Relationship of serum levels of Bone Specific Alkali Phosphatase (bALP) and Alkali Phosphatase (ALP) with vascular calcification in chronic kidney disease patient on chronic hemodialysis

Background@#Vascular calcification is an important non-conventional for cardiovascular disease (CVD) in chronic kidney disease (CKD) patients with chronic hemodialysis (HD). Abdominal aortic calcification (AAC) is reported as an independent predictor for cardiovascular morbidity and mortality. Bone-specific Alkali Phosphatase (bALP) and Alkali Phosphatase (ALP) enzymes are produced and released when changes or disorders of bone and mineral metabolism occur. Given biomarker studies such as bALP and ALP which are more often associated with patient mortality, more research will be needed to assess whether these bALP and ALP biomarkers have a linear distribution of relationships with vascular calcification.@*Objective@#This study aimed to evaluate the serum biomarker to predict calcification and further can be one of diagnosis modality of calcification in hemodialysis patients.@*Methods@#A total of 75 chronic HD CKD patients were included in the study. bALP and ALP serum levels were measured with ELISA, as well as AAC measured by lateral abdominal radiographs (X-Ray).@*Results@#bALP and ALP are positively correlated with AAC scores (p value <0.001 and 0.045). Multivariate logistic regression analysis shows that history of diabetes, bALP levels, and parathyroid hormone (PTH) levels are independent risk factors for AAC in chronic HD CKD patients. Receiver Operating Characteristic (ROC) shows the area under the curve (AUC) of bALP and ALP for AAC prediction are 0.882 (95% CI: 0.801-0.962; p value: <0.001) and 0.634 (95% CI: 0.509-0.760; p value: 0.045).@*Conclusion@#ALP and especially bALP serum correlate closely with vascular calcification in chronic HD CKD patients accompanied by a superior diagnostic value of bALP biomarkers when compared to ALP.

Mineral bone disorder and osteoporosis in hemodialysis patients

Abstract Background: Bone disease is common in patients undergoing hemodialysis. It is the result of bone turnover abnormalities and the decrease of bone mineral density (BMD). We aimed to determine the usefulness of serum bone turnover markers and BMD measurement by dual-energy x-ray absorptiometry (DXA) in hemodialysis patients. Methods: We conducted a cross-sectional study including 90 hemodialysis for more than 12 months. Bone mineral density was assessed by DXA. Peripheral blood samples were obtained from each patient before dialysis in a fasting state within a week of the DXA. Biochemical variables of calcium and phosphate were measured. One bone formation marker (bone-specific alkaline phosphatase (bAP), one bone resorption marker (carboxy-terminal telopeptides of type 1 collagen (CTX)) were measured. Total alkaline phosphatase (TAP), intact parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) which is a bone-derived hormone were also measured. Results: CTX values were 6.25 times higher than the normal limit of the assay. Bone alkaline phosphatase levels were less than 10 ng/mL in 28.8% of cases. 23% of patients have osteoporosis and 45% have osteopenia. Femoral BMD had negative correlations with age and PTH levels. FGF23 levels were significantly increased in patients with osteoporosis affecting the lumbar. The levels of bAP and CTX showed a positive correlation. Both circulating bAP and CTX levels showed also positive correlations with PTH levels. Fractures, observed in 12.2% of cases, were associated with low PTH values and the existence of osteoporosis. Conclusions: Our study showed that osteoporosis and fracture are common in dialysis patients. The reduced BMD was associated with advanced age and elevated levels of PTH. Markers of bone turnover and FGF23 may play a role in the diagnosis of bone disease in hemodialysis patients. DXA measurement is necessary for the monitoring for bone loss.(AU)

Changes of subchondral bone in rat models of knee osteoarthritis treated by elcatonin / 中国组织工程研究

