Hungry Bone Syndrome - Causes, Symptoms, and Treatment

What Is Hungry Bone Syndrome?

A hungry bone syndrome is a rare condition characterized by severe hypocalcemia that persists for a prolonged period. It occurs most commonly after removing the parathyroid or the thyroid glands.

What Are the Causes of Hungry Bone Syndrome?

The causes of the hungry bone syndrome are as follows:

• Parathyroidectomy (removal of parathyroid glands), due to primary or secondary hyperparathyroidism.

• Thyroidectomy (removal of thyroid glands) due to thyrotoxicosis.

• Metastatic prostate cancer.

How Common Is Hungry Bone Syndrome?

• Studies report that the rate of incidence of hungry bone disease has changed over time. It was estimated that it occurs in 13 percent of cases following the parathyroidectomy for primary hyperparathyroidism in the past, but in recent studies, the incidence rate has declined to four percent.

• One cohort study has reported that the incidence rate among the Asian population is 87 percent. The rate of incidence of hungry bone syndrome in patients following secondary hyperthyroidism ranges from 20 to 70 percent.

• The incidence of hungry bone syndrome in patients following thyroidectomy is 39 percent.

• Only a handful of cases of hungry bone syndrome following metastatic prostate cancer are reported in the literature.

How Does Hungry Bone Syndrome Occur?

• Parathyroid glands maintain calcium homeostasis through the synthesis and release of parathyroid hormone. The parathyroid hormone maintains the serum calcium level by increasing the osteoclastic activity and limiting the osteoblastic activity, thereby releasing the calcium stored in the bone into the blood. The calcium-sensing receptors sense the changes in calcium levels and activate the cascade of reactions, such as bone resorption and bone formation, thereby maintaining the serum calcium levels.

• Likewise, the thyroid glands also play an important role in calcium homeostasis by releasing calcitonin when the calcium levels increase in the blood. This calcitonin has a reverse effect on the parathyroid hormone, increasing the osteoblastic activity, limiting the osteoclastic activity, thereby causing the excess calcium to get deposited in the bones and reducing serum calcium levels.

• The pathogenesis behind hypocalcemia in patients with hungry bone disease is due to the high bone turnover rates that happen due to hyperparathyroidism and thyrotoxicosis.

• This would increase the osteoblastic activity in the body when the excess hormones are removed from the blood following parathyroidectomy and thyroidectomy. The increased osteoblastic activity remains unchanged; the osteoblasts take up all the calcium from the blood to build the bone. This, in turn, would result in decreased serum calcium levels (hypocalcemia).

• The same process happens in male patients with metastatic prostate cancer, where the osteoblastic activity is upregulated, resulting in increased excess bone formation and decreased serum calcium levels.

What Other Electrolyte Disturbances Occur in Hungry Bone Syndrome Other Than Calcium?

Phosphate and Magnesium are the electrolytes altered due to abnormal serum calcium levels. As calcium, phosphate, and magnesium are interdependent electrolytes, the alteration in one electrolyte's level would affect the other's level. Hence, in patients with hungry bone disease, in addition to features of hypocalcemia, the features of hypophosphatemia and hypomagnesemia will also be noted.

What Are the Risk Factors of Hungry Bone Syndrome?

The risk factors for hungry bone disease include:

• Elevated parathyroid hormone levels.

• Elevated alkaline phosphatase levels.

• High BMI (body mass index).

• Bone diseases, such as brown tumors and osteitis fibrosa cystica.

• High BUN (blood urea nitrogen) level.

• Vitamin D deficiency.

• Metastatic tumor to the bones.

• Increased number of osteoclasts present in the bone marrow biopsy.

• Primary hyperparathyroidism.

• Secondary hyperparathyroidism.

• Thyrotoxicosis.

What Are the Symptoms of Hungry Bone Syndrome?

The symptoms of this condition are as follows:

• Bone pain.

• Fatigue.

• Muscle spasms.

• Weak bones.

• Muscle cramps.

• Tingling of hands and feet.

• Muscle weakness.

• Altered mental state.

• Easily fracturing bones.

• Seizures.

How Is Hungry Bone Syndrome Diagnosed?

The steps in the diagnosis of hungry bone disease include:

• History: A thorough and complete medical history should be collected from the patient, such as the previous history of hyperparathyroidism and thyrotoxicosis, history of surgery such as parathyroidectomy and thyroidectomy, any metastatic prostate tumors, bone disease, and the symptoms associated with the condition. A proper history from the patient would help reach the diagnosis halfway.

• Physical Examination: The patient should be examined to check for the condition's symptoms, such as weak bones, fractured bones, muscle weakness, etc.

• Blood Test - Serum Calcium Levels: Decreased serum calcium levels below 8.4 mg/dL, indicating hypocalcemia.

• X-Ray: Bone X-rays would help identify the excess bone formation and exclude the presence of metastatic bone tumors.

How Is Hungry Bone Syndrome Treated?

The following options treat the hungry bone syndrome:

• Intravenous Calcium - Intravenous calcium gluconate and calcium chloride should be administered in patients with serum calcium levels less than 7.6 mg/dL. It should be given as a bolus of 10% calcium gluconate, 10 to 20 ml in 50 to 100 ml of D5% IV (intravenous) fluids, given within five to ten minutes. The oral regimens should be started as the patient becomes fit to take medications orally.

• Oral Calcium Supplements - Calcium carbonate and calcium citrate are given as oral supplements.

• Oral Magnesium Supplements - Should be given based on the requirement.

• Phosphate Supplements - Should be given based on the demand.

• Vitamin D Supplements - Vitamin D supplements be given to compensate for vitamin D deficiency.

Can One Avoid the Hungry Bone Syndrome?

Healthcare professionals take precautions to try to prevent HBS because it can occur following thyroid or parathyroidectomy. These precautions include:

• Pre-surgical Evaluation: The doctor will measure the blood calcium, phosphate, PTH, vitamin D, and bone mineral density prior to surgery. Medical professionals can determine whether individuals have a higher chance of developing HBS by using these tests.

• Preventive Measures: A healthcare provider may advise taking medication or supplements before surgery to ensure that the calcium and vitamin D levels are within the normal range if they have a high risk of developing HBS.

• Post-surgical Observation: Following surgery, the medical team will keep a careful eye on the calcium, phosphate, magnesium, and PTH levels. This can help them detect HBS early and begin treatment as soon as it manifests.

What Is the Prognosis of Hungry Bone Syndrome?

The prognosis of the hungry bone syndrome depends on the disease's underlying cause and severity. It shows a good prognosis with proper treatment and monitored serum calcium levels. It has been reported that the patients need to be under supplements for up to one year to normalize the serum calcium levels and balance the levels of electrolytes, such as phosphate and magnesium.

What Are the Complications of Hungry Bone Syndrome?

The complications mainly occur due to hypocalcemia, which are as follows:

• Seizures.

• Cardiomyopathy (disease of the heart muscle).

• Cardiac arrhythmias (irregular heartbeat).

Conclusion:

The hungry bone syndrome is a rare condition characterized by profound hypocalcemia. The complications occur due to decreased serum calcium levels. Most physicians miss the diagnosis of hungry bone disease when approaching a patient with hypocalcemia. Proper history from the patient regarding the history of surgery for removal of the parathyroid or the thyroid gland would help diagnose the condition. There are increased chances of morbidity due to the complications associated with the disease. Hence, early diagnosis and timely treatment are necessary to improve the prognosis