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  1. Article ; Online: Region-specific associations among tissue-level mechanical properties, porosity, and composition in human male femora.

    Mandair, Gurjit S / Bigelow, Erin M R / Viswanathan, Gowri / Ward, Ferrous S / Patton, Daniella M / Schlecht, Stephen H / Jepsen, Karl J / Kohn, David H

    Journal of biomechanics

    2022  Volume 139, Page(s) 111144

    Abstract: Region-specific differences in age-related bone remodeling are known to exist. We therefore hypothesized that the decline in tissue-level strength and post-yield strain (PYS) with age is not uniform within the femur, but is driven by region-specific ... ...

    Abstract Region-specific differences in age-related bone remodeling are known to exist. We therefore hypothesized that the decline in tissue-level strength and post-yield strain (PYS) with age is not uniform within the femur, but is driven by region-specific differences in porosity and composition. Four-point bending was conducted on anterior, posterior, medial, and lateral beams from male cadaveric femora (n = 33, 18-89 yrs of age). Mid-cortical porosity, composition, and mineralization were assessed using nano-computed tomography (nanoCT), Raman spectroscopy, and ashing assays. Traits between bones from young and elderly groups were compared, while multivariate analyses were used to identify traits that predicted strength and PYS at the regional level. We show that age-related decline in porosity and mechanical properties varied regionally, with highest positive slope of age vs. Log(porosity) found in posterior and anterior bone, and steepest negative slopes of age vs. strength and age vs. PYS found in anterior bone. Multivariate analyses show that Log(porosity) and/or Raman 1246/1269 ratio explained 46-51% of the variance in strength in anterior and posterior bone. Three out of five traits related to Log(porosity), mineral crystallinity, 1246/1269, mineral/matrix ratio, and/or hydroxyproline/proline (Hyp/Pro) ratio, explained 35-50% of the variance in PYS in anterior, posterior and lateral bones. Log(porosity) and Hyp/Pro ratio alone explained 13% and 19% of the variance in strength and PYS in medial bone, respectively. The predictive performance of multivariate analyses was negatively impacted by pooling data across all bone regions, underscoring the complexity of the femur and that the use of pooled analyses may obscure underlying region-specific differences.
    MeSH term(s) Aged ; Bone Density ; Bone Remodeling ; Bone and Bones ; Femur/diagnostic imaging ; Humans ; Male ; Minerals ; Porosity
    Chemical Substances Minerals
    Language English
    Publishing date 2022-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218076-5
    ISSN 1873-2380 ; 0021-9290
    ISSN (online) 1873-2380
    ISSN 0021-9290
    DOI 10.1016/j.jbiomech.2022.111144
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Divergent mechanical properties of older human male femora reveal unique combinations of morphological and compositional traits contributing to low strength.

    Bolger, Morgan W / Romanowicz, Genevieve E / Bigelow, Erin M R / Ward, Ferrous S / Ciarelli, Antonio / Jepsen, Karl J / Kohn, David H

    Bone

    2022  Volume 163, Page(s) 116481

    Abstract: Bone strength is generally thought to decline with aging and prior work has compared traits between younger and older cohorts to identify the structural and compositional changes that contribute to fracture risk with age. However, for men, the majority ... ...

