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  1. Article ; Online: Trabecular bone microcrack accumulation in patients treated with bisphosphonates for durations up to 16 years.

    Pienkowski, David / Wood, Constance L / Malluche, Hartmut H

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society

    2022  Volume 41, Issue 5, Page(s) 1033–1039

    Abstract: This study quantified the length, number, and density of microcracks in bone from patients treated with bisphosphonates as a function of duration. Anterior iliac crest bone samples from 51 osteoporotic Caucasian females continuously treated with oral ... ...

    Abstract This study quantified the length, number, and density of microcracks in bone from patients treated with bisphosphonates as a function of duration. Anterior iliac crest bone samples from 51 osteoporotic Caucasian females continuously treated with oral bisphosphonates for 1-16 years were obtained by bone biopsy. Samples were histologically processed and analyzed for bone area, microcrack number, and microcrack length. The analyses used statistical modeling and considered patient age, bone mineral density, bone volume/total volume, trabecular thickness, and bone turnover as potential covariates. Microcrack density (number of microcracks/total examined bone area) was linearly related (p = 0.018) to bisphosphonate treatment duration. None of the analyzed covariates contributed significantly to the observed relationship between microcrack density and bisphosphonate treatment duration. Observed increases in microcrack density with increasing bisphosphonate treatment duration is important because increasing levels of microcracks may not only affect bone remodeling but also reduce elastic modulus and are suspected to adversely affect other mechanical properties that may influence fracture risk. The present findings add to our prior results showing changes in bone material properties and modulus with bisphosphonate treatment duration and thereby provide a more comprehensive assessment of the relationship between bisphosphonate treatment duration and bone quality. Statement of Clinical Significance: The present findings provide information guiding clinical use of oral bisphosphonates for post-menopausal osteoporosis therapy.
    MeSH term(s) Female ; Humans ; Diphosphonates/adverse effects ; Cancellous Bone/diagnostic imaging ; Cancellous Bone/pathology ; Fractures, Bone/pathology ; Bone Density ; Bone and Bones/pathology
    Chemical Substances Diphosphonates
    Language English
    Publishing date 2022-09-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 605542-4
    ISSN 1554-527X ; 0736-0266
    ISSN (online) 1554-527X
    ISSN 0736-0266
    DOI 10.1002/jor.25441
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  2. Article ; Online: Response to "Low Turnover Bone Disease in Early CKD Stages".

    El-Husseini, Amr / Abdalbary, Mohamed / Lima, Florence / Davenport, Daniel / Faugere, Marie-Claude / Malluche, Hartmut H

    Kidney international reports

    2022  Volume 7, Issue 6, Page(s) 1445–1446

    Language English
    Publishing date 2022-04-14
    Publishing country United States
    Document type Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2022.04.011
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  3. Article: FGF-23 and sclerostin in serum and bone of CKD patients.

    Lima, Florence / Monier-Faugere, Marie-Claude / Mawad, Hanna / David, Valentin / Malluche, Hartmut H

    Clinical nephrology

    2023  Volume 99, Issue 5, Page(s) 209–218

    Abstract: Aims: Renal osteodystrophy occurs in the early stages of chronic kidney disease (CKD) and progresses during loss of kidney function. Fibroblast growth factor (FGF)-23 and sclerostin, both produced by osteocytes, are increased in blood of patients with ... ...

