| Partâ… : The Bone Mineral Density in Patients with Idiopathic Hypoparathyroidism(With Aanlvsis of 71 Cases)Background and ObjectivesParathyroid hormone (PTH) is a peptide hormone of 84 amino acids synthesized andsecreted by the parathyroid glands. Its physiological actions include enhancing bone resorptionby stimulating osteoclast, increasing the calcium resorption of kidney, and indirectly enhancingthe calcium reabsorption from small intestine by increasing the synthesis of 1,25(OH)2D3 ofkidney. It regulates calcium homeostasis through those multiple ways. PTH, as one of the threemain calcium-regulating hormones, has considerable actions on bone metabolism. The actionsof PTH on bones are complicated. It can increase both bone formation and bone resorption. Itsnet effect on bone mass depends on the type of bones (trabecular or cortical), the particulartype of target cell, and the continuous or intermittent pattern of PTH administration.In primary hyperparathyroidism, the increase in PTH levels leads to generaldemineralization of the skeleton, which may appear radiologically as osteoporosis. Thisreflects the influence of overproducted PTH on bone. Idiopathic hypoparathyroidism is adisorder with calcium and phosphonium metabolism abnormality due to deficiency of PTHsecretion. Its bone mineral density (BMD) directly indicates the effect of chronic deficiency ofPTH on skeleton. Previously, it has been reported that patients with hypoparathyroidism haveincreased bone mineral density (BMD). The sample size of these studies, however, is toosmall to be conclusive. In addition, in the studies conducted among patients with post surgicalhypoparathyroidism, it is difficult to exclude the confounding effects of pre-existing conditionssuch as hyperthyroidism and L-thyroxine replacement therapy on BMD. In this study, weevaluated BMD changes in 71 patients of idiopathic hypoparathyroidism admitted in thePeking Union Medical College Hospital (PUMCH) to: (1) evaluate the BMD change inidiopathic hypoparathyroidism; (2) analyze the potential influencing factors on BMD inidiopathic hypoparathyroidism.Subjects and Methods71 patients of idiopathic hypoparathyroidism admitted in PUMCH (79 males and 156females) aged 35.9±12.1years (18～71years old) with history of 10.6±9.4years (1month— 40years) were retrospectively analyzed. The year of BMD examination was from 1996～2006.The diagnosis was confirmed by serum calcium, phosphorus and PTH levels. No evidence ofadrenocortical insufficiency and any other endocrine disease were found in these cases. Serumtotal calcium (YCa), ionized calcium (ICa), phosphorus (P), AKP, PTH and urinary Ca, Plevels were determined. BMD was measured by dual energy X-ray absorptionmetry at lumbarspine and proximal femur. BMD of patients with idiopathic hypoparathyroidism was comparedto that of healthy individuals and the influencing factors of BMD in idiopathichypoparathyroidism were evaluated. In order to understand the effects of duration of calciumand vitamin D treatment, duration of the disease, and serum calcium level on BMD, BMD ofpatients was compared between 1) those that received calcium and vitamin D treatment for lessthan one month and those that received the treatment for one or more than one month, 2) thosethat had the disease for less than ten years and those with the disease for ten or more than tenyears, and 3) those with serum calcium levels lower than 1.5mmol/1 and those with serumcalcium levels equal to or higher than 1.5mmol/l.Results1. Comparison of BMD between idiopathic hypoparathyroidism patients and healthyindividuals: Compared to the healthy adults, patients with idiopathic hypoparathyroidismshowed significantly higher BMD at lumbar spine and proximal femur (p＜0.001). The meanvalues of BMD at lumbar spine, neck, ward's triangle and trochanter of the male patients were1.356±0.188 g/cm2, 1.087±0.167g/cm2, 1.036±0.208g/cm2 and 0.954±0.139g/cm2, respectively.Compared with that of the healthy volunteers, BMD values at the aforesaid sites of malepatients increased 20%, 14.9%, 27.3% and 16.9% respectively. The mean values of BMD atlumbar spine, neck, ward's triangle and trochanter of the female patients were 1.400±0.249g/cm2, 1.073±0.151g/cm2, 1.014±0.206g/cm2 and 