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  1. Article ; Online: CXCR4 mediates the effects of IGF-1R signaling in rodent bone homeostasis and fracture repair.

    Esposito, Alessandra / Klüppel, Michael / Wilson, Brittany M / Meka, Sai R K / Spagnoli, Anna

    Bone

    2022  Volume 166, Page(s) 116600

    Abstract: Non-union fractures have considerable clinical and economic burdens and yet the underlying pathogenesis remains largely undetermined. The fracture healing process involves cellular differentiation, callus formation and remodeling, and implies the ... ...

    Abstract Non-union fractures have considerable clinical and economic burdens and yet the underlying pathogenesis remains largely undetermined. The fracture healing process involves cellular differentiation, callus formation and remodeling, and implies the recruitment and differentiation of mesenchymal stem cells that are not fully characterized. C-X-C chemokine receptor 4 (CXCR4) and Insulin-like growth factor 1 receptor (IGF-1R) are expressed in the fracture callus, but their interactions still remain elusive. We hypothesized that the regulation of CXCR4 by IGF-1R signaling is essential to maintain the bone homeostasis and to promote fracture repair. By using a combination of in vivo and in vitro approaches, we found that conditional ablation of IGF-1R in osteochondroprogenitors led to defects in bone formation and mineralization that associated with altered expression of CXCR4 by a discrete population of endosteal cells. These defects were corrected by AMD3100 (a CXCR4 antagonist). Furthermore, we found that the inducible ablation of IGF-1R in osteochondroprogenitors led to fracture healing failure, that associated with an altered expression of CXCR4. In vivo AMD3100 treatment improved fracture healing and normalized CXCR4 expression. Moreover, we determined that these effects were mediated through the IGF-1R/Insulin receptor substrate 1 (IRS-1) signaling pathway. Taken together, our studies identified a novel population of endosteal cells that is functionally regulated through the modulation of CXCR4 by IGF-1R signaling, and such control is essential in bone homeostasis and fracture healing. Knowledge gained from these studies has the potential to accelerate the development of novel therapeutic interventions by targeting CXCR4 signaling to treat non-unions.
    MeSH term(s) Animals ; Receptors, Chemokine ; Rodentia/metabolism ; Receptor, IGF Type 1/metabolism ; Signal Transduction ; Bony Callus/metabolism ; Fractures, Bone ; Homeostasis
    Chemical Substances plerixafor (S915P5499N) ; Receptors, Chemokine ; Receptor, IGF Type 1 (EC 2.7.10.1)
    Language English
    Publishing date 2022-11-09
    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.2022.116600
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  2. Article ; Online: Association of Bariatric Surgery With Risk of Fracture in Patients With Severe Obesity.

    Khalid, Syed I / Omotosho, Philip A / Spagnoli, Anna / Torquati, Alfonso

    JAMA network open

    2020  Volume 3, Issue 6, Page(s) e207419

    Abstract: Importance: Given the complex relationship between body mass index, body composition, and bone density and the correlative nature of the studies that have established the prevailing notion that higher body mass indices may be protective against ... ...

