Alpha D3-Teva and Aquadetrim: comparison, differences, which is better?

Characteristics of the drug Alpha D3-Teva

Belongs to the category of drugs that regulate calcium and phosphorus metabolism . Increases their absorption by the intestines, helps restore a positive calcium balance, and reduces the concentration of parathyroid hormone. In addition, reabsorption in the kidneys increases. By influencing bone remodeling, the active component not only increases the mineral density of bone tissue, but also makes it more elastic. This reduces the risk of fractures. In addition, it regenerates muscle fibers, thereby increasing lost tone.

The following indications for use are distinguished:

• Osteoporosis of various etiologies.
• Violation of bone tissue trophism caused by insufficient absorption of nutrients in kidney disease.
• Violation of phosphorus-calcium metabolism, accompanied by delayed mental and physical development.
• Rickets, a systemic decrease in bone strength.
• Kidney disease with concomitant protein malabsorption.
• A disease in which the kidney tubules are unable to remove acid from the blood through urine.

Contraindications for use:

• Increased concentrations of calcium, phosphates, vitamin D in blood plasma.
• Pregnancy, lactation.
• Children under three years of age.
• Individual intolerance to components.

Caution should be exercised in case of atherosclerosis, diseases of the cardiovascular system, renal failure, and urolithiasis.

Among the adverse reactions, possible disorders of the digestive system in the form of vomiting, heartburn, nausea, and problems with stool. Nervous system disorders with concomitant weakness, increased fatigue, headache, dizziness, and drowsiness are also possible. In addition, discomfort in the muscles, bones, and joints is possible. If these symptoms occur or worsen, you should inform your doctor.

ALPHA D3

Compound:

Active ingredient: alfacalcidol;

1 capsule contains alfacalcidol 0.25 mcg or 0.5 mcg, or 1 mcg;

Excipients: citric acid, propyl galate, vitamin E (DL-alpha-tocopherol), ethanol, peanut butter, gelatin, glycerin 85%, sorbitol (E 420), sorbitan anhydrides, mannitol (E 421), higher polyols, purified water;

Iron oxide red (E172) for a dose of 0.25 mcg

Titanium dioxide (E 171), iron oxide red (E172) for a dose of 0.5 mcg

Titanium dioxide (E 171), iron oxide yellow (E172) for a dose of 1 mcg.

Dosage form. Soft capsules.

Pharmacological group. Vitamins. Vitamin D preparations and its analogues. Alfacalcidol. ATS code A11C C03.

Clinical characteristics.

Indications.

Postmenopausal osteoporosis.

Osteoporosis associated with glucocorticoid treatment.

Softening of bones in old age (osteomalacia) as a result of insufficient absorption, for example in the case of malabsorption and post-gastrectomy syndrome.

To significantly reduce the incidence of falls in older people.

For hypoparathyroidism or hypophosphatemic (vitamin D-resistant) rickets/osteomalacia, additional therapy with Alpha D3-Teva may be indicated if plasma calcium levels are less than 2.2 mmol/l.

Diseases accompanied by impaired 1-alpha-hydroxylation in the kidneys, which in turn cause disturbances in the metabolism of vitamin D (for example, renal osteodystrophy with decreased calcium absorption and plasma calcium levels less than 2.2 mmol/l (less than 8.8 mg/100 ml ), which can occur as a consequence of impaired renal function without or with dialysis, as well as at the beginning of the condition after kidney transplantation).

Contraindications.

• hypersensitivity to alfacalcidol, peanuts, soy or any other components of the drug;
• hypersensitivity to vitamin D and manifestations of vitamin D intoxication;
• plasma calcium level is higher than 2.6 mmol/l, the product of plasma calcium × phosphate concentrations is greater than 3.7 (mmol/l)2;
• alkalosis with a venous blood pH level of more than 7.44 (lactate-alkalosis syndrome, Burnett syndrome);
• metastatic calcification;
• Hypersensitivity to vitamin D analogues.

Method of administration and dose.

The drug is taken orally. The capsule should be swallowed whole with plenty of water. The dose and duration of therapy is determined by the doctor individually and depends on the nature of the disease and the effectiveness of therapy. In some cases, the drug should be used throughout life.

Unless otherwise prescribed by a physician, the starting dose is 1 mcg of alfacalcidol (4 capsules of 0.25 mcg or 2 capsules of 0.5 mcg or 1 capsule of 1 mcg) daily.

For patients with more severe bone disease, give high doses of 1-3 mcg alfacalcidol (4-12 capsules of 0.25 mcg, 2-6 capsules of 0.5 mcg, 1-3 capsules of 1 mcg) daily.

Children over 6 years old weighing over 20 kg who are able to swallow a capsule - 1 mcg/day (except in cases of renal osteodystrophy).

For patients with hypoparathyroidism, the dose should be reduced once normal blood calcium levels are achieved (2.2-2.6 mmol/L 8.8-10.4 mg/100 ml) or when the product of plasma calcium x phosphate concentrations is 3 .5-3.7 (mmol/l)2.

