Abstract
The prevalence of obesity has increased around the world, and the frequency of bariatric surgery, one of the therapeutic alternatives for specific cases, has also increased progressively. Despite the beneficial effects of bariatric surgery on various obesity-related comorbidities, the most significant postoperative weight losses have been associated with negative skeletal repercussions. In this context, serum bone health markers could provide early warning to the higher skeletal risk. In this chapter we will discuss the mechanisms involved in the relationship between obesity, its treatment with bariatric surgery, and bone metabolism, in addition to how changes in this relationship influence the main bone biomarkers.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- ALP:
-
Total alkaline phosphatase
- BSAP:
-
Bone-specific alkaline phosphatase
- BMD:
-
Bone mineral density
- BMI:
-
Body mass index
- BMP:
-
Bone morphogenetic proteins
- BTM:
-
Bone turnover markers
- CTX:
-
Collagen-type I C-telopeptide
- DAN:
-
Differential screening-selected gene aberrative in neuroblastoma
- ICTP:
-
Carboxy-terminal telopeptide of type I collagen
- IGF-1:
-
Insulin growth factor 1
- LRP5:
-
Low-density lipoprotein receptor-related protein 5
- LRP6:
-
Low-density lipoprotein receptor-related protein 6
- NIH:
-
National Institutes of Health
- NTX:
-
Collagen-type I N-telopeptide
- OPG:
-
Osteoprotegerin
- PTH:
-
Parathyroid hormone
- PICP:
-
Carboxy-terminal procollagen propeptides of collagen type I
- PINP:
-
Procollagen type I amino-terminal propeptide
- PIIINP:
-
Amino-terminal procollagen propeptides of collagen type III
- RANK:
-
Receptor that activates the nuclear factor kappa B
- RANKL:
-
RANK ligand
- RYGB:
-
Gastroplasty with Roux-en-Y gastric bypass
- TPH1:
-
1-Tryptophan hydroxylase
- TRAP5b:
-
Tartrate-resistant acid phosphatase isoenzyme 5b
- WHO:
-
World Health Organization
- 1,25OHD:
-
1,25-Hydroxy-vitamin D
- 25OHD:
-
25-Hydroxy-vitamin D
References
Aguirre L, Napoli N, Waters D, Qualls C, Villareal DT, Armamento-Villareal R. Increasing adiposity is associated with higher adipokine levels and lower bone mineral density in obese older adults. J Clin Endocrinol Metab. 2014;99:3290–9.
Armamento-Villareal R, Sadler C, Napoli N, et al. Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. J Bone Miner Res. 2012;27:1215–21.
Armstrong ME, Cairns BJ, Banks E, et al. Different effects of age, adiposity and physical activity on the risk of ankle, wrist and hip fractures in postmenopausal women. Bone. 2012;50:1394–400.
Arterburn DE, Courcoulas AP. Bariatric surgery for obesity and metabolic conditions in adults. BMJ. 2014;349:g3961. doi:10.1136/bmj.g3961.
Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001;10:537–43.
Bellido T, Ali AA, Gubrij I, et al. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005;146:4577–83.
Bezerra MC, Carvalho JF, Prokopowitsch AS, Pereira RM. RANK, RANKL and osteoprotegerin in arthritic bone loss. Braz J Med Biol Res. 2005;38:161–70.
Biagioni MF, Mendes AL, Nogueira CR, Paiva SA, Leite CV, Mazeto GM. Weight-reducing gastroplasty with Roux-en-Y gastric bypass: impact on vitamin D status and bone remodeling markers. Metab Syndr Relat Disord. 2014;12:11–5.
Bloomberg RD, Fleishman A, Nalle JE, Herron DM, Kini S. Nutritional deficiencies following bariatric surgery: what have we learned? Obes Surg. 2005;15:145–54.
Bloomfield SA. Disuse osteopenia. Curr Osteoporos Rep. 2010;8:91–7.
Bonewald LF, Johnson ML. Osteocytes, mechanosensing and Wnt signaling. Bone. 2008;42:606–15.
Bonjour JP, Kohrt W, Levasseur R, Warren M, Whiting S, Kraenzlin M. Biochemical markers for assessment of calcium economy and bone metabolism: application in clinical trials from pharmaceutical agents to nutritional products. Nutr Res Rev. 2014;27:252–67.
Brunkow ME, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68:577–89.