BACKGROUND: Imbalance between subchondral bone resorption and bone formation occurs in osteoarthritis. Our preliminary study has found that the subchondral bone changes precede the articular cartilage changes in knee osteoarthritis rats. OBJECTIVE: To observe the changes of subchondral bone in knee osteoarthritis rats, and to explore the effect of elcatonin on the expression of p38 MAPK and absorption of subchondral bone. METHODS: Female Sprague-Dawley rats, 3 months of age, were randomly divided into three groups: Sham operation group (n=6, the adipose tissue of the same size as the ovary was removed without ovariectomy, the bilateral knee joints were opened, but without cruciate ligament injury); model group (n=6, bilateral ovariectomy plus bilateral cruciate ligament injury, no treatment); elcatonin group (n=6, ovariectomy plus cruciate ligament injury, intramuscular injection of 5 lU/kg elcatonin, twice weekly). The bone mineral density and p38 protein expression levels in subchondral bone were detected at 12 weeks. The serum levels of C-terminal crosslinking telopeptides of type I collagen, C-terminal crosslinking telopeptides of type II collagen, interleukin-1, interleukin- 6 and bone-specific alkaline phosphatase, tartrate resistant acid phosphatase 5b were detected. RESULTS AND CONCLUSION: (1) The bone volume fraction and trabecular bone number in the elcatonin group were significantly higher than those in the model group (P < 0. 05), and the trabecular separation in the elcatonin group was lower than that in the model group (P < 0. 05). (2) The bone volume fraction, trabecular bone number and trabecular thickness in the model group were lower than those in the sham operation group (P < 0. 01 or P < 0. 05), and the trabecular separation was higher than that in the sham operation group (P < 0. 01). (3) The serum levels of C-terminal crosslinking telopeptides of type I collagen, C-terminal crosslinking telopeptides of type II collagen, interleukin-1, interleukin- 6 and tartrate resistant acid phosphatase 5b in the elcatonin group was significantly lower than those the model group (P < 0. 05), and the above levels in the model group were significantly higher than those in the sham operation group (P < 0. 05). (4) The p38 expression level in subchondral bone in the elcatonin group was significantly lower than that in the model group (P < 0. 01), and the level in the model group was significantly higher than that in the sham operation group (P < 0. 01). (5) These results indicate that elcatonin may inhibit the secretion of osteoarthritis pro-inflammatory factors and subchondral bone resorption by down-regulating the expression level of p38 MAPK.

Identification of bone-specific alkaline phosphatase in saliva and its correlation with skeletal age

Bone-specific alkaline phosphatase (B-ALP), a product of osteoblasts, is a bone formation marker whose serum levels fluctuate with puberty and adolescence. Aims: This study aims to assess B-ALP levels in saliva and correlate it with different skeletal maturity stages of hand-wrist radiographs using Hagg and Taranger method. Settings and Design: Observational study and cross-sectional design. Subjects and Methods: Total sample comprised of 90 individuals, right hand-wrist radiographs, and 2 ml unstimulated whole saliva samples taken from each patient on the same day. The hand-wrist radiographs were traced and staged into 5 subgroups (18 individuals each) according to Hagg and Taranger method. Statistical Analysis Used: One-way analysis of variance (ANOVA) and Tukey's multiple post hoc test. Results: The comparison of salivary B-ALP values between the different skeletal subgroups using one-way ANOVA depicted statistically significant results (P = 0.0003). Pairwise comparison using Tukey's multiple post hoc procedures showed that salivary B-ALP levels were comparatively higher in subgroup 3 and that the difference between subgroups 1 and 3 (P = 0.0109) and subgroups 3 and 5 (P = 0.0014) was statistically significant. Conclusion: B-ALP could be successfully identified and quantitatively estimated in saliva and showed significant correlation with different skeletal age subgroups as determined by Hagg and Taranger method.

Bone turnover rate and bone formation/resorption balance during the early stage after switching from a bone resorption inhibitor to denosumab are predictive factors of bone mineral density change

OBJECTIVES: This study aimed to investigate the correlation between bone mineral density (BMD) and the turnover rate [√(MoMf²+ MoMr²), multiple of median formation (MoMf) was calculated as bone-specific alkaline phosphatase (BAP) value/18.6 and multiple of median resorption (MoMr) as tartrate-resistant acid phosphatase 5b (TRACP-5b) value/463] and the balance (MoMf/MoMr) and to compare differences in therapeutic effects evoked by differences in previous treatments. METHODS: In 51 osteoporotic women treated with bisphosphonates (BPs) or selective estrogen receptor modulators (SERMs), BMD was measured at 0, 24, and 48 weeks after denosumab administration. The values of BAP and TRACP-5b were measured at 0, 4, 12, 24, 36, and 48 weeks. RESULTS: The turnover rate decreased at week 4 and decreased further at week 12. The balance indicated a relative predominantly formative state at week 4. This balance became higher in the SERM group than in the BP group at week 4. A correlation was observed between the rate of BMD change and turnover rate at weeks 0 and 4. CONCLUSIONS: It is necessary to evaluate the turnover rate and balance to determine the therapeutic effect of denosumab, which induces dissociation between the trends in the bone turnover markers. Turnover rate and balance during the early stages of denosumab treatment may be predictive factors of BMD. When switching from bone resorption inhibitors to denosumab, it was necessary to consider the beginning values that were affected by the previous treatment. The state of relative anabolism is greater at 4 weeks when the previous treatment involved SERMs rather than BPs.