Alpha D3-Teva 0.25 mcg

If the daily dose is 0.5 mcg of alfacalcidol, take 1 capsule morning and evening daily. If the daily dose is 1 mcg of alfacalcidol, take 2 capsules morning and evening daily.

Alpha D3-Teva 0.5 mcg

If the daily dose is 0.5 mcg, take 1 capsule in the evening daily. If the daily dose is 1-3 mcg of alfacalcidol (2-6 capsules of 0.5 mcg), it should be divided in half and taken one half in the morning and the other in the evening.

Alpha D3-Teva 1 mcg

If the daily dose is 1 mcg of alfacalcidol, take 1 capsule in the evening daily. If the daily dose is 3 mcg of alfacalcidol, take 1 capsule in the morning and 2 capsules of Alpha D3-Teva in the evening.

Adverse reactions.

If the dose of alfacalcidol is not adjusted, there may be an increase in calcium levels in the blood, which disappears when the dose is reduced or the drug is temporarily stopped. Signs of a possible increase in the level of calcium in the blood are fatigue, gastrointestinal disorders (vomiting, heartburn, abdominal pain, nausea, discomfort in the epigastric region, constipation, diarrhea), anorexia, dry mouth, moderate pain in muscles, bones, joints , weight loss, polyuria, increased sweating, headache, thirst, vertigo, increased levels of calcium and phosphate in the urine, nephrocalcinosis, hypersensitivity reactions, including itching, rash, urticaria.

During therapy with alfacalcidol, adverse reactions may occur, which are determined by frequency: very often (≥1/10), often (≥1/100 to <1/10), infrequently (≥1/1000 to <1/100), rarely (≥1/10000 to <1/1000), very rare (<1/10000), unknown (cannot be determined from available data).

Common: hypercalcemia*, hypercalciuria.

Rarely (> 1/10000, <1/1000): hyperphosphatemia, to prevent which the patient can be prescribed phosphate absorption inhibitors (such as aluminum compounds) tachycardia, weakness, headache, dizziness, drowsiness.

Very rare (<1/10,000), including isolated cases: heterotopic calcification (cornea and blood vessels), which disappears after discontinuation of the drug, slight increase in high-density lipoproteins in the blood plasma. In patients with severe renal impairment, hyperphosphatemia may develop; allergic skin reactions (itching) and anaphylactic shock, the latter can be caused by peanut oil, which is part of the drug.

Unknown: hypersensitivity.

* Hypercalcemia is also associated with reactions such as hyperkaliuria, ectopic calcification, kidney and heart damage.

Overdose.

With a single overdose (25-30 mcg) of alfacalcidol, no harm to health is observed. The following cases of alfacalcidol overdose can cause hypercalcemia.

Symptoms of overdose: anorexia, weakness, lethargy, dizziness, headache, nausea, dry mouth, constipation, diarrhea, heartburn, vomiting, abdominal pain, bone pain, increased sweating, drowsiness, itching, tachycardia. Polyuria, polydipsia, nocturia, thirst, weight loss, proteinuria may occur if renal function is impaired.

Treatment of overdose: stop taking the drug. Depending on the severity of hypercalcemia, calcium-free or low-calcium diets, fluid intake, dialysis, loop diuretics, glucocorticosteroids, and calcitonin may be used.

In case of acute overdose, a positive effect can be observed with gastric lavage and/or administration of mineral oil (which helps to reduce absorption and increase excretion of the drug in feces).

There are no specific antidotes for alfacalcidol.

Use during pregnancy or breastfeeding.

Although there has been no evidence of harmful effects on the fetus or infant, Alpha D3-Teva should not be used during pregnancy or lactation.

Due to the possible risk of developing persistent hypercalcemia, which can cause physical and mental retardation, supravalvular aortic stenosis, retinopathy in infants, overdose of vitamin D analogues during pregnancy should be avoided.

The use of Alpha D3-Teva during breastfeeding may increase the level of calcitriol in breast milk. Considering this, the drug should not be used during breastfeeding.

Children.

Use in children over 6 years of age weighing 20 kg or more who can swallow the capsule.

Features of application.

Alfacalcidol should not be prescribed to patients with hypercalcemia.

Prescribe the drug with caution:

• patients prone to hypercalcemia, especially patients with urolithiasis;
• patients who are simultaneously using cardiac glycosides or digitalis preparations since hypercalcemia can lead to arrhythmia in such patients.

During the period of use of the drug, it is necessary to regularly (at least once every 3 months) monitor the level of calcium in the blood plasma and urine, monitor the development of the therapeutic effect and, if necessary, adjust the dose of alfacalcidol to avoid the development of hypercalcemia and hypercalciuria. If there are biochemical signs of normalization of bone structure (normalization of alkaline phosphatase in the blood plasma), it is necessary to reduce the dose of Alpha D3-Teva, which avoids the development of hypercalcemia. Hypercalcemia or hypercalciuria can be eliminated by discontinuing the drug and reducing calcium intake until its plasma concentration normalizes. Typically this period is 1 week. Therapy can then be continued, starting with half the last dose that was used.

