Osteoporosis, known as the silent killer, is a chronic disease that seriously endangers bone health, especially in middle-aged and elderly women. With the accelerated aging process in China, the number of people suffering from osteoporosis in China has been located in the first place in the world.On October 19, 2018, the National Health and Wellness Commission released the first epidemiological survey results of osteoporosis in China, which showed that osteoporosis has become an important health problem for people over 50 years old in China, among which the problem of osteoporosis is particularly serious in middle-aged and elderly women. According to the survey, more than one-third of women over 50 years old in China are currently osteoporosis patients.
I. Definition and classification
Osteoporosis is the most common bone disease, a systemic bone disease characterized by low bone mass and damage to the microstructure of bone tissue, leading to increased bone fragility and susceptibility to fracture.
Primary osteoporosis includes 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; osteoporosis in the elderly generally refers to osteoporosis occurring after the age of 70 years; idiopathic osteoporosis mainly occurs in adolescents, and the cause of the disease is not yet known. Secondary osteoporosis refers to osteoporosis caused by any disease that affects bone metabolism and/or drugs and other clear etiology.
II. Epidemiology
Osteoporosis is a skeletal disease associated with increasing age. Currently, China has more than 210 million people over 60 years of age (about 15.5% of the total population) and nearly 140 million people over 65 years of age (about 10.1% of the total population), making it the country with the largest absolute number of elderly people in the world. With the aging of the population becoming more and more serious, osteoporosis has become an important public health problem in China. Early epidemiological surveys show that the prevalence of osteoporosis among people over 50 years of age in China is 20.7% for women and 14.4% for men; the prevalence of osteoporosis among people over 60 years of age is significantly higher, especially among women.
Osteoporotic fracture (or fragility fracture) refers to a fracture that occurs with minor trauma or during daily activities and is a serious consequence of osteoporosis. The common sites of osteoporotic fractures are the vertebrae, hip, distal forearm, proximal humerus and pelvis, among which the most common are vertebral fractures.
Osteoporotic fractures are extremely dangerous and are one of the main causes of disability and death in elderly patients. Within 1 year after the occurrence of hip fracture, 20% of patients will die from various complications, and about 50% of patients become disabled and have a significantly reduced quality of life. Moreover, the medical treatment and care of osteoporosis and fracture require a lot of human, material and financial resources, causing a heavy family and social burden.
III. Pathogenesis of osteoporosis
Bones need to have sufficient stiffness and toughness to maintain bone strength in order to carry external forces and avoid fractures. To this end, the bone requires an intact hierarchical structure, including the three-stranded helical structure of type I collagen, non-collagenous proteins and the hydroxyapatite deposited therein. The integrity of the bone is maintained by a repetitive, spatiotemporally coupled process of bone resorption and bone formation called “bone reconstruction”. Bone reconstruction is carried out by the basic multicellular units of the skeleton consisting of osteoblasts, osteoclasts, and osteocytes. The positive balance between bone formation and bone resorption increases bone mass and reaches peak bone mass; in adulthood, bone reconstruction is balanced and bone mass is maintained; thereafter, bone formation and bone resorption are negatively balanced with increasing age, and bone loss is caused by imbalance in bone reconstruction.
Postmenopausal osteoporosis is mainly due to the decrease in estrogen levels after menopause, the weakened inhibitory effect of estrogen on osteoclasts, and the increased number, reduced apoptosis, and prolonged life span of osteoclasts, resulting in their enhanced bone resorption. Although osteoblast-mediated bone formation is also increased, it is not sufficient to compensate for excessive bone resorption. Active bone reconstruction and imbalance result in thinning or fracture of trabecular bone and increased porosity of cortical bone, leading to decreased bone strength. The decrease in estrogen reduces the sensitivity of the bone to mechanical stimuli, resulting in a pathological change similar to disuse bone loss.
Age-related osteoporosis results in progressive bone loss due to an imbalance in bone reconstruction caused by aging and an increase in the bone resorption/bone formation ratio on the one hand; on the other hand, aging and estrogen deficiency keep the immune system hypo-activated and in a state of pro-inflammatory response. Inflammatory response mediators tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, IL-6, IL-7, IL-17 and prostaglandin E2 (PGE2) all induce the expression of M-CSF and RANKL, stimulate osteoclasts and inhibit osteoblasts, resulting in reduced bone mass. Both estrogens and androgens have antioxidant stress effects in vivo. The sustained increase in sex hormone-binding globulin in the elderly decreases the bioavailability of testosterone and estradiol, and the accumulation of reactive oxygen species in the body contributes to the apoptosis of mesenchymal stem cells, osteoblasts, and osteocytes, resulting in decreased bone formation. Vitamin D deficiency and chronic negative calcium homeostasis are common in the elderly, leading to secondary hyperparathyroidism. Age-related decreases in adrenal-derived androgen production, decreased growth hormone-insulin-like growth factor axis function, sarcopenia and decreased physical activity resulting in reduced skeletal load also increase bone resorption. In addition, increased oxidative stress and glycosylation with ageing and lifestyle-related diseases cause non-enzymatic cross-linking of collagen molecules in the bone matrix, which can also lead to reduced bone strength.
