Introduction
Postmenopausal osteoporosis(postmenopausal osteoporosis, POP) is a common disease associated with aging, mainly in postmenopausal women, due to lack of bone mass due to estrogen deficiency and changes in bone structure, increased bone fragility and easy fracture, as well as pain caused by fractures Problems such as skeletal deformation, comorbidities, and even death seriously affect the health and quality of life of the elderly, and even shorten the lifespan, increasing the financial and human burden of the state and the family. Osteoporosis associated with menopause is an important health issue that cannot be ignored. In 1993, WHO defined osteoporosis as a systemic reduction in bone mass, accompanied by a microstructural change in the bone, resulting in an increase in bone fragility and an increased risk of fracture. In 2001, the National Institutes of Health Consensus Conference proposed that osteoporosis is a bone disease characterized by impaired bone strength, leading to an increased risk of fracture. Bone strength is concentrated to reflect bone density and bone mass. The pathological features of osteoporosis are a proportional reduction in bone mineral content and bone matrix composition, thinning of the cortical bone, reduction and thinning of the trabecular bone, and trabecular bone fracture during postmenopausal osteoporosis.
Cause
According to the cause, it is divided into primary and secondary osteoporosis.
Type I osteoporosis, also known as postmenopausal osteoporosis, is mainly due to estrogen deficiency, occurring in female patients, aged 50 to 70 years, showing rapid loss of bone mass, loss of bone cancellosis, fractures occur more often In the vertebral body with osteoporosis, the upper end of the femur and the distal end of the humerus.
Type II osteoporosis is also known as senile osteoporosis. Compared with type I, the number of male patients increased, but the ratio of male to female is still 1:2. The age of onset is more than 70 years old, which is characterized by slow loss of bone mass. The rate of loss of bone cancellus and bone density is almost the same. Except for type I, the incidence of hip fractures has increased.
Secondary osteoporosis is caused by other causes. Such as chronic diseases: chronic renal failure, gastrectomy, intestinal diversion, calcium malabsorption syndrome,Multiple myelomaEtc. Endocrine diseases: hyperprolactinemia, hyperthyroidism, excessive secretion of adrenocortical hormone, diabetes, hyperparathyroidism and so on. Iatrogenic factors: long-term application of resistanceepilepsyMedicine, aluminum-containing antacid, overdose of thyroxine or long-term use of glucocorticoids, gonadotropin-releasing hormone (GnRH) agonists.
Postmenopausal osteoporosis is a multifactorial disease, and genetics, lifestyle, and nutrition are all related to the disease. People with high risk factors are susceptible to postmenopausal osteoporosis: white and Asian women, family history of osteoporosis, or women with specific genes affecting bone mass, inadequate calcium intake, lack of physical activity, mass smoking and alcohol consumption , early menopause or bilateral ovarian resection before menopause. Whether or not osteoporosis occurs depends on the peak of bone and the rate of bone loss, high bone peaks and/or slow bone loss, which are not easy to occur, and low bone peaks and/or bone loss are prone to occur.
1. Bone peak Bone peak refers to the highest bone mass in a person's lifetime, usually reached at 25 to 35 years old. There are many factors affecting bone peaks, among which genetic factors are the most important, and nutrition and living habits also have some effects.
(1) Genetic factors: determine 70% to 80% of bone peak. For example, black BMD is higher than whites and Asians, and the incidence of osteoporotic fractures is low. Osteoporosis has a family tendency. The difference in BMD between single and twins is smaller than that of twins. The peak of bone in men is higher than that in women. In some countries, vitamin D receptor gene, estrogen receptor gene, or collagen gene polymorphism is associated with BMD, and the bone peak is affected by genetic factors.
(2) Nutrition: Those with high calcium intake during adolescence have higher bone peaks and up to 6% of mature bone BMC. The World Health Organization recommends that the elemental calcium intake during adolescence should be 1000 mg per day.
(3) Lifestyle: Exercise can increase BMD. If you insist on daily exercise, the amount of physical activity is higher than the average amount of 1SD, and the bone volume is 7% to 10% higher than the average amount of activity below 1SD. However, when excessive exercise causes hypogonadism and amenorrhea occurs, the bone mass decreases. A large number of cigarettes were formed before the peak of bone formation, and the bone peak of alcoholics was low.
(4) Primary hypogonadism and delayed puberty development, low bone peak.
