Nutritional Secondary Hyperparathyroidism
Basic Information 
Definition
A form of metabolic bone disease characterized by hypersecretion of parathormone in response to low blood calcium caused by a diet that does not provide sufficient calcium.
Synonyms
Nutritional secondary hyperparathyroidism (NSHP), metabolic bone disease, rubber jaw, brittle bones
Clinical Presentation
History, Chief Complaint
The amphibian may be anorectic or may have obvious limb or mouth deformities.
Physical Exam Findings
• An amphibian that is unable to maintain sufficient levels of circulating calcium may develop bloating, tetany, hydrocoelom, lethargy, and sudden death.
• An amphibian that has normocalcemic NSHP may have a deformed lower jaw, a slightly protruding tongue, slight rounding of the profile of the snout, an inability to elevate itself from the substrate, a curved spine and a kinked tail, and deformed or obviously fractured limb bones.
Etiology and Pathophysiology
• A calcium-to-phosphorus ratio that is significantly different from 1.5 : 1 or 2 : 1. Most prey items fed to captive amphibians have an inverse ratio of calcium to phosphorus, typically less than 1 : 1.
• An absolute lack of calcium despite an appropriate ratio of calcium to phosphorus
• Calcium in the water may be a significant source of this mineral. Amphibians adapted for hard water may develop NSHP if the calcium hardness of their water is too low.
• Lack of vitamin D3 in the diet may impair calcium absorption and distribution. A ratio of fat-soluble vitamins inappropriately high in vitamin A or vitamin E may impair vitamin D3 absorption and utilization. Typically, the ratio should be 100 IU D3 to 10 IU A to 1 IU E. Domestic rodents may have an inappropriate balance of fat-soluble vitamins.
• An inappropriately acidic substrate may interfere with the proton pump systems needed to maintain normocalcemia and increase the demand for an external source of calcium. This frequently results in gastrointestinal bloating, tetany, seizures, and other signs of hypocalcemia.
• Various other metal ions are present in common calcium supplements such as calcium carbonate and oyster shell flour. These may interfere with calcium uptake if above or below certain levels.
• Oversupplementation with calcium may impair absorption and create NSHP.
Diagnosis 
Initial Database
• Whole-body radiographs to assess radiolucency of bones. Early signs include increased radiolucency of the pelvic bones and lateral spinous processes. With advancing NSHP, additional bones may become radiolucent, and pathologic fractures may occur. Spinal deformities may be present. Endolymphatic sacs may not be mineral dense. Otoliths may be the only significant mineral-dense object visible in very advanced cases.
• A DV digital photo can be used to assess subtle changes in spinal deformities of anurans. Typically, the spine runs in a straight line from between the external nares, between the eyes, and over the center of the urostyle. Deviations are often noticed because the center of the urostyle starts to angle away from the line of the spine.
Advanced or Confirmatory Testing
Bloodwork should include ionized and total calcium and phosphorus and total protein. An amphibian may have near normal total calcium and still have hypocalcemic signs as the result of low ionized calcium. Inverse plasma levels of calcium-to-phosphorus support a diagnosis of chronic NSHP.
Treatment 
Acute General Treatment
• If tetany, paralysis, or gastrointestinal bloating is noted: 10% calcium gluconate or calcium chloride at 100 mg/kg ICe q 4-6 h until tetany subsides. No sooner than 24 hours after resolution of hypocalcemic signs, consider administration of 1000 IU/kg vitamin D3 PO or topically. Caution is warranted because this may reinduce a hypocalcemic state.
Chronic Treatment
• Balance the nutrient intake.
Although calcium, phosphorus, and vitamin D3 are often the sole target of balancing, levels of vitamin A and vitamin E intake should be investigated and balanced if excessively high.
Domestic rodents typically have levels of vitamin A that can interfere with vitamin D3 absorption, so they should be removed from the diet until the disease is corrected.
Supplemental calcium may be provided orally by dusting food items with pure calcium carbonate, calcium citrate, or calcium lactate. A liquid calcium source, such as calcium glubionate, may be compounded for direct oral supplementation.
Vitamin D3 may be provided by dusting food items or through oral dosing of 100-400 IU/kg PO weekly.
• Calcium and vitamin D3 may be absorbed through the skin and may be needed for rapid mineralization of skeletal structures in amphibians with severe deformities.
A 2% to 5% solution of calcium gluconate is well tolerated by many species as an 8- to 12-hour daily bath.
Vitamin D3 may be administered in a continuous bath of 3 IU/mL or may be applied topically at 400 IU/kg weekly.
• A minimum of 30 days of supplementation is needed to correct mild to moderate MBD.
• Whole-body radiographs should be taken every 2 to 4 weeks to assess mineralization and conformation of the skeleton.
Pearls & Considerations 
Comments
This is one of the most common diseases of captive-born and raised amphibians. Although the focus is on dietary correction, a thorough husbandry review is needed to identify any other contributing factors.
Prevention
• Supplementation with an appropriate calcium source and a balanced multivitamin supplement
• Proper handling of nutritional supplements
• Proper feeding practices (e.g., dusting, timing of feeding, appropriate prey items)
• Proper environmental conditions (e.g., do not keep hard water–adapted species in acidic conditions)
Client Education
• Euthanasia may be necessary for amphibians that have significant skeletal lesions or show evidence of chronic pain following remineralization of the skeleton.
• Crickets, fruit flies, mealworms, and waxworms are deficient in calcium and vitamin D3 and will induce NSHP if fed to young growing amphibians without supplementation.
• All supplements are not created equal. A pure calcium source free of other metals is the best choice for a supplement. Calcium lactate, calcium citrate, and pharmaceutical grade calcium carbonate are excellent sources of pure calcium. Other sources of calcium may contain heavy metals such as lead in quantities that may interfere with normal metabolism.
• Most vitamin sources do not have vitamin D3 but carry vitamin D2, which has not been shown to support normal skeletal mineralization in amphibians. Check with a veterinarian for an appropriate source of vitamin D3.
• Ultraviolet B may help some amphibians convert vitamin D2 to vitamin D3, but this remains unproven.
• Nutritional needs change with age. All things being equal in the captive environment, growing amphibians have a much greater demand for calcium compared with mature amphibians.