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Biomedical subjects

A S Turner

Publications and source records attributed to A S Turner.

At least 19 recordsLinked to original sources
PubMed2006

A comparison of two biomaterial carriers for osteogenic protein-1 (BMP-7) in an ovine critical defect model.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant's efficacy for bone regeneration. The biomaterial carriers were a 'putty' carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to "ungrafted" negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.

Animals↗
PubMed2005

Long-term ovariectomy decreases ovine compact bone viscoelasticity.

Changes in bone mineral density associated with estrogen depletion in humans do not account for all of the associated change in fracture risk, and it is possible that some of this variation may lie in changes of other aspects of bone quality. The purpose of this study was to investigate changes in viscoelastic behavior of compact bone that may be associated with estrogen depletion. Changes in compact bone viscoelastic properties associated with three years of ovariectomy were investigated with dynamic mechanical analysis (low-amplitude 3-point bending at frequencies of 1-20 Hz) using beams milled from the diaphysis of the ovine radius. The viscoelastic storage modulus was significantly (5.2%) lower at the higher frequencies for the ovariectomized animals. The general anatomic variation in storage modulus, in which cranial sectors had higher values than caudal sectors, did not change with ovariectomy. The loss tangent (tandelta, a measure of damping) was also greatly decreased (up to 83%) at high frequencies in the ovariectomized animals. Anatomic variation in tandelta at low (6-12 Hz) frequencies (cranial and caudal sectors having higher values than lateral or medial sectors) was enhanced with ovariectomy. Changes in viscoelastic properties associated with long-term estrogen depletion could be responsible for a significant reduction in the toughness or strength of a bone without concomitant changes in screening modalities used to evaluate bone quality (e.g., DXA, QCT, QUA).

Animals↗
PubMed2005

In vivo healing after capsular plication in an ovine shoulder model.

Traditionally, arthroscopic management of shoulder instability has been reserved for patients with isolated Bankart lesions without any capsular laxity or injury. To date, there are no animal studies evaluating the healing potential of capsular plication and/or capsulo-labral repair. The purpose of this in vivo animal study was to determine if the histological capsular healing of an open capsular plication simulating an arthroscopic plication is equivalent to the more traditional open capsular shift involving cutting and advancing the capsule. Twenty-six skeletally mature sheep were randomized to either an open capsular plication simulating arthroscopic plication (n = 13), or an open traditional capsular shift (n = 13). A sham operation (n = 4) was also performed involving exposure to visualize the capsule. Normal non-operated control shoulders were also analyzed. A pathologist blinded to the treatment evaluated both hematoxylin and eosin (H&E) sections and polarized light microscopy. Qualitative scoring evaluated fibrosis, mucinous degeneration, fat necrosis, granuloma formation, vascularity, inflammatory infiltrate and hemosiderin (0 to 3 points). Both the capsular plication and open shift groups demonstrated healing by fibrosis at the site of surgical manipulation. There were no statistical differences in the capsular healing responses between the two groups with regard to fibrosis, granuloma formation and vascularity. The open shift group demonstrated significantly more mucinous degeneration (p = 0.038). Fat necrosis was present in 4/13 specimens in the open shift group and none in the capsular plication specimens. Both groups demonstrated disorganized collagen formation under polarized light microscopy. There were no differences between non-operated control specimens and sham surgery specimens. Our findings support the hypothesis that histologic capsular healing is equivalent between the plication group and the open shift group. In addition, the open shift group demonstrated significantly more changes indicative of tissue injury. This basic science model confirms capsular healing after simulated arthroscopic plication, providing support for arthroscopic capsular plication in practice.

Animals↗
PubMed2004

Dietary-induced metabolic acidosis decreases bone mineral density in mature ovariectomized ewes.

Dietary-induced metabolic acidosis (DIMA) may be a significant confounder in the development of osteoporosis. Diets that are acidifying are typically rich in proteins and grains and relatively poor in fruits and vegetables. Previous studies have not examined whether an interaction between estrogen depletion and DIMA have a compounded affect on bone mineral density loss. Sheep have been used successfully in previous studies to examine the interaction of bone turnover and ovariectomy. Therefore, the goal of this pilot study was to determine if bone mineral density (BMD) loss could be induced using DIMA in skeletally mature ovariectomized (OVX) ewes.

