A condition, known commonly as "black urine disease" or Alkaptonuria is a rare genetic disorder involving protein metabolism, and it has its root in the mutation of the homogentisate 1,2-dioxygenase gene, which in turn causes homogentisic acid accumulation in the body. The appearance of dark urine after exposure to air is due to this kind of accumulation; however, a variety of symptoms can be expected, such as joint stiffness, changes in pigmentation, and other long-term health complications. Although the prevalence has been estimated to be between 1 in 250,000 and 1 in 1 million people in the United States, its effects are indeed high on those affected.

Alkaptonuria is an autosomal recessive disease, meaning that the child must inherit a defective copy of the HGD gene from both parents. If both parents are carriers, their offspring have a 25% chance of inheriting two faulty genes and developing alkaptonuria. The condition is genetic but is often not diagnosed for years because it progresses slowly and its early symptoms appear to be harmless.

Symptoms of Alkaptonuria

The most characteristic and common initial symptom of alkaptonuria is dark urine. The reason for this is due to the fact that excess HGA is excreted in the urine and upon oxidation in the presence of air, it gives the urine a brown or black color. Though it is often considered cosmetic, the long-term accumulation of HGA within the connective tissues produces more complicated health problems.

Progressive joint pain and stiffness: The accumulation of HGA in cartilage leads to early-onset osteoarthritis, making movement increasingly difficult over time.

Skin and eye pigmentation changes: Affected individuals may develop bluish or grayish discoloration of the sclera (white part of the eye) and the skin, particularly in areas exposed to friction.

Cardiovascular and respiratory problems: With age, HGA accumulation can lead to valve calcifications in the heart and stiffening of connective tissues in the respiratory tract, which can cause problems in middle and old age.

Decreased mobility and spinal problems: The spine may become stiff and painful due to chronic cartilage degeneration.

These symptoms usually begin to manifest during adulthood, leading to severe complications in a person's 40s or 50s and significantly affecting the quality of their life.

How is Alkaptonuria Diagnosed?

Because of its rarity, alkaptonuria is often mistaken or overlooked early in life. However, there are several ways to confirm the condition:

Urine Testing: The gold standard in the diagnosis is the testing of urine samples for high levels of homogentisic acid via gas chromatography. In case of oxidation, which changes the color of urine to black, it is indicative of alkaptonuria.

Genetic Testing: Confirmatory genetic testing reveals mutations of the HGD gene to diagnose the condition conclusively.

Blood Tests: High levels of HGA in the blood can be used as further evidence.

Imaging Studies: X-rays and MRIs will expose cartilage and joint damage characteristic of alkaptonuria.

Management of Alkaptonuria: Is There A Cure?

At present, there is no cure for alkaptonuria; however, various treatment approaches can reduce its symptoms and slow the disease's progress:

Nitisinone Therapy: Nitisinone is a drug that inhibits the production of HGA. It has been shown to reduce HGA levels and slow tissue damage. However, it needs to be taken under close medical supervision because of potential side effects.

Low-Protein Diet: Since HGA is a byproduct of protein metabolism, reducing protein intake—especially foods rich in tyrosine and phenylalanine—may help decrease HGA production.

Pain Management: OTC pain relievers and anti-inflammatory medications can be used to relieve joint pain and stiffness.

Physical Therapy: Exercise regularly, as it may improve mobility and strengthen muscles, thus reducing strain on affected joints.

Surgical Interventions: Most people with alkaptonuria develop severe osteoarthritis necessitating joint replacement in their old age. Also, some may require heart valve replacement surgery if cardiovascular complications develop.

Life with Alkaptonuria

Although alkaptonuria is not fatal, it severely affects the quality of life. The progressive deterioration of the joints and associated symptoms can make everyday activities difficult, requiring lifestyle changes and medical interventions. The disease may cause premature aging of the joints, requiring walking aids and mobility assistance earlier than expected.

Ongoing research will continue to work on improving the treatment options by focusing on gene therapy and alternative enzyme replacement therapies. However, because of its rarity, the clinical trials and research remain sparse.

As genetic research advances, more hope for better management and possible curative approaches for alkaptonuria exists. Scientists are searching extensively for enzyme replacement therapies and innovative drugs that can target the root cause of the disorder. Being aware and being diagnosed early helps individuals better their condition and ultimately have better long-term health outcomes.