Plasma phosphate levels should be monitored during alfacalcidol therapy to reduce the risk of ectopic calcification.

Supplementing the diet with vitamin D may be harmful for individuals who already obtain adequate amounts from food and sunlight, since the difference between therapeutic and toxic concentrations is very small.

Because alfacalcidol is the most potent form of vitamin D, it is expected to have the greatest risk of toxicity; however, its effects are rapidly reversible if supplementation is discontinued.

Alfacalcidol increases the absorption of calcium and phosphate in the intestine, so their plasma concentrations should be monitored in patients with renal failure.

Clinical manifestations of hypo- or hypercalcemia in elderly patients should be monitored, especially in the presence of concomitant renal or cardiac pathology.

Early symptoms of hypercalcemia include:

• polyuria;
• polydipsia;
• weakness, headache, nausea, constipation;
• dry mouth;
• muscle and bone pain;
• metallic taste in the mouth.

The medicine contains soybean oil. If you have an allergy to peanuts or soy, do not take this medication.

The ability to influence the reaction rate when driving a vehicle or working with other mechanisms.

No effect on the ability to drive vehicles or operate complex machinery has been identified, but the possibility of adverse reactions such as drowsiness and dizziness should be taken into account.

Interaction with other drugs and other types of interactions.

In the treatment of osteoporosis, Alpha D3-Teva can be prescribed in combination with antiresorptive drugs of different groups and estrogens. The effect of alfacalcidol is enhanced by the simultaneous use of estrogens in premenopausal and postmenopausal women.

Vitamin D and its derivatives should not be used concomitantly with Alpha D3-Teva due to the possibility of additive interactions and an increased risk of hypercalcemia.

With the simultaneous use of Alpha D3-Teva with digitalis preparations, the risk of developing arrhythmia increases.

When used concomitantly with barbiturates, anticonvulsants (for example, carbamazepine, phenobarbital, phenytoin and primidone) and other drugs that activate microsomal oxidation enzymes in the liver, it is necessary to take a higher dose of Alpha D3-Teva.

GCS may counteract the effect of vitamin D.

The absorption of alfacalcidol is reduced when used with cholestyramine, colestipol, sucralfate, and antacids with a high aluminum content.

Alpha D3-Teva and aluminum-based antacids cannot be used simultaneously; the interval between doses should be 2 hours.

When used simultaneously with Alpha D3-Teva, magnesium-based antacids or laxative dialysis increase the risk of developing hypermagnesemia.

With the simultaneous use of calcium supplements and thiazide diuretics, the risk of developing hypercalcemia increases.

The effect of alfacalcidol is enhanced by the simultaneous use of estrogens in premenopausal and postmenopausal women.

Rifampicin and isoniazid may reduce the effectiveness of vitamin D.

Pharmacological properties.

Pharmacodynamics.

Alpha D3-Teva is a highly effective active metabolite of vitamin D3, which regulates the metabolism of calcium and phosphorus. Alphacalcidol (1-alpha-hydrocholecalciferol) is very quickly converted to calcitriol (1,25-dihydrocholecalciferol, D-hormone) in the liver. Calcitriol belongs to the main metabolites of cholecalciferol (vitamin D3) in maintaining calcium and phosphorus homeostasis. Alpha D3-Teva is transformed into 1,25-dihydrocholecalciferol (D-hormone) and thus increases its level in the blood. This leads to an increase in the absorption of calcium and phosphorus in the intestines, an increase in their reabsorption in the kidneys, increased bone mineralization, and a decrease in the level of parathyroid hormone in the blood. In patients with impaired 1-alpha-hydroxylation in the kidneys, which occurs with age, taking Alpha D3-Teva promotes sufficient formation of calcitriol, which neutralizes the deficiency of D-hormone. Alpha D3-Teva restores a positive calcium balance, resulting in a decrease in the intensity of bone resorption, which helps reduce the incidence of fractures. Increases bone mineral density. With a course of use of the drug, there is a weakening of bone and muscle pain associated with impaired phosphorus-calcium metabolism, improved coordination of movements and maintenance of balance, increased muscle strength, as a result of which the frequency of falls decreases.

Pharmacokinetics.

After oral administration, Alpha D3-Teva is rapidly absorbed from the gastrointestinal tract. The time to reach the maximum concentration of the drug in the blood plasma ranges from 8 to 18 hours. The onset of action is after 6 hours, the duration of action is up to 48 hours.

In the liver, alfacalcidol is quickly transformed into calcitriol (1,25-dihydrocholecalciferol, D-hormone). A smaller part of the drug is transformed in bone tissue. Unlike natural vitamin D3, the biotransformation of the drug does not occur in the kidneys, which allows its use in patients with renal pathology.