Acidosis↗
PubMed2004

Determinants of ovine compact bone viscoelastic properties: effects of architecture, mineralization, and remodeling.

Significant decreases in ovine compact bone viscoelastic properties (specifically, stress-rate sensitivity, and damping efficiency) are associated with three years of ovariectomy and are particularly evident at higher frequencies [Proc. Orthop. Res. Soc. 27 (2002) 89]. It is unclear what materials or architectural features of bone are responsible for either the viscoelastic properties themselves, or for the changes in those properties that were observed with estrogen depletion. In this study, we examined the relationship between these viscoelastic mechanical properties and features involving bone architecture (BV/TV), materials parameters (ash density, %mineralization), and histologic evidence of remodeling (%remodeled, cement line interface). The extent of mineralization was inversely proportional to the material's efficiency in damping stress oscillations. The damping characteristics of bone material from ovariectomized animals were significantly more sensitive to variation in mineralization than was bone from control animals. At low frequencies (6 Hz or less), increased histologic evidence of remodeling was positively correlated with increased damping efficiency. However, the dramatic decreases in stress-rate sensitivity that accompanied 3-year ovariectomy were seen throughout the bone structure and occurred even in areas with little or no secondary Haversian remodeling as well as in areas of complete remodeling. Taken together, these data suggest that, while the mineral component may modify the viscoelastic behavior of bone, the basic mechanism underlying bone viscoelastic behavior, and of the changes in that behavior with estrogen depletion, reside in a non-mineral component of the bone that can be significantly altered in the absence of secondary remodeling.

Animals↗
PubMed2003

Central and peripheral temperature changes in sheep following ovariectomy.

OBJECTIVES: To determine if ovariectomized ewes undergo periodic body temperature rises (hot flashes) similar to women at menopause. METHODS: Eighteen mature ewes were assigned to ovariectomy (OVX), ovariectomy+17 beta-estradiol implant (OVXE) or Sham. Electronic temperature loggers placed subcutaneously over the carotid artery and within the abdomen (core) and subcutaneously in the thigh and axilla (peripheral) were programmed to record body temperatures every 2.5 min for 59 days. Circadian rhythm changes were avoided by dividing readings into 1 h intervals. Hot flashes were defined as a 0.2 or 0.4 degrees C increase over the minimum temperature recorded for a 1 h interval for each sheep. RESULTS: Logger placement did not reflect core and peripheral temperatures. The carotid and abdominal sites were most useful. The percentage of readings considered HF at the carotid site was 63% OVX, 54% OVXE and 37% Sham (P<0.001), and at the abdominal site were 32% OVX, 15% OVE and 17% Sham (P<0.001). When only the first 7 days after ovariectomy were analyzed, the percentage of readings considered to be HF at the carotid site was 75% OVX, 63% OVXE, and 49% Sham (P<0.001), and at the abdominal site was 35% OVX, 15% OVXE and 17% Sham (P<0.001). CONCLUSIONS: Ovariectomy in the ewe does illicit changes in body temperature compared with control ewes, which may be interpreted as HF. However, shifts in the circadian rhythm were not apparent. Estradiol treatment led to milder and less frequent HF. Periodic HF in species other than rats have heretofore not been reported.

Animals↗
PubMed2003

Treatment of feline diabetes mellitus using an alpha-glucosidase inhibitor and a low-carbohydrate diet.

The purpose of this study was to determine the effect of an alpha-glucosidase inhibitor (acarbose), combined with a low-carbohydrate diet on the treatment of naturally occurring diabetes mellitus in cats. Eighteen client-owned cats with naturally occurring diabetes mellitus were entered into the study. Dual-energy X-ray absorptiometry (DEXA) was performed prior to and 4 months after feeding the diet to determine total body composition, including lean body mass (LBM) and percent body fat. Each cat was fed a commercially available low-carbohydrate canned feline diet and received 12.5mg/cat acarbose orally every 12h with meals. All cats received subcutaneous insulin therapy except one cat in the study group that received glipizide (5mg BID PO). Monthly serum glucose and fructosamine concentrations were obtained, and were used to adjust insulin doses based on individual cat's requirements. Patients were later classified as responders (insulin was discontinued, n=11) and non-responders (continued to require insulin or glipizide, n=7). Responders were initially obese (>28% body fat) and non-responders had significantly less body fat than responders (<28% body fat). Serum fructosamine and glucose concentrations decreased significantly in both responder and non-responder groups over the course of 4 months of therapy. Better results were observed in responder cats, for which exogenous insulin therapy was discontinued, glycemic parameters improved, and body fat decreased. In non-responders, median insulin requirements decreased and glycemic parameters improved significantly, despite continued insulin dependence. The use of a low-carbohydrate diet with acarbose was an effective means of decreasing exogenous insulin dependence and improving glycemic control in a series of client-owned cats with naturally occurring diabetes mellitus.

