Pediatric Osteoporosis 

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 this definition is functionally valid for adults, it 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 WHO definition of osteoporosis does not pertain to children at present.

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 (BMC) for these 3 parameters. The term osteopenia is no longer used when related to pediatric bone density or BMC.

Although, according to the currently accepted WHO definition of osteoporosis, children appear to be an exception to the disease and do not develop this condition, even secondary to another chronic illness, the pediatrician may elect, given the more recent NIH definition of osteoporosis, to interpret this condition with sufficient latitude as to increase awareness of bone-weakening diseases and medications.

Go to Osteoporosis for complete information on nonpediatric osteoporosis.

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 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 the latter 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.

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.

Children present with many forms of bone loss due to various causes. The roots of adult disease are believed to begin in childhood, though this view has been challenged by the argument that osteoporotic bone from whatever origin is replaced by newer intact bone as bone undergoes modeling.

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 supplementation in the preadolescent years may be a key factor in developing increased 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]

The data on the frequency of low bone density in children are inadequate. For example, through 1991, the rare condition of idiopathic juvenile osteoporosis had been reported in only 60 cases. 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.

Outside the United States and Western Europe, the prevalence of osteoporosis worldwide 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 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.

Classic osteoporosis is a disease of adulthood. 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. Caucasians are at the greatest risk for fractures, whereas blacks and Asians appear to be at the lowest risk.

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 low bone density for age in immobile children with severe developmental delay, crippling bony deformities may lead to cardiopulmonary compromise.

Prognosis depends on the underlying cause. A genetic condition leading to increased bone resorption may have a satisfactory prognosis if the antiresorptive agents can eliminate further bone loss. (See Treatment and Management.) For postmenopausal or senile osteoporosis in which bone formation is reduced, prognosis is improved because of the advent of parathyroid hormone administration to adults for 1 year followed by a bisphosphonate for 1 year. This results in bone gain.

In the case of trauma-induced or burn-induced low bone density for age in which bone formation is primarily affected, prognosis depends on the patient’s genetically determined peak bone mass and efficacy of clinically experimental therapies, such as anabolic steroids and pamidronate along with correction of progressive vitamin D deficiency that is a consequence of the skin’s failure to make adequate vitamin D with ultraviolet light exposure, similar to what is seen elderly persons. (See Treatment and Management.)

Although theories suggest that early-onset bone loss may be overcome as new healthy bone replaces compromised bone, a long-term outcome study in 144 young adults who were born with very low birth weight and were studied around the time of peak bone mass have significantly lower bone density at the lumbar spine and femoral neck compared to term-born peers.^[9]

Use education as a means of prevention and treatment. As early as possible, inform patients of any age with low bone density for age or osteoporosis why bone loss has occurred and how to keep bone loss under control. Also inform patients with low bone density for age or osteoporosis of the consequences of bone loss. Instruct children, adolescents, and their families that the roots of adult-onset osteoporosis may begin in childhood; therefore, ensure adequate calcium intake and weight-bearing exercises to maximize genetically determined peak bone mass. (The reason for the qualification is that there is a school of thought that argues that the constant modeling of bone, ie, the resorption of bone on the endosteal surface and addition of new bone on the periosteal surface, actually removes poor quality bone and can substitute good quality bone if the conditions that produced the poor quality bone are no longer present.)

For patient education resources, see the Bone Health Center, as well as Osteoporosis and Understanding Osteoporosis Medications.