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1.Acute Effects of Oral Phosphate-salt Loading on Serum Phosphate and Parathyroid Hormone in Hypophosphatemic Rickets/Osteomalacia 2.Clinical Features of 56 Patients with Hypophosphatemic Rickets

Author: HeXiaoDong
Tutor: XiaWeiBo;JiangYan
School: Peking Union Medical College , China
Course: Endocrinology
Keywords: Hypophosphatemia Rickets Osteomalacia Phosphorus Parathyroid hormone
CLC: R591
Type: Master's thesis
Year: 2009
Downloads: 12
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Abstract

[Objective]To compare the effets of acute oral phosphate-salt loading on parathyroid hormone(PTH) secretion in patients with hypophosphatemic rickets/osteomalacia with that in normal individuals.[Subjects and Methods]1.Subjects14 patients with hypophosphatemic rickets/osteomalacia were enrolled in hypophosphatemic group and 8 healthy volunteers were enrolled in control group.The hypophosphatemic group,8 males and 6 females,aged 35.1±12.6y in average((?)±s),in whom 3 were diagnosed as tumor-induced osteomalacia(TIO),and the diagnosis of others remained unclear,but renal tubule acidosis was all excluded.The mean age of control group,4 males and 4 females,was 29.0±9.6y,general appearences of whom were all well.History of chronical diseases and abnormal family history were all denied by them.All subjects(including two groups) hadn’t ever taken any preparation of phosphate,calcium and VitD during past 2 months before the test.2.Study protocolAcute oral phosphate loading test was undertaken.All subjects ingested 1.5g Pi given as neutral-buffered sodium-potassium phosphate in 192ml of water in morning after fasting at least 12 h.Venous blood samples were drawn at 30～60-mm intervals from 0 mm to 210 mm to determine serum Pi and iPTH levels.Urine was collected from o mm to 210 mm to determine urinary Pi excretion during this period.With healthy volunteers controlled,the characteristics of fasting serum iPTH and the changing modes of serum Pi,iPTH after digestion of Pi in patients were observed.Furthermore,the correlations of serum Pi level,urinary Pi excretion with serum iPTH level were analyzed.3.Statistical MethodsFor repeated measurement data,statistical analysis was conducted using ANOVA of repeated measurement data.One-Way ANOVA or independent-samples t tests(two-tailed) was used to compare the mean values of iPTH,Pi between groups.Correlation of two variables was analyzed by Pearson correlation coefficient.A p value less than 0.05 was considered statistically significant.Statistical analyses were performed with the SPSS statistical software package.[Results]1.General appearanceThere was no significant difference in ages between hypophosphatemic group and control group.The serum Pi level was significantly lower in hypophosphatemic group than that in control group(P＜0.001),while serum ALP level was significantly higher in former than that in latter (P＜0.001).No significant difference did exist in baseline iPTH level between two groups(P＞0.05). In hypophosphatemic group,the baseline iPTH level was in normal range in 7 individuals and exceeded normal range in another 7 individuals.TmP/GFR was also significantly lower than normal range in hypophosphatemic group.2.Change of serum Pi level before and after phosphate loadThe serum Pi level were all elevated in both two groups after phosphate ingestion and were all significantly above baseline values at each timing point and reached its peak all at 60mm point.Despite of significant elevation,the serum Pi level in hypophosphatemic group was still significantly lower than or just at lower limit of normal range.After phosphate load,the increase value of serum Pi level relative to baseline in hypophosphatemic group was lower than that in control group,especially at 60min point did exist significant difference(hypophosphatemic group: 0.39±0.28mmol/;control group:0.64±0.20mmol/L;P＜0.05).3.Change of serum iPTH level before and after phosphate loadThe serum iPTH levels in hypophosphatemic group was all significantly higher than baseline values(P＜0.05) from 30mm to 150ram after phosphate load and this kind of significance disappeared until 210min,while the serum iPTH in control group was significantly above baseline value only at 30min after phosphate load.According to the baseline iPTH level,the 14 patients of hypophosphatemic group were divided into two subgroups:high iPTH hypophosphatemic group(n=7) and normal iPTH hypophosphatemic group(n=7).In former the iPTH levels were not further elevated at all timing points,while in latter,the iPTH levels were significantly elevated at each timing point after phosphate load(P values all less than 0.05),and the peak of which occurred at 60mm point when the increase values(ΔiPTH) were significantly higher than that in control group,33.4±15.5pg/ml and 10.5±21.7pg/ml,respectively.But no significant difference in iPTH at each timing point after phosphate load did exist between high iPTH hypophosphatemic group and control group.4.The correlations of serum Pi,iCa and urinary Pi excretion with serum iPTH levelBetween the fasting serum iCa and iPTH available in 8 patients(determind simutaneously before the oral phosphate loading test),there existed negative correlation.