71 Osteomalacia and Rickets

Rickets and Osteomalacia

Rickets and osteomalacia are different from osteopenia and osteoporosis.  In osteopenia and osteoporosis, there is a total loss of bone mass resulting in brittle bones.

In rickets and osteomalacia, the bones become softer due to inadequate mineralization.  Rickets is a disease that can affect the growing bones of infants, children and adolescents.  Specifically, bones become progressively weaker as the bone fails to calcify.  In adults, this condition is called osteomalacia.  Osteomalacia comes from the Greek words osteo, meaning bone, and malacia, meaning softness.  To better understand rickets and osteomalacia it is worth remembering the role of Vitamin D (vitamins D2 and D3) in maintaining blood calcium levels, as well as the relationship between blood calcium levels and bone density levels.

The Role of Vitamin D in Maintaining Blood Calcium Levels

Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) play important roles in maintaining blood calcium levels.  Blood calcium concentrations of 8.5 mg/dL to 11 mg/dL is tightly regulated as the proper functioning and intracellular signalling within many cells including: heart muscle cells (cardiomyocytes), smooth muscle cells, and neurons is dependent on blood calcium homeostasis.  Hypocalcemia can result in seizures and heart failure.  Hypercalcemia can also cause problems (e.g., kidney stones, neural problems etc.).

Vitamins D2 and D3 can be formed by epithelial cells in the skin upon exposure to UV.  Alternatively dietary vitamins D2 and D3 can be ingested in the form of oily fish, cod liver oil, beef liver, egg yolk, milk fortified with vitamin D, vitamin supplements as well as various plant, fungi and yeast sources.  Once produced (either by the skin) or ingested, vitamin D2 and vitaminD3 are carried to the liver, where hepatocytes convert these vitamins to a calcitriol precursor, which then travels to the proximal tubular cells of nephrons in the kidney, where it is converted to calcitriol.  Calcitriol is a hormone which is able to help regulate blood calcium levels.  Specifically, calcitriol is released by tubular cells when blood calcium levels are low.

Calcitriol helps to increase blood calcium levels and maintain homeostasis by performing 3 functions:

1. Calcitriol binds to intestinal receptors and facilitates the absorption of dietary calcium and phosphate by intestinal cells, which leads to more calcium and phosphate entering the bloodstream.
2. Calcitriol increases the reabsorption of calcium within the nephron, which leads to less calcium being excreted in the form of urine, and therefore more calcium being retained in the bloodstream.
3. Calcitriol promotes osteoblasts to release RANKL, a signalling protein, which activates osteoclasts to dissolve bone matrix (i.e., osteoid) and release calcium and phosphate into the bloodstream.

The Relationship between Blood Calcium Levels and Bone Density Levels

In order to fully appreciate the relationship between blood calcium levels and bone density levels it’s important to also consider the role of parathyroid hormone, as well as that of vitamin D.

As mentioned in the above section, blood calcium concentrations are tightly regulated to ensure the proper functioning of cardiomyocytes, smooth muscle cells, and neurons.  In order to prevent hypocalcemia, bones serve as a calcium reservoir.  Hypercalcemia is most often prevented by excreting excess calcium.

Let’s further examine the use of bones as reservoirs and the relationship between blood calcium levels and bone density.

When blood calcium levels drop below 8.5 mg/dL, the parathyroid gland secretes parathyroid hormone (PTH) which acts in 3 ways in order to prevent hypocalcemia:

1. PTH stimulates osteoblasts to release the signalling protein RANKL which stimulates osteoclasts to erode bone matrix.  Calcium released from the osteoid enters the blood stream to increase blood calcium levels.
2. PTH enhances the effects of calcitriol on intestinal absorption of dietary calcium.  Absorbed calcium enters the blood stream.
3. PTH increased production of calcitriol from the renal proximal tubular cells.  Calcitriol increases calcium reabsorption by the nephrons, leading to less calcium excreted in the form of urine and therefore maintenance of blood calcium levels.

