Bone Conditions in Children
Subtopic:
Osteogenesis imperfecta
Osteogenesis imperfecta (OI), commonly known as brittle bone disease, is a genetic disorder primarily characterized by bones that are abnormally fragile and prone to fracture.
Alternatively defined, OI is a condition of bone fragility mainly caused by genetic mutations in the COL1A1 and COL1A2 genes, which provide instructions for making type I procollagen, a crucial protein for bone structure.
In essence, Osteogenesis imperfecta (OI) is a genetic disorder leading to weakened bones.
Key characteristics of OI include:
Affects both the quality and mass of bone.
Is an inherited genetic condition.
Represents the most common genetic cause of osteoporosis, a generalized connective tissue disorder.
Osteoporosis, in this context, refers to the fragility of the skeletal system, making bones susceptible to fractures, particularly of the long bones or vertebral compression fractures, even from minor or seemingly insignificant trauma.
Aetiology
OI arises from mutations in genes that disrupt the body’s production of collagen, a vital protein for bone and other tissues. Individuals with OI either have a reduced amount of collagen or their collagen is of substandard quality.
The underlying cause of OI involves defects in or related to type 1 collagen, a fundamental building block for various bodily structures. Type 1 collagen is crucial for making bones strong and is also used to construct tendons, ligaments, and teeth.
These collagen defects are a consequence of specific genetic alterations or mutations.
Approximately 80%-90% of OI cases stem from autosomal dominant mutations in the genes responsible for producing type 1 collagen, namely COL1A1 and COL1A2. These mutations result in the body producing either abnormally formed collagen or an insufficient quantity of normal collagen.
The remaining cases of OI are attributed to autosomal recessive mutations in a set of six other genes: SERPINF1, CRTAP, LEPRE1, PPIB, SERPINH1, and FKBP10.
These gene mutations are typically inherited, meaning they are passed from parents to their offspring.
Epidemiology
The autosomal dominant forms of OI exhibit a consistent occurrence across all racial and ethnic backgrounds. Conversely, recessive forms are more frequently observed in ethnic groups where consanguineous marriages (marriages between close relatives) are more common.
Notably, a specific genetic mutation associated with type VIII OI has a carrier frequency of approximately 1 in 200-300 among African Americans in West Africa.
The incidence of OI that is detectable during infancy is estimated to be around 1 in 20,000 live births.
Pathophysiology
Individuals with OI are born with connective tissue that is either defective or have a reduced capacity to produce it, primarily due to a deficiency in type 1 collagen. This deficiency often arises from an amino acid substitution within the collagen’s triple helix structure, where the smaller amino acid glycine is replaced by a bulkier amino acid.
The presence of these larger amino acid side-chains causes steric hindrance, creating a bulge or distortion in the collagen complex. This structural abnormality compromises both the molecular nanomechanics (the way the molecules function at a very small scale) and the interactions between collagen molecules.
As a consequence of this improper structure, the body may initiate a process of hydrolyzing or breaking down the flawed collagen.
If the body does not effectively destroy the improperly formed collagen, it disrupts the normal relationship and organization between collagen fibrils and hydroxyapatite crystals, the mineral component of bone. This altered interaction leads to the characteristic brittleness of bones seen in OI.
Clinical Manifestations
Short stature: Individuals with OI often have a shorter height than expected for their age and family background.
Weak tissues, fragile skin, muscle weakness and loose joints: Due to the underlying collagen defect, various tissues throughout the body can be weaker than normal, including the skin, which may be thinner and more easily damaged. Muscle weakness and increased joint flexibility (laxity) are also common.
Bone deformities such as bowing of the legs: The fragile nature of the bones can lead to deformities, with the legs frequently exhibiting a bowed shape.
Hearing loss: Hearing impairment is a common complication in individuals with OI, often developing in adulthood.
Discolouration of the sclera, may be blue, purple in colour: The sclera, or the white part of the eye, often has a bluish or purplish tint due to the thinness of the collagen layer, allowing the underlying choroidal veins to be more visible.
Curvature of the spine: Scoliosis (sideways curvature) or kyphosis (forward curvature) of the spine can develop due to the weakened vertebrae.
Breathing problem: Respiratory issues can arise due to chest wall deformities or weakness of the respiratory muscles.
