Which Animal Has The Least Dense Bone Structure?

• Journal List
• Comp Med
• v.61(1); 2011 Feb
• PMC3060425

Comp Med. 2011 Feb; 61(1): 76–85.

Published online 2011 February.

Comparative Bone Anatomy of Commonly Used Laboratory Animals: Implications for Drug Discovery

Received 2010 Jun 22; Revised 2010 Aug ix; Accepted 2010 Oct 3.

Abstract

To accommodate functional demands, the composition and arrangement of the skeleton differ amongst species. Microcomputed tomography has improved our ability markedly to appraise structural parameters of cortical and cancellous bone. The electric current study describes differences in cortical and cancellous bone structure, os mineral density, and morphology (geometry) at the proximal femur, proximal femoral diaphysis, lumbar vertebrae, and mandible in mice, rats, rabbits, dogs, and nonhuman primates. This work enhances our agreement of bone gross and microanatomy across lab brute species and likely will enable scientists to select the about appropriate species and relevant bone sites for research involving skeleton. We evaluated the gross and microanatomy of the femora caput and cervix, lumbar spine, and mandible and parameters of cancellous bone, including trabecular number, thickness, plate separation, and connectivity amid species. The skeletal characteristics of rabbits, including a very brusque femoral neck and modest amounts of cancellous bone at the femoral neck, vertebral body, and mandible, seem to brand this species the least desirable for preclinical enquiry of human bone physiology; in comparison, nonhuman primates seem the most applicable for extrapolation of data to humans. However, rodent (peculiarly rat) models are extremely useful for conducting basic research involving the skeleton and stand for reliable and affordable alternatives to dogs and nonhuman primates. Radiology and microcomputed tomography allow for reliable evaluation of os morphology, microarchitecture, and bone mineral density in preclinical and clinical environments.

Abbreviations: mCT, microcomputed tomography

The skeleton is a mechanically optimized biological system and its composition and organisation accommodate to the functional demands placed on it. In general, the mechanical properties of os are determined by bone geometry, mineral density, and structure.^{6,ix,xvi,64,69} Hydroxyl apatite provides most of the forcefulness and stiffness to the skeleton and permits the use of radiologic technologies to assess bone mass and structure. New technologies including dual-energy Ten-ray absorbtiometry, quantitative computed tomography, and microcomputed tomography (mCT) have been adult to assess the gross and microanatomy of the skeleton during wellness and illness. Using noninvasive methodology to describe os anatomy and structure has wide awarding in several scientific disciplines, including medical and pharmaceutical research, beast wellness and meat industry, and biologic and forensic anthropology.^22,46,52 The electric current study focuses on using radiography and mCT to draw major skeletal differences between several normally used laboratory brute species. These differences manifest in the concrete characteristics of their skeletons, including their morphology and dimensions, but differences in growth rates and laboratory weather might as well influence cortical and cancellous bone structures also every bit the biochemical composition of bone.^ane,three,43 Using Wessler's definition⁷⁰ of an brute model, Kalu³⁷ has suggested that the convenience, relevance, and appropriateness (compatibility to humans) of particular animal models should be considered when deciding what laboratory animals to use to written report the skeletal effects of novel therapeutics aimed to prevent or cure osteoporosis. Kalu'due south suggestions³⁶ likely tin can exist applied to all areas of pharmaceutical research involving animals. Regardless of the animal model or species is used to report intended or undesired skeletal furnishings of novel compounds, the decreased physical activity of animals under laboratory conditions and differences in skeletal mechanical backdrop between humans (bipeds) and lab animals (quadrupeds) should e'er be taken into business relationship.^{12,18,49,51,55,61} Forth these lines, the Food and Drug Administration requires that novel therapies in osteoporosis inquiry must be tested both in rodents (preferably rats) every bit well every bit a large creature model.⁶¹ This requirement is based on the fact that growth plates in rodents remain open throughout their life span, allowing bone growth and modeling to go along, resembling immature skeleton.^28,71 However, the reason for using a second species in preclinical skeletal research is the lack of the Haversian system in rodents; therefore, other species, including dogs, nonhuman primates, pigs, and sheep should be considered.^36,49,55 Because the skeletal organization is highly responsive to mechanical loads that influence bone geometry and structure also equally the charge per unit of bone remodeling, the structural properties of cancellous and cortical bone at several skeletal sites with different mechanical properties, such every bit the femoral neck, vertebrae, and mandible, should be assessed.^{five,9,10,17,53,63,67}

Past using radiology and mCT to depict major skeletal differences amid common laboratory animals, nosotros promise to help investigators to selection the right species when conducting animal studies aiming to address issues associated with skeletal health. In the nowadays written report, we compared bone properties at 3 skeletal sites with dissimilar mechanical properties—the proximal femur, lumbar vertebrae, and mandible—in laboratory mice, rats, rabbits, dogs, and cynomolgus macaques.

Materials and Methods

Bone samples.

Experimentation using laboratory animals including mice (Mus musculus, C57BL6), rats (Rattus norvegicus, CD/SD), rabbits (Oryctolagus cuniculus, New Zealand white), dogs (Canis familiaris, beagle), and nonhuman primates (Macaca fascicularis, Mauritian cynomolgus macaque) is a mandatory footstep regulated by the Food and Drug Administration for each Investigational New Drug Application that is aimed to minimize potential damage of novel drug candidates to patients that participate in the clinical trials. The safe preclinical studies in laboratory species require but pocket-size samples of bone tissue from that used for pathologic test; the vast majority of the skeleton frequently is discarded without use in further research. To evaluate the bone morphology and structure of cancellous and cortical bone at the proximal femur, lumbar vertebrae, and mandible, we nerveless the bones from euthanized animals that were used in diverse preclinical studies. Nosotros used just animals that received vehicle but in these previous studies to minimize the chance of drug-associated changes in os structure and bone mineral density. All animals in the original studies were maintained in an AAALAC-accredited research facility, and the original animal procedures were IACUC-approved and conformed to the Guide for the Intendance and Use of Laboratory Animals.²⁶ The right femurs, lumbar vertebrae (50₄, Fifty₅), and mandibles were collected immediately after necropsy, cleaned of soft tissues, and placed in 10% formalin for 24 h, transferred to 70% alcohol, and stored at 4 °C before being used for Ten-ray and mCT analyses. The numbers of animals used in the current study were 6 male person and 6 female person mice (age, 5 mo); 6 male and 6 female person rats (age, 5 mo); 4 male person and 4 female rabbits (age, 16 mo onetime); 4 male and 3 female dogs (historic period, 3.5 to 4 y quondam); 2 male and iii female person cynomolgus macaques (age, 4 y) and 1 male person cynomolgus macaque (age, five y). Therefore, all animals from which bones were nerveless had reached sexual maturity before they were used in the original studies, and radiography confirmed sealed growth plates in macaques, dogs, and rabbits.

