The specific causes of osteoporosis are not fully understood, but are generally considered to be related to the following factors.
1 .Endocrine factors
1.1 Sex hormone deficiency
The lack and imbalance of estrogen and/or androgen leads to: (1) decreased protein synthesis and insufficient bone matrix production; (2) decreased osteoblast function; (3) increased sensitivity of PTH to bone action; (4) relatively higher intensity of glucocorticoid action on bone; (5) decreased intestinal calcium absorption and renal tubular calcium reabsorption, which may be related to osteoporosis caused by menopause, senility and premature ovarian failure, etc. Estrogen deficiency may be the main cause of osteoporosis during menopause.
In female patients, osteoporosis is caused by estrogen deficiency, while in men, it is caused by a decrease in testosterone levels due to hypogonadism. Osteoporosis is particularly common in postmenopausal women, and premature ovarian failure causes osteoporosis to appear earlier, suggesting that decreased estrogen is an important factor in the development of osteoporosis. Within 5 years after menopause, there will be a sudden and significant accelerated bone loss phase, with annual bone loss of 2% to 5% being common. About 20% to 30% of early menopausal women have bone loss >3%/year, called rapid bone loss, while 70% to 80% of women have bone loss <3%/year, called normal bone loss. Lean women are more prone to osteoporosis and fractures than fat women, as a result of the conversion of androgens to estrogens in the latter's adipose tissue. Compared with normal women of similar age, no significant differences in blood estrogen levels were seen in patients with osteoporosis, suggesting that decreased estrogen is not the only factor causing osteoporosis.
1.2 Increased secretion of parathyroid hormone
Some people with primary osteoporosis (osteoporosis with high bone turnover rate) have mildly increased blood PTH, which is more pronounced in patients with senile hyperalgesia and abnormal glucose tolerance; this, together with sex hormone deficiency and an abnormal ratio of PTH to sex hormones, can lead to osteoporosis.
In general, the presence of physiological decompensation of renal function in the elderly is manifested by reduced production of 1,25-(OH2)D3 and lower blood calcium, which in turn stimulates the secretion of parathyroid hormone, so most scholars report that blood parathyroid hormone concentrations often increase with age, with increases of up to 30% or more. Studies of parathyroid function in postmenopausal women with osteoporosis have shown hypo-, normal-, and hyper-functioning. It is generally believed that osteoporosis and hyperparathyroidism in the elderly are related.
1.3 Calcitonin (CT) deficiency
The decrease in CT levels after menopause may contribute to the development of osteoporosis due to the weakening of factors that inhibit bone resorption. Some studies have shown that women in all age groups have lower blood calcitonin levels than men, and women in the menopausal group have lower blood calcitonin levels than menopausal women, so it is thought that lower blood calcitonin levels may be one of the reasons why women are susceptible to osteoporosis. The increased value of blood calcitonin in women after intravenous calcium drip was significantly lower than that in men, and both the basal and increased values of blood calcitonin were negatively correlated with age. The Department of Endocrinology at Peking Union Medical College Hospital reported that no significant difference in calcitonin reserve function was seen in premenopausal and postmenopausal healthy volunteers who underwent intravenous calcitonin excitation tests. In contrast, calcitonin reserve function was reduced in both patients with reduced bone mass and osteoporosis, with the latter being more pronounced, suggesting that reduced calcitonin reserve function may be involved in the development of osteoporosis. Blood calcitonin levels in postmenopausal women with osteoporosis have mostly been reported to be reduced, but normal and mildly elevated levels have also been reported.
1.4 Role of other hormones
Some data suggest the presence of abnormal secretion of thyroid hormone, glucocorticoid, growth hormone, life factor (especially growth interferon C), and gastrin in patients with primary osteoporosis, but their etiologic significance has not been elucidated.
Osteoblasts (OB) and osteoclasts (OC) make up the bone reconstruction unit. In healthy adults, the balance between osteoclastic and osteogenic processes is maintained, which depends on a good mutual regulation between OB and OC.
Osteoclasts are cells of the monocyte/macrophage lineage and play a key role in maintaining the balance of bone reconstruction and calcium homeostasis in the body, while the activation and inhibition of OC is regulated by OB and other factors. Bone stromal cells, osteoblasts and activated T lymphocytes support the activation of OC and are called “support cells” (SC/OB).
(1) “Support cells” secrete macrophage colony-stimulating factor (M-CSF) to stimulate the development of a pluripotent monocyte/macrophage lineage into OC precursors. RANKL [nuclear factor-κB (NF-κB) receptor-activating factor ligand, also known as osteopontin ligand (OPGL), OC differentiation factor] secreted by “support cells” binds to RANK [(NF-κB) receptor-activating factor] on the OC membrane and transmits signals to the osteoclast precursors, leading to OC differentiation and maturation. maturation. (3) The “support cells” in turn secrete OPG (osteoprotection), which competes with OPGL for RANK binding, thereby inhibiting OC differentiation and maturation.