    Abstract Aims: Renal osteodystrophy occurs in the early stages of chronic kidney disease (CKD) and progresses during loss of kidney function. Fibroblast growth factor (FGF)-23 and sclerostin, both produced by osteocytes, are increased in blood of patients with CKD. The aim of this study was to analyze the impact of decline in kidney function on FGF-23 and sclerostin protein expression in bone and to study their relationship with their serum levels and bone histomorphometry.
    Materials and methods: 108 patients aged 25 - 81 years (mean ± SD: 56 ± 13 years) underwent anterior iliac crest biopsies after double-tetracycline labeling. Eleven patients were CKD-2, 16 were CKD-3, 9 were CKD-4 - 5, and 64 CKD-5D. Patients were on hemodialysis for 49 ± 117 months. 18 age-matched patients without CKD were included as controls. Immunostaining was performed on undecalcified bone sections to quantify FGF-23 and sclerostin expression. Bone sections were also evaluated by histomorphometry for bone turnover, mineralization, and volume.
    Results: FGF-23 expression in bone correlated positively with CKD stages (p < 0.001) increasing from 5.3- to 7.1-fold starting at CKD-2. No difference in FGF-23 expression was seen between trabecular and cortical bone. Sclerostin expression in bone correlated positively with CKD stages (p < 0.001) with an increase from 3.8- to 5.1-fold starting at CKD-2. This increase was progressive and significantly greater in cortical than cancellous bone. FGF-23 and sclerostin in blood and bone were strongly associated with bone turnover parameters. Expression of FGF-23 in cortical bone correlated positively with activation frequency (Ac.f) and bone formation rate (BFR/BS) (p < 0.05), while sclerostin correlated negatively with Ac.f, BFR/BS, and osteoblast and osteoclast numbers (p < 0.05). FGF-23 trabecular and cortical expressions correlated positively with cortical thickness (p < 0.001). Sclerostin bone expression correlated negatively with parameters of trabecular thickness and osteoid surface (p < 0.05).
    Conclusion: These data show a progressive increase in FGF-23 and sclerostin in blood and bone associated with decrease in kidney function. The observed relationships between bone turnover and sclerostin or FGF-23 should be considered when treatment modalities are developed for management of turnover abnormalities in CKD patients.
    MeSH term(s) Humans ; Bone and Bones ; Bone Remodeling ; Chronic Kidney Disease-Mineral and Bone Disorder ; Fibroblast Growth Factors ; Kidney Failure, Chronic/complications ; Osteogenesis ; Renal Insufficiency, Chronic/complications
    Chemical Substances Fibroblast Growth Factors (62031-54-3) ; FGF23 protein, human ; SOST protein, human
    Language English
    Publishing date 2023-03-27
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 185101-9
    ISSN 0301-0430
    ISSN 0301-0430
    DOI 10.5414/CN111111
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  4. Book: Nephrology at the verge of the century

    Malluche, Hartmut H.

    Ulm, Germany, November 11 - 12, 1994

    (Kidney international : Supplement ; 50)

    1995  

    Author's details [guest ed.: Hartmut Malluche ...]
    Series title Kidney international : Supplement ; 50
    Kidney international
    Kidney international ; Supplement
    Collection Kidney international
    Kidney international ; Supplement
    Keywords Nephrology / trends / congresses ; Nephrologie
    Language English
    Size S44 S. : Ill., graph. Darst.
    Publisher Blackwell Science
    Publishing place Cambridge
    Publishing country Great Britain
    Document type Book
    HBZ-ID HT006741165
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    Zs A 797 -Suppl.50- not available for loan Zeitschriften-Lesesaal

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  5. Book ; Conference proceedings: Bone morphometry 1992

    Malluche, Hartmut H.

    sixth international congress proceedings ; Lexington, Kentucky, Oct. 4 - 9, 1992

    (Bone ; 14,3 = spec. issue)

    1993  

    Author's details guest eds.: Hartmut H. Malluche
    Series title Bone ; 14,3 = spec. issue
    Keywords Bone and Bones / anatomy & histology / congresses ; Bone and Bones / ultrastructure / congresses ; Bone Development / congresses ; Bone Diseases / congresses
    Size XXVIII S., S. [185] - 593 : Ill., graph. Darst.
    Publisher Pergamon Pr
    Publishing place New York
    Publishing country United States
    Document type Book ; Conference proceedings
    HBZ-ID HT004557328
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    Zs A 1571 -14- verfügbar in Königswinter Königswinter

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  6. Article ; Online: Importance of bone turnover for therapeutic decisions in patients with CKD-MBD.

    Ott, Susan M / Malluche, Hartmut H / Jorgetti, Vanda / Elder, Grahame J

    Kidney international

    2021  Volume 100, Issue 3, Page(s) 502–505

    Abstract: Patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) frequently have low bone formation rates. A recent review suggested that adynamic bone disease is not always associated with negative outcomes and therefore antiresorptive ... ...

    Abstract Patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) frequently have low bone formation rates. A recent review suggested that adynamic bone disease is not always associated with negative outcomes and therefore antiresorptive medications could be used more often. However, there is currently no evidence to support an improvement in fracture risk or mortality in patients with CKD-MBD and low bone turnover who are treated with antiresorptive medication. There is reasonable pathophysiological evidence suggesting that it may even be harmful.
    MeSH term(s) Bone Density Conservation Agents/therapeutic use ; Bone Diseases ; Bone Remodeling ; Chronic Kidney Disease-Mineral and Bone Disorder/drug therapy ; Chronic Kidney Disease-Mineral and Bone Disorder/etiology ; Humans
    Chemical Substances Bone Density Conservation Agents
    Language English
    Publishing date 2021-08-22
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2021.05.024
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  7. Article: The Role of Alterations in Alpha-Klotho and FGF-23 in Kidney Transplantation and Kidney Donation.