Absorptiometry, Photon↗
PubMed2002

Mechanical strain, induced noninvasively in the high-frequency domain, is anabolic to cancellous bone, but not cortical bone.

Departing from the premise that it is the large-amplitude signals inherent to intense functional activity that define bone morphology, we propose that it is the far lower magnitude, high-frequency mechanical signals that continually barrage the skeleton during longer term activities such as standing, which regulate skeletal architecture. To examine this hypothesis, we proposed that brief exposure to slight elevations in these endogenous mechanical signals would suffice to increase bone mass in those bones subject to the stimulus. This was tested by exposing the hind limbs of adult female sheep (n = 9) to 20 min/day of low-level (0.3g), high-frequency (30 Hz) mechanical signals, sufficient to induce a peak of approximately 5 microstrain (micro epsilon) in the tibia. Following euthanasia, peripheral quantitative computed tomography (pQCT) was used to segregate the cortical shell from the trabecular envelope of the proximal femur, revealing a 34.2% increase in bone density in the experimental animals as compared with controls (p = 0.01). Histomorphometric examination of the femur supported these density measurements, with bone volume per total volume increasing by 32% (p = 0.04). This density increase was achieved by two separate strategies: trabecular spacing decreased by 36.1% (p = 0.02), whereas trabecular number increased by 45.6% (p = 0.01), indicating the formation of cancellous bone de novo. There were no significant differences in the radii of animals subject to the stimulus, indicating that the adaptive response was local rather than systemic. The anabolic potential of the signal was evident only in trabecular bone, and there were no differences, as measured by any assay, in the cortical bone. These data suggest that subtle mechanical signals generated during predominant activities such as posture may be potent determinants of skeletal morphology. Given that these strain levels are three orders of magnitude below strains that can damage bone tissue, we believe that a noninvasive stimulus based on this sensitivity has potential for treating skeletal complications such as osteoporosis.

Animals↗
PubMed2002

The sheep as a model for osteoporosis in humans.

There is great interest in large animal models for studying different aspects of osteoporosis. Several laboratories around the world have used ovariectomized sheep as a model because of their ease of housing and handling, low expense compared to other large animals, availability and acceptance in society as a research animal. They have been used to study the response to new therapies for post-menopausal osteoporosis, low-magnitude mechanical stimulation, orthopedic implants in osteoporotic bone and bioactive ceramics to strengthen vertebral bodies. To produce severely osteopenic bone comparable to that seen in humans, a combination of estrogen deficiency following ovariectomy plus a calcium-wasting diet is currently being investigated.

Animals↗
PubMed2001

Anabolism. Low mechanical signals strengthen long bones.

Although the skeleton's adaptability to load-bearing has been recognized for over a century, the specific mechanical components responsible for strengthening it have not been identified. Here we show that after mechanically stimulating the hindlimbs of adult sheep on a daily basis for a year with 20-minute bursts of very-low-magnitude, high-frequency vibration, the density of the spongy (trabecular) bone in the proximal femur is significantly increased (by 34.2%) compared to controls. As the strain levels generated by this treatment are three orders of magnitude below those that damage bone tissue, this anabolic, non-invasive stimulus may have potential for treating skeletal conditions such as osteoporosis.

Adaptation, Physiological↗
PubMed2001

Animal models of osteoporosis--necessity and limitations.

There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs)) and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty) is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

Journal Article↗
PubMed2001

Metabolic alterations in dogs with osteosarcoma.

