AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

In children, low bone density (formerly termed osteoporosis) can develop because of low bone formation (low bone turnover) or high bone resorption (high bone turnover).

The following conditions elicit low bone formation:

• Medication-induced osteopenia (prominently corticosteroids and cyclosporine)
• Immobilization or prolonged bed rest
• Burn injury
• Hypoparathyroidism that results in hypercalciuria
• Hepatic osteodystrophy with chronic cholestasis (all causative syndromes and conditions)
• Aluminum toxicity in association with TPN or renal osteodystrophy
• Prolonged TPN
• Corticosteroid-induced osteopenia

Conditions giving rise to high bone turnover include the following:

• Corticosteroid-induced bone loss
• Immobilization or bed rest
• Paget disease
• Primary and secondary hyperparathyroidism
• Rickets due to vitamin D deficiency or calcium deficiency
• Idiopathic juvenile osteoporosis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Serum calcium, phosphorus, magnesium, creatinine levels
• • High or normal serum calcium levels and normal or low phosphorus levels suggest secondary hyperparathyroidism.
  • Low serum calcium levels and high or normal phosphorus levels suggest hypoparathyroidism.
  • Creatinine levels provide an indication of renal disease.
  • Magnesium levels provide an index of total body magnesium status and can be affected in perturbations of the parathyroid.
• Serum parathyroid hormone (PTH) levels
• • High PTH levels confirm hyperparathyroidism.
  • Low PTH levels confirm hypoparathyroidism.
• Serum or urinary cross-links of type I collagen (deoxypyridinoline), N-telopeptide of type I collagen (NTx) or C-telopeptide of type I collagen (CTx), urine creatinine
• • Deoxypyridinoline, an index of bone resorption, is high in the urine of children who have rapid bone turnover.
  • Obtain biochemical markers of bone resorption (NTx) and formation (osteocalcin) to clarify the nature of what is occurring in the bone.
• Serum osteocalcin or bone-specific alkaline phosphatase: Values may vary between assays. No expected results are reported. Osteopenia can develop from either high-turnover or low-turnover conditions. These tests help define which condition may be active.
• • Pediatric reference ranges for osteocalcin
  • • Younger than 12 years - 10-25 ng/mL
    • Older than 13 years - 2-8 ng/mL
  • Pediatric reference ranges for bone specific alkaline phosphatase
  • • Preadolescents - 50-150 IU/L
    • Adolescents - 10-50 IU/L

Imaging Studies

• Dual energy x-ray absorptiometry scan
• • The amount of calcium in bone can be quantified in several ways. Bone densitometry based on dual energy x-ray absorptiometry (DEXA) is the most widely used method. DEXA provides 2-dimensional imaging of a region of bone, such as the lumbar spine, hip, or radius.
  • DEXA provides a computerized printout of bone calcium content, which is measured in grams; the bone area is measured in cm²; and the 2-dimensional bone density is measured in g/cm².
  • Pediatric reference ranges are taken from large studies using DEXA and are incorporated into the software that provides the printout; thus, actual individual bone density and its comparison to age-related normal values (Z score) is printed out as part of the report. The main drawback is that DEXA does not measure changes in bone volume and, therefore, changes in bone strength. It also tends to over-read bone density in larger patients and under-read it in smaller patients. Criteria for pediatric DEXA reporting are now available on the Web site of the International Society for Clinical Densitometry as well as the January 2008 issue of the Journal of Clinical Densitometry.⁹
• Investigational methods
• • Other methods under investigation include calcaneal and phalangeal ultrasonography and quantitative CT (qCT), which involves the most radiation of any of the tests. Reference range values for phalangeal ultrasonography results are now available.
  • Peripheral qCT (pqCT), which usually involves a foot or a lower limb and much less radiation than the qCT scan, can also provide an indirect assessment of bone density. However, DEXA is by far the most commonly used technique. Criteria for performing and reporting pQCT imaging are also found on the Web site of the International Society for Clinical Densitometry and the January 2008 issue of the Journal of Clinical Densitometry.⁹

