Effects of cinacalcet on bone mineral density and bone markers in hemodialysis patients with secondary hyperparathyroidism

Background

Cinacalcet markedly reduces the serum intact parathyroid hormone (PTH) level of hemodialysis (HD) patients with secondary hyperparathyroidism. Parathyroidectomy also reduces the serum intact PTH level of HD patients and it increases their bone mineral density (BMD). However, there is little information about the effect of cinacalcet on BMD or on the associations between bone markers and BMD in HD patients.

Methods

We performed a 1-year cohort study of 25 HD patients who had a serum intact PTH level above 300 pg/ml during treatment by conventional therapies, such as with active vitamin D, and cinacalcet was prescribed for 14 of them. BMD of the femoral neck and the serum levels of two circulating bone markers, alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BSAP), were measured before and after treatment. The other 11 HD patients without cinacalcet treatment were defined as control group.

Results

BMD significantly increased by 7.3 % during the 1 year of treatment in the cinacalcet group and decreased by 6.2 % during the same period in the control group, and cinacalcet therapy was independently associated with the changes in BMD after multiple regression analysis that included intact PTH (β = 7.57, P < 0.01). In the cinacalcet group, the serum ALP levels (R ² = 0.315, P < 0.05) and BSAP levels (R ² = 0.682, P < 0.01) levels were significantly negatively correlated with the changes in BMD, but the serum intact PTH levels were not significantly associated with the changes in BMD (R ² = 0.011, P = 0.72).

Conclusions

One year of treatment with cinacalcet increased the BMD of the femoral neck in the HD cohort, especially in the patients who had higher serum ALP and BSAP levels at baseline.     

甲状旁腺切除术对血液透析患者合并继发性甲状旁腺功能亢进骨代谢及骨密度的影响

目的 观察甲状旁腺切除术(parathyroidectomy,PTX)对继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)的维持性血液透析患者骨代谢及骨密度(BMD)的影响.方法 26例SHPT患者行PTX.术前及术后1、3、6、12、18、24个月时常规检测血钙、血磷、血清碱性磷酸酶,化学发光法检测血清全段甲状旁腺素(intact parathyroid,iPTH)、骨钙素(OC)、Ⅰ型前胶原氨基末端前肽(PINP)、β胶原蛋白(β-C TX),术前及术后24个月时双能X线法测定腰椎、股骨颈、骨盆各部位骨密度,观察患者甲状旁腺切除术前、术后骨代谢指标及骨密度变化.结果 (1)与术前比较,血清OC水平[(104.49±25.42) μg/L比(695.46±355.62) μg/L,P＜ 0.01]、PINP水平[(248.36±159.38) μg/L比(809.28±283.50) μg/L,P＜0.01]于手术3个月后明显降低,β-CTX水平于手术1个月后明显降低[(1.60±0.64) μg/L比(3.37±1.34) μg/L,P＜0.01].(2)与术前比较,术后24个月时腰椎BMD[(0.88±0.23) g/cm2比(0.78±0.23) g/cm2,P＜0.01]、股骨颈BMD[(0.96±0.19) g/cm2比(0.84±0.24) g/cm2,P＜ 0.01]及腰椎Z评分[(-1.24±0.55)比(-1.66±0.24),P＜0.01]、股骨颈Z评分[(-1.51±0.72)比(-1.93±0.40),P＜0.01]均升高.(3)相关分析显示,术前血清iPTH水平与⊿腰椎Z评分(r=0.584,P=0.002)、⊿股骨颈Z评分(r=0.400,P=0.043)呈正相关,术前血清OC水平与⊿腰椎Z评分(r=0.651,P＜0.001)、⊿股骨颈Z评分(r=0.509,P=0.008)呈正相关.结论 PTX术可以降低患者升高的iPTH、OC、PINP及β-CTX水平,增加骨密度,同时改善多项生化指标,提高患者生活质量.     