Pharmaceutical characteristics.

Basic physical and chemical properties:

0.25 mcg Capsules: Oval, opaque, red-brown elastic soft gelatin capsules stamped in black ink "0.25" on one side, containing a pale yellow oil solution.

0.5 mcg Capsules: Oval, opaque, pale pink elastic soft gelatin capsules stamped with "0.5" in black ink on one side, containing a pale yellow oil solution.

1.0 mcg Capsules: Oval, opaque, cream to ivory elastic soft gelatin capsules stamped in black ink "1.0" on one side, containing a pale yellow oil solution.

Best before date. 3 years.

Storage conditions. Store in a tightly closed container at a temperature not exceeding 25 °C out of the reach of children.

Package. 30 or 60 capsules per container; 1 container per box.

Vacation category. On prescription.

Manufacturer. Teva Pharmaceutical Industries Ltd.

Location. St. Eli Hurwitz 18 Ind. zone, Kfar Saba /

St. Kiryat Hamad 20 Har Hozvim Prom. zone, Jerusalem, Israel.

Characteristics of the drug Aquadetrim

It is a regulator of calcium and phosphorus metabolism and promotes proper mineralization of bones. The active substance is a natural form of vitamin D, formed in humans under the influence of sun rays. Takes part in the absorption of calcium and phosphates, transports mineral salts, and also regulates their excretion by the kidneys. Thanks to this, the tone of the skeletal muscles increases and the process of blood clotting is regulated. In addition, it regulates carbohydrate and fat metabolism.

Used for the prevention and treatment of the following conditions:

1. Vitamin D deficiency.
2. Rickets, rickets-like conditions.
3. Decreased production of parathyroid hormone.
4. Insufficient mineralization of bone tissue.
5. Bone diseases due to metabolic disorders.
6. Osteoporosis (complex therapy).

Contraindications for use:

• Excess vitamin D.
• Increased calcium concentration.
• Calcium stones.
• Formation of granulomas in tissues.
• Pathologies of the liver, kidneys.
• Active tuberculosis.
• Individual intolerance to incoming substances.

Caution should be exercised when treating with diuretics, as well as in pregnant and lactating women, and patients with fractures.

Possible side effects include:

• Decreased appetite, weight loss.
• Feeling of nausea, vomiting.
• Muscle and joint pain.
• Constipation.
• Dry mouth.
• Depressive states.
• Sleep problems.
• Increase in body temperature.
• The appearance of protein in the urine.
• Excess calcium in the blood.

If an overdose occurs, the drug must be discontinued. Drinking large amounts of clean water is prescribed. Hospitalization may also be required.

Alpha D3 capsules 0.5 mcg 30 pcs. in St. Petersburg

When using the drug Alpha D3-Teva® in children and in patients with chronic renal failure, it is necessary to regularly monitor the calcium and phosphate levels (at the beginning of treatment - once a week, when Cmax is reached in the blood plasma and during the entire treatment period - every 3 -5 weeks), as well as alkaline phosphatase activity (for chronic renal failure - weekly monitoring) in the blood plasma. In chronic renal failure, preliminary correction of hyperphosphatemia is required.

When normal ALP activity in the blood plasma is achieved, the dose of Alpha D3-Teva® must be reduced, which will avoid the development of hypercalcemia.

At the beginning of treatment with Alpha D3-Teva®, it is recommended to measure calcium levels, especially in conditions without significant bone damage, for example, with hypoparathyroidism and in cases where plasma calcium levels are already elevated, and also at later stages of treatment - if there are signs of recovery bone tissue structure.

The risk of developing hypercalcemia is determined by factors such as the degree of bone demineralization, renal function, and drug dose.

Hypercalcemia or hypercalciuria is corrected by reducing the dose of Alpha D3-Teva® and reducing calcium intake until its content in the blood plasma is normalized. Typically this period is 1 week. After normalization, therapy is continued using half of the last dose used.

If hypercalcemia develops or a persistent increase in the content of calcium phosphate compounds beyond the clinical norm, the drug should be immediately discontinued, at least until these indicators return to normal (usually within a week), then use of the drug can be resumed at a dose , which is half the previous one.

Patients with severe bone damage (as opposed to patients with renal failure) can tolerate higher doses of the drug without signs of hypercalcemia. The absence of a rapid increase in calcium levels in the blood plasma in patients with osteomalacia does not always mean that the dose of the drug should be increased, because calcium can penetrate into demineralized bone due to its increased absorption in the intestine.

The development of long-term hypercalcemia should be prevented, especially in chronic renal failure, focusing on indicators such as calcium content in blood serum and urine, alkaline phosphatase activity, parathyroid hormone concentration, radiological and histological data.

To prevent the development of hyperphosphatemia in patients with bone lesions of renal origin, alfacalcidol can be used together with phosphate binders.

