Treatment of osteoporosis in children

Indications for consultation with other specialists

Indications for consultation with other specialists arise when the cause of osteoporosis is unclear, especially in its severe form. In these cases, consultations with an endocrinologist, geneticist, orthopedist, oncologist are possible.

Indications for hospitalization

Children with osteoporosis require hospitalization in the presence of fractures, secondary osteoporosis for treatment of the underlying disease, and also with significantly reduced BMD without fractures, if the cause of osteoporosis is not determined. In this case, hospitalization is necessary for diagnostic purposes.

Treatment goals for osteoporosis in children

• elimination of complaints (pain syndrome);
• prevention of bone fractures;
• slowing or stopping bone loss;
• normalization of bone metabolism indicators;
• ensuring the normal growth of the child.

Correction of osteoporosis in childhood is complicated by the fact that, unlike an adult patient with formed bone tissue, a child still needs to accumulate calcium in the bones to create peak bone mass in the future.

Non-drug treatment of osteoporosis in children

Symptomatic treatment involves a diet balanced in calcium, phosphorus, protein, fats, and microelements.

The following are used as symptomatic analgesics for acute pain:

• immobilization (short-term, usually for several days, no more than 2 weeks);
• extremely careful spinal traction under the guidance of an experienced physical therapy specialist;
• the use of a semi-rigid, close-fitting corset that covers the thoracic and lumbar spine;
• muscle relaxation using drugs that reduce muscle tone, but not more than 3 days;
• NSAIDs.

In chronic pain, which is usually less intense, a gentle motor regimen is of particular importance, excluding sudden movements, jolts, and lifting weights. Dosed physical activity in the form of special exercises to strengthen the back muscles is necessary, which not only increases the stability of the spine, but also improves its blood supply, preventing further reduction in bone mass. Light massage, including underwater, is recommended.

Drug treatment of osteoporosis in children

Symptomatic treatments for osteoporosis, in addition to analgesics, include calcium salt preparations.

Calcium preparations are classified as a group of medications for additional, but not primary, treatment of osteoporosis.

Pathogenetic treatment includes the administration of drugs aimed at various components of the bone remodeling process:

• suppression of increased bone resorption;
• stimulation of bone formation;
• normalization of both of these processes;
• normalization of mineral homeostasis (elimination of possible vitamin D deficiency).

Along with the presented classification of drugs by their predominant mechanism of action, there is a division of drugs by their proven ability to reliably prevent new bone fractures.

The first line drugs are:

• latest generation bisphosphonates (salts of alendronate, risedronic, pamidronate acids);
• calcitonin;
• estrogens, selective estrogen receptor modulators;
• active metabolites of vitamin D.

Pathogenetic drugs for the treatment of osteoporosis

Classes of drugs	Preparations
Inhibiting bone resorption	Estrogens, selective estrogen receptor modulators Calcitonins Bisphosphonates Calcium
Stimulating bone formation	Fluorides Parathyroid hormone Growth hormone Anabolic steroid Androgens
Acting on both links of bone tissue remodeling	Active metabolites of vitamin D Ossein hydroxyapatite complex Ipriflavone Substances containing phosphates, strontium, silicon, aluminum Thiazides

For other antiosteoporotic agents, a reliable reduction in the incidence of new bone fractures has not been proven.

In glucocorticoid osteoporosis, various stages of bone tissue metabolism are disrupted, but in children, resorption processes are intensified to a greater extent. In this case, drugs of the first and third groups are successfully used.

The latest generation of bisphosphonates (salts of alendronate, risedronic acids) are the most powerful in their effect on bone tissue; they not only increase BMD, but also reduce the risk of fractures, including vertebral fractures. Bisphosphonates are the drugs of choice, including in children abroad. They are successfully used to treat not only postmenopausal, but also glucocorticoid osteoporosis. However, in Russia there is no permission to use these bisphosphonates in childhood.

The drug of the previous generation of bisphosphonates, etidronic acid, is available and inexpensive. Data on its positive effect on bone are ambiguous. Some authors believe that the effectiveness of etidronic acid in glucocorticoid osteoporosis is very low (a thousand times less than that of alendronic acid). Other researchers have shown that etidronate, according to their data, reliably reduces bone resorption only in the fourth year of osteoporosis treatment.

It is also known that etidronic acid, when used continuously, has a negative effect on osteoblasts, making the bone not only dense but also fragile (the "frozen bone" effect). To avoid this negative effect, it is recommended to prescribe it according to an intermittent regimen (there is no single protocol), for example, take it for 2 weeks, do not take it for 11 weeks, repeating the cycles. This drug is traditionally used, for example, in Canada and a number of other countries, but is not used in the USA. Russian authors in a few studies have shown the effectiveness of an intermittent etidronate regimen in the treatment of osteoporosis in patients with rheumatic diseases.

Calcitonin (salmon calcitonin is most often used) is one of the drugs with the fastest antiresorptive and analgesic effect. It has a strong effect on bone tissue. The drug has 2 dosage forms - injection (in a bottle) and nasal spray. The effect of calcitonin, including analgesic, is more pronounced when used parenterally than when instilled into the nasal passage. Injectable calcitonin is more effective in osteoporosis of the spine than in osteoporosis of other bones, and intranasal calcitonin, according to some data, is less effective in terms of its effect on the BMD of the spine. However, the spray is more convenient to use, especially in children.

Despite the long-term use of calcitonin in the form of a nasal spray, there are no uniform recommendations on the regimen of its use. Some authors cite data on its positive effect when prescribed daily for one year and even 5 years. Others insist on various intermittent regimens, for example, 1 month - "on" (prescribe), 1 month - "off" (do not prescribe) or 2 months - "on", 2 months - "off". They recommend repeating the cycle at least 3 times.