尿毒症伴重度继发性甲状旁腺功能亢进症骨密度特征 分析

目的研究尿毒症伴重度继发性甲状旁腺功能亢进症患者的骨密度改变特征,分析该组患者骨密度改变与临床特征之间的关系。方法回顾性总结2011年2月至2013年4月在本院接受甲状旁腺全切除联合自体前臂移植术的51例尿毒症伴重度继发性甲状旁腺功能亢进症患者的一般情况、临床特点、股骨近端和腰椎骨密度,及全切除手术所得甲状旁腺质量等数据。比较相同性别患者腰椎L1-L4之间、股骨近端不同部位之间骨密度的差异;对不同部位骨密度减少程度与上述观察变量之间的关系进行相关性分析。结果本组患者临床表现包括皮肤瘙痒、骨痛、身高缩短、面部变形和躯体变形等;血清iPTH高达2227.9±907.3 pg/ml;骨质疏松27例(52.9%),骨量减少23例(45.1%);男女性患者均显示L1至L4椎骨骨密度T值逐渐降低,男性骨密度T值L4显著低于L1(P=0.037),女性骨密度T值L4亦显著低于L1(P=0.039),男女性均显示股骨转子、股骨颈至Ward’s三角区的T值逐渐降低,男性Ward’s三角区T值显著低于股骨转子(P=0.025),女性Ward’s三角区和股骨颈T值显著低于股骨转子(P=0.009和P=0.023)。体重指数、血清白蛋白与骨密度值呈显著正相关,身高缩短、脊柱变形、胸廓变形、面部变形、血清碱性磷酸酶、血清iPTH、甲状旁腺质量与骨密度值呈显著负相关。结论骨质疏松和骨量减少广泛存在于尿毒症伴重度继发性甲状旁腺功能亢进症患者中;身体承重部位骨密度降低更严重;消瘦、低白蛋白血症、面部及躯干变形、iPTH严重升高、甲状旁腺增生程度重等因素提示骨质疏松风险增大。     

Effect of cinacalcet on bone mineral density of the radius in hemodialysis patients with secondary hyperparathyroidism

Background/Aim: Cinacalcet, an allosteric modulator of the calcium sensing receptor, effectively reduces serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. It is not well known whether bone mineral density (BMD) of hemodialysis patients with secondary hyperparathyroidism is altered after cinacalcet treatment. Methods: The BMD in the distal 1/3 of the radius and in the ultradistal radius, which are enriched with cortical and cancellous bone, respectively, was examined by dual X-ray absorptiometry, 1 year prior to, at the start, and 1 year after cinacalcet treatment, in 61 patients. Results: The BMD of both the distal 1/3 and ultradistal radius decreased significantly in the year prior to cinacalcet treatment (p < 0.01). However, the BMD at either site did not change significantly in the year after cinacalcet treatment. The annual changes in the BMD of the distal 1/3 radius increased significantly from -0.023 ± 0.029 g/cm2/year to -0.002 ± 0.033 g/cm2/year, prior to and after cinacalcet treatment, respectively; however, the annual changes in the BMD of the ultradistal radius did not change significantly prior to and after cinacalcet treatment. Conclusion: There was a significant association between cinacalcet treatment and reduction in BMD loss in patients with secondary hyperparathyroidism. Cortical bone, rather than cancellous bone, was particularly affected by cinacalcet treatment.     

Effects of cinacalcet on bone mineral density in patients with secondary hyperparathyroidism.

BACKGROUND: Cinacalcet, a calcimimetic agent, is effective in treating both primary and secondary hyperparathyroidism. Because hyperparathyroidism induces mineralized bone loss, we investigated the effects of cinacalcet treatment on bone mineral density (BMD) in patients with secondary hyperparathyroidism due to chronic kidney disease. METHODS: Ten patients who were receiving haemodialysis and four patients, who had stage 4 chronic kidney disease participated and completed the multicentre, randomized, double-blind, placebo-controlled trials evaluating the safety and efficacy of cinacalcet for treating secondary hyperparathyroidism. The efficacy of cinacalcet was assessed by plasma intact parathyroid hormone (iPTH) levels. A dual energy X-ray absorptiometry was performed to measure the BMD of total proximal femurs and lumbar spine (L2-L4) before and after 26 weeks of treatment. RESULTS: Cinacalcet reduced iPTH from 912+/-296 to 515+/-359 pg/ml in haemodialysis patients and from 210+/-46 to 56+/-51 pg/ml in pre-dialysis patients (means+/-SD; both P<0.05). When data from haemodialysis and pre-dialysis patients were pooled for analysis, cinacalcet treatment increased proximal femur BMD from 0.945+/-0.169 to 0.961+/-0.174 g/cm(2) (P<0.05), but did not affect lumbar spine BMD. There was a correlation between the change in femur BMD and the change in iPTH during the study period (R(2) = 0.39, P<0.05). CONCLUSIONS: Secondary hyperparathyroidism is associated with progressive bone loss. Suppression of plasma iPTH with cinacalcet appears to reverse bone loss in the proximal femur, but does not affect BMD of the lumbar spine. A larger study is warranted to confirm that cinacalcet has a beneficial effect on the skeletal system in patients with secondary hyperparathyroidism.     

