Introduction
Bearded dragons (Pogona vitticeps) are popular pets. Although reports1,2,3,4,5,6,7,8 of neoplasia in bearded dragons are limited, findings from a 2004 retrospective survey9 indicate that the overall prevalence of neoplasia in reptiles may be as high as 6.2% (81/1,297). Chemotherapy in reptiles has many challenges, and there is a paucity of information to help guide such treatments.1,8,10,11,12 Among the challenges is the lack of information describing appropriate dosing of chemotherapeutic agents in reptiles.
Conventionally, many chemotherapy drugs are administered on the basis of BSA rather than body weight.13,14,15,16,17 The formula typically used to calculate BSA is as follows: BSA = K X (body weight in g)2/3, where K is a shape constant that is species specific. Values of K have been determined for multiple species through several methods.15,18,19,20,21,22,23,24,25 Historically, BSA has been determined by use of the traditional tape method14 or by making physical measurements on skinned specimens20,22 or molds of cadavers.24 Recently, CT has been used successfully as a noninvasive, highly accurate modality for determining BSA in ferrets18 and rabbits.19 This method has also been used to determine BSA in human neonates26 and adults.27
The BSA in bearded dragons is currently estimated with the use of either constants derived for dogs and cats or allometric scaling recommendations for reptiles based on empirical clinical experience.3,27 To our knowledge, no K constant for BSA has been calculated for any species of reptile, and we are unaware of any supportive evidence that traditional formulas for BSA provide accurate estimates in reptiles. The objective of the study reported here was to use CT-derived measurements to calculate a K constant and create a formula to calculate BSA on the basis of body weight for bearded dragons (Pogona vitticeps). By establishing a K constant for bearded dragons, we aim to improve the accuracy of chemotherapeutic dosing in this species. However, further research is indicated to determine the efficacy, toxicity, and pharmacokinetics of chemotherapeutic drugs in bearded dragons.
Materials and Methods
Animals
Healthy adult client-owned bearded dragons were recruited for the study through the use of email to owners. The recruitment period was from November 23, 2019, to January 11, 2020. For inclusion, bearded dragons had to have been healthy with no body-deforming injuries or malformations and had to have been displaying clinically normal behavior in their environment. Informed written consent was obtained from the owners of all the bearded dragons enrolled. The study protocol was reviewed and approved by the North Carolina State University Institutional Animal Care and Use Committee (No. 19-709) and the Clinical Core Studies Committee.
Examinations
Each bearded dragon underwent a physical examination performed by a licensed veterinarian (CMHK) for evaluation of health status and to identify any external abnormalities that deformed the body contour. Body weight measurement was recorded for each animal.
For CT, the bearded dragons were awake, and no sedative or anesthetic drugs were administered. This was made possible by the animals' calm and sedentary temperaments. Each animal was positioned in ventral recumbency on an approximately 3-cm-deep piece of foam in a plastic box. The foam supported the animal and achieved separation from the surface of the plastic box, facilitating later 3-D segmentation. Transverse images with a 0.6-mm slice thickness were acquired at 130 kVp and 25 mA and obtained from the tip of the rostrum to the tip of the tail with a 64-slice helical CT scanner.a
3-D CT reconstruction
The CT images were reconstructed and downloaded in a bone window reconstruction algorithm (window width, 2,000 HU; window level, 400 HU) and analyzed with dedicated CT image analysis software.b An automated 3-D surface model was created for each bearded dragon by use of a minimum threshold value of –500 HU with no upper limit so that densities outside the animal were excluded. Air imaged in each animal (eg, in the lungs and gastrointestinal tract) was manually removed with a tracing tool as previously described.18,27 The 3-D model generated through reconstruction for each bearded dragon was visually assessed to ensure it was continuous and complete (CMHK). The CT image analysis software automatically calculated BSA for each subject. This process was performed once for each animal, and the BSA value for each animal was then used for further analysis.
Statistical analysis
Body surface area was plotted against body weight, and a K constant was calculated with the use of nonlinear regression. The R2 and SE of the regression were calculated to determine the goodness of fit. Results were plotted for all animals and animals grouped by sex and age (younger [1 to ≤ 2 years old] vs older [> 2 years old]). A K constant was calculated for each bearded dragon. A 2-tailed t test was performed to determine whether the K constant values differed significantly for males versus females and for younger versus older animals. Values of P < 0.05 were considered significant. All statistical analyses were performed with available software.c
Results
Animals
Twelve adult bearded dragons (5 females and 7 males) were included in the study. The mean age was 2.1 years (range, 1 to 4 years; median, 2 years), with 8 animals that were from 1 to ≤ 2 years of age (younger group) and 4 animals that were > 2 years age (older group; Table 1). The mean body weight was 356 g (range, 159 to 657 g; median, 355 g). All animals were client owned and reportedly healthy and behaving normally at home. Additionally, all animals were confirmed healthy on the basis of findings from physical examination, and none had external abnormalities that deformed their body contour.