Bruno C, Fulford AD, Potts JR, et al. Serum markers of bone turnover are increased at six and 18 months after Roux-en-Y bariatric surgery: correlation with the reduction in leptin. J Clin Endocrinol Metab. 2010;95:159–66.
Brzozowska MM, Sainsbury A, Eisman JA, Baldock PA, Center JR. Bariatric surgery, bone loss, obesity and possible mechanisms. Obes Rev. 2013;14:52–67.
Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013;23:427–36.
Burger EH, Klein-Nulend J. Mechanotransduction in bone-role of the lacuna-canalicular network. FASEB J. 1999;13:S101–12.
Cao JJ. Effects of obesity on bone metabolism. J Orthop Surg Res. 2011;6:30. doi:10.1186/1749-799X-6-30.
Capella JF, Capella RF. The weight reduction operation of choice: vertical banded gastroplasty or gastric bypass? Am J Surg. 1996;171:74–9.
Carlin AM, Rao DS, Yager KM, Genaw JA, Parikh NJ, Szymanski W. Effect of gastric bypass surgery on vitamin D nutritional status. Surg Obes Relat Dis. 2006;2:638–42.
Casagrande DS, Repetto G, Mottin CC, et al. Changes in bone mineral density in women following 1-year gastric bypass surgery. Obes Surg. 2012;22:1287–92.
Coates PS, Fernstrom JD, Fernstrom MH, Schauer PR, Greenspan SL. Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass. J Clin Endocrinol Metab. 2004;89:1061–5.
Collazo-Clavell ML, Jimenez A, Hodgson SF, Sarr MG. Osteomalacia after Roux-en-Y gastric bypass. Endocr Pract. 2004;10:195–8.
Compston JE, Watts NB, Chapurlat R, et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am J Med. 2011;124:1043–50.
Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003;111:1221–30.
Elias E, Casselbrant A, Werling M, et al. Bone mineral density and expression of vitamin D receptor-dependent calcium uptake mechanisms in the proximal small intestine after bariatric surgery. Br J Surg. 2014;101:1566–75.
Ferrer Cañabate J, Tovar I, Martínez P. Osteoprotegrin and RANKL/RANK system: is it the future of bone metabolism? An Med Interna. 2002;19:385–8.
Fleischer J, Stein EM, Bessler M, et al. The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss. J Clin Endocrinol Metab. 2008;93:3735–40.
Frost HM. Bone “mass” and the “mechanostat”: a proposal. Anat Rec. 1987;219:1–9.
Gannagé-Yared MH, Yaghi C, Habre B, et al. Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study. Eur J Endocrinol. 2008;158:353–9.
Giusti V, Gasteyger C, Suter M, Heraief E, Gaillard RC, Burckhardt P. Gastric banding induces negative bone remodelling in the absence of secondary hyperparathyroidism: potential role of serum C telopeptides for follow up. Int J Obes (Lond). 2005;29:1429–35.
Goode LR, Brolin RE, Chowdhury HA, Shapses SA. Bone and gastric bypass surgery: effects of dietary calcium and vitamin D. Obes Res. 2004;12:40–7.
Gortmaker SL, Swinburn BA, Levy D, et al. Changing the future of obesity: science, policy, and action. Lancet. 2011;378:838–47.
Grethen E, Hill KM, Jones R, et al. Serum leptin, parathyroid hormone, 1,25-dihydroxyvitamin d, fibroblast growth factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity. J Clin Endocrinol Metab. 2012;97:1655–62.
Guney E, Kisakol G, Ozgen G, Yilmaz C, Yilmaz R, Kabalak T. Effect of weight loss on bone metabolism: comparison of vertical banded gastroplasty and medical intervention. Obes Surg. 2003;13:383–8.
Hage MP, El-Hajj Fuleihan G. Bone and mineral metabolism in patients undergoing Roux-en Y gastric bypass. Osteoporos Int. 2014;25:423–39.
Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080S–6.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63:2985–3023.
Johnson JM, Maher JW, DeMaria EJ, Downs RW, Wolfe LG, Kellum JM. The long-term effects of gastric bypass on vitamin D metabolism. Ann Surg. 2006;243:701–4.
Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008;29:155–92.
Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone. 2005;37:148–58.