Effect of Alendronate on Serum Total Alkaline Phosphatase and Bone Specific Alkaline Phosphatase in Elderly Female Patients with Postmenopausal Osteoporosis / 中国药师

Objective: To investigate the effect of alendronate on serum total alkaline phosphatase (AKP) and bone specific alkaline phosphatase (BAP) in the elderly female patients with postmenopausal osteoporosis and explore their correlations.Methods: A retrospective study was performed.Totally 286 elderly female patients with postmenopausal osteoporosis were divided into two groups(according to AKP levels before the treatment of alendronate): the normal AKP group (n=245) and the elevated AKP group (n=41).Raised AKP of all the patients in the elevated AKP group was not associated with hepatobiliary problems.The changes of AKP and BAP levels were analyzed after the treatment of alendronate.The correlations between BAP and AKP levels before and after the treatment of alendronate were analyzed, as well as between the changes in AKP (ΔAKP) and BAP (ΔBAP) levels.Results: AKP and BAP tended to be higher in elderly patients.BAP levels in the normal AKP group were higher than those in the elevated AKP group (P＜0.05).BAP was signicantly correlated with AKP both before and after the treatment (P＜0.05), as well as the correlation between ΔAKP and ΔBAP (P＜0.05).Conclusion: AKP and BAP both tend to increase with age.In elderly female patients with postmenopausal osteoporosis and elevated AKP associated with non-hepatobiliary problems, alendronate treatment can lower AKP levels, and the decrease is strongly correlated with the decrease in BAP.

Relationships between the levels of serum bone-specific alkaline phosphatase, cross-linked telopeptide of type Ⅰ collage and bone metastasis in patients with breast cancer / 肿瘤研究与临床

Objective To analysis the relationships between bone markers, bone-specific alkaline phosphatase (BAP) and cross-linked telopeptide of type Ⅰ collage (ICTP), and bone metastasis of breast cancer.Methods A total of 217 patients' serum were collected.The 217 cases were divided into two groups:109 cases with bone metastasis, 108 cases without bone metastasis. Serum BAP and ICTP was measured by ELISA. The relationships between factors of bone metastasis and serum levels of BAP, ICTP were analyzed.Results The levels of serum BAP and ICTP in bone metastases group were significantly higher than those in non-bone metastasis group[BAP:24.8 μg/L(7.60-213.70 μg/L) vs 21.2 μg/L(7.3～68.8 μg/L),ICTP:7.0μg/L(1.4～32.4 μg/L) vs 4.1 μg/L(0.0～15.8 μg/L) (P=0.003,P=0.000)].The level of serum BAP and ICTP in patients with multiple bone metastasis was significantly higher than that in patients with single bone metastasis[BAP:32.3 μg/L(9.A～213.7 μg/L) vs 18.1 μg/L(7.6～60.0 μg/L),ICTP:7.6 μg/L(1.4～32.4 μg/L) vs 4.9 μg/L(1.8～10.5 μg/L),(P=0.001,P=0.010)].The sensibility of BAP and ICTP was 45.0 ％ (49/109)and 46.8 ％ (51/109),respectively.The specificity of ICTP and BAP was 83.3 ％ (90/108)and 84.3 ％ (91/108),respectively.Joint detection of BAP and ICTP had improved sensibility in the diagnosis of bone metastasis in breast cancer patients. Conclusion Joint detection of serum bone biochemical markers ICTP and BAP have a little values for diagnosing bone metastasis in breast cancer patients.