2. Bone Loss Rate Women's bone loss is associated with age and menopause.
(1) Age-related bone loss: Spinal bone loss generally begins at 40 to 50 years old, and the loss rate is 0.8% to 1.2% per year. The loss of limb bones is about 10 years later, that is, from 50 to 60 years old, the loss rate is 0.3% to 0.6% per year, which is linear, and its mechanism is unclear, which may be related to the reduction of bone formation. The consequence of this bone loss is that the trabecular bone becomes thinner and does not undergo perforation changes in the trabecular bone.
(2) Bone loss associated with menopause: Regardless of age, once menopause, the estrogen in the body drops sharply, the bone loss increases logarithmically, and the trabecular bone becomes thinner, thinner, and even broken (perforated). After bilateral ovariectomy, all ovarian-derived sex hormones disappear and bone loss is faster. At this time, the bone loss is twice that of the limb bones, and the loss rate is as high as 4% to 5% per year. After 5 to 10 years, bone loss occurs. The speed is slowed down. Bone loss in the limb bones is slow and the duration of loss is also long.
Animal experiments and clinical observations have confirmed that after excretion of estrogen in ovariectomized or postmenopausal women, the bone turnover rate is reduced, which can effectively prevent bone loss. It is also proved that estrogen deficiency is the main cause of postmenopausal osteoporosis. .
(two) pathogenesis
Normal bones are constantly renewed by bone remodeling. The osteolytic effect of osteoclasts is hollowed out under the bone surface to form a bone lacunae, which is then moved by a group of osteoblasts to the bone lacuna to synthesize and secrete collagen and polypeptide proteins involved in bone formation. After the calcium ion deposition, the bone matrix is formed, and the bone lacuna is repaired by the newly formed bone matrix, and a bone reconstruction unit is completed, and the cycle is about 3 to 4 months. Bone turnover rate refers to the rate of old bone resorption and new bone formation. Postmenopausal estrogen is reduced, bone turnover is increased, bone loss is increased, and high conversion osteoporosis is present. The effect of estrogen on the pathogenesis of osteoporosis is mainly achieved through the following routes.
1. Effects on calcium-regulating hormones Estrogen can enhance liver 25-hydroxylase, renal 1α-hydroxylase activity, increase 1,25-dihydroxyvitamin D levels, promote intestinal calcium absorption, and make calcium and phosphate salts. Deposition in bone promotes bone matrix synthesis. Estrogen also antagonizes the action of parathyroid hormone, and together with parathyroid hormone maintains the balance of calcium and phosphorus in the blood. Parathyroid hormone is a hormone that stimulates osteolysis. When estrogen is reduced, the antagonism of parathyroid hormone is weakened, which can accelerate bone ablation and gradually develop into osteoporosis. Calcitonin inhibits osteoclast activity, and estrogen promotes calcitonin secretion.
2. Participation in bone formation and absorption through the action of cytokines Since Komm demonstrated the presence of estrogen receptors in osteoblasts in 1988, Ernst found that exogenous estrogen promotes IGF-I production by rat osteoblasts. Estrogen receptors are overexpressed due to increased production of IGF-I. It has also been found that estrogen promotes the production of TGF-β in osteoblasts, indicating that these growth factors promote bone formation, and estrogen promotes bone formation through the production of these growth factors.
Experiments have shown that when estrogen is deficient, IL-1 secreted by bone marrow mononuclear cells and IL-6 secreted by mesenchymal cells are increased. Pacifici et al also found that TNF-α and GM-CSF were produced in cultured peripheral blood mononuclear cells; TNF-α and GM-CSF levels were elevated in patients undergoing ovariectomy, and TNF-α and GM in estrogen-treated patients - CSF returns to normal levels. The above cytokines promote the bone resorption process, and estrogen inhibits bone resorption by inhibiting the production of the above cytokines.
