Secondary hyperparathyroidism bone disease is a common type of renal osteodystrophy. It is one of the most important causes affecting the quality of life and its prognosis in dialysis patients with chronic renal failure (CRF). More and more attention is being paid to the study of its pathogenesis, diagnosis and treatment. The following is a review of this. 1. Pathogenesis The exocrine and endocrine functions of the kidney are impaired in patients with end-stage renal insufficiency. The former manifests as impaired renal excretion of phosphorus, causing phosphorus retention; the latter manifests as reduced renal 1α-hydroxylase synthesis, leading to 1,25(OH)2D3 deficiency. Both of these are now considered to be the underlying causes of secondary hyperparathyroidism (SHPT). However, whole segment parathyroid hormone (iPTH) varies over a wide range in patients with chronic renal insufficiency, and pathology can manifest as different types of bone disease. And as SHPT bone disease, there are yet other factors that play an important role in it. These include the upward shift of calcium to the point of iPTH modulation, bone resistance to iPTH, and abnormal iPTH metabolism in peripheral tissues. Several factors are intertwined, interacting and influencing each other, leading to the development of SHPT bone disease – fibrodysplasia. 2. Diagnosis Clinically, maintenance dialysis patients with concomitant SHPT osteopathy may present with bone pain, proximal muscle weakness, skin pruritus, ectopic calcification, and an increased risk of fracture. Biochemical indicators are reduced or normal blood calcium concentrations, increased blood phosphorus concentrations, and elevated blood iPTH levels. Bone biopsy is one of the most important tools for the diagnosis of SHPT bone disease. It shows histomorphologically increased bone-like surface, increased number and surface of osteoblasts and osteoclasts, increased bone formation rate and bone mineralization rate, and peripheral bone trabecular fibrosis area ≥0.5%. In recent years, many blood and urine biochemical indexes and other indexes have been correlated with bone histomorphology in an attempt to select noninvasive tests with higher sensitivity and specificity that can better reflect the morphological changes of bone tissue. The study proved that blood iPTH, osteocalcin (BGP), and bone-specific alkaline phosphatase (BAP) are better indicators of bone metabolism. Biologically active iPTH reflects the level of iPTH secreted and released directly from the parathyroid glands into the blood, and is not affected by liver or kidney metabolism, so it is more sensitive and specific than the measurement of certain fragments of PTH in serum (including mid-range PTH, C-terminal PTH). Some studies have shown that iPTH is linearly and positively correlated with bone formation indicators (osteoid surface, osteoblast surface and number, bone formation rate, bone mineralization rate) peripheral trabecular fibrosis area, reticular osteoid mass, and curvilinearly correlated with bone resorption indicators (osteoclast number and surface, etc.). Some authors also found that in uremic patients, the effect of iPTH to promote bone resorption peaked at an iPTH of 500 ng/L, while its effect on bone formation appeared to be unlimited. Therefore, its role in promoting bone formation is more pronounced at persistently high levels of iPTH, especially when iPTH is greater than 500 ng/L. Moreover, it simultaneously promotes the proliferation of fibroblasts, leading to the development of fibrodysplasia. This supports Torres’ conclusion that iPTH greater than 450 ng/L predicts SHPT bone disease with >95% compliance. bGP is secreted by osteoblasts and it correlates to some extent with both bone formation indexes and bone resorption indexes, but correlates better with bone formation indexes. For more than 50 years, blood alkaline phosphatase (ALP) has been used as an indicator of bone metabolism, but it has many isoenzymes that are present in different tissues and organs in the body, such as the small intestine, liver and biliary system, kidney, leukocytes, and osteoblasts, which makes the total ALP level in serum not accurately reflect bone metabolism. This makes the total serum ALP level not accurately reflect the bone metabolism. In recent years, bone-specific ALP-BAP has been isolated and purified, and BAP-specific antibodies have been prepared, making it possible to measure BAP. Therefore, the determination of BAP in serum can exclude the interference of other factors and make it more consistent with the changes of bone metabolism. Now, for the specific structure of type I collagen in bone tissue, some biochemical indicators reflecting