The occurrence of osteoporosis and its fractures is the result of the interaction of genetic and non-genetic factors. Genetic factors mainly affect bone size, bone volume, structure, microarchitecture and internal properties. Non-genetic factors include mainly environmental factors, lifestyle, diseases, medications, and fall-related factors. Osteoporosis is the common result of the accumulation of multiple genetic-environmental factors and other minor effects.
IV. Clinical manifestations of osteoporosis
There are no obvious symptoms in the early stage of osteoporosis, and the decrease of bone density is found only when some patients are examined. Some women may experience muscle pain, joint abnormalities, decreased physical strength, sore teeth, irritability, and excessive sweating after menopause, all of which are related to the decrease in estrogen levels.
(i) Pain
If there is no intervention in the early stage, bone pain may gradually appear with the development of the disease, mainly in the lower back and lower limbs. The pain usually appears when turning over, when sitting up and after long time walking, and the pain increases at night or during weight-bearing activities, and may be accompanied by muscle cramps such as calf cramps, joint pain and weakness, difficulty in squatting, difficulty in climbing stairs, and even limitation of activities.
(II), spinal deformation
In patients with severe osteoporosis, spinal deformities such as shortening of height or hunchback may occur due to vertebral compression fractures. Multiple thoracic compression fractures may lead to thoracic deformity and even affect cardiopulmonary function; severe lumbar compression fractures may lead to abnormal abdominal organ function, causing constipation, abdominal pain, abdominal distension, decreased appetite and other discomforts.
(iii) Fracture
Osteoporotic fracture is a fragility fracture, which refers to the fracture that occurs when a slight external force is applied in daily life, or even a lower limb fracture when standing, a thoracic vertebra, lumbar vertebra, rib fracture when coughing or toileting with force, a bent rib fracture, or a fracture even when some patients are so serious that they are bedridden. The common sites where fractures occur are the vertebrae (thoracic and lumbar vertebrae), hip (proximal femur), distal forearm and proximal humerus; fractures can also occur in other areas such as ribs, metatarsals, fibula, pelvis, etc. After osteoporotic fractures occur, the risk of re-fracture increases significantly.
(iv) Effects on psychological status and quality of life
The harm of osteoporosis and its associated fractures on patients’ psychological status is often overlooked. The main psychological abnormalities include fear, anxiety, depression, and loss of self-confidence. The decreased ability of elderly patients to live autonomously and the lack of contact and communication with the outside world after fracture can cause a great psychological burden. The psychological abnormalities of patients with osteoporosis should be paid attention and concern, and necessary treatment should be given.
V. Diagnosis of osteoporosis
The diagnosis of osteoporosis is based on medical history, physical examination, bone densitometry, imaging and the necessary biochemical measurements. The clinical diagnosis of primary osteoporosis should include two aspects: to determine whether it is osteoporosis and to exclude secondary osteoporosis.
(i) Bone mineral density measurement
Bone density refers to the amount of bone contained per unit volume (bulk density) or per unit area (area density). There are more methods of bone density and bone measurement, and the role of different methods in the diagnosis of osteoporosis, efficacy monitoring, and fracture risk assessment varies. Currently, the common clinical methods of bone density measurement include dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), peripheral QCT (pQCT), and quantitative ultrasound (QUS). The currently accepted diagnostic criteria for osteoporosis are based on the results of DXA measurements. China has included the bone density testing program into the routine physical examination for people over 40 years old.
(b) Lateral X-ray images of thoracic and lumbar vertebrae and their fracture determination
Vertebral fractures are often missed due to the absence of obvious clinical symptoms, and screening for vertebral fractures needs to be carried out in people at risk for osteoporotic fractures. Lateral X-ray imaging of the thoracolumbar spine can be the preferred method for determining osteoporotic vertebral compression fractures. Routine thoracolumbar X-ray lateral views should include the thoracic 4 to lumbar 1 and thoracic 12 to lumbar 5 vertebrae, respectively.
(iii) Bone turnover marker determination
Bone turnover markers (BTMs), which are the breakdown and anabolic products of bone tissue itself, are referred to as bone markers. BTMs are divided into bone formation markers, which reflect osteoblast activity and bone formation status, and bone resorption markers, which represent osteoclast activity and bone resorption level. The levels of bone turnover markers in blood circulation or urine change to different degrees in normal subjects at different ages and in different disease states, representing the dynamic status of systemic bone metabolism. The measurement of these markers helps to identify primary and secondary osteoporosis, determine the type of bone turnover, predict the rate of bone loss, assess fracture risk, understand disease progression, select interventions, and monitor drug efficacy and compliance.