In the opposite scenario, when blood calcium levels increase over 11 mg/dL, C cells of the thyroid gland secretes calcitonin which acts in 2 ways in order to prevent hypercalcemia:

1. Calcitonin decreases osteoclast activity, reducing the dissolving of bone matrix. At the same time, osteoblast activity is not affected, so the building of matrix and mineralization of bone continues, and bone density increases.
2. Calcitonin decreases reabsorption of calcium by nephrons, leading to more excretion of calcium in the form of urine.
3. At the same time, the high levels of blood calcium, reduce the production of PTH and calcitriol, which results in less intestinal absorption of dietary calcium and phosphate.

Takeaway:

Therefore, it is noted that in ideal circumstances, there is sufficient levels of vitamin D (and it’s active form, calcitriol), as well as dietary calcium and phosphate in order to maintain blood calcium and phosphate homeostasis as well as adequate bone mineralization and bone density levels.

So, one can imagine two scenarios playing out that lead to Rickets or Osteomalacia.

If there is insufficient dietary calcium and phosphate, blood calcium levels decrease, therefore calcitriol and PTH are produced resulting in the dissolving of bone matrix, which could develop into rickets or osteomalacia over time.

If there is insufficient vitamin D2 or D3, blood calcium levels will decrease, therefore PTH will be produced resulting in more bone matrix being dissolved, and less dietary calcium and phosphate being absorbed, which could also develop into rickets or osteomalacia over time.

Risk Factors – Rickets

Rickets is usually caused by nutritional deficiencies leading to low levels of bone mineralization.  Specifically, the osteoid (organic bone matrix composed of glycoproteins) is not calcified sufficiently leading to bones that are not as strong.  The low bone density that occurs with Rickets can lead to the bowing of legs in children over time.

Nutritional Rickets and nutritional osteomalacia can be caused by inadequate intake of vitamin D, calcium, and/or phosphate.  All 3 components (vitamin D, calcium and phosphate) are required for adequate bone density production.  Specifically, Vitamin D is initially required for the intestinal absorption of dietary calcium and phosphate into the blood stream.  This calcium and phosphate is then taken up from the blood by osteocytes and osteoblasts and deposited into the osteoid.  Calcifying the osteoid is important in building bone density.   Not only is building bone density important, but also maintaining bone density throughout life in order to ensure adequate strength and support.  It is important to remember that bones serve as a reservoir for calcium to ensure that blood calcium levels are maintained at a level of 8.5-11 mg/dL.  Blood calcium homeostasis ensures that tissues that rely on set levels of extracellular calcium for cardiac muscle, smooth muscle, neurons, etc. to function properly at all times.

Therefore, it is important to maintain sufficient levels of Vitamin D.  Vitamin D can be acquired through dietary foods which include: milk (specifically vitamin D-fortified milk), oily fish, cod liver oil, eggs, and some mushrooms.  The epidermis is also able to produce Vitamin D2 and D3 when exposed to Ultraviolet (UV) rays.  However, it is recommended that skin be protected against UV by sunscreen especially during peak UV hours of the day which can reduced levels of vitamin D produced by the epidermis.  Dermatologists advise that the safest way to obtain vitamin D is through diet, as exposure of skin to UV at any level puts one at risk for cumulative damage which is a risk factor for skin cancer.  That being said, globally, most individuals obtain the majority of their vitamin D through exposure to sunlight.

Vitamin D:  In order to ensure infants that are exclusively breast-fed aren’t at risk for rickets, vitamin D drop supplements for infants are usually recommended.  Babies that are fed formula and cow’s milk are not at risk for rickets, as both formula and cow’s milk contain vitamin D in addition to calcium and phosphate.  Before supplemental vitamin D was available, humans relied on the ability of their epidermal (skin) cells to produce vitamin D as well as fish and cod liver oil.

Premature infants can be at risk for inadequate calcium and phosphate, and supplemental treatment may be put in place.