X-ray and mCT measurements.

Femurs.

The femurs used for mCT assay in this study were nerveless from animals that were euthanized co-ordinate to their respective written report protocols. Whole femurs were harvested at necropsy, cleaned of soft tissue, and fixed in 10% formalin. Proximal femurs were radiographed by using a digital X-ray system (Faxitron 10-ray, Wheeling, IL) with the following manufacturer-recommended settings according to the size of the bone samples: mouse: ten southward at 25 kV; rat: 12 s at thirty kV; rabbit: 12 s at 35 kV; canis familiaris: 12 s at 35 kV and macaques: 12 s at 35 kV. Radiographic images were used to assess the gross anatomy of the region of interest for every animal used in this study. Because large differences in size and morphology of the skeletal areas between species prevented use of the same region of interest across species, we outset ran 'scout' mCT images for each anatomic site and for each species to ensure that nosotros could consistently and reproducibly browse and analyze detail target regions in each species and that size of the target picked permitted meaningful analysis of cancellous bone structure. At the aforementioned time, the optimal thickness and resolution parameters were determined for each species and each anatomic location that conformed to the limits of the imaging system and written report goals.^xx This optimization ensured that trabecular thickness and number could be captured, measured, and analyzed when the number and thickness of slices chosen to capture bone construction at the target region in each species assessed in this written report were applied. Results from the airplane pilot studies and then were applied to capture the exact cortical or cancellous os areas that we attempted to mensurate past using the optimal mCT settings.²⁰

Femurs were analyzed by using the VivaCT forty mCT organization (Scanco Medical, Bassersdorf, Switzerland) with the post-obit settings: mouse, 45 kVp at 88 µA at loftier resolution (10 µm); rat, 55 kVp at 109 µA at high resolution (12.5 µm); rabbit, 55 kVp at 109 µA at loftier resolution (15 µm); domestic dog, 70 kVp at 85 µA at high resolution (19 µm); and NHP, 70 kVp at 85 µA at high resolution (19 µm). Cancellous bone parameters at the femoral cervix and head were analyzed; these parameters included tissue volume (bone and os marrow combined), bone book, bone book: tissue volume ratio, trabecular number, trabecular thickness, trabecular separation (distance between individual trabeculae), trabecular connectivity (the number of times per unit of measurement surface area that side by side trabeculae touch each other) and bone mineral density (g Ca²⁺/cm²). Cortical bone parameters were analyzed at femoral proximal diaphysis and included tissue volume, os volume, os volume:tissue book ratio, marrow volume, and cortical thickness. A unmarried sample of human proximal femur was obtained through a tissue banking company and was used only as a standard for comparison. Considering of large differences in the size and shape of the proximal femur among species, the setup presented in Tabular array one was applied to analyze cancellous and cortical bone parameters by using mCT.

Table 1.

mCT parameters used to collect and analyze cortical and cancellous os structure and os mineral density

		Mouse	Rat	Rabbit	Canine	Cynomolgus macaque
Mid-diaphysis
	No. of slices	20	20	xx	xx	20
	Thickness (mm)	0.21	0.25	0.thirty	0.38	0.38
	Resolution (µm)	10.5	12.5	15.0	19.0	19.0
Femoral head
	No. of slices	25	fifty	25	50	50
	Thickness (mm)	0.03	0.65	0.thirty	0.95	0.95
	Resolution (µm)	10.5	12.five	fifteen.0	19.0	19.0
Femoral cervix
	No. of slices	25	50	25	fifty	50
	Thickness (mm)	0.03	0.65	0.xxx	0.95	0.95
	Resolution (µm)	10.5	12.5	15.0	xix.0	19.0

Lumbar vertebrae.

L_iv and 50₅ were collected at necropsy and carefully cleaned of soft tissue; iii to 5 d afterwards, only Fifty₄ vertebra from each animal enrolled in the study was radiographed by using a digital X-ray organisation (Faxitron Ten-Ray LLC, Wheeling, IL) at the same settings described earlier for femurs. Simply cancellous bone parameters were analyzed at vertebral bodies and included tissue book, os volume, tissue book: os volume ratio, trabecular number, trabecular thickness, trabecular separation, trabecular connectivity, and bone mineral density. Due to their very thin vertebral bodies which contains very little to no cancellous os, the region of interest for rabbit lumbar vertebrae differed from that of other species and was placed at the lesser of the lumbar vertebral body, which provides sufficient cancellous bone for mCT measurements.

Mandibles.

The right mandibles were collected at necropsy and carefully cleaned of soft tissue; iii to 5 d later the mandibles were radiographed past using a digital X-ray system (Faxitron X-Ray, Wheeling, IL) at the same settings described earlier for femurs. Cancellous os parameters were analyzed at mandibular bodies and included but the area beneath the first and second molars. Connective tissue surrounding roots of the kickoff and second molars and cortical bone shell were not included in the analyses. The post-obit parameters were evaluated by mCT: tissue book, bone book, bone book: tissue volume ratio, trabecular number, trabecular thickness, trabecular separation, trabecular connectivity, and bone mineral density.

Statistical analysis

Statistical analyses of interspecies differences were not carried out due to large variations in size and shape of the bones between species, relatively small sample size, and employ of both genders in each species analyzed. The results obtained from all subjects of a particular species were used (regardless of sex) to generate summary information, reported as mean ± 1 SD.

Results

Femur.

The gross anatomy of the human being proximal femur has singled-out dissimilarity from the laboratory species. The nigh obvious distinctions included the angle between the diaphyseal shaft and femoral neck, the length and width of the femoral cervix, and size and shape of the femoral head (Effigy one).

Radiographic images of the femoral proximal diaphysis captured by digital radiography from human, nonhuman primate, dog, rabbit, rat, and mouse. The human sample was used for reference only. The angle between the femoral shaft and the femoral neck is shown in green. Dotted blue lines and associated numbers signal the sites at the proximal femur where structural parameters were measured by mCT: i, femoral head; 2, femoral neck; and 3, proximal femoral diaphysis.

Femoral caput.