It must be taken into account that sensitivity to vitamin D varies from patient to patient, and sometimes the use of even therapeutic doses may be accompanied by symptoms of hypervitaminosis.

Children who receive vitamin D for a long time are at increased risk of stunted growth.

To prevent hypovitaminosis D, a balanced diet is most preferable. In old age, the need for vitamin D may increase due to a decrease in the absorption of vitamin D, a decrease in the skin's ability to synthesize provitamin D3, a decrease in sun exposure, and an increase in the incidence of renal failure.

The excipients of the drug include peanut oil. The drug is contraindicated in patients with an allergic reaction to peanut oil and soybean oil.

Impact on the ability to drive vehicles and operate machinery

Caution should be exercised when driving vehicles and mechanisms that require increased concentration and speed of psychomotor reactions, since dizziness and drowsiness may develop when using the drug Alpha D3-Teva®.

General properties of drugs

The drugs in question have one goal, which is to compensate for vitamin D deficiency . Regulate the exchange of calcium and phosphorus, increase their absorption in the intestines. They help increase bone mineral density, therefore they are used for osteoporosis, rickets, and phosphorus-calcium metabolism disorders. They have similar contraindications and can cause similar side effects. They belong to the same price category, ranging from 200-550 rubles .

International Journal of Endocrinology 2 (26) 2010

Postmenopausal osteoporosis (PMO) is a disease characterized by increased fragility of bone tissue and a tendency to fracture. This pathology makes a significant contribution to morbidity and mortality rates. Estrogen deficiency and changes in vitamin D metabolism play an important role in the development of PMO.

Decreased intestinal calcium absorption may be due in part to decreased serum concentrations of calcitriol, or D hormone (1,25 dihydroxyvitamin D), secondary to estrogen deficiency. In addition, recently there has been evidence of an age-dependent decrease in the number and sensitivity of receptors for endogenous D hormone, primarily in the intestine, but also in other target organs. To date, it has been proven that D hormone takes part in the functioning of bone tissue modeling and remodeling systems and, therefore, has a pronounced effect on the strength of bone tissue.

A number of prospective, randomized, placebo-controlled clinical trials have demonstrated the ability of D-hormone analogues (alfacalcidol, calcitriol) to increase bone mineral density (BMD) and reduce the risk of vertebral and non-vertebral fractures. A recently published meta-analysis conducted by two independent research groups from the United States (The Osteoporosis Methodology Group) and Canada (The Osteoporosis Research Advisory Group) demonstrated superiority in the effectiveness (prevention of fractures) of proD and D hormones (alfacalcidol, calcitriol) compared with vitamin D .

Currently, vitamin D is used as an adjunct in the treatment of osteoporosis in combination with drugs such as bisphosphonates and raloxifene, however, vitamin D is not effective in monotherapy for PMO, as has been proven in a number of clinical studies. In a randomized controlled trial, Gallagher et al. (1990) compared the effectiveness of D hormone and low doses of vitamin D in 50 patients with PMO. After 18 and 24 months. therapy, statistically significant differences were observed in spine BMD in favor of D hormone. In a randomized trial, Francis et al. (1996) studied the effect of Alpha D3Teva (alfacalcidol) and vitamin D on calcium absorption in women with radiological evidence of vertebral fractures. After 3 months treatment, fractional absorption of calcium increased significantly in the group of patients receiving Alpha D3Teva (alfacalcidol), and remained at the original level in the vitamin D group. Other studies that directly compared drugs for secondary osteoporosis also showed higher effectiveness of Alpha D3Teva ( alfacalcidol) compared to vitamin D.

In elderly patients, administration of a combination of vitamin D and calcium was associated with improved intestinal calcium absorption, reduced bone loss and the risk of nonvertebral fractures.

However, this combination was ineffective in PME.

Regarding the safety of the D hormone analogs alfacalcidol and calcitriol, it should be noted that both drugs may cause an increase in serum calcium levels and urinary calcium excretion. However, in a large post-marketing study involving patients with osteoporosis conducted in Japan, it was demonstrated that the risk of developing hypercalcemia during treatment with D-hormone analogues is very low, and there were no cases of kidney stone formation at all.

In addition, the study by Nishii et al. (1993) when prescribing the same doses of Alpha D3Tev (alfacalcidol) and calcitriol, the level of D hormone in bone tissue during treatment with Alpha D3Tev (alfacalcidol) was higher compared to the calcitriol group.

The purpose of this study was to compare the effectiveness and safety of Alpha D3Tev (alfacalcidol) at a dose of 1 mcg/day (without calcium) and vitamin D in combination with calcium in doses recommended by international guidelines in patients with verified postmenopausal osteoporosis, regardless of the presence of vertebral fractures in medical history.

Materials and methods

The study, which was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, included 170 postmenopausal women with osteoporosis treated at one of 11 clinical centers in Italy. The study included patients aged 55–75 years, who had been menopausal for at least 5 years, with a history of ≥ 1 vertebral fracture (confirmed by spinal radiography) and/or with a BMD T criterion of the lumbar spine or femur < –2, 5.