3. The direct effect of estrogen on bone cells Since 1988, komm has found estrogen receptor (ER) on osteoblasts. In 1990, Penlser found estrogen receptors on osteoclasts, making estrogen more clear. Direct interaction with bone cells. Estrogen binds to estrogen receptors on osteoblasts and osteoclasts, directly inhibits lysosomal enzyme activity of osteoclasts and reduces their ability to produce lacunae on bone sections. In 1996, Shevde demonstrated that estrogen can directly inhibit the recruitment and differentiation of osteoclast precursor cells (bone marrow hematopoietic stem cells) through the receptor-binding pathway, thereby inhibiting osteoclast activity and utilizing cell morphology. Learning methods have shown that this effect of estrogen is achieved by influencing cell cycle-induced apoptosis. In 1997, Kameda also reached a similar conclusion using highly purified mammalian mature osteoclasts. Ernst confirmed that estrogen enhanced the proliferation of rat primitive skull cells and the expression of intracellular collagen and IGF-I mRNA.
symptom
Osteoporosis is a occult disease that often has no symptoms before it breaks. Once a hunchback, short stature, or bone pain is found, fractures often occur. Therefore, clinical symptoms cannot be diagnosed, and the severity of pain can be used to judge the therapeutic effect.
1. Osteoporosis of bone pain, usually due to microfracture of the trabecular bone, caused by muscle and ligament traction when the body position changes, so it can occur with sitting pain, flexion after flexion, walking pain, turning pain And lying pain and so on. The degree of pain is usually measured by a four-level scale. 0 is painless, 1 is sometimes painful, 2 is often painful, but can be tolerated, 3 is painful, and affects work and life.
2. The hunchback or the body becomes shorter when the spine undergoes a compression fracture.
3. Local tenderness or snoring is characterized by no local redness and fever.
According to the above clinical manifestations, laboratory tests and auxiliary tests can make a diagnosis in the early stage of osteoporosis.
Bone mineral content is the standard for diagnosing osteoporosis. In 1994, WHO redefined the diagnostic criteria for bone mineral density as osteoporosis:
1. Normal bone mass BMD or BMC is less than 1 standard deviation from the average of young adults.
2. Bone mass reduction BMD or BMC is 1 to 2.5 standard deviations lower than the average for young adults.
3. Osteoporosis BMD or BMC is on average 2.5 standard deviations or more lower than younger adults.
4. Severe osteoporosis (determined osteoporosis) meets the above diagnostic criteria for osteoporosis. At the same time accompanied by one or more fragility fractures.
Chinese experts believe that the 2.5 standard deviation of the mean bone loss is not conducive to the early diagnosis and treatment of osteoporosis, and it is more suitable for China's national conditions to lose the two standard deviations as the diagnostic criteria.
diagnosis
According to the above clinical manifestations, laboratory tests and auxiliary tests can make a diagnosis in the early stage of osteoporosis.
Bone mineral content is the standard for diagnosing osteoporosis. In 1994, WHO redefined the diagnostic criteria for bone mineral density as osteoporosis:
1. Normal bone mass: BMD or BMC is less than 1 standard deviation from the average of young adults.
2, bone mass reduction: BMD or BMC is 1 to 2.5 standard deviations lower than the average for young adults.
3. Osteoporosis: BMD or BMC are 2.5 years lower than the younger adults.
4. Severe osteoporosis (determined osteoporosis): meets the above diagnostic criteria for osteoporosis. At the same time accompanied by one or more fragility fractures.
Chinese experts believe that the 2.5 standard deviation of the mean bone loss is not conducive to the early diagnosis and treatment of osteoporosis, and it is more suitable for China's national conditions to lose the two standard deviations.
Identification
1. Multiple myeloma and osteoporosis are similar in bone mass, bone pain and pathological fracture. The difference is that multiple myeloma has a bone destruction area on the X-ray photograph, and the condition is progressively aggravated. The lesion is more common in the skull and pelvis. The bone marrow puncture examination is helpful for diagnosis.
2. Bone metastases are common in older women, who may be associated with bone pain, reduced bone mass and/or pathological fractures. The main difference with osteoporosis is that the primary tumor may be found, and there is a bone destruction zone on the X-ray photograph.
3. Osteomalacia is associated with osteoporosis due to a decrease in BMD due to osteomalacia, but osteomalacia often occurs in women of reproductive age, and its incidence is associated with prolificacy and malnutrition, often with hand and foot convulsions, blood calcium And blood phosphorus decreased, blood tALP increased, etc., bone X-ray showed a villous change in the bone boundary, and postmenopausal osteoporosis occurred in postmenopausal women, usually asymptomatic, blood calcium, phosphorus normal, blood tALP in normal The range is elevated, and the bone boundary is clear on the bone radiograph. However, older women lack outdoor activities, lack of vitamin D intake, and may also have osteoporosis and osteomalacia.
