Pathophysiology
Summary
The mechanisms that influence bone mineralization are essential in understanding bone pathologies like osteomalacia. The first step of bone formation is the osteoblastic production of osteoid, a proteinaceous matrix largely composed of type I collagen. This is followed by the deposition of calcium phosphate into the osteoid, which is converted to organized hydroxyapatite.
In osteomalacia and rickets, the underlying mechanism involved decreased mineralization of osteoid, leading to an accumulation of unmineralized collagen matrix while maintaining preserved bone mass. This sets them apart from osteoporosis, which is defined by low bone mass. While osteomalacia can occur at any age, rickets occurs in growing children, and arises from decreased mineralization of type II hyaline cartilage of epiphyseal growth plates, located in long bones.
Vitamin D deficiency commonly underlies impaired bone mineralization, resulting in calcium and phosphate deficiency. Vitamin D is naturally found in foods such as fatty fish and fortified foods. UV light exposure is important for synthesizing active vitamin D, converting 7-dehydrocholesterol to calcitriol in the skin. Individuals with naturally pigmented skin are at a higher risk of deficiency due to decreased UV light absorption. Medical conditions like chronic kidney disease, which leads to a deficiency in 1-alpha hydroxylase and impaired vitamin D activation, as well as malabsorption syndromes (e.g. gastric bypass, IBD, chronic pancreatitis) can also compromise vitamin D levels. The hypocalcemia that arises from vitamin D deficiency triggers secondary hyperparathyroidism, which increases bone resorption to increase calcium, eventually leading to demineralization. This culminates in osteomalacia in adults and rickets in children.
Clinically, the continued osteoblast activity in osteomalacia and rickets leads to increased alkaline phosphatase and are susceptible to fractures, particularly in the vertebrae and femoral neck. Pseudofractures—radiolucent lines resembling bone fractures—common radiographic findings in both conditions.
Rickets presents with age-specific deformities: varus bowing in toddlers, valgus bowing in older children, and cranial abnormalities in infants, including softening of the skull bones and delayed closure of fontanelles. Radiographic hallmarks in rickets includes widening of the epiphyseal growth plate & fraying of the metaphysis. The decreased cartilage mineralization of open epiphyseal growth plates in rickets leads to short stature and enlargement of the costochondral junction, creating visible nodules at the ends of ribs known as 'rachitic rosary’.
Lesson Outline
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FAQs
Osteomalacia and rickets are both conditions resulting from impaired bone mineralization. Osteomalacia occurs in adults and is marked by decreased mineralization of osteoid—the proteinaceous matrix primarily made of type I collagen. On the other hand, rickets affects children and is characterized by defective mineralization of the type II hyaline cartilage in the epiphyseal growth plates of long bones.
Several factors can contribute to the onset of osteomalacia and rickets. Vitamin D deficiency is a primary etiology and can arise from low dietary intake, malabsorption syndromes (gastric bypass, IBD, chronic pancreatitis), limited UV light exposure, or naturally pigmented skin. Additionally, chronic kidney disease can lead to a deficiency in 1-alpha hydroxylase, affecting vitamin D activation. Hypocalcemia can also play a role by stimulating the release of PTH, which in turn causes bone resorption and demineralization.
Osteomalacia manifests in adults as bone pain that intensifies with weight-bearing activities. In children, rickets can lead to various physical abnormalities such as craniotabes, frontal or parietal bossing, and inward ‘knock-knee’ bowing of the legs in older children. Both conditions arise due to deficient mineralization, resulting in bones that are weak and susceptible to fractures, especially in areas like the vertebrae and femoral neck.
Vitamin D plays an important role in bone health by facilitating the deposition of calcium and phosphate, and leads to impaired bone mineralization when deficient. This deficiency can stem from various sources, including malabsorption syndromes, insufficient UV light exposure, or increased melanin in naturally pigmented skin. The outcome of this deficiency is osteomalacia in adults and rickets in children.
Both osteomalacia and rickets can be identified on x-rays by the presence of pseudofractures or ‘looser zones’, which appear as radiolucent lines resembling bone fractures. In children with rickets, other radiographic signs include enlargement of the epiphyseal growth plate, fraying of the metaphysis, leg bowing (either varus or valgus), and nodules at the ends of ribs due to enlargement of the costochondral junction, known as rachitic rosary.
