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Fibrous Osteodystrophy

(Rubber jaw syndrome)


Walter Gruenberg

, DrMedVet, MS, PhD, DECAR, DECBHM, University of Veterinary Medicine Hannover, Foundation

Last full review/revision Apr 2014 | Content last modified May 2014

Primary Hyperparathyroidism

In primary hyperparathyroidism (see Primary Hyperparathyroidism), there is excess production of parathyroid hormone (PTH) by an autonomous functional lesion in the parathyroid gland. The normal control mechanisms for PTH secretion by the concentration of blood calcium are lost, and the parathyroid produces excess PTH despite increased levels of blood calcium. This disease is encountered infrequently in older dogs, and it does not appear to be a sequela of renal secondary hyperparathyroidism (see Renal Secondary Hyperparathyroidism).

PTH acts on cells of the renal tubules initially to promote the excretion of phosphorus and retention of calcium. A prolonged increased secretion of PTH results in accelerated osteocytic and osteoclastic bone resorption. Mineral is removed from the skeleton and replaced by immature fibrous connective tissue. Fibrous osteodystrophy is generalized throughout the skeleton but is accentuated in local areas such as the cancellous bone of the skull. The increased PTH levels also inhibit the renal tubular resorption of phosphorus.

The lesion in the parathyroid gland in dogs is usually an adenoma, occasionally a carcinoma, composed of active chief cells. Usually, adenomas are single, light brown-red, and located in the cervical region near the thyroid gland.

Clinical Findings:

In primary hyperparathyroidism, lameness follows severe osteoclastic bone resorption, and fractures of long bones occur after minor physical trauma. Compression fractures of weakened vertebral bodies may exert pressure on the spinal cord and nerves, resulting in motor and sensory dysfunction.

Facial hyperostosis with partial obliteration of the nasal cavity (by poorly mineralized woven bone and highly vascular fibrous connective tissue) and loss or loosening of teeth has been seen in dogs. This may result in an inability to close the mouth properly and development of gingival ulcers. The maxillae and rami of the mandibles often are coarsely thickened by the excess woven bone. Bones of the skull are markedly thinned by the increased resorption and have a characteristic “moth-eaten” appearance radiographically. In advanced cases, the mandible can be twisted gently due to loss of osteoid and severe fibrous osteodystrophy—hence the name “rubber jaw” syndrome.


Histologic demonstration of a rim of normal tissue and a partial to complete fibrous capsule in an enlarged parathyroid suggests an adenoma rather than focal hyperplasia. Chief-cell carcinomas tend to be larger than adenomas and fixed to the underlying tissues due to local infiltration of neoplastic cells.


Although other laboratory findings may be variable when diagnosing primary hyperparathyroidism, hypercalcemia is consistent and results from accelerated release of calcium from bone. The blood calcium in healthy dogs is ~10 ± 1 mg/dL, depending on age and diet (and assay method). Serum calcium values consistently >12 mg/dL indicate hypercalcemia. Dogs with primary hyperparathyroidism usually have a serum calcium of ≥12–20 mg/dL. The blood phosphorus is low or in the low-normal range (≤4 mg/dL). The urinary excretion of phosphorus, and often of calcium, is increased and may result in nephrocalcinosis and urolithiasis. Accelerated bone matrix metabolism is reflected by increased urinary excretion of hydroxyproline. Serum alkaline phosphatase activity may be increased in animals with overt bone disease. Demonstration of increased levels of PTH by a species-specific assay in an adult to aged dog with hypercalcemia, hypophosphatemia, and evidence of generalized bone disease provides conclusive evidence of primary hyperparathyroidism. PTH can be measured by sensitive radioimmunoassays or immunoradiometric assays.

The intact PTH assay or dual-site assays can be performed using either serum (preferred) or plasma that has been separated and frozen (–70°C [–94°F] in either glass or plastic tubes) as soon as possible after collection. Using this method, circulating levels of PTH in most animals are near 20 pg/mL (dogs, 20 ± 5 pg/mL; cats, 17 ± 2 pg/mL), with levels in nonhuman primates being slightly lower (normal values also vary among laboratories). PTH assays that use antibody generated against the carboxy terminal end of the human molecule usually give less consistent results in animals other than people.

