Pediatric Osteoporosis Workup

The workup includes laboratory studies, dual-energy x-ray absorptiometry (DEXA), quantitative computed tomography (CT) scanning (still experimental), and bone histology.

High or normal serum calcium levels with normal or low phosphorus levels suggest secondary hyperparathyroidism. Low serum calcium levels with high or normal phosphorus levels suggest hypoparathyroidism. High serum parathyroid hormone (PTH) levels confirm hyperparathyroidism. Low PTH levels confirm 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 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 are indicated. 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. See the image below.

Serum osteocalcin or bone-specific alkaline phosphatase values may vary between assays. No expected results are reported. These tests help define whether the bone loss is resulting from a high- or low-turnover condition.

Pediatric reference ranges for osteocalcin are as follows:

• Younger than 12 years - 10-25 ng/mL
• Older than 13 years - 2-8 ng/mL

Pediatric reference ranges for bone-specific alkaline phosphatase are as follows:

• Preadolescents - 50-150 IU/L
• Adolescents - 10-50 IU/L

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. This method yields 2-dimensional imaging of a region of bone, such as the lumbar spine, hip, or radius.

The American Academy of Pediatrics (AAP) has issued a clinical report on bone densitometry in children and adolescents.^[20]

The lumbar spine and total body are preferred sites for DEXA testing in children. The cranium should be excluded if possible. A child with contractures may need to be tested at the lateral distal aspect of the femur, and one with metal hardware may need to be tested at other sites.

According to the AAP clinical report, DEXA is recommended for children with the following conditions. Testing should be performed on initial evaluation and before treatment begins.^[20]

• Primary bone disorders such as idiopathic juvenile osteoporosis and osteogenesis imperfecta
• Secondary conditions known to increase fracture risk (eg, chronic inflammatory diseases, immobilization for long periods, endocrine or hematologic diseases, cancer and associated treatments that adversely affect bone)
• A history of clinically significant fracture, where significance is defined as 1 long-bone leg fracture, ≥ 2 long-bone arm fractures, or vertebral fracture resulting from low trauma (Low trauma is defined as a fall from standing height or less.)

DEXA may also be indicated based on risk factors including: patient’s age at fracture, severity of underlying conditions, exposures to radiation or drugs detrimental to bone, and family history.

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 of DEXA is that it 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.^[21]

The AAP clinical guidelines for DEXA in children and adolescents include the following recommendations for interpretation of results and diagnosis:^[20]

• Pediatric osteoporosis may be diagnosed when there is a clinically significant history of fracture and low bone mass, defined as bone mineral content (BMC) or bone mineral density (BMD) more than 2 standard deviations (SD) below reference data.
• For children with chronic illness or delayed puberty, BMD should be adjusted based on height or should be compared with reference data specific for age, sex, and height.
• Healthy children with a history of fractures are likely to have lower BMC, BMD, and estimated volumetric BMD than similar children with no history of fractures.
• For children with chronic illness, there is little data on correlation between low bone mass and fracture risk.

The AAP clinical guidelines cite the following possible risks and costs for pediatric DEXA interpretation:^[20]

• Misdiagnosis is possible if DEXA results are not interpreted by skilled professionals at pediatric densitometry centers. In particular, some DEXA platforms may report a T score for pediatric patients, although the measure is inappropriate for use in children and adolescents. Use of a spurious T score may produce a high percentage of errors involving a misdiagnosis of osteoporosis.
• Misdiagnosis of osteoporosis may result in parental concern, use of expensive medications, and restrictions on physical activity when none of these are necessary.

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

Go to Imaging of Osteoporosis for complete information on this topic.

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.

Go to Imaging of Osteoporosis for complete information on this topic.

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. Go to Bone Markers in Osteoporosis for complete information on this topic.