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Trials
Published in: Trials 1/2022

Open Access 01-12-2022 | Sleeve Gastrectomy | Study protocol

Zoledronic Acid for prevention of bone and muscle loss after BAriatric Surgery (ZABAS)-a study protocol for a randomized controlled trial

Authors: Søren Gam, Bibi Gram, Claus Bogh Juhl, Anne Pernille Hermann, Stinus Gadegaard Hansen

Published in: Trials | Issue 1/2022

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Abstract

Background

Bariatric surgery has adverse effects on the muscular-skeletal system with loss of bone mass and muscle mass and an increase in the risk of fracture. Zoledronic acid is widely used in osteoporosis and prevents bone loss and fracture. Bisphosphonates may also have positive effects on skeletal muscle. The aim of this study is to investigate the effects of zoledronic acid for the prevention of bone and muscle loss after bariatric surgery. 

Methods/design

This is a randomized double-blind placebo-controlled study. Sixty women and men with obesity aged 35 years or older will complete baseline assessments before randomization to either zoledronic acid (5 mg in 100 ml isotonic saline) or placebo (100 ml isotonic saline only) 3 weeks before surgery with Roux-en-Y-gastric bypass (RYGB) or sleeve gastrectomy (SG). Follow-up assessments are performed 12 and 24 months after surgery. The primary outcome is changes in lumbar spine volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT). Secondary bone outcomes are changes in proximal femur vBMD assessed by QCT. Changes in cortical and trabecular bone microarchitecture and estimated bone strength will be assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical material bone strength at the mid-tibia diaphysis will be assessed using microindentation and fasting blood samples will be obtained to assess biochemical markers of bone turnover and calcium metabolism. 
Secondary muscle outcomes include whole body lean mass assessed using dual-energy X-ray absorptiometry. Dynamometers will be used to assess handgrip, shoulder, ankle, and knee muscle strength. Short Physical Performance Battery, 7.6-m walking tests, 2-min walking test, and a stair climb test will be assessed as biomarkers of physical function. Self-reported physical activity level is assessed using International Physical Activity Questionnaire (IPAQ).

Discussion

Results from this study will be instrumental for the evidence-based care of patients undergoing bariatric surgery.

