Bone Metabolism In Hemodialysis Patients Research Articles

Study of Red Blood Cell Indices and Biochemical Parameters of Mineral Bone Disorders in Hemodialysis Patients

Background: Chronic kidney disease (CKD) is a worldwide public health problem and a major cause of suffering and having a reduced quality of life for those affected. Objective: We aimed to study the changes in red blood cell indices and mineral bone metabolism in hemodialysis patients and to explore the correlation between these studied parameters. Patients and Methods: This is a case control study included 55 adult patients with end stage renal disease on maintenance hemodialysis as well as 55 healthy individuals as a control group. All participants were subjected to laboratory investigations included complete blood count and serum levels of creatinine, urea, total calcium, albumin, phosphate and intact parathyroid hormone (iPTH). Results: Our study showed thathemoglobin (Hb), hematocrit and red blood cell count were significantly reduced in the hemodialysis patients (P<0.001 for all). Regarding mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, no significant differences were found between the hemodialysis patients and the control group (P= 0.362, 0.116, 0.22, respectively). In the hemodialysis group, the albumin-corrected serum calcium level was significantly lower while the serum phosphate and iPTH levels were significantly higher compared to the control group (P<0.001 for all). Hb was inversely correlated with serum iPTH (r=-0.359, P=0.007) and serum phosphate (r=-0.570, P<0.001) in the hemodialysis group and was inversely correlated with serum phosphate (r=-0.495, P<0.001) in the control group. Conclusion: Hemodialysis patients are at high risk of anemia, hypocalcemia, hyperphosphatemia and hyperparathyroidism. In hemodialysis patients, an association was found between anemia and each of hyperphosphatemia and hyperparathyroidism.

Short- and Long-term Effects of Dialysate Calcium Concentrations on Mineral and Bone Metabolism in Hemodialysis Patients: The K4 Study

Rationale & ObjectiveThe short- and long-term impact of conversion of dialysate calcium concentration from either 2.5 or 3.0 mEq/L to 2.75 mEq/L on mineral and bone metabolism remains unknown in hemodialysis patients.Study DesignNonrandomized intervention study.Setting & Population12 hemodialysis patients treated at baseline with a 2.5-mEq/L dialysate calcium concentration and another 12 hemodialysis patients treated with a 3.0-mEq/L dialysate calcium concentration.InterventionUse of 2.75-mEq/L dialysate calcium concentration.OutcomesChanges in intradialytic calcium and phosphate clearance and changes in predialysis and intradialytic serum and ionized mineral and biochemical parameters over the 24 weeks following dialysate calcium conversion.ResultsConversion of dialysate calcium concentration from 2.5 to 2.75 mEq/L increased intradialytic calcium loading and serum total and ionized calcium levels, whereas conversion of dialysate calcium from 3.0 to 2.75 mEq/L decreased intradialytic calcium loading and serum total and ionized calcium levels. Dialysate calcium concentration conversion did not affect intradialytic serum parathyroid hormone level, intradialytic phosphate elimination, or predialysis serum calcium, phosphate, parathyroid hormone, and fibroblast growth factor 23 levels. Intradialytic calcium influx was determined by dialysate calcium concentration and predialysis serum calcium levels, whereas intradialytic phosphate elimination was determined by predialysis serum phosphate levels.LimitationsSmall sample size and no control groups treated with 2.5- and 3.0-mEq/L dialysate calcium concentrations during the 24 weeks of the observation period.ConclusionsConversion of dialysate calcium concentration from either 3.0 or 2.5 to 2.75 mEq/L results in expected changes in calcium loading based on predialysis calcium concentration. The dialysate calcium concentration should be personalized based on clinical factors.FundingNone.Trial RegistrationUniversity Hospital Medical Information Network, www.umin.ac.jp/english/, R000040105, UMIN000035184.

