Based on the theory of “Kidney-blood-bone” to explore the mechanism of GH/IGF-1 system in the prevention and treatment of osteoporosis in Qing 'e pill

SUN Xin, YANG Qi-ning, WANG Qing-yan, LI Jia, YANG Fang, YAN Yan, SHANG Deyang, FU Ye-ping

1.Liaoning University of Traditional Chinese Medicine, Shenyang 110032,China

Keywords:

ABSTRAC T Objective: To observe the changes of growth hormone (GH)/insulin-like growth factor-1(Igf-1) system in blood, kidney and bone tissue of rats, and to explore the preventive and therapeutic effect of Qing 'e pill on osteoporosis due to kidney deficiency and its mechanism,to provide the basis for studying the etiology and pathogenesis of osteoporosis due to kidney deficiency. Methods: The rat osteoporosis model was established by ovariectomy, they were randomly divided into normal group, model group, Western Medicine Group, Jianpi Group, high-dose group, middle-dose group and low-dose group, the levels of serum alkaline phosphatase (ALP) , tartrate acid phosphatase (TRACP), growth hormone (GH) and GHR(Ghr) in kidney, bone and blood were determined by Elisa, the contents of insulin-like growth factor-1(Igf-1) and insulin-like growth factor-1 receptor (IGF-1R) were analyzed by SPSS 25.0 software. Results: 1. Compared with the normal group, the contents of TRACP and ALP in serum of the model group were significantly increased, suggesting that the rats developed highconversion osteoporosis. 2. The levels of serum, bone and renal GHR, Igf-1 and insulin-like growth factor-1 receptor (IGF-1R) in the model group were significantly lower than those in the control group. 3. Compared with the model group, the contents of TRACP and ALP in the high, middle and low dose groups were significantly decreased. 4. Compared with the model group, the contents of GHR, Igf-1 and IGF-1R in blood, bone and kidney tissue of the high,middle and low dose groups were increased. Conclusion: 1. Qing 'e pill can improve the bone metabolism of osteoporosis. 2. Qinge pill may prevent and cure osteoporosis by increasing the contents of GHR, Igf-1 and IGF-1R in blood, bone and kidney.

1. Introduction

Osteoporosis (OP) is a systemic bone disease with the characteristics of bone mass reduction, bone microstructure damage and bone fragility increase [1]. According to traditional Chinese medicine, the kidney stores essence and governs the bone. "The kidney is the main body that stings. It is the source of sealing the bone, and the essence is also... Filled in the bone" (Suwen · six sections on Zang Xiang). The kidney is the primary responsibility for bone diseases. Qinge pill, a classic prescription for tonifying the kidney, is commonly used in the treatment of osteoporosis [2].The growth hormone (GH) / insulin-like growth factor-1 (IGF-1)system plays an important role in bone growth and metabolism [3].In this study, Qing'e pill was used to prevent and treat osteoporosis,to explore the changes of GH, GHR, IGF-1, IGF-1R, ALP and TRACP in the process of GH / IGF-1 system on the occurrence and development of kidney deficiency osteoporosis, and to explore the prevention and treatment of Qing'e Pill on postmenopausal osteoporosis (PMOP) and its mechanism of action, so as to provide a theoretical basis for the study of the pathogenesis and treatment of kidney deficiency osteoporosis.

2. Data And Methods

2.1 grouping and modeling of experimental animals

In this experiment, 70 SPF SD rats (female without mating) aged 3 months were selected. OP rat model was established by ovariectomy.There were 7 experimental groups, including normal group, model group, western medicine group, Jianpi group, high dose group of Qing'e pill, middle dose group of Qing'e pill and low dose group of Qing'e pill. In the normal group, no operation was performed and normal saline was given by gastric perfusion; After ovariectomy, rats in the model group were gavaged with normal saline, and rats in the other groups were gavaged with corresponding drugs for 8 weeks(Western medicine group: fushanmei, Jianpi group: Shengyang Jujin decoction, Qinge pill, high and low experimental groups).This experiment was conducted in accordance with all applicable institutions and government regulations on ethical use of animals.Animal ethics review No.: 21000042021096

2.2 experimental drugs

According to the prescription of Qing'e pill in Chinese Pharmacopoeia, the ratio of Eucommia ulmoides, Psoralea, walnut kernel and garlic is 16:8:5:4. In this experiment, granules were used to prepare the decoction for gastric perfusion.