Parathyroidectomy can improve bone mineral density in patients with symptomatic secondary hyperparathyroidism

HYPOTHESIS: The recovery of osteoporosis or bone mineral density (BMD) after parathyroidectomy and autotransplantation can be improved in patients with symptomatic secondary hyperparathyroidism. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Forty-five patients with symptomatic secondary hyperparathyroidism who underwent total parathyroidectomy and autotransplantation were included. They were divided into an osteoporotic group (n = 20) and a nonosteoporotic group (n = 25) according to preoperative T scores less than -2.5 at either the lumbar spine (L1-L4) or the femoral neck (FN). INTERVENTIONS: Serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were checked before surgery and 1 day, 1 week, and 3 months after surgery. The BMDs of the FN and L1-L4 were measured using dual-energy x-ray absorptiometry before surgery and 6 months after surgery. RESULTS: Patients with osteoporosis were older (mean +/- SD, 50.2 +/- 14.0 years) than those without osteoporosis (42.7 +/- 9.1 years) (P =.04). Except for bone fractures found in 2 women in the osteoporotic group, there were no significant differences between the 2 groups in sex, clinical manifestations, duration of dialysis, weight of removed parathyroid tissue, and types of dialysis. Also, serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were similar in both groups. Both 1 day and 1 week after total parathyroidectomy and autotransplantation, serum levels of calcium and intact parathyroid hormone decreased rapidly and then gradually increased 3 months later; however, serum levels of alkaline phosphatase increased rapidly and then gradually decreased 3 months later. Six months after parathyroidectomy, BMD, T score, and Z score at L1-L4 and the FN increased significantly (P<.001). The increment was much better in the osteoporotic group than in the nonosteoporotic group (P<.001). Also, osteopenia or osteoporosis improved significantly after parathyroidectomy at both L1-L4 and the FN (P<.001 for both). CONCLUSION: Parathyroidectomy and autotransplantation can improve BMD of symptomatic secondary hyperparathyroidism at L1-L4 and the FN.     

Beneficial role of intravenous calcitriol on bone mineral density in children with severe secondary hyperparathyroidism

OBJECTIVES: In this prospective study, the effect of calcitriol therapy on bone mineral density and osteopenia in patients with severe secondary hyperparathyroidism has been investigated. MATERIALS AND METHODS: The study was carried out on 24 chronic dialysis patients consisting of 13 boys and 11 girls, aged between 8-18 years. Patients were divided into 3 groups according to the severity of hyperparathyroidism and therapy regimens. Group I consisted of 5 patients with normal parathormon levels who did not receive calcitriol therapy. In group II and III, there were patients with secondary hyperparathyroidism. Group II consisted of 10 patients receiving oral calcitriol therapy. Group III consisted of 9 patients receiving intravenous (i.v.) calcitriol. Bone mineral density was measured by dual energy x-ray absorptiometry. Osteopenia was defined as a Z-score worse than -2. Bone mineral density was assessed as baseline and at the end of one year. RESULTS: A significant improvement was observed in Z-score in the group III whereas the mean value of Z-score tended to be worse in group I and it was not significantly different in group II from the initial values. The better Z-score in group III was associated with more effective stabilization of alkaline phosphatase level and bone specific alkaline phosphatases (BAP) concentrations. CONCLUSION: Significant improvement of Z-score in group III suggested the beneficial role in i.v. administration of calcitriol in chronic dialysis patients.     

