Introduction
Background
The World Health Organization (WHO) defines osteoporosis as a bone density (or bone mass) at least 2.5 standard deviations below peak bone mass (defined as the bone mass achieved by healthy adults aged 18-30 y). Standard deviation from the mean peak bone mass is termed the T score. Thus, a T score of the lumbar spine or hip at least 2.5 standard deviations below the norm defines osteoporosis.
Although functionally valid for adults, this definition creates difficulty when evaluating pediatric patients. Children have not attained peak bone mass, and sufficient data correlating bone density with fractures are not available. Although preliminary studies have examined the role of lumbar spine bone density and the risk of fracturing in children with burn injuries, more extensive population-based studies have not been conducted. Therefore, the official definition of osteoporosis does not pertain to children at the present time. However, at a National Institutes of Health (NIH) Consensus Conference in 2000, osteoporosis was defined as a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture.1 Adult-onset osteoporosis also involves loss of bone trabecular structure; however, no evidence indicates that this occurs in children.
Encouragingly, at the First Pediatric Consensus Development Conference on the use and interpretation of bone density studies in children (sponsored by the International Society for Clinical Densitometry and held in Montreal in June 2007) pediatric osteoporosis was defined as bone density Z score below -2, in combination with a fracture.2,3,4,5 Z scores are now available for lumbar spine, hip, and total body because of a recently published NIH-sponsored multicenter study that established normative values of bone density and bone mineral content for these 3 parameters. The term osteopenia is no longer used when related to pediatric bone density or bone mineral content.
Pathophysiology
Low bone density in children involves the net loss of bone. Bone density is currently a 2-dimensional measurement. It is the quotient of the bone mineral content (BMC) measured in grams by absorptiometry in a specified bone region (eg, hip, lumbar spine), divided by the bone area (BA) in cm2 to give a reading in g/cm2. This 2-dimensional method of assessing bone density is limited because changes in bone volume and, therefore, bone strength cannot be detected. This leads to an inaccurate estimation of the severity of bone loss or the skeletal response to treatment. Pathways to decreased bone density all lead to an imbalance between the rate of bone formation and the rate of bone resorption. Thus, low-turnover conditions, such as chronic liver disease, burn injuries, or conditions that affect bone marrow (eg, malignancies) or their treatments, may result in a reduction of bone formation.
Other high-turnover states, such as Paget disease or hyperparathyroidism, can result in an increase in bone resorption. Interestingly, almost all preterm infants fall into this group. Because most calcium is transmitted from mother to fetus during the third trimester, infants born prematurely do not receive all the calcium their body needs to normally mineralize. With rapid postnatal increase in bone turnover, fewer opportunities are available for the bones to mineralize.6 Furthermore, most of these children receive total parenteral nutrition (TPN) for at least the first 3 weeks of life. TPN solutions are contaminated with aluminum; however, aluminum load has been decreased by more attention to additives. In addition, calcium and phosphorus requirements cannot be met by TPN in any age group, and the infant, especially the very premature infant, presents with hypophosphatemic metabolic bone disease.
The mechanisms resulting in secondary bone loss also stem from other adaptations to trauma and infection or threat of infection. These include the stress response, in which endogenous glucocorticoids may act in the same manner as exogenously administered steroids. These compounds cause an initial increase in osteoblast production of the receptor activator of nuclear transcription factor kappa B ligand (RANKL), which stimulates marrow to produce osteoclastic cells, increasing bone resorption. However, steroids also promote osteoblast apoptosis and reduce marrow cell osteoblast differentiation, eventually leading to a low-turnover bone loss or adynamic bone.
The other mechanism now linked to bone loss is the inflammatory response. This involves the production of the cytokines interleukin (IL)-1 beta and IL-6, as well as tumor necrosis factor (TNF) alpha. These are all capable of increasing bone resorption via stimulation of osteoblast production of RANKL.
Frequency
United States
Data that indicate the frequency of osteopenia in children are inadequate. The rare condition of idiopathic juvenile osteoporosis had been reported in 60 cases through 1991. By contrast, vertebral fracture prevalence attributed to osteoporosis in elderly women in the United States and Western Europe may be as high as 25%. As many as 54% of American postmenopausal women are estimated to have osteopenia, as defined by a T score between -1 and -2.5; an additional 30% are estimated to be osteoporotic, with a T score below -2.5.