Various upstream hormones [e.g. PTH, 17β-E2, glucocorticoids, l,25(OH)2D3, PGE2, etc.] or cytokines (e.g. TGF-β, IL-1, IL-11, IL-17 and TNF, etc.) act on SC/OB receptors to stimulate or inhibit SC/OB expression of RANKL or 0PG, thereby regulating OC activity. If OC is continuously overactive, osteoporosis will occur.
2. Genetic factors
Osteoporosis is more common in whites, especially in northern Europeans, followed by Asians, and less common in blacks. Bone mineral density is an important indicator for the diagnosis of osteoporosis, and the value of bone mineral density is mainly determined by genetic factors, followed by the influence of environmental factors. The difference in BMD between young twins has been reported to be 4 times greater than the difference between monozygotic twins; while in adults the difference in BMD between twins is 19 times greater than that of monozygotic twins. In 1994, Morrison et al. reported that the vitamin D receptor genotype predicted differences in BMD, accounting for 75% of the overall genetic effect, and that BMD was about 15% higher in bb genotypes than in BB genotypes, after adjusting for various environmental factors; in terms of the incidence of vertebral fractures, bb The preliminary results of this study show that there are significant differences among races and countries, and the final results need to be further investigated. Other studies on the relationship between collagen and estrogen receptor genes and osteoporosis have also been reported, but no definite conclusions have been drawn yet.
3. Nutritional factors
Calcium intake in adolescence has been found to be directly related to peak bone mass in adulthood. Calcium deficiency leads to increased PTH secretion and bone resorption, and people on low-calcium diets are prone to osteoporosis. Vitamin D deficiency leads to impaired mineralization of the bone matrix and can lead to osteochondrosis. Long-term protein deficiency causes insufficient synthesis of bone mechanism protein, resulting in backward new bone production, and if there is also calcium deficiency, osteoporosis will appear faster. Vitamin C is indispensable in the synthesis of bone matrix hydroxyproline, which can maintain the normal growth of bone matrix and maintain bone cells to produce sufficient amount of alkaline phosphatase, such as lack of vitamin C can reduce the synthesis of bone matrix.
4.Waste factor
Muscles produce mechanical force on bone tissue, muscles developed strong bones, then high bone density value. Due to the reduced activity of the elderly, muscle strength is weakened, mechanical stimulation is less, bone volume is reduced, while the weakened muscle strength and coordination disorders make the elderly more prone to falls, accompanied by a reduction in bone volume is prone to fractures. The elderly are prone to osteoporosis because of bone loss due to disuse factors after prolonged bed rest and inactivity after stroke and other diseases.
5, drugs and diseases
Anticonvulsants, such as sodium phenytoin, phenobarbital, and carbamazepine, cause treatment-related vitamin D deficiency, as well as impaired intestinal calcium absorption, and secondary hyperparathyroidism. Excessive use of acid-forming agents, including aluminum preparations, can inhibit phosphate absorption and lead to the breakdown of bone minerals. Glucocorticoids directly inhibit bone formation, decrease intestinal absorption of calcium, increase renal excretion of calcium, secondary parathyroid dysfunction, and production of sex hormones. Long-term use of heparin is associated with osteoporosis, and the exact mechanism is not known. Chemotherapeutic agents, such as cyclosporine A, have been shown to increase bone renewal in rodents.
Cytokines produced by tumor cells in tumors, especially multiple myeloma, activate osteoclasts, as well as leukemia and lymphoma in children or adolescents, in which osteoporosis is often limited. Gastrointestinal disorders, such as inflammatory bowel disease leading to malabsorption and eating disorders; anorexia nervosa leading to rapid weight loss as well as malnutrition, and associated with absence of menstruation. Pearly anemia, which results from hyperplasia of the bone marrow and thinning of the trabecular junction, and secondary hypogonadism are also seen in this group of patients.
6, Genetic factors
Stature, fatness, muscularity and gastrointestinal function are all genetically related. Caucasians (Asians are also similar to Caucasians) are prone to osteoporosis, while South African Bantu and Blacks are less prone to osteoporosis, and the incidence of osteoporosis is much higher in long and lean individuals than in short and fat ones.
7, immune factors
Osteoclasts are derived from large monocytes, which have potential immune function. Immune dysfunction accelerates bone resorption and slows bone growth through various pathways, leading to osteoporosis.
8, bone weight and bone mineral density (BMC) peak level
BMC reaches its peak at the age of 30 for both men and women, and peak BMC is the super-initial value of MBC that decreases year by year after adulthood. Data show that high peak BMC is less likely to osteoporosis after entering menopause or old age, while low peak MBC can quickly reach the “critical risk value”, which is more prominent in women.
9, Other factors
Alcohol abuse has a direct toxic effect on bone. Smoking increases the liver’s metabolism of estrogen and its direct effect on bone, and can also cause weight loss and early menopause. Long-term heavy exercise can lead to idiopathic osteoporosis.