Osteomalacia

Clinical manifestations of osteomalacia are primarily due to the incomplete mineralization of the bone, making it weaker and more flexible, resulting in the bowing of the long bones of the lower extremities. Some of the common symptoms include:

• Bone pain
• Tenderness
• Muscle weakness (commonly of the thigh and knee joints)
• Fragile bones
• Fractures
• Myopathy (diseases affecting the muscles)
• Waddling gait
• Increased falls
• Hypocalcemic seizures or tetany
• Myalgias and arthralgias (pain in the muscles)
• Muscle spasms
• Spinal, limb, or pelvic deformities

Osteomalacia is a metabolic bone disease characterized by impaired mineralization of the bone matrix. Bone creation occurs by the deposition of hydroxyapatite crystals on the bone matrix. The causes include:

• Decreased production of Vitamin D: Vitamin D plays an essential role in bone remodeling and is required for strengthening the bone. Some causes of decreased Vitamin D production are:
• Reduced sun exposure due to cold weather climates leading to low levels of Vitamin D.
• Darker skin and increased melanin hinder Vitamin D ultraviolet-B (UVB) light absorption.
• Obesity can lead to increased removal of fat, resulting in less calcium for the activation of Vitamin D.
• In the elderly, vitamin D production decreases as the storage of Vitamin D declines with age.
• Decreased absorption of Vitamin D: Malabsorption of vitamin D can be due to syndromes such as:
• Crohn's disease: A type of inflammatory bowel disease (IBD) that causes inflammation of the digestive tract, leading to abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition.
• Cystic fibrosis: An inherited disorder that causes severe damage to the lungs, digestive system, and other organs in the body.
• Celiac disease: An immune reaction to eating gluten, a protein found in wheat, barley, and rye.
• Cholestasis: A liver disease that occurs when the flow of bile from the liver is reduced or blocked. Bile is fluid produced by the liver that aids in the digestion of food, especially fats.
• Surgical alteration: Gastric bypass of the gastrointestinal (GI) tract is associated with deficient absorption of fat-soluble vitamins (A, D, E, and K).
• Alterations in the metabolism of Vitamin D: This can be due to the following reasons:
• Pregnancy is associated with decreased levels of calcidiol (a form of vitamin D), and a dose of 1000 to 2000 international units (IU) per day is identified as Vitamin D deficiency in pregnant women.
• Liver diseases such as cirrhosis, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis (inflammation of the liver characterized by fat accumulation) can lead to deficient production of calcidiol.
• Chronic kidney disease leads to structural damage and loss of 1-alpha-hydroxylase, an enzyme required for the activation of Vitamin D.
• Nephrotic syndrome (a kidney disorder that causes excessive protein loss in urine) leads to pathologic excretion of Vitamin D binding protein (DBP), which binds to serum calcidiol.
• Low levels of phosphorus (hypophosphatemia) or calcium (hypocalcemia) in the blood: This is seen in the following diseases:
• Renal tubular acidosis, such as in Fanconi syndrome, alters calcium and other ion absorption and excretion.
• Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare acquired paraneoplastic disease characterized by hypophosphatemia and renal phosphate wasting.
• Medications: Drugs that can cause Vitamin D deficiency leading to osteomalacia include:
• Phenobarbitone
• Phenytoin
• Carbamazepine
• Isoniazid
• Rifampicin
• Theophylline
• Ketoconazole
• Long-term steroid use
• Etidronate
• Fluoride

Anyone who has Vitamin D deficiency is at risk of developing osteomalacia. These risks vary across the world and are contingent on geographic location, cultural preferences, and ethnicity. Individuals who are commonly affected include people who:

• Are too frail or ill to go outside
• Live in climatic conditions with less exposure to sunlight
• Usually stay or work indoors during daylight hours
• Wear clothing that covers a lot of their skin
• Have dark skin, which processes less Vitamin D from sunlight. This can include people from South Asian, Middle Eastern, and Afro-Caribbean races.
• Use very strong sunscreen
• Are from low socio-economic backgrounds and have poor nutrition
• Are pregnant and breastfeeding their children

Some of the rare risk factors of osteomalacia include:

• Kidney failure
• Liver diseases
• Medications, such as antiepileptics, antifungals, or steroids
• Untreated coeliac disease
• Surgery on the gastrointestinal tract

Vitamin D, commonly known as the sunshine vitamin, is needed not just for the absorption of calcium but also for the proper function of muscles and nerves. Understand the right way to take it.

Osteomalacia is difficult to diagnose and no single laboratory finding is specific to it. However, the diagnosis of osteomalacia consists of:

History and physical examination

• When evaluating for osteomalacia, a clinical history should include an understanding of a patient's family and surgical history (e.g., gastric bypass).
• Other relevant questions should focus on activity level, hobbies, diet, and assessment of socioeconomic status.