Alkaptonuria is a striking example of how one gene mutation can have widespread effects on the body. Though still a rare and often misunderstood condition, growing awareness and advances in treatment are paving the way for better care. If you or a loved one suspect symptoms of alkaptonuria, it is essential to seek early diagnosis and medical guidance to manage the disease effectively and preserve quality of life.

GLP-1 receptor agonists (GLP-1 RAs), including semaglutide widely used to improve diabetes control and promote weight loss, may also reduce the risk of colorectal cancer, according to a new study.

The study found that the effect was particularly notable among people with inflammatory bowel disease (IBD), as well as those with both IBD and type 2 diabetes. Both conditions are associated with a higher risk of colorectal cancer due to chronic inflammation and metabolic changes that may promote tumor development.

"GLP-1 RA use was associated with a significantly reduced incidence of colorectal cancer in all patients with IBD, as well as the subpopulation with both IBD and type 2 diabetes," said lead author Sarina Ailawadi of Case Western Reserve University, US.

"Given the elevated colorectal cancer risk in IBD, these findings suggest a potential protective effect of GLP-1 RA use in this high-risk population. Prospective studies will be important to further analyze and confirm this potential benefit," she added.

The findings will be presented at the 2026 American Society of Clinical Oncology (ASCO) Breakthrough meeting, scheduled for June 25–27 in Singapore.

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How Was The Study Conducted?

This retrospective cohort study analyzed data from 69,221 people in the US, including GLP-1 RA users and non-users.

Researchers also identified 209,649 people with both IBD and type 2 diabetes, including 38,567 who had taken a GLP-1 RA.

After matching users and non-users for various characteristics, data from 37,740 patients were analyzed. The GLP-1 RA group included people taking semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, or lixisenatide.

The researchers compared the five-year incidence of colorectal cancer between GLP-1 RA users and non-users.

Among people with IBD, the five-year incidence of colorectal cancer was 0.2% in GLP-1 RA users compared with 0.42% in non-users. The odds ratio was 0.49, indicating a 51% lower likelihood of developing colorectal cancer among GLP-1 RA users.

Among patients with both IBD and type 2 diabetes, the five-year incidence of colorectal cancer was 0.31% in GLP-1 RA users and 0.57% in non-users. The odds ratio was 0.54, suggesting a 46% lower likelihood of developing colorectal cancer.

The researchers noted that prospective studies are needed to confirm the potential protective effect of GLP-1 RAs on colorectal cancer risk.

Do IBD and Type 2 Diabetes Increase Colorectal Cancer Risk?

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Inflammatory bowel disease is associated with a higher risk of colorectal cancer, likely because of chronic inflammation in the intestines. People with IBD are estimated to be six times more likely to develop colorectal cancer than those without the condition.

Type 2 diabetes, the most common form of diabetes, also increases colorectal cancer risk and is becoming more common among people with IBD. Scientists believe that individuals with both conditions may face an especially high risk because of the combined effects of chronic inflammation and metabolic dysfunction.

What Are GLP-1 Receptor Agonists?

GLP-1 receptor agonists are a class of drugs that help lower blood sugar levels and promote weight loss. Originally developed to treat type 2 diabetes, many are now widely used for weight management.

These medications mimic the action of the GLP-1 hormone by stimulating insulin release, slowing digestion, and increasing feelings of fullness.

Beyond blood sugar control and weight loss, GLP-1 RAs have been linked to several health benefits, including lower blood pressure and reduced cardiovascular risk. Previous studies have also suggested that they may lower the risk of colorectal cancer and other obesity-related cancers.

However, their specific impact on colorectal cancer risk among people with IBD has remained unclear until now.

Pop singer Madonna has opened up about knee damage caused by years of dancing in high heels.

The 67-year-old superstar said running and Ashtanga yoga also added stress to her joints, leaving her with “no cartilage” in her knee, according to Interview Magazine.

“I have a bad knee now. I have no cartilage in it, thanks to dancing for so long in high heels and running on pavement and doing Ashtanga yoga,” Madonna told the magazine.

“Up until a year ago, I was jumping on trampolines and doing dance cardio and doing a lot of what a doctor would call loading on my joints. Can’t do that anymore,” she added.

Madonna said she still works out regularly while listening to her new album Confessions II, but has had to modify her fitness routine to accommodate the injury.

The Queen of Pop said she now focuses on “Peloton bikes and the Versa Climber and high-intensity circuit training. I ride my bike outside a lot. I dance.”

Madonna has previously been open about her knee injury and its impact on her career. In October 2019, she postponed a scheduled Madame X show in Brooklyn, New York.