Trial registration

ClinicalTrials.gov NCT04742010. Registered on 5 February 2021.
Appendix
Available only for authorised users
Literature
1.
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81.PubMedPubMedCentralCrossRef
2.
Arterburn D, Gupta A. Comparing the outcomes of sleeve gastrectomy and Roux-en-Y gastric bypass for severe obesity. JAMA. 2018;319(3):235–7.PubMedCrossRef
3.
Lindeman KG, Greenblatt LB, Rourke C, Bouxsein ML, Finkelstein JS, Yu EW. Longitudinal 5-year evaluation of bone density and microarchitecture after Roux-en-Y gastric bypass surgery. J Clin Endocrinol Metab. 2018;103(11):4104–12.PubMedPubMedCentralCrossRef
4.
Mundbjerg LH, Stolberg CR, Bladbjerg EM, Funch-Jensen P, Juhl CB, Gram B. Effects of 6 months supervised physical training on muscle strength and aerobic capacity in patients undergoing Roux-en-Y gastric bypass surgery: a randomized controlled trial. Clin Obes. 2018;8(4):227–35.PubMedCrossRef
5.
Muschitz C, Kocijan R, Haschka J, Zendeli A, Pirker T, Geiger C, et al. The impact of vitamin D, calcium, protein supplementation, and physical exercise on bone metabolism after bariatric surgery: the BABS study. J Bone Miner Res. 2016;31(3):672–82.PubMedCrossRef
6.
Shanbhogue VV, Støving RK, Frederiksen KH, Hanson S, Brixen K, Gram J, et al. Bone structural changes after gastric bypass surgery evaluated by HR-pQCT: a two-year longitudinal study. Eur J Endocrinol. 2017;176(6):685–93.PubMedPubMedCentralCrossRef
7.
8.
Lu CW, Chang YK, Chang HH, Kuo CS, Huang CT, Hsu CC, et al. Fracture risk after bariatric surgery: a 12-year nationwide cohort study. Medicine (Baltimore). 2015;94(48):e2087.CrossRef
9.
Nakamura KM, Haglind EG, Clowes JA, Achenbach SJ, Atkinson EJ, Melton LJ 3rd, et al. Fracture risk following bariatric surgery: a population-based study. Osteoporos Int. 2014;25(1):151–8.PubMedCrossRef
10.
Rousseau C, Jean S, Gamache P, Lebel S, Mac-Way F, Biertho L, et al. Change in fracture risk and fracture pattern after bariatric surgery: nested case-control study. BMJ. 2016;354:i3794.PubMedPubMedCentralCrossRef
11.
Yu EW, Lee MP, Landon JE, Lindeman KG, Kim SC. Fracture risk after bariatric surgery: Roux-en-Y gastric bypass versus adjustable gastric banding. J Bone Miner Res. 2017;32(6):1229–36.PubMedCrossRef
12.
Axelsson KF, Werling M, Eliasson B, Szabo E, Näslund I, Wedel H, et al. Fracture risk after gastric bypass surgery: a retrospective cohort study. J Bone Miner Res. 2018;33(12):2122–31.PubMedCrossRef
13.
14.
Schafer AL, Weaver CM, Black DM, Wheeler AL, Chang H, Szefc GV, et al. Intestinal calcium absorption decreases dramatically after gastric bypass surgery despite optimization of vitamin D status. J Bone Miner Res. 2015;30(8):1377–85.PubMedCrossRef
15.
Oppert JM, Bellicha A, Roda C, Bouillot JL, Torcivia A, Clement K, et al. Resistance training and protein supplementation increase strength after bariatric surgery: a randomized controlled trial. Obesity (Silver Spring). 2018;26(11):1709–20.CrossRef
16.
Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809–22.PubMedCrossRef
17.
Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J, Langdahl B, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012;367(18):1714–23.PubMedCrossRef
18.
Deas CM, Murphy P, Iranikhah M, Freeman MK. Retained skeletal effects of zoledronic acid following discontinuation of treatment: a review of the literature. Consult Pharm. 2017;32(3):144–55.PubMedCrossRef
19.
Liu Y, Côté MM, Cheney MC, Lindeman KG, Rushin CC, Hutter MM, et al. Zoledronic acid for prevention of bone loss in patients receiving bariatric surgery. Bone Rep. 2021;14:100760.PubMedPubMedCentralCrossRef
20.
Børsheim E, Herndon DN, Hawkins HK, Suman OE, Cotter M, Klein GL. Pamidronate attenuates muscle loss after pediatric burn injury. J Bone Miner Res. 2014;29(6):1369–72.PubMedCrossRef
21.
Harada A, Ito S, Matsui Y, Sakai Y, Takemura M, Tokuda H, et al. Effect of alendronate on muscle mass: Investigation in patients with osteoporosis. Osteoporosis and Sarcopenia. 2015;1(1):53–8.CrossRef
22.
Watanabe R, Fujita N, Takeda S, Sato Y, Kobayashi T, Morita M, et al. Ibandronate concomitantly blocks immobilization-induced bone and muscle atrophy. Biochem Biophys Res Commun. 2016;480(4):662–8.PubMedCrossRef
23.
Miedany YE, Gaafary ME, Toth M, Hegazi MO, Aroussy NE, Hassan W, et al. Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia? Clin Rheumatol. 2021;40(10):4225–423.PubMedCrossRef
24.
Park JH, Park KH, Cho S, Choi YS, Seo SK, Lee BS, et al. Concomitant increase in muscle strength and bone mineral density with decreasing IL-6 levels after combination therapy with alendronate and calcitriol in postmenopausal women. Menopause. 2013;20(7):747–53.PubMedCrossRef
25.
26.
