1. Bone resorption inhibitors 1.1. The main mechanism of treatment is to slow down the loss of bone calcium by inhibiting the formation or activity of osteoclasts, thereby inhibiting bone resorption. However, because patients with osteoporosis usually have insufficient calcium absorption, if applied alone, these drugs may cause hypocalcemia, so they are usually required to be taken simultaneously with calcium and vitamin D preparations, especially active vitamin D preparations. Treatment with bone resorption inhibitors can increase bone mass by 11 2% to 81 0% and reduce the risk of new fractures by 30% to 60%. Estrogen replacement therapy (ERT) can prevent postmenopausal osteoporosis caused by estrogen deficiency, prevent the reduction of bone cortex and trabeculae, stabilize or even increase bone mineral density (BMD), and reduce fractures in the spine, hip, and wrist. The purpose of progestin is to counteract the endometrial proliferative effect of estrogen, and progestin also has the effect of inhibiting bone resorption and promoting bone formation. However, ERT is often associated with breast swelling and pain, vaginal bleeding, procoagulant tendency and may increase the incidence of breast cancer, so the use of ERT should be weighed on an individual basis. At present, apart from natural short-acting sex hormones, the combination of estrogen and progestin, such as Bemelia, Clenbuterol, Norethindrone and Norcontrol, and androgen and estrogen capsules, as well as estrogen, progestin and androgen combination Levi’s, and combined estrogen and progestin tablets (Bemetan), are commonly used in clinical practice. Estrogen alone is suitable for patients who have had a hysterectomy, and the most commonly used drug is Nilestrol. The indications should be strictly controlled, follow-up should be strengthened, regular gynecological and breast examinations should be performed, and the thickness of the endometrium should be observed by B ultrasound. Selective estrogen receptor modulators (SERMs) are a class of synthetic non-hormonal agents with estrogen-like chemical structures that bind to estrogen receptors and act selectively on estrogen receptors in different tissues, producing estrogen-like or anti-estrogenic effects in different target tissues. They are characterized by estrogenic activation of the skeletal and cardiovascular systems, with little or no stimulation of the uterus and mammary glands. RA is a new non-steroidal compound that binds to the estrogen receptor, inhibits bone resorption, reduces bone loss, and effectively reduces vertebral fractures in postmenopausal women with osteoporosis (PMO), while acting on organs such as the breast and uterus with estrogen antagonism. It is the first SERM approved by the FDA for the prevention and treatment of postmenopausal osteoporosis, and has a modulating effect on lipid metabolism, lowering LDL-C and TG and not increasing C-reactive protein levels. A randomized, double-blind controlled clinical trial showed that RA at 60 mg/d orally significantly increased BMD in women with PMO at the lumbar and hip sites, reduced bone turnover, and did not result in venous thrombosis or embolism. Since RA has shown unique protective effects on breast and cardiovascular health of postmenopausal women while effectively preventing osteoporosis, it is a promising drug for the prevention and treatment of postmenopausal osteoporosis. 1.4. Phytoestrogens Phytoestrogens (PE) have estrogen-like effects without estrogen-like adverse effects. Cytological studies have confirmed that PE can promote bone formation and inhibit bone resorption through various mechanisms. Animal studies have shown that PE has a protective effect on bone mass in ovariectomized rats, and significantly improves their structural and mechanical properties. However, there is a lack of conclusive data on the efficacy of PE in postmenopausal osteoporosis, and its mechanism needs to be further investigated. Ipr, an isoflavone derivative, acts directly on bone tissue to inhibit bone resorption by suppressing osteoblast proliferation, differentiation, maturation, recruitment and osteoclast activity, while enhancing osteoblast activity and maintaining the dynamic balance between osteoblast and osteoclast activity, thus effectively preventing osteoporosis; promoting the release of calcitonin from the thyroid gland stimulated by estrogen, which has some therapeutic effects of both estrogen and calcitonin. Promotes estrogen-stimulated calcitonin release from the thyroid gland, which has some of the therapeutic effects of both estrogen and calcitonin, without the adverse effects of both. Compared with calcitonin and estrogen, Ipr has unique pharmacological effects, fewer adverse effects and a wider range of applications. Since this drug is an oral dosage form, it is convenient to take it for a long time and can be used as a common drug for the prevention and treatment of osteoporosis. Calcitonin (CT) is a single-chain peptide hormone consisting of 32 amino acids secreted by