“It's Hard for Madame to admit that she is also a human being made of flesh and blood and she must rest for the next 3 days to insure full recovery for her knee,” she wrote on Instagram.

“I am not a quitter. This hurts me more than you can imagine. It's time to take those heels and fishnets off for a few days!”

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Can High Heels Affect Knee Health?

Knee osteoarthritis (OA), a leading cause of disability, is more prevalent in women than men. Wearing high-heeled shoes has been implicated as a potential contributing factor to the higher lifetime risk of osteoarthritis in women.

Several studies have examined the relationship between high heels and knee health. Motion analysis studies have shown changes in knee alignment while walking in heels, changes that researchers have suggested may resemble patterns seen in ageing and knee osteoarthritis progression.

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A 2025 study published in The Knee by researchers from the Singapore Institute of Technology found that wearing 8-cm high-heeled shoes significantly reduced the lateral joint space width of the knee in healthy young women during standing, suggesting increased lateral knee joint stress.

The findings suggest that high heels may specifically affect the lateral compartment of the knee, potentially contributing to increased joint stress during standing.

Wearing heels for long periods can increase the load on the knees. They alter posture and walking patterns, placing additional pressure on the knee joint. Over time, this may strain the ligaments and muscles surrounding the knee, leading to pain, stiffness, and long-term damage.

In 2025, the Nicki Minaj Challenge, inspired by the rapper's 2013 song High School, gained traction on social media. The challenge, which involved balancing in high heels, reportedly resulted in injuries including fractures and, in some cases, deaths.

Most people pay little attention to their knees, legs and ankles until something goes wrong. Once pain sets in, even simple things like walking, climbing stairs, or standing for long can become a real challenge. Left unmanaged, lower limb pain gradually affects mobility, independence and quality of life.

What Is Usually Behind the Pain?

Knee pain commonly traces back to osteoarthritis, ligament injuries, cartilage damage, or years of wear. Pain in the leg can be caused by muscle injuries or conditions involving nerves and poor blood flow. The pain in the ankle is commonly caused by sprains, tendinitis, arthritis, or any injury that may have occurred earlier without complete healing.

Age, obesity, sedentary lifestyles, and constant joint injuries contribute silently to the degenerative condition of the joints.

Signs That Should Not Be Ignored

Persistent pain, swelling, stiffness, or discomfort that keeps getting worse deserves attention. If pain is disturbing your sleep, that is a clear signal to see a doctor.

Habits That Help Protect Your Joints

Walking downstairs puts considerable pressure on the knees, so limiting stair use where possible is sensible. Squatting, sitting on the floor and using Indian-style toilets place similar strain and are better avoided.

Staying active matters just as much. Regular household chores, walking, stretching and strengthening exercises, even 15 to 20 minutes a day, keep muscles strong and reduce the load on joints. Focusing on the adductor muscles around the knee is particularly effective in improving joint support.

Non-Surgical Options Worth Knowing

Surgery is not always the answer. Two non-surgical treatments carried out by a pain physician can make a meaningful difference.

Platelet-Rich Plasma therapy, or PRP, involves concentrating platelets from the patient's own blood and injecting them into the affected joint. In osteoarthritis, where cartilage gradually thins, PRP may help support regeneration and ease symptoms.

Radiofrequency Ablation, or RFA, uses a specialized needle to deliver targeted heat that interrupts the nerves responsible for sending pain signals to the brain. Relief typically lasts one to two years. The procedure is done as day care with no cuts, no stitches and no anesthesia required.

A concern many patients raise is that pain stops them from exercising or losing weight. Once pain is controlled through these treatments, walking and light activity become manageable again, which in turn supports weight loss and takes further pressure off the joints.

Custom Knee Supports

Off-the-shelf knee caps have limited effectiveness. A custom-made support, designed to redistribute body weight and reduce joint stress, works considerably better, especially in early arthritis. Many patients notice relief shortly after wearing one. They are an investment, but a worthwhile one that can reduce dependence on medication while the surrounding muscles gradually strengthen.

When to See a Doctor

If pain has lasted several weeks, is worsening, or is getting in the way of daily life, it is time to consult a specialist. Early diagnosis and the right treatment can protect joint function, restore mobility and often avoid the need for surgery.

(By Dr. Aanchal Sharma, Pain Physician, Principal Consultant and Head of Department, Department of Pain Medicine at BLK MAX Hospital, New Delhi)