| Part 1 Evaluation of the clinical features of adults with osteogenesis imperfecta and of the effects of bisphosphonates treatment Objective:Osteogenesis imperfecta(OI) is a rare genetic bone disease characterized by increased bone fragility and frequent fractures. The fracture incidence of most patients with OI significantly decreases after adulthood, so adult patients with OI had not been paid sufficient attention. There are very rare studies concerning OI in adults. We aim to evaluate the clinical features of OI in adults, and investigate the efficacy and safety of alendronate and zoledronic acid in these patients. Methods:60 adult with OI(OI group) and 60 healthy controls matched in age, gender and body mass index(selected from database of Chinese bone turnover marker study) were enrolled. OI patients were randomly assigned to alendronate treatment group(receive 70 mg alendronate weekly, n = 40) or zoledronic acid group(infusion with 5mg zoledronic acid yearly, n = 20). The treatment period was two years. All patients were supplemented with 500 mg calcium and 200 IU vitamin D daily. Serum β-isomerized carboxy-telopeptide of type I collagen(β-CTX) and total alkaline phosphatase(ALP) levels were measured at baseline, 6 months,12 months,18 months and 24 months by chemiluminescence immunoassay and automatic analyser, respectively. Bone mineral density(BMD) at lumbar spine 2-4(L2-4), femoral neck(FN), troch(TR) and total hip(TH) was measured at baseline, 6 months 12 months, 18 months and 24 months of treatment by dual-energy x-ray absorptiometry. Analyze difference of bone turnover marker levels and BMD at baseline between OI and healthy groups. Analyze changes of bone turnover marker levels, BMD and fracture frequency of OI patients before and after bisphosphonate treatment. Analyze changes of bone turnover marker levels, BMD and fracture frequency after ALN or ZOL treatment. Results: L2-4 BMD(0.751±0.190g/cm2), FN BMD(0.620±0.224 g/cm2), TR BMD(0.510±0.123 g/cm2) of adults with OI were significantly lower than those of normal subjects(1.089±0.139 g/cm2, 0.980±0.162 g/cm2, 0.820±0.158 g/cm2)(P<0.05). However, bone turnover markers levels and fracture frequency were higher than those of healthy subjects. According to Sillence criteria, patients with OI were classified as type Ⅰ(n=22, 36.67%), type Ⅲ(n=11, 18.33%), type Ⅳ(n=27, 45.00%). Serum β-CTX level of type ⅠOI patients(0.25±0.10 ng/ml) was significantly lower than that in type Ⅲ(0.40±0.24 ng/ml) and type Ⅳ OI(0.43±0.11 ng/ml) patients(P=0.037), but there was no obvious difference of ALP levels and BMD among three types of OI patients(P > 0.05). Bisphosphonates treatment could significantly increase BMD, decrease bone turnover markers levels and reduce incidence of bone fractures of adults with OI. No differences of changes in BMD and bone turnover biomarkers was found between alendronate and zoledronic acid groups. After 24 months of treatment, the percent changes from baseline of TH BMD(22.84±13.43%) in type ⅠOI patients was significantly higher than type Ⅲ(15.21±16.27%,P=0.038) and type Ⅳ(14.42±4.77%,P=0.031) OI patients. Conclusions: Adults with OI still need to receive treatment to reduce risks of new fracture, even though their fracture incidence significantly drop after adulthood. Bisphosphonates are effective to increase BMD, reduce turnover biomarkers levels and decrease bone fracture incidence. The therapeutic effect of alendronate and zoldronic acid was similar in adults with OI. Patients with OI type Ⅰhad better response to bisphosphonates than type Ⅲ and type Ⅳ OI patients. Part 2 Observation and intervention of glucocorticoid’s effects on bone and muscle of patients with myasthenia gravis Objective:Myasthenia gravis(MG) is an autoimmune disease of neuromuscular junction characterized by muscle fatigability and weakness. Glucocorticoids are widely used treatment for myasthenia gravis, which can affect bone and muscle through various mechanisms. Osteocalcin(OC), as an important factor of bone metabolism, is also possibly related to glucose metabolism. We aim to explore the relationship between bone and muscle in MG patients, to evaluate the role of OC in glucose metabolism, and to prospectively evaluate the effects of alendronate on glucocorticoid induced osteoporosis. Methods:50 patients with myasthenia were included from Peking Union Medical College Hospital who would accept glucocorticoid treatment. The patients were divided into treatment group(with osteopenia, 70 mg alendronate weekly, n=17) and prevention group(with normal bone mass, n=33). All patients also received 500 mg of calcium and 0.25μg alfacalcidol daily. Serum levels of β-isomerized carboxy-telopeptide of type I collagen(β-CTX), total alkaline phosphatase(ALP) and osteocalcin levels, fasting blood glucose( FBG), 2 hour postprandial blood glucose(2h PBG), fasting insulin(FINS), 2 hour postprandial insulin(2h PINS) and hemoglobin A1C(Hb A1C) were assessed at baseline, 3 months and 6 months of treatment. Bone mineral density(BMD) at lumbar spine 2-4(L2-4), femoral neck(FN) and total hip(TH) at baseline, 6 months of treatment was measured by dual-energy x-ray absorptiometry. Hand grip strength and leg power were measured by electronic hand dynamometer and the standing time on one leg at baseline and 6 months of treatment, respectively. Results:At baseline, 15 patients had impaired glucose tolerance or type 2 diabetes, who were given acarbose(50mg, tid) during the study. The age(P=0.041), TG(P=0.037) and 2h PBG(P=0.004) levels in treatment group were significantly higher than those in prevention group. BMD at L2-4(P=0.003), FN(P=0.000), TR(P=0.000) and TH(P=0.000) in treatment group was significantly lower than those in prevention group. The level of OC was significantly and positively correlated with ALP(r=0.985, P=0.007), β-CTX(r=0.971, P=0.015) and standing time on one leg(r=0.777, P=0.012), but negatively with FN BMD(r=-0.903, P=0.048). The standing time on one leg was positively correlated to ALP(r=0.716, P=0.023), β-CTX(r=0.728, P=0.020) and OC(r=0.777, P=0.012). HGS had no significant correlation with other indexs(P>0.05). After 6 months with GCs treatment, up and lower limber muscle strength had increased compared with that in baseline, but no difference were found(P > 0.05). Percentage changes from baseline of BMD at L2-4(4.54±1.12%) 、 FN(4.68±1.62%)and TH(3.12±1.59%) in treatment group were significantly higher than those in prevention group(-5.11±1.97%、-1.08±2.24%、-1.50±2.07%)(P<0.05). The average dose of GCs and percentage changes from baseline of muscle strength, glucose metabolism markers and bone turnover markers had no significant difference between treatment group and prevention group. Conclusions:We did not found significant correlation between serum OC level and glucose metabolism. Muscle strength of lower limbs was positively correlated to bone turnover biomarkers levels. Alendronate could effectively reduce bone turnover biomarkers and increase BMD in patients with myasthenia gravis who received glucocorticoids treatment, while calcium and alfacalcidol were not powerful enough to prevent bone loss induced by glucocorticoid. |
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