OBJECTIVE: To evaluate changes in resting energy expenditure (REE) as well as protein and carbohydrate metabolism in dogs with osteosarcoma (OSA). ANIMALS: 15 weight-stable dogs with OSA that did not have other concurrent metabolic or endocrine illness and twelve 1-year-old sexually intact female Beagles (control dogs). PROCEDURES: Indirect calorimetry was performed on all dogs to determine REE and respiratory quotient (RQ). Stable isotope tracers (15N-glycine, 4.5 mg/kg of body weight, IV; 6,6-deuterium-glucose, 4.5 mg/kg, IV as a bolus, followed by continuous-rate infusion at 1.5 mg/kg/h for 3 hours) were used to determine rate of protein synthesis and glucose flux in all dogs. Dual-energy x-ray absorptiometry (DEXA) scans were performed to determine total body composition. RESULTS: Accounting for metabolic body size, REE in dogs with OSA was significantly higher before and after surgery, compared with REE of healthy control dogs. The RQ values did not differ significantly between groups. Dogs with OSA also had decreased rates of protein synthesis, increased urinary nitrogen loss, and increased glucose flux during the postoperative period. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations in energy expenditure, protein synthesis, urinary nitrogen loss, and carbohydrate flux were evident in dogs with OSA, similar to results documented in humans with neoplasia. Changes were documented in REE as well as protein and carbohydrate metabolism in dogs with OSA. These changes were evident even in dogs that did not have clinical signs of cachexia.

Absorptiometry, Photon↗
PubMed2001

The effect of immobilization on rotator cuff healing using modified Mason-Allen stitches: a biomechanical study in sheep.

Long-term biomechanical integrity of the surgical site is crucial to the outcome of rotator cuff repair. Usually after rotator-cuff surgery, the arm is immobilized for 6-12 weeks to minimize disruption at the healing site. Unfortunately, currently there is very little clinical data on the effects of immobilization after rotator cuff surgery. This study analyzed the effect of immobilization on rotator cuff healing by comparing the healing strength of the tendon in a bone trough using a sheep model. In sixteen (16) female adult sheep, the right infraspinatus tendons were reattached into a bone trough using a modified Mason-Allen suture pattern. After surgery, each sheep was randomly assigned into either an immobilized or non-immobilized treatment group. The immobilized group was fitted with a softball taped under the foot to restrict limb movement for 6 weeks. The non-immobilized treatment group was allowed to fully bear weight on the treated shoulder. At 26 weeks, the animals were sacrificed and the surgical shoulders were harvested and stored in a -30 degrees C freezer. Biomechanical testing was performed using a MTS 809 Axial/Torsional Servohydraulic System. Special cryo-grips were used to test the infraspinatus tendon-bone interface in anatomical alignment. All samples were preloaded with 10 +/- 5 N, and then force was measured during a crosshead displacement of 500 mm/min until failure. Force and displacement were acquired at 100 Hz and used to calculate load-to-failure and stiffness of the bone-tendon interface. The load-to-failure (N) and stiffness (N/cm) were determined for both treatment groups. For the non-immobilized group, the loads to failure and stiffness means were 2571.95 +/- 329.9 N and 2319.09 +/- 457.72 N/cm. The immobilized group means were 2954.42 +/- 473.52 N (load-to-failure) and 2579.13 +/- 383.51 N/cm (stiffness). A two-tailed two-samples unequal variance student t-test with significance set at 0.05, found no significant difference between the treatment groups for load-to-failure (p = 0.2174) and stiffness (p = 0.8286).

Animals↗
PubMed2000

Direct current electrical stimulation increases the fusion rate of spinal fusion cages.

STUDY DESIGN: A randomized experimental evaluation of direct current stimulation in a validated animal model with an experimental control group, using blinded radiographic, biomechanical, histologic, and statistical measures. OBJECTIVES: To evaluate the efficacy of the adjunctive use of direct current stimulation on the fusion rate and speed of healing of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. SUMMARY OF BACKGROUND DATA: Titanium lumbar interbody spinal fusion cages have been reported to be 90% effective for single-level lumbar interbody fusion. However, fusion rates are reported to be between 70% and 80% in patients with multilevel fusions or with risk factors such as obesity, tobacco use, or metabolic disorders. The authors hypothesized that direct current stimulation would increase the fusion rate of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. METHODS: Twenty-two sheep underwent lumbar discectomy and fusion at L4-L5 with an 11- x 20-mm Bagby and Kuslich (BAK) cage packed with autograft. Seven sheep received a BAK cage and no current. Seven sheep had a cage and a 40-microA current applied with a direct current stimulator. Eight sheep had a BAK cage and a 100-microA current applied. All sheep were killed 4 months after surgery. The efficacy of electrical stimulation in promoting interbody fusion was assessed by performing radiographic, biomechanical, and histologic analyses in a blinded fashion. RESULTS: The histologic fusion rate increased as the direct current dose increased from 0 microA to 40 microA to 100 microA (P < 0.009). Histologically, all animals in the 100-microA group had fusions in both the right and left sides of the cage. Direct current stimulation had a significant effect on increasing the stiffness of the treated motion segment in right lateral bending (P < 0.120), left lateral bending (P < 0.017), right axial rotation (P < 0.004), left axial rotation (P < 0.073), extension (P < 0.078), and flexion (P < 0.029) over nonstimulated levels. CONCLUSION: Direct current stimulation increased the histologic and biomechanical fusion rate and the speed of healing of lumbar interbody spinal fusion cages in an ovine model at 4 months.