Influence of Hemodialysis Treatment on Biochemical Markers of Bone Disease

Abstract Introduction. Bone disease is a chronic complication of chronic kidney disease and major clinical problem in hemodialysis (HD) patients. The aim of our study was to assess the influence of treatment longevity on biochemical parameters of mineral and bone metabolism in HD patients, and to identify the most important parameters. Methods. The research was observational and retrospective, involved 70 patients, mean age 58.69±12.54, divided into groups in respect to the duration of dialysis treatment (Group I-5 years, Group II-5-10 years and Group III-over 10 years). Results. Serum phosphorus was increased, but the values tend to increase along with dialysis duration - (Group I: 1.93±0.45; Group II: 1.97±0.50; Group III: 2.01±0.37; p&gt;0,05). Calcium values were also not significantly increased based on the duration of treatment [Group I: 2.3 (2.2-2.41); Group II: 2.46 (2.15-2.6), Group III: 2.35 (2.10-2.52)]. Dialysis and PTH correlated positively in the first group of patients (Rho=0.470, p=0.013). The values of calcium and alkaline phosphatase correlated positively in all patients (Rho=0.351, p=0.003). PTH was significantly higher in the second and third compared to the first group (p=0.009 and p=0.038, respectively), and there was no significant difference between the second and the third group. Interestingly, parathyroidectomized patients had higher PTH values compared to those without parathyroidectomy (557 vs. 359 pg/ml). Conclusion. The most reliable marker for clinical monitoring of bone disease in dialysis patients is PTH. The values of calcium and phosphorus are highly variable and not reliable parameters for bone disease follow-up.

Association of habitual physical activity with bone metabolism in hemodialysis patients

Association of habitual physical activity with bone metabolism in hemodialysis patients

Poremećaji koštano-mineralnog metabolizma kod hemodijaliznih pacijenata

Introduction: Unless promptly treated, disturbances of bone and mineral metabolism during the course of chronic kidney disease can lead to serious complications. These abnormalities as well as other factors related to the uremic state affect the skeleton and result in disruption of homeostasis in the bone and mineral turnover. It is manifested by abnormal concentration of phosphorus and calcium in serum and tissues and changes in the concentration of PTH. The spectrum of skeletal abnormalities seen in renal osteodystrophy includes: osteitis fibrosa, osteomalacia, adynamic bone disease (ABD), osteopenia or osteoporosis and combinations of these abnormalities termed mixed renal osteodystrophy. Aim of the study: The aim of our study was to assess biochemical parameters of mineral and bone metabolism in hemodialysis patients. Patients and Methods: The research involved 30 patients (retrospective type of study), mean age 62.43; fifteen men (50%) and fifteen women (50%). Patients were divided into groups in respect to the length of dialysis treatment (group I - up to 5 years, group II - 5-10 years and group III - over 10 years). Conclusion: Serum phosphorus, calcium, alkaline phosphatase and PTH values were increased with duration of dialysis. The most reliable marker for clinical monitoring of bone disease in dialysis patients is PTH, which correlates well with the values of alkaline phosphatase (p=0,006) and calcium (p=0,021).

Association between high-molecular-weight adiponectin and bone mineral density in hemodialysis patients

Chronic kidney disease-mineral and bone disorder is a regular complication seen in hemodialysis patients and leads to substantial increases in the fracture rate, morbidity, and mortality. Discovered a few years ago, several clinical studies have shown a negative correlation between adiponectin and bone mineral density (BMD) independently of confounding factors. The relationship between adiponectin and bone metabolism in hemodialysis patients has not been fully described yet. We conducted this study to investigate the relationship between serum adiponectin concentration and the BMD in hemodialysis patients. We enrolled 92 hemodialysis patients who were receiving maintenance hemodialysis therapy at Towa Hospital. A peripheral blood sample was obtained, and standard biological data and the serum high-molecular-weight (HMW) adiponectin level were measured. BMD was assessed using dual-energy X-ray absorptiometry scans. In male hemodialysis patients, BMD was negatively related to age (r = -0.299, P = 0.012), duration of hemodialysis therapy (r = -0.31, P = 0.009), and log [HMW-adiponectin] (r = -0.31, P = 0.009) and positively related to body weight (r = 0.332, P = 0.004) and BMI (r = 0.297, P = 0.013). In female hemodialysis patients, BMD was negatively related to age (r = -0.499, P = 0.018) and log [HMW-adiponectin] (r = -0.46, P = 0.030) and positively related to triglyceride (r = 0.491, P = 0.020). HMW adiponectin may affect bone metabolism in both male and female hemodialysis patients.