Easy bruising of skin: The fragility of blood vessels, also related to collagen defects, makes individuals with OI prone to bruising easily.
Soft, discoloured teeth: Dentinogenesis imperfecta, a condition affecting tooth development, can occur in some types of OI, leading to teeth that are softer than normal and may have a greyish-brown or yellowish discoloration.
Classification of OI
The Sillence classification system categorizes OI into four main types based on clinical and radiographic findings. Types V and VI were later proposed based on distinct histological characteristics of bone.
Osteogenesis Imperfecta Type I (mild): This is the mildest form of OI and is often observed across multiple generations within families (large pedigrees). Individuals with type I OI commonly have blue sclerae, experience recurrent fractures primarily during childhood, and may develop presenile hearing loss (affecting 30%-60%). Other potential connective tissue abnormalities can include overly flexible joints (hyperextensible joints), a tendency to bruise easily, thin skin, scoliosis (spinal curvature), hernias, and mild short stature compared to other family members.
Osteogenesis Imperfecta Type II (Perinatal Lethal): Type II OI represents the most severe form, with infants often being stillborn or dying within the first year of life. Birth weight and length are typically below average for gestational age. There is extreme fragility of the skeleton and other connective tissues. Multiple fractures of the long bones occur before birth (intrauterine), giving them a crumpled appearance on X-rays. Striking micromelia (abnormally short limbs) and bowing of the extremities are present; the legs are often positioned abducted at right angles to the body, resembling a “frog-leg” position. The skull appears large relative to the body size, with enlarged anterior and posterior fontanelles (soft spots). The sclerae have a distinct dark blue-grey color.
Osteogenesis Imperfecta Type III (Progressive Deforming): Type III OI is the most severe non-lethal form, leading to significant physical disability. Birth weight and length are often in the low-normal range. Fractures frequently occur in utero. Individuals with type III OI often have a relatively large head (macrocephaly) and a triangular-shaped face. Disorganization of the bone matrix results in a characteristic “popcorn” appearance at the metaphyses (the wider ends of long bones). All individuals with type III OI experience extreme short stature. Dentinogenesis imperfecta (tooth abnormalities), hearing loss, and kyphoscoliosis (a combination of forward and sideways spinal curvature) may be present at birth or develop over time.
Osteogenesis Imperfecta Type IV (moderately severe): Individuals with type IV OI can present with fractures or bowing of the lower long bones before birth. They may also experience recurrent fractures after they begin walking (ambulation). Their stature ranges from normal to moderately short. Many children with type IV OI exhibit moderate bowing of the limbs, even with infrequent fractures. Orthopedic and rehabilitation interventions are typically required for individuals with type IV OI. The rate of fractures tends to decrease after puberty. Radiographically, their bones appear osteoporotic (thin and less dense), and they may have metaphyseal flaring (widening of the ends of long bones) and vertebral compression fractures. Individuals with type IV OI have moderate short stature, and their scleral color can be either blue or white.
Classification of OI (Forlino and Marini, 2015)
Forlino and Marini proposed an alternative classification system in 2015 that focuses on the underlying genetic and functional defects in OI, categorizing it into five groups:
Group A: This group encompasses OI cases resulting from primary defects in the structure and function of collagen itself.
Group B: This category includes defects related to the modification of collagen molecules after they are initially produced.
Group C: This group involves defects affecting the proper folding and crosslinking of collagen molecules, which are essential for their stability and function.
Group D: This group includes defects that primarily affect the processes of ossification (bone formation) or mineralization (the deposition of minerals in bone).
Group E: This group encompasses defects in the development of osteoblasts (the cells that build bone), leading to insufficient collagen production.
Assessment and Diagnostic Findings
Diagnostic evaluations for individuals with osteogenesis imperfecta (OI) are valuable in distinguishing it from other metabolic bone disorders.
Collagen synthesis analysis: This test involves growing dermal fibroblasts (connective tissue cells from the skin) obtained through a skin biopsy to analyze the type and quality of collagen produced.
Prenatal DNA mutation analysis: When there is a known risk of OI in a pregnancy, this analysis can be performed prenatally. It involves examining the DNA of uncultured cells obtained from chorionic villus sampling (a placental tissue sample) to identify specific gene mutations associated with OI.