the metabolism of type I collagen have been generated, while using them to reflect bone metabolism. Pyridinol (PYD) and deoxypyridinol (DPD) are cross-linkers of mature type I collagen, which are released into the blood during collagen degradation by bone resorption and excreted in the urine without metabolism, and its urinary levels are not affected by diet. Therefore, urinary PYD and DPD are good indicators of bone resorption. However, the changes of urinary PYD and DPD in patients with chronic renal insufficiency and its correlation with bone histomorphology need further study. The pre-collagen type I carboxy pre-peptide (PICP) and type I collagen hydroxyl-regulated peptide (ICTP) are increasingly used in the study of bone metabolism, and PICP is derived from the formation of type I collagen molecules from the pre-collagen peptide chain, which is trimmed by the action of pre-collagen carboxy protease. It has a molecular weight of 100,000 and is cleared by liver metabolism without passing through the glomerular basement membrane, reflecting bone formation. ictp is a type I collagen breakdown metabolite, reflecting bone resorption. Some studies have shown that PICP correlates with bone formation index of bone histomorphology; ICTP correlates with bone resorption index of bone histomorphology. In conclusion, there is no single biochemical index that can accurately diagnose SHPT bone disease, but the combined application of several biochemical indexes can improve the accuracy of diagnosis. Other diagnostic measures include plain X-ray examination, dual energy X-ray absorptiometry (DEXA), and parathyroid ultrasound. Some authors have found that X-ray finger bone intracortical bone resorption signs help to distinguish osteochondrosis from SHPT bone disease, and different degrees of intracortical bone resorption have been found to correlate with iPTH levels. The application of DEXA technique found that there was a negative correlation between the local bone density of skull bone and the level of iPTH. x-ray examination has some diagnostic value for certain types of bone disease, but the sensitivity is low. ultrasound findings of enlarged parathyroid glands can help diagnose SHPT, but it must be combined with medical history, symptoms, clinical and biochemical indicators to make a comprehensive judgment. 3, treatment For the pathogenesis of SHPT bone disease, its treatment measures include the following: (1) limit the intake of phosphorus and the use of phosphorus binding agents? Phosphorus intake is mostly advocated to control 600-1000mg/d, and phosphorus binding agents are mostly applied to calcium carbonate or calcium acetate, especially calcium acetate has high efficiency in binding phosphorus and low absorption of calcium. Studies have shown that in patients with early renal insufficiency, after the blood phosphorus level is controlled, the blood free calcium concentration increases, the calcium regulation point of PTH improves, the synthesis of active VitD3 increases (related to the release of high phosphorus inhibition of α-hydroxylase), and the blood iPTH level decreases; while in patients with advanced renal insufficiency, after phosphorus intake is restricted, the active VitD3 level does not increase, but the blood iPTH also decreases. In patients with advanced renal insufficiency, restriction of phosphorus intake did not increase the level of active VitD3, but also reduced the level of iPTH, suggesting that blood phosphorus may act directly on PTH independently of calcium and active VitD3. It has also been found that high phosphorus inhibits the effect of VitD3 on the parathyroid glands. Therefore, active control of blood phosphorus before applying active VitD3 therapy can help increase the effectiveness of treatment. (2) Application of active VitD3 and its metabolites In patients with CRF, serum active VitD3 levels are lower than normal, or even if they are in the normal range, they do not meet the needs of uremic patients, i.e., there is acquired VitD3 resistance. Current studies have shown that active VitD3 has the following direct effects on the parathyroid glands in addition to promoting intestinal calcium absorption and increasing blood calcium, thereby indirectly inhibiting PTH secretion: ① decreasing pro-PTH pro gene transcription and decreasing pro-PTH pro mRNA levels, thereby decreasing PTH secretion; ② increasing intracellular calcium concentration in parathyroid cells; ③ inhibiting proliferation of parathyroid cells. Chronic renal insufficiency causes SHPT, and parathyroid glands may show diffuse or nodular hyperplasia. Decreased number of 1,25(OH)2D3 receptors on parathyroid glands or decreased sensitivity of parathyroid