4. Secondary osteoporosis is osteoporosis caused by various diseases or long-term use of drugs, such as hyperthyroidism, hypothyroidism, hyperparathyroidism, diabetes, Cushing syndrome, chronic Liver disease, kidney disease, severe malnutrition, etc., drugs such as adrenocortical hormone, thyroid hormone, gonadotropin-releasing hormone analogue (GnRH-α), heparin, chemotherapy drugs, etc. Can occur at any age, detailed medical history and physical examination, supplemented by the necessary laboratory tests, can be identified with postmenopausal osteoporosis.
complication
1. Fracture is the most important complication caused by osteoporosis. If bedridden due to fracture, it is easy to cause pneumonia. Cardiovascular diseases often occur in the spine, forearm and hip fracture. The difference between a fracture with a healthy person is a minor trauma that is a fracture.
(1) Spinal fractures: Spine compression fractures can occur when lifting or pushing heavy objects, bending over, slightly falling, or falling on the buttocks when landing, acute and severe waist and back pain, sometimes accompanied by short stature, or There is nerve root compression pain. If the compression fracture of the spine occurs gradually, chronic low back pain occurs.
(2) Forearm fracture: It is easy to occur when one hand or both hands touch the ground when falling.
(3) Hip fracture: Slight slip can occur, usually in older postmenopausal women. After the occurrence of hip fracture, 15% to 30% die of various comorbidities within 1 year. About half of the survivors are unable to take care of themselves, and thus are the most serious complication of osteoporosis.
2. Because the thoracic body loses its elasticity and lumbar protrusions interfere with the blood circulation and functional activities of the heart, lungs and digestive system, it can be complicated by chest tightness, shortness of breath, cough, bloating, constipation and other symptoms.
treatment
Western medicine treatment
medical treatement:
1. Hormone replacement therapy (HRT) A large number of studies have confirmed that postmenopausal women with estrogen alone or in combination with progesterone can prevent bone loss. A 36-month study of estrogen and progesterone intervention in a postmenopausal study confirmed that the placebo group had a 1.8% decrease in lumbar spine BMD and a 1.7% decrease in hip BMD. The estrogen group combined estrogen with the estrogen and progesterone combination. Meili CEEs) 0.625mg / d group, combined estrogen (CEEs) + medroxyprogesterone (ancillary progesterone MPA) 2.5mg / d group, combined estrogen (CEEs) + medroxyprogesterone (MPA) 10mg / Group d, combined estrogen (CEEs) + micronized progesterone 200mg / d × 12 days / month group, lumbar spine BMD increased by 3.5% ~ 5.0%, hip bone BMD increased by 1.7%. Another multicenter study included 9,074 non-black women, aged 65 years or older, who currently used estrogen. The risk of carpal fracture was 0.39 (95% Cl 0.24 to 0.64) compared with non-users, all non-vertebral fractures. The hazard is 0.66 (95% Cl 0.54 to 0.80). Deng et al. pointed out that different vitamin D receptors and estrogen receptor gene types have different effects on bone mineral density.
The dose of estrogen has a significant relationship with the efficacy. The minimum effective dose of different drugs is different, such as the combined estrogen dose is 0.625mg / d,EstradiolAt 1 mg/d, emphasis is placed on using the lowest effective dose to avoid side effects.
George's study of postmenopausal twin-twist women found that the use of HRT in the lumbar spine and hip bone density was higher than that of the unemployed, but the previous use of HRT had no similar beneficial effects. It indicates that HRT needs to be applied continuously. If it needs to stop, other treatments should be added to maintain the beneficial effect on bone mass.
2. Calcium supplementation Calcium intake is essential for obtaining bone mass and maintaining osteophyte health. The daily calcium intake recommended for postmenopausal women is 1000-1500 mg elemental calcium. The dietary structure of Chinese residents is in the state of low-calcium food and beverage. In 1992, the National Nutrition Survey found that the average daily calcium intake per person in urban and rural adult males was only 458 mg and 378 mg: a survey in 1994 found that daily elderly women in Beijing were taking calcium. The intake is also less than 400mg. Change your eating habits and increase the intake of calcium in your diet. You should eat more calcium-rich foods such as milk, soy products, sea fish, dried shrimps, seaweed and dark green leafy vegetables. This is one of the effective measures to supplement calcium from food. . In addition, it can also be supplemented by calcium preparations, such as Maxim's calcium, each containing 315mg of calcium citrate, in addition to vitamin D, 300IU, 1 tablet per day. Leli calcium contains amino acid chelated calcium and various trace elements, each containing 250mg of calcium, 1 / d. Calcium D contains calcium carbonate and vitamin D 400 U per tablet, and the calcium content is 600 mg, 1 capsule/d.