There is some information in the literature about the promising possibility of using oral calcitonin in adult patients, but this dosage form is currently undergoing clinical trials.

For many years, vitamin D supplements have been traditionally used to treat osteoporosis.

They are divided into 3 groups:

• Native vitamins - cholecalciferol (vigantol, vitamin D4 ₎, ergocalciferol (vitamin D2 ₎.
• Structural analogues of vitamin D ₂ (liver metabolites) - dihydrotachysterol (tachystin); 25-OH-D ₄ (calcidiol) - are used primarily in the treatment of hypocalcemia.
• Active metabolites of vitamin D are alpha-OH-D^ (alphacalcidol), 1-alpha-25-OH ₂ -0 ₃ - calcitriol (rocaltrol).

The liver metabolite calcidiol has no advantages over native forms of vitamin D. It is believed that replenishment of vitamin D deficiency with native forms is not a treatment, but a dietary recommendation.

Foreign authors have shown that native vitamin D and liver metabolites, even in high doses, are not able to increase bone mineral density and prevent bone loss, including in glucocorticoid osteoporosis.

Calcitriol has a good speed of action and a narrow therapeutic range, so when using it there is a high risk of developing hypercalcemia and hypercalciuria. The safest in this regard are alphacalcidol preparations.

Alfacalcidol has a multifaceted effect on bone tissue, acts quickly, is easily dosed, is excreted from the body fairly quickly, and does not require hydroxylation in the kidneys to achieve its metabolic effect. The peculiarity of this form is that for conversion to the final product (alpha-25-OH-D., (calcitriol) only hydroxylation in the liver at position 25 is necessary. The rate of such conversion is regulated by the physiological needs of the body, which to a certain extent prevents the risk of hypercalcemia. Alfacalcidol can also be effective in kidney disease, since the impaired stage of renal hydroxylation is not involved.

Thus, only active metabolites of vitamin D actually increase BMD and reduce the risk of bone fractures.

Alfacalcidol is the only antiosteoporotic drug that can be used without calcium preparations. However, adding calcium salts to osteoporosis therapy increases the effectiveness of the basic drug (bone loss slows down to a greater extent, the incidence of bone fractures decreases). Alfacalcidol in combination with calcium carbonate is successfully used to treat glucocorticoid osteoporosis. It acts as a "freight elevator", delivering calcium to the "place of demand".

A kind of "breakthrough" in the treatment of osteoporosis in the 21st century was the appearance of a medicinal form of parathyroid hormone. It has a dual effect on bone - it reduces resorption and has an anabolic effect (stimulates osteogenesis). In terms of effectiveness, it surpasses all known anti-osteoporotic drugs.

But the injection method of administration for 1-1.5 years daily limits its use. In addition, data has appeared that osteosarcomas may occur in rats with prolonged use of parathyroid hormone. The drug is very promising, but it needs further study, especially in children.

Most studies on the treatment of osteoporosis are based on the long-term use of 1 or 2 osteotropic drugs affecting one of the many mechanisms of disease development. Given the heterogeneity and multifactorial nature of the pathogenesis of osteoporosis, the physiology of bone tissue, in which the processes of bone resorption and bone formation are inextricably linked throughout life, it seems appropriate to combine drugs that affect different aspects of the bone remodeling process. Schemes are used for both the simultaneous long-term use of 2 or 3 drugs affecting bone resorption or bone formation, and their sequential administration. Continuous or intermittent treatment regimens can be used. Active metabolites of vitamin D are most often combined with calcitonin and bisphosphonates, including in children. For example, hypocalcemia and a secondary increase in parathyroid hormone levels are possible during treatment with calcitonin. Adding alphacalcidol to the treatment helps prevent these undesirable effects and potentiate the positive effect of calcitonin.

Treatment of osteoporosis in children is a difficult and not fully resolved problem.

For the treatment of osteoporosis, including glucocorticoid osteoporosis, in children, bisphosphonates, calcitonin, and active metabolites of vitamin D in combination with calcium preparations are used.

The use of hormonal drugs (estrogens, selective estrogen receptor modulators) in childhood is unacceptable due to unwanted interference in the hormonal background of the child or adolescent.

Domestic researchers note the good therapeutic effect of calcitonin in osteoporosis and alphacalcidol in osteopenia in children.

Alphacalcidol preparations are safe, well tolerated by children, and can be used for a long time.

Combination therapy for osteoporosis in children (as well as in adults) is used quite successfully; calcitonin spray is most often combined with alphacalcidol.

Thus, despite the large number of drugs for the treatment of osteoporosis on the pharmaceutical market, there are not many first-line drugs available to a practicing pediatrician. Among them are bisphosphonates (only etidronic acid salts in Russia), calcitonin, active metabolites of vitamin D in combination with calcium preparations. In the available literature, no clear unified recommendations for the appointment of these drugs in children have been found, which requires further research in this area.

Surgical treatment of osteoporosis in children

Surgical treatment of osteoporosis in children is not used.

Prognosis for osteoporosis

The prognosis for life with various types of osteoporosis in childhood is generally favorable.

The prognosis for potential fractures depends on the degree of reduction in BMD, the adequacy of anti-osteoporotic therapy, the child’s compliance with dietary recommendations, and adherence to a physical regimen.

In secondary osteoporosis, if the underlying cause is eliminated or minimized, complete normalization of BMD is possible.

Osteoporosis in children is often a complication of severe somatic diseases, a consequence of drug therapy. Timely prevention, symptomatic treatment in combination with pathogenetic therapy have a beneficial effect on bone remodeling processes, calcium homeostasis, and significantly improve the prognosis.