- Email: [email protected]
Effects of bariatric surgery on bone
Joint Bone Spine 83 (2016) 271–275
Available online at
ScienceDirect www.sciencedirect.com
Review
Effects of bariatric surgery on bone Brigitte Uebelhart Département des spécialités de médecine, service des maladies osseuses, hôpitaux universitaires, faculté de médecine de Genève, 4, rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland
a r t i c l e
i n f o
Article history: Accepted 21 February 2013 Available online 15 March 2016 Keywords: Bone mineral density Fractures Biochemical bone turnover markers
a b s t r a c t Bariatric surgery currently relies on combinations of restrictive and malabsorptive procedures. Early decreases in bone mineral density (BMD) have been reported. However, the accuracy of dual-energy X-ray absorptiometry used to measure BMD can be diminished by the major weight loss, whereas quantitative computed tomography (QCT) measurements are less affected. The nutritional deficiencies induced by mixed bariatric surgery procedures, together with changes in hormones produced by adipocytes and/or the gastrointestinal tract, are often associated with elevations in serum levels of bone resorption markers. Although the data are limited, the incidence of fractures does not seem higher after bariatric surgery than in non-operated obese patients. © 2016 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Bariatric surgery includes various procedures aimed at inducing weight loss in obese patients. These procedures restrict the amount of food eaten and/or induce malabsorption, thereby causing considerable and long-lasting weight loss [1]. This large decrease in weight has highly beneficial effects on the diseases and risk factors associated with excess body fat, most notably in obese patients with type 2 diabetes [2]. The improved glycemic control seen in these diabetic patients after bariatric surgery may also involve endocrine and metabolic factors that increase feelings of satiety or decrease appetite. Finally, prospective data have documented a decrease in mortality [3]. 1. Bariatric surgery techniques Bariatric surgery techniques include restrictive, malabsorptive, and mixed procedures [4]. They are increasingly performed laparoscopically. Restrictive bariatric surgery (Fig. 1) was introduced in the 1950s. The objective is to decrease the capacity of the stomach and/or to delay gastric emptying. This method is effective in inducing weight loss in the short term. However, it is associated with gastrointestinal symptoms, most notably bowel transit abnormalities. Furthermore, patients tend to gain weight secondarily by changing their eating patterns. As a result, restrictive procedures are no longer performed. Malabsorptive procedures (Fig. 1) were first developed in the late 1960s. They involve creating a bypass between the duodenum
E-mail address: [email protected]
and the ileum. Thus, weight loss occurs regardless of the patient’s diet. This method has been discarded for two reasons: it induces metabolic complications (e.g., increased oxalate absorption responsible for renal lithiasis) and it causes blind loop syndrome (i.e., bacterial overgrowth responsible for various symptoms including polyarthralgia). Since the early 1980s, mixed procedures that combine restrictive and malabsorptive techniques have gained preference. Many variants exist, all of which derive from the Roux-en-Y gastric bypass (RYGBS) developed by the Swiss surgeon César Roux (Fig. 2). The variant developed by the Italian surgeon Nicola Scopinaro (1974) is characterized by a short common intestinal segment, which results in a predominantly malabsorptive mechanism. 2. Systemic metabolic impact of mixed bariatric surgery (Roux-en-Y gastric bypass surgery [RYGBS] and variants) The combination of decreased energy intake from food and malabsorption would be expected to result in at least partial deficiencies in the absorption of various nutrients [5] (Fig. 2). Vitamin B12 deficiency is related to decreases in both intrinsic factor and acidification [6,7]. Decreased acidification can also lead to iron deficiency responsible for anemia. Patients may lack fat-soluble vitamins (A, D, E, and K) [8,9], and the lower vitamin D stores may cause calcium deficiency, often with secondary hyperparathyroidism, which may persist even after vitamin D repletion [10]. In clinical practice, the most consistently prescribed vitamin supplement is intramuscular vitamin B12. Calcium and vitamin D supplements are also frequently given. The other vitamins, nutrients, and ions are prescribed on an as-needed basis.
http://dx.doi.org/10.1016/j.jbspin.2016.02.013 1297-319X/© 2016 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
272
B. Uebelhart / Joint Bone Spine 83 (2016) 271–275 Table 1 Changes in body mass index, bone mineral density, and T-scores in 62 women with morbid obesity before and 12 months after Roux-en-Y gastric bypass surgery.