    Gupta, Meera / Orozco, Gabriel / Rao, Madhumati / Gedaly, Roberto / Malluche, Hartmut H / Neyra, Javier A

    Frontiers in medicine

    2022  Volume 9, Page(s) 803016

    Abstract: Cardiovascular disease and mineral bone disorders are major contributors to morbidity and mortality among patients with chronic kidney disease and often persist after renal transplantation. Ongoing hormonal imbalances after kidney transplant (KT) are ... ...

    Abstract Cardiovascular disease and mineral bone disorders are major contributors to morbidity and mortality among patients with chronic kidney disease and often persist after renal transplantation. Ongoing hormonal imbalances after kidney transplant (KT) are associated with loss of graft function and poor outcomes. Fibroblast growth factor 23 (FGF-23) and its co-receptor, α-Klotho, are key factors in the underlying mechanisms that integrate accelerated atherosclerosis, vascular calcification, mineral disorders, and osteodystrophy. On the other hand, kidney donation is also associated with endocrine and metabolic adaptations that include transient increases in circulating FGF-23 and decreases in α-Klotho levels. However, the long-term impact of these alterations and their clinical relevance have not yet been determined. This manuscript aims to review and summarize current data on the role of FGF-23 and α-Klotho in the endocrine response to KT and living kidney donation, and importantly, underscore specific areas of research that may enhance diagnostics and therapeutics in the growing population of KT recipients and kidney donors.
    Language English
    Publishing date 2022-05-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2022.803016
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  8. Article ; Online: Renal osteodystrophy: something old, something new, something needed.

    David, Valentin / Salusky, Isidro B / Malluche, Hartmut / Nickolas, Thomas L

    Current opinion in nephrology and hypertension

    2023  Volume 32, Issue 6, Page(s) 559–564

    Abstract: Purpose of review: Renal osteodystrophy (ROD) is a complex disorder of bone metabolism that affects virtually all adults and children with chronic kidney disease (CKD). ROD is associated with adverse clinical outcomes including bone loss, mineralization ...

    Abstract Purpose of review: Renal osteodystrophy (ROD) is a complex disorder of bone metabolism that affects virtually all adults and children with chronic kidney disease (CKD). ROD is associated with adverse clinical outcomes including bone loss, mineralization and turnover abnormalities, skeletal deformities, fractures, cardiovascular events, and death. Despite current therapies, fracture incidence is 2-fold to 100-fold higher in adults and 2-fold to 3-fold higher in children when compared to without CKD. Limited knowledge of ROD pathogenesis, due to the lack of patient-derived large-scale multimodal datasets, impedes development of therapeutics aimed at reducing morbidity and mortality of CKD patients. The purpose of the review is to define the much needed infrastructure for the advancement of RDO treatment.
    Recent findings: Recently, we created a large-scale data and tissue biorepository integrating clinical, bone quality, transcriptomic, and epigenomic data along with stored urine, blood, and bone samples. This database will provide the underpinnings for future research endeavors leading to the elucidation and characterization of the pathogenesis of ROD in CKD patients with and without dialysis.
    Summary: The availability of an open-access NIH-funded resource that shares bone-tissue-based information obtained from patients with ROD with the broad scientific community represents a critical step in the process of discovering new information regarding unrecognized bone changes that have severe clinical complications. This will facilitate future high-impact hypothesis-driven research to redefine our understanding of ROD pathogenesis and pathophysiology and inform the development of disease-modifying and prevention strategies.
    MeSH term(s) Adult ; Child ; Humans ; Chronic Kidney Disease-Mineral and Bone Disorder/epidemiology ; Chronic Kidney Disease-Mineral and Bone Disorder/therapy ; Renal Dialysis ; Bone Diseases, Metabolic ; Bone and Bones ; Calcinosis ; Fractures, Bone
    Language English
    Publishing date 2023-08-08
    Publishing country England
    Document type Review ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1151092-4
    ISSN 1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
    ISSN (online) 1473-6543 ; 1535-3842
    ISSN 1062-4813 ; 1062-4821
    DOI 10.1097/MNH.0000000000000918
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    Zs.A 3686: Show issues Location:
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  9. Article ; Online: Prevalence of low bone formation in untreated patients with osteoporosis.