Exclusion criteria:

- secondary osteoporosis, other bone diseases, significant concomitant diseases, hypercalcemia, hypercalciuria;

- treatment with drugs that affect bone metabolism (estrogens, progesterone, selective estrogen receptor modulators, calcitonin, vitamin D, calcium supplements - for > 1 month in the previous 3 months; bisphosphonates, fluorides, ipriflavone, glucocorticoids, immunosuppressants - for > 1 month in the previous 6 months).

If the inclusion/exclusion criteria were met, patients were randomly assigned to three groups:

— to obtain alfacalcidol 1 mcg (Alfa D3®Teva);

— placebo vitamin D3 + calcium carbonate 2500 mg;

— placebo alfacalcidol in combination with vitamin D3 880 IU + calcium carbonate 2500 mg (1000 mg calcium) (combined drug in sachet form Cacit D3®, Procter & Gamble) in a ratio of 1: 1. All drugs were prescribed once a day. According to the instructions, patients were to take sachets in the afternoon and capsules in the evening.

Patients were examined after 3, 6, 12 and 18 months. therapy. During screening at 12 and 18 months. treatment, BMD of the lumbar spine and femur was measured using dual-energy X-ray absorptiometry.

results

Of the 170 women, 22 were ineligible. The double-blind phase of the study included 148 women of European descent. Participants were randomized to receive alfacalcidol (76) or a combination of vitamin D and calcium (72). Data from 136 of them (91.9%; 69 patients in the alfacalcidol group and 67 in the control group) were used for ITT analysis (Fig. 1). One patient in the alfacalcidol group and two in the comparison group had a Tcriterion > –2.5 and at least one vertebral fracture.

Baseline characteristics in both groups were comparable in both the ITT analysis group (Table 1) and the overall population. A significant difference was detected only in terms of the average BMD of the lumbar region. A significant difference was noted in the number of patients with previous vertebral fractures (not significant; P = 0.208).

Only 102 patients (75% of the ITT group)—52 in the alfacalcidol group and 50 in the vitamin D and calcium group—completed the study (18 months of treatment).

BMD of the lumbar spine was studied in 97 women - 50 patients who received alfacalcidol, and 47 patients who took calcium + vitamin D3. Initially, there were no statistical differences between the groups. In the alfacalcidol group, BMD after 12 months. treatment increased by an average of 0.017 g/cm2 (2.33%) after 18 months. - by 0.021 g/cm2 (2.87%), and in both cases this increase was statistically significant (p < 0.001 after 12 and 18 months compared with the initial value) (Table 2).

In the group that took calcium + vitamin D3, after 12 and 18 months. treatment, the increase in BMD was insignificant and amounted to only 0.005 g/cm2 (0.70%). The differences between the mean increases in BMD between the alfacalcidol and calcium + vitamin D3 groups were statistically significant at both 12 and 18 months. treatment (p = 0.018 and p = 0.005 compared with the initial value, respectively).

In the alfacalcidol group, ≥1 treatment-related adverse effect was observed in 22 (30.1%) patients; in the calcium + vitamin D group there were 19 such patients (27.1%). The most common symptoms were dyspeptic symptoms (in 10 and 9 patients receiving alfacalcidol and calcium + vitamin D, respectively). There were no cases of kidney stone formation.

In table Table 3 shows the average values ​​of calcium, phosphorus and creatinine in the blood serum before and after treatment. Pre-treatment calcium levels were similar in both groups: 9.35 ± 0.70 in the alfacalcidol group and 9.39 ± 0.48 in patients taking vitamin D and calcium. At the end of the study, serum calcium levels were slightly higher in the alfacalcidol group compared with the group receiving the combination of vitamin D and calcium (9.56 ± 0.48 and 9.45 ± 0.49, respectively). However, phosphate and creatinine levels did not change significantly after 18 months of treatment. Statistical analysis demonstrated no benefit between groups at the 2.5% level (95% CI of geometric mean ratio: calcium 1.00–1.03; phosphorus 0.93–1.00; creatinine 0.96–1.05).

Discussion

The data obtained showed that in women with PMO, treatment with Alpha D3Teva (alfacalcidol) 1 mcg/day without additional calcium intake led to a statistically significant increase in BMD of the lumbar spine after 12 and 18 months. therapy compared to treatment with vitamin D 880 IU/day + calcium 1 g/day. In addition, treatment with Alpha D3Teva (alfacalcidol) was associated with a clinically significant, although not statistically significant, reduction in the risk of developing new vertebral fractures. A history of fractures is an important risk factor for future fractures, so it should be emphasized that before treatment, there were more patients in the Alpha D3Tev (alfacalcidol) group with ≥ 1 history of fracture compared to the calcium + vitamin D3 group (Table 4). The fact that Alpha D3Teva (alfacalcidol) was shown to be a more effective drug despite this difference is certainly noteworthy.