Long-term calcium supplementation in older women may partially reverse the increase in age-related serum parathyroid hormone (PTH) and bone resorption, and reduce bone loss. However, this effect is weaker, compared with estrogen, bisphosphonate, calcitonin, can not replace their therapeutic effects, can be used as adjuvant therapy, combined application. Due to the safety of calcium, higher tolerance and lower cost, daily calcium supplementation is an effective way to reduce the risk of fracture. Although calcium supplementation is relatively safe, attention should be paid to monitoring blood and urine calcium concentrations. If blood calcium is in the normal range, 24h urinary calcium is 100-200mg, indicating that the dose is appropriate; if urinary calcium is 300-400mg, it indicates calcium or vitamin. If the D dose is too large, it should be reduced; if the urinary calcium is >400mg, it should be stopped to avoid kidney or bladder stones.
3. Vitamin D (vitamin D) One of the causes of negative calcium balance in patients with osteoporosis is due to intestinal calcium absorption disorders. The most important hormone affecting intestinal calcium absorption is 1,25(0H)2D3. If the content is small, even if the food contains more calcium, it is difficult to absorb. Vitamin D is hydrolyzed into 25(OH)D3 by hepatocyte mitochondrial 25-hydroxylase in the liver, transported to the kidney, and again by 1α-hydroxylase or 24-hydroxylase. It is hydroxylated to 1,25(OH)2D3 or 24,25(0H)2D3 and the like. Among them, 1,25(0H)2D3 is an active metabolite of vitamin D, which is a hormone secreted by the kidney. 1,25(OH)2D3 has a direct effect on bone, and physiological concentration of 1,25(OH)2D3 can promote bone resorption and bone formation. There are 1,25(OH)2D3 receptors in osteoblasts, and the addition of physiological concentration of 1,25(OH)2D3 can increase alkaline phosphatase activity and collagen production. It has been confirmed that 1,25(0H)2D3, in addition to promoting intestinal calcium absorption, has direct effects on bone tissue such as bone calcification, bone formation, bone growth and bone salt mobilization.
Vitamin D plays an important role in calcium absorption and bone health. Vitamin D in foods includes milk containing vitamin D (400 U per quart), porridge, egg yolk, sea fish and cod liver oil. Some calcium and multivitamin tablets also contain vitamin D. Komulainen et al believe that low-dose vitamin D supplementation has less preventive effects in early postmenopausal women, non-osteoporosis women, and no more significant effects on patients using HRT. Supplementation of 400 U of vitamin D3 per day for elderly women can slightly reduce the secretion of PTH and increase the bone density of the femoral neck, but the biochemical indicators of bone turnover have not changed. High-risk elderly women who are deficient in vitamin D, such as chronic diseases, lack of outdoor activities, long-term homes, or elderly people in nursing homes, recommend 400-800 U of vitamin D per day. Adults can get enough vitamin D through UV skin and food intake. In the elderly, due to liver 25-hydroxylase and kidney 1α-hydroxylase deficiency, it is advisable to choose active vitamin D, such as 1α(OH)D3 (Afadi III), calcitriol (1,25(0H)2D3, Luo calcium all) and other supplementation effect is better, the dose is generally 0.25 ~ 0.5μg / d, orally.
4. In women with low bone mass after menopause, bone loss is slow and may be prevented by exercise plus calcium supplementation or with HRT. Some studies have found that exercise plus estrogen is more effective than estrogen alone, and the amount and type of exercise required to prevent bone loss is unclear. One study found that exercise can prevent or reverse the loss of bone mass in the lumbar spine and femoral neck about 1% per year before and after menopause. Another study showed that physical activity had a significant effect on bone mineral density at the level of lumbar vertebrae 2 to 4, but no effective effect on the amount of bone in the forearm and hip was found.
