Black bone disease, also known as black urine disease and alkaptonuria (AKU), is an extremely rare metabolic disorder. The genetic disease was first identified by Dr. Archibald Garrod in the early 1900s. Generally, it affects 1 in 250,000 individuals. But this figure can be up to 10 times higher in some parts of the world, namely the Dominican Republic, Jordan, Slovakia, and South India. It is believed that there are just a few thousand people with the disease globally, but online resources like the AKU Society offer solidarity and hope for treatment.
Black bone disease is usually noticed after urine darkens to a black or brown color when left exposed to the air. Some people are diagnosed in childhood, while others don’t find out until their symptoms have reached a more advanced stage.
Hidden harms to the heart, bones, and cartilage can profoundly alter the quality of life for those affected. People with the condition can’t break down homogentisic acid (HGA) in the digestive process. The acid buildup causes joint pain and other serious conditions. Recent drug research has shown that the use of nitisinone can help slow the progression of AKU symptoms and improve health outcomes for people living with the chronic condition. Here’s everything you need to know about black bone disease.
What is black bone disease?
Medical Director and founder of OC Breast Surgery, Dr. Mark Anton says, “Black bone disease, also known as alkaptonuria, is a rare genetic disorder characterized by the inability to break down certain amino acids, leading to a buildup of homogentisic acid, which can darken the bones and connective tissues over time.”
One of the earliest symptoms of alkaptonuria is dark stains on baby’s diapers. However, affected individuals may remain asymptomatic during childhood, only to discover the condition in adulthood, after experiencing dark urine or early-onset osteoarthritis.
While the primary cause of black bone disease is genetics, the condition could also come as a side effect of certain medications like minocycline. Early diagnosis helps determine why the condition has manifested and what can be done to prevent the progression.
What causes black bone disease?
Dr. Kevin Huffman, Doctor of Osteopathic Medicine, says “People with black bone disease have a deposition of homogentisate in their body: a consequence of a genetic mutation that affects the enzyme that processes the amino acid tyrosine. Unmetabolized homogentisate accumulates in bones, cartilage, and earwax.” Other symptoms include bluish-black discoloration of tissue in the body, dark spots in the whites of the eyes, black earwax, and progressive arthritis of the spine and large joints.
Alkaptonuria (AKU)
AKU is a rare genetic disorder in which the body fails to produce enough homogentisic dioxygenase (HGD). This enzyme is needed to break down a toxic substance called homogentisic acid (HGA). An HGD deficiency causes the accumulation of HGA, sometimes at 2,000 times the normal rate.
Minocycline-Induced Black Bone Disease
The condition is also inherited in an autosomal recessive pattern or caused by prolonged usage of minocycline. Minocycline is a broad-spectrum antibiotic routinely used for acne, rosacea, and rheumatoid arthritis. Although very rare, minocycline-induced black bone disease is a pharmacological side effect. While symptoms like dark urine and pigmented bone tissue are common in both the genetic and drug-induced AKU, the latter isn’t as harmful to the underlying bone structure. However, dark pigmentation might be visible on the teeth, skin, and thyroid.
How to diagnose black bone disease
“For diagnosis, it’s typically identified [by] dark-colored urine that turns black when exposed to air—a result of accumulated homogentisic acid, a diagnostic biomarker. Further, blood tests, urine tests, and genetic testing confirm the diagnosis by detecting abnormal levels of homogentisic acid or by identifying mutations in the HGD gene,” advises Dr. Anton.
Dr. Huffman adds that black bone disease is often diagnosed after examining medical history and progressive conditions. “The bones themselves become dark on X-rays, leading to the condition’s name, but blood and urine tests can also show a buildup of excess homogentisate,” he explains. Doctors can undertake clinical evaluation, coupled with radiographic imaging, which aids in confirming the diagnosis and differentiating it from other causes of bone discoloration.
Black bone disease treatment options
Vitamin C
There is no cure, but there are some treatments that can help manage the symptoms. Dr. Anton says vitamin C is often prescribed to decrease the buildup of homogentisic acid, while drugs like nitisinone reduce HGA production. Often surgical intervention might be necessary for severe joint or tissue deterioration, or worsening heart conditions.
Reducing tyrosine
“Reducing dietary intake of tyrosine can help to limit homogentisate production,” adds Huffman. “Tyrosine is found in food sources rich in protein, such as meat, poultry, and dairy. In some cases, a medication called nitisinone can be prescribed. This medication helps the body eliminate homogentisate more effectively. Physical therapy and pain management are also essential to preserve joint function and improve quality of life.”
Stopping minocycline-based drugs
Minocycline-induced black bone disease typically stops progressing as soon as patients stop taking the drug.
Black bone disease FAQs
Is black bone disease serious?
Black bone disease is not always life-threatening, but it becomes progressively worse over time. For example, HGA buildup can cause the heart valves to harden leading to heart disorders and high blood pressure.
Can black bone disease be cured?
“There is no cure for black bone disease, but it can be managed well to slow down its progression, and help the individual lead a better quality of life,” reiterates Dr. Huffman.