(D) Diagnostic criteria of osteoporosis
The diagnosis of osteoporosis is mainly based on DXA bone densitometry and/or fragility fracture. bone density measured by DXA is currently the common diagnostic index of osteoporosis. For postmenopausal women and men aged 50 years and older, it is recommended to refer to the diagnostic criteria recommended by WHO. Based on the DXA measurement results: Bone density value is normal if it is 1 standard deviation or less than the peak bone value of healthy adults of the same sex and race, low bone mass if the measurement value is 1 to 2.5 standard deviations, osteoporosis if it is equal to and more than 2.5 standard deviations; severe osteoporosis if the degree of bone density reduction meets the diagnostic criteria of osteoporosis and is accompanied by one or more fragility fractures.
VI. Prevention and treatment of osteoporosis
The prevention and treatment of osteoporosis should be carried out throughout the life course, and osteoporotic fracture can increase the rate of disability or death, so the prevention of osteoporosis is as important as the treatment. The primary goals of osteoporosis prevention and treatment include improving bone growth and development, promoting ideal peak bone mass in adulthood, maintaining bone mass and bone quality, preventing age-related bone loss, and avoiding falls and fractures.
Primary prevention of osteoporosis: refers to those who do not yet have osteoporosis but have risk factors for osteoporosis, and should prevent or delay the development of osteoporosis and avoid the first fracture; secondary prevention and treatment of osteoporosis: refers to those who already have osteoporosis or have already had a fragility fracture, and the prevention and treatment aim is to avoid fractures or re-fractures.
The prevention and treatment measures of osteoporosis mainly include basic measures, pharmacological intervention and rehabilitation treatment.
(I) Basic treatment
Including lifestyle modification and basic bone health supplements.
1.Adjustment of lifestyle
(1) Strengthen nutrition and balanced diet: It is recommended to consume a balanced diet rich in calcium, low salt and moderate amount of protein, the recommended daily protein intake is 0.8-1.0g/kg body mass, and to consume 300ml of milk or equivalent amount of milk products daily.
(2) Adequate sunlight: It is recommended that between 11:00 a.m. and 3:00 p.m., as much skin as possible be exposed to the sun for 15-30 min twice a week to promote the synthesis of vitamin D in the body, and try not to apply sunscreen so as not to affect the sunlight effect. However, care should be taken to avoid strong sunlight exposure to prevent burning of the skin.
(3) Regular exercise: Physical exercise and rehabilitation that contribute to bone health are recommended. Exercise can improve agility, strength, posture and balance of the body and reduce the risk of falls. Exercise also helps to increase bone density. Exercises suitable for people with osteoporosis include weight-bearing exercises and resistance exercises. Regular weight-bearing and muscle strength exercises are recommended to reduce the risk of falls and fractures. Muscle strength exercises include weight training, other resistance exercises and walking, jogging, tai chi, yoga, dance and table tennis. Exercise should be gradual and consistent. Patients with osteoporosis should consult a clinician for evaluation before starting new exercise training.
(4) Others: Quit smoking, limit alcohol, avoid excessive coffee consumption, avoid excessive carbonated beverages, and avoid or minimize the use of drugs that affect bone metabolism.
2.Bone health basic supplements
(1) Calcium: Adequate calcium intake is beneficial for obtaining the ideal bone peak, slowing down bone loss, improving bone mineralization and maintaining bone health. 2013 edition of the Dietary Reference Intake for Chinese Residents recommends a daily calcium intake of 800mg (elemental calcium) for adults and 1000-1200mg for people aged 50 and above. If calcium intake in the diet is insufficient, calcium supplements can be given. Nutritional survey shows that the daily dietary intake of elemental calcium in China is about 400mg, so there is still a need to supplement elemental calcium about 500~600mg/d.
(2) Vitamin D: Adequate vitamin D can increase intestinal calcium absorption, promote bone mineralization, maintain muscle strength, improve balance and reduce the risk of falls. Vitamin D deficiency can lead to secondary hyperparathyroidism and increase bone resorption, which can cause or worsen osteoporosis. Simultaneous calcium and vitamin D supplementation may reduce the risk of osteoporotic fractures. In China, vitamin D deficiency is widespread and can affect the efficacy of other anti-osteoporosis drugs. 2013 edition of the Chinese Dietary Reference Intake suggests that the recommended intake of vitamin D for adults is 400 IU (10 μg)/d; for elderly people aged 65 and above, vitamin D deficiency is common due to lack of sunlight and impaired intake and absorption. For people at high risk of vitamin D deficiency, such as those with inadequate sunlight exposure and the elderly, it is recommended that serum 25-hydroxyvitamin D levels be measured as appropriate to understand the nutritional status of patients and to guide vitamin D supplementation. Some studies suggest that serum 25-hydroxyvitamin D levels in the elderly should be at or above 75 nmol/L (30 μg/L) to reduce the risk of falls and fractures.
