Serum osteocalcin and bone mineral metabolism following successful renal transplantation

Serum osteocalcin (bone gla protein, BGP), a vitamin K-dependent non-collagenous bone protein and its relationship to other markers of bone and mineral metabolism were studied cross-sectionally in varying numbers of patients before and over 240 days following renal transplantation. Marked elevation of serum creatinine (11.9 +/- 0.76 mg/dl), osteocalcin (216.9 +/- 7 ng/ml), parathyroid hormone (PTH, mid-molecule fragment) (24.5 +/- 3.6 ng/ml), alkaline phosphatase (255.2 +/- 54.7 IU/l) and phosphorus (5.6 +/- 0.3 mg/dl) were noted preoperatively. Serum calcium levels remained normal throughout the study period while phosphate levels normalized within one week after transplantation. PTH levels progressively decreased postoperatively over the study period but were still elevated well above normal. Serum osteocalcin decreased to near normal values at 60-90 days after surgery. Both PTH and alkaline phosphatase correlated significantly with osteocalcin preoperatively and postoperatively. The relatively depressed values of osteocalcin in the face of still elevated PTH levels post-transplantation was attributed to the effect of immunosuppressive corticosteroid therapy. The significant correlation between PTH and osteocalcin suggests that osteocalcin may be as or more sensitive a measurement of bone turnover than alkaline phosphatase pre- and post-transplantation.     

Efficacy of whole PTH assay and 1-84/non-(1-84) PTH ratio in patients on hemodialysis or undergoing parathyroidectomy

For measurement of parathyroid hormone (PTH), the intact PTH (I-PTH) assay is generally used. However, I-PTH assay apparently detects PTH 7-84 fragments, in addition to PTH 1-84. The whole PTH (W-PTH) assay exhibits no cross-reactivity with PTH 7-84. Ratio of PTH 1-84 to non-(1-84) PTH has been proposed as a non-invasive indicator of bone turnover in patients with end-stage renal disease (ESRD). We evaluated the efficacy of W-PTH assay and 1-84/non-(1-84) PTH ratio in hemodialysis patients and patients who had undergone parathyroidectomy. PTH levels were measured using W-PTH and I-PTH assays in 138 hemodialysis patients, 27 healthy controls and 10 patients who were scheduled to undergo parathyroidectomy for secondary hyperparathyroidism. Alkaline phosphatase, bone alkaline phosphatase and intact osteocalcin were also measured for comparison with 1-84/non-(1-84) PTH ratio. W-PTH was strongly correlated with I-PTH in both groups, and with all three bone metabolic markers in hemodialysis patients. In hemodialysis patients, both PTH and bone metabolic markers were significantly lower in the subgroup with a PTH ratio < 1.0 than in the subgroup with a PTH ratio > or = 1.0. However, PTH ratio exhibited no significant correlation with bone metabolism markers. PTH ratio was higher after parathyroidectomy than before. W-PTH and I-PTH assays offer identical indicators of bone metabolism in ESRD patients. However, 1-84/non-(1-84) PTH ratio may be of limited diagnostic use regarding bone turnover if a cut-off value of 1.0 is used. PTH 1-84 may be secreted relatively more than non-(1-84) PTH after parathyroidectomy, due to decreases in serum calcium. As the W-PTH assay allows easy calculation of non-(1-84) PTH by subtracting the I-PTH value, this assay contributes to identification of the function of non-(1-84) PTH fragments in various conditions.     

A new assay method that detects only intact osteocalcin. Two-step non-invasive diagnosis to predict adynamic bone disease in haemodialysed patients.