(r=-0.844,P=0.008). There were no correlation between serum Pi and iPTH level at baseline in 14 patients.In all subjects,no correlation did exist between the peak values of serum Pi and the peak values of iPTH after phosphate load.In all subjects,no correlation did exist between the maximal changing velocity of serum Pi level and the changing velocity of iPTH at same time span after phosphate load.In all subjects,no correlation did exist between the area under curve of serum Pi and that of serum iPTH.[Conclusion]The changing pattern of serum Pi after acute digestion of Pi in hypophosphatemic rickets/ osteomalacia is similar to that seen in normal individuials,in which serum Pi level reachs its peak at 60mm after Pi load,but the growth rate in hypophosphatemic rickets/osteomalacia patients is lower than that in normal individuals.There exists notable heterogenicity in the baseline serum iPTH levels in patients and a remarkable portion present a striking rise.In contrast with the transient,unremarkable rise that remains in normal range as a whole after Pi load in normal individuals,the rise of serum iPTH levels after Pi load is longer-lasting,more significant and outside normal range in general.The effect is more evident in patients whose serum iPTH is normal at baseline.The elevation of fasting serum iPTH may be related to potential hypocalcemia.On aggregate,parahyroid gland of patients presents a kind of sthenic response to Pi loading,which have some clinical meanings and deserve serious consideration in clinical practice. Objective:To analyze the clinical features of 56 patients with hypophosphatemic rickets(HR) followed at our institution,and to summarize the effects of medication therapy on this disease. Methods:56 patients with HR followed in our hospital were retrospectively analysed.The clinical featrues and therapeutic responses were summaried,with emphasis on the BMD characteristic and the impact of combination therapy with VitD metabolites and phosphate on patients’ height.Results:56 patients with HR came from 51 unrelated family,the male-to-female ratio is 23:33 and 23 patients was familial.Their median age at the time of diagnosis was 11.0 years old,the duration of follow-up ranged from 0.1 to 37 years(median:2.5). The mean birth length of 9 patients with related records available was 49.3±2.9cm.The rickets manifestations such as lower limb deformities,gait abnormality,and growth retard were all found before 4 years old,mostly during the period of learning walking.Low-trauma fractures (all sites were long bone of extremites) occurred in 6/56 individuals;55/56 patients had lower limb deformities,among them 19 patients had ever undergone osteotomies on at least one occasion.6/16 individuals had experienced dental problems.The height of the group of combination treatment with active VitD metabolite and phosphate(n=9) was significantly higher than that of untreated group(n=37)(-1.71±1.00,-3.04±1.11;P＜0.05),The mean Z-score of 14 patients with final height achieved in untreated group is -3.63±0.93.The BMD was determind by DXA in total 20 patients,the Z-score of which in L2～4 is elevated as a whole either in untreated patients(n=7) or in patients that had been treated(n=13)(median:1.9,2.0, respectively);During the treatment,PTH was markedly elevated to be higher than 150pg/ml in 4/26 patients,and nephrolithiasis was found in 2 patints;In follow-up period,no spontaneous relieve was found.Conclusions:Typical manifestations of rickets can occur in most patients with HR if effective therapy are not given in time;With age bone pain and arthralgia can occur more frequently and obviously.The birth length of HR patients isn’t low;The combination therapy with active VitD metabolites and phosphate can be effective to improve the height.The BMD characteristic of HR patients can be:the BMD in lumbar isn’t low,but that in long bone of extremities can be low.Medication therapy can induce the significant elevation of serum PTH level,so strict follow-up is needed.

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