Differential diagnoses include other causes of hypercalcemia, such as vitamin D intoxication (overdosage), enzootic calcinosis (see Enzootic Calcinosis), malignant neoplasms with osseous metastasis, and humoral hypercalcemia of malignancy (see Hypercalcemia of Malignancy). The hypercalcemia of hypervitaminosis D may be as high as that in primary hyperparathyroidism but is accompanied by varying degrees of hyperphosphatemia and normal serum alkaline phosphatase activity. Skeletal disease usually is absent, because the increased concentrations of blood calcium and phosphorus are derived principally from augmented intestinal absorption rather than from bone resorption.

Malignant neoplasms with osseous metastases may cause moderate hypercalcemia and hypercalciuria, but the alkaline phosphatase activity and serum phosphorus level usually are normal or only slightly increased. These changes are believed to be due to the release of calcium and phosphorus into the blood from areas of bone destruction at rates greater than can be cleared by the kidneys and intestine. Bone involvement is more sharply demarcated and localized to the area of metastasis. Osteolysis associated with tumor metastases results not only from a physical disruption of bone by proliferating neoplastic cells but also from local production of humoral substances that stimulate bone resorption, such as prostaglandins and interleukin-1.

Primary parathyroid hyperplasia has been described in German Shepherd pups. The condition was associated with hypercalcemia, hypophosphatemia, increased immunoreactive PTH, and increased fractional clearance of inorganic phosphorus in the urine. Clinical signs include stunted growth, weakness, polyuria, polydipsia, and a diffuse reduction in bone density. IV infusion of calcium fails to suppress the autonomous secretion of PTH by the diffuse hyperplasia of chief cells in all parathyroids. Lesions include nodular hyperplasia of thyroid C cells and widespread mineralization of the lungs, kidneys, and gastric mucosa. The disease is inherited as an autosomal recessive.

Hypercalcemia also may be associated with multifocal osteolytic lesions associated with septic emboli, complete immobilization, osteosarcoma, hypoadrenocorticism (Addison-like disease), hypocalcitoninism due to a destructive thyroid lesion, chronic renal disease, hemoconcentration, or hyperproteinemia. Hypercalcemia is detected occasionally in dehydrated animals but usually is mild. It is attributed to fluid volume contraction that results in hyperproteinemia and increased concentrations of ionized and nonionized calcium; it resolves rapidly after fluid therapy.


The objective in treating primary hyperparathyroidism is to eliminate the source of excessive PTH production. An attempt should be made to identify all four parathyroid glands before excising any tissue. Single or multiple adenomas should be removed in toto. If all identifiable parathyroids in the cervical region appear to be of normal or smaller size, and the diagnosis is reasonably certain, surgical exploration of the thorax near the base of the heart may be necessary to localize the parathyroid neoplasm.

Removal of the functional parathyroid lesion results in a rapid decrease in circulating PTH levels, because the half-life of PTH in plasma is <15 min. Because plasma calcium levels in animals with overt bone disease may decrease rapidly and be subnormal within 12–24 hr after surgery, they should be monitored frequently. Postoperative hypocalcemia (≤6 mg/dL) can result from the following: 1) depressed secretory activity of chief cells due to suppression by the chronic hypercalcemia or injury to the remaining parathyroid tissue during surgery, 2) abruptly decreased bone resorption due to decreased PTH levels, and 3) accelerated mineralization of osteoid matrix formed by the hyperplastic osteoblasts, which was previously prevented by the increased PTH levels (known as “hungry-bone syndrome”). Infusions of calcium gluconate to maintain the serum calcium between 7.5 and 9 mg/dL, plus feeding high-calcium diets and supplemental vitamin D therapy, corrects this serious postoperative complication. If hypercalcemia persists for ≥1 wk after surgery, or recurs after initial improvement, a second adenoma or metastases from a carcinoma should be suspected.

