Hungry Bone Syndrome

What is Hungry Bone Syndrome?

Hungry bone syndrome resultant of mineral imbalance that produces profound, extended and speedy hypocalcaemia, which is linked with hypophosphataemia and hypomagnesaemia.

This mineral imbalance is the outcome of parathyroid endocrinal dysfunction leads to suppression of parathyroid hormone (PTH) levels. This can be occurred due to parathyroidectomy.

Parathyroidectomy usually conducted in patients with an increased level of parathyroid hormone and resultant of this increase bone resorption. However, the Hungry bone syndrome does not occur in every patient conducting parathyroidectomy^1,4,5.

Symptoms

In hungry bone syndrome, the deficit amount of calcium in the blood causes hypocalcaemia related symptoms:

Sudden fall of blood pressure leads to fainting (Syncope)

• Angina i.e. a localized pain in the chest and that can spread to arms, shoulders, and neck due to insufficient blood supply
• Reversible congestive heart failure
• Numbness
• Tingling of finger
• Lower limb muscles cramps and back pain
• Bronchospasm causes wheezing
• Laryngeal spasm leads to voice alteration
• Mood swing and irritability
• Convulsion
• Uncontrolled movement
• Muscular contraction of upper and lower limbs, especially wrist and ankle joint
• Chvostek sign is characterized by hyperexcitability of nerve (tetany)
• Compression of the upper arm causes carpal spasm or clinically termed as Trusseau sign
• Difficulty in swallowing (Dysphagia)³

Pathophysiology

Clinicians reported that after successful parathyroidectomy, serum calcium levels may go down to less than 2.1 mmol/L within 3-4 days. But if this condition continues for a prolonged period, then Hungry Bone Syndrome occurs³.

Prevalence

Hungry Bone Syndrome is a not a very frequently observed condition. Research data showed the prevalence of the Hungry Bone Syndrome is approximately 13 percent in the case of primary hyperparathyroidism. and mainly develops after parathyroidectomy.

In the Asian region, the prevalence rate is high and total estimated incidence is almost 24 to 87 percent of total incidence, whereas in Saudi Arabia only 4% prevalence rate is recorded².

Risk Factors

• Older aged people with parathyroidectomy have more risk to develop Hungry Bone Syndrome than younger aged patient conducting parathyroidectomy.
• Certain physiological parameters like increase serum calcium, PTH and alkaline phosphatase in pre-operative condition increase the risk of incidence of Hungry Bone Syndrome in comparison of a patient with a normal value of these parameters.
• Primary hyperparathyroidism related bone disease presence prior to parathyroidectomy increase the risk of Hungry Bone Syndrome².

Treatment

In healthy human being, the regulation of serum calcium, level, phosphate and parathyroid hormone level is regulated by circadian rhythm. Alternative fashion, the peak level of calcium and phosphate regulated at a different time of a day and that is regulated by PTH secretion.

This rhythm is disturbed in the development of primary hyperparathyroidism and this is lost after parathyroidectomy. Therefore, after parathyroidectomy, a sudden calcium level reduction in serum may be the consequence of excessive amplification by the magnification of bone formation.

In Hungry Bone Syndrome, maintaining calcium level is the most important management criteria. After the surgical process of parathyroidectomy, it needs to assess the serum calcium level. Repeated blood samples are collected few hours after surgery to check the calcium level. It is also important to monitor serum phosphate and magnesium level to balance the mineral level.

Vitamin D supplementation requires managing Hungry Bone Syndrome because this vitamin is important for calcium metabolism and bone remineralization.

Calcium supplementation up to 12 grams per day is required for treatment of Hungry Bone Syndrome.

Some patients require the calcium gluconate intravenous administration to manage acute symptoms related to hypocalcaemia develops in Hungry Bone Syndrome.

It is important to note that electrocardiographic monitoring is required to prevent the risk of dysrhythmias during IV administration of a large quantity of calcium-containing fluids, as quick improvement of hypocalcaemia can cause dysrhythmias.

Calcium carbonates and calcium citrates are the two salts usually use for maintaining adequate serum calcium levels. Other preparations of calcium salts need a larger dose to make up the calcium level. In addition, patient compliance is also very important to managing calcium level in Hungry Bone Syndrome.

Usually, patients need long-term calcium and vitamin D supplementation in the management of Hungry Bone Syndrome^1,3.

Options to Prevent

It has been estimated that almost 76% percent of patients with primary hyperparathyroidism have vitamin D depletion. Therefore it is considered that vitamin D depletion is a risk factor for the development of the postoperative hypocalcaemia and Hungry Bone Syndrome. Therefore, supplementation of vitamin D at pre-operative stage may assist in controlling hypercalcaemia and bone turnover in a better way in PTH levels reduction.

It is expected that bisphosphonates administration can also prevent Hungry Bone Syndrome, as bisphosphonates able to inhibit osteoclastic incidence and also improve remineralization activity.

But benefits of bisphosphonates in Hungry Bone Syndrome prevention may observe after a long term application. There is no clinical trial data available for bisphosphonates in the preventive measure of Hungry Bone Syndrome.

Researchers already demonstrated that deficiency of magnesium and bone turnover normalization is a long term process after parathyroidectomy³.

References

1. Witteveen JE, van Thiel S, Romijn JA, Hamdy NA. Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol. 2013 Feb 20;168(3):R45-53. doi: 10.1530/EJE-12-0528. Print 2013 Mar. Retrieve from https://www.ncbi.nlm.nih.gov/pubmed/23152439
2. J E Witteveen, S van Thiel,  J A Romijn, N A T Hamdy. THERAPY OF ENDOCRINE DISEASE: Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol March 1, 2013 168R45-R53. Retrieve from http://www.eje-online.org/content/168/3/R45.full
3. Ghilardi G, De Pasquale L (2014) Hungry Bone Syndrome after Parathyroidectomy for Primary Hyperthyroidism. Surgery Curr Res 4:168. doi: 10.4172/2161-1076.1000168.
4. Retrieve from https://www.omicsonline.org/open-access/hungry-bone-syndrome-after-parathyroidectomy-for-primary-hyperthyroidism-2161-1076-4-168.php?aid=23916
5. Nicole Stankus. Hungry Bone Syndrome. Encyclopedia of Molecular Mechanisms of Disease
6. pp 865-866. Retrieve from https://link.springer.com/referenceworkentry/10.1007%2F978-3-540-29676-8_821
7. Michael Berkoben, L Darryl Quarles. Hungry bone syndrome following parathyroidectomy. Retrieve from https://www.uptodate.com/contents/hungry-bone-syndrome-following-parathyroidectomy