Relationships of Serum Leptin Levels with Bone Metabolism in the Childhood Obesity / 대한소아소화기영양학회지

PURPOSE: The aim of this study was to evaluate the influence of leptin on biochemical markers of bone metabolism in childhood obesity. METHODS: A total of 50 male children (25 obese and 25 controls) were recruited from the pediatric outpatient clinic at the Chosun University Hospital from November 1st 2005 to May 30th 2006. BMI, body fat percentage, serum leptin, bone-specific alkaline phosphatase (B-ALP), C-terminal propeptide of type 1 collagen (CICP), total deoxypyridinoline crosslinks (total DPD) were measured. The correlations of leptin with BMI, body fat percentage, B-ALP, CICP, total DPD were analyzed by Pearson's correlation. In a multiple stepwise regression analysis, leptin after correction for body weight was evaluated if there was a correlation with biochemical markers of bone formation and resorption respectively. RESULTS: The leptin levels of the obese group were significantly higher than those of the control group (p=0.012). In the obese group, the leptin level was significantly positively correlated with the BMI (r=0.551, p=0.01) and the percentage of body fat (r=0.584, p=0.018). In the obese group, of bone markers, B-ALP (r=-0.613, p=0.026) and CICP (r=-0.583, p=0.037) were negatively correlated with leptin. B-ALP (r=-0.728, p=0.007) and CICP (r=-0.684, p=0.014) were negatively correlated with leptin when corrected for body weight. In the control group, bone markers were not correlated with leptin. In the multiple stepwise regression analyses, there was a negative correlation between the leptin and B-ALP (Y=-39.653X+356.341, p=0.026), CICP (Y=-13.437X+116.013, p=0.037) respectively in the obese group. CONCLUSION: Leptin was a significant factor in the bone formation but not in bone resorption in childhood obesity.

Effects of Deer Antler Extract on Serum IGF-I, Bone Growth and Splenocyte Proliferation in Growing Rats

Although it has traditionally known that deer antler and medicinal herbs extract contain some functional components for health promotion, the nutritional significance remains to be elucidated. This study examined the efficacy of deer antler extract (DA) , medicinal herbs extract (MH) and their mixture (DAMH) on serum IGF-I, bone growth with growing rats in vivo and splenocyte proliferation with spleen cells in vitro. Three week-old young female rats (Sprague-Dawley) were divided into 4 groups and then fed basal diet (AIN-93G) or experimental diets containing DA, MH, DAMH, respectively, for 7 weeks. We collected blood, liver, kidney, spleen, femur and tibia from rats. There was no significant difference in weight gain, but food intake increased in DA- and MH-fed groups. There were no signs of liver and kidney damage in the DA, MH and DAMH-fed groups compared to basal diet group. In femur and tibia, wet weights, breaking forces and bone minerals (Ca, Mg and Zn) were significantly higher in the DA-fed group than in the other groups. Serum alkaline phosphatase (ALP) , bone-specific alkaline phosphatase (BALP) activities were significantly lower in the DA, MH, DAMH-fed groups than in basal diet group. Also, serum insulin-like growth factor-I (IGF-I) concentrations were significantly increased in DA-fed group compared to the other groups. Therefore DA was shown to have an activity of bone growth promotion by increasing the IGF-I, a major bone growth factor. The deer antler extract showed an enhanced immune action on the primary cultured-cells from spleen of rats, representing that splenocytes were proliferated by lipopolysaccharide (LPS) , but not by concanavalin A (Con A) . These results indicate that deer antler extract has beneficial effects on bone growth via IGF-I and on splenocyte activation.

The Clinical Usefulness of Biochemical Markers of Bone Formation in Patients with Multiple Myeloma / 대한진단검사의학회지

BACKGROUND: Bone lesions in multiple myeloma (MM) are related to an uncoupling of bone resorption and formation. This study was to evaluate the potential clinical value of biochemical markers of bone formation in patients with MM. METHODS: Serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC) were measured in 217 sera from 77 patients with MM, 1 patient with plasma cell leukemia, and 12 patients with monoclonal gammopathy of undetermined significance (MGUS); 30 age- and sex-matched controls were also enrolled. RESULTS: Serum OC, but not serum BAP, was lower in MM and MGUS patients than in controls. Serum BAP decreased significantly as the tumor burden increased (P=0.035), but serum OC did not decrease. On the other hand, serum OC increased significantly in patients in an advanced stage according to the new international staging system (P=0.036), whereas serum BAP did not exhibit such a change. Serum OC and BAP showed positive correlations with albumin; serum OC also showed positive correlations with beta2-microglobulin and creatinine. CONCLUSIONS: Serum BAP, rather than serum OC, appears to be helpful in monitoring MM. The clinical usefulness of serum BAP may be enhanced in MM patients with renal impairment.

