Osteomalacia and Its Most Common Drug List

Osteomalacia, also known as Adult Rickets, has a Greek etymological origin with osteon referring to “bone” and malakos referring to “soft”. It is a metabolic bone disease, characterized by an impaired mineralization of bones, leading to development of soft and weak bones. Bone mineralization is the process of deposition of minerals namely calcium and phosphate in the bony matrix. Vitamin D is essential for this process to take place effectively. Vitamin D enhances calcium absorption in the gut. It also maintains an optimal level of calcium and phosphate for bone mineralization. Hence, deficiency of vitamin D is the most significant cause of osteomalacia.

Deficiency of vitamin D can be due to number of reasons. It can occur due to a low dietary intake of Vitamin D or an inadequate sun exposure or some rare conditions affecting the metabolism of Vitamin D such as, crohn’s disease, celiac disease, kidney disorders, liver disorders, and drugs, like phenytoin, phenobarbital, rifampin or carbamazepine. People with lactose intolerance are also at a greater risk of developing osteomalacia. Reduced phosphate levels due to consumption of low phosphate diet or hereditary diseases such as X-linked hypophosphatemia also predisposes a person to osteomalacia. A tumor may also lead to a condition, known as tumor-induced osteomalacia or Oncogenic osteomalacia. Also, low concentrations of calcium and phosphate in blood can lead to secondary hyperparathyroidism.

The softened weak bones can severely deteriorate the quality of life in Osteomalacia. However, it can be easily managed through Vitamin D, calcium or phophate supplementation.

Symptoms

The soft bones in osteomalacia may present with following symptoms.

• A dull aching pain may be felt in bones, most commonly affecting lower back, pelvis, hip, leg and ribs. The pain may worsen at night or on application of pressure
• Decrease in the tone of muscles and leg muscles may manifest as a waddling gait (swaying or rolling from side-to-side)
• Muscle cramps
• Muscle weakness
• Bending of bones
• Fragile bones

The symptoms of osteomalacia may resemble the symptoms of other bone disorders, such as Paget’s disease of bone and Osteoporosis. It must be remembered that osteomalacia is a disorder of defective mineralization of bone, whereas osteoporosis is a disorder causing thinning of already mineralized bone. Osteoporosis is one of the major finding in women after menopause.

Treatment

The treatment of osteomalacia is aimed at treating the underlying cause. Treatment varies from simple supplementation to complex surgical procedures. Usually, supplement with vitamin D, its synthetic analogues and calcium are used in the mainstay treatment.

If the deficiency of Vitamin D, calcium or phosphate is caused by a low dietary intake, less sunlight exposure or malabsorption (caused by intestinal disorders), it is usually managed by supplementation, either through oral route or through injections. However, the supplements have to be taken life-long to prevent the recurrence of the disease. You may also be advised to spend more time outdoors to augment your sunlight exposure.

In some cases even after adequate intake of vitamin D and minerals, osteomalacia occurs due to some underlying disorder of kidney or liver. In such cases, the underlying disorder is treated, combined with supplementation with calcitriol, alfacalcidol or dihydrotachysterol.

If X-linked hypophospatemia or oncogenic osteomalacia is the causative factor, calcitriol or alfacalcidol along with phosphate supplements can effectively combat the condition.

People on long-term anti-epileptic therapy, need vitamin D supplement in their drug regime to prevent the onset of osteomalacia.

However, if these conventional medical approaches fail to counteract osteomalacia, wearing braces or surgical intervention may be adopted to align the defective bone(s).

Various drugs used in the treatment of Osteomalacia are described below.

1. Vitamin D supplements

So far, it has been made clear that Vitamin D, calcium and phosphate are necessary for normal bone mineralization and for regulation of bone turnover.

Now, vitamin D enters your body in different forms. Vitamin D2 (ergocalciferol or calciferol) is present in dietary sources, whereas vitamin D3 (cholecalciferol) is synthesized in skin by the action of UV rays. Both these forms of vitamin D enter liver and kidneys to finally form calcitriol. Calcitriol is the most active form of vitamin D. This calcitriol enhances calcium absorption in intestine and is thus, necessary for maintaining an optimal level of calcium and phosphorus. As per the National Institute of Health, the recommended daily intake of vitamin D should be 600 International Units (IU) for people aged 1 year to 70 years and 800 IU after 70 years of age.^[1]

Thus, based on the underlying cause, different analogues of vitamin D supplements are advised. However, vitamin D3 is more effective than vitamin D2 in counteracting the disease.

Available as: Oral preparations and Injectable preparations

I. Vitamin D2 (Ergocalciferol)
US-FDA Status: Approved for Osteomalacia
Availability: Prescription only
Generic name: ergocalciferol
Brand name: Drisdol capsule
Side-effects: Increased frequency of urination, increased thirst, increased blood pressure, mental retardation
Indicated in pregnancy: Only if benefit outweighs fetal risk.
Alcohol content: Absent

II. Doxercalciferol
It is a synthetic analogue of vitamin D2 (ergocalciferol).

US-FDA Status: Approved for Osteomalacia
Availability: Prescription only
Generic name: doxercalciferol
Brand name: Hectorol capsule; Doxercalciferol injections
Side-effects: Irregular heartbeat, difficulty breathing, hives, rash, abdominal pain
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol content: Absent

III. Dihydrotachysterol
It is another synthetic analogue of vitamin D2. However, it is activated in the liver and does not undergo any activation in kidney.

