By Mike Corcoran, DVM, DABVP (R/A), CertAqV

A new client comes to your practice with a 3-year old rescue bearded dragon. The client expresses concern that their new pet may have “Metabolic Bone Disease” after doing some internet research. They want to know more about how this happens and how to tell if the new pet may be affected. 

Unfortunately, metabolic bone disease is an incomplete term that addresses only the end-stage aspect of a more involved disease process. Read on to learn more about how to handle this concern along with its associated real-world implications.

What exactly is metabolic bone disease?

Metabolic bone disease (MBD) is a weakening of the bones due to loss of mineralization. To be radiographically evident, approximately 50% of the mineral content of the bone must be lost (Mans 2014). Metabolic bone disease is a sequela of several different conditions and often represents an end-stage disease process. 

In the reptile caretaker community, MBD has unfortunately been used as a misnomer for Nutritional Secondary Hyperparathyroidism (NSHP), one of the disease conditions that can ultimately lead to MBD and other metabolic derangements. Even more unfortunately, the veterinary community has carried on with the misnomer for a long time. 

When and why did the name change?

The name hasn’t really changed. NSHP has been referenced in veterinary literature since before the turn of the century. As mentioned, veterinarians have referred to the condition incorrectly as MBD, or discussed MBD without using the terminology for the underlying cause as an attempt to ease communication with clients. Continuing to discuss the condition as MBD allows the client to focus only on bones. Using NSHP corrects their way of thinking about the seriousness of the disease condition. In the past few years, there has been a more concerted effort on the part of reptile veterinarians to use more correct terminology in order to distinguish NSHP from Renal Secondary Hyperparathyroidism (RSHP) and other disease processes that affect calcium uptake and utilization. 

What are the real implications for veterinarians with this terminology?

First, and most importantly, framing disease as NSHP helps guide the veterinarian into a more preventative role. If MBD actually represents an end-stage process of NSHP, then focusing on husbandry and more early recognition of disease becomes more sensible. Just like other pets, reptiles should be getting routine wellness examinations to ensure that any lapses in husbandry, diet, or vitamin supplementation are caught before there are outward signs of end-stage metabolic disease. Another important aspect of the wellness examination is routine blood testing. Utilizing a veterinary diagnostic laboratory familiar with reptiles and their associated annual CBC and serum chemistry testing can help identify problems at a stage where they are more easily corrected. Total calcium levels near the lower end of the reference ranges may lead to more in-depth conversation about care and diet to help the animal lead a healthier life. 

Second, proper use of the terminology helps guide the diagnostic process and client education. NSHP is diagnosed and treated very differently than RSHP, hepatic disease, or malabsorption from other conditions. Redirecting clients to the proper terminology offers the opportunity for education, which will ultimately lead to better care. The more informed a client is with regard to the severity of the condition and the systems affected, the better compliance can be expected from the treatment plan. Demonstrating the knowledge of the processes helps to build trust with clients, especially clients who are skeptical of a veterinarian’s ability to properly treat reptile species. 

What’s the normal physiology of calcium in reptiles? 

In a normal, healthy animal, serum calcium accounts for only 1% of the total calcium in the body. The remaining 99% of the body’s calcium is stored in the bones. In reptiles, diets insufficient in calcium, diets with an improper calcium to phosphorus ratio and inadequate Vitamin D3 (from diet and/or UV access) will result in a lowered serum ionized calcium. This causes increased activity from the parathyroid gland and that leads to movement of calcium from the bone stores into circulation (Mans, 2014).

The increased parathyroid activity can also result from medical conditions that interfere with normal Vitamin D activation or that affect calcium absorption from the gastrointestinal tract. It’s important to remember that formation and activation of vitamin D in most reptiles requires UV radiation, healthy skin, healthy kidneys, and a healthy liver (Watson 2014). 

What tests or diagnostics are used to diagnose NSHP?

Understanding the physiologic process of NSHP provides a clearer clinical picture and insight into the complex role calcium plays. Consequently, it helps with understanding why no one single diagnostics test is sufficient. 