Renal Secondary Hyperparathyroidism

Renal secondary hyperparathyroidism is a complication of chronic renal failure characterized by increased endogenous levels of parathyroid hormone (PTH). It is more common than primary hyperparathyroidism. In contrast to primary hyperparathyroidism, renal secondary hyperparathyroidism tends not to be autonomous. It is seen frequently in dogs, occasionally in cats, and rarely in other species.

With progressive renal disease, serum hyperphosphatemia develops as the glomerular filtration rate decreases. Hyperphosphatemia leads to lower serum concentration of ionized calcium. Renal synthesis of calcitriol is also reduced. Calcitriol normally acts on the intestine and kidneys to maintain normal calcium levels. Decreased ionized calcium and calcitriol concentrations cause an increase in serum PTH concentrations. As glomerular filtration rate decreases with advancing renal disease, PTH concentrations progressively increase, leading to the clinical manifestations of renal secondary hyperparathyroidism.

Clinical Findings:

The predominant signs of renal insufficiency (eg, vomiting, dehydration, polydipsia, polyuria, and depression) are usually present. Skeletal lesions range from minor changes with early (or mild) renal disease to severe fibrous osteodystrophy of advanced renal failure. The volume of affected bones usually is normal (isostatic), particularly in older dogs because of the slow onset of renal failure and lower metabolic activity of bones. Hyperostotic bone lesions, such as facial swelling, may be seen in younger dogs in which deposition of unmineralized osteoid by hyperplastic osteoblasts and production of fibrous connective tissue exceed the rate of bone resorption.

Skeletal involvement is generalized but not uniform. Lesions become apparent earlier and reach a more advanced stage in certain areas, such as cancellous bones of the skull. Resorption of alveolar bone occurs early and results in loose teeth, which may be dislodged easily and interfere with mastication. As a result of accelerated resorption of cancellous bone of the maxilla and mandible, bones become softened and pliable (“rubber jaw” syndrome), and the jaws fail to close properly. This often results in drooling and protrusion of the tongue. Severely demineralized mandibles are predisposed to fractures and displacement of teeth from alveoli. Long bones are less dramatically affected. Lameness, stiff gait, and fractures after minor trauma may result from increased bone resorption.


All parathyroid glands are enlarged, initially due to hypertrophy of chief cells and subsequently by compensatory hyperplasia. Although the parathyroids are not autonomous, the concentration of PTH in the peripheral blood often exceeds that of primary hyperparathyroidism. Changes such as osteoclastosis, marrow fibrosis, and a higher concentration of woven osteoid may be seen histologically. Severe hypercalcemia, hyperphosphatemia, and high concentrations of PTH seen in advanced disease may cause osteosclerosis.


Renal secondary hyperparathyroidism is diagnosed by laboratory abnormalities consistent with renal insufficiency accompanied by an increase in serum PTH. Radioimmunoassay of PTH that must be species specific is commercially available for most companion animal species and horses. Assays that measure fragments of the PTH molecule should not be used, because the concentration of biologically inactive metabolites of PTH increases with renal failure.


Treatment options for renal secondary hyperparathyroidism include dietary modification, administration of calcitriol (the bioactive metabolite of vitamin D3) in combination with oral supplementation of phosphate binders, and management of the underlying renal disease. Prescription diets with restricted dietary phosphorus are available. Oral calcitriol (1.5–3.5 ng/kg/day) has reversed hyperparathyroidism of chronic renal failure, but calcitriol therapy is contraindicated with hyperphosphatemia or hypercalcemia. (Special compounding of calcitriol is needed, because the dosages currently available commercially are much larger than those needed clinically.) Dietary phosphorus binders are used to decrease the amount of phosphorus available for absorption in the intestines and should be administered with meals. This therapy is especially important during calcitriol supplementation, because calcitriol increases the absorption of phosphorus and calcium.


If untreated, secondary hyperparathyroidism results in irreversible hypertrophy of the parathyroid glands, a condition also known as tertiary hyperparathyroidism. In this stage, hyperparathyroidism becomes unresponsive to treatment and requires surgical extirpation of the hypertrophic parathyroid glands.

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