline]
  50. Arsenault, A. L., B. W. Frankland, and F. P. Ottensmeyer. 1991. Vecorial sequence of mineralization in the turkey leg tendon determined by electron microscopic imaging. Calcif. Tissue Int. 48:46–55.[ISI][Medline]
  51. Berthet-Colominas, C., A. Miller, and S. W. White. 1979. Structural study of the calcifying collagen in turkey leg tendons. J. Mol. Biol. 134:431–445.[ISI][Medline]
  52. Landis, W. J. 1986. A study of calcification in the leg tendons from the domestic turkey. Ultrastruct. Mol. Struct. Res. 94:217–238.
  53. Olsen, B., A. Reginato, and W. Wang. 2000. Bone development. Annu. Rev. Cell. Dev. Biol. 16:191–220.[ISI][Medline]
  54. Murakami, S., H. Akiyama, and B. de Crombrugghe. 2004. Development of bone and cartilage. Pages 133–in Oxford Monographs on Medical Genetics. C. Epstein, R. Erickson, and B. Wynshaw, ed. Oxford Univ. Press, New York, NY.
  55. Rath, N. C., J. M. Balog, W. E. Huff, G. R. Huff, G. B. Kukarni, and J. F. Tierce. 1999. Comparative differences in the composition and biomechanical properties of tibiae of seven- and seventy-two-week-old male and female broiler breeder chickens. Poult. Sci. 78:1232–1239.[Abstract/Free Full Text]
  56. Sauer, G. R., L. N. Wu, M. Iijima, and R. E. Wuthier. 1997. The influence of trace elements on calcium phosphate formation by matrix vesicles. J. Inorg. Biochem. 65:57–65.[ISI][Medline]
  57. Carlton, W. W., and W. Henderson. 1964. Skeletal lesions in experimental copper-deficiency in chickens. Avian Dis. 8:48–55.[ISI]
  58. Wu, L. N., T. Yoshimori, B. R. Genge, G. R. Sauer, T. Kirsch, Y. Ishikawa, and R. E. Wuthier. 1993. Characterization of the nucleational core complex responsible for mineral induction by growth plate cartilage matrix vesicles. J. Biol. Chem. 268:25084–25094.[Abstract/Free Full Text]
  59. Starcher, B. C., C. H. Hill, and J. G. Madaras. 1980. Effect of zinc deficiency on bone collagenase and collagen turnover. J. Nutr. 110:2095–2102.[Abstract/Free Full Text]
  60. Nie, D., Y. Ishikawa, T. Yoshimori, R. E. Wuthier, and L. N. Wu. 1998. Retinoic acid treatment elevates matrix metalloproteinase-2 protein and mRNA levels in avian growth plate chondrocyte cultures. J. Cell. Biochem. 68:90–99.[ISI][Medline]
  61. Sauer, G. R., D. M. Smith, M. Cahalane, L. N. Wu, and R. E. Wuthier. 2003. Intracellular zinc fluxes associated with apoptosis in growth plate chondrocytes. J. Cell. Biochem. 88:954–969.[ISI][Medline]
  62. Fraker, P. J. 2005. Roles for cell death in zinc deficiency. J. Nutr. 135:359–362.[Abstract/Free Full Text]
  63. Hatori, M., K. J. Klatte, C. C. Teixeira, and I. M. Shapiro. 1995. End labeling studies of fragmented DNA in the avian growth plate: Evidence of apoptosis in terminally differentiated chondrocytes. J. Bone Min. Res. 10:1960–1968.[ISI][Medline]
  64. Ho, E., C. Courtemanche, and B. Ames. 2003. Zinc deficiency induces oxidative DNA damage and increases p53 expression in human lung fibroblasts. J. Nutr. 133:2543–2548.[Abstract/Free Full Text]
  65. Miao, D., H. Liu, P. Plut, M. Niu, R. Huo, D. Goltzman, and J. E. Henderson. 2004. Impaired endochondral bone development and osteopenia in Gli2-deficient mice. Exp. Cell Res. 294:210–222.[ISI][Medline]
  66. Underwood, E., and N. Suttle. 2001. The Mineral Nutrition of Livestock. CABI Publishing, London, UK.
  67. Leeson, S. 2005. Trace mineral requirements of poultry—validity of the NRC recommendations. Pages 107–118 in Redefining Mineral Nutrition. J. Taylor-Pickard and L. Tucker, ed. Nottingham Univ. Press, UK.