Bone mineral density (DEXA scan): A dual-energy X-ray absorptiometry (DEXA) scan is used to measure bone mineral density. In individuals with OI, bone mineral density is typically lower than normal, indicating less dense and more fragile bones.
X-ray: Radiographic images can reveal characteristic features of OI, such as thinning of the long bones with slender outer layers (cortices). In some cases, the ribs may appear beaded, and the bones may be wider than normal. The presence of numerous fractures and deformities of the long bones is also a common finding.
Biochemical testing: This may involve analyzing a skin sample to directly examine the structure and composition of collagen.
Blood tests or urine tests: These are typically performed to rule out other conditions that may affect bone health, such as rickets (vitamin D deficiency) or other metabolic disorders.
Differential Diagnosis
It’s important to differentiate OI from other conditions that may present with similar symptoms or findings:
Child abuse (non-accidental injury)
Rickets (vitamin D deficiency affecting bone development)
Scurvy (vitamin C deficiency affecting collagen production)
Osteopetrosis (a rare condition causing abnormally dense bones)
Leukaemia (cancer of the blood-forming tissues, which can cause bone pain and fragility)
Cushing syndrome (a hormonal disorder that can lead to osteoporosis)
Treatment and Management
Currently, there is no cure for Osteogenesis Imperfecta. Management focuses on alleviating symptoms and improving quality of life.
Aims of Management:
To reduce the frequency of fractures.
To prevent or minimize long bone deformities.
To alleviate chronic pain.
To maximize the individual’s functional abilities and independence.
The main approaches to treatment involve medications, surgical interventions, physical and occupational therapy, and experimental therapies.
Medications:
Bisphosphonate therapy: This is a primary medication approach for preventing fractures in most types of OI. Studies have shown that bisphosphonates can significantly reduce fracture frequency in children with OI.
Intravenous pamidronate: Pamidronate, administered intravenously (IV), is generally recommended for individuals with most forms of OI, except possibly Type VI, where the benefits are weighed against potential long-term risks. It is particularly considered for those with long bone deformities, vertebral compression fractures, and a history of frequent fractures (≥3 per year).
Pamidronate is given intravenously in cycles, typically over 3 consecutive days, every 2 to 4 months. The dosage ranges from 0.5 to 1 mg/kg per day, adjusted based on age, resulting in an annual dose of approximately 9 mg/kg.
The lowest effective dose is used, with careful monitoring for changes in vertebral shape and the occurrence of long-bone fractures.
Note: Pre-treatment evaluation and monitoring are crucial. Before starting treatment, ensure adequate calcium and vitamin D intake based on the child’s age (recommended dietary allowance is 700–1300 mg/day calcium and 400–600 IU vitamin D). Supplementation is recommended if dietary intake is insufficient. Assess calcium homeostasis (calcium, phosphorus, parathyroid hormone levels) and kidney function before starting treatment and monitor these every 6–12 months.
Calcium levels should be checked before each IV bisphosphonate infusion to ensure the child does not have hypercalcemia (high calcium levels).
Surgical Intervention:
Management of fractures: Prompt and appropriate management of fractures is essential, with emphasis on early mobilization to minimize bone loss due to inactivity.
Placement of intramedullary rods: These rods are surgically inserted into the long bones to provide support, prevent bowing, and correct existing deformities. For actively growing children older than 2 years, telescoping rods are often used, as they can extend in length as the bone grows. Surgery may also be beneficial for individuals with severe scoliosis.
Intramedullary rod replacement: In cases of bowed long bones, replacing existing rods can improve weight-bearing ability, potentially enabling the child to walk earlier than they otherwise would.
Surgery for basilar impression: This surgical procedure is reserved for cases where the base of the skull is pressing on the brainstem, causing neurological problems.
Correction of scoliosis: While challenging due to bone fragility, surgical correction of scoliosis through spinal fusion may be beneficial for individuals with severe spinal curvature.
In utero bone marrow transplant: In some cases, experimental in utero bone marrow transplantation using adult bone marrow has shown promise in decreasing the severity of OI in newborns, particularly reducing perinatal lethality (death around the time of birth).
Physical and Occupational Therapy:
Physical therapy: Physical therapists play a key role in designing exercise programs tailored to minimize fracture risk while promoting mobility and preventing joint contractures (stiffness) and bone loss from immobility.