    Abstract Importance: Given the complex relationship between body mass index, body composition, and bone density and the correlative nature of the studies that have established the prevailing notion that higher body mass indices may be protective against osteopenia and osteoporosis and, therefore, fracture, the absolute risk of fracture in patients with severe obesity who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) compared with those who do not undergo bariatric surgery is unknown.
    Objective: To assess the rates of fractures associated with obesity and compare rates between those who do not undergo bariatric surgery, those who undergo RYGB, and those who undergo SG.
    Design, setting, and participants: In this retrospective multicenter cohort study of Medicare Standard Analytic Files derived from Medicare parts A and B records from January 2004 to December 2014, patients classified as eligible for bariatric surgery using the US Centers of Medicare & Medicaid criteria who either did not undergo bariatric surgery or underwent RYGB or SG were exactly matched in a 1:1 fashion based on their age, sex, Elixhauser Comorbidity Index, hypertension, smoking status, nonalcoholic fatty liver disease, hyperlipidemia, type 2 diabetes, osteoporosis, osteoarthritis, and obstructive sleep apnea status. Data were analyzed from November to December 2019.
    Exposures: RYGB or SG.
    Main outcomes and measures: The primary outcome measured in this study was the odds of fracture overall based on exposure to bariatric surgery. Secondary outcomes included the odds of type of fracture (humerus, radius or ulna, pelvis, hip, vertebrae, and total fractures) based on exposure to bariatric surgery.
    Results: A total of 49 113 patients were included and were equally made up of 16 371 bariatric surgery-eligible patients who did not undergo weight loss surgery, 16 371 patients who had undergone RYGB, and 16 371 patients who had undergone SG. Each group consisted of an equal number of 4109 men (25.1%) and 12 262 women (74.9%) and had an equal distribution of ages, with 11 780 patients (72.0%) 64 years or younger, 4230 (25.8%) aged 65 to 69 years, 346 (2.1%) aged 70 to 74 years, and 15 (0.1%) aged 75 to 79 years. Patients undergoing RYGB were found to have no significant difference in odds of fractures compared with bariatric surgery-eligible patients who did not undergo surgery. Patients undergoing undergone SG were found to have decreased odds of fractures of the humerus (odds ratio [OR], 0.57; 95% CI, 0.45-0.73), radius or ulna (OR, 0.38; 95% CI, 0.25-0.58), hip (OR, 0.49; 95% CI, 0.33-0.74), pelvis (OR, 0.34; 95% CI, 0.18-0.64), vertebrae (OR, 0.60; 95% CI, 0.48-0.74), or fractures in general (OR, 0.53; 95% CI, 0.46-0.62). Compared with patients undergoing SG, patients undergoing RYGB had a significantly greater risk of total fractures (OR, 1.79; 95% CI, 1.55-2.06) and humeral fractures (OR, 1.60; 95% CI, 1.24-2.07).
    Conclusions and relevance: In this cohort study, bariatric surgery was associated with a reduced risk of fracture in bariatric surgery-eligible patients. Sleeve gastrectomy might be the best option for weight loss in patients in which fractures could be a concern, as RYGB may be associated with an increased fracture risk compared with SG.
    MeSH term(s) Aged ; Bariatric Surgery/adverse effects ; Bariatric Surgery/statistics & numerical data ; Female ; Fractures, Bone/epidemiology ; Gastrectomy/adverse effects ; Gastrectomy/statistics & numerical data ; Humans ; Male ; Middle Aged ; Obesity, Morbid/epidemiology ; Obesity, Morbid/surgery ; Postoperative Complications/epidemiology ; Retrospective Studies
    Language English
    Publishing date 2020-06-01
    Publishing country United States
    Document type Journal Article
    ISSN 2574-3805
    ISSN (online) 2574-3805
    DOI 10.1001/jamanetworkopen.2020.7419
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  3. Article ; Online: Roux-en-Y gastric bypass decreases serum inflammatory markers and cardiovascular risk factors in obese diabetics.

    Rossi, Isolina / Omotosho, Philip / Poirier, Jennifer / Spagnoli, Anna / Torquati, Alfonso

    Surgery

    2020  Volume 169, Issue 3, Page(s) 539–542

    Abstract: Background: Obesity and type 2 diabetes mellitus are associated with elevated levels of inflammatory markers. This chronic inflammation is known to contribute to increased risk of cardiovascular disease in these populations. Laparoscopic Roux-en-Y ... ...