According to pharmacological experimental methods, the equivalent dose of rats is 6.3 times that of human according to the conversion of body surface area. In the experiment, the low, medium and high dose groups of Qingre pill were 1.26, 2.52 and 5.04 g · kg-1, respectively,and were given by gavage every 1 mL / 100 g. The positive Chinese medicine reference drug is Buzhong Yiqi Decoction, which has the function of Tonifying the middle and supplementing the Qi and raising the Yang. The prescription is composed of ten drugs such as Astragalus, Codonopsis pilosula, Atractylodes macrocephala and roasted licorice. The reference drug of Western medicine is fushanmei (Hangzhou moshadong Pharmaceutical Co., Ltd.). The equivalent dose of intragastric administration in rats was 6.3 times that of adults, and the volume was 0.875 mL/100 g body weight.

2.3 material acquisition

After 8 weeks of intragastric administration, the kidney, blood and bone were taken and the related indexes were detected.

2.4 index detection

The bone mineral density (BMD) of rat femur was measured by dual energy X-ray, and the expression of TRACP, ALP, GH,GHR, IGF-1 and IGF-1R protein in rat kidney, blood and bone was detected by ELISA.

2.5 statistical treatment

SPSS 25.0 software applied one-way analysis of variance (oneway ANOVA) to the data for statistical processing. The results were expressed as mean ± standard deviation (±s), and P ＜ 0.05 was statistically significant.

3. Results

3.1 changes of BMD, serum TRACP and ALP in each group

(1) The results of BMD test showed that the BMD of the model group was significantly lower than that of the normal group (P ＜0.01); Compared with the model group, the normal group, the spleen strengthening group, the western medicine group and the high dose group of Qing'e pill increased significantly (P ＜ 0.01), and the middle dose group of Qing'e pill increased significantly (P ＜ 0.05);But there was no difference in the low dose group. Among them, the high dose group of Qing'e pill has the best effect (Table 1).

Tab 1 Bone mineral density of femur in each group(n=10, ±s)

Tab 1 Bone mineral density of femur in each group(n=10, ±s)

Note: compared with normal group,*P＜0.05、** P＜0.01; compared with model group●P＜0.05、●●P＜0.01.

Group BMD(g/cm2)Normal group 0.287±0.059●●Model group 0.155±0.071**Spleen strengthening group 0.277±0.039●●Western medicine group 0.266±0.090●●High concentration group of Qing'e pill 0.286±0.125●●Middle concentration group of Qing'e pill 0.232±0.097●Qinge pill low concentration group 0.215±0.069 P 0.006 F 3.406

(2) The statistical results of TRACP content showed that the model group was significantly higher than the normal group (P＜0.01); It was significantly higher in the spleen strengthening group (P＜0.01);There was no difference in the western medicine group; Qinge pill high dose group, Qinge pill middle dose group and Qinge pill low dose group increased significantly (P＜0.01). Compared with the model group, there was no difference in the spleen strengthening group; Significantly lower in western medicine group (P＜0.01);Qinge pill high dose group, Qinge pill middle dose group and Qinge pill low dose group decreased significantly (P＜0.01). The high dose group of Qing'e pill was superior to the middle dose and low dose groups (Table 2).