BACKGROUND: We studied the usefulness of a new assay method that detects only the intact human osteocalcin molecule in haemodialysed patients. METHODS: Iliac bone biopsy specimens obtained from 62 haemodialysed patients were analysed. RESULTS: Bone formation rates (BFR/BS) correlated positively with serum intact osteocalcin concentrations (n=62), osteocalcin concentrations assayed by a conventional method (n=31), parathyroid hormone (PTH) concentrations (n=62), and total alkaline phosphatase concentrations (r=0.602, 0. 588, 0.650, and 0.401 respectively). Based on ROC curve and Youden index analysis, the optimal cut-off value to distinguish adynamic bone disease from a mild lesion was 195 pg/ml of serum PTH concentration (Youden index=0.233) or 30 ng/ml of serum intact osteocalcin concentration (Youden index=0.628). The optimal cut-off value to distinguish between hyperparathyroid bone and a mild lesion was 455 pg/ml of serum PTH level (Youden index=0.63) or 50 ng=ml of serum intact osteocalcin concentration (Youden index=0.634). Since both ROC curve and Youden index suggested that the serum PTH concentration was not a good marker to distinguish adynamic bone from a mild lesion or hyperparathyroid bone, we designed a two-step procedure. The first step was the diagnosis of adynamic bone (cut-off: 65 pg/ml) or hyperparathyroid bone (cut-off: 455 pg/ml) according to serum PTH concentration. In a second step, we assessed serum intact osteocalcin concentration in patients with serum PTH concentrations between 65 and 455 pg/ml. The cut-off values for adynamic and hyperparathyroid bone in this diagnostic approach were 30 and 70 ng/ml respectively. As a result, 49 out of 62 patients were diagnosed properly. The Youden index of this two-step diagnosis was 0.527 and 0.661 for adynamic bone and hyperparathyroid bone respectively. Sensitivity markedly improved to 94.4% and 96.2% for adynamic bone and hyperparathyroid bone respectively, without sacrificing specificity (84.0 and 88.8% respectively). CONCLUSION: Measurement of serum intact osteocalcin concentration is useful for the diagnosis of adynamic bone in haemodialysed patients. A two-step procedure involving also simultaneous measurement of serum PTH concentration further improved the sensitivity of each individual marker while maintaining specificity.     

Vitamin K status in relation to bone metabolism in patients with renal failure

Vitamin K abnormalities may be involved in the pathogenesis of bone disease in patients with advanced renal failure since vitamin K plays a role in the synthesis of osteocalcin, a marker of bone formation. Vitamin K may also indirectly suppress parathyroid function. The aim of this study was to evaluate vitamin K status in patients with renal failure and in healthy volunteers in relation to some biochemical markers of bone turnover. The studies were performed on: patients with chronic renal failure (CRF) on conservative treatment; hemodialyzed patients treated with continuous ambulatory peritoneal dialysis (CAPD); kidney transplant patients, and a control group. Intact PTH, osteocalcin, vitamin 1,25-(OH)(2)D(3), 25-OH-D(3), bone-specific alkaline phosphatase, procollagen type-I cross-linked carboxyterminal telopeptide, deoxypyridinoline, and osteonectin were assayed using commercially available kits, and the vitamin K concentration by HPLC. We found that vitamin K concentrations did not differ significantly between all the groups studied. Only in CRF patients was the vitamin K concentation low, almost reaching statistical significance when compared to the healthy volunteers (p = 0.05) and correlated positively with age, serum calcium and osteonectin. No statistically significant correlations were found between vitamin K and osteocalcin, PTH or other biochemical parameters of bone metabolism studied in patients with CRF and renal replacement therapy. In patients after renal replacement therapy, the only significant positive correlation was found between phylloquinone and osteonectin (r = 0.027, p = 0.004). The same applied when we also included healthy volunteers. The correlations of osteonectin and vitamin K are of unknown clinical relevance. Our study does not support the hypotheses of a possible role of vitamin K deficiency in patients with CRF and the influence of vitamin K on bone metabolism.     

Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients

BACKGROUND.: Adynamic bone disease was recently described to be increasinglyprevalent in the dialysis population. At present the diagnosisof this type of renal osteodystrophy can only be made by bonehistomorphometry. We assessed the value of different biochemicalserum markers in the diagnosis of adynamic bone disease. METHODS.: In 103 haemodialysis patients a bone biopsy was performed afterdouble tetracycline labelling, the serum levels of intact PTH,osteocalcin, and the bone isoenzyme of alkaline phosphatasewere determined. Bone alkaline phosphatase was measured an optimizedagarose gel electrophoretic method, recently shown to have ahigh accuracy, precision and reproducibility, also in the lowerrange. RESULTS.: In 38 (37%) of the patients the diagnosis of adynamic bone diseasewas histologically established. Constructing receiver operatorcurves optimal cut-off levels for the diagnosis of adynamicbone disease were determined, being 27 U/litre for the boneisoenzyme of alkaline phosphatase, 14 µg/litre for osteocalcinand 150 pg/ml for intact PTH. Concentrations of bone alkalinephosphatase or intact PTH below these cut-off levels, were shownto be the best performing tests in the detection of adynamicbone disease as indicated by a sensitivity of 78.1 and 80.6%and a specificity of 86.4 and 76.2% respectively. Applying Bayes'theorema, it was calculated that in the current haemodialysispopulation in which a prevalence adynamic bone disease up to35% has been described, the positive predictive values for theproposed cut-off values are 75% for bone alkaline phosphatase,65% for intact PTH and 55% for osteocalcin. Moreover, in thispopulation, levels of bone alkaline phosphatase and intact PTHbelow the optimal cut-off excluded hyperparathyroid bone disease. CONCLUSION.: In view of the relative easy and accurate methodology for bonealkaline phosphatase determination, the closer physiologicallink with osteoblast function and the lesser expense for itsdetermination we suggest that this marker is a useful tool inthe non-invasive diagnosis of the adynamic type of bone diseasein the individual patient.     

Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis.

We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase. INTRODUCTION: In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone. MATERIALS AND METHODS: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. RESULTS AND CONCLUSIONS: The average serum phosphorus and calcium x phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p < 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.     

Race is a major determinant of secondary hyperparathyroidism in uremic patients

In the general population, blacks have higher parathyroid gland mass and circulating parathyroid hormone (PTH) levels than whites. This may predispose black patients to more severe parathyroid disease when renal failure develops. Therefore, racial differences in the severity of uremic hyperparathyroidism were examined in a population of patients with end-stage renal disease (ESRD). Among ESRD patients receiving hemodialysis or peritoneal dialysis, two or more values of intact PTH (immunoradiometric assay, pg/ml) obtained at least 90 d apart were available in 1270 prevalent cases (61.1% blacks, 51% males, and 31.1% diabetic), including 466 incident cases with onset of ESRD after 1993. Maximum PTH levels were analyzed as a function of race, gender, age, diabetic status, and levels of serum calcium, phosphorus, alkaline phosphatase, and aluminum. Using a stepwise multiple regression model, the determinants of maximum PTH in the order of their importance were black race, serum phosphorus, absence of diabetes, younger age, serum calcium, and female gender. The maximum PTH levels averaged 641.7 in blacks and 346.0 in whites after adjusting for age, gender, diabetic status, serum calcium, and phosphorus (P < 0.0001). In blacks compared with whites, the odds ratio (95% confidence interval) for adynamic bone disease (maximum PTH <150 pg/ml) was 0.26 (0.17 to 0.41), whereas the odds ratio for hyperparathyroid bone disease (mean PTH >500 pg/ml) was 4.4 (2.10 to 9.25). Race is a major independent determinant of uremic secondary hyperparathyroidism. Among ESRD patients, blacks may be at an increased risk for hyperparathyroid bone disease and whites for adynamic bone disease.     

Markers of bone turnover in patients with nephrolithiasis

A total of 19 patients with active nephrolithiasis, 14 patients with non-active nephrolithiasis and 17 healthy subjects were examined under standardized intake of calcium, phosphorus, purine and protein. In patients with both active and non-active renal stone disease the following abnormalities were found: elevated plasma levels of PTH and osteocalcin, increased activity of the bone isozyme of alkaline phosphatase, low plasma levels of phosphate and increased urinary excretion of calcium and oxalic acid. These abnormalities were more marked in patients with active than nonactive nephrolithiasis. No correlation was found between plasma PTH levels and parameters of bone turnover as well as calciuria and oxaluria. Results presented in this paper suggest that (a) Smith's criteria of active renal stone disease are of minor pathogenetic and therapeutic value and (b) patients with active nephrolithiasis differ from non-active renal stone formers by more elevated oxaluria and markers of bone turnover and more marked abnormalities in calcium-phosphate metabolism related parameters.     