Results from mCT analyses of the cancellous bone at the femoral caput provide values for cancellous bone book (in mm³) in cynomolgus macaques (43.96 ± 5.03), dogs (59.72 ± x.87), rabbits (3.22 ± 0.58), rats (two.59 ± 0.xc) and mice (0.19 ± 0.06; Tables 2 to ​ 6, Figures 2 to ​ 6). The ratio of os volume to tissue book ranged from 0.77 ± 0.12 and 0.74 ± 0.06 in mice and rats, equally compared with 0.58 ± 0.04 in rabbits, 0.37 ± 0.05 in dogs, and 0.36 ± 0.05 in cynomolgus macaques. Trabecular number (per mm) was two.70 ± 0.27 in cynomolgus macaques, 3.58 ± 0.14 in dogs, 3.83 ± 0.65 in rabbits, 5.58 ± 0.54 in rats, and 6.16 ± 1.55 in mice. Trabecular thickness was fairly consistent amid species and ranged from 0.10 μm in dogs to 0.15 μm in rabbits. Every bit a effect, trabecular connectivity was high in mice, followed by rats and rabbits, dogs, and cynomolgus macaques. Mineral density of cancellous os at the femoral head was like among all species involved in this written report.

Table two.

Cancellous and cortical bone parameters obtained from cynomolgus macaques by using mCT

	Femoral caput	Femoral cervix	Proximal diaphysis	Lumbar vertebrae	Mandible
Tissue volume (mm3)	124.67 ± 33.22	59.25 ± 21.84	355.9 ± 83.4	72.42 ± 34.iii	8.95 ± 0.31
Os volume (mm3)	43.96 ± five.03	17.93 ± 4.25	176.0 ± 37.vii	8.thirteen ± 1.43	5.xxx ± 1.20
Bone volume:tissue volume (ratio)	0.36 ± 0.05	0.32 ± 0.08	0.50 ± 0.03	0.12 ± 0.03	0.59 ± 0.14
No. of trabeculae (per mm)	ii.70 ± 0.27	2.04 ± 0.23	non done	one.89 ± 0.39	ii.36 ± 0.39
Trabecular thickness (μm)	0.xiv ± 0.02	0.15 ± 0.02	non done	0.06 ± 0.004	0.25 ± 0.05
Trabecular separation (μm)	0.24 ± 0.04	0.34 ± 0.08	not done	0.49 ± 0.1	0.18 ± 0.09
Trabecular connectivity (per mm3)	63.44 ± xix.05	23.4 ± 6.viii	non washed	lxxx.6 ± 34.three	31.69 ± 13.16
Bone mineral density (g/cmii)	816.8 ± 14.8	823.half-dozen ± 17.four	19.v ± two.viii	814.2 ± xix.eight	844.iii ± 29.3
Cortical thickness (mm)	not done	non done	1041.0 ± 17.viii	non washed	not washed
Marrow volume (mmthree)	not done	not done	179.9 ± 47.vii	not washed	not done

Table 6.

Cortical and cancellous bone parameters obtained from mice by using mCT

	Femoral head	Femoral cervix	Proximal diaphysis	Lumbar vertebrae	Mandible
Tissue volume (mm3)	0.25 ± 0.06	0.08 ± 0.02	0.56 ± 0.07	0.77 ± 0.15	0.xi ± 0.00
Bone book (mmthree)	0.19 ± 0.06	0.05 ± 0.01	0.22 ± 0.04	0.17 ± 0.03	0.08 ± 0.01
Bone volume:tissue book (ratio)	0.77 ± 0.12	0.62 ± 0.05	0.38 ± 0.03	0.22 ± 0.03	0.69 ± 0.11
No. of trabeculae (per mm)	six.16 ± 1.55	viii.53 ± 0.76	not done	5.98 ± 0.49	5.44 ± 0.47
Trabecular thickness (μm)	0.thirteen ± 0.05	0.13 ± 0.05	not washed	0.04 ± 0.003	0.xiii ± 0.02
Trabecular separation (μm)	0.04 ± 0.01	0.04 ± 0.003	not done	0.xiii ± 0.02	0.06 ± 0.02
Trabecular connectivity (per mm3)	247.5 ± 127.5	482.v ± 127.5	not washed	541.5 ± 91.0	62.76 ± 33.36
Os mineral density (g/cm2)	898.five ± 85.iv	973.7 ± 36.ix	1206.four ± 24.v	845.three ± 10.7	1286.9 ± 62.vi
Cortical thickness (mm)	non done	not done	0.23 ± 0.03	non done	not done
Marrow book (mmiii)	non washed	not done	0.35 ± 0.3	not done	not done

2D (black) and 3D (blue) images of the femoral caput obtained past mCT.

Radiographs of the mandible captured by (A) digital radiography and (B) 2D and (C) 3D mCT images of the cross-sectional areas made through the first or second molar as indicated past the dotted line. (D) Cancellous bone parameters were measured in the areas beneath the first or 2nd molar indicated by the ruby squares.

Table 4.

Cancellous and cortical bone parameters obtained from rabbits past using mCT

	Femoral head	Femoral neck	Proximal diaphysis	Lumbar vertebrae	Mandible
Tissue volume (mmiii)	5.60 ± one.19	xi.79 ± ane.56	156.8 ± nine.8	half dozen.96 ± 0.46	ane.00 ± 0.03
Bone book (mm3)	three.22 ± 0.58	3.44 ± ane.02	59.7 ± ii.9	0.67 ± 0.26	0.46 ± 0.17
Bone volume:tissue book (ratio)	0.58 ± 0.04	0.29 ± 0.07	0.38 ± 0.02	0.24 ± 0.04	0.46 ± 0.17
No. of trabeculae (per mm)	3.83 ± 0.65	2.28 ± 0.35	not done	2.68 ± 0.21	2.fifteen ± 0.53
Trabecular thickness (μm)	0.xv ± 0.02	0.xv ± 0.02	non done	0.09 ± 0.01	0.21 ± 0.04
Trabecular separation (μm)	0.11 ± 0.02	0.32 ± 0.07	non done	0.29 ± 0.03	0.30 ± 0.22
Trabecular connectivity (per mm3)	138.2 ± 48.one	39.2 ± 10.three	not done	68.nine ± 22.ii	half dozen.74 ± 5.48
Os mineral density (chiliad/cmtwo)	718.9 ± 27.1	785.1 ± 12.5	1167.five ± 17.5	718.ix ± x.four	973.half dozen ± 44.7
Cortical thickness (mm)	non done	not done	9.five ± 0.4	not done	not washed
Marrow volume (mmthree)	not washed	not done	97.two ± 8.6	not done	not done

Table 5.