Body mass index (kg/m2 ) Bone mineral density (g/cm2 ), femoral neck Bone mineral density (g/cm2 ), lumbar spine T-Score (SD), femoral neck T-Score (SD), lumbar spine *
Before surgery
12 months after surgery
43.9 ± 4.2 1.1 ± 0.11
29.1 ± 4.5* 0.98 ± 0.11*
1.1 ± 0.12
1.06 ± 0.13*
1.1 ± 0.98 0.68 ± 1.2
0.13 ± 0.98* 0.25 ± 1.2*
P < 0.005 versus the value before surgery [17].
serum compounds reflecting activity of the calcium-parathyroid hormone-vitamin D axis. Only recently have retrospective data on fractures after bariatric surgery become available. Fig. 1. Examples of restrictive and malabsorptive bariatric procedures. Restrictive bariatric procedures consist in decreasing the size of the stomach. Techniques include transverse gastrectomy (A), sleeve gastrectomy (B), and implantation of an inflatable band around the proximal stomach (C). Malabsorptive bariatric procedures involve creating a bypass between the jejunum and the ileum. In the Payne procedure (D), a 35-cm long segment of proximal jejunum is anastomosed to the ileum 10 cm proximal to the ileocecal valve. The distal jejunum and proximal ileum form a blind loop, through which food does not travel, and where bacterial overgrowth may develop.
3. Impact of bariatric surgery on bone The decreased absorption of vitamin D and calcium would be expected to substantially increase the risk of osteomalacia. This expectation is not borne out by the data in the literature. The anecdotal case-reports published to date describe patients with clinical, laboratory, or radiological features indicating suspected osteomalacia, without histological documentation (no bone biopsy or mineralization rate measurement by double tetracycline labeling). Whether these features are entirely ascribable to bariatric surgery remains unclear. For instance, 1 patient was African-American, and the risk of vitamin D deficiency is known to be markedly increased in blacks [11]. Another patient was dependent on corticosteroid therapy for severe asthma [12]. Many published studies of bariatric-surgery patients monitored bone mineral density (BMD), serum bone turnover markers, and
Fig. 2. Mixed Roux-en-Y gastric bypass surgery and resulting malabsorption. The Roux-en-Y procedure creates three small-bowel loops: (A) receives food but no bile or pancreatic secretions; (B) receives the bile and pancreatic secretions; and (C) receives the outputs from loops A and B. There is malabsorption of vitamin B12, fatsoluble vitamins (A, D, E, and K), iron, and calcium. In contrast, oxalate is absorbed in increased amounts because of the diminished formation of non-absorbable calciumoxalate complexes that are normally eliminated in the feces.
3.1. Bone mineral density (BMD) Studies consistently found decreased BMD values, which were usually measured by dual-energy X-ray absorptiometry (DXA). These decreases occurred despite calcium and vitamin D supplementation. Early BMD decreases were demonstrated using various study designs, including a cross-sectional evaluation several years after bariatric surgery [13], a 2-year prospective study after gastric banding [14], and a comparison of data collected preoperatively, then 1 to 4 years after bypass gastric surgery [15–18]. The BMD decline starts within the first year after surgery, then continues at a slower pace. The hip is the most severely affected site, with an up to 10% decrease compared to the preoperative value. Bone loss occurs less consistently at the spine and only rarely at the radius. The BMD decrease is larger in postmenopausal women than in younger women before the menopause. Despite the magnitude of the bone loss, given the baseline values, the postoperative T-scores usually remain within the normal range. For instance, in a study of 62 women with morbid obesity who were evaluated preoperatively then 1 year after RYGBS, both the BMD and the T-score values diminished significantly yet remained within the normal ranges (Table 1) [17]. Fig. 3 shows the size of the BMD decreases after gastric bypass surgery [18]. In this study, BMD values were measured over a 9-month period in 25 patients. The BMD declines were largest at the hip, where the values decreased by 6% at the femoral neck and 8% at the greater trochanter. Bone mineral content (BMC) showed smaller declines. In this study, mean weight loss was 13% after 3 months and 27% after 9 months. A similar discrepancy between BMD and BMC values was documented in another study (Table 2), which evaluated 70 patients with morbid obesity before and 1 year after RYGBS [16]. After 1 year, as is usual with this procedure, the patients had lost about 30% of their body weight and 54% of their fat mass. The preoperative to postoperative changes measured using DXA (GE Lunar densitometer) were significant and BMC showed a larger decline (−9%) compared to BMD (−3%). Oddly, enough, there was a significant 