    Abstract Bone strength is generally thought to decline with aging and prior work has compared traits between younger and older cohorts to identify the structural and compositional changes that contribute to fracture risk with age. However, for men, the majority of individuals do not fracture a bone in their lifetime. While fracture occurrence is multifactorial, the absence of fracture in the majority of males suggests that some individuals maintain bone strength or do not lose enough strength to fracture, whereas others do lose strength with aging. Consequently, not all structural and material changes observed with age may lead to strength-decline. We propose that consideration of different subgroups of older individuals will provide a more precise understanding of which structural and material changes directly contribute to strength-decline. We identified subgroups using latent profile analysis (LPA), which is a clustering-based algorithm that takes multiple continuous variables into account. Human cadaveric male femoral diaphyses (n = 33, 26-89 years) were subjected to whole bone and tissue-level mechanical tests. Morphological traits, porosity, and cortical tissue mineral density (Ct.TMD) were obtained, as were measures of enzymatic cross-links and the advanced glycation end product, pentosidine (PEN). A univariate analysis first identified a younger cohort (YNG, n = 11) and older cohort (n = 22). LPA was then conducted using three mechanical traits (whole bone strength, tissue-level strength, and tissue-level post-yield strain), resulting in a further stratification of the older group into two similarly aged groups (p = 0.558), but one with higher (OHM, n = 16) and another with lower mechanical properties (OLM, n = 6). The OLM group exhibited lower whole bone strength (p = 0.016), tissue-level strength (p < 0.001), and tissue-level post-yield strain (p < 0.001) compared to the YNG group. Meanwhile, the OHM only exhibited significantly lower tissue-level post-yield strain (p < 0.001), compared to the YNG group. Between the two older groups, the OHM group exhibited higher whole bone strength (p = 0.037), tissue-level strength (p = 0.006), and tissue-level post-yield strain (p = 0.012) than the OLM group. Probing the morphological and compositional relationships among the three groups, both OHM and OLM exhibited increased PEN content (p < 0.001, p = 0.008 respectively) and increased Log(cortical pore score) relative to YNG (p = 0.003, p < 0.001 respectively). Compared to the OHM group, the OLM also exhibited increased marrow area (p = 0.049), water content (p = 0.048), and decreased Ct.TMD (p = 0.005). The key traits that were unique to the OLM group compared to YNG were decreased Ct.TMD (p < 0.001) and increased Log(porosity) (p = 0.002). There were many properties that differed between the younger and older groups, but not all were associated with reduced mechanical properties, highlighting the relative importance of certain age-related traits such as porosity, Ct.TMD, water content, and marrow area that were unique to the OLM group. Overall, this work supports the hypothesis that there are subgroups of men showing different strength-decline trajectories with aging and establishes a basis for refining our understanding of which age-related changes are directly contributing to decreased strength.
    MeSH term(s) Aged ; Biomechanical Phenomena ; Bone Density ; Bone and Bones ; Femur ; Fractures, Bone ; Humans ; Male ; Water
    Chemical Substances Water (059QF0KO0R)
    Language English
    Publishing date 2022-07-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 632515-4
    ISSN 1873-2763 ; 8756-3282
    ISSN (online) 1873-2763
    ISSN 8756-3282
    DOI 10.1016/j.bone.2022.116481
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: External bone size identifies different strength-decline trajectories for the male human femora.

    Bolger, Morgan W / Romanowicz, Genevieve E / Bigelow, Erin M R / Ward, Ferrous S / Ciarelli, Antonio / Jepsen, Karl J / Kohn, David H

    Journal of structural biology

    2020  Volume 212, Issue 3, Page(s) 107650

    Abstract: Understanding skeletal aging and predicting fracture risk is increasingly important with a growing elderly population. We hypothesized that when categorized by external bone size, the male femoral diaphysis would show different strength-age trajectories ... ...

    Abstract Understanding skeletal aging and predicting fracture risk is increasingly important with a growing elderly population. We hypothesized that when categorized by external bone size, the male femoral diaphysis would show different strength-age trajectories which can be explained by changes in morphology, composition and collagen cross-linking. Cadaveric male femora were sorted into narrow (n = 15, 26-89 years) and wide (n = 15, 29-82 years) groups based upon total cross-sectional area of the mid-shaft normalized to bone length (Tt.Ar/Le) and tested for whole bone strength, tissue-level strength, and tissue-level post-yield strain. Morphology, cortical TMD (Ct.TMD), porosity, direct measurements of enzymatic collagen cross-links, and pentosidine were obtained. The wide group alone showed significant negative correlations with age for tissue-level strength (R
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Aging/metabolism ; Aging/physiology ; Bone Density/physiology ; Collagen/metabolism ; Femur/metabolism ; Femur/physiology ; Humans ; Male ; Middle Aged
    Chemical Substances Collagen (9007-34-5)
    Language English
    Publishing date 2020-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1032718-6
    ISSN 1095-8657 ; 1047-8477
    ISSN (online) 1095-8657
    ISSN 1047-8477
    DOI 10.1016/j.jsb.2020.107650
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: De novo Powered Air-Purifying Respirator Design and Fabrication for Pandemic Response.