Cancellous and cortical bone parameters obtained from rats past using mCT

	Femoral head	Femoral cervix	Proximal diaphysis	Lumbar vertebrae	Mandible
Tissue volume (mmiii)	3.51 ± 1.17	1.49 ± 0.xx	2.66 ± 0.12	3.35 ± 0.twenty	0.97 ± 0.06
Bone volume (mm3)	2.59 ± 0.xc	0.99 ± 0.15	i.01 ± 0.03	one.x ± 0.11	0.60 ± 0.14
Os book:tissue volume (ratio)	0.74 ± 0.06	0. 66 ± 0.07	0.38 ± 0.02	0. 33 ± 0.03	0. 61 ± 0.fifteen
No. of trabeculae (per mm)	5.58 ± 0.54	five.32 ± 0.18	non done	4.77 ± 0.31	3.33 ± 0.29
Trabecular thickness (μm)	0.13 ± 0.02	0.thirteen ± 0.02	not done	0.07 ± 0.003	0.nineteen ± 0.06
Trabecular separation (μm)	0.05 ± 0.01	0.06 ± 0.01	non done	0.xiv ± 0.01	0.11 ± 0.04
Trabecular connectivity (per mmthree)	227.6 ± 39.1	171.seven ± 33.7	non done	178.6 ± 29.2	23.65 ± 8.33
Os mineral density (thousand/cmtwo)	788.1 ± 11.6	928.1 ± fifteen.9	1117.6 ± 9.five	760.4 ± 8.0	1024.3 ± 42.5
Cortical thickness (mm)	non done	not washed	0.44 ± 0.03	not done	not washed
Marrow volume (mmthree)	not washed	non done	one.64 ± 0.12	not done	not done

2d (blackness) and 3D (bluish) images of the proximal femoral diaphysis obtained by mCT.

Femoral cervix.

The morphology of the femoral neck and adjoining area, including the greater trochanter and intertrochanteric region, showed a slap-up deal of variability amidst the lab animal species evaluated (Figure three). The tissue volume parameter in the femoral neck varied between compared species. The cancellous bone volume (in mm³) at the femoral neck was 17.93 ± 4.25 in cynomolgus macaques, eight.83 ± 1.50 in dogs, three.44 ± ane.02 in rabbits, 0.99 ± 0.15 in rats, and 0.l ± 0.01 in mice (Tables 2 to ​ 6). Trabecular number at the femoral neck was 0.32 ± 0.08 in cynomolgus macaques, 0.22 ± 0.04 in dogs, 0.29 ± 0.07 in rabbits, 0.66 ± 0.07 in rats, and 0.62 ± 0.05 in mice. Trabecular thickness was fairly consequent among all species, ranging from 0.09 to 0.xv μm. The mineral density of cancellous bone at the femoral neck was also fairly consistent among all laboratory species involved in this study (Table iii).

Tabular array 3.

Cancellous and cortical bone parameters obtained from dogs by using mCT

	Femoral caput	Femoral neck	Proximal diaphysis	Lumbar vertebrae	Mandible
Tissue volume (mm3)	160.14 ± 12.23	39.68 ± 2.xx	422.iv ± 54.0	72.65 ± 22.9	viii.83 ± 0.34
Bone volume (mm3)	59.72 ± x.87	8.83 ± 1.50	201.1 ± 17.0	9.65 ± 1.95	3.13 ± 1.xvi
Bone volume:tissue volume (ratio)	0.37 ± 0.05	0.22 ± 0.04	0.48 ± 0.02	0.xiv ± 0.02	0.35 ± 0.12
No. of trabeculae (per mm)	iii.58 ± 0.14	2.44 ± 0.21	not washed	ii.54 ± 0.08	i.93 ± 0.27
Trabecular thickness (μm)	0.ten ± 0.02	0.09 ± 0.01	not washed	0.05 ± 0.01	0.eighteen ± 0.05
Trabecular separation (μm)	0.18 ± 0.01	0.32 ± 0.04	non done	0.34 ± 0.003	0.35 ± 0.10
Trabecular connectivity (per mmthree)	92.xxx ± fourteen.42	52.ii ± 11.2	not washed	112.7 ± twenty.0	31.94 ± seven.71
Bone mineral density (g/cmii)	850.iii ± 7.0	871.2 ± 9.5	1058.5 ± 13.3	855.ix ± 12.viii	904.39 ± 14.2
Cortical thickness (mm)	not done	not done	14.3 ± 2.7	not done	non done
Marrow book (mmthree)	non done	not done	221.three ± 37.0	non done	non done

2D (black) and 3D (blue) mCT images of the femoral neck with cancellous and cortical bone and intertrochanteric region in canis familiaris. The intertrochanteric region in dog was captured because the gross anatomy of the proximal femur and limitations of the mCT holder did non allow for capturing simply the femoral cervix region.

Proximal diaphysis.

The ratio of cortical bone volume to tissue volume was 0.50 ± 0.03 in cynomolgus macaques, 0.48 ± 0.04 in dogs, 0.38 ± 0.02 in rabbits, 0.38 ± 0.02 in rats, and 0.38 ± 0.03 in mice. The cortical bone thickness (in mm) was 19.5 ± ii.8 in cynomolgus macaques, 14.three ± 2.7 in dogs, ix.5 ± 0.iv in rabbits, 0.44 ± 0.03 in rats, and 0.23 ± 0.03 in mice. Cortical os mineral density (1000/cm²) was 1041.0 ± 17.eight in cynomolgus macaques, 1058.5 ± thirteen.three in dogs, 1167.v ± 17.v in rabbits, 1117.6 ± 9.5 in rats, and 1206.4 ± 24.5 in mice. (Tables ii to ​ 6, Figures 2 to ​ 6).

Lumbar vertebrae.

Radiographs and mCT images revealed large differences in bone morphology and microanatomic construction of the cancellous bone of lumbar vertebrae (Figures 2 to ​ half-dozen). The ratio betwixt os volume and tissue volume ranged from 0.22 ± 0.03 to 0.33 ± 0.03 in mice and rats, as compared with 0.24 ± 0.04 in rabbits, 0.14 ± 0.02 in dogs, and 0.12 ± 0.03 in cynomolgus macaques. Trabecular number (per mm) at the lumbar vertebral bodies was 1.89 ± 0.39 in cynomolgus macaques, ii.54 ± 0.08 in dogs, 2.68 ± 0.21 in rabbits, 4.77 ± 0.31 in rats, and 5.98 ± 0.49 in mice. Trabecular thickness (in mm) at the lumbar vertebral was 0.060 ± 0.004 in cynomolgus macaques, 0.05 ± 0.01 in dogs, 0.09 ± 0.01 in rabbits, 0.070 ± 0.003 in rats, and 0.040 ± 0.003 in mice (Tables 2 to ​ 6). Relative to other species, rabbits exhibited a very narrow mid-portion of the vertebral trunk (Figures 5).

