Osteoporosis is a multifactorial disease characterized by a progressive decrease in bone mass per unit volume of bone in relation to the normal index in individuals of a corresponding gender and age.
The deficiency of sex steroids (both estrogen and androgen) is one of the causes leading to the development of osteoporosis.
The effect of estrogen on the human skeleton is traced at the organ, tissue and cellular levels. At the organ level, estrogens contribute to the maintenance of skeletal mass, at the tissue level – maintain a balance between bone formation and resorption, at the cellular level – affect the formation, lifespan and functional activity of both osteoblasts and osteoclasts. In the late 1980s, estrogen receptors were found on osteoblasts in humans and rats, which indicates the direct effect of sex hormones on bone cells.
Estrogens inhibit the formation and activity of osteoclasts, and by increasing apoptosis, they decrease their lifespan. Many studies confirm the positive effect of estrogens on the formation, differentiation, proliferation and functional activity of osteoblasts. Recent studies have also confirmed the ability of estrogens to prevent osteoblast apoptosis caused by high doses of glucocorticoids. For a normal remodeling process, estrogen is required. Estrogen deficiency affects the cycle of bone re-modeling as follows. First, the frequency of BME activation increases, which leads to an increased metabolism of bone tissue. Secondly, the resorption phase is prolonged as a result of a decrease in osteoclast apoptosis and the formation phase is reduced due to increased osteoblast apoptosis. As a result of the above changes, the volume of the resorption lacuna increases so much that osteoblasts are not able to fill it. In the cancellous bone, an increase in the life span of osteoclasts leads to an increase in the resorption and perforation depth of the trabecular plate.
Androgens, like estrogens, suppress bone resorption. Androgens have both direct and indirect (mediated) effects on bone tissue. The direct effect of androgens lies in their effect on apoptosis, which is manifested in an increase in the lifespan of both osteoblasts and osteoclasts. Androgens also slightly stimulate the proliferation of osteoblasts. Most of the effects of testosterone on redovanno through the action of estrogen, which are formed from androgens under the influence of aromatase. In boys with homozygous estrogen-receptor or aromatase gene mutations, there was no rapid increase in growth in adolescence, despite normal or elevated testosterone levels. However, it is the direct effect of testosterone on bone tissue that introduces differences in the structure of male and female skeletons. Testosterone and estrogens affect both the different stages of osteoblast differentiation and the different areas of bone tissue. So, testosterone stimulates periosteal bone growth, while estrogens inhibit it. In post-pubertal age, bone mass in boys is 25% more than in girls, which is explained by an increase in the level of serum testosterone, because the level of growth hormone and insulin-like growth factor type 1 are the same or even more in girls.
Many works confirm the dominant importance of estrogen in bone formation. In their work, Mueller and colleagues demonstrated the ability of estrogens to increase bone density in transgender people (M / F) receiving anti-androgen therapy (GnRH agonist) and estradiol valerate.
Similar results were obtained in the work of van Kesteren and colleagues (1996).
Among our patients, we are more often confronted with osteoporosis in M / M-transsexualism than in M / M-transsexualism, since with the latter there are practically no cases of late appointment of androgen therapy. When F / M-transsexualism, as a rule, patients begin to receive androgens long before the operation and clearly monitor the regularity of injections due to fearrecovery of menstruation (before surgery), and by the time of the surgery, including hysterectomy, patients in most cases already have good virilization, barionia, mustaches appear and patients are well aware that the reason for their masculinity is in ampoules containing androgens. Recently, however, we have accumulated data on the high prevalence of osteopenia in these patients who require analysis.
With M / F-transsexualism, the situation is different. Often, the treatment of these patients begins with a surgical correction of the genitals, and if surgeons do not recommend consulting an endocrinologist, the patients themselves do not realize this. What for? The testicles are removed, the male hormones are no more. The issue of mammary glands is solved by endo-prosthetics, and the issue of excessive hair growth is solved by epilation. In the meantime, the patient is progressing muscle weakness and gradually leaching of calcium from the bones.