Safety of Raloxifene in Hemodialysis Patients

Dear Editor, With interest I read the article from Saito and colleagues about “the effects of raloxifene on bone metabolism in hemodialysis patients with type 2 diabetes” (1). The article addresses the possibility of treatment with raloxifene for osteoporosis in these patients. Raloxifene, a selective estrogen receptor modulator could be a good option, because it has no known renal side effects like bisphosphonates. Additionally, bisphosphonate use in chronic kidney disease is associated with adynamic bone disease, compared with a low bone turnover (2). In another trial in a group of 17 postmenopausal hemodialysis patients raloxifene improved lumbar spine Bone Mineral Density (BMD) by 2.6% in 53% of the patients while 70% of the control group consisting of 10 aged-matched women showed a reduction in BMD by 4%. The effects of raloxifene on serum calcium and serum iPTH level suggest it improves bone resorption (3). Primary, in these patients treatment of secondary hyperparathyroidism should be performed as is recommended (4). However of concern is the safety of raloxifene treatment in this patient group with multimorbidity. Long term studies should be performed to determine the efficacy and safety of raloxifene in hemodialysis patients. Diabetes mellitus and chronic kidney disease both have a negative effect on bone metabolism and there is an increased risk of vascular complications. In the dialysis population the incidence of myocardial infarction and stroke is 5- to 15 fold higher (5) and cardiovascular mortality is 10- to 30-fold higher (6) than seen in the general population (7-9). In this hemodialysis population with or without diabetes mellitus I would expect an increased risk of fatal stroke with raloxifene therapy. Taking into account the data of the RUTH-trial in 10101 postmenopausal women with a mean age of 67 years, with a high Framingham Stroke Risk Score (FSRS) ( ≥ 13), a 75% increased risk of raloxifene–associated fatal stroke was found. (HR 1.75; 95% CI, 1.01-3.02) (10). The FSRS includes the classical risk factors for cardiovascular disease including age, sex, systolic blood pressure, total and high density lipoprotein cholesterol, diabetes mellitus, smoking and echocardiogram based left ventricular hypertrophy (11-13). This score was originally validated for people aged up to 75 years (14). The FSRS also seems to underestimate the vascular risk in hemodialysis patients. The prevalence of traditional cardiovascular disease risk factors is very high in this hemodialysisgroup, but seems not to explain all of the increased cardiovascular risk (15). I would recommend a longer term randomized, double-blind, placebo-controlled trial in hemodialysis patients (subgroup analysis with or without diabetes mellitus). Raloxifene versus placebo should be given for 3 years with attention to the change in BMD and monitoring fractures and vascular complications. First it should be shown that the number needed to treat to prevent fracture is clearly smaller than the number needed to harm in a clinical trial of the duration of the required raloxifene treatment before raloxifene can be safely recommended as common practice in the treatment of osteoporosis in hemodialysis patients. Saito et al. performed an important preliminary study that warrants the investment of such a trial to reach the quality standard of safe and evidence based therapy in this vulnerable patient group.

