I. Overview
(A) Definition and classification
Osteoporosis (OP) is a systemic bone disease characterized by low bone mass, destruction of bone microarchitecture, resulting in increased bone fragility and susceptibility to fracture (WHO). In 2001, the National Institutes of Health (NIH) proposed that osteoporosis is a disease of the skeletal system characterized by decreased bone strength and increased risk of fracture, with bone strength reflecting two major aspects of bone, namely bone mineral density and bone mass.
The disease can occur in different genders and at any age, but is more commonly seen in postmenopausal women and older men. Osteoporosis is divided into two main categories: primary and secondary. Primary osteoporosis is subdivided into three types: postmenopausal osteoporosis (type I), senile osteoporosis (type II), and idiopathic osteoporosis (including adolescent type). Postmenopausal osteoporosis generally occurs within 5-10 years after menopause; senile osteoporosis generally refers to osteoporosis that occurs after the age of 70 years; secondary osteoporosis refers to osteoporosis caused by any disease or drug that affects bone metabolism; and idiopathic osteoporosis mainly occurs in adolescents, the cause of which is unknown.
(ii) Epidemiology
Osteoporosis is a degenerative disease with an increased risk of developing with age. With the increase of human life expectancy and the aging of society, osteoporosis has become an important human health problem. A large-scale national epidemiological survey from 2003 to 2006 showed that the total prevalence of osteoporosis based on vertebral and femoral neck bone density values over the age of 50 was 20.7% for women and 14.4% for men. The prevalence of osteoporosis is significantly higher among people over 60 years of age, especially among women. According to the survey, it is estimated that in 2006, about 69.44 million people over 50 years old suffered from osteoporosis, and about 210 million people had low bone mass.
It is estimated that the hip fracture rate of Chinese people will also increase significantly in the coming decades. The lifetime risk of osteoporotic fracture in women (40%) is higher than that of breast, endometrial, and ovarian cancers combined.
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. Common sites for osteoporotic fractures are the spine, hip, and distal forearm. Osteoporotic fractures are very dangerous and lead to increased disability and mortality. For example, within 1 year after a hip fracture, 20% of people die from various complications, while about 50% of survivors are disabled and cannot take care of themselves, and the quality of life is significantly reduced. Moreover, the treatment and care of osteoporosis and its fractures require huge human and material resources and are expensive, causing a heavy family, social and economic burden.
It is worth emphasizing that osteoporotic fractures are preventable and treatable. Early prevention can prevent osteoporosis and its fractures. Even if a fracture has occurred, the risk of re-fracture can still be effectively reduced with appropriate and reasonable treatment. Therefore, it is important to popularize the knowledge of osteoporosis, to achieve early diagnosis, to predict the risk of fracture in time and to take standardized prevention and treatment measures.
II. Clinical manifestations
Pain, spinal deformation and fragility fractures are the most typical clinical manifestations of osteoporosis. However, many patients with osteoporosis often have no obvious symptoms in the early stage, and are often found to have osteoporosis only after the fracture occurs by X-ray or bone density examination.
Patients with pain may have low back pain or circumferential skeletal pain, increased pain or restricted movement when the load increases, and in severe cases, difficulty in turning over, sitting up and walking.
Spinal deformity osteoporosis can be severe with height shortening and hunchback, spinal deformity and limited extension. Compression fractures of the thoracic spine can lead to thoracic deformity and affect cardiopulmonary function. Fractures of the lumbar spine may alter the abdominal anatomy, causing constipation, abdominal pain, bloating, decreased appetite, and a feeling of premature fullness.
Fragility fractures are low-energy or non-violent fractures, such as those that occur as a result of daily activities, are fragility fractures. Common sites are the thoracic and lumbar spine, the hip, the distal radius and ulna, and the proximal humerus. Fractures can also occur at other sites. After a fragility fracture has occurred, the risk of another fracture increases significantly.
III. Risk factors and risk assessment of osteoporosis
(A) Risk factors for osteoporosis
1. Intrinsic factors: ethnicity (the risk of osteoporosis is higher in Caucasians and Caucasians than in Blacks), old age, female menopause, maternal family history.
2. Non-inherent factors: low body weight, low sex hormones, smoking, excessive alcohol consumption, excessive coffee consumption, lack of physical activity, nutritional imbalance in the diet, too much or not enough protein, high sodium diet, calcium and/or vitamin D deficiency (low light exposure or low intake), diseases affecting bone metabolism and application of drugs affecting bone metabolism.
