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.     

Increases in BMD correlate with improvements in bone microarchitecture with teriparatide treatment in postmenopausal women with osteoporosis.

Increases in BMD are correlated with improvements in 2D and 3D trabecular microarchitecture indices with teriparatide treatment. Therefore, improvements in trabecular bone microarchitecture may be one of the mechanisms to explain how BMD increases improve bone strength during teriparatide treatment. INTRODUCTION: Bone strength is determined by BMD and other elements of bone quality, including bone microarchitecture. Teriparatide treatment increases BMD and improves both cortical and trabecular bone microarchitecture. Increases in lumbar spine (LS) BMD account for approximately 30-41% of the vertebral fracture risk reduction with teriparatide treatment. The relationship between increases in BMD and improvements in cortical and trabecular microarchitecture has not yet been studied. MATERIALS AND METHODS: The relationship between increases in BMD and improvements in cortical and trabecular microarchitecture after teriparatide treatment was assessed using data from a subset of patients who had areal BMD measurements and structural parameters from transiliac bone biopsies in the Fracture Prevention Trial. 2D histomorphometric and 3D microCT parameters were measured at baseline and 12 (n = 21) or 22 (n = 36) mo. LS BMD was assessed at baseline and 12 and 18 mo, and femoral neck (FN) BMD was measured at baseline and 12 mo. Pearson correlation was performed to assess the relationship between actual changes in BMD and actual changes in microarchitectural parameters. RESULTS: Changes in LS BMD at 12 mo were significantly correlated with improvements in trabecular bone structure at 22 mo: 2D bone volume (r = 0.45, p = 0.02), 2D mean wall thickness (r = 0.41, p = 0.03), 3D bone volume (r = 0.48, p = 0.006), 3D trabecular thickness (r = 0.44, p = 0.01), 3D trabecular separation (r = -0.37, p = 0.04), 3D structural model index (r = -0.54, p = 0.001), and 3D connectivity density (r = 0.41, p = 0.02). Changes in LS BMD at 18 mo had similar correlations with improvements in bone structure at 22 mo. Changes in FN BMD at 12 mo were significantly correlated with changes in 2D mean wall thickness (r = 0.56, p = 0.002), 3D bone volume (r = 0.51, p = 0.004), 3D trabecular thickness (r = 0.44, p = 0.01), 3D trabecular separation (r = -0.46, p = 0.01), and 3D structural model index (r = -0.55, p = 0.001). CONCLUSIONS: Increases in BMD are correlated with improvements in trabecular microarchitecture in iliac crest of patients with teriparatide treatment. Therefore, improvements in trabecular bone microarchitecture may be one of the mechanisms to explain how BMD increases improve bone strength during teriparatide treatment.     

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

Summary

Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug.

Introduction

The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1–34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis.

Methods

Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N?=?65) or quarterly intravenous IBN (N?=?122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared.

Results

Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9?±?7.4 years, body mass index 23.8?±?3.8 kg/m², BMD L1–L4 0.741?±?0.100 g/cm², and TBS 1.208?±?0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 %?±?6.3 vs. +2.9 %?±?3.3 and +4.3 %?±?6.6 vs. +0.3 %?±?4.1, respectively; P?<?0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r ²?=?0.04) with no correlation between the changes in BMD and TBS over 24 months.

Conclusions

In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.     

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.     

Vertebral Fracture Risk Is Reduced in Women Who Lose Femoral Neck BMD With Teriparatide Treatment

Response to osteoporosis therapy is often assessed by serial BMD testing. Patients who lose BMD without secondary causes of bone loss may be considered to be “nonresponders” to treatment. We examined vertebral fracture (VF) risk, change in lumbar spine (LS) BMD, and change in amino‐terminal extension peptide of procollagen type I (PINP) in postmenopausal women whose femoral neck (FN) BMD decreased, increased, or was unchanged after receiving teriparatide (TPTD) or placebo (PL) in the Fracture Prevention Trial. FN and LS BMD were measured at baseline and 12 mo. VFs were assessed by lateral spine radiographs at baseline and study endpoint. A BMD change from baseline of >4% was considered to be clinically significant. Decreases of >4% FN BMD were less common in women receiving TPTD (10%) versus PL (16%, p < 0.05), yet women on TPTD who lost FN BMD still had significant reductions in VF risk compared with PL (RR = 0.11; 95% CI = 0.03–0.45). VF risk reduction with TPTD compared with PL was similar across categories of FN BMD change from baseline at 12 mo (loss >4%, loss 0–4%, gain 0–4%, or gain >4%; interaction p = 0.40). Irrespective of FN BMD loss or gain, TPTD‐treated women had statistically significant increases in LS BMD and PINP compared with PL. In both groups, losses or gains in FN BMD at 12 mo corresponded to losses or gains in BMC rather than changes in bone area. In conclusion, loss of FN BMD at 12 mo in postmenopausal women with osteoporosis treated with TPTD is nevertheless consistent with a good treatment response in terms of VF risk reduction.     

