Advanced Pathophysiology

Rickets/Osteomalacia

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Speaker 2: Bone softening caused by a faulty process of bone mineralization manifests as either rickets in children or osteomalacia in adults. Inadequate bone mineralization could be due to a deficient or impaired metabolism of vitamin D, phosphate or calcium. But first, a bit about bones. Now long bones like the femur are made up of two epiphyses, which are its ends, and the diaphysis, which is the shaft. Between each epiphysis and the diaphysis, there's a region called metaphysis. And the metaphysis contains the epiphyseal plate or the growth plate, which is the part of the bone that grows during childhood. Once growth stops, the growth plate is replaced by an epiphyseal line and this is known as epiphyseal closure.

Now for bones to grow and develop properly, special bone cells called osteoblasts are hard at work. To build bone, osteoblasts secrete osteoid, which is an organic matrix made up of type one collagen. These collagen fibers are the framework for the osteoblast's work. Osteoblasts then deposit calcium and phosphate crystals into the framework. This process is called bone mineralization and it confers strength to the growing bones. Bone mineralization is dependent on an enzyme called alkaline phosphatase, which increases in response to osteoblast activity. So at the end of the day, bones are like a storage warehouse for calcium and phosphate.

Now the levels of calcium and phosphate in the bone, but also in the blood, are regulated by vitamin D and parathyroid hormone or PTH. Vitamin D wise, two steps are necessary for optimal metabolism. First, there must be enough vitamin D in the body, either from food or created in the skin in response to sunlight exposure. Secondly, vitamin D must become metabolically active, and this process also has two steps. First one happens in the liver where inactive vitamin D is converted into 25 hydroxy vitamin D by the enzyme 25 hydroxylase. 25 hydroxy vitamin D then travels to the kidneys where the enzyme one alpha hydroxylase converts it to one 25 hydroxy vitamin D or calcitriol, which is the active form of vitamin D. Calcitriol increases renal tubular reabsorption of calcium, which reduces the loss of calcium in the urine. Calcitriol also increases the intestinal absorption of calcium and phosphate.

Okay, now let's have a quick look at parathyroid hormone. Parathyroid hormone is secreted in response to low blood calcium levels, and it stimulates the resorption of calcium and a small amount of phosphate from the bone and into the bloodstream. Additionally, parathyroid hormone can boost one alpha hydroxylase activity, which forms more active vitamin D, increasing gut absorption of calcium. Lastly, parathyroid hormone increases calcium reabsorption and reduces the reabsorption of phosphate from the kidneys so more phosphate is excreted through the urine.

Now, when there's not enough active vitamin D, calcium or phosphate, there's inadequate mineralization. This means that osteoblasts don't have enough calcium and phosphate to deposit into the organic matrix. In children, because the growth plates haven't closed yet, this leads to softening of the bones, impaired growth of bones and bone malformations. Whereas in adult where the epiphyseal plates have already closed, it only causes weakening and softening of bones, which makes them easier to fracture.

Okay, now vitamin D deficiency is the most common cause of both rickets and osteomalacia. Causes a vitamin D deficiency include intestinal malabsorption, which can be seen with celiac disease or Crohn's disease, not enough UV light exposure, like in home bound elderly populations, medications like phenytoin an anti-convulsant uses liver and kidney hydroxylase enzymes for its own metabolism. So especially with longterm use, there's not enough vitamin D being generated. And finally, there's liver and kidney disease. For example, rickets or osteomalacia can occur in chronic liver disease due to the liver's inability to turn inactive vitamin D into 25 hydroxy vitamin D. The same goes for chronic kidney disease, where the kidneys can't turn 25 hydroxy vitamin D into one 25 hydroxy vitamin D. Both conditions result in an active vitamin D deficiency, which leads to impaired bone mineralization.

With both rickets and osteomalacia, symptoms include diffuse bone and joint pain, proximal muscle weakness, bone fragility, and increased risk of fractures with minimal trauma. Because of low levels of calcium, there may also be muscle spasms and numbness. Rickets specific symptoms include thin soft skull bones, which is called craniotabes, delay in the closure of fontanelles and bowlegs also known as genu varum. There may also be an enlarged prominent frontal bone, and with severe disease, a protruding abdomen. Additionally, a rachitic rosary may be seen. This is when little bumps appear along the chest due to the widening of the junction between the ribs and the costal cartilage in front of the rib cage.

Rickets and osteomalacia are usually diagnosed with lab tests, which show abnormally low vitamin D levels in blood serum, low blood calcium and elevated serum alkaline phosphatase. As a result of low calcium, there may also be high PTH, which may also lead to low serum phosphate.

Now x-ray imaging of rickets and osteomalacia might show signs of decreased bone mineral density or osteopenia. First, there's looser zones, which are bands of low bone density that form on the surface of the bone and they look a bit like bone fractures so they're also called pseudo fractures. Looser zones frequently develop in the inferior and superior pubic rami of the pelvic bone. In rickets, an x-ray image of the wrist and long bone metaphyses might demonstrate metaphyseal cupping and flaring. With metaphyseal cupping, the edges of the metaphysis widen laterally like flared jeans and the metaphysis itself drops inwards towards the diaphysis, which makes it look a bit like a cup. Another x-ray finding in rickets is metaphyseal fraying. Instead of the metaphyseal surface appearing smooth, it appears fuzzy and irregular. Finally, another x-ray finding with rickets may be bowing of the legs.

Treatment for both rickets and osteomalacia typically involves oral vitamin D supplementation and treating the underlying cause, which could be any condition affecting the organs responsible for vitamin D activation. In addition, preventative measures include vitamin D supplementation during pregnancy and administering vitamin D drops to neonates and infants.

All right, as a quick recap, rickets and osteomalacia are conditions in which bone softening occurs due to a mineral deficiency or lack of vitamin D. Now rickets presents in children and osteomalacia happens in adults, which depends if there was growth plate closure. Some key symptoms of rickets are craniotabes and bowlegs. For osteomalacia and rickets, the key symptoms are diffuse bone and joint pain, proximal muscle weakness, bone fragility, and increased risk of fractures with minimal trauma. There may also be looser zones on x-rays. The treatment typically involves oral vitamin D supplementation and treating the underlying cause.

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