5. Bisphosphonate diphosphate is a potent bone resorption inhibitor developed in the 1950s for the treatment of accelerated bone resorption diseases such as deformed bone (Pagets disease), malignant tumor bone metastasis and its accompanying high calcium. Blood, etc.; when bone turnover is accelerated, the effect is best, and therefore also applies to postmenopausal osteoporosis. The bisphosphonate is similar in structure to pyrophosphate, a calcium metabolism regulator in the body. It has strong affinity for hydroxyapatite, and combines with it to accumulate in the bone, inhibiting the formation of calcium phosphate crystals and delaying the agglomeration of apatite. It dissolves. At the cellular level, bisphosphonates inhibit bone resorption, although its mechanism of action is not well understood, but it has been found to alter osteoclast morphology, inhibit osteoclast activity, and reduce its number, resulting in reduced bone turnover. There are several types of bisphosphonates currently in clinical use:
(1) Etidronic acid (disodium hydroxyethylphosphonate, phosphine, bonadin), the first generation of bisphosphonate, long-term or large-scale application can block the mineralization of normal bone tissue, making the risk of fracture Increase in sex. Therefore, it is advocated for periodic use and at the same time supplementing calcium. The use of etidronate (phosphine) is 2 tablets (200mg each) 1 hour before breakfast every morning, swallowed with a cup of warm water, or 1 tablet, twice a day orally, and even after 14 days, the drug is stopped. In the evening, take 1 tablet of calcium (500-600mg calcium) and take it for 3 months. Can repeat 2 to 4 courses.
(2) Disodium clodronate (bone phosphine), intermittent medication, oral 400mg / d, 1 month of application, withdrawal for 2 months.
(3) Alendronate (Alendronate, Fushanmei, Tianke, Gubang), 10 mg / tablet, orally, once / d or once every other day. Take it on an empty stomach and drink about 200ml of water at the same time. Do not drink milk or other calcium-containing beverages at the same time, and keep it in an upright position to prevent the drug from irritating the esophagus. You need to take the medicine for half an hour before you can eat breakfast or drink other drinks or medicines. Alendronate is a new generation of bisphosphonates. By changing the side chain groups, it not only eliminates the defects of blocking the mineralization of normal bone tissue, but also greatly increases the intensity of inhibition of bone resorption. These drugs, once absorbed, can be rapidly distributed in bone tissue, especially at the most metabolically active bone surface of cancellous bone. The half-life in the blood circulation is very short, about 2h, but the half-life in the bone tissue is long, and for several years, it can strongly inhibit the absorption of bone. The rate of bone turnover decreases, eventually leading to an increase in bone mass and a decrease in the incidence of fractures. An experience with 447 menopausal women treated with alendronate (Fushanmei) demonstrated an increase in bone mineral density of 1% to 4% in the lumbar spine, femoral neck and greater trochanter, and a 0.3% to 1.0% increase in systemic bone density. A 3 year study of 5 mg, 10 mg, 20 mg of 3 different doses of alendronate (Fusam) confirmed that bone density increased during treatment, and the bone density increased most in the 10 mg dose group compared to the 5 mg, 20 mg dose. obvious. A dose of 5 mg alendronate (Fusam) has been approved by the US FDA for the prevention of osteoporosis. Meng Xunwu of our country conducted a multi-center open study of 81 cases of primary osteoporosis. The patient took oral alendronate (Fushanmei) 10 mg and elemental calcium 500 mg daily. The result was 2 to 4 bone mineral density in the lumbar spine. The months, 6 months and 12 months were significantly higher than before treatment, 2.8%, 4.1% and 6.3%, respectively. The hip bone density also increased significantly at 3, 6, and 12 months. The greater trochanter was the most significant, rising by 2.6% to 2.9%, followed by the femoral neck and Wards triangle.
The main side effect of bisphosphonate is digestive tract reaction, which may include nausea, vomiting, diarrhea, etc. Those with digestive tract diseases should be used with caution. Care should be taken to reduce the irritation to the gastrointestinal tract.
6.Calcitonin(CT) Calcitonin (CT) is a polypeptide composed of 32 amino acids secreted by thyroid follicular cells (C cells) and is one of the hormones that regulate calcium and bone metabolism. It mainly acts on bone and kidney and inhibits bone resorption factors caused by PTH and vitamin D. The effect of calcitonin (CT) on bone is to directly inhibit the dissolution of bone salts, inhibit the transformation of primordial cells into osteoclasts, and accelerate the transformation of osteoclasts into osteoblasts, so that the dissolution process is weakened. The second is to antagonize the rise of blood calcium. When blood calcium is high, calcitonin (CT) secretion is increased, and when blood calcium is lowered, calcitonin (CT) secretion is decreased. This effect is important for maintaining physiological bone mass. Third, calcitonin (CT) can antagonize PTH and promote the release of bone calcium into the blood. Calcitonin (CT) has an analgesic effect, which may be related to the improvement of calcium metabolism, central analgesic effects, and effects on muscle contractile function.