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.     

Decreased mineralization in hemodialysis patients after subtotal parathyroidectomy

Summary Many hemodialysis patients undergo subtotal parathyroidectomy (sPTx) because of the complications of severe secondary hyperparathyroidism. In some patients, however, renal osteodystrophy fails to regress. In uremia, the high levels of circulating immunoreactive parathyroid hormone (iPTH) which accompany osteitis fibrosa are associated with accelerated bone formation. After sPTx, the fall in iPTH may decrease mineralization and increase osteoid formation. Bone histomorphometry, densitometry, and serum biochemical determinations were done in 20 patients on regular maintenance hemodialysis and after sPTx in 3 additional patients. Densitometry at the radial diaphysis was inversely related to osteoid volume so that low bone mineral content indicated excess osteoid. Elevated serum alkaline phosphatase activity was associated with osteitis fibrosa. Tetracycline double labels identified 5 patients with an increased rate of mineralization. Levels of iPTH and serum phosphorus were positively correlated to the mineralization rate. The fall in iPTH after sPTx was accompanied by a reduction in osteitis fibrosa and decreased mineralization. The nonosteoblastic osteoid became more abundant. After sPTx some hemodialysis patients may convert the osteitis fibrosa to a poorly treatable low turnover osteomalacia.     

Fractures and vertebral bone mineral density in patients with renal osteodystrophy

We investigated the relationship of CT determined vertebral bone mineral density (BMD), type of renal osteodystrophy, N terminal PTH levels and fracture history in 31 dialysis patients. BMD for patients with bone biopsy documented osteitis fibrosa was 1.6 standard deviation (SD) above the normal value for age and sex matched controls, while those patients with low turnover osteodystrophy had a mean BMD 1.2 SD below normal (p less than 0.0001). Three patients with osteitis fibrosa who had previously been treated with prednisone had a low BMD (1.8 SD below normal, different than O, p = 0.0015). There was no correlation between BMD and time on dialysis (r = 0.1). An N terminal PTH level greater than 150 pg/ml was a sensitive (94%) and specific (100%) method of separating those patients with osteitis fibrosa from those with low turnover osteodystrophy, while BMD was much less useful in this differentiation. A low BMD was not predictive of fracture history but the type of renal osteodystrophy was. Patients with low turnover osteodystrophy had a fracture rate of 0.2 fractures/dialysis year in comparison to those with osteitis fibrosis who had 0.1 fractures/dialysis year. Patients with the former bone disease fractured mainly axial rather than appendicular bones in contrast to those patients with osteitis fibrosa. In conclusion we found that patients with osteitis fibrosa had increased BMD compared to normal while those with low turnover osteodystrophy had decreased BMD, but that the N terminal PTH level was a better predictor of the type of bone disease present than was BMD.     

Effect of raloxifene after recombinant teriparatide [hPTH(1–34)] treatment in postmenopausal women with osteoporosis

Summary Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. Introduction We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide. Methods Following a year of open-label teriparatide 20 μg/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry. Results The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (−1.0 ± 0.3%, P = 0.004; and −4.0 ± 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (−2.6 ± 0.4% (raloxifene-raloxifene) and −2.7 ± 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 ± 0.5% vs. 5.1 ± 0.5%; FN: 3.4 ± 0.6% vs. 3.0 ± 0.5%). Conclusion Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. Preliminary data presented previously at the International Osteoporosis Foundation World Congress on Osteoporosis, Toronto Canada June 2–6, 2006, abstract published: Adami S, Munoz-Torres M, Econs MJ, Sipos A, Xie L, Dalsky GP, McClung M, Felsenberg D, Brown JP, Brandi ML, San Martin J. Effect of raloxifene after teriparatide treatment in postmenopausal women with osteoporosis. Osteoporos Int. 2006;17(Suppl 2):S137.     