Histologic Findings

Because of the availability of kits to measure biochemical markers of bone turnover, the use of bone histology obtained by iliac crest bone biopsy is no longer routine. Histology for bone biopsies is generally carried out using quantitative histomorphometry. For patients older than 10 years, administer tetracycline or one of its analogs 14 days before biopsy and then 2 days prior to biopsy. Using one of several specialized orthopedic needles, obtain a biopsy sample consisting of a 6-mm core of trabecular bone tissue.

When processed, the amounts of mineralized bone, unmineralized bone, and bone surface can be quantitated. In addition, the tetracycline binds to newly calcified bone at the mineralization front, which is the boundary between mineralized bone and unmineralized matrix where new bone forms. Each time a dose of tetracycline is administered, it forms a band at the mineralization front that can be detected under a fluorescent microscope. The distance between the 2 fluorescent bands can be quantitated. When divided by the time interval between doses and multiplied by the length of bone surface taking up the tetracycline yields, the rate of new bone formation is achieved. The eroded or resorbed bone surface also can be quantitated, and all can be compared to reference values for age.

Perform these studies if analysis of bone markers and other biochemical determinations are inconclusive regarding the nature of the activity of the bone in a particular condition. These studies also form the basis for validating the biochemical bone marker analyses.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Management is primarily medical, depending on the underlying condition. If the underlying condition is optimally managed and osteopenia persists, then management depends on bone dynamics.
• When bone resorption exceeds bone formation, try an antiresorptive agent (eg, bisphosphonate). The most current generation of oral bisphosphonates includes alendronate and risedronate. The primary parenterally administered bisphosphonate is pamidronate. Safe and effective pediatric doses have not been established; however, current clinical trials are investigating the use of alendronate in children with osteogenesis imperfecta, and preliminary results indicate that the drug is safe.
• Pamidronate is currently under study in children with burn injuries. The dose of pamidronate is 1.5 mg/kg weekly for 2 weeks with a maximum dose at any one time of 90 mg, which is the adult upper limit of normal. In a 2-year follow-up study by Przkora et al evaluating changes in bone density and histology following the initial treatment with pamidronate, data supported a long-term effect on trabecular bone density and bone mineral content of the lumbar spine.¹⁰ Total body bone mineral content eventually showed recovery in patients with burn injuries on placebo therapy; therefore, the effect on cortical bone did not appear long lasting. Data obtained from clinical studies in adults are very promising. However, caution in the overuse of these drugs is warranted because the drugs remain in bone for a long time and an osteopetrosislike condition has been reported.
• Osteopenia secondary to low bone formation is more difficult to manage because of the absence of a safe and effective anabolic agent. PTH, which is potentially very promising when given intermittently to osteoporotic adults, is not approved for use in children because of the detection of osteogenic sarcoma in rats that were given very high test doses.¹¹
• Recombinant human growth hormone is a useful anabolic agent for children with growth hormone deficiency; its benefits for others with osteopenia have not been extensively studied. It does improve bone mineral content in burned children if given for a year, but the need for repeated injections and the cost are limiting.¹²
• Anabolic steroids (eg, testosterone, oxandrolone) may be helpful in forming new bone; however, consider the risks of premature closure of the epiphyses, short stature, and hirsutism. Also consider the potentially increased risk for tumor development. However, in a 2004 study, oxandrolone was given for 1 year to a group of children following burn injury.^{13, 14, 15, 16} No epiphyseal closure was demonstrated, and only 2 cases of clitoral hypertrophy were observed (both were reversed after cessation of the drug).

Surgical Care

• Unless a resectable tumor can be identified as the cause of osteopenia or osteoporosis, surgery is unlikely to play a role in treatment. In most cases, the cause is systemic and results in widespread disease.