    Abstract Background: Obesity and type 2 diabetes mellitus are associated with elevated levels of inflammatory markers. This chronic inflammation is known to contribute to increased risk of cardiovascular disease in these populations. Laparoscopic Roux-en-Y gastric bypass is associated with a high rate of diabetes remission. We hypothesize that laparoscopic Roux-en-Y gastric bypass decreases systemic inflammatory markers and cardiovascular disease risk factors in obese diabetics.
    Methods: This was a single-institution prospective cohort study of 61 obese patients with type 2 diabetes mellitus. A total of 30 patients underwent laparoscopic Roux-en-Y gastric bypass surgery, and 31 patients underwent standard medical therapy with diabetes support and education. Collected data included preoperative and postoperative inflammatory biomarkers and clinical parameters.
    Results: Twelve months after undergoing laparoscopic Roux-en-Y gastric bypass, controlling for sex and age, there was a significant correlation between a change in interleukin-6 and a change in systolic blood pressure (Spearman r = 0.41, P = .03). Similarly, when sex and age were controlled for in the laparoscopic Roux-en-Y gastric bypass group, a statistically significant relationship remained between percent excess weight loss and change in interleukin-6 (P = .001).
    Conclusion: A significant relationship exists between decreased systemic interleukin-6 levels and both excess weight loss and lowered systolic blood pressure after laparoscopic Roux-en-Y gastric bypass in obese patients with diabetes mellitus. These correlations may explain the decreased risk of cardiovascular disease after surgical weight reduction in this patient population.
    MeSH term(s) Adult ; Biomarkers ; Cardiovascular Diseases/etiology ; Clinical Trials as Topic ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/etiology ; Female ; Gastric Bypass/methods ; Heart Disease Risk Factors ; Humans ; Inflammation Mediators/blood ; Male ; Middle Aged ; Obesity/complications ; Obesity/diagnosis ; Obesity/surgery ; Prospective Studies
    Chemical Substances Biomarkers ; Inflammation Mediators
    Language English
    Publishing date 2020-11-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 202467-6
    ISSN 1532-7361 ; 0039-6060
    ISSN (online) 1532-7361
    ISSN 0039-6060
    DOI 10.1016/j.surg.2020.09.039
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  4. Article ; Online: Role of Prx1-expressing skeletal cells and Prx1-expression in fracture repair.

    Esposito, Alessandra / Wang, Lai / Li, Tieshi / Miranda, Mariana / Spagnoli, Anna

    Bone

    2020  Volume 139, Page(s) 115521

    Abstract: The healing capacity of bones after fracture implies the existence of adult regenerative cells. However, information on identification and functional role of fracture-induced progenitors is still lacking. Paired-related homeobox 1 (Prx1) is expressed ... ...

    Abstract The healing capacity of bones after fracture implies the existence of adult regenerative cells. However, information on identification and functional role of fracture-induced progenitors is still lacking. Paired-related homeobox 1 (Prx1) is expressed during skeletogenesis. We hypothesize that fracture recapitulates Prx1's expression, and Prx1 expressing cells are critical to induce repair. To address our hypothesis, we used a combination of in vivo and in vitro approaches, short and long-term cell tracking analyses of progenies and actively expressing cells, cell ablation studies, and rodent animal models for normal and defective fracture healing. We found that fracture elicits a periosteal and endosteal response of perivascular Prx1+ cells that participate in fracture healing and showed that Prx1-expressing cells have a functional role in the repair process. While Prx1-derived cells contribute to the callus, Prx1's expression decreases concurrently with differentiation into cartilaginous and bone cells, similarly to when Prx1+ cells are cultured in differentiating conditions. We determined that bone morphogenic protein 2 (BMP2), through C-X-C motif-ligand-12 (CXCL12) signaling, modulates the downregulation of Prx1. We demonstrated that fracture elicits an early increase in BMP2 expression, followed by a decrease in CXCL12 that in turn down-regulates Prx1, allowing cells to commit to osteochondrogenesis. In vivo and in vitro treatment with CXCR4 antagonist AMD3100 restored Prx1 expression by modulating the BMP2-CXCL12 axis. Our studies represent a shift in the current research that has primarily focused on the identification of markers for postnatal skeletal progenitors, and instead we characterized the function of a specific population (Prx1+ cells) and their expression marker (Prx1) as a crossroad in fracture repair. The identification of fracture-induced perivascular Prx1+ cells and regulation of Prx1's expression by BMP2 and in turn by CXCL12 in the orchestration of fracture repair, highlights a pathway in which to investigate defective mechanisms and therapeutic targets for fracture non-union.
    MeSH term(s) Animals ; Bony Callus ; Cell Differentiation ; Fracture Healing ; Fractures, Bone ; Mesenchymal Stem Cells
    Language English
    Publishing date 2020-07-03
    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.2020.115521
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  5. Article: Mesenchymal stem cells and fracture healing.

    Spagnoli, Anna

    Orthopedics

    2008  Volume 31, Issue 9, Page(s) 855–6; discussion 856

    MeSH term(s) Bone Morphogenetic Proteins/administration & dosage ; Fracture Healing/physiology ; Humans ; Mesenchymal Stem Cell Transplantation
    Chemical Substances Bone Morphogenetic Proteins
    Language English
    Publishing date 2008-09-18
    Publishing country United States
    Document type Interview
    ZDB-ID 424447-3
    ISSN 0147-7447
    ISSN 0147-7447
    DOI 10.3928/01477447-20080901-33
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  6. Article ; Online: Rates, Risks, and Time to Fracture in Patients Undergoing Laparoscopic Vertical Sleeve Gastrectomy versus Roux-en-Y Gastric Bypass.

    Khalid, Syed I / Thomson, Kyle B / Becerra, Adan Z / Omotosho, Philip / Spagnoli, Anna / Torquati, Alfonso

    Annals of surgery open : perspectives of surgical history, education, and clinical approaches

    2021  Volume 2, Issue 4, Page(s) e099

    Abstract: Objective: To assess the rates, risks, and time to fracture in patients undergoing laparoscopic vertical sleeve gastrectomy (VSG) versus those undergoing Roux-en-Y gastric bypass (RYGB).: Summary background data: Metabolic and bariatric surgery has ... ...

    Abstract Objective: To assess the rates, risks, and time to fracture in patients undergoing laparoscopic vertical sleeve gastrectomy (VSG) versus those undergoing Roux-en-Y gastric bypass (RYGB).
    Summary background data: Metabolic and bariatric surgery has been implicated in significant bone loss and may increase fracture risk. Preoperative patient characteristics that might impact fracture risk and the time to fractures have not been established. Furthermore, the patient characteristics that might impact fracture risk and the time to fractures by surgical approach are unknown.
    Methods: This population-based retrospective cohort analysis used Humana claims data from January 1, 2007 to March 31, 2017, and included 4073 patients undergoing laparoscopic RYGB and VSG as a first surgical intervention for weight loss. The primary outcomes were the incidence of fractures (Humeral, Radial or Ulnar, Pelvic, Hip, and Vertebral) within 48 months after laparoscopic VSG versus RYGB and days to these fractures.
    Results: An analysis of total fractures (odds ratio [OR] 0.53; 95% confidence interval [CI], 0.38-0.73), vertebral fractures (OR 0.61; 95% CI, 0.38-0.99), hip fractures (OR 0.36; 95% CI, 0.15-0.84), and humeral fractures (OR 0.44; 95% CI, 0.22-0.90) demonstrated a reduction in fracture risk in patients undergoing VSG versus RYGB. Furthermore, postmenopausal status was independently associated with increased odds of total fractures and hip fractures (OR 2.18; 95% CI, 1.06-4.50; OR 5.83; 95% CI, 1.16-29.27; respectively). Likewise, osteoporosis at the time of surgery was associated with increased odds of total fractures (OR 1.61; 95% CI, 1.09-2.37), vertebral fractures (OR 2.01; 95% CI, 1.19-3.39), and hip fractures (OR 2.38; 95% CI, 1.19-4.77). Except for a significantly decreased odds of vertebral fractures in osteoporotic patients undergoing VSG versus RYGB (OR 0.41; 95% CI, 0.18-0.95), osteoporotic or postmenopausal status at the time of surgery was not found to increase odds of fracture depending on surgical intervention. However, time to fracture (total) and for all site-specific fractures, except for pelvic fractures, was significantly reduced in postmenopausal women undergoing RYGB versus VSG. Time to fracture (total) and for all site-specific fractures except pelvic and radial or ulnar fractures was significantly reduced in osteoporotic patients undergoing RYGB versus VSG.
    Conclusions and relevance: Though bariatric surgery is associated with several health-related benefits, increased fracture risk is an important factor to discuss with patients undergoing bariatric surgery. Bariatric surgery strategy, RYGB versus VSG, carries a differential risk of fracture, with RYGB carrying a higher risk of fracture and decreased time to fracture. Furthermore, patients who are postmenopausal or osteoporotic at the time of surgery carry an increased risk of total fractures, independent of bariatric surgery strategy. Being mindful of patient-specific fracture risk after bariatric surgery may help anticipate, identify, and prevent fractures.
    Language English
    Publishing date 2021-10-12
    Publishing country United States
    Document type Journal Article
    ISSN 2691-3593
    ISSN (online) 2691-3593
    DOI 10.1097/AS9.0000000000000099
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  7. Article ; Online: A randomised placebo-controlled clinical trial on the efficacy of local lidocaine injections and oral citalopram for the treatment of complex regional pain syndrome.

    Fallico, Nefer / Padmanabhan, Rahul / Rahman, Shakeel / Somma, Francesco / Spagnoli, Anna Maria

    Journal of plastic, reconstructive & aesthetic surgery : JPRAS

    2021  Volume 75, Issue 3, Page(s) 970–979

    Abstract: Background: Complex regional pain syndrome (CRPS) is a neuropathic pain condition with no universally recognised treatment. The study evaluates the efficacy of a therapeutic protocol consisting of oral citalopram and lidocaine injections in patients ... ...

    Abstract Background: Complex regional pain syndrome (CRPS) is a neuropathic pain condition with no universally recognised treatment. The study evaluates the efficacy of a therapeutic protocol consisting of oral citalopram and lidocaine injections in patients affected by CRPS.
    Methods: Between January 2010 and December 2014, 150 consecutive patients with CRPS were enrolled in the study and randomly assigned into three groups: group one - lidocaine injection and oral citalopram; group two - lidocaine injection and oral placebo; and group three - injective and oral placebo. The Impairment Sum Score (ISS) was used to assess the severity of CRPS before, as well as at regular intervals after treatment commenced. Statistical significance (p < 0.05) was determined by paired t-tests.
    Results: The combined treatment proved to be more effective (ISS 47.6 to 12.6) than local anaesthetic alone (ISS 47.5 to 21.5) and to placebo (ISS 47.2 to 29.9).
    Conclusion: This study indicates that CRPS may be managed with well-tolerated association of oral citalopram and lidocaine injections.
    MeSH term(s) Anesthetics, Local ; Citalopram/therapeutic use ; Complex Regional Pain Syndromes/drug therapy ; Double-Blind Method ; Humans ; Lidocaine ; Neuralgia
    Chemical Substances Anesthetics, Local ; Citalopram (0DHU5B8D6V) ; Lidocaine (98PI200987)
    Language English
    Publishing date 2021-11-14
    Publishing country Netherlands
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 2217750-4
    ISSN 1878-0539 ; 1748-6815 ; 0007-1226
    ISSN (online) 1878-0539
    ISSN 1748-6815 ; 0007-1226
    DOI 10.1016/j.bjps.2021.11.022
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  8. Article: Tissue engineering a tendon-bone junction with biodegradable braided scaffolds.

    Ramakrishna, Harshini / Li, Tieshi / He, Ting / Temple, Joseph / King, Martin W / Spagnoli, Anna

    Biomaterials research

    2019  Volume 23, Page(s) 11

    Abstract: Background: Tendons play an important role in transferring stress between muscles and bones and in maintaining the stability of joints. Tendon tears are difficult to heal and are associated with high recurrence rates. So, the objective of this study was ...

    Abstract Background: Tendons play an important role in transferring stress between muscles and bones and in maintaining the stability of joints. Tendon tears are difficult to heal and are associated with high recurrence rates. So, the objective of this study was to develop a biodegradable scaffold for tendon-bone junction regeneration.
    Methods: Two types of polylactic acid (PLA) yarns, having fibers with round and four deep grooved cross-sections, were braided into tubular scaffolds and cultured with murine Transforming growth factor beta type II receptor (Tgfbr2)-expressing joint progenitor cells. The scaffolds were designed to mimic the mechanical, immuno-chemical and biological properties of natural mouse tendon-bone junctions. Three different tubular scaffolds measuring 2 mm in diameter were braided on a Steeger 16-spindle braiding machine and biological and mechanical performance of the three scaffolds were evaluated.
    Results: The mechanical test results indicated that three different braided scaffold structures provided a wide range of mechanical properties that mimic the components of tendon bone junction and results of the biological tests confirmed cell viability, active cell attachment and proliferation throughout all three scaffolds.
    Conclusions: This study has identified that the three proposed types of braided scaffolds with some improvement in their structures have the potential to be used as scaffolds for the regeneration of a tendon bone tissue junction.
    Language English
    Publishing date 2019-05-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2775188-0
    ISSN 2055-7124 ; 1226-4601
    ISSN (online) 2055-7124
    ISSN 1226-4601
    DOI 10.1186/s40824-019-0160-3
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  9. Article ; Online: Perioperative changes in prouroguanylin hormone response in severely obese subjects after bariatric surgery.

    Torquati, Alfonso / Shantavasinkul, Prapimporn Chattranukulchai / Omotosho, Philip / Corsino, Leonor / Spagnoli, Anna

    Surgery

    2019  Volume 166, Issue 4, Page(s) 456–459

    Abstract: Background: Prouroguanylin is a gut hormone converted into uroguanylin in the hypothalamus. Uroguanylin induces satiety through guanylyl-cyclase-2C receptor signaling. However, little is known about the role of this hormone in regulating human food ... ...

    Abstract Background: Prouroguanylin is a gut hormone converted into uroguanylin in the hypothalamus. Uroguanylin induces satiety through guanylyl-cyclase-2C receptor signaling. However, little is known about the role of this hormone in regulating human food intake.
    Methods: In prospective-cohort study, prouroguanylin profile changes were determined during meal stimulation in obese patients 2 weeks before and 2 weeks after Roux-en-Y gastric bypass surgery. We also investigated whether these changes play a role in the anorexigenic effect of Roux-en-Y gastric bypass.
    Results: The study enrolled 8 healthy lean volunteers and 10 obese patients with type 2 diabetes. Prouroguanylin levels were postprandially decreased at 30 minutes (P = .04) and 60 minutes (P = .008) in obese patients before surgery, and they were increased at 60 minutes (P = .003), 90 minutes (P = .008), and 120 minutes (P = .009) after surgery. We observed a significant difference (P = .001) in fasting prouroguanylin levels before (8.82 ± 1.2 ng/mL) and after (6.05 ± 1.2 ng/mL) Roux-en-Y gastric bypass. Hunger ratings in the fasted state did not change after Roux-en-Y gastric bypass. Instead, subjects demonstrated significantly (P = .01) lower hunger visual analog scale scores than before Roux-en-Y gastric bypass. No correlations between circulating prouroguanylin levels and hunger perception were found before or after Roux-en-Y gastric bypass.
    Conclusion: Prouroguanylin levels decrease after meal stimulation in obese patients, and they increase after Roux-en-Y gastric bypass, but no correlations exist with hunger visual analog scale scores.
    MeSH term(s) Adult ; Analysis of Variance ; Biomarkers/blood ; Body Mass Index ; Case-Control Studies ; Comorbidity ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Follow-Up Studies ; Gastric Bypass/methods ; Humans ; Male ; Middle Aged ; Obesity, Morbid/diagnosis ; Obesity, Morbid/surgery ; Postoperative Period ; Preoperative Period ; Prospective Studies ; Protein Precursors/blood ; Treatment Outcome ; Weight Loss/physiology
    Chemical Substances Biomarkers ; Protein Precursors ; prouroguanylin
    Language English
    Publishing date 2019-08-29
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 202467-6
    ISSN 1532-7361 ; 0039-6060
    ISSN (online) 1532-7361
    ISSN 0039-6060
    DOI 10.1016/j.surg.2019.06.037
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  10. Article ; Online: Effects of Roux-en-Y Gastric Bypass on Osteoclast Activity and Bone Density in Morbidly Obese Patients with Type 2 Diabetes.

    Tangalakis, Laurel L / Tabone, Lawrence / Spagnoli, Anna / Muehlbauer, Mike / Omotosho, Philip / Torquati, Alfonso

    Obesity surgery

    2019  Volume 30, Issue 1, Page(s) 290–295

    Abstract: Introduction: Roux-en-Y gastric bypass (RYGB) is a well-established treatment for morbid obesity and type 2 diabetes. The effects of RYGB on bone metabolism and bone health are largely unknown.: Objective: Determine the changes in osteoclast function ...

    Abstract Introduction: Roux-en-Y gastric bypass (RYGB) is a well-established treatment for morbid obesity and type 2 diabetes. The effects of RYGB on bone metabolism and bone health are largely unknown.
    Objective: Determine the changes in osteoclast function and bone density 1 year after RYGB as compared with a control group undergoing a diabetes support and education program (DSE).
    Design: A prospective cohort study with patients matched for weight and age assigned to RYGB or DSE.
    Setting: Large academic institution.
    Patients or other participants: Patients with type 2 diabetes mellitus and morbid obesity (body mass index greater than 35 kg/m
    Intervention: Subjects either received laparoscopic RYBG or DSE, which consisted of nutritional, exercise, and dietary counseling performed by a certified diabetic educator and a nutritionist three times over a year.
    Main outcome measure: Osteoclast activity, bone mineral density.
    Results: One year after, intervention subjects undergoing RYGB have a 280% increase in osteoclast activity as compared with a 7.6% increase in the DSE control group (P < 0.001). Furthermore, there was a statistically significant increase in sclerostin levels in subjects undergoing RYGB compared with an increase in the control group. The total bone mineral density was statistically unchanged within 1 year of intervention in both groups. A statistically significant decrease in bone mineral density in the left ribs (decrease of 6.8%, P < 0.05) and lumbar spine (decrease of 4.0%, P < 0.05) was seen 1 year after RYGB.
    Conclusions: There is a significant increase in osteoclast activity observed 1 year after RYGB; the long-term clinical implications of this increased bone metabolism are unknown.
    MeSH term(s) Adult ; Body Mass Index ; Bone Density/physiology ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/physiopathology ; Diabetes Mellitus, Type 2/surgery ; Female ; Gastric Bypass/adverse effects ; Gastric Bypass/methods ; Humans ; Laparoscopy/methods ; Male ; Middle Aged ; Morbidity ; Obesity, Morbid/complications ; Obesity, Morbid/metabolism ; Obesity, Morbid/physiopathology ; Obesity, Morbid/surgery ; Osteoclasts/physiology ; Prospective Studies ; Weight Loss/physiology
    Language English
    Publishing date 2019-08-30
    Publishing country United States
    Document type Controlled Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1070827-3
    ISSN 1708-0428 ; 0960-8923
    ISSN (online) 1708-0428
    ISSN 0960-8923
    DOI 10.1007/s11695-019-04154-2
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