    Kothakonda, Akshay / Atta, Lyla / Plana, Deborah / Ward, Ferrous / Davis, Chris / Cramer, Avilash / Moran, Robert / Freake, Jacob / Tian, Enze / Mazor, Ofer / Gorelik, Pavel / Van, Christopher / Hansen, Christopher / Yang, Helen / Sinha, Michael S / Li, Ju / Yu, Sherry H / LeBoeuf, Nicole R / Sorger, Peter K

    medRxiv : the preprint server for health sciences

    2021  

    Abstract: The rapid spread of COVID-19 and disruption of normal supply chains resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of information ... ...

    Abstract The rapid spread of COVID-19 and disruption of normal supply chains resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of information describing design and performance criteria represents a substantial barrier to new approaches to address these shortages. We sought to apply open-source product development to PAPRs to enable alternative sources of supply and further innovation. We describe the design, prototyping, validation, and user testing of locally manufactured, modular, PAPR components, including filter cartridges and blower units, developed by the Greater Boston Pandemic Fabrication Team (PanFab). Two designs, one with a fully custom-made filter and blower unit housing, and the other with commercially available variants (the "Custom" and "Commercial" designs respectively) were developed. Engineering performance of the prototypes was measured and safety validated using NIOSH-equivalent tests on apparatus available under pandemic conditions, at university laboratories. Feedback on designs was obtained from four individuals, including two clinicians working in an ambulatory clinical setting and two research technical staff for whom PAPR use is a standard part of occupational PPE. Respondents rated the PanFab Custom PAPR a 4 to 5 on a 5 Likert-scale 1) as compared to current PPE options, 2) for the sense of security with use in a clinical setting, and 3) for comfort. The three other versions of the designs (with a commercial blower unit, filter, or both) performed favorably, with survey responses consisting of scores ranging from 3-5. Engineering testing and clinical feedback demonstrate that the PanFab designs represents favorable alternative PAPRs in terms of user comfort, mobility, and sense of security. A nonrestrictive license promotes innovation in respiratory protection for current and future medical emergencies.
    Language English
    Publishing date 2021-03-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.03.25.21252076
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: External Bone Size Is a Key Determinant of Strength-Decline Trajectories of Aging Male Radii.

    Bigelow, Erin Mr / Patton, Daniella M / Ward, Ferrous S / Ciarelli, Antonio / Casden, Michael / Clark, Andrea / Goulet, Robert W / Morris, Michael D / Schlecht, Stephen H / Mandair, Gurjit S / Bredbenner, Todd L / Kohn, David H / Jepsen, Karl J

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

    2019  Volume 34, Issue 5, Page(s) 825–837

    Abstract: Given prior work showing associations between remodeling and external bone size, we tested the hypothesis that wide bones would show a greater negative correlation between whole-bone strength and age compared with narrow bones. Cadaveric male radii (n = ... ...