2nd (black) and 3D (bluish) images of lumbar vertebrae obtained past mCT. The light-green box in the 2D images indicates the region of interest where concellous os structural analyses was performed. Notation that the target region in rabbit lumbar spine is dissimilar from that of other species because of the very sparse vertebral torso in rabbits, which contains very niggling to no cancellous os. Therefore, the region of interest for rabbit lumbar vertebrae was placed at the bottom of the lumbar vertebral trunk to obtain sufficient cancellous bone for mCT measurements.

Mandible.

The morphology of the mandible was very dissimilar amongst the lab fauna species studied (Figure 6). Mice and rats have very similar mandibular bones: the incisors extend throughout the entire mandible. Incisor teeth in rabbits are much shorter and extend but through the rostral third of the mandible. The morphologic features of the premolar and molar teeth of rabbits are likewise very different from those of all other evaluated species. Because of differences in root morphology, obtaining precise measurements in the identical surface area of trabecular bone at the site of the 2nd molar was difficult. The assembly of the trabecular network and cortico-cancellous morphology was qualitatively dissimilar among species due to presence of the long incisors underneath the molars in mice and rats, as well as the depth, number, and position of the molar roots (Tables 2 to ​ 6, Figures 6).

Discussion

The bulk of skeletal research in laboratory animals is focused on metabolic os diseases because osteoporoses of various etiologies are recognized as some of the nearly important public problems today.³⁵ The entire region of the proximal femur, including the intertrochanteric area, femoral neck, and femoral head, is of enormous importance for human pathophysiology because hip fractures consequence in considerable morbidity and mortality with massive socio-economic consequences.³⁹ In addition to that in the proximal femur, os loss in the spine and jaws is associated with osteoporosis and aging.^23,37,41,42 For case, there is a stiff correlation between mandibular os mass and the decline in os mass at other skeletal sites.^iii,xx,29 Therefore, the primary focus of our study was to compare anatomic and structural bone features in the proximal femur, lumbar vertebrae, and mandible amid different laboratory animals because these anatomic sites are involved in the pathophysiology of human osteoporoses and are used most oft in preclinical research involving the skeleton. In addition to their obvious value for studies involving osteoporoses, the imaging techniques used in this written report have the potential to be applied to any research involving skeleton. Because bone strength is difficult to assess in dispensary, radiologic methods typically are used to assess 2 primary determinants of bone strength: mineralization and structure.⁴⁵ Even though researchers concord that bone mineral density is the single virtually of import predictor of bone wellness and strength, recent studies have shown that this measure alone may exist insufficient to determine the strength of cancellous bone and that trabecular architecture plays a crucial part in determining os mechanical properties and risk of fracture.^{32,34,46,52,58,68}

The size and gross anatomy of the proximal femur varied substantially among the laboratory species considered in this written report. The features with about obvious variation include the size of the femoral head, length and angle of the femoral neck, size and morphology of the greater trochanter, and shape and size of the intertrochanteric expanse. Variation among species in the 3D orientation of the femoral neck relative to the diaphysis created difficulties in consistently positioning os specimens and accurately scanning the regions of interest. Consequently, the cantankerous-sectional surface area (20 to 50 slices per anatomic site) of cancellous bone chosen for mCT evaluation was not identical among individual measurements in the aforementioned species or among the different species used in our analysis. The results obtained past mCT revealed that trabecular bone volume, number, and separation measured at the femoral head and neck vary greatly among laboratory animals. Similar to the proximal femur of humans, the femoral head and neck areas of the proximal femur from dogs and cynomolgus macaques contain a considerable quantity of cancellous bone.^2,30,40,73 Results from the nowadays study bespeak that the trabecular network in the proximal femur has fairly constant thickness across all species, leading us to conclude that trabecular separation and connectivity contributes to variation in trabecular number among species. Results in dogs and cynomolgus macaques from this report back up earlier findings that at proximal femur where cancellous bone predominates, the combination of volumetric os mineral density should be measured in concert with trabecular structural parameters, particularly trabecular thickness and number, because these 2 parameters used in combination better predict biomechanical backdrop of the proximal femur rather than does any single parameter alone.^34,57 Despite subtle variation in the mineral density of the cancellous and cortical bone at femoral neck and head, density values were similar among species. The somewhat higher values in mice and rats could be due to fewer, simply thicker, trabeculae in rodents relative to dogs and nonhuman primates.³¹ Similarly, the cortical bone mineral density at the proximal femoral diaphysis was slightly college in mice and rat) and rabbits relative to domestic dog and cynomolgus macaques, peradventure due to the presence of Haversian systems and intracortical remodeling that is seen in dogs and nonhuman primates but far less in rabbits and rodents.^15,30,40 Rodents, dogs, and cynomolgus macaques had like ratios of bone to tissue volume. Equally expected, larger species had thicker cortex to maintain organ dimensionality in terms of bone length and thickness and to ensure that the mechanical demands imposed on the skeleton are met. Equally depicted in Figure one, the proximal femur of dogs and cynomolgus macaques more closely resemble the gross and microanatomy of the man proximal femur than does that of rabbits, rats, and mice and therefore likely are better models for studying the physiology of the human proximal femur and hip joint. Even though the mechanical loads in the proximal femur differ between humans and quadrupeds, and the reduced physical activity of laboratory animals has an event on biomechanical studies, the anatomic and structural similarities of the proximal femur and hip articulation betwixt humans, dogs, and nonhuman primates allow for biomedical research under laboratory conditions using dogs and nonhuman primates.^{8,31,45,46,47,threescore,66} Still, information technology should be remembered that bone mass, gross and microanatomy are optimally designed to ensure maximal rubber of the skeleton during natural activities that are unique for each species.^v,63 Our study of skeletal variations among laboratory animals indicates that absolute values recorded for os parameters cannot be directly compared betwixt species. Our data do not let the conclusion that based on, for example, higher bone mineral density or better connected cancellous structure, a skeleton in one species is superior to that in others.