thyroid C cells, which is involved in the regulation of calcium metabolism. Its mechanism of action: (1) inhibit the activity of osteoclasts by binding to their CT receptors, reducing the number of osteoclasts on the one hand and slowing down their maturation rate on the other hand, exerting an inhibitory effect on bone resorption and lowering the rate of bone transformation to reduce bone loss; (2) promote osteoblast proliferation, promote bone repair and improve bone quality, which is conducive to improving bone biomechanical properties and reducing the rate of fracture in patients with osteoporosis; (3) act as a (3) Acting on nerve center-specific receptors, increasing B-endorphin levels, preventing calcium ions from entering nerve cells, and inhibiting the synthesis of the pain transmitter prostaglandin, which is effective in the treatment of systemic pain caused by osteoporosis. However, long-term use of CT can cause hypocalcemia and secondary hyperparathyroidism, and attention should be paid to the use of calcium and vitamin D. At present, the CTs that have been put into clinical use are micarbazide and calcitonin, which are safe and well tolerated, and are suitable for PMO with bone pain or fracture. 1.6. Bisphosphonates Bisphosphonates (BP) are bone resorption inhibitors that have been used in clinical practice since the 1980s. These drugs can reduce the number of osteoclasts, inhibit osteoclastic activity, block pathological osteolysis, counteract cancer-induced hypercalcemia, prevent the formation of new osteolytic lesions, reduce or eliminate bone pain, reduce the occurrence of pathological fractures, and significantly improve the quality of life of patients. BP inhibits osteoclast-mediated bone resorption mainly by: (1) inhibiting the differentiation and recruitment of osteoclast precursor cells, thus inhibiting osteoclast formation; (2) osteoclast phagocytosis, leading to osteoclast apoptosis; (3) attaching to the bone surface, affecting osteoclast activity; (4) interfering with the osteoclast’s ability to move from the bone to the bone. (4) Interfering with osteoclasts receiving bone resorption signals from the matrix; (5) Mediating through osteoblasts to reduce osteoclast activity. At present, the main drugs used in clinical practice are etidronephosphate (sodium hydroxyethyl phosphate), clodronephosphate (disodium chloromethophosphate), patronephosphate (sodium pamiphosphate, disodium pamiphosphate), aldrinephosphate (sodium alanophosphate), tiruvophosphate, ebenophosphate, lithium phosphate and smangophosphate. The representative drug of the third generation is sodium alemphate, which selectively binds to the active site of bone resorption and inhibits the activity of osteoclasts, thus reducing bone resorption. Clinical observation shows that the BMD can be increased rapidly after 3 months of taking alunphosphate, and the incidence of vertebral fracture is significantly reduced after 12 months. 2.Bone formation promoting drug 2.1.Fluoride Fluoride is one of the elements necessary for human bone production and maintenance, using fluoride to treat osteoporosis can promote bone formation and increase bone mass, the effect on vertebral bone is better than limb bone; it can effectively stimulate the mitosis of osteoblasts, promote osteoblast proliferation, and thus promote new bone formation. However, some overseas studies have shown that although fluoride can increase the BMD of the lumbar spine, it does not reduce the rate of vertebral fracture, and increasing the dose of fluoride has no effect on vertebral fracture. The duration of fluoride treatment for osteoporosis is generally about 3 years, and blood fluoride levels and serum alkaline phosphatase levels should be monitored during administration to ensure safety and responsiveness to fluoride treatment. The effect of fluoride on bone tissue depends on its dose. At low doses (< 30 mg/ d), it can promote bone formation and mitosis of osteoblasts and increase bone density; however, at higher doses, it has a toxic effect on osteoblasts and can lead to delayed bone mineralization and even osteochondrosis. Therefore, when using fluoride treatment, it is necessary to use low-dose and slow-release formulations as much as possible to improve the efficacy and avoid adverse effects. The fluoride currently used in clinical practice is monofluorophosphate (Toledine), disodium fluorophosphate, etc. Parathyroid hormone (PTH) is a single-chain polypeptide hormone secreted by parathyroid cells. Its main physiological function is to maintain blood calcium balance and regulate calcium and phosphorus metabolism. In bone, PTH has both osteogenic and osteoclastic effects. The results of animal experiments confirm that the intermittent application of small doses of PTH can promote bone formation and increase bone mass, while the continuous application of large doses of PTH can promote bone resorption and cause bone mass loss. Teriparatide is a human parathyroid hormone derivative synthesized by genetic engineering recombinant technology, its amino acid structure is identical to the 34 amino acids at the N-terminal end of natural human parathyroid hormone, and the two have similar affinity for PTH/PTHrP receptor, which activates osteoblast signaling channel and has the same effect on bone. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are commonly used in clinical practice to lower serum cholesterol. Among them, lovastatin is more effective, and the new product cerivastatin is more suitable for the treatment of OP because the dose is only 1% of lovastatin. A retrospective study reported that elderly women taking statins had a significant increase in hip bone density and a decrease in hip fracture risk while lowering cholesterol, but the results were not confirmed by a large prospective survey. 3, bone mineralization promoting drugs 3.1, vitamin D and its active metabolites vitamin D is the main element to promote human calcium absorption. The effects of vitamin D on OP include: (1) increasing gastrointestinal absorption of calcium; (2) promoting renal reabsorption of calcium; (3) directly inhibiting parathyroid hormone secretion; (4) promoting bone cell differentiation; (5) regulating neuromuscular tissue coordination. Clinically used preparations include vitamin D osteotriol and alfacalcidol. Vitamin D 400 U / d is a safe dose, its adverse effects include hypercalcemia and hypercalciuria, as well as gastrointestinal and neurological symptoms and metabolic reactions, etc., should be regularly monitored when using serum calcium and creatinine levels to prevent poisoning. The purpose of calcium supplementation is not only to correct the negative calcium balance in bone resorption and bone formation, but also to ensure the material basis of bone mass. Calcium supplementation can transiently increase serum calcium concentrations, reduce bone turnover, decrease parathyroid hormone production and increase the activation of bone remodeling sites. Some studies have shown that calcium alone for 2 years or longer has no significant effect on increasing bone mineral density compared to the placebo group, although it does reduce bone loss; the relative risk of vertebral fracture tends to decrease, but has no significant effect on reducing the incidence of extravertebral fractures. The Institute of Medicine of the National Academy of Sciences recommends a daily intake of 1000 mg of calcium for all adults aged 19 to 50 years and 1200 mg of calcium for all adults aged 50 years and older. Calcium intake above 2 g/d may increase the incidence of kidney stones, cause hypercalcemia, and affect vitamin D metabolism. Calcium is often combined with vitamin D and other medications, and the dose of calcium should be limited to less than 800 mg/day. Since the body cannot absorb and store excess calcium, and calcium absorption stops at night, but excretion continues, calcium must be taken from the bones to maintain the blood calcium balance. Therefore, calcium supplementation should be balanced on a daily basis, preferably in divided doses, and is more effective when taken before bedtime. Strontium is a chemically similar element to calcium, and low doses of strontium have a stimulating effect on osteoblasts and an inhibiting effect on osteoclasts. In vitro and in vivo experimental results show that strontium can reduce bone resorption and stimulate bone formation, which can increase BMD and reduce the fracture rate of vertebrae. In addition to calcium supplementation, zinc and copper supplementation are also needed for the elderly. Histoproteinase is an important cysteine protease in human tissues. Histoproteinase K and L inhibitors can effectively inhibit bone resorption, which is still under clinical research and has an optimistic development prospect, and will be a key research topic in the next few years. Osteoprotegerin has the biological effect of inhibiting osteoclast differentiation and increasing bone mineral density. It works by binding or neutralizing osteoclast differentiation factors, reducing the differentiation of precursor osteoclasts and inhibiting the activity of mature osteoclasts to reduce bone resorption. Vitamin K has been used in the treatment of osteoporosis, and circulating levels of vitamin K, especially vitamin K2, decline with age. Growth hormone has also been used to treat osteoporosis, but it is unclear whether it can prevent bone loss in postmenopausal patients with osteoporosis. Thiazide diuretics reduce calcium reabsorption by the renal tubules and decrease bone turnover and bone loss, but their role in the treatment of osteoporosis is unclear. In Chinese medicine, studies on osteoporosis have proposed treatments such as tonifying the kidney and strengthening the bones, strengthening the spleen and benefiting the qi, and activating the blood circulation. The Chinese herbs Epimedium, Cistanches, Bone marrow, Angelica, Safflower, Astragalus and Eucommia can increase BMD, improve bone pain symptoms, and prevent or treat fractures caused by osteoporosis.