There are two drugs, calcitonin (salmon calcitonin, Yiganning) and (salmon calcitonin, dense calcium). Binding to the surface receptor of osteoclast membrane, activating adenylate cyclase to increase CAMP, and activating phospholipid inositol system to increase cytosolic free calcium, two effects inhibit osteoclast absorption, increase bone mass and Significant analgesic effect. Calcitonin (Yijiangning) is 10U, 20U per dose, and is used 10U twice a week or 20U once a week. Calcitonin (milk calcium) 50U per injection, once a day or every other day for 2 weeks, then every 2 days, for 3 months, every 3 months for a cycle, with 2 to 4 cycles , can increase bone mass. Calcitonin (milk calcium) also has a nasal spray, 50 or 100U / spray, generally 100U / time.
The main side effects are dizziness, palpitation, facial flushing, nausea and other discomforts. Those with allergies and history of bronchial asthma should be used with caution.
7. Selective Estrogen Receptor Modulators (SERM) Serm is a synthetic estrogen-like compound that selectively acts on estrogen receptors in different tissues to produce estrogen or antiestrogenic effects, respectively. Studies of SERM suggest that estrogen receptors acting on bone can also exert estrogen-like effects. Richard found that in postmenopausal breast cancer patients treated with tamoxifen (tamoxifen) two years later, lumbar spine bone density increased by an average of 0.61% per year, while the control group decreased by 1.00% per year, a significant difference between the two. For ovariectomized and adult rats, tamoxifen (tamoxifen), raloxifene, etc. also have the effect of maintaining bone mass and reducing bone loss, but some authors believe that SERM affects bone and estrogen levels. related. Tamoxifen (TAM) is used in healthy premenopausal women to reduce the amount of bone in the lumbar spine and hip. It indicates that the net effect of tamoxifen (TAM) on bone metabolism is antiestrogenic at higher estrogen levels before menopause, and tamoxifen when endogenous estrogen levels are low after menopause. TAM) exhibits an inherent estrogen-like effect on bone tissue. This may be related to the sensitivity of estrogen receptors at different estrogen concentrations. Raloxifene and tamoxifen (tamoxifen) have a good effect on bone mass and blood lipids, but in the clinical study of tamoxifen (tamoxifen), it causes endometrial hyperplasia and even induces endometrial cancer. Report. Animal experiments have found that high doses of tamoxifen (tamoxifen) can induce liver cancer in rats, so the clinical application prospect of raloxifene is more promising. The dose of tamoxifen (tamoxifen) was 10 mg, 2 times/d orally, and the dose of raloxifene was 60 mg/d orally.
8. Epalin is an isoflavone derivative synthesized in Hungary in the late 1960s and is 7-isopropoxy isoflavone. It belongs to the class of phytoestrogens. It has no estrogen activity in animals and humans, but it increases estrogen activity. In the early 1970s, it was found that it can increase the total amount of calcium in bone by administering a natural synthetic derivative of eprapfen to mice, chickens and sheep. Therefore, it was first proposed as a drug for the treatment of osteoporosis.
Some basic studies on eprapatin have been shown to increase bone formation by increasing the number of osteoblasts and inhibit bone resorption. The mechanism by which epoprene inhibits bone resorption is associated with the recruitment and differentiation of osteoclasts prior to inhibition, and this inhibition can be indirectly regulated by reducing the response of osteoblasts to PTH.
Epilin sealant is similar to estrogen in the treatment of osteoporosis, but there is no change in serum gonadotropin, estrogen or prolactin levels in postmenopausal women treated with Epragen. To understand the possible interaction between Epsilon and estrogen receptors, the human pre-osteogenic cell line FLG29.1 and the human breast cancer cell line MCF7 were studied. Studies have found that estradiol and other steroid substances are not a substitute for [3H]-labeled Epilin seals for binding to FLG29.1 cells. Similarly, epilaplatin is not a substitute for [3H]-labeled estradiol in combination with MCF7 cells. After pre-incubation of the metabolite, the binding of estrogen to FLG29.1 cells is increased. Epileptatin and its metabolites did not cause expression of the FLG29.1 estrogen receptor-related gene, nor did it cause MCF7 effects on the information gene (CAT) and estrogen response components.