Firstly, calcium homeostasis affects far more than skeletal health. Calcium is essential in muscle function, including cardiac muscle. Actin and myocin interaction is a calcium-dependent process (Szent-Gyorgyi 1975). Calcium is involved with conduction of impulses in NMDA, serotonin, nicotinic acetylcholine and other nerve receptors (Kawamoto 2012). Calcium is important for the normal pacemaker function of the heart, with calcium-dependent processes in the SA node, AV node, and Purkinje fibers (Bers 2002). Cell signaling through influx of calcium is a principal means of activating lymphocytes (Vig 2009). 

Considering the importance of calcium in all of these functions, it should be clear that no single diagnostic test in isolation can give a full clinical picture. Then what combination of reptile diagnostics testing should be done to confidently diagnose NSHP? 

Radiographs have been described in evaluation of MBD, but again, there needs to be 40-50% loss of mineralization for radiographic change. Other testing can find concerns much earlier, including serum calcium. In fact, serum calcium should always be evaluated, but keep in mind that there are many reasons why total calcium could be within published reference ranges even with moderate disease. With so many important functions linked to calcium homeostasis, the body will sacrifice a great deal to maintain normal serum levels. 

Additionally, it’s common to see signs of NSHP worsen with active reproductive activity. Oogenesis in a normal reptile will cause significant increases in serum calcium levels (Divers 2019). If elevated calcium from reproductive activity is countered by lowered calcium with severe NSHP, the result could be a value within the published reference ranges. In addition to total calcium, ionized calcium should be evaluated in suspected NSHP cases. Ionized calcium is arguably more clinically relevant, since it’s the active form of usable calcium in the body and should more accurately reflect the health status. 

A reptile serum chemistry panel from a veterinary diagnostic laboratory familiar with reptiles is important to evaluate renal and hepatic health, electrolytes, and gastrointestinal health, so don’t forget to get a comprehensive panel rather than focusing only on the calcium levels. Fecal examination can also help look for parasites that may affect absorption of nutrients. A CBC can evaluate the status of the immune system, look for signs of inflammation or infection, and look for signs of stress indicated by anemia. Finally, protein electrophoresis will be the most accurate measure of acute phase proteins and albumin to look for protein loss or systemic inflammation. 

‍What can we expect in the future with other developments? 

In reptile veterinary medicine, we are continuing to learn more about the natural behaviors and diets for many captive species, seasonal variations in CBC and serum chemistry reference ranges, best practices for calcium supplementation of food items, and inflammatory markers on blood testing, just to scratch the surface. Continuing to learn is the hallmark of the profession and is what allows us to always improve on the preventative health that we use to keep animals healthy so that in the future we see far less end-stage presentation of disease conditions.

Understanding the complete physiology and all of the diagnostic options allows the veterinarian to more fully educate clients in prevention, diagnostic options, and treatment options for reptiles with regard to NSHP. 

‍References

Bers D. Calcium and Cardiac Rhythms. Circulation Research. 2002;90:14–17.

Divers S, and Stahl S. Chapter 105: Reproductive Tract In: Mader’s Reptile and Amphibian Medicine and Surgery, 3^rd Ed. Elsevier. 2019. 

Kawamoto E, Vivar C, and Camandola S. Physiology and Pathology of Calcium Signaling in the Brain. Frontiers in Pharmacology 2012 Apr; 3: https://doi.org/10.3389/fphar.2012.00061. 

Mans C, and Braun J. Update on Common Nutritional Disorders of Captive Reptiles. Vet Clin Exot Anim 17 (2014) 369-395.

Szent-Gyorgyi A. Calcium Regulation of Muscle Contraction. Biophys J 1975 Jul; 15(7): 707-723.

Watson M, and Mitchell M. Vitamin D and  Ultraviolet B Radiation Considerations for Exotic Pets. Journal of Exotic Pet Medicine 23 (2014), pp 369–379.

Vig M, and Kinet J. Calcium Signaling in Immune Cells. Nat Immunol. 2009 Jan; 10(1): 21–27.