glands to 1,25(OH)2D3. Adequate suppression of iPTH secretion requires supraphysiologic doses of 1,25(OH)2D3. administration of active VitD3 reverses or attenuates the pathologic changes in bone and improves patient symptoms. In some patients with moderate to severe SHPT bone disease, regular oral administration of active VitD3 may not achieve the peak 1,25(OH)2D3 concentrations required by the patient and may predispose to hypercalcemia, especially when combined with phosphorus binding agents such as calcium carbonate. peak 1,25(OH)2D3 concentrations are an important determinant in the control of SHPT bone disease. To improve treatment effectiveness and reduce adverse effects, many authors advocate intravenous or oral shock therapy. Intravenous 1,25(OH)2D3, which is not metabolized by the gastrointestinal tract and is distributed directly to the surrounding tissues, has a low incidence of hypercalcemia and a high biological effect, i.e., maximum suppression of iPTH. Oral shock doses of α-D3 and 1,25(OH)2D3, especially at night when the intestinal calcium load is lowest before sleep, have a low incidence of hypercalcemia and the same effect of suppressing iPTH. Some authors have also compared the efficacy of oral versus intravenous shock application of 1,25(OH)2D3 in SHPT bone disease and found that intravenous 1,25(OH)2D3 concentrations were higher at 6h and for 24h after dosing than oral dosing. It also caused a shorter time required for iPTH and bone-specific ALP (BAP) to start decreasing and a greater decrease. Bone biopsies also confirmed that after 38 months of intravenous application of 1,25(OH)2D, a decrease in osteoblast surface and number, a decrease in bone erosion surface, and a decrease in bone formation and bone mineralization rates were seen on bone histomorphology. In contrast, no significant changes in bone histomorphology were observed with oral administration. It has been hypothesized that the morphological changes in bone histology caused by the application of 1,25(OH)2D3 are due to its inhibitory effect on iPTH, and now 1,25(OH)2D3 has been found to have a direct effect on bone. Animal studies have demonstrated that 1,25(OH)2D3 directly inhibits osteoblast proliferation and reduces the rate of collagen synthesis and bone mineralization.Llach [12] suggested that the dose of 1,25(OH)2D3 should be applied with reference to the pre-treatment iPTH level, but some authors have suggested that the pre-treatment iPTH level is not related to the patient’s response to treatment. In conclusion, it is worthwhile to continue exploring the application of 1,25(OH)2D3 dose and duration of treatment. In addition to α-D3 and 1,25(OH)2D3, the currently applied VitD3 derivatives include α-D2, 1,25(OH)2D2, 2β-1,25(OH)2D3 (ED71), 22-oxa-1,25(OH)2D3 (OCT), 24,25(OH)2D3, etc. Studies have shown that α-D2 stimulates osteoblast activity without hypercalcemia; ED71 increases bone formation, decreases bone resorption, and increases bone mineral density; OCT has little effect on intestinal calcium transport, which accumulates mainly in parathyroid cells and reduces PTH secretion by inhibiting the growth of parathyroid cells; 24,25(OH)2D3 directly inhibits PTH without depending on plasma calcium levels effects on bone. We should select different drugs or combinations of drugs according to the patient’s condition to maximize the efficacy of the treatment, taking into account the different effects of various active VitD3 and its derivatives. Regardless of the therapy used, changes in blood calcium, phosphorus, PTH, BGP, and BAP must be closely monitored during the treatment process, and drug doses should be adjusted in a timely manner to avoid or reduce the occurrence of side effects. (3) Subtotal parathyroidectomy and total parathyroidectomy plus autologous transplantation In recent years, 1,25(OH)2D3 intravenous or oral shock therapy has been used to significantly improve the treatment effect of moderate and severe SHPT osteopathy, making the need to perform surgery greatly reduced. However, hyperparathyroidism that cannot be corrected by oral or intravenous application of drugs, and recalcitrant hypercalcemia that occurs during the use of drugs are still indications for surgery. It is best to make bone biopsy before surgery to clarify the diagnosis of SHPT bone disease, especially excluding aluminum toxic bone disease. Otherwise, it can cause aggravation of bone disease after surgery. Although there has been great progress in the diagnosis and treatment of SHPT bone disease, more in-depth research is still needed to develop new drugs and diagnostic and therapeutic tools to increase the correctness of diagnosis and improve the effectiveness of treatment.