Osteoporosis is currently considered to be a disease phenomenon characterized by a decrease in bone mass, damage to the microstructure of the bone, and an increase in the brittleness of the bone, which leads to an increased risk of fracture. When these phenomena are present and the patient has certain clinical symptoms caused by osteoporosis, such as low back pain, it is called osteoporosis.
I. Classification
Osteoporosis is divided into three main categories.
The first category is primary osteoporosis, which is divided into two types, namely type I (postmenopausal osteoporosis) and type II (senile osteoporosis). This is a “physiological” degenerative lesion that occurs with aging or after menopause in women, and is one of the most common diseases in the middle-aged and elderly population and the current focus of prevention and treatment.
The second category is secondary osteoporosis, which is induced by other diseases or drugs, and when the cause is eliminated, osteoporosis can be significantly improved.
The third category is idiopathic osteoporosis, which commonly occurs in adolescents or adults between the ages of 8 and 14. This group of patients has a family history of osteoporosis and is more common in women than men. Some people also include osteoporosis that occurs in women during pregnancy and lactation in the scope of idiopathic osteoporosis.
Second, the onset
According to the statistics of some provinces and cities in China, the prevalence of osteoporosis in people over 60 years old is about 59.89%. The annual incidence of fracture complicated by osteoporosis is about 9.6%, and the trend is increasing year by year.
III. Etiology
(A) Postmenopausal and senile osteoporosis
(B) hereditary osteoporosis
1, osteogenesis imperfecta
2.Homocystinuria
(C) endocrine disorders caused by osteoporosis
1, hypogonadism
2, hyperthyroidism
3.Hyperparathyroidism
4. Hyperadrenocorticism
(D) Diet-related osteoporosis
1. Calcium deficiency
2. Deficiency of vitamin D
3.Deficiency of vitamin C
4, chronic alcoholism
(E) Drug-induced osteoporosis
1.Long-term use of heparin
2.Long-term application of aminoglutethimide
(F) Disuse osteoporosis
(vii) other diseases caused by osteoporosis
1, various chronic diseases
2, a variety of intramedullary tumors multiple myeloma lymphoma and leukemia
(H) Idiopathic osteoporosis
1, idiopathic juvenile osteoporosis
2, idiopathic adult osteoporosis
IV. Clinical manifestations
(a) pain primary osteoporosis is the most common symptom, low back pain is common in 70%-80% of patients with pain pain spread along the spine to both sides pain when lying down or sitting, reduce the pain when upright posterior extension or prolonged standing and sitting pain increased daytime pain light night and early morning when waking up increased bending muscle movement, coughing and bowel movement aggravated general bone loss of 12% or more bone pain can occur, elderly In osteoporosis the number of vertebral trabeculae atrophy decreases vertebral compression deformation spinal forward flexion lumbar rash muscle.
In order to correct the forward flexion of the spine doubled contraction muscle fatigue or even spasm produces pain new thoracolumbar compression fracture can also produce acute pain corresponding parts of the spinal spinous process can have strong pressure pain and percussion pain generally 2-3 weeks later can gradually reduce some patients can be chronic low back pain if compression of the corresponding spinal nerve can produce extremity radiating pain double lower extremity sensorimotor disorders intercostal neuralgia retrosternal pain similar to angina pectoris can also appear on If the spinal cord is compressed, the cauda equina may also affect the function of the bladder and rectum.
(b) Shortening of body length hunchback mostly occurs after pain and the anterior part of the vertebrae of the spine is almost mostly composed of cancellous bone and this part is the pillar of the body with high weight, especially the 1112th thoracic vertebrae and the 3rd lumbar vertebrae are easily compressed and deformed so that the forward dorsal curvature of the spine increases to form a hunchback as the age of osteoporosis increases the curvature of the hunchback increases resulting in significant knee contracture. cm or so in the elderly when osteoporosis vertebral compression per vertebral body shortened by about 2mm body length shortened by an average of 3-6cm
(iii) Fracture is the most common and serious complication of degenerative osteoporosis
(iv) decreased respiratory function thoracolumbar compression fractures backbend thoracic deformity can significantly reduce lung capacity and maximum ventilation patients often have chest tightness shortness of breath dyspnea and other symptoms
(E) Bone densitometry
Diagnosis of degenerative osteoporosis needs to rely on a comprehensive analysis of clinical manifestations, bone mass measurement, X-ray films and indicators of bone conversion biochemistry.
V. Auxiliary examinations
1, biochemical examination: the measurement of blood and urine minerals and certain biochemical indicators can help determine the state of bone metabolism and the speed of bone renewal rate, which is important for the differential diagnosis of osteoporosis.
(1) Bone formation index.
(2)Bone resorption indexes.
1)Urinary hydroxyproline.
2)Urinary hydroxylysine glycoside.
3)Plasma anti-tartrate phosphatase.
4)Urinary collagen pyridine cross-linking (PYr) or type I collagen cross-linking N-terminal peptide (NTX).