Summary results for 12 healthy client-owned bearded dragons stratified by sex and age (1 to ≤ 2 years old [younger] vs > 2 years old [older]) that underwent CT between December 4, 2019, and April 2, 2020, so that 3-D CT reconstructed surface models could be created and used to determine each animal's BSA.
Variable | All bearded dragons | Females (n = 5) | Males (n = 7) | Younger (n = 8) | Older (n = 4) | |||||
---|---|---|---|---|---|---|---|---|---|---|
Mean | Median (range) | Mean | Median (range) | Mean | Median (range) | Mean | Median (range) | Mean | Median (range) | |
Age (y) | 2.1 | 2 (1–4) | 2 | 1 (1–4) | 2.1 | 2 (1–3) | 1.5 | 1.5 (1–2) | 3.3 | 3 (3–4) |
Body weight (g) | 356 | 355 (159–657) | 317 | 260 (159–657) | 383 | 393 (177–272) | 314 | 308 (159–449) | 438 | 415 (265–392) |
CT-derived BSA (cm2) | 580 | 614 (371–784) | 526 | 503 (371–784) | 619 | 624 (566–650) | 559 | 591 (280–371) | 23 | 620 (469–784) |
All CTs were performed without complication between December 4, 2019, and April 2, 2020. Adequate separation from the CT table was achieved such that the reconstruction software was able to isolate the subject without the need for manual outlining or reconstruction for 11 of the 12 bearded dragons. For the remaining animal, the reconstructed model required minimal manual editing to achieve separation at the connection point for the body outline and underlying support. The rest of the reconstruction and calculations for this animal were then performed in the same fashion as for the other 11 bearded dragons. The resulting reconstructions had subjectively uniform visual detail (Figure 1). The mean CT-derived BSA was 580 cm2 (range, 371 to 784 cm2; median, 614 cm2; Table 1).
Results were compiled for BSA plotted against body weight for each bearded dragon and for animals grouped by sex and age (Figure 2). Results for K constants were compiled (Table 2). When results for all 12 bearded dragons were considered, the K constant derived was 11.6 (SE = 0.27; R2 = 0.994). For K constants derived for bearded dragons grouped on the basis of sex and age, results of a 2-tailed t test revealed no significant (P = 0.911) difference in K constants for males (11.7) versus females (11.3); however, the K constant was significantly (P = 0.015) higher for animals in the younger group (12.1) versus the older group (10.9).
Results of nonlinear regression analysis of the CT-derived BSA versus body weight for the 12 bearded dragons described in Table 1 to determine the shape constant (K) for creating a species-specific formula for calculating BSA on the basis of body weight in bearded dragons: BSA in cm2 = K X (body weight in g)2/3.
Groups of bearded dragons | K constant | SE | R2 | P value* |
---|---|---|---|---|
All | 11.6 | 0.275 | 0.994 | 1.72E-13 |
Females | 11.3 | 0.516 | 0.992 | 2.56E-05 |
Males | 11.7 | 0.328 | 0.995 | 3.27E-08 |
Younger | 12.1 | 0.305 | 0.996 | 1.69E-09 |
Older | 10.9 | 0.257 | 0.998 | 2.93E-05 |
Reported as the exponential notation (E) for powers of 10 (eg, 1.72E-13 means 1.70 × 10−13).
Discussion
The use of 3-D CT reconstruction to derive BSA is relatively new. The technique has rarely been reported18,19 in veterinary medicine, and to our knowledge, the present report was the first to describe the use of the technique in reptiles. The technique was minimally invasive, required no anesthesia of the bearded dragons, and produced detailed and accurate 3-D CT surface models without the need for manual editing of the body contour, except for the model for 1 animal that required minimal editing to eliminate represented contact with the CT table.
On the basis of our results, the CT-derived BSA formula for bearded dragons is as follows: BSA in cm2 = 11.6 × (body weight in g)2/3. The nonlinear regression model had excellent goodness of fit (SE = 0.275; R2 = 0.994; P < 0.01). The derived K constant, 11.6, was larger than the constants used in dogs and cats (10.1 and 10.0, respectively)13 and those derived with CT reconstruction techniques in ferrets (9.94)18 and rabbits (9.9).19 Previously, the K constant for reptiles was estimated as K = 10 on the basis of metabolic energy requirements.28 Thus, the K constant derived in the present study could have clinical impacts because the higher value suggested that doses of chemotherapeutic agents may need to be higher than previously thought. Further research is indicated to determine whether the K constant we derived is applicable across reptilian species or specific to bearded dragons.