Blood tests

• Serum calcium and phosphorous: Patients with osteomalacia will usually have hypophosphatemia or hypocalcemia.
• Serum alkaline phosphatase: Increased alkaline phosphatase activity is typically characteristic of diseases with impaired osteoid mineralization. Some sources suggest that either hypophosphatemia or hypocalcemia and increased bone alkaline phosphatase level are necessary even to suspect osteomalacia.
• Serum Vitamin D: The serum level of 25(OH)D (vitamin D) is currently regarded as the best marker of vitamin D status and is usually severely low (<10 ng/mL) in patients with nutritional osteomalacia.
• Other sensitive biomarkers of early calcium deprivation include increased serum intact PTH (parathyroid hormone) and decreased urinary calcium. The lack of exposure to the sun significantly impacts our body, especially on Vitamin D levels.

Bone radiograph

• Low bone mineral density (BMD) and focal uptake at Looser zones (pseudofractures) that can appear on bone scintigraphy.
• Poorly repaired insufficiency fractures are visible as transverse lucencies perpendicular to the osseous cortex, typically occurring bilaterally and symmetrically at the femoral necks, shafts, and pubic and ischial rami.
• Decreased distinctness of vertebral body trabeculae due to inadequate mineralization of osteoid.
• Although not required for diagnosis, studies have demonstrated reduced bone mineral density in the spine, hip, and forearm.

Bone biopsy

Iliac crest bone biopsy is considered the gold standard for establishing the diagnosis but should not be advised when the diagnosis is in doubt or the cause of osteomalacia can be determined by other noninvasive methods. Here are some of the definite or possible findings of osteomalacia that would require further validation:

• Hypophosphatemia or hypocalcemia
• High bone alkaline phosphatase
• Muscle weakness or bone pain
• Less than 80% BMD of the young-adult mean
• Multiple uptake zones by bone scintigraphy or radiographic evidence of Looser zones.

Osteomalacia is generally caused by a deficiency of Vitamin D due to inadequate sun exposure or a diet low in Vitamin D. It can be prevented to a larger extent by:

• Eating foods high in Vitamin D
• Adding naturally rich Vitamin D foods like salmon and egg yolks
• Maintaining a well-balanced diet that contains fortified items with Vitamin D and calcium, such as cereal, bread, milk, and yogurt
• Taking supplements, if needed
• Getting enough sun exposure
• Understanding the underlying cause if there is a family history

The goals of therapy for vitamin D-deficiency osteomalacia are to alleviate symptoms, promote fracture healing, restore bone strength, and improve quality of life while correcting the abnormalities. The treatment should focus on the healing of osteomalacia and the resolution of secondary hyperparathyroidism. It consists of:

1. Maintaining PTH levels
   There are no well-established guidelines for this therapy. Most regimens target maintaining serum 25OHD levels at >30 ng/mL and PTH levels within the reference range. With effective therapy, clinical symptoms begin to improve within a few weeks; however, complete resolution of symptoms may take several months. Following treatment, certain common findings are observed, such as:
   • Increase in serum alkaline phosphatase that gradually decreases in patients with prolonged vitamin D deficiency.
   • Hyperparathyroidism may persist for a long time.
   • In rare cases, it may progress to hypercalcemic tertiary hyperparathyroidism.
   • Depending on the amount of osteoid accumulation, a striking increase in BMD is observed after curing osteomalacia.
2. Oral preparations of Vitamin D
   Therapy consists of vitamin D in the following range:
   • 800 to 1200 IU daily oral doses.
   • 50,000 IU of native vitamin D weekly for 8 to 12 weeks, followed by a maintenance dose of 1000 to 2000 IU daily.
   • 10,000 to 50,000 IU may be necessary in cases of impaired GI absorption.
   Because these regimens may take a long time to reach vitamin D sufficiency, higher loading doses should not exceed 100,000 IU.
3. Vitamin D with calcium
   Treatment with vitamin D must always be accompanied by adequate calcium supplements. One thousand milligrams of elemental calcium divided into two or three doses is sufficient in most cases. Higher amounts in the range of 2000 to 3000 mg daily are needed in patients with:
   • Malabsorption: After bariatric surgery or gastric bypass surgery, calcifediol (wherever available) can be utilized because it is a more polar metabolite that is absorbed via the portal system.
   • Hyperparathyroidism: The use of calcitriol along with vitamin D may be preferred in these cases.
   The use of another antiepileptic drug that does not interfere with vitamin D metabolism can be a choice.