Beneficial role of intravenous calcitriol on bone mineral density in children with severe secondary hyperparathyroidism

Objectives: In this prospective study, the effect of calcitriol therapy on bone mineral density and osteopenia in patients with severe secondary hyperparathyroidism has been investigated. Materials and methods: The study was carried out on 24 chronic dialysis patients consisting of 13 boys and 11 girls, aged between 8–18 years. Patients were divided into 3 groups according to the severity of hyperparathyroidism and therapy regimens. Group I consisted of 5 patients with normal parathormon levels who did not receive calcitriol therapy. In group II and III, there were patients with secondary hyperparathyroidism. Group II consisted of 10 patients receiving oral calcitriol therapy. Group III consisted of 9 patients receiving intravenous (IV) calcitriol. Bone mineral density was measured by dual energy x-ray absorptiometry. Osteopenia was defined as a Z-score worse than −2. Bone mineral density was assessed as baseline and at the end of one year. Results: A significant improvement was observed in Z-score in the group III whereas the mean value of Z-score tended to be worse in group I and it was not significantly different in group II from the initial values. The better Z-score in group III was associated with more effective stabilization of alkaline phosphatase level and bone specific alkaline phosphatases (BAP) concentrations. Conclusion: Significant improvement of Z-score in group III suggested the beneficial role in IV administration of calcitriol in chronic dialysis patients. This revised version was published online in August 2006 with corrections to the Cover Date.     

Effect of cinacalcet on hypercalcemia and bone mineral density in renal transplanted patients with secondary hyperparathyroidism

BACKGROUND: Persistent secondary hyperparathyroidism (SHP) is the most frequent cause of hypercalcemia observed in approximately 10% of renal transplanted (RT) patients 1 year after surgery. Persistent SHP with hypercalcemia is an important factor of bone loss after renal transplantation. This study prospectively evaluates the effects of Cinacalcet therapy on serum calcium (SCa) and parathyroid hormone (PTH) blood levels, and basically on bone mineral density (BMD) in RT patients with persistent hyperparathyroidism. METHODS: Nine RT patients (eight women, one man) with allograft function more than 6 months were included based on total SCa more than 10.5 mg/dL and intact parathyroid hormone (iPTH) concentration more than 65 pg/mL. After inclusion, patients started on a single daily oral dose of 30 mg of Cinacalcet. At inclusion and every study visit blood levels of creatinine, Ca, P, alkaline phosphatase, iPTH 1,25- dihydroxyvitamin D3, and 25-hydroxyvitamin D3 were assessed. Baseline and at the end of study radial BMD were measured. Study follow-up was 12 months. RESULTS: During the study period, SCa decreased from 11.72+/-0.39 to 10.03+/-0.54 mg/dL (P<0.001). iPTH decreased from 308.85+/-120.12 to 214.66+/-53.75 mg/dL (P<0.05). The mean serum creatinine decreased from 1.58+/-0.34 to 1.25+/-0.27 mg/dL (P=0.03) and the mean radial BMD increased from 0.881+/-0.155 to 0.965+/-0.123 gr/cm2 (P<0.05). There were no significant changes in the other parameters assessed. One patient was excluded for gastrointestinal intolerance. CONCLUSIONS: In RT patients with hypercalcemia secondary to persistent SHP, Cinacalcet corrects hypercalcemia and PTH, simultaneously improving BMD.     

Fracture and bone mineral density in hemodialysis patients

AIM: The aim of this cross-sectional study was to determine in hemodialysis patients the pattern of low trauma fracture, the ability of dual X-ray absorptiometry (DXA) to discriminate between patients with and without fracture, and the magnitude, distribution and mechanism of bone loss. PATIENTS AND METHODS: Eighty-eight patients were studied. Bone mineral density (BMD) was measured by DXA at lumbar spine (LS), femoral neck (FN) and 3 radius sites (UD, MID and 1/3R). In 11 patients (12.5%), 16 fractures occurred and were predominant at the distal forearm and ribs. RESULTS: Patients with fracture had a significatively lower BMD Z-score at LS (-1.34 +/- 1.66 vs -0.42 +/- 1.23), at FN (-1.58 +/- 1.25 vs -0.60 +/- 1.01), at MID radius (-2.59 +/- 1.34 vs -0.93 +/- 1.76) and 1/3 radius (-1.62 +/- 1.60 vs -0.39 +/- 1.32). They also had a longer history of dialysis (113 +/- 64 vs 53 +/- 65 months). Prevalence of osteoporosis varied from 23% at LS to 50% at MID radius. CONCLUSION: Multiple regression analysis showed that there was no influence of gender, age, parathormone status and primary renal disease on BMD. However, at FN, UD, MID and 1/3 radius, a significantly negative correlation was found between length of dialysis and BMD Z-score. By contrast at LS, there was a positive correlation between age at onset of dialysis and BMD Z-score. Despite occurrence of fracture at the fistula forearm, BMD levels were similar in both arms.     

