Primary osteoporosis
Osteoporosis (OP) is a systemic bone disease characterized by low bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture (World Health Organization, WHO). 2001, the National Institutes of Health (NIH) proposed that osteoporosis is a disease of the osteoiliac system characterized by decreased bone strength and increased risk of fracture. Bone strength reflects two major aspects of the skeleton, namely bone mineral density and bone mass. The disease can occur in different genders and at any age, but is more common in postmenopausal women and older men. Osteoporosis is divided into two major categories: primary and secondary. Primary osteoporosis is divided into postmenopausal osteoporosis (type I), senile osteoporosis (type II), and idiopathic osteoporosis (including adolescent type). Postmenopausal osteoporosis generally occurs within 5 to 10 years after menopause in women; senile osteoporosis generally refers to osteoporosis occurring after the age of 70 years in the elderly: and idiopathic osteoporosis mainly occurs in adolescents, the cause of which is still unknown.
Osteoporosis is a health problem with well-defined pathophysiological, psychosocial and economic consequences. A serious consequence of osteoporosis is the occurrence of osteoporotic fractures (fragility fractures), which are fractures that can occur with minor trauma or during daily activities due to decreased bone strength. Osteoporotic fractures greatly increase disability and mortality in the elderly.
I. Risk factors
1. Uncontrollable factors: ethnicity (Caucasians and yellow people have a higher risk of osteoporosis than blacks), old age, female menopause, maternal family history.
2, controllable factors: low body weight, low sex hormones, smoking, excessive alcohol consumption, coffee and carbonated beverages, etc., lack of physical activity, dietary calcium and/or vitamin D deficiency (low light exposure or low intake), diseases affecting bone metabolism and application of drugs affecting bone metabolism (see secondary osteoporosis section).
II. Clinical manifestations
Pain, crestal deformation and the occurrence of fragility fractures are the most typical clinical manifestations of osteoporosis. However, many patients with osteoporosis often have no obvious conscious symptoms in the early stage, and are often found to have osteoporotic changes only after the fracture occurs by X-ray or bone density examination.
Pain: Patients may have low back pain or peripheral pain, and the pain may increase when the load increases or the activity is limited, and in severe cases, there are difficulties in turning, sitting and walking.
2. Crest deformation: Severe osteoporosis may lead to height shortening and hunchback. Vertebral compression fracture can lead to thoracic deformation, abdominal compression and affect cardiopulmonary function, etc.
3. Fracture: A fracture after mild trauma or daily activities is a fragility fracture. The common sites where fragility fractures occur are the thoracic and lumbar spine, hip, radius, distal ulna and proximal humerus. Fractures can also occur at other sites. After a fragility fracture, the risk of a second fracture increases significantly.
III. Diagnosis
The common clinical indicators used to diagnose osteoporosis are: the occurrence of a fragility fracture and/or low bone density, and there is a lack of clinical means to directly measure bone strength.
1, fragility fracture: is the ultimate manifestation of bone strength decline, there has been a fragility fracture clinically can be diagnosed osteoporosis.
Bone mineral density (BMD) is the best quantitative indicator for diagnosing osteoporosis, predicting the risk of osteoporotic fracture, monitoring the natural course of the disease, and evaluating the efficacy of drug interventions. BMD reflects only about 70% of bone strength. The risk of fracture is associated with low BMD, and the risk of fracture is increased when accompanied by other risk factors.
(1) Bone density measurement methods: Dual-energy X-ray absorptiometry (DXA) is currently the internationally recognized method of bone density examination, and its measured value is used as the gold standard for the diagnosis of osteoporosis. Other bone density examination methods such as various single photon (SPA), single energy X-ray (SXA), quantitative computed tomography (QCT,) etc. can also be used for reference in the diagnosis of osteoporosis according to specific conditions.