The statistical results of ALP content showed that compared with the normal group, the ALP content in the model group was significantly higher (P＜0.01); It was significantly higher in the spleen strengthening group (P＜0.01); There was no difference in the western medicine group; Qinge pill high dose group, Qinge pill middle dose group and Qinge pill low dose group increased significantly (P＜0.01). Compared with the model group, there was no difference in the spleen strengthening group; Significantly lower in western medicine group (P＜0.01); Qinge pill high dose group, Qinge pill middle dose group and Qinge pill low dose group decreased significantly (P＜0.01). The high dose group of Qing'e pill was superior to the middle dose and low dose groups (Table 2).

Tab 2 Comparison of TRACP and ALP contents in serum of rats in each group(n=8, ±s)

Tab 2 Comparison of TRACP and ALP contents in serum of rats in each group(n=8, ±s)

Note: compared with normal group,*P＜0.05、** P＜0.01; compared with model group●P＜0.05、●●P＜0.01.

Group TRACP(pg/mL) ALP(U/L)Normal group 1594.86±110.04●● 125.40±11.17●●Model group 3054.39±127.05** 233.53±5.85**Spleen strengthening group Western medicine group High concentration group of Qing'e pill2815.43±134.74** 208.88±6.78**●●1867.10±175.40●● 131.78±5.46●●1940.16±99.68**●● 167.57±6.58**●●Middle concentration group of Qing'e pill 2122.05±47.84**●● 187.20±7.04**●●Qinge pill low concentration group 2413.47±76.67**●● 197.75±6.38**●●P 0.000 0.000 F 164.70 241.32

3.2 changes of GH / IGF-1 system in various organizations

3.2.1 changes of GH, GHR, IGF-1 and IGF-1R in rat serum

(1) Statistical results of serum GH content in rats

Compared with the normal group, the contents in each group were significantly lower (P＜0.01); Compared with the model group, the content of each group was significantly increased (P＜0.01).

(2) Statistical results of serum GHR content in rats

Compared with the normal group, the model group, the high-dose group of Qing'e pill, the middle dose group of Qing'e pill and the low-dose group of Qing'e pill were significantly lower (P＜0.01),the spleen strengthening group was lower (P＜0.05), and the western medicine group was lower, without difference; Compared with the model group, the normal group was significantly higher (P＜0.01),and each drug group had a certain increase, but there was no difference.

(3) Statistical results of serum IGF-1 content in rats

Compared with the normal group, the serum IGF-1 in the model group was significantly decreased (P＜0.01), the spleen strengthening group was decreased without difference, the western medicine group was decreased without difference, and the high dose group,the middle dose group and the low dose group of Qing'e pill were significantly decreased (P＜0.01). Compared with the model group,the normal group, the spleen strengthening group, the western medicine group, the high-dose group of Qing'e pill and the middle dose group of Qing'e pill increased significantly (P＜0.01), and the low-dose group of Qing'e pill increased, without difference.

(4) Statistical results of serum IGF-1R content in rats

Compared with the normal group, the model group, the Jianpi group, the high-dose group of Qing'e pill, the middle dose group of Qing'e pill and the low-dose group of Qing'e pill were significantly lower (P＜0.01), and the western medicine group was lower, with no difference. Compared with the model group, the normal group, the spleen strengthening group, the western medicine group, the high dose group of Qing'e pill, the middle dose group of Qing'e pill and the low dose group of Qing'e pill increased significantly (P＜0.01).

Tab 3 Comparison of serum GH, GHR, Igf-1, IGF-1R levels in rats of each group(n=8, ±s)

Tab 3 Comparison of serum GH, GHR, Igf-1, IGF-1R levels in rats of each group(n=8, ±s)

Note: compared with normal group,*P＜0.05、** P＜0.01; compared with model group●P＜0.05、●●P＜0.01.