Consultations

• Consult an endocrinologist to assist in the management of any patient with bone loss.

Diet

• Calcium and vitamin D are the most important dietary nutrients to help prevent adult osteoporosis.
• The NIH Consensus Conference on Osteoporosis recommended a calcium intake of 800 mg/d until age 10 years, 1200 mg/d during adolescence, and 1000 mg/d after adolescence.¹
• Calcium intake should be increased for women who are pregnant, for women who are lactating (1200 mg/d), and for individuals older than 65 years (1500 mg/d).
• An intake of 400-800 international U/d is also recommended. 
• A diet rich in dairy products is recommended to help provide the calcium and vitamin D required.

Activity

• Activity plays a role in the prevention of osteoporotic fractures.
• Several recent studies in the United States and in Europe have established that regular weight-bearing exercise, such as jumping, in school-aged children improves bone mass.¹⁷ However, once the exercises are stopped, the gains are lost.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Therapy includes antiresorptive agents such as bisphosphonates (eg, alendronate, risedronate, pamidronate). Hormone replacement therapy (eg, estrogen, estrogen analogs) does not have a role in pediatric therapy.

Drug Category: Bisphosphonate bone-resorption inhibitors

These agents prevent bone loss from diminishing bone mass on an ongoing basis. They are available in parenteral and oral dosage forms for acute and chronic treatment, respectively.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Generally, individuals suffering from bone loss alone (formerly termed osteoporosis) do not require hospitalization unless they have a complication such as a hip fracture. This is a very uncommon occurrence in children; however, following a fracture, anticipatory intervention is needed to minimize future hospital stays and to identify individuals at risk for repeated fractures.

Further Outpatient Care

• The aim of further outpatient care is to closely monitor bone density to determine if ongoing bone loss occurs or if the process has reached a plateau. In these situations, measurements of biochemical markers of bone formation and resorption can help guide therapy choices and duration.

In/Out Patient Meds

• Currently, antiresorptives are the only consistently reliable medications.

Transfer

• Transferring a patient is not necessary unless pediatric subspecialty care is unavailable at the institution.

Deterrence/Prevention

• Prevention includes patient education and early recognition of the symptoms and signs of hypercalcemia and hypercalciuria.

Complications

• The main complication is fractures, including a nondisplaced fracture in the vertebral column.

Prognosis

• 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.
• 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 osteopenia 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.

Patient Education

• Use education as a means of prevention and treatment. Instruct children, adolescents, and their families that the roots of adult-onset osteoporosis begin in childhood; therefore, ensure adequate calcium intake and weight-bearing exercises to maximize genetically determined peak bone mass.
• As early as possible, inform patients of any age with osteopenia or osteoporosis why bone loss has occurred and how to keep bone loss under control. Also inform patients with osteopenia or osteoporosis of the consequences of bone loss.
• For excellent patient education resources, visit eMedicine's Bone Health Center. Also, see eMedicine's patient education articles Osteoporosis and Understanding Osteoporosis Medications.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Bone demineralization on DEXA does not always indicate osteoporosis. If a workup for osteopenia is not initiated, many potentially severe and disabling causes of osteopenia, such as Paget disease or bone loss secondary to an underlying disease, may be missed.