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients

Dear Editor, Saito et al. (1) reported that raloxifene (RAL) suppressed bone turnover and increased the quantitative ultrasound (QUS) parameter, speed of sound (SOS) of the calcaneus in hemodialysis postmenopausal women with type 2 diabetes or without type 2 diabetes. Baseline bone turnover markers like serum cross-linked N-terminal telopeptides of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) indicated high bone turnover in hemodialysis postmenopausal women, and the response of these bone turnover markers to RAL treatment did not differ significantly between diabetic and non-diabetic patients. No adverse events were detected in any patients. Thus, RAL was suggested to be beneficial in improving bone turnover and bone mass in hemodialysis postmenopausal women regardless of the presence of type 2 diabetes. However, owing to the small sample size and short duration of observation (one year), the incidence of fragility fractures was not assessed. Hemodialysis patients (chronic kidney disease [CKD] stage 5) have renal osteodystrophy, reflecting increased bone turnover caused by secondary hyperparathyroidism. Bone turnover is further increased in hemodialysis postmenopausal women compared with hemodialysis men because of the menopause-related increase in bone turnover. Although bone formation may be decreased in diabetic patients as indicated by low serum insulin-like growth factor-I (IGF-I) and osteocalcin concentrations (2-4), hemodialysis postmenopausal women showed high bone turnover similarly in patients with or without type 2 diabetes in the study conducted by Saito et al. (1) so that the effect of RAL on bone turnover markers was similar in diabetic and non-diabetic patients. Osteoporosis most commonly affects postmenopausal women, placing them at a significant risk of fractures. RAL is widely used for the treatment of postmenopausal osteoporosis. The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a double-blind, placebo-controlled randomized clinical trial encompassing 7705 postmenopausal women (aged 31–80 years) with osteoporosis, has shown that RAL increases bone mineral density (BMD) at the spine and femoral neck and reduces the risk of vertebral fracture in women with postmenopausal osteoporosis (5). Short stature, age, years since menopause, impaired cognitive function, visuospatial capabilities, impaired musculoskeletal strength, low femoral neck BMD, and prior vertebral fracture are significant factors affecting the incidence of new vertebral fractures (6). Recently, however, researchers have paid attention to CKD and type 2 diabetes in postmenopausal osteoporotic women treated with RAL, because establishing a strategy for the prevention of fragility fractures in postmenopausal osteoporitic women with CKD or type 2 diabetes has been suggested to be a matter of great urgency. An increased burden of osteoporosis exists in elderly people with CKD. CKD is associated with an increased risk of fragility fractures (7-11). CKD may lead to metabolic abnormalities that accelerate bone loss, such as chronic metabolic acidosis, hypogonadism, hyperparathyroidism, and abnormalities in vitamin D metabolism (12). Thus, the risk of fractures is considered to be higher in postmenopausal osteoporotic women with CKD than in those without CKD. Treatment approved for osteoporosis in postmenopausal women may be used in patients with stage 1–3 CKD (13). Consensus on the diagnosis of osteoporosis among those with advanced CKD stage 5 patients on dialysis is lacking (13). Because treatment decisions are difficult in stage 5 CKD, bone biopsy may be required and most treatments would be off-label (13). However, the results of the study conducted by Saito et al. (1) suggest the beneficial effect of RAL on bone turnover in hemodialysis postmenopausal women who show high bone turnover. According to the post-hoc analyses of the MORE study, RAL increases BMD at both the hip and the spine and reduces the risk of vertebral fracture among individuals with CKD (14). The effect of RAL on hip BMD is greater among those with mild to moderate CKD (14). RAL slows a yearly rate of increase in creatinine and a yearly rate of decrease in estimated glomerular filtration rate (eGFR) (15). These findings suggest the efficacy, safety and renoprotective effect of RAL. The number of patients with type 2 diabetes is increasing. Type 2 diabetes is associated with significantly increased risks of non-vertebral (relative risk: 1.2), hip (relative risk: 1.7), and foot (relative risk: 1.3) fractures (16). Patients with type 2 diabetes are susceptible to low-trauma fractures, especially hip fractures, despite having a normal or high BMD (17). The existence of an increased risk of fractures in type 2 diabetes suggests the potential involvement of other pathogenic influences on bone (e.g., hyperglycaemia, diabetic complications and lifestyle factors) than BMD (17). Because bone strength primarily reflects the integration of BMD and bone quality, the increased risk of fractures in type 2 diabetic patients may be partly explained by poor bone quality. The risk of fractures is considered to be higher in postmenopausal osteoporotic women with type 2 diabetes than in those without type 2 diabetes. Another analysis of the MORE study has shown that the risk reduction of vertebral fracture after RAL treatment is greater in patients with type 2 diabetes (odds ratio: 0.13, 95 % confidence interval: 0.03–0.55) than in those without type 2 diabetes (odds ratio: 0.49, 95 % confidence interval: 0.49–0.71), suggesting a higher efficacy of RAL against vertebral fractures in patients with type 2 diabetes (6). A preclinical study using ovariectomized rabbits showed that RAL ameliorated hyperhomocysteinemia-induced detrimental cross-linking and improved bone strength via the amelioration of collagen cross-links (18). Collagen cross-link formation is recognized as one of the factors that determine bone quality. Impaired enzymatic crosslinking and/or an increase in non-enzymatic cross-links (advanced glycation end-products [AGEs]) such as glucosepane and pentosidine in bone collagens is proposed to be a determinant of impaired bone mechanical properties in aging, osteoporosis, and diabetes (18). The efficacy of RAL against vertebral fractures in patients with type 2 diabetes may partly be attributable to its effect on bone quality including the collagen-cross linking profile. The endpoint of treatment for osteoporosis is to prevent fractures. Saito et al. (1) clearly showed the effect of RAL on surrogate markers. I would like to encourage them to assess the prevalence and incidence of vertebral fracture, homocystein, pentosidine (one of the AGEs), renal function, and BMD measured by dual energy x-ray absorptiometry in hemodialysis postmenopausal women treated with RAL.

Bone mineral density and bone metabolism in hemodialysis patients. Correlation with PTH, 25OHD3 and leptin.

