Diagnosis of osteoporosis in children

Laboratory diagnostics of osteoporosis in children

For the biochemical evaluation of bone mineral density, the following research methods are available:

• characteristic of phosphorus-calcium metabolism;
• the definition of biochemical markers of bone remodeling.

In the evaluation of biochemical indicators, routine methods of investigation are required-determination of the content of calcium (ionized fraction) and blood phosphorus, daily excretion of calcium and phosphorus in the urine, and urinary excretion of urine in relation to creatinine concentration in the same urine.

A large number of studies on osteoporosis in childhood prove that most of the routine biochemical indices of phosphorus-calcium metabolism are not changed or change only slightly and briefly even with severe osteoporosis with fracture.

Highly specific, sensitive methods for diagnosing osteoporosis are the determination of the level of parathyroid hormone, calcitonin, active metabolites of vitamin D in the blood. These methods have strict indications for their use and in practical medicine are not yet widely used. Parathyroid hormone is diagnosed with suspected hyperparathyroidism (primary or secondary) as the cause of osteoporosis; active metabolites of vitamin D - for the diagnosis of genetic osteomalacia vitamin D-dependent rickets.

To determine the state of bone remodeling in blood and urine, investigate highly sensitive biochemical markers of bone metabolism. In a pathological situation, they reflect the predominance of impaired bone formation or bone resorption. Bone markers include general alkaline phosphatase (mostly bone isoenzyme), human type I collagen propeptide, osteocalcin. The last indicator is considered the most informative. Markers of bone resorption - tartrate-resistant acidic blood phosphatase, hydroxyproline, collagen cross-links: pyridinoline and deoxypyridinoline in urine on an empty stomach; H-terminal telopeptide of urine. The most accurate and important markers of bone resorption are pyridinoline and deoxypyridinoline urine.

Biochemical markers of bone remodeling

Indicators of bone formation activity	Indicators of bone resorption activity
Activity of alkaline phosphatase (blood): total alkaline phosphatase, bone alkaline phosphatase	Oxiproline (urine)
	Collagen cross-sections: pyridinoline (urine); deoxypyridinoline (urine)
Osteocalcin (blood)	H-terminal telopeptide (urine)
	Tartrate-resistant
Propeptide of human type I collagen (blood)	Acid phosphatase (blood)

Determination of biochemical markers of bone metabolism is important not only for characterizing bone metabolism, but also for choosing a drug that increases bone mineral density, monitoring the effectiveness of therapy, optimal prevention of osteoporosis.

Instrumental diagnosis of osteoporosis in children

The most accessible method of instrumental diagnosis of osteoporosis is a visual assessment of the radiographs of bones (with glucocorticoid osteoporosis - bones of the spine).

Characteristic radiographic signs of a decrease in bone mineral density:

• increase of "transparency", change of trabecular pattern (disappearance of transverse trabeculae, coarse vertical trabecular striation);
• thinning and increased contrast of the end plates;
• decrease in the height of vertebral bodies, their deformation as wedge-shaped or "fish" (with severe forms of osteoporosis).

However, when analyzing radiographic images with the naked eye, it is practically impossible to quantify the mineral density of bone tissue. Demineralization of bone can be detected by radiography in the case of a decrease in density of not less than 30%. Radiographic studies are of great importance in assessing deformations and compression changes in the vertebrae.

Quantitative methods of assessing bone mass are more accurate (densitometry, from the English word density - "density"). Densitometry can detect bone loss in the early stages with an accuracy of 2-5%. There are ultrasonic, as well as X-ray and isotope methods (mono- and dual-energy densitometry, mono- and two-photon absorptiometry, quantitative CT).

X-ray methods of bone densitometry are based on the transfer of X-rays from an external source through the bone to the detector. A narrow beam of X-rays is sent to the measured area of the bone. The intensity of the beam transmitted through the bone is recorded by the detector system.

The main indicators that determine the bone mineral density:

• mineral content of bone, expressed in grams of mineral in the study area;
• bone mineral density, which is calculated on the bone diameter and expressed in g / cm ²;
• Z-test, expressed as percentage of the standard age and sex, and the standard deviation (standard deviation) of media non-theoretical standards (SD, or Sigma).

The first two criteria are absolute values of the bone density of the investigated area, the Z-criterion is the relative value. Children and adolescents use only this relative indicator of densitometry.

In adults, in addition to the Z-criterion, a T-test is calculated, which is expressed as a percentage of the peak of bone mass in individuals of the corresponding sex and race at the age of 40 (when the mineral composition of the bone is considered optimal), as well as in standard deviation values. This indicator is the main one for assessing the degree of bone demineralization by WHO criteria in adults.

Both criteria (Z- and T-) are expressed in numbers with the signs (+) or (-). The value of sigma from -1 to -2.5 is interpreted as osteopenia, which requires mandatory preventive treatment and monitoring, since there is a real risk of fractures.

With a decrease in bone density to values exceeding the standard deviation by more than 2.5, the risk of fractures increases - the condition is treated as osteoporosis. If there is a fracture (fracture) and a Z-test that exceeds the standard deviation by more than 2.5 (for example, -2.6, -3.1, etc.), severe osteoporosis is noted.

Diagnostic "instrumental" categories for reducing bone mineral density

T-score or T-test	Diagnosis	Risk of fractures
From +2.0 to -0.9	Normal BMD	Low
From-1.0 to-2.49	Osteopenia	Moderate
-2.5 or less without fractures	Osteoporosis	Tall
-2.5 or less with fractures	Severe osteoporosis	Very tall

All instruments calculate the Z and T criteria in terms of percentage and standard deviation values from the standard sigma parameters.