Group GH(ug/L) GHR(ng/L) IGF-1(ng/L) IGF-1R(ng/L)Normal group 20.35±0.31●● 133.51±8.19●● 10.20±0.56●● 5.47±0.07●●Model group 13.14±Spleen strengthening group 18.30±Western medicine group 18.13±High concentrationgroup of Qing'e pill 16.83±Middle concentration group of Qing'e pill 16.50±Qinge pill low concentration group 15.40±0.40** 99.70±15.23** 8.07±0.32** 4.23±0.06**0.82**●● 117.80±7.43* 9.63±0.33●● 4.91±0.49**●●1.99**●● 122.76±3.50 9.94±0.26●● 5.28±0.06●●0.41**●● 112.61±3.56** 8.96±0.18**●● 4.92±0.09**●●0.42**●● 103.72±3.63** 8.95±0.29**●● 4.79±0.07**●●0.41**●● 98.49±1.91** 8.21±0.12** 4.82±0.28**●●P 0.000 0.000 0.000 0.000 F 55.16 23.84 52.88 25.68

3.2.2 changes of GH, GHR, IGF-1 and IGF-1R contents in rat bone tissue

(1) Statistical results of GH content in bone tissue of rats

Compared with the normal group, the model group, the Jianpi group, the high-dose group of Qing'e pill, the middle dose group of Qing'e pill and the low-dose group of Qing'e pill were significantly lower (P＜0.01), and the western medicine group was lower(P＜0.01); Compared with the model group, the normal group,the spleen strengthening group and the western medicine group increased significantly (P＜0.01), and the high, medium and low dose groups of Qing'e pill increased slightly, but there was no difference.

(2) Statistical results of GHR content in bone tissue of rats

Compared with the normal group, the model group, the Jianpi group, the high-dose group of Qing'e pill, the middle dose group of Qing'e pill and the low-dose group of Qing'e pill were significantly lower (P＜0.01), and the western medicine group was lower, but there was no difference; Compared with the model group, the normal group, the western medicine group, the high dose group of Qing'e pill, the middle dose group of Qing'e pill and the low dose group of Qing'e pill increased significantly (P＜0.01).

(3) Statistical results of IGF-1 content in bone tissue of rats

Compared with the normal group, the model group, the Jianpi group, the high-dose group of Qing'e pill, the middle dose group of Qing'e pill and the low-dose group of Qing'e pill were significantly lower (P＜0.01), and the western medicine group was lower(P＜0.01); Compared with the model group, the normal group, the western medicine group, the high-dose group of Qing'e Qing'e pill and the middle dose group of Qing'e pill were significantly increased(P＜0.01), and the low-dose group of Qing'e pill was increased without difference.

(4) Statistical results of IGF-1R content in bone tissue of rats

Compared with the normal group, it was significantly lower in the model group and the high dose group of Qing'e pill (P＜0.01);Compared with the model group, the normal group, the spleen strengthening group, the western medicine group, the middle dose group of Qing'e Qing'e pill and the low dose group of Qing'e pill increased significantly (P＜0.01), and the high dose group of Qing'e pill increased without difference.

Tab 4 Comparison of bone Gh, GHR, Igf-1, IGF-1R contents in each group(n=8, ±s)

Tab 4 Comparison of bone Gh, GHR, Igf-1, IGF-1R contents in each group(n=8, ±s)

Note: compared with normal group,*P＜0.05、** P＜0.01; compared with model group●P＜0.05、●●P＜0.01.

Group GH(ug/L) GHR(ng/L) IGF-1(ng/L) IGF-1R(ng/L)Normalgroup 19.85±0.76●● 166.36±2.38●● 12.95±0.65●● 6.67±0.21●●Modelgroup 13.42±0.2 Spleenstrengthening group 16.12±0.3 Western medicine group 18.45±1.2 High concentrationgroup of Qing'e pill 14.38±0.67** 94.47±1.51** 9.12±0.18** 5.11±0.41**2●●** 132.20±1.59** 10.93±0.20**●● 6.25±0.27●●6●● 151.94±11.36●● 12.61±0.16●● 6.54±0.08●●3** 133.47±2.89**●● 11.20±0.46**●● 5.68±1.12 Middleconcentration group of Qing'e pill 13.32±0.37** 125.16±4.70**●● 10.66±1.46**●● 6.15±0.12**●●Qinge pill low concentration group 13.84±1.02** 117.42±4.91**●● 10.10±1.26** 6.56±0.50●●P 0.000 0.000 0.000 0.000 F 98.13 156.23 22.82 9.84