Serum osteoprotegerin and renal osteodystrophy.

BACKGROUND: Numerous growth factors and cytokines are known to modulate bone turnover. An important, recently discovered complex involved in osteoclastogenesis is the osteoprotegerin/osteoprotegerin-ligand (OPG/OPGL) cytokine complex, which is produced by osteoblasts. Many factors, including parathyroid hormone (PTH), appear to affect bone turnover through this pathway. In this disorder, the role of the OPG/OPGL system in the pathogenesis of renal osteodystrophy, a disease with either low or high bone turnover, has not been investigated so far. METHODS: Thirty-nine chronic haemodialysis patients had bone biopsies, including histomorphometric and histodynamic examinations. In addition, the following serum biochemistry parameters were measured: serum OPG, intact PTH, PTH 1-84, total PTH, osteocalcin, total and bone alkaline phosphatases, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. RESULTS: On average, serum OPG levels were above the normal range. They were lower in adynamic bone disease (ABD) patients, than in patients with predominant hyperparathyroidism (HP) or mixed osteodystrophy (MO). Significant negative correlations were found between serum OPG and PTH levels, and between serum OPG and parameters of bone resorption (ES/BS) and bone formation (ObS/BS and BFR/BS) in HP and MO patients with PTH values < or =1000 pg/ml. For intact PTH levels < or =300 pg/ml, serum OPG was significantly lower in the group with ABD than in those with HP or MO (P<0.05). CONCLUSION: In renal osteodystrophy the OPG/OPGL system is involved in the regulation of bone turnover induced by PTH. The determination of serum OPG levels could be of use in the diagnosis of low turnover bone disease, at least in association with PTH levels < or =300 pg/ml.     

An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism

AIMS: Cinacalcet lowers plasma parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism (sHPT), but the bone histologic response has not been described. This prospective, double-blind, placebo-controlled trial assessed the effects of cinacalcet on bone histology and serum markers of bone metabolism in dialysis patients with sHPT. METHODS: Patients with intact PTH (iPTH) > or = 300 pg/ml were randomly assigned 2:1 to receive cinacalcet or placebo with concurrent vitamin D and/or phosphate binder therapy. Cinacalcet (30 - 180 mg/day) was used to achieve iPTH levels < or = 200 pg/ml. Bone biopsies were performed before and after one year of treatment. RESULTS: Baseline and end-of-study data were available from 32 patients (19 cinacalcet, 13 placebo). Baseline bone turnover was elevated in 27, reduced in 3 and normal in 2 patients. Serum bone-specific alkaline phosphatase (BSAP) and N-telopeptide (NTx) were elevated. Cinacalcet treatment decreased PTH and diminished activation frequency, bone formation rate/bone surface, and fibrosis surface/bone surface. Adynamic bone was observed in three patients receiving cinacalcet; in two of these, PTH levels were persistently low (< 100 pg/ml). The histomorphometric parameter changes in bone corresponded to PTH, BSAP and NTx reductions. Bone mineralization parameters remained normal. CONCLUSIONS: Treatment with cinacalcet lowered PTH and reduced bone turnover and tissue fibrosis among most dialysis patients with biochemical evidence of sHPT.     