Nevitt MC, Thompson DE, Black DM, Rubin SR, Ensrud K, Yates AJ, et al. Effect of alendronate on limited-activity days and bed-disability days caused by back pain in postmenopausal women with existing vertebral fractures. Fracture Intervention Trial Research Group. Arch Intern Med. 2000;160(1):77–85.PubMedCrossRef
27.
Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–7.PubMedPubMedCentralCrossRef
28.
29.
Hart NH, Newton RU, Tan J, Rantalainen T, Chivers P, Siafarikas A, et al. Biological basis of bone strength: anatomy, physiology and measurement. J Musculoskelet Neuronal Interact. 2020;20(3):347–71.PubMedPubMedCentral
30.
Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2005;90(12):6508–15.PubMedCrossRef
31.
Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone. 2010;47(3):519–28.PubMedPubMedCentralCrossRef
32.
Pistoia W, van Rietbergen B, Lochmüller EM, Lill CA, Eckstein F, Rüegsegger P. Image-based micro-finite-element modeling for improved distal radius strength diagnosis: moving from bench to bedside. J Clin Densitom. 2004;7(2):153–60.PubMedCrossRef
33.
Diez-Perez A, Bouxsein ML, Eriksen EF, Khosla S, Nyman JS, Papapoulos S, et al. Technical note: Recommendations for a standard procedure to assess cortical bone at the tissue-level in vivo using impact microindentation. Bone Rep. 2016;5:181–5.PubMedPubMedCentralCrossRef
34.
Fess E, Moran C. Clinical assessment recommendations. 1st ed. Indianapolis: American Society of Hand Therapists; 1981.
35.
Freire AN, Guerra RO, Alvarado B, Guralnik JM, Zunzunegui MV. Validity and reliability of the short physical performance battery in two diverse older adult populations in Quebec and Brazil. J Aging Health. 2012;24(5):863–78.PubMedCrossRef
36.
Ekelund U, Sepp H, Brage S, Becker W, Jakes R, Hennings M, et al. Criterion-related validity of the last 7-day, short form of the International Physical Activity Questionnaire in Swedish adults. Public Health Nutr. 2006;9(2):258–65.PubMedCrossRef
37.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.PubMedCrossRef
38.
Campanha-Versiani L, Pereira DAG, Ribeiro-Samora GA, Ramos AV, de Sander Diniz MFH, De Marco LA, et al. The effect of a muscle weight-bearing and aerobic exercise program on the body composition, muscular strength, biochemical markers, and bone mass of obese patients who have undergone gastric bypass surgery. Obes Surg. 2017;27(8):2129–37.PubMedCrossRef
39.
Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Wong S, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med. 2018;379(25):2407–16.PubMedCrossRef
40.
Andersen S, Frederiksen KD, Hansen S, Brixen K, Gram J, Støving RK. Bone structure and estimated bone strength in obese patients evaluated by high-resolution peripheral quantitative computed tomography. Calcif Tissue Int. 2014;95(1):19–28.PubMedCrossRef
41.
Sornay-Rendu E, Boutroy S, Vilayphiou N, Claustrat B, Chapurlat RD. In obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight: the Os des Femmes de Lyon (OFELY) study. J Bone Miner Res. 2013;28(7):1679–87.PubMedCrossRef
42.
Compston JE, Watts NB, Chapurlat R, Cooper C, Boonen S, Greenspan S, et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am J Med. 2011;124(11):1043–50.PubMedPubMedCentralCrossRef
43.
Prieto-Alhambra D, Premaor MO, Fina Avilés F, Hermosilla E, Martinez-Laguna D, Carbonell-Abella C, et al. The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women. J Bone Miner Res. 2012;27(2):294–300.PubMedCrossRef
44.
Bredella MA, Greenblatt LB, Eajazi A, Torriani M, Yu EW. Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on bone mineral density and marrow adipose tissue. Bone. 2017;95:85–90.PubMedCrossRef
45.
Brzozowska MM, Tran T, Bliuc D, Jorgensen J, Talbot M, Fenton-Lee D, et al. Roux-en-Y gastric bypass and gastric sleeve surgery result in long term bone loss. Int J Obes (Lond). 2021;45(1):235–46.CrossRef
46.
Cadart O, Degrandi O, Barnetche T, Mehsen-Cetre N, Monsaingeon-Henry M, Pupier E, et al. Long-term effects of Roux-en-Y gastric bypass and sleeve gastrectomy on bone mineral density: a 4-year longitudinal study. Obes Surg. 2020;30(9):3317–25.PubMedCrossRef
47.
Hart NH, Nimphius S, Rantalainen T, Ireland A, Siafarikas A, Newton RU. Mechanical basis of bone strength: influence of bone material, bone structure and muscle action. J Musculoskelet Neuronal Interact. 2017;17(3):114–39.PubMedPubMedCentral
48.
Sylvia LG, Bernstein EE, Hubbard JL, Keating L, Anderson EJ. Practical guide to measuring physical activity. J Acad Nutr Diet. 2014;114(2):199–208.PubMedCrossRef
Metadata
Title
Zoledronic Acid for prevention of bone and muscle loss after BAriatric Surgery (ZABAS)-a study protocol for a randomized controlled trial
Authors
Søren Gam
Bibi Gram
Claus Bogh Juhl
Anne Pernille Hermann
Stinus Gadegaard Hansen
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-022-06766-z

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