Bone metabolism disorders in hemodialysed patients (HD) involve several humoral factors, of which PTH plays the central role. Leptin is usually found increased in renal failure and its link with bone metabolism has not been elucidated. We investigated the BMD and bone metabolism in association with serum PTH, 25OHD3 and leptin in HD patients. We measured bone alkaline phosphatase (bSAP), cross linked N telopeptide of type 1 collagen (NTx), PTH, 25OHD3 and leptin in 37 HD patients. We also evaluated BMI and BMD in lumbar spine (LS) and in femoral neck (FN) by DXA. Statistical evaluations were based on simple regression analysis. 1) Osteopenia was found in 32,1% in LS and 50% in FN and osteoporosis in 14.3% and 21.4% of our patients, respectively. LS or FN Z score was not related to HD duration. 2) Bone markers, PTH, phosphorus and leptin levels were increased. 3) 25OHD3 was low and was not related to NTx, bSAP or PTH. 4) PTH correlated with bone markers and Z score in LS and FN. 5) Leptin had no correlation with bone markers or Z score (except BMI). In our hemodialysed patients bone metabolism markers were increased in relation with high serum PTH levels. The observed high serum leptin was not associated with bone metabolism. Additionally the duration of hemodialysis did not appear to affect bone density.

Which Method is More Efficient in Determining Osteoporosis, QUS or DEXA?

Dear Editor, We read with much interest the recently published article, “Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients With Type 2 Diabetes,” by Saito et al (1). First, we would like to congratulate the authors. We wish to share a few scientific facts related to this interesting article. It was a pleasure to inform from this article that no difference was observed in BMD (bone mineral density) changes between patients with diabetes and nondiabetics after using raloxifene one year long. We have previously shown that the effects of low dose HRT and raloxifene on BMD at the lumbar spine and hip sites and biochemical markers of bone turnover in a randomized trial (2). In our study, the bone mineral density measurements with dual energy Xray absorptiometry (DEXA) method is accepted by the WHO as the gold standard for the diagnosis of osteoporosis. Satoi et al. proposed the SOS value has been shown to be significantly and positively correlated with lumbar BMD in the general population using methods such as DEXA in Patients and Methods section (1, 3). Quantitative calcaneal ultrasound has several potential advantages, including relatively low cost, no need for ionizing radiation, compact size, and ease of use. These advantages would make Quantitative calcaneal ultrasound an ideal screening tool if it can be shown to be an accurate indicator of skeletal density and fracture risk (4). The BMD measurement is accepted by the WHO as the gold standard for the diagnosis of osteoporosis. In another study, we have found a poor to moderate correlation between Quantitative ultrasound parameters (BUA, SOS, SI) and femoral and spinal BMD in pre and postmenopausal women (5). Tuna et al also reported, that the diagnostic value of tibial SOS did not seem to be high for discriminating between normal and low BMD at the femur and lumbar spine in postmenopausal women (6). I think that their results would be more precise if the authors’ preferred DEXA in spite of the measurement of calcaneal quantitative ultrasound parameters (SOS). We appreciate the authors and editor for publishing an important clinical article that may be beneficial to clinicians.

Oxidative Stress and Raloxifene

Dear Editor, We read “Effects of raloxifene on bone metabolism in hemodialysis patients with type 2 diabetes” by Saito et al. (1) with a great interest. This paper shows that raloxifene works in diabetic or non-diabetic hemodialysis patients to reduce bone loss. This was shown by means of significant decrease in NTx and a significant increase in SOS measurements in both treatment groups compared to the un-treated control arms. We would like to draw attention to the possible anti-oxidant role of raloxifene regarding beneficial effects on the bone turnover markers as well as bone mass. The targeted population in this study consisted hemodialysis patients with type 2 diabetes who under a great oxidative stress related to both renal failure and diabetes (2, 3). We have previously demonstrated that women with post-menopausal osteoporosis had lower erythrocyte catalase (CAT) enzyme activity and higher erythrocyte malondialdehyde (MDA) levels (4). Interestingly, in another study we showed that raloxifene treatment for 3 months significantly enhanced CAT enzyme activity and reduced the MDA levels in women with PMO (5). Similar anti-oxidant effects of raloxifene were confirmed by others (6). Although neither discussed nor studied by means of enzymatic parameters, we would like to attract Authors’ attention to the potent anti-oxidant effect of raloxifene particularly in this special study population. Significant decrease in N-terminal cross-linking telopeptide of type I collagen (NTx) as well as oxidative stress parameters has been achieved with the use of potent anti-oxidants (lycopene) in patients with PMO (7). We think the results of this present study should also be admissible regarding the anti-oxidant effects of raloxifene particularly in hemodialysis patients with type 2 diabetes who are under great oxidative stress.