Special Concerns

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

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement. Mar 27-29 2000;17(1):1-45. [Medline].
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3. Rauch F, Plotkin H, DiMeglio L, et al. Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2007 Pediatric Official Positions. J Clin Densitom. Jan-Mar 2008;11(1):22-8. [Medline].
4. Baim S, Leonard MB, Bianchi ML, et al. Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Pediatric Position Development Conference. J Clin Densitom. Jan-Mar 2008;11(1):6-21. [Medline].
5. Bishop N, Braillon P, Burnham J, Cimaz R, Davies J, Fewtrell M, et al. Dual-energy X-ray aborptiometry assessment in children and adolescents with diseases that may affect the skeleton: the 2007 ISCD Pediatric Official Positions. J Clin Densitom. Jan-Mar 2008;11(1):29-42. [Medline].
6. Naylor KE, Eastell R, Shattuck KE. Bone turnover in preterm infants. Pediatr Res. Mar 1999;45(3):363-6. [Medline].
7. Johnston CC, Miller JZ, Slemenda CW. Calcium supplementation and increases in bone mineral density in children. N Engl J Med. Jul 9 1992;327(2):82-7. [Medline].
8. Kelly HW, Van Natta ML, Covar RA, et al. Effect of long-term corticosteroid use on bone mineral density in Children: A prospective longitudinal assessment in the childhood asthma management program (CAMP) study. Pediatrics. 2008;122:e53-e61. [Medline].
9. Zemel B, Bass S, Binkley T, et al. Peripheral quantitative computed tomography in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom. Jan-Mar 2008;11(1):59-74. [Medline].
10. Przkora R, Herndon DN, Sherrard DJ, Chinkes DL, Klein GL. Pamidronate preserves bone mass for at least 2 years following acute administration for pediatric burn injury. Bone. Aug 2007;41(2):297-302. [Medline].
11. Finkelstein JS, Hayes A, Hunzelman JL, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. Sep 25 2003;349(13):1216-26. [Medline]. [Full Text].
12. Hart DW, Herndon DN, Klein G, et al. Attenuation of posttraumatic muscle catabolism and osteopenia by long-term growth hormone therapy. Ann Surg. Jun 2001;233(6):827-34. [Medline]. [Full Text].
13. Klein GL, Chen TC, Holick MF, et al. Synthesis of vitamin D in skin after burns. Lancet. Jan 24 2004;363(9405):291-2. [Medline].
14. Klein GL, Herndon DN, Goodman WG. Histomorphometric and biochemical characterization of bone following acute severe burns in children. Bone. Nov 1995;17(5):455-60. [Medline].
15. Klein GL, Herndon DN, Langman CB. Long-term reduction in bone mass after severe burn injury in children. J Pediatr. Feb 1995;126(2):252-6. [Medline].
16. Klein GL, Nicolai M, Langman CB. Dysregulation of calcium homeostasis after severe burn injury in children: possible role of magnesium depletion. J Pediatr. Aug 1997;131(2):246-51. [Medline].
17. MacKelvie KJ, Petit MA, Khan KM, et al. Bone mass and structure are enhanced following a 2-year randomized controlled trial of exercise in prepubertal boys. Bone. Apr 2004;34(4):755-64. [Medline].
18. Baroncelli GI, Federico G, Vignolo M, et al. Cross-sectional reference data for phalangeal quantitative ultrasound from early childhood to young-adulthood according to gender, age, skeletal growth, and pubertal development. Bone. Feb 10 2006;[Medline].
19. Cooper C. Epidemiology of osteoporosis. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 5^th ed. 2003:307-13.
20. Eyre D. Biochemical markers of bone turnover. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 3^rd ed. 1996:114-9.
21. Fleming R, Patrick K. Osteoporosis prevention: pediatricians' knowledge, attitudes, and counseling practices. Prev Med. Apr 2002;34(4):411-21. [Medline].
22. Greenspan SL, Luckey M. Evaluation of post-menopausal osteoporosis. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 5^th ed. 2003:355-59.
23. Khosla S, Kleerekoper M. Biochemical markers of bone turnover. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 5^th ed. 2003:166-72.
24. Klein GL, Fitzpatrick LA, Langman CB, et al. The state of pediatric bone: summary of the ASBMR pediatric bone initiative. J Bone Miner Res. Dec 2005;20(12):2075-81. [Medline].
25. Leonard MB, Shore RM. Radiological evaluation of bone mineral in children. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 5^th ed. 2003:173-88.
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Article Last Updated: Aug 21, 2008