Anti-osteoporosis drugs
(ii) Anti-osteoporosis drugs
Effective anti-osteoporosis drugs can increase bone density, improve bone quality and significantly reduce the risk of fracture.
Anti-osteoporosis drugs can be divided into bone resorption inhibitors, bone formation promoters, other mechanism-based drugs and traditional Chinese medicine according to their mechanism of action. Drugs with a broad anti-fracture spectrum (e.g., alendronate, zoledronic acid, risedronate, and denosumab) are usually preferred. Oral drug therapy is preferred for those at low or moderate risk of fracture (e.g., young postmenopausal women with low BMD levels but no history of fracture). Injectable agents (e.g., zoledronic acid, teriparatide, or denosumab) may be considered for those who are intolerant of oral administration, contraindicated, have poor compliance, and are at high fracture risk (e.g., elderly patients with multiple vertebral fractures or hip fractures, patients with very low BMD). Estrogens or selective estrogen receptor modulators (SERMs) may be considered in patients who are at high risk for vertebral fractures only and not at high risk for hip and non-vertebral fractures. Short-term use of calcitonin may be considered in patients with new fractures with pain. Chinese medicine has been shown to improve clinical symptoms and other effects, but the evidence for reducing osteoporotic fractures is insufficient.
(iii) Chinese herbal medicine treatment
According to the main clinical manifestations of osteoporosis, a similar condition in Chinese medicine is bone impotence, which is seen in patients with osteoporosis who do not have obvious clinical manifestations or who only feel weakness and soreness in the lower back. According to the theory of Chinese medicine that “kidney is the master of bone” and “spleen is the master of muscle” and “pain is caused by lack of circulation of qi and blood”, the basic treatment for osteoporosis is to tonify kidney and essence, strengthen spleen and qi, and activate blood to dispel blood stasis. Chinese medicine is mainly used to improve the symptoms of osteoporosis, and the clinically proven effective Chinese medicine can be used according to the condition.
(iv) Rehabilitation treatment
Rehabilitation therapy for osteoporosis mainly includes exercise therapy, physical factor therapy, occupational therapy and rehabilitation engineering, etc.
1, exercise therapy: exercise therapy is simple and practical, not only can enhance muscle strength and muscle endurance, improve balance, coordination and walking ability, but also can improve bone density, maintain bone structure, reduce the risk of falls and fragility fractures, etc., play a comprehensive prevention and treatment role. Exercise therapy should follow the principles of individualization, gradual progress and long-term adherence. Therapeutic exercises include aerobic exercises (e.g. jogging, swimming), resistance exercises (e.g. weight-bearing exercises), impact exercises (e.g. gymnastics, rope skipping), vibration exercises (e.g. whole-body vibration training), etc. Tai chi can increase hip and lumbar spine bone density, enhance muscle strength, improve the flexibility of ligaments and muscles and tendons, improve proprioception, strengthen balance, and reduce the risk of falling. Exercise should pay attention to less trunk flexion and rotation movements. In the early stage of osteoporotic fracture, passive movements of the joints adjacent to the fracture (such as joint flexion and extension) and isometric contraction training of the muscles around the fracture should be strengthened to prevent pulmonary infection, joint contracture, muscle atrophy and disuse osteoporosis on the premise of ensuring the stability of the fracture end; in the later stage, active exercises, progressive resistance exercises and balance coordination and core muscle strength training should be given priority.
2.Physical factor treatment
Physiotherapy such as pulsed electromagnetic field, extracorporeal shock wave, whole-body vibration and ultraviolet light can increase bone mass; ultrashort wave, microwave, transcutaneous electrical nerve stimulation and medium-frequency pulse can reduce pain; for osteoporotic fracture or delayed fracture healing, low-intensity pulsed ultrasound and extracorporeal shock wave can be chosen to promote fracture healing. Neuromuscular electrical stimulation, acupuncture and other treatments can enhance muscle strength, promote nerve repair and improve limb function. Combination therapy and treatment dosage should be chosen according to the patient’s condition and tolerance level.
In conclusion, osteoporosis is a chronic disease that involves various tissues and organs such as bones and muscles, and requires comprehensive prevention and treatment. In addition to conventional drug and surgical treatment, active, standardized and comprehensive rehabilitation treatment can improve bone strength and reduce fracture occurrence, and also promote the recovery of patients’ life and work ability.