(ii) Risk assessment of osteoporosis
There are many clinical methods to assess the risk of osteoporosis, and two simple assessment methods with high sensitivity and easy operation are recommended here as screening tools.
1. International Osteoporosis Foundation (IOM)
Osteoporosis 1-minute test questions
(1) Have you ever injured your bones due to a slight bump or fall?
(2) Have your parents ever had a hip fracture after a minor bump or fall?
(3) Do you regularly take hormonal drugs such as cortisone and prednisone for more than 3 months in a row?
(4) Has your height decreased by more than 3 cm from your youth?
(5) Do you regularly drink a lot of alcohol?
(6) Do you smoke more than 20 cigarettes a day?
(7) Do you often have diarrhea? (caused by gastrointestinal diseases or enteritis)
(8) Answer: Did you go through menopause before the age of 45?
(9) Answer: Have you ever had no menstruation for more than 12 months in a row? (Except during pregnancy)
(10) Men answered: Have you ever experienced impotence or lack of sexual desire?
As long as the answer to one of the questions is “yes”, it is positive.
2.Osteoporosis Self Assessment Tool for Asian (OSTA)
OSTA index = (weight – age) × 0.2
Risk level OSTA index
Low > -1
Medium -1 to -4
High < -4
(iii) Risk prediction of osteoporosis
The WHO recommends the application of the Fracture Risk Prediction Easy Tool (FRAX) for calculating the risk of hip fracture and any significant osteoporotic fracture in subjects over the next 10 years. The current fracture risk recommendation prediction tool, FRAX, is available at: www.shef.ac.uk/FRAX/1 Method of application of FRAX The calculation of this tool includes femoral neck bone density and clinical risk factors. In the absence of femoral neck BMD is can be replaced by total hip BMD, however, in this calculation method, BMD of non-hip sites is not recommended. In the absence of bone densitometry, FRAX also provides a calculation method using only body mass index (BMI) and clinical risk factors for assessment.
1. The common risk factors for fracture identified in FRAX are
Age: fracture risk increases with age Gender Low BMD Low BMI: ≤19 kg/m2.
History of previous fragility fractures, especially hip, distal ulnar radius and vertebral fractures;
Parental hip fracture treated with glucocorticoids: any dose, oral for 3 months or longer.
Smoking and excessive alcohol consumption combined with other diseases causing secondary osteoporosis in rheumatoid arthritis Because of the lack of systematic pharmacoeconomic studies in China, there is no treatment threshold calculated based on FRAX results in China. Clinically, reference can be made to information from other countries, such as the FRAX tool mentioned in the US guidelines calculates the probability of hip fracture ≥ 3% or the probability of any significant osteoporotic fracture occurring ≥ 20% are classified as patients at high risk for osteoporotic fracture.
2. Problems and limitations in the application of FRAX
(1) Application of the population not applicable to the population: clinically diagnosed osteoporosis, that is, bone mineral density (T value) below -2.5, or has occurred a fragility fracture, should have started treatment in a timely manner, without the need for FRAX assessment.
Applicable population: People who have not had a fracture and have low bone mass (T-value > 2.5), due to clinical difficulties in making treatment decisions, apply the FRAX tool to conveniently calculate the absolute risk of fracture for the individual and provide a basis for developing treatment strategies. The applicable population is men and women aged 40 to 90 years old, and individuals <40 and >90 years old are counted as 40 and 90 years old, respectively.
(D) Falls and their risk factors
1, environmental factors dark light road obstacles slippery road carpet loose bathroom lack of handrails.
2, health factors: age female arrhythmia poor vision should be acute incontinence previous history of falls upright hypotension mobility disorders drugs (sleep medications, anticonvulsants and drugs affecting the mind, etc.) sedentary lack of exercise depression mental and cognitive disorders anxiety and impulsiveness vitamin D deficiency [blood 25 hydroxyvitamin D < 30ng/mL (75nmol/L)] malnutrition.
3, neuromuscular factors poor balance muscle weakness hunchbacked sensory retardation.
4, fear of falling
IV. Diagnosis and differential diagnosis
The complete clinical diagnosis of osteoporosis should include two aspects: determining osteoporosis and excluding other diseases that affect bone metabolism.
(A) Diagnosis of osteoporosis
The general criteria used clinically to diagnose osteoporosis are the occurrence of fragility fractures and/or low bone mineral density. There is a lack of clinical means to directly measure bone strength; therefore, bone mineral density and bone mineral content measurements are objective quantitative indicators for the clinical diagnosis of osteoporosis and for evaluating the extent of the disease.