Veganism is a risk factor for both rickets and osteomalacia, as without eggs, fish, and milk, dietary calcium and vitamin D levels may be low unless vitamin D supplements are put in place.  It is important to follow the Recommended Dietary Allowance for vitamin D to ensure that levels are not too low, but also not too high.  High doses of vitamin D can become toxic and harmful to the body.  Recommended Dietary Allowance for adults 19 years and older is 600 IU (15 mcg) daily for men and women, and for adults >70 years it is 800 IU (20 mcg) daily.

Other causes of Rickets include hormone imbalances, renal failure, liver failure.

Signs and Symptoms – Rickets

Infants and children with rickets show many signs and symptoms of hypocalcemia, which can include:

• General Muscle Hypotonia:  Decreased muscle tone can occur due to hypocalcemia
• Skull Bone Abnormalities:  Craniotube, or thinning and softening of bones in the skull can occur in infants.  Rickets can also cause delayed closure of the anterior fontanelle and then protruding forward as the skull thickens later in age.
• Bone Deformities:  Rickets in children can cause weight-bearing legs to bend and become bowlegged and/or exhibit knock-knees.  Rickets can also cause deformations of the sternum, ribs, humerus, and other bones such as the vertebrae (which can lead to kyphoscoliosis).
• Greenstick fractures: Rickets makes one susceptible for greenstick fractures.

Diagnosis – Rickets and Osteomalacia

Rickets is typically diagnosed using:

• physical examinations
• imaging (e.g., x-ray)
• blood tests for serum levels of calcium, phosphorus, parathyroid hormone, and various forms of vitamin D, including calcitriol.
• bone biopsy

Risk Factors – Osteomalacia

The development of osteomalacia takes place later in life after bones have grown to full length.

Risk factors for developing osteomalacia are very similar to rickets and include: deficiencies in vitamin D, calcium and/or phosphate.  As dietary deficiencies are a risk factor, osteomalacia can be found more frequently in individuals with malnourishment, low socioeconomic status, and/or poor diet.  If there is a reliance on UV (instead of diet or supplements) for the production of vitamin D, then full body covering and/or dark skin reduces UV exposure to the epithelial cells responsible for producing vitamin D, and are therefore risk factors that can lead to vitamin D deficiencies and osteomalacia.

Malabsorption syndromes that affect the intestinal absorption of fat-soluble vitamins (A, D, E, and K) are risk factors for the development of osteomalacia.  Malabsorption syndromes include Chron disease, celiac disease, cystic fibrosis.  Gastric bypasses can also lead to impaired ability to absorb dietary vitamin D.

Both liver and kidney disease can lead to impaired vitamin D conversion to calcitriol, as well as renal reabsorption of calcium, both problems putting one at risk for osteomalacia.

Hereditary risk factors that negatively affect vitamin D production, or bone mineralization are typically identified in childhood.

Some medications are risk factors for developing osteomalacia.

Signs and Symptoms – Osteomalacia

In comparison with rickets, osteomalacia is milder.

Signs and symptoms of mild to moderate osteomalacia can include: bone pain, muscle pain and weakness, and hypotonia (decreased muscle tone).

Severely affected individuals exhibit waddling gait or have difficulty walking.  Individuals may have multiple insufficiency fractures, vertebral compression fractures, bone deformities, or even seizures, twitching, or tetany

Treatment – Rickets and Osteomalacia

Treatment usually includes: vitamin D supplements and/or change to diet that includes recommended levels of: calcium, phosphate and vitamin D.

For bone deformities, orthopedic correction may be performed.

Summary:

• Osteomalacia and Rickets:
  • Metabolic disorders affecting calcium levels in osteoid.
  • Softening of bones due to lack of calcium/vitamin D.
  • Causes: malnutrition, lack of sunlight exposure.
  • Signs/symptoms: skeletal pain, bone deformities.
  • Diagnosis: blood tests, bone biopsy.
  • Treatment: calcium carbonate, vitamin D supplementation.
  • Vitamin D Recommended Dietary Allowance for adults 19 years and older is 600 IU (15 mcg) daily for men and women, and for adults >70 years it is 800 IU (20 mcg) daily.  Caution should be used not to exceed this dose as vitamin D can build up to excessive and harmful levels in the body.