Clinical study of concerning factors of decreased bone mineral content in hemodialysis patients

We investigated bone mineral content and factors related to decreased bone mineral content in maintenance hemodialysis patients. Bone mineral contents, epsilon GS/D, radius-bone mineral content (R-BMC) and L3-bone mineral density (L3-BMD), were measured with a micro densitometer, a bone mineral analyzer and a dual energy quantative CT scanner, and relative bone mineral contents (% epsilon GS/D, %R-BMC and %L3-BMD) were calculated respectively. The desferrioaxmine infusion test was carried out for diagnosis of aluminium associated bone disease, and an elevated level of aluminium (delta aluminium) was observed. There was reverse correlation between epsilon GS/D and age in female hemodialysis patients. Serum bone gla protein, alkaline phosphatase and PTH-C levels were high in cases with increased epsilon GS/D and who were receiving little medication with activated Vitamin D in maintenance hemodialysis patients. A correlation was observed between delta aluminium and total medication of aluminium hydroxide-gel. Hemodialysis patients with bone pain had long term hemodialysis, high total medication of aluminium and high aluminium. Relative bone mineral contents (% epsilon GS/D, %R-BMD) were useful for estimating bone mineral content in hemodialysis patients. Hemodialysis patients were divided in four groups by PTH-C and delta aluminium levels as follow, 1) normal, 2) aluminium associated bone disease, 3) secondary hyperparathyroidism with aluminium associated bone disease, 4) secondary hyperparathyroidism. These results indicate that secondary hyperparathyroidism, and medication with aluminium may play a role in decreased bone mineral content in hemodialysis patients, and menopause may also be an important factor in female hemodialysis patients.     

Osteoprotegerin and bone mineral density in hemodialysis patients

Introduction Osteoprotegerin is a soluble glycoprotein that belongs to the tumor-necrosis-factor receptor superfamily. In vitro, osteoprotegerin blocks osteoclastogenesis in a dose-dependent manner. The serum osteoprotegerin level shows a positive correlation with bone metabolism markers and a negative correlation with bone mineral density in healthy persons, but these relationships are unclear in hemodialysis patients. We investigated the role of osteoprotegerin in bone loss in hemodialysis patients. Methods We measured baseline serum osteoprotegerin, bone metabolism markers, and bone mineral density in hemodialysis patients. A total of 201 patients (114 men and 87 women) were followed for 12 months, and bone mineral density was measured again to calculate the annual percent change in bone mineral density. Serum osteoprotegerin was also measured in 20 healthy persons. Results The osteoprotegerin levels of the hemodialysis patients were about three times higher than those of the healthy controls. The osteoprotegerin level showed a negative correlation with various bone metabolism markers. In multiple regression analysis, the annual percent change in bone mineral density showed a positive correlation with osteoprotegerin level, while there was a negative correlation with duration of hemodialysis and intact parathyroid hormone level. The osteoprotegerin levels of the hemodialysis patients were about three times higher than those of the healthy controls. The osteoprotegerin level showed a negative correlation with various bone metabolism markers. In multiple regression analysis, the annual percent change in bone mineral density showed a positive correlation with osteoprotegerin level, while there was a negative correlation with duration of hemodialysis and intact parathyroid hormone level. Conclusions These correlations of osteoprotegerin are opposite to those found in healthy persons. However, osteoprotegerin might act to prevent bone loss even in hemodialysis patients.     

Total and regional bone mineral density by dual photon absorptiometry in patients on maintenance hemodialysis.