(3) blood, urine bone mineral composition detection: 1) serum total calcium. 2) serum inorganic phosphorus. 3) serum magnesium. 4) urine calcium, phosphorus, magnesium determination.
2.X-ray examination:, X-ray is still a more popular method to check osteoporosis.
3, bone mineral density measurement.
(1) single photon absorptiometry (SPA).
(2) Dual-energy X-ray absorptiometry (DEXA).
(3)Quantitative CT (QCT).
(4)Ultrasound (USA).
VI. Treatment
Since osteoporosis is caused by a group of diseases with different causes and individual differences, etiological treatment and symptomatic treatment should be taken, both of which are important.
(A) Drugs Different drugs or a combination of applications are selected according to different causes. For example, for osteoporosis caused by aging or long-term use of adrenocorticosteroids, a high-protein diet, vitamin D and calcium salt supplementation, trial of sex hormones, and encouragement of moderate activity can be used.
1. Periodic application of sex hormones: Female hormones can reduce bone resorption. Oral hexestrol (diethyl stilb estrol) or 17βestradiol (17βestradiol) 0.5~1.0mg daily can be used, and then stop for 1 week after 4 weeks, sometimes progesterone can be added in the last 5 days. In recent years, pegylated estriol (Nylestriol) has been used more often, with 2 mg every 2 weeks and medroxyprogesterone acetate (Medroxyprogesterone.Acetate) for 5 to 6 days a month, 4 mg daily. use with caution in cases of lobular hyperplasia.
Estrogen can also be used in combination with protein-synthesizing hormones such as testosterone propionate. It may reduce side effects and may increase the effect. The latter is administered intramuscularly at 25 mg every 3 to 5 days, and masculinizing side effects are noted in female patients. Sex hormone therapy is more effective in postmenopausal osteoporosis and can prevent the progression of the disease, and is also effective in preventing the occurrence of postmenopausal osteoporosis. Regular gynecological and breast examinations should be performed during estrogen use, and attention should be paid to withdrawal bleeding.
2, calcium: the trade-off in the treatment of osteoporosis depends mainly on the cause, malnutrition or gastrointestinal lesions caused by calcium supplementation is more significant, and commonly used calcium lactate or calcium gluconate, the former 2 to 4g per day, or calcium glycerophosphate 6 grams per day.
3, vitamin D: can promote the absorption of calcium in the intestine, resulting in positive calcium balance, the general dosage of 2000 to 5000 international units per day. Also can take 1, 25 (OH2) D, 0.5 μg daily. application of vitamin D and calcium should be noted when the blood calcium hypercalcemia.
4, sodium fluoride: fluorine can be combined with hydroxyapatite crystals, which has the effect of stabilizing the crystal structure of bone salt and inhibiting bone resorption, so it has a therapeutic effect on this disease. Generally 40-60mg daily, the course of treatment can be up to 1 year, if necessary, combined with calcium and vitamin D treatment. Excessive dose can cause excessive calcification of bone.
5, calcitonin: calcitonin to reduce bone resorption, stimulate the role of osteoblasts, available salmon or eel calcitonin 20 ~ 50 units every 2-3 days subcutaneous injection, for high conversion rate osteoporosis patients (serum osteocalcin levels and urinary hydroxyproline excretion increased) the effect is better.
(B) Nutrition and physical therapy Since both bone protein and calcium salts are lost in osteoporosis, proper supplementation of dietary protein, calcium salts and various vitamins, especially D and C, can be helpful. Physical activity should be encouraged because it can stimulate osteoblast activity, which is beneficial to bone formation. If temporary bed rest is required due to bone pain, active or passive exercise of the limbs and abdominal and back muscles should also be encouraged in bed as much as possible to prevent the occurrence of disuse muscle atrophy and further aggravation of osteoporosis. After the pain improves, one should strive to get up and walk for exercise as soon as possible.
(C) Etiological treatment If there is a clear cause, such as hyperadrenocorticism or primary hyperparathyroidism, the hyperplastic or tumor tissue of the gland should be removed first, and then treated with the appropriate combination of the above methods.
Since the onset of osteoporosis is slow, it usually takes more than several years before positive findings appear on X-ray, so after treatment, although there is a certain amount of anabolic bone tissue, X-ray findings also require a long course of treatment before showing improvement.
VII. Current status and outlook
(A) Coupled regulation studies of bone metabolism
Mature bone tissue mainly relies on bone reconstruction to carry out a continuous and cyclic process of osteolysis and osteogenesis, and the orderly coupled regulation of this process is the basis for maintaining normal bone mass and physiological functions of bone. A number of hormones, cytokines and growth factors are interrelated and mutually regulated to control the level of bone metabolism (bone metabolic rate) and the balance of osteoclastic/osteogenic activity in order to maintain normal bone mass and bone biological quality. Bone reconstruction is characterized by:
(1) It occurs on all bone surfaces and lining surfaces of all bone tissues;
(2) Unlike bone architecture, bone reconstruction is non-directional, but there is a cyclic cycle (bone reconstruction cycle);
(3) Bone formation and resorption are performed by the cells of bone, but the site of action is mainly in the bone matrix;
(4) The osteogenesis and osteolysis processes of bone reconstruction are interdependent and mutually influenced and regulated, and it can be said that there is no osteogenesis without osteolysis, and vice versa.