6% decrease in total bone surface area. This finding suggests that the large decrease in soft-tissue thickness related to the up to 50% decrease in fat mass may substantially affect the accuracy of DXA measurements. The weight loss, which is chiefly due to a decrease in body fat, strongly influences the accuracy of BMD measurements yet is often not specified in study reports. Other measurement tools such as quantitative computed tomography (QCT) may be less sensitive than DXA to the effects of the initial excess body fat and subsequent major weight loss. This possibility has been assessed by comparing DXA and QCT used to obtain measurements of lumbar-spine phantoms and of healthy volunteers. Changes in the thickness of the soft tissues and body
B. Uebelhart / Joint Bone Spine 83 (2016) 271–275
273
Table 2 Changes in anthropometric parameters and bone mineral density and content in 70 patients with morbid obesity before and 12 months after Roux-en-Y gastric bypass surgery. Patients took 1 g of supplemental calcium and 800 IU of supplemental vitamin D per day [16]. Before surgery (mean ± SD) Weight (kg) Body mass index (kg/m2 ) Total body fat (kg) Bone mineral content (g) Bone mineral density (g/cm2 ) Total bone surface area (m2 )
132.81 48.06 75.21 2968.6 1.26 2356.16
± ± ± ± ± ±
26.52 7.3 21.25 71.44 0.03 35.4
fat were simulated. The results suggest that an increase in body fat thickness within the soft tissues has a major adverse effect on the accuracy of bone measurements, most notably at the lumbar spine, and that this effect is greater with DXA than with QCT [19]. Although more reliable, QCT involves greater patient exposure to radiation. BMD changes were evaluated using both DXA and QCT in 30 patients with morbid obesity during the first 12 months after mixed bariatric surgery and in 20 non-operated obese patients. At the end of the 12-month follow-up, the surgically treated group had a mean weight loss of 37 ± 2 kg and the non-operated group a mean weight gain of 3 ± 2 kg. Both DXA and QCT showed an about 3% decrease in BMD at the spine in the surgically treated group. At the femoral neck and total hip, BMD was decreased by DXA but not by QCT [20]. 3.2. Laboratory parameters involved in bone metabolism Many published studies have addressed this issue, and their findings are conflicting. Most studies are prospective or retrospective evaluations of patients with morbid obesity, whose data
Fig. 3. Changes in bone mineral density and content at various sites 9 months after Roux-en-Y gastric bypass surgery [18]. Nine months after Roux-en-Y gastric bypass surgery, bone mineral density values (A) measured by DXA (Hologic QDR-4500A) are significantly decreased at all measurement sites (spine, total hip, femoral neck, trochanter, distal third of the radius, and whole body). The decreases in bone mineral content (B) are significant only at the femoral neck and total hip. Ultrasound attenuation values at the heel are provided for purposes of comparison. The data are mean ± SD. Compared to preoperative values: *P < 0.05, **P < 0.01, ***P < 0.001.
12 months after surgery (mean ± SD) 90.31 32.64 34.46 2700.82 1.22 2216.28
± ± ± ± ± ±
17.29 4.13 13.63 45.36 0.015 43.51
P-value
Change (%)
0.001 0.001 0.001 0.001 0.001 0.001
−32 −33 −54 −9 −3 −6
collected before and after bariatric surgery were compared. Many found no differences or abnormalities, particularly regarding serum calcium, parathyroid hormone, and 25-OH-vitamin D [15–17,19]. It should be borne in mind, however, that calcium and vitamin D supplements are prescribed routinely after bariatric surgery. Other studies comparing patients before and after surgery showed secondary parathyroid hormone elevation which, in some cases, was clearly ascribable to persistently low 25-OH-vitamin D levels throughout follow-up [10,21]. An important point is that the main source of vitamin D is not food but, instead, synthesis in the skin via a mechanism activated by ultraviolet radiation in sunlight. Consequently, the prevalence of vitamin D insufficiency or deficiency among operated or non-operated patients with morbid obesity is probably similar to that in the general population. In contrast, the absorption of supplemental vitamin D (a fat-soluble vitamin) decreases after bariatric surgery, and vitamin D insufficiency is therefore difficult to correct. Consequently, serum 25-OH-vitamin D levels should be assayed regularly, supplements given in higher doses than recommended in the general population, and intramuscular vitamin D administered if needed. Finally, vitamin D can be sequestered in excess body fat that may persist despite the postoperative weight loss [22]. Whatever the mechanism, patients who have had bariatric surgery to treat morbid obesity are at increased risk for severe vitamin D deficiency. They are therefore classified as a population at risk