    Abstract Given prior work showing associations between remodeling and external bone size, we tested the hypothesis that wide bones would show a greater negative correlation between whole-bone strength and age compared with narrow bones. Cadaveric male radii (n = 37 pairs, 18 to 89 years old) were evaluated biomechanically, and samples were sorted into narrow and wide subgroups using height-adjusted robustness (total area/bone length). Strength was 54% greater (p < 0.0001) in wide compared with narrow radii for young adults (<40 years old). However, the greater strength of young-adult wide radii was not observed for older wide radii, as the wide (R
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/metabolism ; Aging/pathology ; Bone Density ; Humans ; Male ; Middle Aged ; Organ Size ; Radius/metabolism ; Radius/pathology
    Language English
    Publishing date 2019-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632783-7
    ISSN 1523-4681 ; 0884-0431
    ISSN (online) 1523-4681
    ISSN 0884-0431
    DOI 10.1002/jbmr.3661
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  6. Article ; Online: A xenograft model to evaluate the bone forming effects of sclerostin antibody in human bone derived from pediatric osteogenesis imperfecta patients.

    Surowiec, Rachel K / Battle, Lauren F / Ward, Ferrous S / Schlecht, Stephen H / Khoury, Basma M / Robbins, Christopher / Wojtys, Edward M / Caird, Michelle S / Kozloff, Kenneth M

    Bone

    2019  Volume 130, Page(s) 115118

    Abstract: Osteogenesis imperfecta (OI) is a rare and severe skeletal dysplasia marked by low bone mass and poor bone quality which is especially burdensome during childhood. Since clinical trials for pediatric OI are difficult, there is a widespread reliance on ... ...

    Abstract Osteogenesis imperfecta (OI) is a rare and severe skeletal dysplasia marked by low bone mass and poor bone quality which is especially burdensome during childhood. Since clinical trials for pediatric OI are difficult, there is a widespread reliance on genetically modified murine models to understand the skeletal effects of emerging therapeutics. However a common model does not yet exist to understand how patient-specific genotype may influence treatment efficacy. Recently, sclerostin antibody (SclAb) has been introduced as a novel putative anabolic therapy for diseases of low bone mass, but effects in pediatric patients remain unexplored. In this study, we aim to establish a direct xenograft approach using OI patient-derived bone isolates which retain patient-specific genetic defects and cells residing in their intrinsic extracellular environment to evaluate the bone-forming effects of SclAb as a bridge to clinical trials. OI and age matched non-OI patient bone typically discarded as surgical waste during corrective orthopaedic procedures were collected, trimmed and implanted subcutaneously (s.c.) on the dorsal surface of 4-6-week athymic mice. A subset of implanted mice were evaluated at short (1 week), intermediate (4 week), and long-term (12 week) durations to assess bone cell survival and presence of donor bone cells in order to determine an appropriate treatment duration. Remaining implanted mice were randomly assigned to a two or four-week SclAb-treated (25mg/kg s.c. 2QW) or untreated control group. Immunohistochemistry determined osteocyte and osteoblast donor/host relationship, TRAP staining quantified osteoclast activity, and TUNEL assay was used to understand rates of bone cell apoptosis at each implantation timepoint. Longitudinal changes of in vivo μCT outcomes and dynamic histomorphometry were used to assess treatment response and ex vivo μCT and dynamic histomorphometry of host femora served as a positive internal control to confirm a bone forming response to SclAb. Human-derived osteocytes and lining cells were present up to 12 weeks post-implantation with nominal cell apoptosis in the implant. Sclerostin expression remained donor-derived throughout the study. Osterix expression was primarily donor-derived in treated implants and shifted in favor of the host when implants remained untreated. μCT measures of BMD, TMD, BV/TV and BV increased with treatment but response was variable and impacted by bone implant morphology (trabecular, cortical) which was corroborated by histomorphometry. There was no statistical difference between treated and untreated osteoclast number in the implants. Host femora confirmed a systemic bone forming effect of SclAb. Findings support use of the xenograft model using solid bone isolates to explore the effects of novel bone-targeted therapies. These findings will impact our understanding of SclAb therapy in pediatric OI tissue through establishing the efficacy of this treatment in human cells prior to extension to the clinic.
    MeSH term(s) Animals ; Bone Density ; Child ; Glycoproteins ; Heterografts ; Humans ; Intercellular Signaling Peptides and Proteins ; Mice ; Osteogenesis ; Osteogenesis Imperfecta/diagnostic imaging ; Osteogenesis Imperfecta/drug therapy ; X-Ray Microtomography
    Chemical Substances Glycoproteins ; Intercellular Signaling Peptides and Proteins
    Language English
    Publishing date 2019-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 632515-4
    ISSN 1873-2763 ; 8756-3282
    ISSN (online) 1873-2763
    ISSN 8756-3282
    DOI 10.1016/j.bone.2019.115118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: De Novo Powered Air-Purifying Respirator Design and Fabrication for Pandemic Response.