Effects of raloxifene on bone metabolism in hemodialysis patients with type 2 diabetes

BackgroundOsteoporosis and chronic kidney disease are common conditions in older adults, and often occur concurrently. Bone disease is caused by increased bone turnover accompanying secondary hyperparathyroidism, and by factors such as bone metabolic disorder accompanying kidney disease and postmenopausal or age-related osteoporosis, even in hemodialysis patients. Raloxifene is commonly used for the treatment of postmenopausal osteoporosis in the general population, and may be a treatment option for osteoporosis in hemodialysis patients. However, the effects of raloxifene in hemodialysis patients with type 2 diabetes have not been examined in detail.ObjectivesThis study was performed to investigate the effects of raloxifene on bone turnover markers and bone density in postmenopausal women with type 2 diabetes mellitus who were undergoing hemodialysis in Japan.Patients and MethodsThe subjects were 60 female patients on maintenance hemodialysis (non-diabetic, n=30; diabetic, n=30). Raloxifene hydrochloride (60 mg) was administered to 14 diabetic patients and 14 non-diabetic patients for one year, and these patients were compared with control groups (no raloxifene) of 16 diabetic patients and 16 non-diabetic patients. Serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx), bone alkaline phosphatase, and intact parathyroid hormone (iPTH) were measured, and bone density was determined by quantitative heel ultrasound at the speed of sound (SOS) in the calcaneus during this period.ResultsThere were no significant differences in the levels of bone turnover markers except for iPTH after treatment of diabetic and non-diabetic patients with raloxifene for one year. SOS increased after treatment with raloxifene, but was significantly decreased in the control groups. Treatment with raloxifene resulted in a significant decrease in NTx and a significant increase in SOS in both diabetic and non-diabetic patients. There were no significant differences between the diabetic and non-diabetic patients who received raloxifene.ConclusionsTreatment with raloxifene can suppress reduction in bone density in postmenopausal women with type 2 diabetes who are undergoing hemodialysis.

Effect Of 12-week Modified Tai Chi Exercise On Bone Metabolism In Hemodialysis Patients

Effect Of 12-week Modified Tai Chi Exercise On Bone Metabolism In Hemodialysis Patients

The Impact of Chronic Inflammation on Bone Turnover in Hemodialysis Patients

Background. Renal osteodystrophy is very common in hemodialysis (HD) patients. HD is a chronic inflammatory state. Studies in other pathological entities have shown an impact of chronic inflammation on bone metabolism. In the present study, the impact of chronic inflammation on bone turnover in HD patients was evaluated. Patients and methods. Thirty-three anuric HD patients free of other pathological conditions or medications that affect immune system or bone metabolism and 30 healthy volunteers enrolled into the study. Intact parathyroid hormone (iPTH), the markers of inflammation IL-6 and CRP, as well as the markers of bone turnover osteocalcin (OCN) and beta-isomerized C-terminal cross-linked peptide of collagen type I (β-CTx) were measured in the serum. Results. All evaluated factors were increased in HD patients. In the HD group, the serum marker of osteoblastic activity OCN was related inversely to patients' age (r = −0.469, p = 0.006), CRP (rho = −0.460, p = 0.007), and IL-6 (r = −0.485, p = 0.004) but positively to iPTH (r = 0.707, p < 0.001). Similarly, the serum marker of osteoclastic activity β-CTx was related inversely to patients' age (r = −0.383, p = −0.028), CRP (rho = –0.466, p = 0.006), and IL-6 (r = −0.460, p = 0.007) but positively to iPTH (r = 0.657, p < 0.001). Multiple linear regression analysis revealed that IL-6 affects bone turnover independently of PTH and to the opposite direction. Conclusion. Chronic inflammation has a negative impact on bone turnover in HD patients. Certainly, further research and large clinical trials are needed for definite conclusions and for clarifying the exact molecular mechanisms implicated in the interaction between the immune system and bone metabolism in HD patients.

[Parathyroid and bone. Management of parathyroid function and evaluation of bone metabolism in hemodialysis patients].