Some researchers have suggested that a polymorphism in the vitamin D receptor gene may be responsible for the greater therapeutic response to vitamin D and its metabolites observed in Asian populations compared to Europeans. However, the present study confirmed the high effectiveness of Alpha D3Teva (alfacalcidol) in European patients. In addition, according to the study by Rapuri et al. (2004), different vitamin D receptor genotypes have no effect on the response to calcitriol treatment.

In the medical literature, there are still often conflicting discussions regarding whether D-hormone analogs are actually superior to vitamin D in patients with osteoporosis. It should be noted that the effectiveness of the calcium + vitamin D combination has been proven only in the presence of vitamin D deficiency, while as in women with PMO and normal vitamin D levels, no significant effects from this combination develop at all. Prescribing vitamin D, in fact, is not drug therapy, but only a replacement dietary supplement to the diet. Due to the existence of a negative feedback mechanism that regulates the final step in the conversion of 25(OH)D to the active hormone 1,25dihydroxyvitamin D in the kidneys, oral vitamin D supplementation will never increase D hormone levels. This means that in patients with replenished vitamin D levels, the therapeutic effect on bone tissue, muscles and other target organs can only be achieved by prescribing D hormone analogues. Similarly, patients with D-hormone deficiency due to decreased 1-alpha hydroxylase activity in the kidneys (eg, women with PMO) are more or less resistant to vitamin D treatment. The phenomenon of vitamin D resistance has also been observed in patients with reduced vitamin D receptor affinity.

Alpha D3Teva (alfacalcidol) is activated in the liver and other target organs, including bone tissue, and is a prodrug of D hormone. Thanks to this, D-hormone deficiency can be effectively replenished, bypassing the natural renal regulatory system. Vitamin D resistance caused by deficiency of the corresponding receptors can also be successfully treated with D hormone analogues, since they affect the expression, activation and restoration of normal properties of vitamin D receptors.

Alpha D3Teva (alfacalcidol) prevents the rapid bone loss characteristic of postmenopause and improves bone quality by correcting intestinal calcium malabsorption and normalizing increased bone turnover. The latter effect is achieved through a direct inhibitory effect on osteoclast precursors, as shown in an in vivo study, as well as through fine regulation of osteoblast differentiation and function. In addition, specific immunoregulatory T cells may be involved in this complex process, influencing the effectiveness of alfacalcidol through mechanisms such as the appearance of more tolerogenic antigen-presenting cells, a decrease in the number of helper cells, an increase in the number of suppressor cells, and activation of cytokine homeostasis.

In an ovariectomized rat model of osteoporosis, histomorphometric and biochemical studies have shown that oral administration of alfacalcidol causes a dose-dependent suppression of osteoclastic bone resorption, which is contrary to the known “stimulation” in vitro. The direct suppression of bone resorption with the use of a D hormone analogue is explained by recent discoveries: alfacalcidol inhibits osteoclastogenic mechanisms in vivo by reducing the pool of osteoclast precursors in the bone marrow, which are a key pathogenetic factor in bone loss in the postmenopausal period [28]. Unlike conventional bone resorption inhibitors such as estrogen and bisphosphonates, alfacalcidol stimulates bone formation [32]. This helps to improve the “quality” of bone, and also increases the number of tubular and spongy bones. In patients suffering from osteoporosis, taking alfacalcidol is more effective in increasing BMD and increasing bone strength compared to using vitamin D alone [33]. These potential benefits of alfacalciferol compared to vitamin D on bone microstructure were confirmed by microCT scanning [34]. It has also been shown in deparathyroidism rat models that alfacalcidol has a direct anabolic effect on bone strength and bone mass, independent of calcium absorption and PTH suppression [33], when administered with chronic PTH infusion.

The direct effect of the D hormone analogue on osteoblast function (proliferation, apoptosis, expression of specific bone proteins and growth factors), as well as on mineralization, has been reliably confirmed [20, 29, 35]. Recently, the anabolic effect of D hormone on bone in ovariectomized rats was demonstrated, especially in combination with another drug with a potent antiresorptive effect [36]. This anabolic effect occurs even despite a significant decrease in osteoclast activity, that is, this effect of D hormone does not depend on the functioning and activity of the osteoblast.

Dendrites are very important for recognizing the mechanisms of bone loss in the postmenopausal period [21]. Some researchers have demonstrated in vitro suppression of dendrites by vitamin D receptors and in vivo their ability to detect antigen that stimulates T cell activation and proliferation, as well as the production of cytokines that promote resorption, which is caused by the release of D hormone [31, 37]. These data suggest that dendrites provide a new target for the D hormone analogue, which will reduce bone loss in PME.

