What Is Hungry Bone Syndrome?

Overview

Hungry Bone Syndrome (HBS), also known as postoperative hypocalcaemia, is a rare but potentially severe complication that usually occurs following neck surgery; however, it has been known to also occur in patients following some bone cancers. It is characterised by a rapid decrease in blood calcium levels (hypocalcaemia) due to increased uptake of calcium into bones.¹ 

Calcium is a chemical element and the most abundant mineral in the body. Calcium plays a crucial role in numerous physiological processes, including the development and maintenance of strong bones and teeth. It is also essential in the regulation of vascular contractions (narrowing of the blood vessels), muscle function (including heart muscle), and nerve transmission.²

Despite its importance, calcium cannot be made by the body and can only be absorbed from the foods we eat or calcium supplements. Its levels are regulated by a hormone called parathyroid hormone (PTH), which is found in the parathyroid – a small pea-sized gland on the surface of the thyroid gland in the neck. 

PTH works to increase calcium levels in the blood by acting on organs like the bones, kidneys, and the small intestines. In the bones, PTH stimulates cells that break down bones (osteoclasts) and, in doing so, release calcium into the bloodstream. 

In the kidneys, PTH acts to directly increase calcium reabsorption into the blood and decrease phosphate reabsorption. Similarly, in the small intestine, PTH acts through Vitamin D to increase the reabsorption of calcium and increase its levels in the blood.³ Vitamin D promotes enhanced absorption of dietary calcium from the small intestine.^1,3

This article will explore the causes, signs and symptoms, diagnosis, and management associated with hungry bone syndrome.

Risk factors of hungry bone syndrome

Several factors increase the risk of developing HBS following parathyroidectomy or surgeries involving the removal of a significant number of parathyroid glands. These risk factors include but are not limited to:

• Pre-existing parathyroid disease (hyperparathyroidism)
• High preoperative PTH and calcium levels (hypercalcaemia)
• Extensive total or partial parathyroid gland removal (parathyroidectomy)
• Young age
• Female gender
• Vitamin D deficiency
• Renal insufficiency or chronic kidney disease
• History of high bone turnover or bone disease (osteoporosis or bone cancer)

How these risk factors may contribute to the development of HBS is explored in the section below. Keep reading to find out more.

Causes of hungry bone syndrome

HBS is primarily caused by the removal or damage to the parathyroid glands during surgery (parathyroidectomy). 

Parathyroidectomy is often performed to treat hyperparathyroidism, a condition characterised by excessive production of PTH. When a significant number of parathyroid glands are removed, or their function is compromised, there is an abrupt decrease in PTH production,  which can lead to increased uptake of calcium from the blood into the bones and cause subsequent hypocalcaemia.^5,6 The remaining parathyroid glands may not be able to compensate adequately, leading to significant PTH deficiency and subsequent HBS.  

Listed below are some of the main causes of hungry bone syndrome following parathyroidectomy:

Young children and people assigned female at birth (AFAB)

Certain patient factors, such as young age and being assigned female at birth (AFAB)  have been associated with an increased risk of developing HBS. 

Younger patients tend to have higher bone turnover rates due to ongoing skeletal growth.⁷ In addition, systemic factors such as hormonal status, nutrition, and physical activity can influence bone turnover and consequently increase the chances of developing this condition.⁸ People with AFAB  are more prone to hormonal changes and conditions like primary hyperparathyroidism, which predispose them to the syndrome, and may also have increased calcium needs during pregnancy and lactation.⁹ 

In both young children and people with AFAB, there is an increased need for calcium during growth spurts, and inadequate levels of calcium may lead to problems such as HBS following the removal of their parathyroid gland.⁴

History of high bone turnover

Conditions characterised by increased bone resorption (bone cancer) or decreased bone density (osteoporosis) can predispose individuals to excessive calcium uptake by bones after parathyroid surgery. Osteoporosis is a condition that weakens bones due to inadequate bone production. 

Individuals with a history of high bone turnover or underlying osteoporosis may have a greater likelihood of developing HBS because the damaged bone will try to heal itself by reabsorbing calcium from the blood. Following parathyroid surgery, low levels of PTH mean that the body cannot regulate this bone activity, which can, therefore, lead to hypocalcaemia.