Kirchengast S, Peterson B, Hauser G, Knogler W. Body composition characteristics are associated with the bone density of the proximal femur end in middle- and old-aged women and men. Maturitas. 2001;39:133–45.
Knoke JD, Barrett-Connor E. Weight loss: a determinant of hip bone loss in older men and women. The Rancho Bernardo Study. Am J Epidemiol. 2003;158:1132–8.
Lewiecki EM. Sclerostin: a novel target for intervention in the treatment of osteoporosis. Discov Med. 2011;12:263–73.
Li J, Sarosi I, Yan XQ, et al. Rank is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci U S A. 2000;97:1566–71.
Liu H, Zhang R, Ko SY, et al. Microtubule assembly affects bone mass by regulating both osteoblast and osteoclast functions: stathmin deficiency produces an osteopenic phenotype in mice. J Bone Miner Res. 2011;26:2052–67.
Liu C, Wu D, Zhang JF, et al. Changes in bone metabolism in morbidly obese patients after bariatric surgery: a meta-analysis. Obes Surg. 2015. http://link.springer.com/article/10.1007/s11695-015-1724-5
Martins MVDC. Why Roux-em-Y gastric bypass is nowadays the best surgery to treat obesity. Rev bras videocir. 2005;3:102–4.
Mason EE. Bone disease from duodenal exclusion. Obes Surg. 2000;10:585–6.
Mechanick JI, Garber AJ, Handelsman Y, Garvey WT. American Association of Clinical Endocrinologists’ position paper on obesity and obesity medicine. Endocr Pract. 2012;18:642–8.
Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient–2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Endocr Pract. 2013;19:337–72.
Miyazaki T, Matsunaga T, Miyazaki S, Hokari S, Komoda T. Changes in receptor activator of nuclear factor-kappaB, and its ligand, osteoprotegerin, bone-type alkaline phosphatase, and tartrate-resistant acid phosphatase in ovariectomized rats. J Cell Biochem. 2004;93:503–12.
Moester MJ, Papapoulos SE, Löwik CW, van Bezooijen RL. Sclerostin: current knowledge and future perspectives. Calcif Tissue Int. 2010;87:99–107.
Molina PE. Glândulas paratireoides e regulação do Ca2+ e do PO-4. In: Molina PE, editor. Fisiologia endócrina. 1st ed. São Paulo: McGraw-Hill Interamericana do Brasil; 2007. p. 95–121.
Monteiro Júnior FD, Silva Júnior WS, Salgado Filho N, et al. Effects of weight loss induced by bariatric surgery on the prevalence of metabolic syndrome. Arq Bras Cardiol. 2009;92:452–6.
Muschitz C, Kocijan R, Marterer C, et al. Sclerostin levels and changes in bone metabolism after bariatric surgery. J Clin Endocrinol Metab. 2015;100:891–901.
Ng M, Fleming T, Robinson M, 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;384:766–81.
NIH – National Institute Health conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med. 1991;115:956–61.
Novack DV, Teitelbaum SL. The osteoclast: friend or foe? Annu Rev Pathol. 2008;3:457–84.
Nusse R. Wnt signaling in disease and in development. Cell Res. 2005;15:28–32.
Papapietro K, Massardo T, Riffo A, et al. Bone mineral density disminution post Roux-Y bypass surgery. Nutr Hosp. 2013;28:631–6.
Pérez-Castrillón JL, Riancho JA, de Luis D, et al. Effect of two types of bariatric surgery (gastrojejunal bypass and sleeve gastroplasty) on gene expression of bone remodeling markers in goto-kakizaki rats. Obes Surg. 2014;24:37–41.
Pugnale N, Giusti V, Suter M, et al. Bone metabolism and risk of secondary hyperparathyroidism 12 months after gastric banding in obese premenopausal women. Int J Obes Relat Metab Disord. 2003;27:110–6.
Reid IR. Obesity and osteoporosis. Ann Endocrinol (Paris). 2006;67:125–9.
Ricci TA, Heymsfield SB, Pierson Jr RN, et al. Moderate energy restriction increases bone resorption in obese postmenopausal women. Am J Clin Nutr. 2001;73:347–52.
Robling AG, Niziolek PJ, Baldridge LA, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283:5866–75.
Rodríguez-Carmona Y, López-Alavez FJ, González-Garay AG, Solís-Galicia C, Meléndez G, Serralde-Zúñiga AE. Bone mineral density after bariatric surgery. A systematic review. Int J Surg. 2014;12:976–82.
