Renal osteodystrophy in the first decade of the new millennium: Analysis of 630 bone biopsies in black and white patients

Malluche, Hartmut H.; Mawad, Hanna; Monier‐Faugere, Marie‐Claude

doi:10.1002/jbmr.309

Cited by 279 publications

(256 citation statements)

References 42 publications

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“…Vitamin D is customarily prescribed to patients with high PTH levels. Higher PTH levels are, in turn, associated with lower cortical bone mass (12). The presented results show that baseline BMD does not predict future changes in BMD.…”

Section: Discussionmentioning

confidence: 55%

“…The following biochemical parameters were measured because of their novelty or correlation with bone parameters in cross-sectional prior studies: serum parathyroid hormone (PTH; commonly used to assess bone turnover abnormalities, which have been shown to be associated with changes in bone volume) (12), bone-specific alkaline phosphatase (BSAP) and procollagen type 1 N-terminal propeptide (P1NP; which are markers of osteoblastic activity) (13,14), tartrate-resistant acid phosphatase-5b (TRAP-5b; a marker of osteoclastic activity) (15), sclerostin (a protein produced by osteocytes [16,17] and expressed at bone formation sites [18,19]), Dickkopf-1 (DKK-1; found in bone and other tissues [20], and like sclerostin, it leads to increased bone formation and bone volume when knocked out) (21,22), and fibroblast growth factor 23 (FGF23; involved in mineral metabolism with a role in bone mineralization/remodeling) (23)(24)(25). In addition, serum calcium and phosphorus were measured.…”

Section: Determinations Of Blood Parametersmentioning

confidence: 99%

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Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Malluche¹,

Davenport

Cantor³

et al. 2014

Clinical Journal of the American Society of Nephrology

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119

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Background and objectives Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.Design, setting, participants, & measurements This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.Results Eighty-one patients completed the study (mean age=52.6612.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.Conclusions QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.

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Section: Discussionmentioning

confidence: 55%

Section: Determinations Of Blood Parametersmentioning

confidence: 99%

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Malluche¹,

Davenport

Cantor³

et al. 2014

Clinical Journal of the American Society of Nephrology

Self Cite

119

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“…1 Studies of pediatric ROD find a greater prevalence of abnormal mineralization than in the adult skeleton. 20,21 This discrepancy could be explained by the higher remodeling of bone in the growing skeleton in addition to increases in bone turnover because of secondary hyperparathyroidism. The present findings are also consistent with prior studies showing that a reduction in relative mineralization, a decreased mineral to matrix ratio, is associated with reduced stiffness in human 22 and animal bone.…”

Section: Discussionmentioning

confidence: 99%

Differences in Bone Quality in Low- and High-Turnover Renal Osteodystrophy

Malluche

Porter

Monier‐Faugere

et al. 2012

Journal of the American Society of Nephrology

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114

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Abnormal bone turnover is common in CKD, but its effects on bone quality remain unclear. We qualitatively screened iliac crest bone specimens from patients on dialysis to identify those patients with low (n=18) or high (n=17) bone turnover. In addition, we obtained control bone specimens from 12 healthy volunteers with normal kidney function. In the patient and control specimens, Fourier transform infrared spectroscopy and nanoindentation quantified the material and mechanical properties of the specimens, and we used bone histomorphometry to assess parameters of bone microstructure and bone formation and resorption. Compared with high or normal turnover, bone with low turnover had microstructural abnormalities such as lower cancellous bone volume and reduced trabecular thickness. Compared with normal or low turnover, bone with high turnover had material and nanomechanical abnormalities such as reduced mineral to matrix ratio and lower stiffness. These data suggest that turnover-related alterations in bone quality may contribute to the diminished mechanical competence of bone in CKD, albeit through different mechanisms. Therapies tailored specifically to low-or high-turnover bone may treat renal osteodystrophy more effectively. Bone turnover abnormalities are well known in patients with chronic kidney disease (CKD). 1 These abnormalities encompass a spectrum from severely suppressed to markedly elevated bone turnover. Abnormal bone turnover occurs in approximately 85% of patients with CKD stage 5 on dialysis (CKD-5D), 2 and within this patient group, there is a greater risk of bone fracture than within the general population. [3][4][5] Although turnover abnormalities are well described, 1 little information is available on whether these abnormalities are associated with changes in bone quality. Bone quality is the contemporary term used to refer to the structural and material parameters that collectively enable bone to bear load and resist fracture or excessive deformation. 6,7 The potential link between bone turnover and bone quality is an important question meriting study because of the relatively high incidence of fractures reported to occur with abnormal turnover. [8][9][10][11][12][13][14] Thus, the specific aim of this study was to advance the understanding of this potential link by quantifying how the microstructural parameters, material composition, and nanomechanical properties vary in bone with low-or high-turnover renal osteodystrophy (ROD) compared with bone with normal turnover from normal volunteers. RESULTSAmong 163 iliac crest bone biopsies sequentially screened from patients with CKD-5D on dialysis, 35

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“…The histomorphological changes revealed by bone biopsy are the gold standard for diagnosis of renal osteodystrophy. However, several serum bone markers are more conveniently used to measure changes in bone turnover (Malluche et al 2011). None of our patients had biochemical hypoparathyroidism, which was defined as iPTH levels < 20 pg/ml (Puccini et al 2010) at long-term follow up.…”

Section: Biochemical Parameter Changes After Ptxmentioning

confidence: 99%

Association between Increased Serum Osteoprotegerin Levels and Improvement in Bone Mineral Density after Parathyroidectomy in Hemodialysis Patients

Zheng

Chu

et al. 2012

Tohoku J. Exp. Med.

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Secondary hyperparathyroidism (SHPT) is a common complication in chronic renal disease. Osteoprotegerin (OPG), an extracellular cytokine receptor secreted by osteoblasts, can promote bone formation by inhibiting the function of osteoclasts. Hemodialysis (HD) patients have elevated serum OPG levels. OPG secretion can be suppressed with high parathyroid hormone (PTH) levels. HD patients with refractory SHPT can benefit from parathyroidectomy (PTX) treatment, but the changes of serum OPG, bone turnover markers and bone mineral density (BMD) following PTX in HD patients remain unclear. In this study, patients on maintenance HD who received PTX for refractory SHPT (n = 28) were prospectively followed for 1 year. Serum intact PTH (iPTH), alkaline phosphatase (Alk-P), and OPG were measured serially; BMD was measured pre-PTX and at 1 year after PTX. After PTX, serum iPTH levels reduced profoundly. Serum Alk-P levels increased rapidly, peaking at 2 weeks post-PTX, while serum OPG levels gradually increased at 2 weeks after PTX and peaked at 2 months. BMD improved in both femoral neck (FN; cancellous and cortical bone) and lumbar spine (LS; cancellous bone). Higher baseline iPTH levels were associated with greater FN and LS BMD improvements at one year after PTX. The increment of serum OPG was correlated with the increase in LS BMD, implying that inhibition of osteoclastic bone resorption may improve BMD within the first year after PTX. These findings suggest that PTX removes the suppressive effects of high PTH on OPG secretion, resulting in the increased serum OPG levels that may contribute to BMD improvement.

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Renal osteodystrophy in the first decade of the new millennium: Analysis of 630 bone biopsies in black and white patients

Cited by 279 publications

References 42 publications

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Differences in Bone Quality in Low- and High-Turnover Renal Osteodystrophy

Association between Increased Serum Osteoprotegerin Levels and Improvement in Bone Mineral Density after Parathyroidectomy in Hemodialysis Patients

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