Effect of Massage Therapy on Growth of Preterm Infants: Relationship with Ghrelin, Leptin and Bone Specific Alkaline Phosphatase Levels / 대한소아내분비학회지

PURPOSE: Numerous studies have reported that premature birth is associated with neurodevelopmental impairment and that minimal handling is recommended. Limited physical activity of premature infants increases the risk of developing bone demineralization and osteopenia. This study aimed to evaluate the relationship between anthropometric parameters and growth in massage therapy (MT) groups and control group, the relationship between ghrelin, leptin and growth, and its association with B-ALP with anthropometric parameters. METHODS: The study comprised sixteen healthy, preterm infants below 36 weeks of gestational age assigned to two groups - one (n=8) received massage therapy and the other (n=8) did not receive. Blood samples of level of ghrelin, leptin, B-ALP were taken at the onset of MT and 1 week and 2 weeks after MT. RESULTS: There was no difference in gestational age, sex, birth weight, height, head circumference, skinfold thickness between two groups at birth. Despite a similar nutrient intake, gains in body weight and head circumference, subscapular skinfold thickness, and triceps skinfold thickness were greater in MT groups. There was no difference of height in two groups. There was no difference of ghrelin, leptin in two groups at the onset of MT, 1 week and 2 weeks after MT. The concentration of B-ALP showed positive correlation with age. but it was not statistically significant. Massage therapy led to a significant increase in ghrelin, not leptin, B-ALP. There was positive correlation between the concentration of ghrelin and weight gain. CONCLUSION: MT in preterm infants increases growth and weight gain is correlated positively with ghrelin levels.

Status of Osteoblast in Children with Idiopathic Short Stature / 实用儿科临床杂志

Objective To detect serum bone specific alkaline phosphatase(BAP) and osteocalcin(OC) in children with idiopathic short stature(ISS),and explore the status of osteoblast.Methods Thirty-six cases of ISS in this study were divided into two groups(preaddescence group and adolescence group),50 healthy children as control group.The height,weight and body mass index in every group were measured.Left hand and wrist were measured with CHN way for bone age.Serum BAP and OC were measured by enzyme linked immunosorbent assay(ELISA).Results BAP and OC in ISS group of preadolescence were(79.90?25.96) U/L,(60.96?18.46)?g/L,and(152.17?35.36)U/L,(76.16?28.03)?g/L in normal children.In the ISS group of adolescence BAP and OC were(108.33?35.20)U/L,(63.82?24.81)?g/L,and(156.30?35.29)U/L,(104.92?28.26)?g/L in normal group.There was significant difference between ISS and control group in both age in the levels of BAP and OC(Pa

Effects of rotary magnetic field on bone calcium content and related factor in rats with ovariotomy / 中华物理医学与康复杂志

Objective To observe the effects of rotary magnetic to bone mineral content(BMC), bone specific alkaline phosphatase (BAP) and deoxypyridinoline crosslinks (DPD), and to explore if there is synergistic action between the rotary magnetic field and the Chinese Medicine. Methods Experimental rats were exposed to the magnetic field 2 hours a day for 15 days then measured BMC, BAP and DPD then compared with that of the control rats. Results After rotary magnetic treatment, both female and male rats demonstrated a significant increase in BMC and BAP, and a simultaneous decrease in DPD content. Addition of Chinese medicine did not cause any significant difference of these parameters. Conclusion In rats with ovariotomy, rotary magnetic field can increase BAP and decrease DPD in a short time,and increase bone mineral content. These effects were similar in both female and male rats.