  68. Tamim, N., and R. Angel. 2003. Phytate phosphorous hydrolysis as influenced by dietary calcium and miro-mineral source in broiler diets. J. Agric. Food Chem. 51:4687–4693.[ISI][Medline]
  69. Bremner, I., and J. Beattie. 1995. Copper and zinc metabolism in health and disease: Speciation and interactions. Proc. Nutr. Soc. 54:489–499.[ISI][Medline]
  70. Wedekind, K., E. Titgemeyer, A. Twardock, and D. Baker. 1991. Phosphorus, but not calcium, affects manganese absorption and turnover in chicks. J. Nutr. 121:1776–1786.[Abstract/Free Full Text]
  71. Carlton, W.W., and W. Henderson. 1965. Studies in chickens fed a copper-deficient diet supplemented with ascorbic acid, reserpine and diethylstilbestrol. J. Nutr. 85:67–72.[Abstract/Free Full Text]
  72. NRC. 1994. Nutrient Requirements of Poultry. 9th rev. ed. J. L. Sell, F. Kratzer, J. Latshaw, S. Leeson, E. Moran, C. Parsons, and P. Waldroup, ed. Natl. Acad. Press, Washington, DC.
  73. Leeson, S., and J. Summers. 2001. Nutrition of the Chicken. 4th ed. Univ. Books, Guelph, Ontario, Canada.
  74. Cao, J., P. Henry, R. Guo, R. Holwerda, J. Toth, R. Littell, R. Miles, and C. Ammerman. 2000. Chemical characteristics and relative bioavailability of supplemental organic zinc sources for poultry and ruminants. J. Anim. Sci. 78:2039–2054.[Abstract/Free Full Text]
  75. Paik, I., J. Seo, J. Um, M. Chang, and B. Lee. 1999. Effects of supplementary copper-chelate on the performance and cholesterol level in plasma and breast muscle of broiler chickens. Asian-Australas. J. Anim. Sci. 12:794–798.
  76. Wedekind, K., A. Hortin, and D. Baker. 1992. Methodology for assessing zinc bioavailability: Efficacy estimates for zinc-methionine, zinc sulfate, and zinc oxide. J. Anim. Sci. 70:178–187.[Abstract]
  77. Caskey, C., W. Gallup, and L. Norris. 1939. The need for manganese in the bone development of the chick. J. Nutr. 17:407–410.[Free Full Text]
  78. Kienholz, E., M. Sunde, and W. Hoekstra. 1964. Influences of dietary zinc, calcium and vitamin D for hens on zinc content of tissues and eggs and on bone composition. Poult. Sci. 43:667–675.[ISI]
  79. Lyons, M., and W. Insko Jr. 1937. Chondrodystrophy in the chick embryo produced by a mineral deficiency in the diet of the hen. Science 80:328–330.
  80. Baker, D., and N. Augspurger. 2002. Means of improving phosphorus utilization in poultry and swine. Pages 97–114 in Proc. West. Poult. Dis. Conf., Edmonton, Alberta, Canada. AAAP, Kennett, PA.
  81. Kornegay, E. 2001. Digestion of phosphorus and other nutrients: The role of phytases and factors influencing their activity. Pages 237–271 in Enzymes in Farm Animal Nutrition. M. Bedford and G. Partridge, ed. CABI Publishing, Oxon, UK.