Disturbances in mineral and bone metabolism due to loss of kidney function greatly influence morbidity and quality of life, so Kidney Disease: Improving Global Outcomes (KDIGO) proposed the concept of chronic kidney disease-mineral and bone disorder (CKD-MBD). Japanese Society for Dialysis Therapy has created guidelines for the management of secondary hyperparathyroidism associated prognosis in hemodialysis patients, and we are managing parathyroid function of hemodialysis patients under this guideline. Bone biopsy is not recommended as part of routine evaluation for CKD-MBD because bone biopsy is the invasive examination. KDIGO proposed new histological classification of renal osteodystrophy, TMV classification, for standardizing a result of bone histomorphometry. We expect that new guideline improve the prognosis of hemodialysis patients.

Sevelamer Hydrochloride Improves Hyperphosphatemia in Hemodialysis Patients With Low Bone Turnover Rate and Low Intact Parathyroid Hormone Levels

Sevelamer improves hyperphosphatemia without increasing the calcium load. However, it remains unknown whether sevelamer restores bone metabolism in hemodialysis patients with low bone turnover osteodystrophy and hypoparathyroidism. We investigated the changes in serum intact parathyroid hormone (iPTH) and bone metabolic marker levels after replacing calcium carbonate with sevelamer in these patients. We also conducted stratified analysis based on patient background and multivariate analysis to determine the factors affecting these parameters. During sevelamer replacement therapy, serum calcium and phosphate concentrations, and the calcium phosphate product were measured at 0, 1, 3, and 6 months. Serum iPTH, bone alkaline phosphatase and osteocalcin concentrations were measured at 0 and 6 months. In hemodialysis patients (71 men and 46 women, 63 +/- 12 years old) serum calcium levels and the calcium phosphate product decreased significantly at 1 month. Serum iPTH, bone alkaline phosphatase and osteocalcin levels increased significantly at 6 months. Increases in serum iPTH concentrations were observed in all stratified groups. Significant increases in serum bone alkaline phosphatase and osteocalcin concentrations were found only in the relative hypoparathyroidism group (iPTH levels > or =51.5 pg/mL, the median pretreatment level). Multivariate analysis showed that the factors affecting change in serum iPTH level are baseline serum iPTH, baseline calcium level (> or =9.5 mg/dL), and dialysis duration of 10 years or longer. Sevelamer appears useful for the treatment of hyperphosphatemia in these patients. Particularly, in the relative hypoparathyroidism group, the iPTH secretory response is probably enhanced and bone turnover may have been improved as a result of reducing the calcium load.

[Acute response of serum PTH and bone markers after injection of 1alpha,25 (OH)2D3 and 22-oxacalcitrol in hemodialysis patient].

Time-course changes of serum PTH and various bone markers were compared after injection of 1alpha,25 (OH)(2)D(3) with that of 22-oxacalcitriol (OCT) in hemodialysis patients. Five patients (M/F; 3/2, mean ages of 61.6 years) were enrolled into the present study. Oral administration of vitamin D(3) derivatives was stopped at least one week before initiation of vitamin injection. After 1 week of single intravenous injection of OCT (5 microg), 1alpha,25 (OH)(2)D(3) (0.5 microg) was followed. Serum levels of intact PTH, intact osteocalcin, bone alkaline phosphatase, cross-linked N-telopeptides of type I collagen, calcium, and phosphate were measured before, 24h, and 48 h after injections of vitamin D(3) derivatives. Significant difference did not exist in time-course changes of serum PTH, any of bone markers, calcium and phosphate between after OCT and 1alpha,25 (OH)(2)D(3) injection. In conclusion, the present study may not support the presence of significant direct effect of vitamin D(3) derivatives on bone metabolism in hemodialysis patients.

A clinical assessment of the relationship between bone scintigraphy and serum biochemical markers in hemodialysis patients

Renal osteodystrophy is a metabolic bone disease and a common complication of end-stage chronic renal failure and maintenance dialysis treatment. In this study, we examined the correlation between quantifying bone scintigraphy and serum biochemical markers in hemodialysis patients. Bone scintigraphy with technetium-99m-hydroxy-methylene-diphosphonate (99mTc-HMDP) was performed on 28 patients on maintenance hemodialysis. Bone scintigraphy was performed using a standard protocol and was quantified by setting regions of interest (ROIs) over selected regions. The bone-to-soft-tissue ratio (B/ST ratio) at each region was calculated in all patients. The B/ST ratios were then compared with serum biochemical markers. The B/ST ratio for the skull correlated well with serum bone-specific alkaline phosphatase (BAP) (r = 0.735, p < 0.001), serum deoxypyridinoline (DPD) (r = 0.806, p < 0.001) and intact parathyroid hormone (intact PTH) (r = 0.701, p < 0.001). The B/ST ratio for the lumbar spine correlated with intact PTH (r = 0.387, p < 0.05) but not with serum BAP or serum DPD. The B/ST ratio for the femoral neck correlated with serum DPD (r = 0.431, p < 0.05) and intact PTH (r = 0.449, p < 0.05) but not with serum BAP. Our data suggest that quantitative bone scintigraphy is a sensitive and useful method for evaluating bone metabolism in hemodialysis patients. The B/ST ratio for the skull may reflect changes of bone metabolism in hemodialysis patients.