The gross and microanatomic structure of the lumbar vertebrae varies considerably among common laboratory species. Because bone mineral density was fairly similar among all species, we believe that measurements of volumetric bone mineral density and cancellous bone construction should be used for prediction of bone strength at the lumbar spine.^34,58 Because the mechanical loads on the horizontal spine in quadrupeds differ from mechanical loads in humans, in which the spine maintains an upright (vertical) position, biomechanical results and data describing structural bone changes in the vertebral column of laboratory animals crave careful rationalization when extrapolating to the biomechanics in humans.^7,25,64,64 However, rat models can exist used successfully to provide valuable information regarding the physiology of long bones and the spine, and diverse rat models and laboratory weather tin can be modeled further to ameliorate resemble the consequences of human osteoporoses on the skeleton.^{19,27,28,l,72}

Although mechanical forces provide critical signals for os modeling and remodeling events throughout the skeleton, the biomechanics of the jaws is unique and differs from that of weight-bearing bones in the centric skeleton.^4,67 During biting, a complex design of stress and strains (compressive, tensile, shear, and torsional) occurs in the jaws. The range and distribution of mechanical loads varies amongst species just always depends on the nature of the loads practical and the material properties and geometry of the jaws.^13,24 The occlusal force during biting is transferred from the teeth to the cancellous and cortical os of the jaws; fifty-fifty though its volume of trabecular bone is considerably lower than that of cortical bone, the cancellous bone surrounding the tooth socket plays a key office in tooth grafting and load distribution. Moreover, trabecular structural change (harm) reflects the fragility of bone tissue more directly than does a decrease in bone volume; therefore, it is of the utmost importance to use animal models whose jaws reflect a cancellous bone distribution that is like to that of the human mandible.^54,56,57

Numerous investigators have emphasized the lack of animal models as a major impediment to supporting dental inquiry associated with bone loss in the jaws, which is known for its complex pathogenesis and etiology.^21,59 Attributes of the ideal model for dental research would include anatomic and physiologic features that are comparable to those in humans, systemic skeletal and craniofacial affliction progression resembling human conditions, and an opportunity to study both systemic and local factors.⁵⁹ Existing brute models all have advantages and disadvantages. Rodents and rabbits are readily bachelor and could exist used to answer some bones questions. However, they have substantial physiologic and anatomic differences from humans and do not nowadays a good model for dental research, mainly due to the presence of incisors and relatively small areas with cancellous os.^14,33,44 Of all the species nosotros investigated, rabbits seem to be the least desirable model to report oral mechanics and pathophysiology for extrapolation of data to humans because the incisors and rootless teeth of rabbits are embedded deep into the bony parts of the mandible, which contains very minor areas of cancellous os. Furthermore, the presence of the incisors and small cancellous bone area greatly limit the use of rodents to report madibular physiology. On the basis of results from the current study, cynomolgus macaques and dogs seem to be the models of choice for preclinical studies of periodontal illness and the dental effects associated with bone loss because the bony construction of jaws and the anatomy of molars mimic human anatomy and physiology; nevertheless, other species including pigs might also be used in dental research.⁴⁸ The size and shape of the mandibular corpus are linked functionally to the biomechanics of chewing and bitter and therefore are specific to species.^xi In addition to bone mass and structure, other relevant differences in class and part, including forces that act on the mandible during mastication, be between laboratory animals and humans, and those differences should be weighed when extrapolating information from animal studies to humans.

Taken together, the results of this study emphasize primal parameters of the gross anatomy and microanatomy of the proximal femur, lumbar spine, and mandible of commonly used laboratory species. Combination of radiology and mCT allows for quick, reliable, and noninvasive evaluation of os morphology, the complex microarchitecture of cortical and cancellous bone, and bone mineral density, with great translational value from the preclinical to clinical environment. The described skeletal characteristics and human being relevance suggest that rabbit seems to be the least desirable species to carry preclinical research of os physiology due to morphology of the proximal femur, including a very short femoral cervix and pocket-size amounts of cancellous bone at femoral neck, vertebral trunk, and mandible, whereas cynomologus macaques likely are the nearly appropriate among the species we studied. However, rodent models, particularly rat models, are extremely useful for conducting basic research involving the skeleton and represent a expert and affordable alternative to dogs and nonhuman primates. Even though direct comparisons between species are difficult and extrapolating the information obtained to humans can be circuitous, we believe that a better delineation of anatomic and structural characteristics of skeletal sites in the laboratory species presented hither will assistance scientists in choosing the advisable beast models and skeletal sites that all-time support their particular enquiry. This choice may help researchers to reduce unnecessary piece of work involving animals.

Acknowledgments

Nosotros give thanks all of our colleagues from Comparative Medicine and Drug Safety Inquiry and Development at Pfizer (Groton, Connecticut) for their help when collecting the basic from laboratory animals.

References

one. Aerssens J, Boonen S, Lowet Yard, Dequeker J. 1998. Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research. Endocrinology 139: 663–670 [PubMed] [Google Scholar]

2. Bagi CM, Wilkie D, Georgelos K, Williams D, Bertolini D. 1997. Morphological and structural characteristics of the proximal femur in human and rat. Bone 21:261–267 [PubMed] [Google Scholar]

3. Banu J, Orchii PB, Okafor MC, Wang L, Kalu DK. 2001. Assay of the effects of growth hormone, do and nutrient restriction on cancellous bone in different bone sites in centre-anile female rats. Mech Ageing Dev 122:849–864 [PubMed] [Google Scholar]

4. Bidez MW, Misch CE. 1992. Issues in bone mechanics related to oral implants. Implant Paring 1:289–294 [PubMed] [Google Scholar]

5. Biewener AA. 1991. Musculoskeletal design in relation to trunk size. J Biomech 24:nineteen–29 [PubMed] [Google Scholar]

6. Boskey AL. 2003. Biomineralization: an overview. Connect Tissue Res 44 Suppl 1:five–9 [PubMed] [Google Scholar]

7. Bromley RG, Dockum NL, Arnold JS, Jee WS. 1966. Quantitative histological written report of human lumbar vertebrae. J Gerontol 21:537–543 [PubMed] [Google Scholar]

8. Brommage R. 2001. Perspectives on using nonhuman primates to understand the etiology and handling of postmenopausal osteoporosis. J Musculoskelet Neuronal Collaborate one:307–325 [PubMed] [Google Scholar]

9. Currey JD. 1999. The blueprint of mineralized hard tissues for their mechanical functions. J Exp Biol 202:3285–3294 [PubMed] [Google Scholar]

10. Currey JD. 2003. The many adaptations of bone. J Biomech 36:1487–1495 [PubMed] [Google Scholar]

11. Daegling DJ, Hylander WL. 1997. Occlusal forces and mandibular os strain: is the primate jaw "overdesigned"? J Hum Evol 33:705–717 [PubMed] [Google Scholar]

12. Davison KS, Siminoski K, Adachi JD, Hanley DA, Goltzman D, Hodsman AB, Josse R, Kaiser S, Olszynski WP, Papaioannou A, Ste-Marie LG, Kendler DL, Tenenhouse A, Brown JP. 2006. Bone force: the whole is greater than the sum of its parts. Semin Arthritis Rheum 36:22–31 [PubMed] [Google Scholar]