We Use Too Much Vitamin D in Hemodialysis Patients

Current Kidney Disease Improving Global Outcomes guidelines for chronic kidney disease–mineral and bone disorder recommend maintaining the PTH level between 2 and 9 times the upper limit of normal. PTH levels function as a surrogate for bone turnover to differentiate forms of renal osteodystrophy. Vitamin D receptor agonists are primarily used to treat osteitis fibrosa in hemodialysis patients. However, there is concern that overtreatment may put HD patients at risk for adynamic bone disease, which has been associated with fracture and vascular calcification. This raises the issue as to whether “we use too much vitamin D in hemodialysis patients.”     

Efficacy of Antiosteoporotic Medications in Patients With Rebound-Associated Fractures After Denosumab Discontinuation

Denosumab discontinuation results in rapid bone loss and increased risk of multiple rebound-associated vertebral fractures (RAVFs). The optimal treatment for patients who have sustained such fractures is currently unknown. We aimed to investigate the bone mineral density (BMD) changes achieved with various regimens in postmenopausal women who had sustained RAVFs after denosumab discontinuation in everyday clinical practice. In this multicenter, retrospective observational study, 39 Greek postmenopausal women from six regional bone centers throughout Greece with RAVFs after denosumab discontinuation were included. We collected BMD and fracture data before and 1 year after treatment with denosumab (n = 20), teriparatide (n = 8), zoledronate (n = 8) or teriparatide/denosumab combination (n = 3). Both lumbar spine (LS)-- and femoral neck (FN)-BMD were preserved with all regimens used. With the exception of zoledronate, a trend towards increase was observed with all regimens in LS-BMD. Three patients sustained additional fractures despite treatment reinstitution (2 with zoledronate and 1 with teriparatide). Among patients with RAVFs following denosumab discontinuation both antiresorptive (zoledronate and denosumab) and anabolic (teriparatide) treatment as well as the combination of denosumab with teriparatide seem to be effective in terms of BMD response.     

Effect of Teriparatide or Risedronate in Elderly Patients With a Recent Pertrochanteric Hip Fracture: Final Results of a 78‐Week Randomized Clinical Trial

We present final results of a study comparing teriparatide 20 μg every day (QD) with risedronate 35 mg once per week (QW) started within 2 weeks after surgery for a pertrochanteric hip fracture. Patients with BMD T‐score ≤ –2.0 and 25OHD ≥9.2 ng/mL were randomized to receive 26‐week double‐dummy treatment plus calcium and vitamin D, followed by 52‐week open‐label treatment with the same assigned active drug. Primary endpoint was change from baseline in lumbar spine (LS) BMD at 78 weeks. Secondary and exploratory endpoints were change in BMD at the proximal femur, function, hip pain (Charnley score and 100 mm Visual Analog Scale [VAS]), quality of life (Short Form‐36), radiology outcomes, and safety. Data were analyzed with mixed models for repeated measures (MMRM) and logistic regression. Totally, 224 patients were randomized; 171 (teriparatide: 86) contributed to the efficacy analyses (mean ± SD age: 77 ± 7.7 years, 77% females). Mean baseline LS, femoral neck (FN), and total hip (TH) T‐scores were –2.16, –2.63, and –2.51, respectively. At 78 weeks, BMD increased significantly more with teriparatide compared to risedronate at the LS (+11.08% versus +6.45%; p < 0.001) and FN (+1.96% versus –1.19%; p = 0.003), with no significant between‐group difference in TH BMD. Timed up‐and‐go (TUG) test was significantly faster with teriparatide at 6, 12, 18, and 26 weeks (differences: –3.2 to –5.9 s; p = 0.045 for overall difference). Hip pain during TUG test by 100 mm VAS was significantly lower with teriparatide at 18 weeks (adjusted difference: –11.3 mm, p = 0.033; –10.0 and –9.3 mm at 12 and 26 weeks, respectively; p = 0.079 for overall difference). Other secondary and exploratory outcomes were not different. Teriparatide group showed two new hip fractures versus seven with risedronate (p = 0.171) and more frequent hypercalcemia and hyperuricemia. In conclusion, 78‐week treatment with teriparatide showed significantly greater increases in LS and FN BMD, less pain, and a faster TUG test versus risedronate. © 2016 American Society for Bone and Mineral Research.     