3.2.3 changes of GH, GHR, IGF-1 and IGF-1R contents in rat kidney tissue

(1) Statistical results of GH content in rat kidney tissue

Compared with the normal group, the model group, the Jianpi group, the high-dose group of Qing'e pill, the middle dose group of Qing'e pill and the low-dose group of Qing'e pill were significantly lower (P＜0.01), and the western medicine group was lower(P＜0.01); Compared with the model group, the normal group,the spleen strengthening group and the western medicine group increased significantly (P＜0.01), and the high-dose group and the low-dose group of Qing'e pill increased slightly, but there was no difference.

(2) Statistical results of GHR content in rat kidney tissue

Compared with the normal group, it was significantly lower in the model group and the high dose group of Qing'e pill (P＜0.01);Compared with the model group, the normal group, the spleen strengthening group, the western medicine group, the high-dose group of Qing'e Qing'e pill increased significantly (P＜0.01), the middle dose group of Qing'e pill increased (P＜0.05), and the highdose group of Qing'e pill increased without difference.

(3) Statistical results of IGF-1 content in rat kidney tissue

Compared with the normal group, the model group, the spleen strengthening group, the western medicine group, the high dose group of Qing'e pill, the middle dose group of Qing'e pill and the low dose group of Qing'e pill were significantly lower (P＜0.01);Compared with the model group, the normal group, the spleen strengthening group, the western medicine group, the high dose group of Qing'e pill, the middle dose group of Qing'e pill and the low dose group of Qing'e pill increased significantly (P＜0.01).

(4) Statistical results of IGF-1R content in rat kidney tissue

Compared with the normal group, the model group, the western medicine group, the middle dose group of Qing'e pill and the low dose group of Qing'e pill were significantly lower (P＜0.01);Compared with the model group, the normal group, the western medicine group, the middle dose group of Qing'e pill and the low dose group of Qing'e pill increased significantly (P＜0.01).

Tab 5 Comparison of GH, GHR, Igf-1, IGF-1R contents in renal tissue of rats in each group(n=8, ±s)

Tab 5 Comparison of GH, GHR, Igf-1, IGF-1R contents in renal tissue of rats in each group(n=8, ±s)

Note: compared with normal group,*P＜0.05、** P＜0.01; compared with model group●P＜0.05、●●P＜0.01.

Group GH(ug/L) GHR(ng/L) IGF-1(ng/L) IGF-1R(ng/L)Normalgroup 19.85±0.76●● 150.14±1.95●● 12.40±0.43●● 6.10±0.07●●Modelgroup 13.42±0.27**Spleenstrengthening group 16.12±0.32●●**Western medicine group 18.45±1.26●●High concentrationgroup of Qing'e pill 14.38±0.63**Middleconcentration group of Qing'e pill 13.32±0.37****105.17±4.02** 7.76±0.38** 4.73±0.12**151.76±19.39●● 10.78±0.19**●● 5.18±1.14 143.53±5.07●● 11.34±0.14**●● 5.75±0.17**●●122.99±2.70**●● 10.20±0.21**●● 5.11±0.62 111.80±2.89**● 10.11±0.21**●● 5.11±0.11**●●Qinge pill low concentration group 13.84±1.02109.81±3.11** 9.18±0.16**●● 4.37±0.11**●●P 0.000 0.000 0.000 0.000 F 170.89 50.86 250.83 10.79

4. Discussion

4.1 evaluation of bone metabolism in osteoporosis with kidney deficiency

The PMOP model established by ovariectomy can well simulate postmenopausal high conversion osteoporosis and is recommended by the World Health Organization. In this study, TRACP and ALP in the blood of the model group were significantly higher than that of the normal group, which was consistent with the characteristics of high conversion osteoporosis.