The K constant derived for males did not differ substantially from that for females, and this finding was consistent with the fact that bearded dragons are not sexually dimorphic in their size.29 There was a significant difference between the K constant derived for younger versus older animals, and the clinical impact of this finding warrants further investigation. Reptile growth rates can be influenced by many extrinsic factors, including food intake, habitat, and habitat temperature.30 Their growth also can continue past sexual maturity and throughout the entirety of their lifespan.30
A limitation of the present study was that we did not evaluate bearded dragons of ages across the species' life span, which is approximately 10 years.7 There were also few animals in each group. Further research is indicated with the use of larger sample sizes and wider age ranges to determine whether an age-based difference exists for bearded dragons across their life span. Measuring the BSA of individuals at multiple time points throughout their lives could also be useful in answering this question. Another concern was whether the scales covering bearded dragons could artificially increase their BSA. However, a recent study31 that used gel-based stereo-profilometry to examine scaling patterns of lizards shows that scale size increases isometrically with body size and that scale shape does not change with ontogeny.31 Given the small size of bearded dragons and the fact that their scales are relatively small and minimally alter their body contour, their scales were considered to have had little clinical influence on BSA.
Questions exist regarding the utility of BSA for chemotherapeutic drug dosing in human and veterinary medicine.13,27,32 This type of dosing is reliant on the assumption that processes such as glomerular filtration rate and metabolic rate are proportional to BSA. Given the fact that reptile species have lower metabolic rates, compared with mammals, the question regarding the utility of BSA is important and is worthy of further research. In addition, studies evaluating pharmacokinetics and pharmacodynamics of chemotherapeutic agents in bearded dragons are indicated so that the most appropriate recommendations on dosing these agents can be obtained. In dogs, the dosing of chemotherapeutic drugs is based on BSA, and that basis has been questioned owing to the great variability in body size across breeds. For instance, the use of BSA has been reported13 to lead to a greater risk of overdosing chemotherapeutic drugs in smaller breeds, and the use of dosing by body weight (eg, milligrams of drug per kilogram of body weight) may be more appropriate for smaller breeds to avoid toxicoses.13 However, in standard oncologic practice, chemotherapeutic doses for dogs that weigh < 15 kg are calculated on the basis of body weight rather than BSA for only the most toxic chemotherapeutic agents, such as doxorubicin.13 Therefore, we appreciate that BSA continues to be useful for accurate chemotherapeutic dosing, even in smaller species such as bearded dragons; however, we also recommend caution when veterinarians need to prescribe highly toxic chemotherapeutic agents and suggest that the calculation of dosage on the basis of body weight rather than BSA be considered on a case-by-case basis.
The present study provided a minimally invasive method for determining the BSA and a species-specific formula for bearded dragons. This information could be used to calculate doses of chemotherapeutic agents or other medications that have low therapeutic indices for use in bearded dragons. Further research is indicated to determine pharmacokinetic data in this species, the effects of age on BSA in reptiles, and BSA formulas in other reptilian species.
Acknowledgments
The study was funded by the North Carolina State University Turtle Rescue Team.
The authors declare that there were no conflicts of interest.
Footnotes
SOMATOM Perspective, Siemens Healthcare, Malvern, Pa.
Mimics Innovation Suite, Materialise NV, Leuven, Belgium.
R: A language and environment for statistical computing, version 3.6.1, R Foundation for Statistical Computing, Vienna, Austria. Available at: www.R-project.org. Accessed Apr 8 and Oct 18, 2020.
Abbreviations
BSA | Body surface area |
References
- 1. ↑
Christman J, Devau M, Wilson-Robles H, et al. Oncology of reptiles. Vet Clin North Am Exot Anim Pract 2017;20:87– 110.
- 2. ↑
Hannon DE, Garner MM, Reavill DR. Squamous cell carcinomas in inland bearded dragons (Pogona vitticeps). J Herpetol Med Surg 2011;21:101–106.
- 3. ↑
Jankowski G, Sirninger J, Borne J, et al. Chemotherapeutic treatment for leukemia in a bearded dragon (Pogona vitticeps). J Zoo Wildl Med 2011;42:322–325.
- 4. ↑
Gardhouse S, Eshar D, Lee-Chow B, et al. Diagnosis and treatment of a periocular myxosarcoma in a bearded dragon (Pogona vitticeps). Can Vet J 2014;55:663–666.
- 5. ↑
Darrow BG, Johnstone McLean NS, Russman SE, et al. Peri-orbital adenocarcinoma in a bearded dragon (Pogona vitticeps). Vet Ophthalmol 2013;16:177–182.
- 6. ↑
Jakab C, Miklos R, Zoltan S, et al. Claudin-7-positive synchronous spontaneous intrahepatic cholangiocarcinoma, adenocarcinoma and adenomas of the gallbladder in a bearded dragon (Pogona vitticeps). Acta Vet Hung 2011;59:99–112.