and should undergo serum 25-OH-vitamin D assays at regular intervals [23]. Alterations in bone turnover are the most often reported abnormalities. The bone resorption marker C-terminal telopeptide (CTX, the C-terminal end of type I collagen, which is released into the bloodstream during osteoclastic resorption) increases after bariatric surgery. This increase in a bone resorption marker is not consistently accompanied with parathyroid hormone elevation or vitamin D insufficiency. Other factors, such as hormones, may therefore be involved [24,25]. Bone resorption marker elevation has also been reported in patients after RYGBS compared to matched non-operated obese patients, both 1 year after surgery [18] and up to 5 years after surgery [26]. The adverse bone changes seen after bariatric surgery are widely ascribed to the decreased nutrient absorption and reduction in mechanical loading related to the weight loss. Nevertheless, a growing body of evidence suggests a role for changes in the release of hormones produced in fat tissue, i.e., adipokines, and in the gastrointestinal tract (peptide YY, glucagon-like peptide-1, and ghrelin) [27–29]. The most extensively studied hormones are the two main adipokines, leptin and adiponectin. Leptin is produced by adipocytes and its levels therefore decrease when body fat is lost after bariatric surgery. A strong correlation has been reported between the decrease in body mass index (BMI) and serum leptin levels [30]. In a prospective study of 20 patients who underwent bariatric surgery, a serum leptin decrease predicted increased bone resorption with CTX elevation, suggesting an effect of leptin on bone cells [31]. Adiponectin is also produced by adipocytes, although in smaller amounts in obese patients. Serum adiponectin levels may correlate negatively with BMD. Gastrointestinal
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B. Uebelhart / Joint Bone Spine 83 (2016) 271–275
hormones, of which one effect is to control appetite and feelings of satiety, may contribute to the changes in bone metabolism, although their effect remains unclear [29].
the close patient follow-up with the prescription of supplements to correct the main surgery-related deficiencies, particularly in calcium and, above all in vitamin D.
3.3. Fractures
Disclosure of interest
The incidence of fractures after bariatric surgery to treat morbid obesity is generating avid interest, particularly given the possible BMD decline and combination of deleterious biological changes including calcium and vitamin D deficiency, secondary hyperparathyroidism, and accelerated bone turnover. Nevertheless, the available information is scant. A descriptive retrospective study was conducted in 167 patients from a possible participant pool of 444 [32]. The patients were interviewed by telephone 12 to 60 months after RYGBS to treat morbid obesity. Among them, 8 (5%) reported having had a fracture since their surgical procedure, after a mean postoperative follow-up of 2.4 years. Although this fracture rate is low, important findings are that 57 (34%) patients experienced one or more falls postoperatively and that only 15 (9%) reported taking vitamin D supplements. A population-based retrospective cohort study reported in 2012 used data collected between January 1987 and December 2010 from 625 primary-care practices in the UK. All patients treated with bariatric surgery for morbid obesity and all bone events such as fractures were recorded. The 2079 operated patients had a mean age of 45 years (and still had BMI values > 30 kg/m2 ). They were compared to non-operated patients matched on age and weight. During the mean follow-up of 2.2 years, no significant increase in the frequency of fractures was noted in the bariatric-surgery group. A nonsignificant trend towards a higher fracture rate 3 to 5 years after surgery was noted in the subgroup with the greatest decrease in BMI [33]. A second study on the fracture risk after bariatric surgery was published in 2014 [34]. Again, a retrospective cohort design was used. The study included only 258 patients with a history of bariatric surgery, living in Minnesota and included in the Rochester Epidemiology Project. Mean age was 44 ± 10 years. The mean follow-up of 7.7 years was substantially longer than in the previous study. In this cohort, 79 patients experienced 132 fractures, yielding a 2.3-fold increase in relative risk compared to the overall population in the Rochester Epidemiology Project. The operated patients were not matched to the controls on weight, which may have induced bias, since excess weight may be an independent risk factor for fractures, at least at some sites. 