Effects of Reduced Dialysate Calcium on Calcium-Phosphorus Product and Bone Metabolism in Hemodialysis Patients

Background: The safety of using reduced calcium dialysate (RDC) in hemodialysis (HD) patients is controversial due to related changes in bone metabolism. In the present study we investigated whether an 18-month treatment period with RDC may induce significant changes in calcium-phosphorus product (CaxP), bone metabolism, and components of the insulin-like growth factor (IGF) system in HD patients. Study Design: In this prospective study, 13 HD patients with biochemical signs of diminished or low-normal bone turnover and high CaxP due to high serum calcium level were treated by lowering dialysate calcium from 3.5 to 2.5 mEq/l for 18 months. By specific immunometric assays, serum levels of intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), pyridinoline (PYR), desoxypyridinoline (D-PYR), 25-OH-vitamin D₃ (25-vit D₃), 1,25-(OH)₂-vitamin D₃ (1,25-vit D₃), free IGF-I, IGF-II, and IGF-binding protein (IGFBP)-1 to -6 were measured. Results: CaxP decreased significantly from 5.62 (baseline) to 3.95 mmol²/l² (at 18 months), whereas PTH increased from 81 ± 57 pg/ml at baseline to 236 ± 188 at 12 months (p < 0.01), remaining in this range thereafter. Parameters of bone resorption (PYR) as well as formation (B-ALP) significantly increased during RDC, with peak levels after 12 months. Despite increasing doses of oral alfacalcidol, levels of 25-vit D₃ and 1,25-vit D₃ subsequently declined during RDC. In parallel with the changes in bone markers, free IGF-I levels decreased (baseline: 1.9 ± 0.9 ng/ml, after 18 months: 1.1 ± 0.7; p < 0.01). The decline of free IGF-I correlated with decreasing levels of IGFBP-3 and increasing levels of IGFBP-1/-4. Conclusion: The treatment with RDC effectively lowered CaxP and stimulated bone formation and resorption. The different changes in bone markers and IGF system components mirror the complex effects on bone metabolism.

Conjunctival and corneal calcification and bone metabolism in hemodialysis patients.

Conjunctival and corneal calcification is well recognized as a metastatic calcification in patients undergoing hemodialysis. In 44 male hemodialysis patients, we examined the relationship between the severity of conjunctival and corneal calcification and age; duration of hemodialysis; serum levels of calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and osteocalcin; and bone mineral density (BMD). The mean age was 58.3 years (range, 33-79 yr), and the mean duration of hemodialysis was 94.3 months (range, 25-258 mo). The serum level of Ca was 9.6 +/- 0.1 mg/dL, P was 5.9 +/- 0.1 mg/dL, Ca x P was 57.5 +/- 1.2, iPTH was 204.0 +/- 34.6 pg/mL, ALP was 173.8 +/- 11.8 U/L, and osteocalcin was 62.8 +/- 9.5 ng/mL. Lumbar BMD was 0.997 +/- 0.022 g/cm2 and radial BMD was 0.642 +/- 0.015 g/cm2. There was a significant positive correlation between the severity of conjunctival and corneal calcification and the duration of hemodialysis (P < 0.0001), the serum levels of P (P = 0.0035), the Ca x P (P = 0.0034), the iPTH (P = 0.0154), the ALP (P < 0.0001), and the osteocalcin (P = 0.0010), and was negatively correlated with radial BMD (P = 0.0008). However, the severity of conjunctival and corneal calcification was not significantly correlated with age (P = 0.986), serum Ca levels (P = 0.138), or lumbar BMD (P = 0.449). Based on these findings, we suggest that the conjunctival and corneal calcification developed by excessive serum levels of Ca and P associated with abnormal bone and mineral metabolism. This resulted in an increased bone turnover and decreased BDM after prolonged hemodialysis even though efforts were made to maintain the homeostasis of Ca and P metabolism in hemodialysis patients by using various therapeutic approaches.