According to more recent BMD studies in children (2003), other densitometric criteria for estimating bone density were suggested. To establish "low bone density in accordance with age" or "below the expected parameters for the age group" should be at Z-criteria less than -2.0 SD (for example, -2.1, -2.6 SD, etc.).

Monophotonic and monoenergetic densitometers are convenient for screening studies, control of treatment, but they can determine the mineral bone density only in the peripheral parts of the skeleton (for example, in the radius bone). With the help of this method, it is impossible to estimate bone mass in the proximal part of the femur, vertebrae. The possibilities of two-photon and dual-energy bone densitometers are much wider.

Mono- and dual-energy (x-ray) densitometers have an advantage over photonic ones, since they do not require replacement of the source of isotopes, have a high resolving power, and have a lower radiation load.

Quantitative CT allows us to determine and measure the cortical and spongy layers of the bone, to present the true bone density. The accuracy of the method is high, but the radial load considerably exceeds that of the above methods.

Ultrasonic bone densitometry is based on measurement of the speed of ultrasonic wave propagation in the bone. Basically it is used as a screening method.

What kind of bone area should a pediatrician choose for the most informative densitometric study? Strict recommendations do not exist. The choice of the measurement site depends on a number of factors. The loss of bone mass occurs in all parts of the skeleton, but it is uneven. It is advisable to examine those bones that have a greater risk of fracture. More often X-ray densitometry is performed in the area of the proximal parts of the femurs and lumbar spine. This is due to the fact that bone loss is heterogeneous and there are differences between the two points of the definition, requiring two studies at the same time.

Since glucocorticosteroid therapy has a greater effect on the BMD of the spine than the femur or forearm, it is advisable to use the x-ray two-energy densitometry of the lumbar vertebrae for early diagnosis of osteoporosis and evaluation of the effectiveness of its treatment. Despite the use in clinical practice, the densitometry of the bones of the forearm is not considered a universally accepted method, the data of which are sufficient for the final diagnosis of osteoporosis.

Densitometry reveals the most reliable risk factor for fractures - reduced BMD. That is why its definition should be included in the list of instrumental studies with suspicion of osteoporosis, and it is preferable to use dual-energy densitometry of the spine bones.

According to international recommendations, the definition of BMD (spine, proximal femur) using bone densitometry should be performed by all adult patients who are scheduled for treatment with a glucose dose greater than 7.5 mg / day for more than 6 months. For patients who are not receiving osteoporosis therapy, densitometry should be repeated every 6 months, and for those receiving this treatment - at least once a year. With some changes, these recommendations can be transferred to the children's contingent.

With the accumulation of research material on osteoporosis, it became clear that there are situations where osteoporosis treatment results in an increase in BMD, but the incidence of fractures remains the same. Or conversely, BMD does not increase, despite specific therapy, while the incidence of fractures significantly decreases. It is assumed that this may be due to a change in the quality (microarchitectonics) of the bone, which can not be tested with modern techniques. That is why some authors call densitometry a "surrogate" method for determining the risk factor for fractures, despite the specificity and sensitivity of this study.

Nevertheless, bone densitometry remains the most valuable instrumental tool for diagnosing osteoporosis and preventing fractures. The most common classification of osteoporosis WHO, based on the evaluation of the densitometric T-test (for children - Z-test).

The software of bone densitometers includes normative indices of bone tissue density of different parts of the skeleton depending on sex and age, and races calculated on the basis of large population studies. In Russia, densitometric programs are designed to examine children from the age of 5. It is not possible to perform densitometry in a child under 5 years of age, and from the age of 5 it is permissible only on an apparatus that has this age program.

In a number of pediatric studies, special attention was paid to the analysis of BMD parameters with regard to bone age and puberty stage according to Tanner. With the subsequent recount of the results of the survey, taking into account the above-mentioned indicators, significant differences were obtained. This is due to the frequent inconsistency of the biological and passport age of a child who has osteoporosis.

There are no unified recommendations for densitometric studies in children.

Indications for X-ray dual-energy absorption densitometry in childhood can be:

• fracture (fracture), which occurred when falling from a height without acceleration;
• therapy with glucocorticosteroids with drugs more than 2 months;
• presence of risk factors for osteoporosis;
• Control of therapy of osteoporosis (not earlier than 1 year from the beginning of treatment).

Differential diagnosis of osteoporosis in children

Differential diagnosis of osteoporosis in children is not very difficult. In the presence of clinical symptoms (see above), instrumental methods of investigation (densitometry, in the extreme case - radiography of the spine bones) are necessary to confirm osteoporosis, otherwise the diagnosis can not be confirmed. With instrumental detection of a reduced BMD, the diagnosis of osteoporosis is obvious, it is only necessary to decide whether osteoporosis is a syndrome or a major disease.

In young children, osteoporosis must be differentiated with osteomalacia, which is characterized only by demineralization and softening of the bones without pronounced changes in protein synthesis in the matrix. The basis of osteomalacia is an increased amount of unmineralized osteoid tissue.

A classic example of osteomalacia is a lesion of the bone system with mineral deficiency rickets (during the height), much less often - with a disease from the group of genetic osteomalacies. In rickets, clinical manifestations include, depending on age, changes in the shape of the skull (craniotabes, flattening of the bones of the skull, presence of frontal and parietal tubercles), O-shaped curvature of the legs, muscle hypotension. Routine laboratory tests reveal a decrease in the level of phosphorus (less often calcium), an increase in the level of alkaline phosphatase of the blood. For osteoporosis, such biochemical changes are not characteristic.

With a significant decrease in bone mineral density of unknown origin, biopsy of bone tissue, histological and histomorphometric studies are of great importance in differential diagnosis. However, the use of this method is limited (especially in children in Russia) both because of invasiveness and traumatism, and because there are not enough pathomorphological laboratories with special equipment for histomorphometry.

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