0.912±0.129g/cm2, respectively. Comparedwith that of the healthy volunteers, BMD values at the aforesaid sites of female patientsincreased 29.2%, 22.2%, 31.5% and 24.4%, respectively.2. Comparion of BMD between patients with therapic duration of vitamin D and calciumless than one month and patients with therapic duration equal to or more than one month: Themean BMD values at lumbar spine, neck, ward's triangle and trochanter of group with therapicduration less than one month were 1.350±0.213g/cm2, 1.054±0.131g/cm2, 0.987±0.182g/cm2 and 0.912±0.135g/cm2, respectively. The mean BMD values at the aforesaid sites of groupwith therapic duration equal to or longer than one month were 1.397±0.231g/cm2,1.097±0.174g/cm2, 1.050±0.220g/cm2 and 0.946±0.135g/cm2, respectively. There was nosignificant difference between BMD values of these two groups (P＞0.05). BMD values atlumbar spine, ward's triangle and trochanter of the male patients were significantly higher thanthat of the healthy volunteers, while the Neck BMD values showed no significantly differencebetween the male patients and the male healthy volunteers (P=0.089). BMD values at theaforesaid sites of female patients were significantly higher than that of the female healthyvolunteers (P＜0.001).3. Analysis of the influencing factors of idiopathic hypoparathyroidism BMD: Lumbarspine BMD was significantly negatively correlated with untreated serum calcium level (Beta=-0.392, P=0.001), while significantly positively correlated with the duration of the disease(Beta=0.392, P=0.001). Femoral neck BMD was significantly positively correlated with theheight of the patients (Beta=0.263, P=0.036).Ward's Triangle BMD was significantlynegatively correlated with the age of BMD examination (Beta=-0.358, P=0.004). TrochanterBMD was significantly positively correlated with the height of the patients (Beta=0.252,P=0.044).There was no significant relationship between BMD and serum AKP, PTH, P, urinary Ca,P levels, age of idiopathic hypoparathyroidism onset(P＞0.05).4. Influence of untreated serum calcium level and the duration of the disease on BMD:Lumbar spine BMD of patients with duration of disease equal to or more than 10 years weresignificantly higher than that of patients with duration of disease less than 10 years(1.442±0.248g/cm2 VS 1.320±0.184g/cm2, P=0.019) . Lumbar spine BMD of the patientswith untreated serum calcium level lower than 1.5mmol/1 were significantly higher than that ofthe patients with untreated serum calcium level equal to or higher than 1.5mmol/l (1.430±0.209g/cm2 VS 1.333±0.229g/cm2, P=0.017).Conclusions1. BMD at lumbar spine and proximal femur of idiopathic hypoparathyroidism patients wassignificantly higher than that of the healthy volunteers. The increasing percentage of meanBMD values was from 14.9% to 31.5%. 2. BMD of the patients received calcium and vitamin D treatment for less than one monthshowed no significant difference compared to that of patients received the treatment for one ormore than one month. BMD values at lumbar spine, ward's triangle and trochanter of the malepatients were significantly higher than that of the healthy volunteers. BMD values at theaforesaid sites of female patients were significantly higher than that of the female healthyvolunteers. This indicated that the increased BMD of idiopathic hypoparathyroidism patientswas directly caused by PTH deficiency.3. Lumber spine BMD was significantly negatively correlated with untreated serum calciumlevel, while significantly positively correlated with the duration of the disease. Lumber spineBMD of patients with relatively severer hypocalcemia were significantly higher than that ofpatients with relatively mild hypocalcemia. As the disease duration prolonged, the BMD atlumber spine increased. It suggested that idiopathic hypoparathyroidism patients with severerillness state and relatively longer disease duration had higher BMD level.4. There was no significant association between serum AKP, PTH, P, urinary Ca, P levels, ageof onset and BMD at different sites. Partâ…¡: The association of Vitamin D Receptor Gene Polymorphism and IdiopathicHypoparathyroidismBackground and ObjectivesIdiopathic hypoparathyroidism is a disorder with calcium and phosphonium metabolismabnormality due to insufficiency of PTH