Elevation of intact parathyroid hormone level is a risk factor for low bone mineral density in pretransplant patients with liver diseases

The purpose of this study was to investigate the frequency and risk factors for low bone mineral density (BMD) among patients awaiting liver transplantation. BMD of the lumbar spine (LS) and femoral neck (FN), measured by dual-energy X-ray absorptiometery (DEXA), were obtained in 64 pretransplant patients. We measured markers of bone metabolism including serum calcium, phosphorus, serum 25-hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline/creatinine (DPD/Cr) ratio. Osteoporosis and osteopenia (low BMD) were observed in 36 patients (36/64, 56.2%), including 6 cases of osteoporosis (6/64, 9.3%) and 30 cases of osteopenia (30/64, 46.9%). Of all variables, cholestatic liver disease and elevated levels of iPTH were significantly associated with low BMD. Moreover, elevated iPTH level was identified as an independent risk factor for low BMD (P<.05, OR=1.017, 95% CI=1.001-1.032) by multivariate analysis. The median level of iPTH was increased to 55.6 pg/mL (range, 7.8-337 pg/mL) in the low BMD group, while the median level was 33 pg/mL (range, 3-162 pg/mL) in the normal BMD group (P<.05). This study revealed a high incidence of low BMD in the pretransplant patients with liver diseases. The elevated iPTH level was the predominant risk factor for low BMD. We suggest that both BMD and iPTH examinations be considered routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.     

Bone histomorphometry is still the golden standard for diagnosing renal osteodystrophy

AIM: The clinical picture of renal osteodystrophy (RO) is very uncharacteristic. The diagnosis is made by means of biochemical indicators, intact parathormone (iPTH) concentration, bone X-rays, bone densitometry and particularly bone histomorphometry. The aim of our study was to establish whether a combination of non-invasive methods can bring us closer to the diagnosis as to avoid bone biopsy. PATIENTS AND METHODS: We chose 30 patients treated by chronic hemodialysis. Only 4 of them had no symptoms of RO. Biochemical parameters (Ca, P) and iPTH concentrations were determined. bone X-rays were taken (the parathyroid series), bone mineral density was measured by quantitative digital radiography (QDR), and bone biopsy specimens were taken for bone histomorphometry. The data were analyzed by the Statistica by StatSoft and SPSS computer programs. RESULTS: With respect to bone histomorphometry, 10 patients had osteitis fibrosa (OF), 15 had mixed osteodystrophy (MO), 5 adynamic bone disease (ABD). There was a good correlation of iPTH and alkaline phosphatase (AP) concentrations with histomorphometric parameters. There was also a correlation between radiological changes and histomorphometric parameters. After the analysis of discrimination using the SPSS computer program, taking only iPTH into consideration, 36.6% of patients were correctly classified according to their diagnosis. Considering iPTH and densitometry, 46.6% were classified correctly. Considering iPTH and radiological changes, 60% of patients were classified correctly. CONCLUSION: To diagnose 73.3% of patients correctly, it was necessary to consider the above mentioned non-invasive parameters, as well as AP, P, concentrations and the patient age. Histomorphometry remains the "golden standard" for diagnosing RO.     

Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study

Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. This phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis (HD) and peritoneal dialysis (PD) patients with PTH > or =300 pg/ml despite traditional therapy. A total of 395 patients received once-daily oral cinacalcet (260 HD, 34 PD) or placebo (89 HD, 12 PD) titrated from 30 to 180 mg to achieve a target intact PTH (iPTH) level of < or =250 pg/ml. During a 10-wk efficacy assessment phase, cinacalcet was more effective than control for PTH reduction outcomes, including proportion of patients with mean iPTH levels < or =300 pg/ml (46 versus 9%), proportion of patients with > or =30% reduction in iPTH from baseline (65 versus 13%), and proportion of patients with > or =20, > or =40, or > or =50% reduction from baseline. Cinacalcet had comparable efficacy in HD and PD patients; 50% of PD patients achieved a mean iPTH < or =300 pg/ml. Cinacalcet also significantly reduced serum calcium, phosphorus, and Ca x P levels compared with control treatment. The most common side effects, nausea and vomiting, were usually mild to moderate in severity and transient. Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH, Ca x P, calcium, and phosphorus levels in patients who received HD or PD. Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.     

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.     

Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate.

We investigated the effects of 18 months of treatment with teriparatide in patients previously treated with long-term antiresorptive therapy using bone turnover markers and bone densitometry. Previous raloxifene treatment allowed for teriparatide-induced early bone marker and BMD increases comparable with previously published results for treatment-n?ive patients. Conversely, previous alendronate treatment reduced the bone marker and BMD response. INTRODUCTION: Teriparatide [rhPTH(1-34)] has been shown to increase BMD and reduce the risk of fracture in postmenopausal women with osteoporosis. Our objective was to investigate the skeletal effects of 18 months of treatment with teriparatide in women whose osteoporosis was previously treated with either alendronate or raloxifene. MATERIALS AND METHODS: Daily subcutaneous injections of 20 microg teriparatide were administered for 18 months to 59 postmenopausal women, 60-87 years of age, with BMD T-scores 相似文献   

Natural history and risk factors for bone loss in postmenopausal Caucasian women: a 15-year follow-up population-based study

SUMMARY: In this 15-year follow-up study, we found that the estimated rate of bone loss at the femoral neck (FN) for women aged 45-68 was linear at a rate of 1.67% per year, but quadratic for lumbar spine (LS) at a rate of 3.12% initially, and slowing down with age. We also confirmed the protective role of HRT, increasing weight, and lean mass in long-term bone loss. INTRODUCTION: The objective was to describe the natural history of bone loss and explore the role of environmental factors in postmenopausal women over a 15-year period. METHODS: Bone mineral density (BMD) at the FN and the LS were measured in postmenopausal women from the Chingford Study. Height, weight, HRT status, and calcium/vitamin D supplement were assessed at each visit. Osteoarthritis of hip and spine was assessed by X-ray at baseline and at year 8. RESULTS: A total of 955 postmenopausal women with an average age of 54.7 at baseline were included. Both FN and LS BMD decreased significantly with age (p<0.0001). The decline was larger in the LS (-3.12% per year), which showed a quadratic relationship, than in the FN (-1.67% per year) with a linear relationship. The rate of bone loss was reduced by one third annually for the FN and LS respectively in current HRT users. Change in weight was positively associated with both DeltaFN and DeltaLS BMD (beta=0.16% and 0.09% change in DeltaFN and DeltaLS BMD per kilogramme change in weight respectively, p<0.0001 for both sites). Spine OA and progression were positively associated with DeltaLS BMD (beta=1.22% change in DeltaLS BMD per grade in spine OA and 0.45% change in DeltaLS BMD for patients who progressed, p<0.0001 for spine OA and p=0.002 for spine OA progression). Spine OA (beta=0.54% change in DeltaFN BMD per grade, p<0.0001), but not progression, and hip OA were positively associated with DeltaFN BMD. Furthermore, both age and body weight at baseline were positively associated with both DeltaFN and DeltaLS BMD (beta=0.02-0.04% change in DeltaFN and DeltaLS BMD per year increase in age at baseline and 0.004-0.007% change in DeltaFN and DeltaLS BMD per kilogramme increase in weight at baseline, all p<0.0001). CONCLUSION: This large population-based longitudinal study demonstrated that the decline of BMD over 15 years is linear with age for the FN, but quadratic for the LS. The study confirmed the protective role of HRT, increased weight and lean mass in long-term bone loss.     

Correlation of bone mineral density with the histological findings of renal osteodystrophy in patients on hemodialysis

AIMS: To examine the distribution of bone mineral density (BMD) in different histological groups of renal osteodystrophy. PATIENTS: We prospectively studied 62 patients, 41 men and 21 women, aged 57+/-11.5 years, who had been on hemodialysis for 60+/-55 months. The women had been amenorrheic for 13+/-4 years and 7 patients (11%) had a positive fracture history. METHODS: A bone biopsy was taken after tetracycline labelling and BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry (DEXA); serum intact parathyroid hormone (iPTH), bone Gla protein (BGP), phosphorus, calcium and alkaline phosphatase (ALP) were also determined. RESULTS: Histologically, 40 patients showed secondary hyperparathyroidism (sHPT), 6 mixed bone disease, 14 adynamic bone disease (A) and 2 osteomalacia. BMD of the lumbar spine was decreased in 43 patients (69%) and in 9 (14.5%) it was lower than -2 Z score units. BMD of the femoral neck was low in 55 patients (89%) and in 22 (35.5%) it was lower than -2 Z scores. BMD was lower in patients with sHPT than in those with adynamic bone disease (p<0.05) in which it was close to normal. BMD in both these sites correlated inversely with the biochemical markers (serum iPTH, BGP and ALP) and the histomorphometric indices of bone turnover. CONCLUSIONS: Osteopenia is frequent in patients on hemodialysis, especially those with biochemical and histological findings of sHPT.