Osteomalacia can cause problems with bone formation or the bone-building process, making the bones weak and susceptible to fractures. Along with treatment, here are some tips that can help manage the symptoms:

• Get adequate Vitamin D
  The body produces its own Vitamin D when bare skin is exposed to sunlight. This can be enhanced by sun exposure during morning hours. While it is crucial for bone health to get sunshine, you need to be careful to avoid sunburn. Certain food items also contain small amounts of Vitamin D, including:
  • Egg yolk
  • Oily fish
  • Red meat
  • Liver
  • Butter
  • Cereals
  • Fortified spreads
• Add calcium for bone health
  Calcium is essential for making bones strong, and a lack of calcium can lead to osteomalacia. Good sources of calcium include:
  • Tofu
  • Nuts
  • Soya beans
  • Fortified bread
  • Fish like sardines
  • Milk, cheese, and other dairy products
  • Green leafy vegetables, such as broccoli, cabbage, and okra (but not spinach)
• Make lifestyle modifications
  There are many things you can do to promote healthy bones, such as:
  • Moderating alcohol consumption
  • Eating a well-balanced diet
  • Avoiding smoking
  • Maintaining a healthy weight
  • Taking proper supplements
• Exercise regularly
  Exercise helps to strengthen bones and muscles, providing resistance and making them stronger. This can include walking, running, or lifting weights. However, one should avoid intensive exercise while any fractures or cracks in the bones are healing.

Due to poor osteoid mineralization, several complications can occur if osteomalacia is left untreated. Symptoms can return if the deficiency of vitamin D and underlying conditions like kidney failure are not addressed. Here are some of the complications:

• Insufficiency fractures, also known as looser zones, can present as bone pain and occur with little or no trauma in the legs.
• Reports also exist of looser zones in the ribs, scapulae, and clavicles.
• Researchers have also reported kyphoscoliosis (deviation and excessive curvature of the spine) in long-standing osteomalacia.
• In children, osteomalacia and rickets often occur together, which can lead to bowing of the legs or premature tooth loss.
• Spinal compression fractures are less common and are usually associated with osteoporosis.

Osteoporosis is a condition in which bones become thin and weak due to low bone density. This makes bones fragile and increases the risk of fractures from the slightest trauma.

Octreotide therapy for tumor-induced osteomalacia

Tumor-induced osteomalacia (also known as oncogenic osteomalacia) is a rare disorder characterized by:

• Phosphaturia (phosphorus in urine)
• Hypophosphatemia (low levels of phosphorus in the blood)
• Osteomalacia

Tumor-induced osteomalacia develops due to tumors that are predominantly of benign origin but may occasionally be malignant. Surgical removal of the tumor may relieve all symptoms. Hemangiopericytoma, a type of rare tumor involving blood vessels and soft tissues, is the most common type associated with tumor-induced osteomalacia. The tumor may secrete unknown factors termed “phosphatonins” that cause renal tubular phosphate wasting. Studies have shown that subcutaneous administration of octreotide, a synthetic somatostatin analog, abolished renal tubular phosphate wasting prior to subsequent surgical removal of the tumor.

Phosphorus supplements

Next to calcium, phosphorus is the most abundant mineral in the body. About 85% of the body's phosphorus is found in bones and teeth. Phosphorus is also necessary for balancing and utilizing other vitamins and minerals, including Vitamin D, iodine, magnesium, and zinc. Most individuals obtain sufficient phosphorus from their diets, as it is present in milk, grains, and protein-rich foods. Some inorganic phosphorus supplements include:

• Dibasic potassium phosphate
• Monobasic potassium phosphate
• Dibasic sodium phosphate
• Monobasic sodium phosphate
• Tribasic sodium phosphate
• Phosphatidylcholine
• Phosphatidylserine

The recommended dosage is as follows:

• Adults, 19 years and older: 700 mg
• Pregnant and breastfeeding females: 700 mg

Note: Consult your doctor before taking any supplements.

Osteomalacia is a disease that weakens bones and can cause them to break more easily. It is a disorder of decreased mineralization, which results in the breakdown of the bone matrix faster than its re-formation. It may take several months before any bone pain and muscle weakness are relieved. You should continue taking vitamin D supplements regularly to prevent the condition from returning. Osteomalacia can be managed by:

• Having a diet rich in Vitamin D and calcium
• Getting a healthy amount of sunshine
• Eliminating gluten from the diet
• Moderating physical activities
• Starting physiotherapy
• Applying hot and cold compresses
• Avoiding strenuous activities
• Limiting the use of alcohol and carbonated beverages
• Avoiding certain medications like antiepileptics
• Maintaining a healthy weight
• Quitting smoking
• Taking supplements for vitamins and minerals