To evaluate bone loss in renal osteodystrophy, we measured total and regional (head, trunk, pelvis, leg and arm) bone mineral density (BMD) by dual photon absorptiometry in 72 patients on maintenance hemodialysis (HD). We also examined the validity of serum carboxy-terminal parathyroid hormone (C-PTH) and intact-PTH as an indicator of secondary hyperparathyroidism. Total BMD correlated inversely with age in female patients (r = -0.57, p less than 0.01), but not in male patients. Female patients older than 50 years were omitted from analysis to exclude the effect of menopause on bone. Among clinical and biochemical parameters, only trunk BMD correlated inversely with the duration of HD (r = -0.26, p less than 0.05). Head, trunk and total BMD correlated inversely with serum alkaline phosphatase, C-PTH and intact-PTH, while pelvis BMD did not. Leg and arm BMD also correlated inversely with serum intact-PTH, but not with serum C-PTH. The serum level of C-PTH correlated positively with the duration of HD (r = 0.40, p less than 0.005), while intact-PTH did not. As compared with 18 control male volunteers aged 25-42 years, trunk, pelvis, leg, arm and total BMD were significantly lower in male patients on HD aged 22-49 years, whereas head BMD did not differ significantly between the two groups. The percent decrease of BMD was most prominent in the trunk (-19.6%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

影响维持性血液透析患者骨密度相关因素分析

目的观察维持性血液透析患者骨质疏松现状,研究骨密度及骨代谢指标间关系,讨论影响骨质疏松的危险因素。方法选取维持性血液透析患者125例,收集一般资料及透析相关信息,检测25羟维生素D,骨源性碱性磷酸酶,跟骨骨密度,进行横断面研究。应用SPSS19.0软件,P0.05为差异有统计学意义。结果维持性血液透析患者骨质疏松发生率为48%,25羟维生素D缺乏为30.4%。不同性别间骨质疏松患病率差异无统计学意义。绝经女性骨密度显著低于未绝经女性(P0.001)。女性25羟维生素D水平显著低于男性(P=0.026)。肾小管间质性疾病者骨密度明显低于慢性肾小球肾炎者(P=0.001)。不运动者骨密度明显低于运动者(P0.001)。骨密度与年龄,透析龄显著负相关(r=-0.387,P0.001,r=-0.190 P=0.034)。老龄、绝经、轻体重、不运动、肾移植是维持性透析患者骨质疏松的危险因素。结论维持性血液透析患者骨质疏松和25羟维生素D缺乏发生率高,但二者间无相关性。老龄、绝经、轻体重、不运动、肾移植后应用激素及免疫抑制剂是终末期肾病维持性透析患者骨质疏松的危险因素。     

Reoperation for secondary hyperparathyroidism in hemodialysis patients

Parathyroidectomy (PTx) in uremic patients is only performed in case of severe hyperparathyroidism. In some instances, PTx may be either insufficient or, on the contrary, lead to intolerable hypoparathyroidism. Recurrence is always possible because of persistent renal failure. Reoperations may, therefore, be necessary. We report here on 25 reoperations done in 21 patients who are part of a series of 248 patients operated on for secondary hyperparathyroidism. Nine patients had initial parathyroidectomy (PTx) at another institution. Six patients underwent reoperation after initial surgery, which was incomplete leaving 1–3 glands in place. In 7 patients reoperation was done after initially successful, subtotal PTx. In these we found hypertrophic remnants and a supernumerary gland in 1. Seven patients had total PTx, with immediate parathyroid reimplantation in 5 instances. Reoperation on the graft was judged necessary in 5 patients, but hypertrophy of grafted fragments was observed in only 3 of them. In 3 patients secondary autografting was performed with cryopreserved tissue. The analysis of our cases shows the difficulties of localizing unique or multiple sites of parathyroid hormone overproduction despite the availability of many diagnostic approaches. From a practical point of view, we try at present to resect all parathyroid tissue in case of reoperation for recurrent hyperparathyroidism. If hypoparathyroidism results by this procedure or in case of hypoparathyroidism obtained unexpectedly, we then proceed to delayed parathyroid autotransplantation with cryopreserved tissue.