An illustration of the effect of lack of sex steroids on the state of the bone tissue can serve as a patient, which in 1993 was conducted gonadectomy without the appointment of appropriate HRT. For 3 years, the patient did not receive estrogen therapy. She came to us with complaints of weakness (a professional athlete who was sick in the past, but because of severe muscle weakness that appeared after the operation, she had to leave the sport), spinal pain, and increased fatigue. The diagnosis is clear: postcastration syndrome. When conducting ultrasound densitometry, it was found that the loss of bone mass was 29% of the age norm.
This patient is currently in the risk group for the occurrence of pathological fractures, because the bone affected by osteoporosis becomes fragile, and this can lead to fractures even with a small injury.
It is known that up to 70% of fractures in people older than 45 years are associated with osteoporosis, i.e. osteoporosis is the leading cause of fractures, and 50% of them develop spontaneous fractures. Most often fractures affect the femoral neck, spine and peripheral forearms. The greatest danger is a fracture of the hip.
To prevent such serious complications, timely administration of HRT in an adequate dose is necessary. Patients with transsexualism who have reached the age of 45, as well as patients who for one reason or another do not receive HRT or have a long break in their reception, it is necessary to conduct a bone tissue densitometry for evaluation.
To assess the state of the bone tissue, currently used are: dual-energy X-ray absorptiometry (dual-energy X-ray absorbtiometry – DЕХА), ultrasonometry and quantitative CT. The most widely recognized diagnosis of osteoporosis has been DEHA, since, based on numerous assessment methods, it has been shown that the incidence of fractures correlates with the bone mineral density of the lumbar spine and proximal femurs.
When osteoporosis is found in a patient, it is necessary to assess the adequacy of HRT and, if necessary, correct it, as well as to additionally prescribe therapy aimed at improving the state of bone tissue: bisphosphonates, calcitonins, agents that have a multifaceted effect on bone tissue (vitamin D and its metabolites) . The main objectives of this therapy are the normalization of the process of bone remodeling, primarily the suppression of increased bone resorption and stimulation of reduced bone formation, which leads to an increase in bone mineral density or at least its stabilization, an increase in bone quality and a decrease in the frequency of fractures.
Bisphosphonates are considered today as first-line drugs in the treatment of osteoporosis. The mechanism of their action is as follows: direct action on osteoclasts, leading to impairment of their metabolism and functional activity, induction of their apoptosis and suppression of bone resorption, stimulation of the formation of new bone.
Alendronate (fosamax) is available in the pharmacy network of Russia from bisphosphonates. Alendronate is prescribed at 70 mg once a week for a long time, for 3-5 years. Contraindications to the appointment of alendronate are hypersensitivity to the drug, hypocalcemia, diseases of the esophagus (achalasia or stricture). Alendronate is relatively contraindicated in patients with acute diseases of the upper gastrointestinal tract. Hypocalcemia and other disorders of mineral metabolism should be corrected before prescribing alendronate — simultaneously with alendronate, calcium should be given at a dose of 500–1000 mg / day (with food or additionally) and vitamin D at a dose of 400–800 IU / day.
Calcitonin is a polypeptide hormone produced by parafollicular cells of the thyroid gland. The main effects are hypocalcemic and hypophosphatemic, which are realized as a result of the inhibition of differentiation and activity of osteoclasts and, as a consequence, inhibition of bone resorption. Most preferred odds my administration of calcitonin is a nasal spray due to a significantly smaller number of side effects compared with the parenteral administration form.
The necessary intake of calcium and vitamin D is important. Calcium enhances the antiresorptive effect of estrogen on bone. To minimize side effects, improve the absorption of calcium preparations should be taken during or after meals.
Vitamin D is necessary for sufficient calcium absorption and normal bone metabolism.
In the absence of calcium hypercalcemia, carbonate in a daily dose of 1000 mg and vitamin D at a dose of 800 IU can be used as a combination therapy with sex steroids, bisphosphonates, calcitonin.
A certain role in the prevention of osteoporosis play the rejection of bad habits (smoking, alcohol), moderate exercise, prevention of falls.
In conclusion, it is necessary to emphasize once again that the actual surgery for surgical sex change in transsexuals is one of the stages in the treatment of this disease. There is no doubt that all patients who underwent sex reassignment surgery should be under the supervision of an endocrinologist for the rest of their lives to control the adequacy of the hormone replacement therapy they receive. Only a properly selected dose of hormonal drugs can prevent the development of side effects caused by the removal of the gonads, that is, the development of the post-attrition syndrome.