Vitamin D deficiency

Vitamin D plays a critical role in calcium metabolism as it enhances calcium absorption from the intestines into the blood and promotes bone health. Vitamin D deficiency can impair calcium absorption, leading to lower calcium levels in the body. In patients with inadequate vitamin D levels, the risk of developing HBS following surgery is increased.²

Renal insufficiency or chronic kidney disease

Patients with renal insufficiency or chronic kidney disease often have disturbed mineral metabolism and imbalances in calcium and phosphorus levels. These imbalances can contribute to high bone turnover and altered bone metabolism. As a result, such individuals are at an increased risk of experiencing hungry bone syndrome following parathyroid surgery.²

Signs and symptoms of hungry bone syndrome

The signs and symptoms of hungry bone syndrome typically manifest within the first few days to weeks following surgery. Because HBS is due to low PTH, resulting in low calcium levels, the symptoms are very similar to hypocalcaemia, such as:²

• Numbness and tingling in the extremities (paraesthesia)
• Muscle cramps and spasms
• Tetany (muscle stiffness and involuntary contractions)
• Seizures
• Heart problems such as irregular heartbeats (cardiac arrhythmias)
• Bone pain
• Fractures or osteoporosis in severe cases
• Delayed wound healing

Diagnosis of hungry bone syndrome

Diagnosing HBS requires a combination of clinical evaluation, laboratory tests, and imaging studies. The following diagnostic approaches are commonly employed:

Clinical evaluation

Clinicians will carry out an assessment to look for symptoms and signs associated with hypocalcaemia and bone metabolism abnormalities. These include:

• Altered sensation – including tingling and burning around the lips (perioral paraesthesia), 
• History of convulsions, 
• Frequent involuntary muscle contraction in the hands and feet (carpopedal spasms),
• Spasms of the vocal cords, making it difficult to breathe or speak (laryngospasm) 
• irregular heartbeats (cardiac arrhythmias)⁸

Laboratory tests

Measurements of calcium, phosphate, magnesium, and PTH levels in the blood are taken to confirm hypocalcaemia and assess mineral imbalances. Further, a marker of increased bone turnover is alkaline phosphatase and increased levels of this substance, in addition to mineral imbalances, may indicate ongoing HBS.¹⁰

Imaging studies

X-rays, dual-energy X-ray absorptiometry (DEXA), or other imaging techniques are used to evaluate bone density and identify fractures and existing conditions like osteoporosis or bone malignancy.

Management of hungry bone syndrome

The primary cause of HBS is a lack of PTH, which leads to low calcium levels. Hence, the management of HBS involves a multidisciplinary approach and focuses on correcting hypocalcaemia and managing bone metabolism.¹⁰ The primary treatment measures include:

Calcium and vitamin D supplementation

Oral or intravenous calcium supplements are administered to restore calcium levels, followed by frequent monitoring of blood calcium levels to guide treatment adjustments.

Vitamin D supplementation is vital for calcium absorption and bone metabolism. In addition to calcium supplementation, vitamin D supplements may be used to maintain serum calcium within the normal range.

Monitoring and management of phosphate levels

Excessively low phosphate levels may worsen hypocalcaemia. Monitoring and appropriate phosphate replacement may be necessary.

Bisphosphonate therapy

In some cases of expected HBS, treatment with bisphosphonates may be used before surgery to reduce the severity of hypocalcaemia. Although the mechanism is not entirely understood, it is thought that bisphosphonate pre-treatment may help to prevent HBS by inhibiting bone resorption and reducing the uptake of calcium by the bones before surgery.¹¹ However, some research has found that bisphosphonate pre-treatment may actually worsen HBS.¹² 

Complications of hungry bone syndrome

If left untreated or inadequately managed, hungry bone syndrome can lead to various complications, including:

Cardiac arrhythmias and seizures

Severe hypocalcaemia can disrupt the electrical conduction of the heart, leading to life-threatening arrhythmias and seizures.¹³

Fractures and osteoporosis

Prolonged or severe hypocalcaemia can result in weakened bones, increasing the risk of fractures and osteoporosis.¹⁴

Delayed wound healing and infection

Low calcium levels can impair the healing process and increase the risk of postoperative wound infections.¹⁵

Summary

Hungry bone syndrome is a rare but significant complication that usually occurs following parathyroidectomy, or surgeries involving the removal or damage to the parathyroid glands. The primary cause of this syndrome is the sudden decrease in parathyroid hormone (PTH) levels, leading to increased bone uptake of calcium and, subsequently, low calcium levels in the blood (hypocalcaemia).

The signs and symptoms of hungry bone syndrome include numbness, tingling, muscle cramps, and cardiac arrhythmias. Prompt recognition and diagnosis are crucial to prevent complications associated with hypocalcaemia and abnormal bone metabolism. Management involves close monitoring of calcium levels, vitamin D supplementation, and individualized treatment plans. Calcium and vitamin D supplementation helps restore calcium levels in the blood, while frequent monitoring allows for adjustments in the dosage.

Several risk factors can predispose individuals to Hungry Bone Syndrome, such as extensive parathyroid gland removal, high preoperative PTH and calcium levels, young age, being assigned female at birth, and underlying conditions like hyperparathyroidism and vitamin D deficiency.

If left untreated or inadequately managed, hungry bone syndrome can lead to complications such as cardiac arrhythmias, fractures, osteoporosis, delayed wound healing, and infections. Therefore, it is crucial to provide appropriate calcium and vitamin D replacement therapy and closely monitor patients to prevent and address any potential complications.

Overall, with early recognition, diligent management, and regular monitoring, the risks associated with Hungry Bone Syndrome can be reduced, ensuring optimal patient outcomes.