原发性甲状旁腺机能亢进症手术治疗后骨量和骨代谢指标的变化

目的 了解甲状旁腺切除术对原发性甲状旁腺机能亢进症病人的骨矿密度及骨代谢指标变化的影响。方法 ４０例病人,其中３０例未治疗组（男：女＝３：２７）;１０例已手术治疗组（男：女＝３：７）,手术后时间１～２４月（平均５．３±７．９月）。用ＤＥＸＡ测量腰椎及股骨颈的骨矿密度,同时,测定血清中的甲状旁腺素（ＰＴＨ）,骨钙素（ＯＣ）,及骨唾液酸蛋白（ＢＳＰ）。结果 在已手术组病人其腰椎及股骨颈骨矿密度再没有明     

Measurement of PTH fragments for assessment of renal bone disease in hemodialysis patients

BACKGROUND: Renal bone pathology involves a spectrum from 'high-turnover' to 'low-turnover bone disease' (adynamic bone disease, classical osteomalacia). The diagnosis of the latter usually requires bone biopsy. Inhibitory parathyroid hormone (PTH) fragments may be useful for its noninvasive diagnosis. METHODS: A cross-sectional study was performed in 54 patients on chronic hemodialysis which involved measurements of intact PTH (iPTH; Nichols assay), total PTH (tPTH; Scantibodies assay), and the cyclase-activating PTH fragment (CAP). The level of cyclase-inactive PTH fragment (CIP) was calculated. At the same time, serum calcium, phosphorus, and alkaline phosphatase levels as well as the current therapy for secondary hyperparathyroidism were recorded. In selected patients, bone radiographs were evaluated for osteitis fibrosa. RESULTS: A high correlation (r = 0.94) was found between iPTH and tPTH, with the tPTH levels being lower by 30-40%. A similar association was also found for CAP (r = 0.988) and for CIP (r = 0.93). 3 out of the 54 patients had a CAP/CIP ratio of < or =1 which has been associated with adynamic bone disease. A higher CIP ratio was significantly associated with the use of aluminum-hydroxide- and calcium-containing phosphate binders. CONCLUSIONS: iPTH and tPTH assays are highly correlated. In a general hemodialysis patient population, low-turnover bone disease appears to be rare, when the CAP/CIP ratio is used as a marker. A high CIP value was associated with therapy using aluminum hydroxide, a drug known to carry a risk of adynamic bone disease.     

Urinary deoxypyridinoline excretion for the evaluation of bone turnover in chronic renal failure

BACKGROUND: The urinary excretion of deoxypyridinoline (DPD) was evaluated in predialysis chronic renal failure (CRF), together with intact PTH and several classic markers of bone turnover in order to assess whether urine free and total DPD excretion are equivalent parameters of bone turnover in CRF, and to evaluate the relationship between urine DPD excretion, PTH and the other bone markers. METHODS: The study was carried out in 94 patients with different degrees of renal failure due to various kidney diseases. Besides urinary DPD expressed as free DPD, total DPD, free/total DPD, free DPD/Cr and total DPD/Cr, the following determinations were made: intact PTH, bone alkaline phosphatase (BALP), total alkaline phosphatase (AP), osteocalcin (BGP), serum C-terminal telopeptide of collagen type I (ICTP) and hydroxyproline (OHpro). The patients were divided into 3 groups according to the increasing severity of renal failure (Ccr >40, 40-20, <20 ml/min). RESULTS: The ratio free/total DPD decreased (NS) with advancing renal failure, and was inversely correlated with total DPD excretion. While PTH increased progressively to about four times the values observed in the Ccr >40 group, there was a parallel increase only in BGP and ICTP, parameters retained in the serum with decreasing renal function, while AP, BALP, total DPD and OHpro did not change. However, significant correlations between total DPD/Cr and PTH, BALP, BGP and ICTP were also found. CONCLUSIONS: In CRF free DPD is an unreliable index of bone turnover due to a probable interference in its production from the peptide-bound DPD. Total DPD or total DPD/Cr are better used. In spite of the significant correlations observed in advanced renal failure between PTH and most of the parameters examined, a resistance of bone tissue to PTH action in CRF must be considered.     

Postoperative Elevated Serum Levels of Intact Parathyroid Hormone after Surgery for Parathyroid Adenoma: Sign of Bone Remineralization and Decreased Calcium Absorption

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.     

K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.     