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Resumen La paratiroidectomía (PTx) en pacientes urémicos sólo se realiza en caso de hiperparatiroidismo severo. En algunos casos la PTx puede resultar insuficiente o, por el contrario, dar lugar a hipoparatiroidismo manifiesto. La recurrencia del hiperparatiroidismo siempre es posible debido a la falla renal persistente, lo cual puede requerir reoperación. En el presente trabajo presentamos los resultados en 25 reoperaciones realizadas en 21 pacientes que son parte de una serie de 248 casos operados por hiperparatiroidismo secundario. Nueve pacientes tuvieron la PTx inicial en otra institución. Seis pacientes fueron reoperados después de una cirugía inicial que resultó incompleta al dejar una a 3 glándulas en su lugar. En 7 casos la reoperación fue realizada después de una PTx subtotal inicialmente exitosa. En estos casos encontramos remanentes hipertróficos, y una glándula supernumeraria en un paciente. Siete pacientes recibieron PTx total con reimplantación inmediata de paratiroides en 5 casos. La reoperación sobre el transplante fue juzgada como necesaria en 5 pacientes, aunque solo se observó hipertrofia de los fragmentos transplantados en 3 de ellos. En 3 casos se realizó autotransplante secundario usando tejido criopreservado. El análisis de nuestros casos demuestra las dificultades en localizar una fuente única o múltiple de superproducción de hormona paratiroidea a pesar de la disponibilidad de numerosos métodos de diagnóstico. Desde el punto de vista práctico, actualmente nosotros tratamos de resecar todo el tejido paratiroideo en casos de reoperación por hipertiroidismo recurrente. Si este procedimiento resulta en hipoparatiroidismo, o si se presenta hipoparatiroidismo inesperado, procedemos entonces con un autotransplante tardío de paratiroides utilizando tejido criopreservado.

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Résumé La parathyroïdectomie chez les sujets urémiques est indiquée seulement en présence d'un hyperparathyroïdisme grave. Dans quelques cas elle peut être insuffisante ou au contraire elle peut se solder par un hypoparathyroïdisme grave. La récidive est également toujours possible en raison de la persistance de l'insuffisance rénale. En conséquence une réintervention peut être nécessaire. Les auteurs rapportent 25 cas de réinterventions chez 21 sujets appartenant à une série de 248 malades qui ont été opérés pour hyperparathyroïdisme secondaire. Neuf d'entre eux avaient subi une parathyroïdectomie dans une autre formation chirurgicale. Six patients furent réopérés alors que l'intervention initiale avait été incomplète laissant en place de 1 à 3 parathyroïdes. Dans 7 cas la réintervention fut pratiquée après une parathyroïdectomie subtotale qui avait été d'abord suivie de succès et il fut alors trouvé des fragments résiduels hypertrophiques et une parathyroïde en surnombre. Sept patients subirent une parathyroïdectomie totale avec réimplantation parathyroïdienne immédiate dans 5 cas. Chez 5 sujets une réintervention concernant la greffe fut nécessaire mais c'est seulement chez 3 d'entre eux que fut constaté l'hypertrophie des fragments greffés. Dans 3 cas l'autogreffe secondaire fut réalisée avec du tissu conservé par le froid. L'analyse de ces cas démontre la difficulté de localiser les sites uniques et multiples où siègent les éléments hyperfonctionnels et ce malgré la mise en oeuvre de nombreuses techniques de diagnostic. Actuellement sur le plan pratique les auteurs essaient de réséquer la totalité du tissu parathyroïdien lorsqu'ils réinterviennent pour traiter l'hyperparathyroïdisme récidivant. S'il en résulte un hypoparathyroïdisme ils procèdent alors à une autre transplantation à l'aide de tissu conservé par le froid.

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At present, secondary hyperparathyroidism (HPTH) in patients with chronic renal failure is

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Presented at the International Association of Endocrine Surgeons in Paris, September 1985.     