US-FDA Status: Unapproved for Osteomalacia
Availability: Discontinued
Generic name: dihydrotachysterol
Brand name: DHT tablet
Side-effects: Headache, vomiting, anorexia, nausea, constipation
Indicated in pregnancy: Only if absolutely indicated
Alcohol content: Absent

IV. Vitamin D3 (Cholecalciferol)
US-FDA Status: Approved for Osteomalacia
Availability: Over-the-counter
Generic name: cholecalciferol
Brand name: Cholecalciferol
Side-effects: Poor appetite, nausea, vomiting, cough, hives, dizziness
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol content: Absent

V. Calcitriol
Inactive forms of vitamin D undergo activation in kidney and liver. Therefore, administration of vitamin D2 or D3 will be ineffective in patients of kidney or liver disorder. Such patients should receive activated form of vitamin D only i.e., calcitriol.

Calcitriol Oral

US-FDA Status: Approved for Osteomalacia
Availability: Prescription only
Generic name: calcitriol
Brand name: Rocaltrol capsule
Side-effects: Nausea, weakness, headache, constipation, metallic taste, muscle or bone pain
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol content: Absent

Calcitriol Injection

US-FDA Status: Unapproved for Osteomalacia
Availability: Discontinued
Generic name: calcijex
Brand name: Calcijex intravenous injection
Side-effects: Constipation, vomiting, nausea, abdominal cramps, agitation
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol content: Absent

VI. Paricalcitol
It is a synthetic analogue of calcitriol. It is indicated in patients with kidney disorders.

US-FDA Status: Approved for Osteomalacia
Availability: Prescription only
Generic name: paricalcitol
Brand name: Zemplar capsule (oral); Zemplar intravenous solution (injection)
Side-effects: Blurred vision, difficulty with swallowing, headache, cough or hoarseness
Indicated in pregnancy: Only if absolutely indicated
Alcohol content: Absent

VII. Alfacalcidol
It is a vitamin D analogue. It is a prodrug i.e., it is activated in the liver to form calcitriol, an active form of vitamin D.

Since, it does not require activation in kidney, it can be safely taken in the presence of a kidney disorder. Another interesting fact here is that although it is activated in liver, it does not pose any problem even in severe liver disorders.

It is as effective as calcitriol in the treatment of osteomalacia.

US-FDA Status: Unapproved for Osteomalacia
Availability: Discontinued in USA. However, it is available in other countries.
Generic name: alfacalcidol
Brand name: Alfacalcidol
Side-effects: Constipation, feeling thirsty, frequent urination, dry mouth
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol content: Absent

2. Phosphate Supplement

Although Vitamin D deficiency is the most common cause of osteomalacia, a rare familial disorder known as X-linked hypophosphatemia may also be the causative factor. This disorder is marked by an ineffective reabsorption of phosphate in the kidney, leading to reduced phosphate levels in blood. Therefore, in such patients, vitamin D supplementation alone may not be able to treat the condition. Phosphate supplements are combined with calcitriol or alfacalcidol to effectively manage the condition.

Available as: Oral preparations (capsules, tablets or packets)

I. Sodium phosphate/ Potassium phosphate
US-FDA Status: Not authorized to approve^[2]
Availability: Prescription/ Over-the-counter
Generic name: sodium phosphate/ potassium phosphate
Brand name: Neutra phos, K Phos M.F
Side-effects: Bone pain, dizziness, convulsions, joint pain, fast or irregular heartbeat, headache
Indicated in pregnancy: Only if absolutely indicated
Alcohol content: Absent

3. Calcium Supplements

As already stated, calcium is necessary for bone mineralization. Hence, its deficiency can lead to soft and weak bones.

As per National Institute of Health, the recommended daily intake of calcium varies with age and gender. Adults aged 19 years to 50 years must consume 1000 mg of calcium daily. Male aged 51 years to 70 years need less calcium daily (1000 mg) as compared to females of the respective age group (1200 mg). However, it must be noted that pregnant and lactating women need more calcium due to growing body demand.^[3]

In osteomalacia, severe deficiency of calcium necessitates supplementation to increase the strength of bone.

Available as: Oral preparations

I. Calcium Carbonate
Calcium carbonate is a potent antacid and can also be used to increase the blood calcium levels in osteomalacia.

US-FDA Status: Not authorized to approve
Availability: Over-the-counter
Generic name: calcium carbonate
Brand name: Caltrate tablet
Side-effects: Hives, peeling skin, itching, trouble breathing, fever, wheezing
Indicated in pregnancy: Can be taken in recommended dosages
Alcohol content: Absent

II. Calcium Citrate
US-FDA Status: Not authorized to approve
Availability: Over-the-counter
Generic name: calcium citrate
Brand name: Citracal tablet
Side-effects: Decreased urination, rapid weight gain, constipation, nausea, vomiting
Indicated in pregnancy: Only if absolutely indicated
Alcohol content: Absent

A notable point here is that a regular monitoring of blood calcium levels is necessary during the entire treatment of osteomalacia. If blood tests reveal hypercalcemia, treatment should be stopped for a while as hypercalcemia can be a serious condition.

OTC

Based on differing criteria of drug regulatory bodies of different countries, the over-the-counter availability of drugs varies. Usually, a low dose of vitamin D is available as an over-the-counter supplement, whereas a higher dose would require a prescription. The various OTCs used in the treatment of osteomalacia in several countries have been summarized in the table below.

Although the supplements are readily available in most of the countries,the dosage recommendations may vary based on the severity of your condition. Hence, unsupervised consumption of any medication can cause major complications in osteomalacia. Seek doctor’s consultation to effectively manage the condition.