    Kothakonda, Akshay / Atta, Lyla / Plana, Deborah / Ward, Ferrous / Davis, Chris / Cramer, Avilash / Moran, Robert / Freake, Jacob / Tian, Enze / Mazor, Ofer / Gorelik, Pavel / Van, Christopher / Hansen, Christopher / Yang, Helen / Li, Yao / Sinha, Michael S / Li, Ju / Yu, Sherry H / LeBoeuf, Nicole R /
    Sorger, Peter K

    Frontiers in bioengineering and biotechnology

    2021  Volume 9, Page(s) 690905

    Abstract: The rapid spread of COVID-19 and disruption of normal supply chains has resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of ... ...

    Abstract The rapid spread of COVID-19 and disruption of normal supply chains has resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of information describing design and performance criteria for PAPRs represents a substantial barrier to mitigating shortages. We sought to apply open-source product development (OSPD) to PAPRs to enable alternative sources of supply and further innovation. We describe the design, prototyping, validation, and user testing of locally manufactured, modular, PAPR components, including filter cartridges and blower units, developed by the Greater Boston Pandemic Fabrication Team (PanFab). Two designs, one with a fully custom-made filter and blower unit housing, and the other with commercially available variants (the "Custom" and "Commercial" designs, respectively) were developed; the components in the Custom design are interchangeable with those in Commercial design, although the form factor differs. The engineering performance of the prototypes was measured and safety validated using National Institutes for Occupational Safety and Health (NIOSH)-equivalent tests on apparatus available under pandemic conditions at university laboratories. Feedback was obtained from four individuals; two clinicians working in ambulatory clinical care and two research technical staff for whom PAPR use is standard occupational PPE; these individuals were asked to compare PanFab prototypes to commercial PAPRs from the perspective of usability and suggest areas for improvement. Respondents rated the PanFab Custom PAPR a 4 to 5 on a 5 Likert-scale 1) as compared to current PPE options, 2) for the sense of security with use in a clinical setting, and 3) for comfort compared to standard, commercially available PAPRs. The three other versions of the designs (with a Commercial blower unit, filter, or both) performed favorably, with survey responses consisting of scores ranging from 3 to 5. Engineering testing and clinical feedback demonstrate that the PanFab designs represent favorable alternatives to traditional PAPRs in terms of user comfort, mobility, and sense of security. A nonrestrictive license promotes innovation in respiratory protection for current and future medical emergencies.
    Language English
    Publishing date 2021-09-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2021.690905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: De novo Powered Air-Purifying Respirator Design and Fabrication for Pandemic Response

    Kothakonda, Akshay / Atta, Lyla / Plana, Deborah / Ward, Ferrous / Davis, Chris / Cramer, Avilash / Moran, Robert / Freake, Jacob / Tian, Enze / Mazor, Ofer / Gorelik, Pavel / Van, Christopher / Hansen, Christopher / Yang, Helen / Sinha, Michael S. / Li, Ju / Yu, Sherry H. / LeBoeuf, Nicole R. / Sorger, Peter K.

    medRxiv

    Abstract: Importance: The rapid spread of COVID-19 and disruption of normal supply chains resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of ... ...