Ryan DH, Johnson WD, Myers VH, et al. Nonsurgical weight loss for extreme obesity in primary care settings: results of the Louisiana Obese Subjects Study. Arch Intern Med. 2010;170:146–54.
Salamone LM, Cauley JA, Black DM, et al. Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial. Am J Clin Nutr. 1999;70:97–103.
Santos MT, Souza FI, Fonseca FL, Lazaretti-Castro M, Sarni RO. Changes in bone metabolism markers in women after Roux-en-Y gastric bypass. Arq Bras Endocrinol Metabol. 2012;56:376–82.
Schoenau E. Bone mass increase in puberty: what makes it happen? Horm Res. 2006;65:S2–10.
Slater GH, Ren CJ, Siegel N, et al. Serum fat soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery. J Gastrointest Surg. 2004;8:48–55.
Sousa CP, Dias IR, Lopez-Peña M, et al. Bone turnover markers for early detection of fracture healing disturbances: a review of the scientific literature. An Acad Bras Cienc. 2015;87:1049–61.
Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378:804–14.
ten Dijke P, Krause C, de Gorter DJ, Löwik CW, van Bezooijen RL. Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am. 2008;90:31–5.
Trémollières F, Pouilles JM, Ribot C. Effect of long-term administration of progestogen on post-menopausal bone loss: result of a two year, controlled randomized study. Clin Endocrinol (Oxf). 1993;38:627–31.
Tsiftsis DD, Mylonas P, Mead N, Kalfarentzos F, Alexandrides TK. Bone mass decreases in morbidly obese women after long limb-biliopancreatic diversion and marked weight loss without secondary hyperparathyroidism. A physiological adaptation to weight loss? Obes Surg. 2009;19:1497–503.
van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199:805–14.
van Bezooijen RL, Svensson JP, Eefting D, et al. Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation. J Bone Miner Res. 2007;22:19–28.
Vasconcelos RS, Viégas M, Marques TF, et al. Factors associated with secondary hyperparathyroidism in premenopausal women undergoing Roux-en-Y gastric bypass for the treatment of obesity. Arq Bras Endocrinol Metabol. 2010;54:233–8.
Viégas M, Vasconcelos RS, Neves AP, Diniz ET, Bandeira F. Bariatric surgery and bone metabolism: a systematic review. Arq Bras Endocrinol Metabol. 2010;54:158–63.
Vilarrasa N, Gómez JM, Elio I, et al. Evaluation of bone disease in morbidly obese women after gastric bypass and risk factors implicated in bone loss. Obes Surg. 2009;19:860–6.
WHO – World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:1–253.
WHO – World Health Organization. Global action plan for the prevention and control of noncommunicable diseases. 2013–2020. http://apps.who.int/iris/bitstream/10665/94384/1/9789241506236_eng.pdf?ua=1. Accessed 16 Mar 2015.
Yadav VK, Ryu JH, Suda N, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum: an entero-bone endocrine axis. Cell. 2008;135:825–37.
Yamauchi M, Sugimoto T, Yamaguchi T, et al. Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol (Oxf). 2001;55:341–7.
Youssef Y, Richards WO, Sekhar N, et al. Risk of secondary hyperparathyroidism after laparoscopic gastric bypass surgery in obese women. Surg Endosc. 2007;21:1393–6.
Yu EW. Bone metabolism after bariatric surgery. J Bone Miner Res. 2014;29:1507–18.
Yu EW, Bouxsein ML, Roy AE, et al. Bone loss after bariatric surgery: discordant results between DXA and QCT bone density. J Bone Miner Res. 2014;29:542–50.
Zhang R, Oyajobi BO, Harris SE, et al. Wnt/β-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts. Bone. 2013;52:145–56.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media Dordrecht
About this entry
Cite this entry
Biagioni, M.F.G., Mendes, A.L., Paiva, S.A.R., Mazeto, G.M.F.S. (2017). Use of Bone Biomarkers After Weight Loss: Example of Bariatric Surgery. In: Patel, V., Preedy, V. (eds) Biomarkers in Bone Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7693-7_8
Download citation
DOI: https://doi.org/10.1007/978-94-007-7693-7_8
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-7692-0
Online ISBN: 978-94-007-7693-7
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences