Introduction
Osteoporosis (OP) is a disorder where the bones get thinner and more fragile. It is characterized by less bone formation, more bone loss, or a combination. Hence, the bones become weaker and are at high risk of fracture. OP is common in older adults (especially older women) and rare in adolescents and children. However, during childhood, it is called juvenile osteoporosis. It is crucial to identify this condition to manage it at its earliest.
What Is the Pathophysiology of Pediatric Osteoporosis?
In childhood, bone mass and strength are determined by new bone accumulation and existing bone remodeling. Three specialized cells establish and maintain bone strength: osteoblasts (bone-forming cells), osteoclasts (bone-resorbing cells), and osteocytes (cells involved in regulation). Osteoblasts and osteoclasts renew and repair the bone constantly. Signaling between all three is important for skeletal integrity. The compromise of this signaling can result in decreased bone strength. In children, there is more bone deposition than resorption. In OP, this balance is disrupted due to genetic or secondary causes. As a result, it leads to insufficient bone mass and decreased resilience to withstand stress.
What Are the Types and Causes of Pediatric Osteoporosis?
There are many causes of OP in children. However, most are secondary to other illnesses or treatments.
1. Primary Osteoporosis: Primary OP in children covers a range of bone fragility conditions with a genetic origin. The most common form of primary OP in children is osteogenesis imperfecta (OI). It comprises a group of disorders characterized by defective collagen synthesis and regulatory abnormalities. It also arises from other factors, including high bone turnover, osteoblast dysfunction, and abnormal bone mineralization. The diagnosis of OI is made based on clinical history, family history, examination, and other investigations, such as imaging techniques, genetic analysis, and histopathology. However, genetic analysis for known genes is not diagnostic.
2. Secondary Osteoporosis: Secondary OP occurs due to chronic conditions or their treatment (especially corticosteroid use). Anticonvulsants (used for seizures) and proton pump inhibitors (PPIs; used for acidity) also affect bone mineral density (BMD) or cause fractures. There has been an increase in the number of children with secondary OP. Hence, the long-term effects of secondary OP have become more eminent.
What Are the Investigations Done in Pediatric Osteoporosis?
1. Genetics: With recent advancements in genetics, there is an increased understanding of the multiple genes linked to bone fragility. A definite genetic diagnosis can confirm clinical speculation and the management of OP. It also enables screening of other family members, genetic counseling, and early disease detection. It is helpful for children with frequent fractures. However, the likelihood of finding a mutation is small.
2. Computed Tomography (CT): CT can describe the trabecular (inner spongy bone) and cortical bone (outer layer of bone) and also measure the BMD along with muscle geometry. It is specifically useful for children with spinal deformities, where DXA imaging can be challenging.
3. Bone Turnover Markers: Bone turnover markers (BTMs), that is, osteocalcin, have limited use in the pediatric population. Children have elevated bone marker levels due to increased growth and rapid bone turnover.
4. Vertebral Fracture Assessment (VFA): VFA with DXA is of high accuracy for diagnosing vertebral fractures (VF). The ability to obtain the image at the same time as BMD with lower radiation exposure, better image quality, and a lower cost makes VFA a preferred method for detecting VF in children.
5. Bone Biochemistry: After proper history and examination, baseline investigations are calcium, phosphate, magnesium, and vitamin D. It is because the primary bone disorders must be excluded. Furthermore, calcium, vitamin D, and a bone profile are essential before OP treatment.
6. Dual-Energy X-ray Absorptiometry (DXA): DXA for assessing BMD got approval from the United States Food and Drug Administration (US FDA) in 1988. DXA is the preferred method for bone mineral content (BMC) and BMD assessment. Estimating BMD should be part of the assessment for children at risk of a significant fracture. Femur (thigh bone) DXA measurements can be used for assessing children with decreased weight tolerance or increased bone fragility. The advantages of DXA are its low radiation dose, short scan time, and easy availability. DXA can underestimate BMD in children with short stature or growth delays (as it is a two-dimensional scan). Similarly, it can overestimate BMD in tall children.
How Is Pediatric Osteoporosis Managed?
1. General Approach: Management of child OP requires a patient-centered approach. Physiotherapists and occupational therapists are the most important for optimizing mobility and daily living. In neonatal cases, rib fractures can compromise breathing. Hence, respiratory support is crucial. It is also essential to support the head and spine and encourage prone (straight) positioning. In severe cases, parents should receive instructions on safe baby handling after diagnosis to prevent future fractures.
2. Medications:
- Antiresorptive: Antiresorptive therapies increase bone strength in individuals by inhibiting bone resorption in OP patients.
- Bisphosphonates: Bisphosphonates are the preferred medical treatment for OP. Intravenous (into the vein) Pamidronate, Neridronate, or Zoledronate are given in moderate to severe OI. Risedronate is the strongest oral bisphosphonate, and a trial showed increased lumbar vertebral BMD and a decreased risk of long bone fractures. On the other hand, Zoledronate is the most potent intravenous bisphosphonate treatment. It can be given as an infusion over 30 minutes and repeated for six months. It should be noted that in bisphosphonate therapy, zebra lines are seen on X-rays. These represent drug-inhibiting osteoclast activity periods and increased bone with low remodeling activity.
- Denosumab: It is a monoclonal antibody (an artificially produced antibody that mimics human antibodies) used in children with OI and OP. However, its duration of action is shorter as compared to adults.
- Anabolics: In some OP cases, antiresorptive therapy causes a reduction in bone turnover. As a result, there has been increased interest in anabolic (favoring anabolism) therapies. Growth hormone (GH), testosterone, and parathyroid hormone (PTH) are some anabolics.
3. Whole-Body Vibration (WBV): WBV is a term used when vibrations of any frequency are given to the human body. Several trials in studies of children with OP have demonstrated a beneficial effect of WBV therapy on walking speed, muscle strength, and balance. Also, in children with OI, WBV resulted in an increase in lean mass without changes in muscle function.
Conclusion
Prevention and treatment of fractures in children with OP are essential. The data regarding the effect of medications on reducing fractures is equivocal. Many drugs are tried by adults, but they are not licensed for children. Hence, increasing awareness of pediatric osteoporosis, screening, and referral to a specialist team for appropriate management can lead to early treatment of fractures and prevention of further bone damage.