    Abstract Importance: The rapid spread of COVID-19 and disruption of normal supply chains resulted in severe shortages of personal protective equipment (PPE), particularly devices with few suppliers such as powered air-purifying respirators (PAPRs). A scarcity of information describing design and performance criteria represents a substantial barrier to new approaches. Objective: We sought to apply open-source product development to PAPRs to enable alternative sources of supply and further innovation. Design: We describe the design, prototyping, validation, and user testing of locally manufactured, modular, PAPR components, including filter cartridges and blower units, developed by the Greater Boston Pandemic Fabrication Team (PanFab). Two designs, one with a fully custom-made filter and housing, and the other with commercially available variants (the "Custom" and "Commercial: designs) were developed. Prototype testing was conducted at academic laboratories using equipment available during COVID-19. The designs and software are in the common domain for use or further modification. Setting: User feedback on the functionality and comfort of the design was obtained at a major US academic medical center. Participants: Feedback on designs was obtained from four individuals, including two clinicians working in an ambulatory clinical setting and two research technical staff for whom PAPR use is a standard part of occupational PPE. Main Outcomes and Measures: Engineering performance was measured using NIOSH-equivalent tests on an apparatus available in university laboratories. Clinical feedback was assessed by (1) comparison to existing PPE; (2) sense of security in a clinical setting; and (3) comfort. Results: Custom and Commercial Designs were developed for filter cartridges and blower units. The two PAPR variants passed testing for PAPR certification using an apparatus available under pandemic shortages. Respondents rated the PanFab Custom PAPR a 4 to 5 on a 5 Likert-scale across every survey question. The three other versions of the designs (with a commercial blower unit, filter, or both) also performed favorably, with survey scores of 3-5. Conclusions and Relevance: Engineering testing and clinical feedback demonstrate that the PanFab design represents a favorable alternative PAPR in terms of user comfort, mobility, and sense of security. A nonrestrictive license promotes innovation in respiratory protection for current and future medical emergencies.
    Keywords covid19
    Language English
    Publishing date 2021-03-29
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.03.25.21252076
    Database COVID19

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  9. Article ; Online: Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

    Perosky, Joseph E / Khoury, Basma M / Jenks, Terese N / Ward, Ferrous S / Cortright, Kai / Meyer, Bethany / Barton, David K / Sinder, Benjamin P / Marini, Joan C / Caird, Michelle S / Kozloff, Kenneth M

    Bone

    2016  Volume 93, Page(s) 79–85

    Abstract: Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in ... ...

    Abstract Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation.
    MeSH term(s) Adaptor Proteins, Signal Transducing ; Animals ; Antibodies/pharmacology ; Antibodies/therapeutic use ; Biomechanical Phenomena ; Bone Resorption/diagnostic imaging ; Bone Resorption/drug therapy ; Bone Resorption/pathology ; Bone and Bones/drug effects ; Bone and Bones/pathology ; Cortical Bone/diagnostic imaging ; Cortical Bone/drug effects ; Cortical Bone/pathology ; Diphosphonates/pharmacology ; Diphosphonates/therapeutic use ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Femur/diagnostic imaging ; Femur/drug effects ; Femur/pathology ; Glycoproteins/immunology ; Intercellular Signaling Peptides and Proteins ; Male ; Organ Size/drug effects ; Osteoclasts/drug effects ; Osteoclasts/metabolism ; Osteoclasts/pathology ; Osteogenesis Imperfecta/diagnostic imaging ; Osteogenesis Imperfecta/drug therapy ; Osteogenesis Imperfecta/pathology ; Spectroscopy, Near-Infrared ; X-Ray Microtomography
    Chemical Substances Adaptor Proteins, Signal Transducing ; Antibodies ; Diphosphonates ; Glycoproteins ; Intercellular Signaling Peptides and Proteins ; Sost protein, mouse
    Language English
    Publishing date 2016-09-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632515-4
    ISSN 1873-2763 ; 8756-3282
    ISSN (online) 1873-2763
    ISSN 8756-3282
    DOI 10.1016/j.bone.2016.09.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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