Maxacalcitol therapy decreases circulating osteoprotegerin levels in dialysis patients with secondary hyperparathyroidism

BACKGROUND: Osteoprotegerin is a natural glycoprotein which plays a critical role in osteoclast physiology. Elevated levels of circulating osteoprotegerin may account for the development of bone and mineral metabolic abnormalities in uremia. Little is known about the effects of vitamin D therapy on the circulating osteoprotegerin levels in dialysis patients. PATIENTS AND METHODS: Fifty chronic dialysis patients whose plasma intact PTH levels were greater than 300 pg/ml were analyzed for the study. Following a four-week washout time during which all vitamin D administration was halted, 10 microg of maxacalcitol was intravenously injected thrice a week. RESULTS: The circulating intact PTH, bone-specific alkaline phosphatase and intact osteocalcin levels were significantly lowered, while the serum calcium levels were elevated after the therapy. The osteoprotegerin levels significantly decreased after the therapy (p < 0.0001). CONCLUSION: Maxacalcitol therapy reduced the circulating osteoprotegerin levels and improved secondary hyperparathyroidism. The observed effects were the opposite of those expected from previous in vitro studies. Osteoprotegerin may mediate and/or modify the effect of active vitamin D therapy in dialysis patients.     

Elevated Serum Parathormone after Roux-en-Y Gastric Bypass

Background: Abnormalities in calcium and vitamin D metabolism are observed early after gastric bypass, whereas clinical or biochemical evidence of metabolic bone disease might not be detected until many years after the procedure. The aim of the present study was to evaluate the impact of bariatric surgery on bone metabolism determined on the basis of postoperative laboratory changes in calcium, phosphorus, magnesium, alkaline phosphatase and parathormone (PTH) levels. Methods: 110 patients submitted to Roux-en-Y gastric bypass (RYGBP) were followed after surgery, and the following parameters were determined: intact PTH molecule (PTHi; chemiluminescence), alkaline phosphatase (colorimetric method), ionic calcium (selective electrode), phosphorus and magnesium (colorimetric method). Results: Elevated serum PTHi levels were observed in 29% of the patients and hypocalcemia in 0.9% from the 3rd postoperative month and afterwards (3 to 80 months after surgery). Conclusion: There is a need for careful evaluation of bone metabolism and for routine calcium replacement after RYGBP.     

Bone metabolism after cinacalcet administration in patients with secondary hyperparathyroidism

Cinacalcet, an allosteric modulator of a calcium (Ca)-sensing receptor, significantly suppresses parathyroid hormone (PTH) secretion and bone turnover rate in chronic hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). In this study, bone metabolism after cinacalcet treatment was examined, because hungry bone syndrome is sometimes experienced after parathyroidectomy in severe SHPT. We conducted a prospective observational study in 17 HD patients with SHPT. Cinacalcet was started at 25 mg/day, and the dose was increased step by step based on serum calcium level. A significant decrease in serum Ca and intact PTH concentration was found within 2 weeks. Tartrate-resistant acid phosphatase 5b, a good bone resorption marker, was significantly decreased at week 2 of the study. Serum bone alkaline phosphatase, a marker of bone formation, was increased at week 2 compared with the basal level. It became, however, gradually decreased until week 14. Only one patient whose bone turnover was considerably high had a mild numbness feeling. These results suggest that cinacalcet treatment might transiently accelerate bone formation with rapid suppression of bone resorption. This uncoupling could be involved in a mechanism by which cinacalcet decreases serum Ca level.     