(2) Diagnostic criteria: It is recommended to refer to the diagnostic criteria recommended by the World Health Organization (WHO). Based on DXA measurement: Bone density value less than 1 standard deviation below the peak bone value of healthy adults of the same sex and race is normal; a decrease of 1 to 2.5 standard deviations is low bone mass (bone loss); a decrease equal to and greater than 2.5 standard deviations is osteoporosis; a decrease in bone density in line with the diagnostic criteria for osteoporosis accompanied by one or more fractures is severe osteoporosis. Nowadays, it is also usually expressed by T-Score (T-value), i.e. T-value ≥ -1.0 is normal, -2.5
(3) Clinical indications for bone densitometry.
①Females over 65 years of age and males over 70 years of age without other risk factors for osteoporosis;
②Females under 65 years of age and males under 70 years of age with one or more risk factors for osteoporosis;
③Adults of both genders with a history of fragility fracture or (and) a family history of fragility fracture;
④Adults of both sexes with low sex hormone levels due to various causes;
(⑤) Those who have osteoporotic changes on X-ray;
(6) Those who are being monitored for the efficacy of osteoporosis treatment;
⑦History of diseases and drugs that affect bone mineral metabolism (refer to the relevant section).
3.Other assessment (screening) methods of osteoporosis
(1) Quantitative ultrasonography (QUS): It also has a reference value for the diagnosis of osteoporosis, and there are no uniform diagnostic criteria. It has similar effect to DXA in predicting the risk of fracture, and is economical and convenient, more suitable for screening, especially for pregnant women and children. However, monitoring response to drug therapy is not yet a substitute for direct measurement of bone mass (bone mineral content) in the lumbar spine and hip.
(2) X-ray radiography: the morphological structure of bone tissue can be observed, which is a better method for qualitative and localized diagnosis of various fractures caused by osteoporosis, and also a method to differentiate osteoporosis from other diseases. Commonly used radiographic sites include vertebrae, hip, wrist, metacarpal, heel and tubular bones. Due to various technical factors, the sensitivity and accuracy of diagnosing osteoporosis by X-ray radiography is low, and only when the bone volume decreases by 30% can it be revealed in the X-ray, so it is not significant for early diagnosis. Since patients with osteoporosis often lack obvious symptoms, many people are only discovered during physical examinations or radiographs for other purposes, such as vertebral fractures. If back pain worsens and height shortens significantly, vertebral X-ray should be performed.
4.Laboratory tests
(1) Routine blood and urine tests, liver and kidney functions, blood glucose, calcium, phosphorus, alkaline phosphatase, sex hormones, 25(OH)D and parathyroid hormone can be selected according to the need of differential diagnosis.
(2) According to the needs of disease monitoring, drug selection and efficacy observation and differential diagnosis, the following indicators of bone metabolism and bone transformation (including bone formation and bone resorption indicators) can be selected respectively by the conditional units. These indicators are useful for the typing of bone turnover, assessment of the rate of bone loss and the risk of fracture in elderly women, and the selection and evaluation of disease progression and interventions. Common clinical indicators: serum calcium, phosphorus, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. Bone formation indicators: serum alkaline phosphatase (ALP), osteocalcin (OC), bone-derived alkaline phosphatase (BALP), type l procollagen C-terminal peptide (PICP), N-terminal peptide (PINP); bone resorption indicators: urinary calcium/creatinine ratio at 2 hours fasting, or plasma antitartaric acid Acid phosphatase (TPACP) and l-type collagen C-terminal peptide (S-CTX), urinary pyridinoline (Pyr) and deoxypyridinoline (d-Pyr), urinary type I collagen C-terminal peptide (U-CTX) and N-terminal peptide (U-NTX), etc.
IV. Prevention and treatment
Once osteoporotic fracture occurs, the quality of life decreases and various complications occur, which can be disabling or fatal, so prevention of osteoporosis is more realistic and important than treatment. Moreover, osteoporosis can be prevented. Primary prevention of osteoporosis is for those who have not had fractures but have risk factors for osteoporosis.