Effect of body fat stores on total and regional bone mineral density in perimenopausal Chinese women

Accumulation of body fat is known to be beneficial to bone mass through increased body weight. However, not all the skeleton is loaded by body weight. Therefore, we assume that fat stores would exert different effects on bone mass at different skeletal sites. In this study, 84 perimenopausal Chinese women were recruited. Using dual-energy X-ray absorptiometry, total body fat mass (TBFM), total body lean mass (TBLM), percent body fat (PBF), and total body and regional bone mineral density (BMD) were measured. Correlation analysis indicated that PBF correlated negatively with BMD at ribs and both arms (all P < 0.05). After adjusting for TBLM, PBF had a significantly negative correlation with BMD at head, ribs, both arms, and whole body (all P < 0.05). With adjustment for body weight and height, a significantly negative correlation between PBF and BMD was present, not only at ribs and arms but also at legs and whole body (all P < 0.05, except right leg, at P = 0.094). There was a significantly positive correlation between body weight and leg BMD (all P < 0.001). Body weight was positively correlated with TBFM (r ² = 0.783, P < 0.001) and TBLM (r ² = 0.770, P < 0.001). Based on the results, we conclude that increased body fat stores would exert a detrimental effect on BMD, but this effect is more prominent on non-weight-bearing bone. On weight-bearing bone, the detrimental effect of increased body fat could be offset or outweighed by the beneficial effect of increased body weight.     

Usefulness of pamidronate in severe secondary hyperparathyroidism in patients undergoing hemodialysis

BACKGROUND: Although bisphosphonates have been widely used to treat bone diseases characterized by increased bone resorption, there are limited data showing their possible usefulness in patients on hemodialysis (HD) with secondary hyperparathyroidism. METHODS: The aim of this study was to evaluate the efficacy and safety of pamidronate in HD patients affected by severe secondary hyperparathyroidism and moderate hypercalcemia who were receiving intravenous calcitriol (Calcijex). RESULTS: In this prospective one-year, open-labeled study, 13 patients (9 women/4 men) with a mean age of 64 +/- 9 years and a mean time on dialysis of 94 +/- 61 months were evaluated. The inclusion criteria were: iPTH>500 pg/mL, Ca>11 mg/dL, P <6 mg/dL, and osteopenia (T-score <-1 SD). Blood levels of Ca, P, alkaline phosphatase (AP), and iPTH were assessed at the beginning of the study and every month. Radiographs of the vertebral spine and bone mineral density (BMD) (lumbar spine and femoral neck) were assessed basal and every 6 months. All patients received 60 mg of pamidronate intravenously every two months throughout the study period. Calcitriol and phosphate binders were adjusted according to iPTH, Ca, and P blood levels. BMD increased in both the lumbar and femoral neck scans (mean increase of 33%) at 6 and 12 months. iPTH increased at 3 months in all patients, and decreased more than 50% in 10 patients after increasing the calcitriol doses. Three patients had no response. A slight decrease in Ca and P was observed in all patients with no significant changes in AP. There were no adverse events. CONCLUSION: Pamidronate is effective in controlling hypercalcemia in patients on HD with secondary hyperparathyroidism and allows for a more aggressive use of intravenous calcitriol.     

Predictors of bone mineral density in patients on hemodialysis

Renal osteodystrophy is a universal complication of uremia. Renal failure patients are at risk for low bone mineral density (BMD) and fractures. Parathyroid hormone (PTH) plays a pivotal role in the pathophysiology of uremic bone disease. Histomorphometric studies suggest that the maintenance of PTH levels between two and four times the upper limit of normal is associated with the lowest prevalence of two common forms of osteodystrophy: osteitis fibrosa cystica and adynamic bone disease. The purpose of this study was to investigate whether the above recommendation for PTH levels in dialysis patients corresponds to a more optimal BMD with a special emphasis on diabetic versus nondiabetic subjects. Twenty-eight patients with chronic renal failure on hemodialysis underwent measurement of PTH levels, as well as BMD at the lumbar spine, hip, and forearm. They were divided into three groups based on the mean PTH level over the 5 years prior to having BMD measured. Osteoporosis was diagnosed in 55% of men and 87% of women on dialysis. Predictors of BMD were gender, duration on hemodialysis, and diabetes. Our study supports the histomorphometry-based studies suggesting that the maintenance of intact PTH levels two to four times the upper limit of normal may be associated with better skeletal health in uremic patients on hemodialysis, and that the diabetic subgroup is at particular risk for low BMD.