It is known that bone loss is common after ovarian surgery. The DEXA study examined the effects of alfacalcidol in women following bilateral oophorectomy [38]. The study included women who underwent oophorectomy before menopause (> 6 months after surgery) and had bone loss greater than a standard deviation (–1 SD) according to the T-criterion. They were divided into three groups: control; taking alfacalcidol at a dose of 0.25 mg; use of alfacalcidol at a dose of 0.5–0.75 mg per day. All patients followed a diet that consisted of a mandatory intake of approximately 800 mg of calcium per day. One year later, in the placebo group, BMD in the lumbar region decreased by 3.6%. At the same time, in the group receiving alfacalcidol at a dose of 0.25 mg, this figure was only –3.2%. In the group using alfacalcidol at a dose of 0.5–0.75 mg per day, a significant reduction in bone loss was achieved (–0.8%) [38]. This study convincingly demonstrated the dose-dependent effect of alfacalcidol.

A meta-analysis of studies demonstrated greater effectiveness of D-hormone analogues (alfacalcidol, calcitriol) compared to the use of vitamin D alone [9], since the former have a greater effect on BMD. After 12 months of treatment, the difference between the groups was statistically significant both for the body as a whole (P < 0.03) and for the forearm area (P < 0.01). Taking D-hormone analogues can significantly reduce the risk of vertebral fractures (RR = 0.64; 95% CI 0.44–0.92); a similar effect is absent when using vitamin D alone [9].

In another meta-analysis, a D-hormone analogue was shown to have a positive effect on bone mass and, most importantly, on the risk of vertebral fractures (RR = 0.53; 95% CI 0.47–0.60) [40] and non-vertebral fractures ( RR = 0.34; 95% CI 0.16–0.71). The fact that two different independent meta-analyses showed similar results provides strong evidence for the effectiveness of D-hormone analogues in reducing the risk of vertebral fractures. In a comparative meta-analysis, Richy et al. [41] also obtained information confirming the higher effectiveness of D hormone analogues in increasing vertebral bone mass and reducing the risk of vertebral and non-vertebral fractures compared to taking vitamin D alone in PME.

There were no cases of hypercalcemia observed in the alfacalcidol-treated group during the study. It is important to note that the formation of kidney stones was not observed during treatment with this drug. Our data were confirmed in the Postmarketing Surveillance Study [18]. 13,550 patients with PMO over the age of 60 years who received alfacalcidol at a dose of 0.5–1 mg per day were observed for 6 years. Side effects were reported in only 1.1% of participants. Hypercalcemia (serum calcium > 11 mg/dL) occurred in 0.22% of patients; There were no cases of stone formation in the kidneys at all [18]. The risk of developing hypercalcemia when taking calcitriol is higher. When ingested, calcitriol immediately and directly affects the VDR cells of the intestinal mucosa, which promotes the absorption of calcium in the intestine. This, in turn, leads to a rapid increase in serum calcium [25]. During the study period, no changes in creatinine levels were observed during treatment.

A meta-analysis of clinical studies has convincingly demonstrated the higher effectiveness of D-hormone analogues (alfacalcidol (Alpha D3Teva), calcitriol) compared to vitamin D in PME. In all of these studies, D-hormone analogues had a significantly greater effect on BMD.

The present study confirmed the position of Alpha D3Tev (alfacalcidol) as an effective drug for the treatment of PMO. Alpha D3Teva (alfacalcidol) was significantly superior to vitamin D in increasing bone mass and possibly reducing the risk of vertebral fractures. The results obtained can serve as a convincing answer to the question of the advisability of treatment with Alpha D3Teva (alfacalcidol): on the one hand, vitamin D was not enough for the effective treatment of PMO, and on the other hand, side effects developed with the same frequency in both treatment groups.

Considering the high efficiency and good tolerability, the safety of long-term treatment and a simple dosage regimen that promote long-term patient adherence to treatment, as well as the moderate cost of the daily dose, in women with postmenopausal osteoporosis, Alpha D3Teva (alfacalcidol) can be considered as the drug of choice.

The list of references is in the editorial office

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First published: Rheumatology International, 2006; 26: 445543

Comparison, differences, what is more effective

Although the drugs have common functions, there are important differences between them. Therefore, you need to familiarize yourself with them in more detail:

1. Compound . This is their main difference. The first drug contains a synthetic analogue of vitamin D - alfacalcidol. The active ingredient of the second remedy is colecalciferol, which is vitamin D3.
2. Manufacturer country . Both drugs are foreign, but the countries differ. Alpha D3-Teva is manufactured in Israel, Aquadetrim - in Poland.
3. Form, conditions of release . The first drug is in capsule form and is available only with a doctor's prescription. The Polish product is available in the form of drops and can be purchased without a prescription form.
4. Contraindications . The Israeli drug is contraindicated for pregnant and lactating women, as well as children under three years of age. The second medication is allowed in small dosages.

There are some studies where it was found that the form of vitamin D that the first drug contains is more effective. Patients with osteoporosis had better results than using regular D3. However, the decision to prescribe should only be made by a doctor, since each case is individual, and the wrong choice of drug can lead to adverse consequences.

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