13. Drozdzowska B, Pluskiewicz W. 2002. Longitudinal changes in mandibular bone mineral density compared with hip bone mineral density and quantitative ultrasound at calcaneus and hand phalanges. Br J Radiol 75:743–747 [PubMed] [Google Scholar]

14. Elovic RP, Hipp JA, Hayes WC. 1995. Ovariectomy decreases the bone area fraction of the rat mandible. Calcif Tissue Int 56:305–310 [PubMed] [Google Scholar]

15. Enlow DH. 1962. Functions of the Haversian system. Am J Anat 110:269–305 [PubMed] [Google Scholar]

16. Felsenberg D, Boonen Southward. 2005. The os quality framework: determinants of os strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27:1–11 [PubMed] [Google Scholar]

17. Frost HM. 1990. Structural adaptation to mechanical usage (SATMU). 1. Redefining Wolff's law: The os remodeling problem. Anat Rec 226:414–422 [PubMed] [Google Scholar]

18. Frost HM. 1996. Perspectives: a proposed general model of the "mechanostat" (suggestions from a new skeletal-biologic epitome). Anat Rec 244:139–147 [PubMed] [Google Scholar]

nineteen. Frost HM, Jee WS. 1992. On the rat model of human osteopenias and osteoporoses. Bone Miner 18:227–236 [PubMed] [Google Scholar]

20. Gasser JA, Ingold P, Grosios Thousand, Laib A, Hämmerle S, Koller B. 2005. Non-invasive monitoring of changes in structural cancellous bone parameters with a novel prototype microCT. J Os Miner Metab 23:xc–96 [PubMed] [Google Scholar]

21. Geurs NC, Lewis CE, Jeffcoat MK. 2003. Osteoporosis and periodontal disease progression. Periodontol 2000 32:105–110 [PubMed] [Google Scholar]

22. Hillier ML, Bong LS. 2007. Differentiating human being os from animal bone: a review of histological methods. J Forensic Sci 52:249–263 [PubMed] [Google Scholar]

23. Hordon LD, Itoda M, Shore PA, Shore RC, Heald M, Brown M, Kanis JA, Rodan GA, Aaron JE. 2006. Preservation of thoracic spine microarchitecture by alendronate: comparison of histology and microCT. Os 38:444–449 [PubMed] [Google Scholar]

24. Horner K, Devlin H, Alsop CW, Hodgkinson IM, Adams JE. 1996. Mandibular os mineral density equally a predictor of skeletal osteoporosis. Br J Radiol 69:1019–1025 [PubMed] [Google Scholar]

25. Hotchkiss CE, Stavisky R, Nowak J, Brommage R, Lees CJ, Kaplan J. 2001. Levormeloxifene prevents increased bone turnover and vertebral bone loss following ovariectomy in cynomolgus monkeys. Bone 29:7–15 [PubMed] [Google Scholar]

26. Establish for Laboratory Creature Research 1996. Guide for the care and employ of laboratory animals. Washington (DC): National Academies Printing [PubMed] [Google Scholar]

27. Jee WS, Ma Y. 1999. Animal models of immobilization osteopenia. Morphologie 83:25–34 [PubMed] [Google Scholar]

28. Jee WS, Yao W. 2001. Overview: animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Collaborate 1:193–207 [PubMed] [Google Scholar]

29. Jeffcoat MK, Chesnut CH., 3rd 1993. Systemic osteoporosis and oral bone loss: evidence shows increased risk factors. J Am Dent Assoc 124:49–56 [PubMed] [Google Scholar]

30. Jerome CP. 1998. Primate models of osteoporosis. Lab Anim Sci 48:618–622 [PubMed] [Google Scholar]

31. Jerome CP, Peterson PE. 2001. Nonhuman primate models in skeletal enquiry. Bone 29:1–half-dozen [PubMed] [Google Scholar]

32. Jiang C, Giger ML, Kwak SM, Chinander MR, Martell JM, Favus MJ. 2000. Normalized BMD as a predictor of bone forcefulness. Acad Radiol 7:33–39 [PubMed] [Google Scholar]

33. Jiang G, Matsumoto H, Yamane J, Kuboyama Due north, Akimoto Y, Fujii A. 2004. Prevention of trabecular bone loss in the mandible of ovariectomized rats. J Oral Sci 46:75–85 [PubMed] [Google Scholar]

34. Jiang Y, Zhao J, Augat P, Ouyang X, Lu Y, Majmudar S, Genant HK. 1998. Trabecular bone mineral and calculated structure of human being bone specimens scanned by peripheral quantitative computed tomography: relation to biomechanical properties. J Os Miner Res thirteen:1783–1790 [PubMed] [Google Scholar]

35. Johnell O, Kanis JA. 2006. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733 [PubMed] [Google Scholar]

37. Kalu DN. 1991. The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175–191 [PubMed] [Google Scholar]

38. Kanis JA. 2002. Assessing the risk of vertebral osteoporosis. Singapore Med J 43:100–105 [PubMed] [Google Scholar]

39. Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, Oden A, Zethraeus Northward, Pfleger B, Khaltaev N. 2005. Assessment of fracture risk. Osteoporos Int sixteen:581–589 [PubMed] [Google Scholar]

forty. Kimmel DB, Jee WS. 1982. A quantitative histologic study of bone turnover in young adult beagles. Anat Rec 203:31–45 [PubMed] [Google Scholar]

41. Krall EA, Garcia RI, Dawson-Hughes B. 1996. Increased hazard of tooth loss is related to bone loss at the whole body, hip, and spine. Calcif Tissue Int 59:433–437 [PubMed] [Google Scholar]

42. Kribbs PJ. 1990. Comparing of mandibular bone in normal and osteoporotic women. J Prosthet Dent 63:218–222 [PubMed] [Google Scholar]

43. Kuhn LT, Grynpas Md, Rey CC, Wu Y, Ackerman JL, Glimcher MJ. 2008. A comparison of the physical and chemic differences between cancellous and cortical bovine bone mineral at two ages. Calcif Tissue Int 83:146–154 [PMC gratis commodity] [PubMed] [Google Scholar]

44. Lerouxel E, Libouban H, Moreau MF, Basle MF, Audran Yard, Chappard D. 2004. Mandibular bone loss in an creature model of male person osteoporosis (orchidectomized rat): a radiographic and densitometric report. Osteoporos Int 15:814–819 [PubMed] [Google Scholar]

45. Lloyd RD, Taylor GN, Miller SC, Bruenger FW, Jee WS. 2006. Ancestry of beagles in lifespan studies of radionuclide toxicity at the University of Utah. Health Phys 90:580–582 [PubMed] [Google Scholar]