There are many factors regulating the bone metabolic coupling process, which can be usually divided into the following types and levels.
1. Circulating hormones (overall level): mainly parathyroid hormone (PTH), calcitonin and 1,25-(OH) 2D3; growth hormone (GH) may act locally mainly through insulin-like growth factor (IGF)-Ⅰ.
2. Genetic determinants of bone mass (genetic-molecular level): Since the recognition of the relationship between vitamin D receptor gene variants and bone mass, it is now believed that about 75% of bone mass is determined by genetic factors, which may also include the genotypes of estradiol receptor, calcitonin receptor, β3 adrenergic receptor, glucocorticoid receptor, as well as transforming growth factor (TGF)-β1, interleukin (IL)-6, and IL-1 receptor antagonist. The genetic polymorphisms of transforming growth factor (TGF)-β1, interleukin (IL)-6, IL-1 receptor antagonist, PTH, IGF-Ⅰ, type I collagen α1 chain, osteocalcin and so on.
3. Paracrine regulation (tissue-cell level): In a particular individual, since the above-mentioned circulating hormone levels and gene types are basically fixed, the factors that determine individual bone metabolism levels and regulate bone metabolic coupling are mainly derived from cytokines and paracrine hormones. The important regulators of bone metabolism coupling are IL-1α, IL-1β, tumor necrosis factor (TNF)-α, TNF-β, IL-6, granulocyte macrophage colony-stimulating factor (GM-CSF), prostaglandins (PGs), endothelial growth factor (EGF), IGF, bone forming protein (BMP), TGF, platelet-derived growth factor (PDGF), etc. Osteoprotegerin (OPG) and its ligand (OPGL) and NF-κB receptor activator (RAN K) are a group of cytokines that have significant regulatory effects on bone metabolism.
(B) Cellular and animal models of osteoporosis
At present, the main models used for osteoporosis research are cellular models and animal models. The current research materials are mainly osteoblasts, which are derived from animals or humans. The isolated and purified normal human osteoblasts cannot be passed on in the in vitro culture system, which limits the timeliness of the study. Moreover, due to the different sources of the obtained cells, it is impossible to construct a model of cultured cells and an index system for evaluation. On the other hand, it is very difficult to establish osteoclast strains. In recent years, various osteoclast culture techniques have been developed and established, and inducing agents have been used to induce osteoclast predecessor cells in bone marrow fluid to differentiate into osteoclasts.
However, both osteoblast and osteoclast culture techniques have the following drawbacks:
(1) In a single cell culture system, since there is no regulatory factor from another cell, only certain cytokines of that cell under in vitro conditions are expressed, and the coupling factor secreted by the cultured cell has no target cell effect, the experimental results can hardly reflect the nature of bone tissue metabolism in vivo;
(2) The absence of bone tissue in the culture system makes it difficult to reflect the effect of cells on bone matrix and bone minerals (which account for more than 90% of bone tissue).
(3) Research on the evaluation index of osteoporosis and anti-osteoporosis drugs
At present, the diagnosis of OP mainly includes BMD measurement and biochemical markers of bone metabolism in blood and urine. However, the following drawbacks of BMD measurement should be overcome in the application:
(1) The equipment is expensive and difficult to be widely used;
(2) Early detection of OP patients is not possible: the minimum change in BMD measured by the most sensitive dual-energy X-ray absorptiometry (DEXA) is more than 6 months later than bone biochemical markers and more than 3 months later than bone morphometric markers, so the sensitivity of BMD for monitoring changes in disease and drug efficacy needs to be further improved;
(3) The diagnostic criteria for OP are based on the peak bone mineral density (PBM) in the normal population (PBM – 2.5 standard deviations), which varies greatly in humans and is too strict for those with high original PBM and too loose for those with low original PBM;
(4) BMD only reflects the amount of bone mineral content, but not the changes in the bone matrix, which accounts for more than 90% of the bone;
(5) The fundamental task of OP prevention and treatment is to reduce the incidence of fracture and improve the fracture resistance of bone (i.e., the biological quality of bone), and BMD, as the current golden index of OP diagnosis, still has the shortcoming of not reflecting the biological quality of bone.
(D) The development and application of anti-osteoporosis drugs
At present, the procedure of developing anti-OP drugs at home and abroad is divided into two major steps. The first step is to conduct animal experiments with the drugs to be developed to explore the drug efficacy, pharmacokinetics, pharmacology, acute and chronic toxic side effects, etc. The most widely used is the OVX animal model, but its specificity and sensitivity are still not high in the evaluation of efficacy indicators. The second step is clinical trials, such as animal experiments to prove the effectiveness of drugs, and after the approval of the relevant state departments, can enter clinical trials. However, this traditional method of drug screening and drug development has lagged behind the situation and needs to be improved.