secretion. Chronic hypocalcemia is the main clinicalmanifestation. Symptoms including mentality impairment, remembrance decrescence, cataractaand ectopic calcification may develope as the progress of the disease. Administration ofvitamin D or its analogue combined with calcium is often necessary to correct hypocalcemia inhypoparathyroidic patients. But it is unable to re-establish the physiologicalcalcium/phosphorus homeostasis. Investigation about the genetic foundation should havesome considerable meaning on the therapy of this disease.Vitamin D is one of the main calcium regulating hormones. It can execute itsphysiological activity by binding to vitamin D receptor (VDR) and forming a vitamin D-VDRcompound. There are several polymorphism sites in human VDR gene. The VDR gene 3' endpolymorphisms (i.e., Bsmâ… , Apaâ… , and Taqâ… ) have been reported to be associated with severalcommon metabolic bone diseases, including osteoporosis and parathyroid hyperplasia disease. Up to now, there is no report about the relationship of VDR gene polymorphism andhypoparathyroidism.Patients with same serum PTH level may have different manifestation, and the dosagesof vitamin D also differ significantly. From this we can presume that VDR genepolymorphisms may have some association with idiopathic hypoparathyroidism. Thus, the aimof this study is to investigate the frequencies of the genotypes of vitamin D receptor gene 3'endpolymorphisms, and to evaluate the association between different VDR genotypes and theclinical manifestation of idiopathic hypoparathyroidism, and finally to identify the significanceof VDR gene genetic variation to idiopathic hypoparathyroidism.Subjects and Methods106 patients of idiopathic hypoparathyroidism admitted in PUMCH during 2004～2007(52 males and 54 females) aged 23±12years were retrospectively analyzed. BMD wasmeasured in 63 patients. The mean age and the mean duration when they did the BMD examination were as follows: 36±12 years and 11±10 years. Genome DNA was extracted byQIAGEN DNA extraction kit from peripheral white blood cell. VDR genotypes weredetermined by PCR-RFLR Serum total calcium (TCa), ionized calcium (ICa), phosphorus(P), AKP, PTH and urinary Ca, P levels were determined. BMD was measured by dualenergy X-ray absorptionmetry at lumbar spine and proximal femur.Results1. The frequencies of the genotypes of vitamin D receptor gene 3' end polymorphisms:The frequencies of the Bsmâ… polymorphisms site were as follows: bb genotype: 88.7%; Bbgenotype: 11.3%; no BB. The frequencies of the Apaâ… polymorphisms site were as follows: aagenotype: 49.1%; Aa genotype: 44.3%; AA genotype: 6.6%. The frequencies of the Taqâ… polymorphisms site were as follows: no tt; Tt genotype: 8.5%; TT genotype: 91.5%. Allele b, Tand a account for 94.3%, 95.8% and 71.2%, respectively. Hardy-Weinberg equilibrium wasevident. Comparison between idiopathic hypoparathyroidism patients and normal individual:There was no significant difference about the VDR gene 3'end polymorphism distributions(P＞0.05).2. The association between VDR gene 3'end polymorphisms and clinical manifestationsof idiopathic hypoparathyroidism: No differences in various clinical manifestations of eachgenotypes were found (P＞0.05).3. The association between VDR gene 3'end polymorphisms and biochemical indexes ofidiopathic hypoparathyroidism: No differences in serum Ca, P, AKP, PTH and urinary Ca werefound in different polymorphisms.4. The association between VDR gene 3'end polymorphisms and BMD of idiopathichypoparathyroidism: No differences were found in different polymorphisms.Conclusions1. The frequencies of the genotypes of vitamin D receptor gene 3'end polymorphism ofidiopathic hypoparathyroidism were as follows: allele b: 94.3%, allele a: 71.2%, and allele T:95.8%. Hardy-Weinberg equilibrium was evident. There was no significant difference about theVDR gene 3'end polymorphism distributions between idiopathic hypoparathyroidism patientsand normal individual.2. There were no significant differences in clinical manifestations, BMD values, serum Ca, P, AKP, PTH and urinary Ca, P levels between idiopathic hypoparathyroidism patients of eachgenotype of various polymorphisms in this study. |
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