Animals↗
PubMed2000

Effects of diet on pharmacokinetics of phenobarbital in healthy dogs.

OBJECTIVE: To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate. DESIGN: Prospective study. ANIMALS: 27 healthy sexually intact adult female Beagles. PROCEDURE: Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, p.o., q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], i.v.) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA. RESULTS: Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t1/2 (hours) was lower in groups 2 (mean +/- SD; 25.9 +/- 6.10 hours) and 3 (24.0 +/- 4.70) than in group 1 (32.9 +/- 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 +/- 0.05 ml/kg/min) than in groups 1 (0.17 +/- 0.03) or 2 (0.18 +/- 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 +/- 47.5 U/L) and 3 (202.0 +/- 98.2) than in group 1 (125.0 +/- 47.5). CONCLUSIONS AND CLINICAL RELEVANCE: Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions.

Alkaline Phosphatase↗
PubMed2000

The effect of raloxifene on coronary arteries in aged ovariectomized ewes.

BACKGROUND: Ovariectomized sheep are a useful model of postmenopausal osteoporosis and other postmenopausal conditions. Estrogen may have a protective effect on the coronary arteries in postmenopausal women. The effects of raloxifene, a selective estrogen receptor modulator, on coronary arteries in aged ovariectomized ewes was investigated. METHODS AND RESULTS: Forty eight aged ewes were randomly assigned to undergo sham surgery (Sham, n = 7), ovariectomy (OVX, n = 10), ovariectomy with estradiol supplementation (OVXE, n = 8), ovariectomy with raloxifene supplementation, 0.02 mg/kg per day (RAL1, n = 10), or ovariectomy with raloxifene supplementation, 0.10 mg/kg per day (RAL2, n = 13). Contrast coronary angiography was performed 6 months after intervention. Diameters of the right main and left anterior descending coronary arteries in the RAL1, RAL2 and Sham groups were not different from each other, but were significantly greater than the OVX and OVXE groups. Intracoronary nitroglycerin did not affect the relationships of the diameters in any group. There were no differences in vascular remodeling between the groups. CONCLUSIONS: The results indicate that raloxifene in this sheep model allows greater dilation of coronary arteries than estrogen. Raloxifene may provide a significant protective functional effect on coronary arteries in postmenopausal heart disease.

Animals↗
PubMed2000

Ultrasound therapy for the prevention and correction of contractures and bone mineral loss associated with wing bandaging in the domestic pigeon (Columba livia).

Figure-of-eight wing bandaging is widely used to treat wing injuries, to immobilize wings before and after fracture repair, and during transient wing paralysis. However, prolonged bandaging can lead to bone loss and to contractures and reduced range of joint motion. Studies evaluating the efficacy of therapeutic ultrasound to reverse and prevent bandaging-associated contractures in pigeons (Columba livia) showed a significant increase in elbow and carpal extension after 10 twice weekly ultrasound treatments when started either 4 or 11 days after bandage placement. In addition, after 42 days of wing bandaging, three ultrasound treatments stimulated a faster reversal of carpal wing rotation loss than removal of the bandage over the 10-day treatment period. Finally, bone loss in response to 28 days of bandaging was significant, progressed at 2.8% per week, and was not affected by ultrasound treatment twice weekly during this period. Therefore, therapeutic ultrasound prevented and reversed loss of wing extension associated with figure-of-eight bandaging but did not lessen the disuse osteoporosis created by bandaging in these birds.

Absorptiometry, Photon↗