Pediatric Osteoporosis Workup

Updated: May 25, 2016
  • Author: Manasa Mantravadi, MD, MS; Chief Editor: Jatinder Bhatia, MBBS, FAAP  more...
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Workup

Approach Considerations

The workup includes of children with suspected osteoporosis often clinically includes laboratory studies and dual-energy x-ray absorptiometry (DXA) assessments.  Rarely quantitative computed tomography (CT) scans may be employed (primarily for research purposes), and/or bone biopsy for bone histology.

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Lab Studies

A basic laboratory panel to assess calcium status and bone turnover is often warranted.  This includes a serum calcium (total or ionized), phosphorus, creatinine (to ascertain that renal function is normal), and parathyroid hormone concentrations (PTH).  Spot measurements of urine calcium and creatinine (ideally collected as second morning voids) can be helpful to assess the adequacy of calcium intake and the possibility of hypercalciuria.

Alkaline phosphatase (total or bone-specific) and osteocalcin can be measured to assess bone formation rates.  Serum and urine cross-links of type I collagen (deoxypyridinoline), N-telopeptide of type I collagen (NTx) or C-telopeptide of type I collagen (CTx), urine creatinine can assess bone resorption rates, although normative data for these measures may be limited. These tests help define whether the bone loss is resulting from a high- or low-turnover condition.

Magnesium levels provide an index of total body magnesium status. Low serum magnesium can inhibit PTH secretion and function.

Children with osteoporosis of unclear etiology should also be screened for celiac disease and inflammatory bowel disease.

Sometimes the labs can be suggestive of a diagnosis.   High or normal serum calcium levels with normal or low phosphorus levels and high PTH concentrations suggest secondary hyperparathyroidism. Low serum calcium levels with high or normal phosphorus levels suggest hypoparathyroidism (when PTH is low) and pseudohypoparathyroidism (if PTH is high or normal).

Pediatric reference ranges for many of these measures based on age and gender can be found here: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8340

Prediction of bone loss with biochemical bone mark Prediction of bone loss with biochemical bone markers. Adapted from Ross PD, Knowlton W. Rapid bone loss is associated with increased levels of biochemical markers. (DPD stands for deoxypyridinoline.) J Bone Miner Res 1998 Feb; 13(2): 297-302.

 

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Dual Energy X-Ray Absorptiometry

The amount of calcium in bone – both absolute amounts and the amount for bone size - can be quantified in several ways. In pediatrics, bone densitometry based on dual energy x-ray absorptiometry (DXA) is the most widely used method. This method yields 2-dimensional imaging (quantified as grams per centimeter squared) of the total body (usually reported total body less head in children) or of regions of bone, such as the lumbar spine, hip, or radius.

In 2013, the ICSD updated previous position on DXA assessment in children and adolescents as follows [3] :

  • DXA measurement is part of a comprehensive skeletal health assessment in patients with increased risk of fracture. It is the preferred method for assessing BMC and areal BMD. In patients with primary bone disease, or at risk for a secondary bone disease, a DXA should be performed when the patient may benefit from interventions to decrease their elevated risk of a clinically significant fracture, and the DXA results will influence that management. DXA should not be performed if safe and appropriate positioning of the child cannot be assured.
  • In children and adolescents, posterior-anterior (PA) spine and total body less head (TBLH), are the preferred skeletal sites for performing BMC and areal BMD measurements in most pediatric subjects. Other sites may be useful depending on the clinical need. Soft tissue measures in conjunction with whole body scans may be helpful in evaluating patients with chronic conditions associated with malnutrition or with muscle and skeletal deficits. The hip is not a preferred measurement site in growing children due to variability in skeletal development. If a follow-up DXA scan is indicated, the minimum interval between scans is 6-12 months.
  • In children with short stature or growth delay, spine and TBLH BMC and areal BMD results should be adjusted. For the spine, adjust using either BMAD or the height Z-score.  For TBLH, adjust using the height Z-score.
  • An appropriate reference data set must include a sample of healthy representatives of the general population sufficiently large to capture variability in bone measures that takes into consideration gender, age, and race/ethnicity. When upgrading densitometer instrumentation or software, it is essential to use reference data valid for the hardware and software technological update.
  • Serial DXA reports should include the same information as for baseline testing. Additionally, indications for follow-up scan; technical comparability of studies; changes in height and weight; and change in BMC and areal BMD Z-scores should be reported.

The American Academy of Pediatrics (AAP) has issued a clinical report on bone densitometry in children and adolescents. [32] According to the report, DXA is recommended for children with the following conditions.

  • 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

DXA 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. Testing should be performed on initial evaluation and before treatment begins. [32]

DXA provides an assessment bone calcium content, which is measured in grams; the bone area is measured in cm2; and the 2-dimensional BMD is measured in g/cm2. Pediatric reference ranges are taken from large studies using DXA and are incorporated into the software that provides the printout; thus, actual individual BMD and its comparison to age-related normal values (Zscore) is printed out as part of the report.

The main drawback of DXA is that it is an areal rather than true volumetric density, and therefore tend to over-estimate BMD in larger patients and under-estimate it in smaller patients. Additionally it does not provide data on bone strength.  Criteria for pediatric DXA reporting are now available on the Web site of the International Society for Clinical Densitometry.

Bone demineralization on DXA does not always indicate osteoporosis. If a workup for reduced BMD 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.

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Quantitative CT Scanning

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.

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Bone Histology

Because of the availability of blood and urine biochemical markers of bone turnover, the use of bone histology obtained by iliac crest bone biopsy is no longer routine. When done, histology for bone biopsies is generally carried out using quantitative histomorphometry.

For patients older than 10 years, tetracycline or one of its analogs is administered 14 days before biopsy and then 2 days prior to biopsy. Using one of several specialized orthopedic needles, a biopsy sample is obtained 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.

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