4. Conclusion Bariatric surgery induces significant health benefits in patients with morbid obesity. Weight loss is known to have adverse effects on bone in other situations, and bariatric surgery induces malabsorption with deficiencies in a number of factors. Nevertheless, the studies have shown little or no increase in the fracture risk after bariatric surgery. This finding should be interpreted in the light of the large reduction in body fat and invites questions about possible links between adipose tissue and bone tissue, which may be modest or related to other mechanisms. The decrease in BMD values shown in DXA studies should be viewed with circumspection, as the considerable weight loss affects the accuracy of DXA. QCT measurements may be more reliable. Finally, bone resorption markers seem to increase consistently, although the underlying pathophysiological mechanism remains obscure. Hypotheses that may explain the limited impact on bone of bariatric surgery include the persistence of excess weight even after a period of considerable weight loss, persistence of normal BMD and T-score values, and probably
The author declares that she has no competing interest. References [1] Colquitt JL, Picot J, Loveman E, et al. Surgery for obesity. Cochrane Database Syst Rev 2009:CD003641. [2] Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009;122:248–5600000. [3] Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741–52. [4] Demaria E, Jamal M. Surgical options for obesity. Gastroenterol Clin N Am 2005;34:127–42. [5] Mason M, Jalagani H, Vinik A. Metabolic complications of bariatric surgery: diagnosis and management issues. Gastroenterol Clin N Am 2005;34: 25–33. [6] Smith C, Herkes S, Behms K, et al. Gastric acid secretion and vitamin B12 absorption after vertical Roux-en-Y gastric bypass for morbid obesity. Ann Surg 1993;218:91–6. [7] Marcuard S, Sinar D, Swanson M, et al. Absence of luminal intrinsic factor after gastric bypass surgery for morbid obesity. Dig Dis Sci 1989;34: 1238–42. [8] Hatzifotis M, Dola K, Newbury L, et al. Symptomatic vitamin A deficiency following biliopancreatic diversion. Obes Surg 2003;13:655–7. [9] Slater G, Ren C, Siegel N, et al. Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery. J Gastrointest Surg 2004;8:48–55. [10] Hanoui N, Kim K, Anthone G, et al. The significance of elevated levels of parathyroid hormone in patients with morbid obesity before and after bariatric surgery. Arch Surg 2003;138:891–7. [11] Goldner W, O’Dorisio T, Dillon J, et al. Severe metabolic bone disease as a longterm complication of obesity surgery. Obes Surg 2002;12:685–92. [12] Collazo-Clavell M, Jimenez A, Hodgson S, et al. Osteomalacia after Roux-en-Y gastric bypass. Endocr Pract 2004;10:195–8. [13] Bano G, Rodin DA, Pazianas M, et al. Reduced bone mineral density after surgical treatment for obesity. Int J Obes (Lond) 1999;23:361–5. [14] Cundy T, Evans MC, Kay RG, et al. Effects of vertical-banded gastroplasty on bone and mineral metabolism in obese patients. Br J Surg 1996;83:1468–72. [15] Johnson J, Maher J, Samuel I, et al. Effects of gastric bypass procedures on bone mineral density, calcium, parathyroid hormone and vitamin D. J Gastrointest Surg 2005;9:1106–11. [16] Mahdy T, Atia S, Farid M. Effect of Roux-en Y gastric bypass on bone metabolism in patients with morbid obesity: Mansoura experiences. Obes Surg 2008;18:1526–31. [17] Vilarrasa N, Gomez 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. [18] Coates P, Fernstrom J, Fernstrom M, et al. 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. [19] Yu EW, Thomas BJ, Brown JK, et al. Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT. J Bone Miner Res 2012;27:119–24. [20] 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. [21] DiGiorgi M, Daud A, Inabnet W, et al. Markers of bone and calcium metabolism following gastric bypass and laparoscopic adjustable gastric banding. Obes Surg 2008;18:1114–48. [22] Earthman CP, Beckman LM, Masodkar K, et al. The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications. Int J Obes 2012;36:387–96. [23] Bischoff-Ferrari H, Keller U, Burckhardt P, et al. Recommandations de la commission fédérale de l’alimentation concernant l’apport de vitamine D. Forum Med Suisse 2012;12:775–8. [24] Giusti V, Gasteyger C, Suter M, et al. Gastric banding induces negative bone remodelling in the absence of secondary hyperparathyroidism: potential role of serum C telopeptides for follow-up. Int J Obes 2005;29:1429–35. [25] Olmos J, Vazquez L, Amado J, et al. Mineral metabolism in obese patients following vertical banded gastroplasty. Obes Surg 2008;18:197–203. [26] Valderas J, Velasco S, Solari S, et al. Increase of bone resorption and the parathyroid hormone in post-menopausal women in the long-term after Roux-en-Y gastric bypass. Obes Surg 2009;19:1132–8. [27] Yu EW. Bone metabolism after bariatric surgery. J Bone Miner Res 2014;29:1507–18. [28] Hage MP, El-Hajj Fuleihan G. Bone and mineral metabolism in patients undergoing Roux-en-Y gastric bypass. Osteoporos Int 2014;25:423–39.