Biochemical Bone Markers in Postmenopausal Women with Hormone Replacement Therapy / 대한산부인과학회잡지

OBJECTIVES: To investigate the patterns of biochemical bone markers, such as urinary deoxypyridinoline (DPD), N-telopeptide of type I collagen (NTX), and serum osteocalcin (OC), bone-specific alkaline pbosphatase (BSAP) in postmenopansal women with hormone replacement therapy (HRT). Materials and METHOD: From July 1997 to January 1998, total 239 postmenopausal women were emolled in the present study, and 198 healthy premenopausal women with regular menstruation were served as control. The postmenopausal women were pouped into the HRT group and the non-HRT group. The women in the HRT poup have received estrogen with continuous or cyclic progestin therapy far more tban 6 months. The biochemical bone markers of all women were assayed. Results were analysed with Students t-test. RESULTS: The urinary DPD of the non-HRT group was sigaificantly higher than both the HRT poup and the premenopausal group(5.51 +/- 2.47 vs. 3.36 +/- 1.02 and 4.01 +/- 3.86 nM/mM, p < 0.05, repectively). The urinary NTX of the non-HRT group was also higher in comparison to the HRT group and the premenopausal group(48.71 +/- 11.54 vs. 33.70 +/- 17.43 and 33.70 +/- 17.43 nM BCE/mmol, p < 0.05, repectively). However, there were no significant differences in the concentrations of serum BSAP and OC among the three poups. CONCLUSION: The urinary DPD and NTX were more sensitive indicators of bone metabolism tban serum BSAP and OC in postmenopausal women undergoing HRT.

Clinical Significance of Bone-Specific Alkaline Phosphatase as a Marker of Bone Turn-Over In Hemodialysis Patients: Impact of Metabolic Acidosis on Various Bone Markers / 대한신장학회잡지

Renal osteodystrophy is a leading cause of morbidity in patients with end stage renal disease(ESRD), including a diverse clinical spectrum and histologic lesions. Since the invasiveness and practical limitations of bone biopsy to diagnose the exact nature of bone disease in ESRD patients, many attempts have been made to investigate the biologic markers of bone disease. Bone-specific alkaline phosphatase(bAP) is localized in the plasma membrane of osteoblast to be involved in bone formation and skeletal mineralization. This study was undertaken to evaluate the value of bAP in the diagnosis of renal osteodystrophy and to examine the correlation between bAP (Immunoassay, Metra, U.S.A.) and other known markers of bone turn-over, total alkalilne phosphatase (tAP), intact parathyroid hormone(iPTH) and osteocalcin in 49 HD patients(M:F 29:20, mean age 51 years, mean HD duration 57 months). We also evaluated the impact of metabolic acidosis, which is known to stimulate the osteoclastic activity and bone resorption, on plasma levels of these bone markers. The median value of bAP in HD patients was 30.1ng/ml with a distribution of 8.8-140.1ng/ml (normal 12-23ng/ml). There was a significant positive correlation between the duration of HD and plasma levels of tAP, bAP, iPTH and osteocalcin. Significant positive correlaton was also observed between iPTH and other markers of bone turn- over-bAP, tAP and osteocalcin. bAP was correlated better with iPTH(r=0.8483, P<0.001) than tAP(r= 0.7588, P<0.01). In the patients group whose arterial blood bicarbonate below 20mEq/L(30 cases), plasma iPTH and bAP were significantly higher compared to the patients with arterial bicarbonate higher than 20mEq/L(19 cases). In conclusion, high bAP can be an useful marker of increased bone turn-over in HD patients. Increased concentrations of iPTH and bAP in patients with metabolic acidosis(arterial bicarbonate below 20 mEq/L) may reflect an increased bone resorption with resultant increase in osteoblast activity. However, a prospective study with alkali supplementation and bone biopsy will be necessary to define the exact role of metabolic acidosis in the development and progression of renal osteodystrophy.

Cell function changes of bone tissue in early glucocorticoid-induced femoral head necrosis and the therapeutic effects of external application of Chinese medicines / 解放军医学杂志

Objective To investigate the clinical significance of cell function changes of bone tissue in glucocorticoid-induced avascular necrosis of femoral head(GANFH),and the preventive and therapeutic effects of "Cugusugao" ointment,a mixture of traditional Chinese medicines,on GANFH.Methods Sixty-four New Zealand white rabbits were randomly divided into four groups(16 each): control group,model group,therapy group and prevention group.The contents of bone-specific alkaline phosphatase(BSAP) and bone gla protein(BGP),and the activity of tartrate-resistant acid phosphatase(TRAP) in serum were determined at the 0,2nd,4th,6th,8th and 12th week after treatment.Meanwhile,rabbits were sacrificed at the 4th,6th,8th and 12th week,and bilateral femoral heads were obtained for histopathological examination.Results Compared with control group,the contents of serum BSAP were elevated at the 4th and 6th week,while TRAP elevated from the 2nd week and BGP lowered from the 4th week in model group(P