1. Basic measures.
(1) Lifestyle modification: a balanced diet rich in calcium, low in salt and moderate in protein. Pay attention to appropriate outdoor activities, physical exercise and rehabilitation that contribute to bone health. Avoid smoking, alcohol abuse and careful use of drugs that affect bone metabolism, etc. Take various measures to prevent falls: for example, pay attention to the presence of diseases and medications that increase the risk of falls, and strengthen protective measures for yourself and the environment (including various joint protectors), etc.
(2) Basic supplements for bone health.
①Calcium: The recommended daily intake of calcium for adults is 800 mg (elemental calcium amount), which is the appropriate dose to obtain the ideal bone peak and maintain bone health. Calcium intake can slow down the loss of bone and improve bone mineralization. When used for the treatment of osteoporosis, it should be used in combination with other drugs. There is insufficient evidence that calcium supplementation alone can replace other anti-osteoporosis drug therapy. Calcium selection should take into account its safety and efficacy.
②Vitamin D: facilitates the absorption of calcium in the gastrointestinal tract. Vitamin D deficiency can lead to secondary hyperparathyroidism, which increases bone resorption and thus causes or exacerbates osteoporosis. The recommended dose for adults is 200 units (5ug)/d. Elderly people often have vitamin D deficiency due to lack of sunlight and impaired intake and absorption, so the recommended dose is 400 to 800 IU (10 to 20ug)/d. Some studies have shown that vitamin D supplementation increases muscle strength and balance in the elderly, thus reducing the risk of falls and thus the risk of fractures. Vitamin D should be used in combination with other drugs when used for the treatment of osteoporosis. Clinical application should pay attention to individual differences and safety, regularly monitor blood and urine calcium, and adjust the dose as appropriate.
2.Medication: Indications: Osteoporosis (T≤-2.5) or fragility fracture; or bone loss (-2.5)
(1) Anti-bone resorption drugs.
(1) Bisphosphonates: effectively inhibit osteoclast activity and reduce bone conversion. Evidence from a large sample of randomized double-blind controlled clinical trials shows that alendronate (Fosamax or Gubang) can significantly increase bone density in the lumbar spine and hip and significantly reduce the risk of fracture in the vertebrae and hip. Alendronate preparations are available in China. Other bisphosphonates such as hydroxyethyl bisphosphonate (Etidronate) can also be applied exploratively (cyclic dosing). The application should be based on the characteristics of each preparation, and the correct method of administration should be strictly followed (e.g. alendronate should be taken in the morning on an empty stomach with 200 ml of water, and not lying down and eating within 30 minutes after taking the drug). Therefore, it should be used with caution in patients with esophagitis, active gastric and duodenal ulcers, and reflux esophagitis. The latter is more convenient to take, less irritating to the digestive tract, effective and safe, and thus has better compliance.
Calcitonin: It can inhibit the biological activity of osteoclasts and reduce the number of osteoclasts. It can prevent bone loss and increase bone mass. There are two types of calcitonin analogs currently in clinical use: salmon calcitonin and eel calcitonin analogs. Evidence from randomized double-blind controlled clinical trial studies has shown that 200 IU of synthetic salmon calcitonin nasal spray (migestrol) daily reduces the incidence of vertebral fractures in patients with osteoporosis. Another outstanding feature of calcitonin analogs is their ability to significantly relieve bone pain, which is effective in chronic pain due to osteoporotic fractures or skeletal deformities, as well as bone pain caused by diseases such as bone tumors, making them more suitable for osteoporotic patients with painful symptoms. The course of application of calcitonin-based preparations depends on the condition and other conditions of the patient. In general, the application dose is 50 IU/time of salmon calcitonin, subcutaneously or intramuscularly, 2 to 5 times a week depending on the condition, 200 IU/day of salmon calcitonin nasal spray; 20 IU/week of eel calcitonin, intramuscularly. Application of calcitonin, a small number of patients may have adverse reactions such as facial flushing, nausea, and occasional allergic phenomena.