1. Fragility fracture refers to fractures occurring from non-trauma or minor trauma, which is a clear manifestation of decreased bone strength and the end result and comorbidity of osteoporosis. When a fragility fracture occurs, osteoporosis can be clinically diagnosed.
2. Diagnostic criteria (based on bone densitometry)
The occurrence of osteoporotic fracture is related to the decrease of bone strength, which is determined by bone density and bone mass. Bone density reflects about 70% of bone strength, and if low bone density is accompanied by other risk factors will increase the risk of fracture. Because there is no ideal method for direct measurement or assessment of bone strength, BMD measurement is used clinically as the best quantitative standard for diagnosing osteoporosis, predicting the risk of osteoporotic fracture, monitoring the natural course of disease, and evaluating the efficacy of pharmacological interventions.
BMD is the amount of bone per unit volume (bulk density) or per unit area (area density), both of which are measured in vivo by noninvasive techniques.
There are more methods of BMD and bone measurement, and the role of different methods in the diagnosis of osteoporosis, monitoring of the efficacy, and assessment of fracture risk varies. Clinical applications include dual-energy X-ray absorptiometry (DXA), peripheral dual-energy X-ray absorptiometry (pDXA), and quantitative computed tomography (QCT). Among them, DXA measurement is currently recognized as the gold standard for the diagnosis of osteoporosis by the international academic community.
[Diagnostic criteria based on bone densitometry].
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 mass of normal adults of the same sex and race is considered normal; a decrease of 1 to 2.5 standard deviations is considered low bone mass (reduced bone mass); a decrease equal to or greater than 2.5 standard deviations is considered osteoporosis. Severe osteoporosis is considered when the diagnostic criteria for osteoporosis are met and accompanied by one or more fractures.
Bone density is usually expressed as T-Score (T-value), T-value = (measured value – peak bone) / standard deviation of normal adult bone density.
Diagnostic T-score Normal > -1 Low bone mass -1 to -2.5 Osteoporosis < -2.5 T-score is used for BMD levels in postmenopausal women and men over 50 years of age. For children, premenopausal women and men under 50 years of age, BMD levels are recommended to be expressed as Z values.
Z value = (measured value – mean BMD value for the same age)/standard deviation of BMD for the same age [clinical indications for BMD measurement
Bone densitometry is recommended in accordance with any of the following.
1) Women over 65 years of age and men over 70 years of age, with or without other risk factors for osteoporosis
2) Under 65 years of age for women and under 70 years of age for men with one or more osteoporosis risk factors
3) Adults of both sexes with a history of fragility fracture or/and family history of fragility fracture
4) Adults of both sexes with low sex hormone levels from various causes.
5) those with pre-existing osteoporotic changes on x-ray radiographs
6) Those who are receiving osteoporosis treatment and are monitored for efficacy.
7) those with a history of disease affecting bone metabolism or use of drugs affecting bone metabolism.
8) those who have positive results in response to the IOF one-minute test questions
(9) OSTA results ≤ -1
(B) Differential diagnosis of osteoporosis and laboratory tests
1, the differential diagnosis of osteoporosis osteoporosis can be caused by a variety of etiologies. Before diagnosing primary osteoporosis, attention must be paid to the exclusion of other diseases affecting bone metabolism to avoid omission and misdiagnosis. Diseases that need to be differentiated include endocrine diseases affecting bone metabolism (gonadal, adrenal, parathyroid and thyroid diseases, etc.), immune diseases such as rheumatoid arthritis, intestinal and renal diseases affecting the absorption and regulation of calcium and vitamin D, malignant diseases such as multiple myeloma, long-term use of glucocorticoids or other drugs affecting bone metabolism, and various congenital and acquired abnormalities of bone metabolism.
2.Basic examination items
(1) Skeletal X-ray: focus on the relationship between any imaging changes in the bones and the disease.
(2) Laboratory tests: blood and urine routine; liver and kidney function; calcium, phosphorus, alkaline phosphatase, serum protein electrophoresis, etc. Patients with primary osteoporosis usually have blood calcium, phosphorus, and alkaline phosphatase values in the normal range, and when there is a fracture, there is a mild increase in blood alkaline phosphatase levels. If abnormalities are found in the above tests, further examination or referral to the relevant specialist is required for further differential diagnosis.