Occupational therapy: Occupational therapists help individuals adapt to limitations and improve their ability to perform daily living activities, addressing challenges caused by upper or lower limb deformities.
Experimental Therapies:
Growth hormone: A limited study involving children with OI on bisphosphonate therapy showed that adding recombinant growth hormone resulted in a higher growth velocity compared to those receiving bisphosphonates alone. However, no significant difference in fracture risk was observed.
Cell replacement therapies: A pilot study investigating allogeneic hematopoietic cell transplantation (transplantation of blood stem cells from a donor) in a small group of children with OI showed promising results. In the children where the transplant was successful, improvements in growth velocity and a reduction in fracture rate were noted. Further research is needed to explore this treatment modality.
Complications:
Individuals with OI may experience various complications, including:
Respiratory infections such as pneumonia
Kidney stones
Joint problems (pain, stiffness, dislocations)
Hearing loss
Eye conditions and vision loss
Basilar invagination (where the top of the spinal column pushes into the base of the skull)
Brain stem compression (due to basilar invagination)
Hydrocephalus (a buildup of fluid in the brain)
Nursing Care
| Nursing Diagnosis | Desired Outcomes | Intervention | Rationale |
| Knowledge Deficit <br> Related to new diagnosis of osteogenesis imperfecta, as evidenced by patient’s verbalization of “I want to know more how to manage my illness.” | By the end of the health education session, <br> The patient will: <br> – Articulate adequate understanding of their condition. <br> – Demonstrate comprehension of its management strategies. | To effectively address knowledge gaps: <br> – Evaluate the patient’s cognitive abilities and current mental state regarding their diagnosis. <br> – Identify and address any misconceptions or barriers to learning, such as denial or lifestyle factors. <br> – Facilitate the patient’s active participation in the learning process to overcome obstacles and enhance understanding. | |
| Activity Intolerance <br> Related to bone pain, as evidenced by bone pain score of 7/10, fatigue, disinterest in ADLs due to pain, verbalization of tiredness and generalized weakness. | The patient will: <br> – Exhibit active participation in necessary and desired activities. <br> – Show gradual increase in activity levels as tolerated. | – Evaluate baseline activity levels: Assess daily living activities and perceived limitations due to physical condition. Inquire about preferred forms of exercise or activities. <br> – Promote progressive activity: Encourage gradual increases in self-care and exercise as tolerated. <br> – Educate on activity modification: Explain the importance of reducing prolonged sedentary behaviors, such as extended television viewing or social media use. <br> – Pre-activity analgesia: Administer prescribed analgesics prior to exercise or physical activity. <br> – Teach relaxation techniques: Instruct in deep breathing and other relaxation methods. | To establish safe activity progression: <br> – Determine initial activity capacity and mental state linked to chronic pain, fatigue and activity limitations. <br> – Gradually build patient’s tolerance to physical exertion. <br> – Provide pain relief measures before exercise sessions. <br> – Enable patient relaxation during rest periods to facilitate effective stress management. |
| Acute Pain <br> Related to the fragility of the bones, evidenced by pain score of 7/10, verbalization of sharp pain, guarding sign on the affected areas especially long bones, facial grimace, crying, and restlessness. | The patient will: <br> – Demonstrate pain relief as evidenced by a pain score of 0-3 out of 10. <br> – Maintain stable vital signs. <br> – Exhibit absence of restlessness. | – Ensure adequate ventilation in the patient’s room. <br> – Administer prescribed pain medications promptly. <br> – Assess pain characteristics and vital signs: Evaluate pain levels at least 30 minutes post-medication administration. <br> – Promote rest: Position patient for comfort, ideally in complete bed rest during severe pain episodes. | To manage acute and chronic bone pain: <br> – Improve oxygen availability in the environment. <br> – Alleviate acute/chronic bone pain (often described as sharp and spasmodic). <br> – Monitor the effectiveness of medical pain management. <br> – Time vital sign monitoring to align with the medication’s peak effect. <br> – Enable patient rest and enhance comfort levels. <br> – Utilize standardized pain assessment tools for consistent evaluation. |
Practice Test: Osteogenesis Imperfecta
Question 1:
When instructing parents of a newborn diagnosed with Osteogenesis Imperfecta, which action should the nurse emphasize?