The effect of a short course of calcium and vitamin d on bone turnover in older women

Calcium and vitamin D (1200 mg/day + 800 IU) has been shown to reduce hip fracture incidence in older women living in long-term care facilities who had borderline low vitamin D levels. We examined the effect of a short course of calcium and vitamin D on biochemical markers of bone turnover in older community-living women. Twelve community-living women (mean age 75 years) in good general health, without diseases or on medications known to affect bone, were entered into the study. All women were treated with calcium citrate (1500 mg/day of elemental calcium) and vitamin D₃ (1000 IU/day) (Ca + D) for 6 weeks. Biochemical markers of bone turnover were measured in serum and urine collected at baseline (two samples), 5 and 6 weeks on Ca + D, and 5 and 6 weeks after termination of Ca + D. Markers of bone formation were osteocalcin, bone alkaline phosphatase and type I procollagen peptide. Markers of bone resorption were urinary hydroxyproline, free pyridinoline and deoxypyridinoline crosslinks, and N-telopeptides of type I collagen. Parathyroid hormone (PTH) and 25-hydroxyvitamin D were also measured at baseline, 6 weeks on treatment and 6 weeks after termination of treatment. All markers of bone resorption decreased on Ca + D and returned to baseline after termination of Ca + D (p<0.05). Markers of bone formation did not change with Ca + D treatment. PTH decreased on Ca + D and returned to baseline after treatment, and 25-hydroxyvitamin D increased with treatment and remained elevated 6 weeks after the end of treatment. We conclude that Ca + D reduces bone resorption in older women, possibly by suppressing PTH levels.     

Markers of Bone and Calcium Metabolism Following Gastric Bypass and Laparoscopic Adjustable Gastric Banding

BACKGROUND: Several studies have suggested that morbid obesity is associated with vitamin D deficiency and elevated parathyroid hormone (PTH). Studies have also suggested that there is an increase in vitamin D deficiency, bone resorption, and elevated PTH after gastric bypass surgery. Few studies have evaluated markers of bone and calcium metabolism after laparoscopic adjustable gastric banding or compared these results to those after gastric bypass. METHODS: Data on all patients undergoing primary gastric bypass (GBP; n = 979) and laparoscopic adjustable gastric banding (LAGB; n = 269) procedures at a tertiary-referral center from June 1996 through March 2005 were reviewed from a prospective database. Only patients with 25OH vitamin D levels available were included in this study (n = 534; GBP = 403, LAGB = 131). All patients were advised to take at least 1,200 mg calcium and 800-1,200 IU of vitamin D daily before and subsequent to their operation. Markers for bone metabolism [25OH Vitamin D, corrected serum calcium, alkaline phosphatase (AP), and PTH] were evaluated preoperatively and 3, 6, 12, and 24 months postoperatively. An analysis of variance and chi-square were performed to determine differences between the operative groups. Linear regression analysis was performed to evaluate the relationship between preoperative body mass index (BMI) and 25OH vitamin D and PTH levels and between percent excess weight loss and 25OH vitamin D and PTH after surgery. RESULTS: Sixty-four percent of all patients presented with vitamin D deficiency (<20 ng/ml) and 14% presented with elevated PTH preoperatively. Mean 25OH vitamin D levels and AP levels increased significantly after GBP surgery (vitamin D, 17 to 25 ng/ml 12 months post-op; AP, 80 to 90 IU/L 24 months post-op). Corrected calcium levels remained within normal limits and showed no change over time after both procedures. AP levels significantly increased from 76 IU/l preoperatively to 82 IU/l 6 months after LAGB surgery and then decreased to 59 IU/l 24 months after LAGB surgery. Linear regression analysis of preoperative vitamin D, PTH, and BMI values showed a significant positive relationship between initial BMI and PTH (r = 0.29) and a significant negative relationship between vitamin D and initial BMI (r = -0.19). A significant positive linear relationship between vitamin D and percent excess weight loss was evident 12 and 24 months after GBP surgery (r = 0.39 and 0.57, respectively). A negative relationship was evident between PTH and vitamin D 6 months after GBP surgery (r = -0.35) and 12 months after LAGB surgery (r = -0.61). CONCLUSIONS: These findings suggest that morbid obesity is associated with vitamin D deficiency, and elevated PTH and with adequate supplementation, GBP, and particularly LAGB, patients can improve their bone metabolism abnormalities related to obesity. Furthermore, adequate supplementation for GBP patients may attenuate the increased risk for bone loss associated with malabsorption from the bypass.