    Malluche, Hartmut H / Davenport, Daniel L / Lima, Florence / Monier-Faugere, Marie-Claude

    PloS one

    2022  Volume 17, Issue 7, Page(s) e0271555

    Abstract: Background: Osteoporosis treatment usually starts with an antiresorber and switches to an anabolic agent if it fails. It is known that suppressing bone resorption also results in reduced bone formation. In addition, patients with prior treatment with ... ...

    Abstract Background: Osteoporosis treatment usually starts with an antiresorber and switches to an anabolic agent if it fails. It is known that suppressing bone resorption also results in reduced bone formation. In addition, patients with prior treatment with antiresorbers may have reduced response to subsequent anabolic treatment. This study determined the prevalence of low bone formation in untreated osteoporosis patients to identify patients who may not be optimally treated under the current paradigm.
    Methods: This is a cross-sectional study of bone samples stored in the Kentucky Bone Registry. Included samples were from adult patients presenting for workup of osteoporosis. Exclusion criteria were other diseases or treatments affecting bone. Patients underwent iliac crest bone biopsies after tetracycline labeling for identification of bone formation.
    Results: 107 patients met study criteria, 92 White and 5 Black women and 10 White men. Forty percent of patients (43/107) had low bone formation/bone surface (BFR/BS < 0.56 mm3/cm2/yr). Clinical and serum parameters did not differ between formation groups, except for type II diabetes, which was found exclusively in the low formation group.
    Conclusions: Starting treatment of osteoporotic patients with an antiresorber in all patients appears not optimal for a significant portion.
    MeSH term(s) Adult ; Bone Density ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/pathology ; Female ; Humans ; Ilium ; Male ; Osteogenesis ; Osteoporosis/complications ; Osteoporosis/epidemiology ; Osteoporosis/pathology ; Prevalence
    Language English
    Publishing date 2022-07-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0271555
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  10. Article: Treatment of bone loss in CKD5D: Better survival in patients with non-high bone turnover.

    Malluche, Hartmut H / Davenport, Daniel L / Monier-Faugere, Marie-Claude / Lima, Florence

    Clinical nephrology

    2022  Volume 98, Issue 5, Page(s) 219–228

    Abstract: 67% of CKD5D patients have low bone mass and present with high (HTO) or non-high (N-HTO) bone turnover. HTO has excessive resorption calling for anti-resorbers, while in N-HTO, anabolic therapy appears preferable. There are no data on this tailored ... ...

    Abstract 67% of CKD5D patients have low bone mass and present with high (HTO) or non-high (N-HTO) bone turnover. HTO has excessive resorption calling for anti-resorbers, while in N-HTO, anabolic therapy appears preferable. There are no data on this tailored approach. Adult CKD5D patients with dual energy X-ray absorptiometry (DXA) t-scores ≤ -1.0 were enrolled into this 12-month randomized controlled trial and stratified as HTO or N-HTO using values of parathyroid hormone (PTH), PTH-ratio, and TRAP5b. HTO patients were randomized into treatment with alendronate or controls, and N-HTO patients into teriparatide or controls. Clinical, lab, DXA, quantitative computed tomography bone mineral density (QCT BMD), and coronary artery calcifications (CAC) and aorta calcifications (AoC) MSQCT data were obtained at 0 and 12 months. Primary outcome was change (Δ) in BMD by QCT, secondary outcomes were changes in CAC (ΔCAC), in AoC (ΔAoC), and death. There were 80 HTO and 61 N-HTO patients. Median HTO baseline PTH was 664 and N-HTO 183. Bone loss improved in treated N-HTO (5.7 g/cm
    MeSH term(s) Adult ; Humans ; Absorptiometry, Photon ; Alendronate/therapeutic use ; Bone Density ; Bone Diseases, Metabolic/drug therapy ; Bone Diseases, Metabolic/etiology ; Bone Remodeling ; Parathyroid Hormone ; Teriparatide/therapeutic use ; Renal Insufficiency, Chronic/complications
    Chemical Substances Alendronate (X1J18R4W8P) ; Parathyroid Hormone ; Teriparatide (10T9CSU89I)
    Language English
    Publishing date 2022-10-06
    Publishing country Germany
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 185101-9
    ISSN 0301-0430
    ISSN 0301-0430
    DOI 10.5414/CN110993
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