The above conclusions suggest that Epilin seals on osteoclast precursors rather than the regulation of estrogen receptor interactions. The problems of estrogen-like estrogen and the site of direct or indirect interaction with estrogen receptors are still controversial, and further research is needed at the molecular level.
The dose was 600 mg orally per day and administered in 3 divided doses. The adverse reactions were mainly gastrointestinal reactions, and the incidence rate was 10% to 16.1%. Very few patients have reversible leukopenia and return to normal after discontinuation.
9. Fluoride preparation Fluoride is a trace element necessary for bone and tooth growth and development. It has a special affinity for bone and replaces OH- on hydroxyapatite in bone. The formed fluoroapatite can antagonize the dissolution of osteoclasts. Bone action, and stimulate the activity of osteoblasts, promote bone formation, especially increase the formation of cancellous bone. When using fluoride, sufficient calcium must be used to convert new bone into mature bone. Detlex chewable tablets made of monofluorophosphate glutamine and calcium (5mg of fluorine-containing element and 150mg of calcium) are currently used in clinical, 3~4 tablets/d, orally, with digestive tract irritation reaction.
10. Parathyroid hormone (PTH) Subcutaneous injection of PTH in small doses has an osteogenesis effect in animal experiments, which can increase bone mass and improve anti-fracture ability. At present, there are few clinical application data, and further clinical observation is needed.
prevention
After menopause, with increasing age, bone density will gradually decrease, and the risk of osteoporosis and the risk of fracture will increase dramatically. The primary goal of prevention is to control the risk factors for osteoporosis throughout the life of a woman.
1. High-risk factors for avoiding osteoporosis from youth to old age These factors include smoking, alcoholism, sedentary lifestyle, anorexia and taking certain drugs (such as corticosteroids, heparin and certain anti-epileptic drugs). Should pay attention to outdoor activities, sunshine, nutrition, moderate weight-bearing exercise and prevent falls.
2. Pay attention to the supplement of calcium in youth. This method combined with regular and moderate exercise can give women a better peak bone mass.
3. Prevention of estrogen loss after menopause The effect of using hormone replacement therapy to prevent osteoporosis in the first 5 to 10 years after menopause is positive. However, because hormone replacement therapy has its indications and contraindications, it should be safe to use it under the supervision of a doctor.
4. Calcium supplementation and vitamin D in the elderly can partially prevent bone loss and osteoporotic fracture, but if combined with anti-bone resorption drugs (estrogen, calcitonin bisphosphate, etc.) will play a significant treatment effect. Although some risk factors such as early menopause and family history of osteoporosis cannot be changed, the above interventions can indeed benefit high-risk groups and reduce the incidence of osteoporosis and fractures.
5. Preventing falls in the elderly It has been reported that about one-third of the elderly aged 65 or older fall down each year, and half of them fall again in a healthy search. About 10 times in 10 falls caused serious injuries, such as pelvic fractures, fractures in other parts, subdural hematoma, severe soft tissue damage in other areas, and head injuries. Elderly patients with osteoporotic fractures are more difficult to treat, such as prolonged bed rest, slow blood flow, poor secretion of lung and trachea, and cardiovascular disease and lung infection, which will increase mortality in elderly patients. Therefore, preventing the elderly from falling and avoiding the occurrence of fractures can effectively improve the quality of life of the elderly. Factors associated with falls include arthritis; depression; static homeostasis (orthostasis); cognitive function, visual balance, gait or muscle strength disorders; use of multiple drugs. Drugs associated with increased risk of falling fall are serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, chlordiazepoxide, anticonvulsants, and some antiarrhythmic drugs. The doctor should know if the patient has a history of falling and identify the risk factors that cause the fall and avoid it. Targeted recommendations should be made to patients after assessment of risk factors at home. The most recommended measures are to remove loose carpets and use safer shoes (suitable shoes that fit the foot, low heel, and thin bottom). ), use a non-slip bath mat, use lighting at night and add railings to the stairs. These effective measures can reduce the risk of falling down by the elderly by about 20%. The balance and gait training under the guidance of professionals and the exercise to enhance muscle strength, the gradual reduction and discontinuation of psychotropic substances are also associated with a decline in the incidence of falls. For patients with eye disease, syncope, and arrhythmia, they should go to the ophthalmology department and the cardiologist to find out the cause-specific treatment to prevent the occurrence of falls.
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