Research Of Determination Of Level Of Serum Osteocalcin And Bone Age And Its Relationship With Growth And Development Of Children With OSAHS

BackgroundObstructive sleep apnea hypopnea syndrome (OSAHS) refers to partial or complete obstruction of upper airway frequently during sleeping, which leads to hypoxia, hypercapnia and disrupts patients’normal sleep structure and then causes a series of pathophysiological changes. It is characterized by sleep snoring, frequently apnea and/or hyponea and interrupted sleep, and its main pathophysiological change is hypoxia, carbon dioxide retention and bad sleep structure caused by frequently waken up. It has been wide attention that OSAHS is a disease with high incidence and serious harmfulness. Middle and old men are the high-risk group. The incidence of men with OSAHS is4%to9%and that of women is1%-2%. For a series of pathology and physiological changes caused by OSAHS, it could lead to patients daytime sleepiness, inattention, memory loss and then to impact the quality of study, work and life. More attention, there is close relationship between OSAHS and the development of multi-organ and multiple systems diseases, such as high blood pressure, cardiovascular system disorders, metabolic disease, neurological diseases. It is a harmful threat to human healthy. Along with the development of sleep medicine, it has been wide attention for healthcare professionals that children are another high-risk group with OSAHS. Because of the special growth stage of children, sleep disorders especially OSAHS is harmful to their growth. OSAHS is one of common diseases of children. It occurs in children of2to6years and its incidence is about1%-3%.There is difference between children and adults with OSAHS in gender distribution, etiology, diagnosis standards, treatments, main harm and so on. It is not different in gender of children with OSAHS. It is mostly caused by physiological or pathological hypertrophy of adenoid and/or tonsil and low ventilation is the common performance. It is not only harmful to body growth of children, but also to the mental development.A critical period of growth and development is during childrenhood. However, the metabolism of brains and the growth of bodies are interferenced by physiological imbalance such as hypoxia, hypercapnia caused by long-term frequent sleep apnea of OSAHS children. Restless sleep, frequently waken up and other bad sleep structure cause endocrine disorders. For example, growth hormone is reduced which could lead to loss of the related bone and stunted growth. During long-term clinical observation, it was found that children with OSAHS not only affected the growth of their bodies, but also influenced the development of their intelligence. Once suffered, without timely and appropriate treatment, it could lead to serious consequences. And thus early screened and correct diagnosis are especially important.Osteocalcin is a non-collagen bone protein secreted by osteoblasts, which could promote the normal process of calcification of bone mineral. The level of serum osteocalcin could be used as a sensitive biochemical indicator for bone growth and development of children according to reports in the literature. Calcification and maturation of bone tissue related to growth hormone(GH), which could promote bone transformation of ostrogenie cell. The level of osteocalcin which could reflect secretion status of growth hormone, could be used to evaluate growth and development of children and monitor the response of treatment of children with growth retardation. Therefore, this study would analyze the relationship between osteocalcin level and the growth and development of children with OSAHS.Bone age is a measurement of the degree of skeletal maturity of children and could be obtained by comparison of the bone growth levels and the standard level of the same age. Compared with height, weight, BMI and other indexes, bone age could reflect the actual level of children’s growth and development accurately. The biological age of children could be determined and the growth potential of children could be predicted by the determination of bone age. In this study, the influence of OSAHS on children’s bone growth was discussed through comparison of bone age of children with OSAHS and healthy children.At present, it has been reported the pathogenesis of OSAHS in children, the relationship with growth hormone and thyroid hormone and so on. While the mechanism of children growth retardation caused by OSAHS is not clear. There is no repot about the relationship between bone age, serum osteocalcin and growth and development of OSAHS in children. So this study was trying to discuss the influence of OSAHS on growth and development of children, especially on the growth and development of bone through the analysis of the indicators for OSAHS children such as bone age, level of serum osteocalcin, height, weight, etc.ObjectiveTo discuss the influence of obstructive sleep apnea hypopnea syndrome on children’s growth, especially on their bone growth, by the determinations and analysis of serum osteocalcin level and bone age, including height, weight and other indicators.Methods1.Questionnaire preparationPrepared a questionnaire used to evaluate the growth and development of children, according to the indicators