A. Routine administration of daily calcium supplements.
B. Supporting the infant by the buttocks during diaper changes and lifting.
C. Understanding the temporary nature of this condition.
D. Recognizing that only the skeletal system is involved.
Answer: B. To lift the baby by the buttocks when diapering.
Rationale:
Incorrect A: Children with Osteogenesis Imperfecta typically have normal calcium and phosphorus levels; supplementation is not a standard treatment for this condition itself.
Incorrect C: Osteogenesis Imperfecta is a chronic, genetic disorder, not a temporary condition.
Incorrect D: Osteogenesis Imperfecta can affect tissues beyond bones, including teeth (potentially causing dentinogenesis imperfecta) and the sclera of the eyes (leading to blue sclera).
Question 2:
A home healthcare nurse is visiting an 18-year-old patient with Osteogenesis Imperfecta. Which observation during the visit would be of greatest concern? The patient:
A. Enjoys playing football.
B. Consumes several carbonated beverages daily.
C. Has siblings with sickle cell trait.
D. Uses acetaminophen for pain relief.
Answer: A. Likes to play football.
Rationale:
Correct A: Participation in contact sports like football significantly elevates the risk of pathological fractures in individuals with Osteogenesis Imperfecta due to their fragile bones.
Incorrect B: While excessive carbonated drink consumption is unhealthy, it is not the most pressing concern in comparison to the risk of injury.
Incorrect C: The presence of sickle cell trait in siblings is not directly relevant to the patient’s Osteogenesis Imperfecta management.
Incorrect D: Acetaminophen is a common over-the-counter pain reliever and its use is not inherently alarming unless there are concerns about dosage or effectiveness.
Question 3:
A patient presents with frequent fractures and exhibits blue sclera. In infants with the same condition, potential outcomes include:
A. Fatality.
B. A, C, and D.
C. Fractures.
D. Blue sclera.
Answer: B. A, C, D.
Rationale:
Correct B: Osteogenesis Imperfecta encompasses a spectrum of severity. In its most severe forms, particularly Type II, it can be lethal in infancy. Fractures and blue sclera are also characteristic features across different types of Osteogenesis Imperfecta.
Options A, C, D: These are all recognized manifestations of Osteogenesis Imperfecta, particularly in infants.
Question 4:
Identify the bone disorder resulting from an autosomal dominant genetic defect in type 1 collagen synthesis.
A. Osteogenesis Imperfecta.
B. Achondroplasia.
C. Osteopetrosis.
D. Osteomyelitis.
Answer: A. Osteogenesis Imperfecta.
Rationale:
Correct A: Osteogenesis Imperfecta is primarily caused by genetic mutations that disrupt the production or processing of type 1 collagen, a vital protein for bone strength and structure. This condition is often inherited in an autosomal dominant pattern.
Incorrect B: Achondroplasia is caused by mutations in the FGFR3 gene, leading to excessive protein activity that interferes with bone growth and results in a form of dwarfism.
Incorrect C: Osteopetrosis, also known as “marble bone disease,” is a rare genetic disorder characterized by abnormally dense and brittle bones due to impaired bone resorption.
Incorrect D: Osteomyelitis is a bone infection, typically bacterial in origin, most commonly caused by Staphylococcus aureus.
Question 5:
Which pharmacological agent is known to reduce fracture incidence and enhance bone mineral density, potentially leading to pain reduction and increased energy levels in Osteogenesis Imperfecta patients?
A. Risedronate.
B. Gentamicin.
C. Tramadol.
D. Pamidronate.
Answer: D. Pamidronate.
Rationale:
Correct D: Intravenous Pamidronate, administered in cycles, is clinically used to decrease fracture rates and improve bone mineral density in individuals with Osteogenesis Imperfecta. Patients may also experience reduced pain and improved energy as a result of treatment.
Incorrect A: Risedronate, an oral bisphosphonate, can be used in Osteogenesis Imperfecta management to help reduce fracture risk, but Pamidronate (given intravenously) is often considered a more potent option.
Incorrect B: Gentamicin is an antibiotic medication used to treat bacterial infections and is not relevant to the management of Osteogenesis Imperfecta itself.
Incorrect C: Tramadol is an opioid analgesic used for pain management, but it does not address the underlying bone fragility or density issues associated with Osteogenesis Imperfecta.