- 7. ↑
Ritter JM, Garner MM, Chilton ER, et al. Gastric neuroendocrine carcinomas in bearded dragons (Pogona vitticeps). Vet Pathol 2009;46:1109–1116.
- 8. ↑
Hahn KA. Chemotherapy dose calculation and administration in exotic animal species. Semin Avian Exotic Pet Med 2005;14:193–198.
- 9. ↑
Hernandez-Divers SM, Garner MM. Neoplasia of reptiles with an emphasis on lizards. Vet Clin North Am Exot Anim Pract 2003;6:251–273.
- 10. ↑
Graham JE, Kent MS, Théon A. Current therapies in exotic animal oncology. Vet Clin North Am Exot Anim Pract 2004;7:757–781.
- 11. ↑
Harrison TM, Kitchell BE. Principles and applications of medical oncology in exotic animals. Vet Clin North Am Exot Anim Pract 2017;20:209–234.
- 12. ↑
Zehnder A, Graham J, Antonissen G. Update on cancer treatment in exotics. Vet Clin North Am Exot Anim Pract 2018;21:465–509.
- 13. ↑
Chun R, Garrett LD, Vail DM. Cancer chemotherapy. In: Withrow SJ, Vail DM, eds. Withrow and MacEwen's small animal clinical oncology. 4th ed. St Louis: Saunders, 2007;163–192.
- 14. ↑
Du Bois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916;17:863–871.
- 15. ↑
Price GS, Frazier DL. Use of body surface area (BSA)-based dosages to calculate chemotherapeutic drug dose in dogs: I. Potential problems with current BSA formulae. J Vet Intern Med 1998;12:267–271.
- 16. ↑
Pinkel D. The use of body surface area as a criterion of drug dosage in cancer chemotherapy. Cancer Res 1958;18:853– 856.
- 17. ↑
Grochow LB, Baraldi C, Noe D. Is dose normalization to weight or body surface area useful in adults? J Natl Cancer Inst 1990;82:323–325.
- 18. ↑
Jones KL, Granger LA, Kearney MT, et al. Evaluation of a ferret-specific formula for determining body surface area to improve chemotherapeutic dosing. Am J Vet Res 2015;76:142– 148.
- 19. ↑
Zehnder AM, Hawkins MG, Trestrail EA, et al. Calculation of body surface area via computed tomography-guided modeling in domestic rabbits (Oryctolagus cuniculus). Am J Vet Res 2012;73:1859–1863.
- 20. ↑
Liu CT, Higbee GA. Determination of body surface area in the rhesus monkey. J Appl Physiol 1976;40:101–104.
- 21. ↑
Sreekumar KP, Nirmalan G. Estimation of the total surface area in Indian elephants (Elephas maximus indicus). Vet Res Commun 1990;14:5–17.
- 22. ↑
Spiers DE, Candas V. Relationship of skin surface area to body mass in the immature rat: a reexamination. J Appl Physiol 1984;56:240–243.
- 23. ↑
Liu CT. Changes in body weight and body surface area in strain 13 guinea pigs infected with Pichinde virus. Life Sci 1989;44:95–101.
- 25. ↑
Mitchell G, van Sittert S, Roberts D, et al. Body surface area and thermoregulation in giraffes. J Arid Environ 2017;145:35–42.
- 26. ↑
Schloesser RL, Lauff M, Buxmann H, et al. Three-dimensional body scanning: a new method to estimate body surface area in neonates. Neonatology 2011;100:260–264.
- 27. ↑
Villa C, Primeau C, Hesse U, et al. Body surface area determined by whole-body CT scanning: need for new formulae? Clin Physiol Funct Imaging 2017;37:183–193.
- 28. ↑
Mayer J. Allometric scaling. In: Divers SJ, Scott SJ, eds. Mader's reptile and amphibian medicine and surgery. 3rd ed. St Louis: Elsevier, 2010;1186–1190.
- 29. ↑
Barten S, Simpson S. Lizard taxonomy, anatomy and physiology. In: Divers SJ, Scott SJ, eds. Mader's reptile and amphibian medicine and surgery. 3rd ed. St Louis: Elsevier, 2010;63–74.
- 30. ↑
Andrews RM. Patterns of growth in reptiles. In: Gans C, Pough FH, eds. Biology of the reptilia. Vol 13. New York: Academic Press, 1982;273–320.
- 31. ↑
Baeckens S, Wainwright DK, Weaver J, et al. Ontogenetic scaling patterns of lizard skin surface structure as revealed by gel-based stereo-profilometry. J Anat 2019;235:346–356.
- 32.
Dooley MJ, Poole SG. Poor correlation between body surface area and glomerular filtration rate. Cancer Chemother Pharmacol 2000;46:523–526.