The women's "July 7th" coincides with the onset period of PMOP. In Suwen · ancient innocence, it is described that "the sky is exhausted, the tunnel is not clear, and the shape is bad without children" [4], which is consistent with the characteristics of modern female menopause. The most important reason for the exhaustion of Tiangui is the serious deficiency of kidney essence, which is the basis for generating marrow and transforming blood. The deficiency of kidney essence and the deficiency of generating marrow make it impossible for marrow reduction to generate blood and nourish bone,and bone loss will lead to bone necrosis. Osteoporosis is the main manifestation of bone necrosis. Therefore, we take PMOP model as our model to study bone necrosis and marrow reduction due to kidney deficiency. The results of this study show that the high-dose group of Qinge pill, a Chinese medicine for tonifying the kidney,has a better regulatory effect on TRACP and ALP than the spleen strengthening group, which to a certain extent proves that the main etiology and pathogenesis of PMOP is kidney deficiency.

4.2 regulating effect of Qing'e Pill on bone metabolism in osteoporosis due to kidney deficiency

Qing'e pill is a representative prescription for the treatment of kidney deficiency low back pain and is often used in the treatment of OP low back pain [5]. Previous clinical studies have shown that Qing'e pill has an obvious effect on improving the symptoms of kidney deficiency, back pain and waist and knee tenderness in PMOP patients [6]. Some achievements have also been made in experimental research. For example, the therapeutic effect of Qing'e Pill on PMOP rats may be achieved by increasing bone marrow perfusion and improving bone marrow microcirculation [7]; Qinge pill containing serum can promote OC apoptosis through mmp3-opn-p53 signaling pathway, reduce bone loss, and achieve the prevention and treatment of PMOP [8]. Chen Fan [9] et al. Found through meta-analysis results that Qing'e pill has obvious improvement on osteoporosis pain and bone density of femur, and its therapeutic effect is better than that of conventional Western Medicine (P = 0.004). In this study, Qing'e pill can significantly reduce the content of ALP and TRACP in blood of model rats, and play a role in regulating bone metabolism of PMOP.

4.3 GH / IGF-1 system and kidney deficiency osteoporosis

GH / IGF-1 system is closely related to the growth, development and metabolism of bone. The performance of GH function in vivo is realized through GHR and IGF-1 [10]. GHR belongs to the cytokine receptor superfamily, which is stored in important organs represented by the liver and tissues such as cartilage and bone [11].IGF-1 mediates most of the effects of GH on the body, including the effects on bone tissue [12]. GHR exists on the surface of osteoblasts and osteoclasts. GH directly or indirectly regulates the proliferation and differentiation of osteoblasts by activating and aggregating osteoclasts, promotes the differentiation of osteoclasts, and further affects bone resorption [13]. Electroacupuncture of Shenshu and Zusanli combined with Zishen Qianggu decoction can regulate GH/ IGF-1 system in bone tissue and serum, and increase BMD of ovariectomized osteoporosis rats [14]; The anti osteoporosis effect of Ligustrum lucidum may be achieved by regulating the GH / IGF-1 signaling pathway to reduce the serum GH level of ovariectomized rats and increase the expression of IGF-1 in bone and liver [15].IGF-1 and its signaling pathway are widely involved in the growth and development of bone. It was found that the down-regulation of bone formation and bone resorption in IGF-1 knockout mice is the main reason for their abnormal bone development [16]. Moreover,in the bone marrow of IGF-1 gene deleted mice, the osteogenesis and osteoclastogenesis were insufficient, and the number of corresponding cells decreased. IGF-1 receptor IGF-1R deficient mice also have abnormalities in bone development [17], and it has also been proved in human studies that IGF-I plays a key role in bone development. In addition, the decrease of IGF-1 expression and/ or its activity can trigger low-level bone formation and bone loss related to age [18].