International
The prevalence of osteoporosis worldwide (outside the United States and western Europe) varies. For example, the incidence of hip fracture in Koreans has increased from 3.3 per 10,000 to 13.3 per 10,000 between 1991 and 2001. In a 2005 study in Tehran, women aged 60-69 years had a 32.4% prevalence of spinal osteoporosis and a 5.9% prevalence of femoral osteoporosis, in contrast to a prevalence in similarly aged men of 9.4% and 3.1%, respectively. In Taiwan, the prevalence was 11.35% for women and 1.35% for men older than 50 years, based on bone density determinations.
Mortality/Morbidity
Contributing factors to mortality and morbidity, especially in the elderly, are primarily related to trauma. These factors include falls with resultant hip fractures necessitating immobilization with resultant pulmonary embolism. In extreme cases, including idiopathic juvenile osteoporosis and osteopenia in immobile children with severe developmental delay, crippling bony deformities may lead to cardiopulmonary compromise.
Race
Caucasians are at the greatest risk for fractures, whereas blacks and Asians appear to be at the lowest risk.
Sex
Osteoporosis mainly affects postmenopausal women and the elderly of both sexes. The protective effects of estrogens on bone are well known. During menopause, women lose their estrogen-producing capacity and develop a greater risk for significant osteoporosis.
Age
Classic osteoporosis is a disease of adulthood. Children present with many forms of bone loss from various causes. The roots of adult disease are believed to begin in childhood, but this concept is challenged by the argument that osteoporotic bone from whatever origin is replaced by newer intact bone as bone undergoes modeling.
Clinical
History
- Patients with reduced bone density (formerly termed osteoporosis) may be asymptomatic or may present with severe bone pain.
- In the elderly, severe back pain and limitation of motion may signify a vertebral compression fracture, although patients may be asymptomatic. Pain is often worse when standing and is relieved by walking. Loss of height is observed following vertebral fracture.
- In the peripubertal child with idiopathic juvenile osteoporosis, a gradual onset of pain occurs, primarily in the lower body (eg, hips, ankles, knees, feet), manifested by discomfort when walking.
Physical
- Children may present with spinal deformities (eg, kyphosis, kyphoscoliosis).
- Pigeon breast deformity, a crown-pubis/pubis-heel ratio less than 1, short stature, long bone deformities, and limping are other findings that may be observed.
- In adults, loss of height and progressive kyphosis are the most prominent findings with thoracic vertebral compression fractures; lordosis or scoliosis are observed with lumbar-vertebral compression fractures.
- Hip fractures are often observed following falls, especially in individuals who are elderly; women are more likely than men to fall on their hips.
Causes
- The most likely risk factor for idiopathic juvenile osteoporosis is genetic. Genetic factors may also play a role in some of the secondary causes of bone loss (eg, inflammatory bowel disease, rheumatoid arthritis).
- Children present with many forms of bone loss due to various causes. The roots of adult disease are believed to begin in childhood. Although a genetic determinant of peak bone mass is likely, a significant relationship between the calcium intake and peak bone mass is observed in preadolescent and young adolescent girls. The NIH Consensus Conference on Osteoporosis recommends that preadolescent and young adolescent girls have a calcium intake that is 50% more than the intake recommended for younger children and older adults.7 Dietary calcium intake in the preadolescent years may be a key factor in the development of peak bone mass. However, when dietary calcium supplementation is stopped, the increase in bone mass is not maintained.
- Trauma is a risk factor for bone loss following burn injury; the bone loss is complicated by immobilization, inflammatory responses leading to production of large quantities of resorptive cytokines and high endogenous glucocorticoid production that rapidly accelerate bone loss.
- Medications, such as corticosteroids, cyclosporine, and other cytotoxic agents, may contribute to bone loss secondary to other conditions. Chronic long-term steroid use contributes to loss of bone. A recently published study indicated that the risk of bone loss secondary to oral steroid use is higher in boys than in girls, whereas cumulative inhaled corticosteroids did not increase the risk of bone loss in either boys or girls.8
More on Osteoporosis |
 Overview: Osteoporosis |
| Differential Diagnoses & Workup: Osteoporosis |
| Treatment & Medication: Osteoporosis |
| Follow-up: Osteoporosis |
| References |
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Further Reading
Keywords
osteoporosis, low bone mass, pediatric osteoporosis, juvenile osteoporosis, fracture, compromised bone strength, osteopenia, chronic liver disease, burn injuries, Paget disease, hyperparathyroidism, hypophosphatemic metabolic bone disease, idiopathic juvenile osteoporosis, bony deformities, cardiopulmonary compromise, reduced bone density, kyphosis, kyphoscoliosis, short stature, long bone deformities, lordosis, scoliosis, pigeon breast deformity, hip fractures, inflammatory bowel disease, rheumatoid arthritis, trauma