46. Majumdar S, Genant HK, Grampp S, Newitt DC, Truong VH, Lin JC, Mathur A. 1997. Correlation of trabecular bone structure with age, bone mineral density, and osteoporotic status: In vivo studies in the distal radius using high resolution magnetic resonance imaging. J Bone Miner Res 12:111–118 [PubMed] [Google Scholar]

47. Martin RK, Albright JP, Jee WS, Taylor GN, Clarke WR. 1981. Bone loss in the beagle tibia: influence of age, weight, and sexual practice. Calcif Tissue Int 33:233–238 [PubMed] [Google Scholar]

48. Martinez-Gonzales JM, Cano-Sanchez J, Campo-Trapero J, Gronzalo-Lafuente JC, Diaz-Reganon J, Vasquez-Pineiro MT. 2005. Evaluation of minipigs as an animal model for alveolar lark. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:11–16 [PubMed] [Google Scholar]

49. Miller SC, Bowman BM, Jee WS. 1995. Available animal models of osteopenia–minor and large. Bone 17:117S–123S [PubMed] [Google Scholar]

50. Mo A, Yao W, Li C, Tian X, Su M, Ling Y, Zhang Q, Setterberg RB, Jee WS. 2002. Bipedal stance exercise and prostaglandin E2 (PGE2) and its synergistic effect in increasing bone mass and in lowering the PGE2 dose required to prevent ovariectomized-induced cancellous os loss in anile rats. Bone 31:402–406 [PubMed] [Google Scholar]

51. Mosekilde 50, Danielsen CC, Sogaard CH, Thorling E. 1994. The effect of long-term exercise on vertebral and femoral bone mass, dimensions, and strength–assessed in a rat model. Bone fifteen:293–301 [PubMed] [Google Scholar]

52. Nielsen DH, McEvoy FJ, Madsen MT, Jensen JB, Svalastoga E. 2007. Relationship between bone strength and dual-energy 10-ray absorptiometry measurements in pigs. J Anim Sci 85:667–672 [PubMed] [Google Scholar]

53. Pearson OM, Lieberman DE. 2004. The aging of Wolff's "police": ontogeny and response to mechanical loading in cortical os. Am J Phys Anthropol 39:63–99 [PubMed] [Google Scholar]

54. Recker RR. 1989. Depression bone mass may not exist the only cause of skeletal fragility in osteoporosis. Proc Soc Exp Biol Med 191:272–274 [PubMed] [Google Scholar]

55. Rodgers JB, Monier-Faugere MC, Malluche H. 1993. Animal models for the study of bone loss after cessation of ovarian function. Bone 14:369–377 [PubMed] [Google Scholar]

56. Seeman E. 2003. Bone quality. Osteoporos Int 14 Suppl 5:S3–S7 [PubMed] [Google Scholar]

57. Seeman Eastward. 2005. Loading and os fragility. J Bone Miner Metab 23 Suppl:23–29 [PubMed] [Google Scholar]

58. Stenström M, Olander B, Lehto-Axtelius D, Madsen JE, Nordsletten L, Carlsson GA. 2000. Bone mineral density and bone structure parameters as predictors of os forcefulness: an analysis using computerized microtomography and gastrectomy-induced osteopenia in the rat. J Biomech 33:289–297 [PubMed] [Google Scholar]

59. Takaishi Y, Okamoto Y, Ikeo T, Morii H, Takeda M, Hide Thou, Arai T, Nonaka K. 2005. Correlations between periodontitis and loss of mandibular bone in relation to systemic bone changes in postmenopausal Japanese women. Osteoporos Int 16:1875–1882 [PubMed] [Google Scholar]

60. Taylor GN, Christensen WR, Jee WS, Rehfeld CE, Fisher W. 1962. Anatomical distribution of fractures in beagles injected with Pu-239. Wellness Phys 8:609–613 [PubMed] [Google Scholar]

61. Thompson DD, Simmons HA, Pirie CM, Ke HZ. 1995. FDA Guidelines and creature models for osteoporosis. Bone 17:125S–133S [PubMed] [Google Scholar]

62. Turner CH. 1991. Homeostatic control of bone structure: an awarding of feedback theory. Bone 12:203–217 [PubMed] [Google Scholar]

63. Turner CH. 1998. Three rules for bone adaptation to mechanical stimuli. Os 23:399–407 [PubMed] [Google Scholar]

64. Turner CH. 2002. Biomechanics of bone: determinants of skeletal fragility and os quality. Osteoporos Int 13:97–104 [PubMed] [Google Scholar]

65. Turner CH, Burr DB, Hock JM, Brommage R, Sato Chiliad. 2001. The effects of PTH (1-34) on bone construction and force in ovariectomized monkeys. Adv Exp Med Biol 496:165–179 [PubMed] [Google Scholar]

66. Vajda EG, Kneissel 1000, Muggenburg B, Miller SC. 1999. Increased intracortical bone remodeling during lactation in beagle dogs. Biol Reprod 61:1439–1444 [PubMed] [Google Scholar]

67. van der Meulen MC, Jepsen KJ, Mikic B. 2001. Understanding bone strength: size isn't everything. Bone 29:101–104 [PubMed] [Google Scholar]

68. van Eijden TM. 2000. Biomechanics of the mandible. Crit Rev Oral Biol Med 11:123–136 [PubMed] [Google Scholar]

69. Wallach S, Feinblatt J, Avioli Fifty. 1992. The bone quality problem. Calcif Tissue Int 51:169–172 [PubMed] [Google Scholar]

70. Wessler Southward. 1976. Introduction: what is a model?, p xi–xvi In: Committee on Beast Models for Thrombosis and Hemorrhagic Diseases; Constitute of Laboratory Animate being Resources. Animal models of thrombosis and hemorrhagic disease. Bethesda (Doctor): National Institutes of Wellness [Google Scholar]

71. Wronski TJ, Cintron M, Dann LM. 1988. Temporal relationship between os loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int 43:179–183 [PubMed] [Google Scholar]

72. Yao W, Jee WS, Chen J, Liu H, Tam CS, Cui L, Zhou H, Setterberg RB, Frost HM. 2000. Making rats ascension to erect bipedal opinion for feeding partially prevented orchidectomy-induced os loss and added bone to intact rats. J Bone Miner Res 15:1158–1168 [PubMed] [Google Scholar]

73. Zebaze RM, Jones A, Welsh F, Knackstedt M, Seeman E. 2005. Femoral neck shape and the spatial distribution of its mineral mass varies with its size: clinical and biomechanical implications. Os 37:243–252 [PubMed] [Google Scholar]

---

Articles from Comparative Medicine are provided here courtesy of American Association for Laboratory Animal Science

---

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060425/

Posted by: hortonanderfarom.blogspot.com

Share this post