  82. Fawcett, D. W. 1994. Bone. Pages 194–229 in A Textbook of Histology. 12th ed. Chapman and Hall, New York, NY.
  83. Whitehead, C. C. 2002. Nutrition and poultry welfare. World’s Poult. Sci. J. 58:349–356.[ISI]
  84. Oviedo-Rondon, E., and P. R. Ferket. 2005. Nutritional factors that affect leg problems in meat poultry: A review. Pages 58–88 in Proc. Ann. Carolina Poult. Nutr. Conf., Research Triangle Park, NC. North Carolina State Univ., Raleigh.
  85. Masse, P., A. Boskey, I. Ziv, P. Hauschka, S. Donovan, D. Howell, and E. Cole. 2003. Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model. http://www.biomedcentral.com/1471-2474/4/2 Accessed Jan. 2007.
  86. Watkins, B., Y. Li, K. Allen, W. Hoffmann, and M. Sieifert. 2000. Dietary ratio of (n-6):(n-3) polyunsaturated acids alters the fatty acid composition of bone compartments and biomarkers of bone formation in rats. J. Nutr. 130:2274–2284.[Abstract/Free Full Text]
  87. Liu, D. 2000. The effects of dietary lipids on bone chemical, mechanical, and histological properties in Japanese quail (Coturnix c. japonica). Pages 1–148 in Animal and Poultry Sciences. Virginia Tech., Blacksburg.
  88. Liu, D., H. P. Veit, and D. M. Denbow. 2004. Effects of long-term dietary lipids on mature bone mineral content, collagen, crosslinks, and prostaglandin E2 production in Japanese quail. Poult. Sci. 83:1876–1883.[Abstract/Free Full Text]
  89. Horowitz, M., A. Bothwell, D. Hesslein, D. Pflugh, and D. Schatz. 2005. B cells and osteoblast and osteoclast development. Immun. Rev. 208:141–153.[Medline]
  90. Mireles, A., S. Kim, and K. Klasing. 2005. An acute inflammatory response alters bone homeostasis, body composition, and the humoral immune response of broiler chickens. Poult. Sci. 84:553–560.[Abstract/Free Full Text]
  91. Taichman, R., M. Reilly, R. Verma, and S. Emerson. 1997. Augmented production of interleukin-6 by normal human osteoblasts in response to CD34+ hematopoietic bone marrow cells in vitro. Blood 89:1165–1172.[Abstract/Free Full Text]
  92. Taichman, R. 2005. Blood and bone: Two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105:2631–2639.[Abstract/Free Full Text]
  93. Taichman, R., and S. Emerson. 1998. The role of osteoblasts in the hematopoietic microenvironment. Stem Cells 16:7–15.[Abstract/Free Full Text]
  94. Manolagas, S. 1998. The role of IL-6 type cytokines and their receptors in bone. Ann. N. Y. Acad. Sci. 840:194–204.[Abstract/Free Full Text]
  95. Dibner, J. 2005. Early nutrition of zinc and copper in chicks and poults: Impact on growth and immune function. Pages 23–32 in Proc. Mid-Atl. Nutr. Conf. Timonium, MD.
  96. Mintrex is a trademark of Novus Int. Inc. and is registered in the United States and other countries.
  97. Predieri, G., L. Elviri, M. Tegoni, I. Zagnoni, E. Cinti, G. Biagi, S. Ferruzza, and G. Leonardi. 2005. Metal chelates of 2-hydroxy-4-methylthiobutanoic acid in animal feeding. Part 2: Further characterizations, in vitro and in vivo investigations. J. Inorg. Biochem. 99:627–636.[ISI][Medline]
  98. Richards, J., M. Quiroz, W. Williams, and J. Dibner. 2006. Benefit of MINTREX P blend of organic trace minerals on breaking strength, ash content, tibial dyschondroplasia, synovitis and pododermatitis in heavy weight tom turkeys. Poult. Sci. 85:30 (Abstr.)




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