Our results showed that the contents of GH, GHR, IGF-1 and IGF-1R in the kidney, blood and bone of model rats were significantly lower than those in the normal group, while the Qing'e pill group could increase the contents of GHR, IGF-1 and IGF-1R in the kidney, blood and bone of model rats and play a regulatory role on PMOP. The abnormal change of GH / IGF-1 system in kidney, blood and bone tissue is one of the mechanisms of PMOP, and Qing'e pill can improve PMOP by regulating GH / IGF-1 system. Therefore, the abnormal change of GH / IGF-1 system is one of the mechanisms of kidney deficiency.

4.4 "kidney blood bone" system and osteoporosis due to kidney deficiency

In humans, the role of gh/igf-1 system peaks during puberty growth.Clinical studies have shown that BMD increases by 40-50% during puberty growth, mainly due to the expression and activity levels of sex steroid hormones and gh/igf axis [19]. And regulates bone acquisition by stimulating the production of extracellular matrix and the increase of BMD. In multiple tissues, there is a close interaction between gh/igf-1 and the sex steroid axis [20]. In the process of aging,the activity of related hormones decreases. This state is called "body bone" state, which is related to the damage to the musculoskeletal system. This trend is consistent with the extreme height of "Tiangui"and the bone changes that occur at the same time.

The kidney stores essence, and "it is filled in the bone" (Suwen ·six sections of Zang Xiang Lun). Under physiological conditions,the kidney essence is filled and can promote the growth and development of bone and the strength of bone. The maintenance of this function cannot be separated from the role of blood and marrow.The kidney stores essence and the essence can generate marrow. The bone marrow is located in the bone, constantly nourishes the bone,and the marrow is strong; The kidney stores essence, which can transform blood and nourish the whole body, including nourishing bone, blood foot nourishing bone and strong bone. However, when the kidney essence is insufficient and the bone marrow is unable to generate marrow and blood, the bone marrow is not nourished,and the osteoporosis will be easily broken. Through the prevention and treatment of kidney tonifying Chinese medicine, the bone condition can be improved. The results of this study show that when the kidney is deficient in essence, the contents of GH, GHR, IGF-1 and IGF-1R in the kidney, blood and bone tissue are significantly decreased, the bone metabolism is accelerated, the bone mass is lost,and the content of ALP and TRACP in the blood is significantly increased when osteoporosis occurs. It suggests that the abnormality of GH / IGF-1 system is closely related to the enhancement of bone metabolism and the occurrence of high conversion type osteoporosis. The abnormal change of GH / IGF-1 system is one of the mechanisms of kidney essence deficiency and bone marrow reduction; After the intervention with Qinge pill, a representative prescription for tonifying the kidney, the abnormal changes of GH/ IGF-1 system were improved. GH played a role in maintaining the balance of bone metabolism by promoting the secretion and expression of IGF-1 in the body [16]. BMD was increased, and the contents of ALP and TRACP in blood were significantly decreased,further explaining the correlation between GH / IGF-1 system and osteoporosis due to kidney deficiency.

To sum up, the kidney stores the essence, which can generate marrow and blood, which is filled in the bone. "Kidney blood bone"is closely related. The strength of bone can not be separated from the filling of kidney essence. The function of kidney essence filling its raw marrow blood is strong, so the bone can be nourished, ensuring the growth and development of bone and the strength and toughness of bone. Qing'e pill is a classic prescription for tonifying kidney. As a commonly used therapeutic prescription for kidney deficiency and low back pain, it can regulate GH / IGF-1 system in kidney, blood and bone, thus playing a role in preventing and treating PMOP; To a certain extent, it shows that the regulating effect of GH / IGF-1 system on bone is one of the biological bases for the kidney to store essence and regulate bone. The abnormal change of GH /IGF-1 system in "kidney blood bone" is one of the etiology and pathogenesis of osteoporosis due to kidney deficiency. Qinge pill, a kidney tonifying prescription, plays a role in preventing and treating osteoporosis by regulating the content of GH / IGF-1 in "kidney blood bone".