(iii) Selective estrogen receptor modulators (SERMs): effectively inhibit osteoclast activity and reduce bone conversion to premenopausal levels in women. Evidence from a large sample of randomized double-blind controlled clinical trial studies indicates that one tablet of raloxifene (60 mg) daily stops bone loss, increases bone mineral density, and significantly reduces the incidence of vertebral fractures, making it an effective drug for the prevention and treatment of postmenopausal osteoporosis. It is only used for female patients and is characterized by selective action on estrogen target organs, with no adverse effects on the breast and endometrium. It reduces the incidence of estrogen receptor-positive invasive breast cancer and does not increase the risk of endometrial hyperplasia or endometrial cancer. It has a modulating effect on blood lipids. A small number of patients may experience hot flashes and lower extremity cramps while taking the drug. It is temporarily contraindicated in perimenopausal women with severe hot flashes. Foreign studies have shown that this drug mildly increases the risk of venous embolism, so it is prohibited for people with a history of venous embolism and a tendency to thrombosis, such as during prolonged bed rest and sedentary periods.
Estrogens: These drugs should only be used for female patients. Estrogenic drugs can inhibit bone turnover and prevent bone loss. Clinical studies have well demonstrated that estrogen or estrogen-progestin supplementation therapy (ERT or HRT) can reduce the risk of osteoporotic fractures and is an effective measure to prevent and treat postmenopausal osteoporosis. Based on a comprehensive assessment of the pros and cons of hormone supplementation therapy, it is recommended that hormone supplementation therapy follow the following principles: Indications: Women with menopausal symptoms (hot flashes, sweating, etc.) and/or osteoporosis and/or risk factors for osteoporosis, especially advocating greater benefit and less risk when started early in menopause. Contraindications: Estrogen-dependent tumors (breast cancer, endometrial cancer), thrombophilia, unexplained vaginal bleeding, and active liver disease and connective tissue disease are absolute contraindications. Use with caution in cases of uterine fibroids, endometriosis, family history of breast cancer, gallbladder disease and pituitary lactinoma. Estrogen should be used in conjunction with appropriate doses of progestin preparations to counteract the stimulation of the endometrium by estrogen in women with a hysterectomy, and only estrogen without progestin should be used in women who have undergone hysterectomy. The regimen, dose, preparation selection and duration of treatment of hormone therapy should be individualized according to the patient’s condition. Apply the lowest effective dose. Adhere to regular follow-up and safety monitoring (especially of the breast and uterus). Whether to continue the drug should be evaluated annually for pros and cons according to the characteristics of each woman.
(2) Drugs to promote bone formation: parathyroid hormone (PTH): Randomized double-blind controlled trials have confirmed that small doses of rhPTH (1-34) have a role in promoting bone formation and are effective in treating severe postmenopausal osteoporosis, increasing bone density and reducing the risk of vertebral and non-vertebral fractures, and are therefore indicated for patients with severe osteoporosis. It must be applied under the guidance of a medical professional. The duration of treatment should not exceed 2 years. The general dose is 20ug/d, injected intramuscularly. Blood calcium levels should be monitored during administration to prevent the occurrence of hypercalcemia.
(3) Other drugs.
① Active vitamin D: appropriate doses of active vitamin D can promote bone formation and mineralization and inhibit bone resorption. Some studies have shown that active vitamin D is beneficial in increasing bone density, increasing muscle strength and balance in the elderly, reducing the risk of falls, and thus reducing the risk of fractures. Active vitamin D is more appropriate for the elderly, and includes both 1α-hydroxyvitamin D (α-osteol) and 1,25-bishydroxyvitamin D (osteotriol), the former being effective when liver function is normal and the latter not affected by liver or kidney function. They should be used under the guidance of a physician and blood and urine calcium levels should be monitored regularly. Osteotriol dose
The amount is 0.25-0.5ug/d; α-osteotriol is 0.25-0.75 ug/d. In the treatment of osteoporosis, it can be used in combination with other anti-osteoporosis drugs. ②Chinese medicine: clinically proven effective Chinese medicine such as strong bone capsule can also be used according to the condition.
③Phytoestrogens: There is no strong clinical evidence that the current phytoestrogen preparations are effective in the treatment of osteoporosis.