which could reflect the growth and development of children and commonly used in questionnaires, including general conditions of children, pregnancy and the situation of birth, sickness and sleeping, physical examination.2.Diagnosis standard of OSAHS in childrenThe diagnosis standard of OSAHS children in this study was according to the guidelines draft of the diagnosis and treatment of children OSAHS. According to the data monitored by instrument PSG (polysomnography), Hypopnea was defined as the airflow amplitude of nasal and buccal decreased by50%last more than6s and associated with the oxygen saturation of arterial blood decreased more than3%and/or waken up. Sleep apnea was defined as the airflow of nose and buccal stopped more than6s while the thoracic and abdominal movements was existed. Once the sleep apnea-hypopnea index(AHI)≥5times per hour and associated with hypoxia, OSAHS could be diagnosed. AHI5-10times/h and LaSO20.85-0.91for the mild,10-20times/h and LaSO20.75-0.84for moderate,more than20times/h and LaSO2<0.75for severe.3.Experimental group and control groupAccording to the above standard of children with OSAHS,29children cases(male21,female8) with OSAHS, who came to the Second Hospital of Shandong University for treatment from september,2010to april,2011, were selected as the experimental group.Meanwhile,13children cases(male13, female4) without snoring and breathing problems were selected as the control group. There was no other significant differences between the two groups except whether or not suffered from OSAHS according to the characteristics of the control group, such as age(t=0.82,P>0.05), gender(χ2=0.044, P>0.05), etc.4.Questionnaire surveyTo obtain information about diseases history and basic status of children’s growth and development, the parents of the two groups was investigated with the questionnaire. Quality control of the survey was done at the same time, for example, the children on-set measurements. After data was collected, the body mass index (BMI), height standard deviation score (HtSDS) and weight standard deviation score (WtSDS) were calculated according to data from the questionnaire.5.PSG monitoringAll of the subjects were monitored with polysomnography continuously at least7hours, the indicators including nasal and buccal airflow, arterial oxygen saturation, chin electromyogra(CEG), electromyography(EMG), electro-oculogram(EOG), electroencephalogram(EEG), electrocardiogram(ECG), snore,thoracic and abdominal movements,etc.6.Blood samples and X-rays of left wristThe fasting venous blood of all children was taken in the morning. The blood was centrifuged for serum,and then the serum was stored at-80degree refrigerator. Moreover, all the children were taken X-rays on left hand wrist. Then the X-rays were given random numbers, and then assessed.7.Determination of serum osteocalcin and assessment of bone ageThe level of serum osteocalcin was determined by enzyme-linked immunosorbent assay (ELISA). Wrist X-rays was randomly assessed for bone age by an experienced radiologist with the method of TW2.Results1.Bone ageThe bone age of the experimental and control group were6.31±1.12years and6.45±1.57years, respectively. There was no statistical difference between the two groups (t=0.15,P>0.05).2. D-values of the bone age and the real ageThe real age of the experimental and control group were6.81±1.08years and6.07±1.51years, respectively. There was no statistical difference between the two groups (t=0.82, P>0.05). While there was significant difference between the D-values of the bone age and the real age (t=8.07, P<0.05). The D-value of the experimental group was lower than the control group.3. Level of serum osteocalcinThe level of serum osteocalcin of the experimental and control group were7.41±0.31ug/L and10.22±0.50ug/L, respectively. There was statistical difference between the two groups (t=10.17, P<0.05). The level of serum osteocalcin of the experimental group was lower than the control group.4. Indicators of growth and developmentThe height, weight, BMI, HtSDS and WtSDS were1.06±0.07m,25.70±3.55kg,22.42±1.26kg/m2,0.81±1.42,1.83±1.27. While the above five indicators of the control group were1.12±0.10m,25.41±4.36kg,20.05±1.06kg/m2,0.67±0.79,1.56±0.39. The height, weight, HtSDS and WtSDS of the two groups were no differences(P<0.05). While the BMI of the two groups was significant difference(P<0.05). And the experimental group was higher. In addition, there were 3children (7%) existing growth retardation in the experimental group while no one of the control group by contrast.Conclusions1. The mean age of children with OSAHS was0.74year older than the control group, while the mean height was0.06meter lower than the control group. It was indicated that children with OSAHS could impact their height growth.2. The D-value of the real age and the bone age of the OSAHS group was greater than that of the control group and the level of serum osteocalcin of children with OSAHS was still lower than that of control group. It was suggested that children with OSAHS could impact the growth of the bone and then cause growth retardation.3. So there is need to be early screened diagnosis and treatment to children with OSAHS to reduce or avoid the adverse effects to the growth and development of children, especially to that of bone.