3.Checking items as appropriate: For further differential diagnosis, the following tests can be performed selectively as appropriate, such as: blood sedimentation, gonadotropin, 25OHD, 1,25(OH)2D, parathyroid hormone, urinary calcium and phosphorus, thyroid function, cortisol, blood gas analysis, blood and urine light chain, tumor markers, and even radionuclide bone scan, bone marrow aspiration or bone biopsy, etc.
4.Bone conversion biochemical markers
Biochemical markers of bone turnover are the metabolic (breakdown and synthesis) products of bone tissue itself, referred to as bone markers. They are divided into bone formation markers and bone resorption markers. The former represents bone metabolites during osteoblast activity and bone formation, while the latter represents metabolites during osteoclast activity and bone resorption, especially bone matrix degradation products. The measurement of these markers helps to determine the type of bone transformation, the rate of bone loss, the assessment of fracture risk, the understanding of disease progression, the selection of interventions, and the monitoring of treatment efficacy.
Markers of bone formation
Serum alkaline phosphatase (ALP); osteocalcin (OC); bone-derived alkaline phosphatase (BALP); type I procollagen C-terminal prepeptide (PICP); type I procollagen N-terminal prepeptide (CINP) markers of bone resorption; fasting 2-hour urinary calcium/creatinine ratio; serum antitartaric acid phosphatase (TPACP); type I collagen C-terminal peptide (S-CTX); urinary pyridinoline ( Pyr); urinary deoxypyridinoline (D-Pyr); urinary type I collagen cross-linked C-terminal peptide (U-CTX); urinary type I collagen cross-linked N-terminal peptide N-terminal peptide (U-NTX) Among the above indicators, the International Osteoporosis Foundation (IOF) recommends type I procollagen N-terminal pre-peptide (CINP) and serum type I collagen C-terminal peptide (S-CTX) as relatively good sensitive bone conversion biochemical markers.
V. Prevention and treatment
Once an osteoporotic fracture occurs, the quality of life decreases and various comorbidities occur, which can be disabling and fatal. Therefore, the prevention of osteoporosis is more realistic and important than the treatment.
(I) Basic measures
The foundation is important and indispensable, but it is not the “all” and “only”. The scope of “basic measures” includes
1.Primary prevention and secondary prevention of osteoporosis
2, osteoporosis drug treatment and rehabilitation treatment
The content of “basic measures” includes
1.Adjustment of lifestyle
(1) A balanced diet rich in calcium, low in salt and moderate in protein.
(2) appropriate outdoor activities and sunshine, physical exercise and rehabilitation that contribute to bone health.
(3) Avoid smoking and alcohol abuse, and be careful with drugs that affect bone metabolism.
(4) Take various measures to prevent falls, and pay attention to the presence of diseases and drugs that increase falls.
(5) Strengthen protective measures for yourself and the environment (various joint protectors), etc.
2.Bone health basic supplements
(1) Calcium: China Nutrition Association has set the recommended daily calcium intake for adults 800mg (elemental calcium) as the appropriate dose to obtain the ideal bone peak and maintain bone health, if the supply of calcium in the diet is insufficient, calcium supplements can be used; the recommended daily calcium intake for postmenopausal women and the elderly is 1000mg. Calcium intake can slow down the loss of bone and improve bone mineralization. When used for the treatment of osteoporosis, it should be combined 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 effectiveness and safety.
(2) Vitamin D: promotes calcium absorption, is beneficial for bone health, maintains muscle strength, improves physical stability, and reduces the risk of fracture.
Vitamin D deficiency can cause secondary hyperparathyroidism and increase bone resorption, which can cause and worsen osteoporosis. The recommended dose for adults is 200 IU/d; for the elderly, the recommended dose is 400-800 IU/d due to lack of sunlight and impaired intake and absorption. vitamin D should be used at a dose of 800-1200 IU/d for the treatment of osteoporosis and can also be used in combination with other drugs. The International Osteoporosis Foundation recommends that serum 25OHD levels in the elderly be equal to or higher than 30ng/mL (75nmol/L) to reduce the risk of falls and fractures.
(II) Pharmacological interventions
[Indications for pharmacological intervention].
Pharmacological treatment should be considered for those who have one of the following conditions.
(1) Those with confirmed osteoporosis (BMD: those with T≤-2.5), regardless of whether there has been a fracture or not.
(2) Patients with low bone mass (bone mineral density: -2.5)