B. Uebelhart / Joint Bone Spine 83 (2016) 271–275 [29] Brzozowska MM, Sainbury A, Eisman JA, et al. Bariatric surgery, bone loss, obesity and possible mechanisms. Obesity 2013;14:52–67. [30] Edwards C, Kindle AK, Fu S, et al. Downregulation of leptin and resistin expression in blood following bariatric surgery. Surg Endosc 2011;25:1962–8. [31] Bruno C, Fulford A, Potts J, et al. Serum markers of bone turnover are increased at 6 and 18 months after Roux-en-Y bariatric surgery: correlation with the reduction of leptin. J Clin Endocrinol Metab 2010;95:159–66.
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[32] Berarducci A, Haines K, Murr M. Incidence of bone loss, falls and fractures after Roux-en-Y gastric bypass for morbid obesity. Appl Nurs Res 2009;22:35–41. [33] Lalmohamed A, de Vries F, Bazelier M, et al. Risk of fracture after bariatric surgery in the United Kingdom: population-based, retrospective cohort study. BMJ 2012;345:e5085. [34] Nakamura KM, Haglind EG, Clowes JA, et al. Fracture risk following bariatric surgery: a population-based study. Osteoporos Int 2014;25:151–8.
Available online at
ScienceDirect www.sciencedirect.com
Review
Effects of bariatric surgery on bone Brigitte Uebelhart Département des spécialités de médecine, service des maladies osseuses, hôpitaux universitaires, faculté de médecine de Genève, 4, rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland
a r t i c l e
i n f o
Article history: Accepted 21 February 2013 Available online 15 March 2016 Keywords: Bone mineral density Fractures Biochemical bone turnover markers
a b s t r a c t Bariatric surgery currently relies on combinations of restrictive and malabsorptive procedures. Early decreases in bone mineral density (BMD) have been reported. However, the accuracy of dual-energy X-ray absorptiometry used to measure BMD can be diminished by the major weight loss, whereas quantitative computed tomography (QCT) measurements are less affected. The nutritional deficiencies induced by mixed bariatric surgery procedures, together with changes in hormones produced by adipocytes and/or the gastrointestinal tract, are often associated with elevations in serum levels of bone resorption markers. Although the data are limited, the incidence of fractures does not seem higher after bariatric surgery than in non-operated obese patients. © 2016 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Bariatric surgery includes various procedures aimed at inducing weight loss in obese patients. These procedures restrict the amount of food eaten and/or induce malabsorption, thereby causing considerable and long-lasting weight loss [1]. This large decrease in weight has highly beneficial effects on the diseases and risk factors associated with excess body fat, most notably in obese patients with type 2 diabetes [2]. The improved glycemic control seen in these diabetic patients after bariatric surgery may also involve endocrine and metabolic factors that increase feelings of satiety or decrease appetite. Finally, prospective data have documented a decrease in mortality [3]. 1. Bariatric surgery techniques Bariatric surgery techniques include restrictive, malabsorptive, and mixed procedures [4]. They are increasingly performed laparoscopically. Restrictive bariatric surgery (Fig. 1) was introduced in the 1950s. The objective is to decrease the capacity of the stomach and/or to delay gastric emptying. This method is effective in inducing weight loss in the short term. However, it is associated with gastrointestinal symptoms, most notably bowel transit abnormalities. Furthermore, patients tend to gain weight secondarily by changing their eating patterns. As a result, restrictive procedures are no longer performed. Malabsorptive procedures (Fig. 1) were first developed in the late 1960s. They involve creating a bypass between the duodenum
E-mail address: [email protected]
and the ileum. Thus, weight loss occurs regardless of the patient’s diet. This method has been discarded for two reasons: it induces metabolic complications (e.g., increased oxalate absorption responsible for renal lithiasis) and it causes blind loop syndrome (i.e., bacterial overgrowth responsible for various symptoms including polyarthralgia). Since the early 1980s, mixed procedures that combine restrictive and malabsorptive techniques have gained preference. Many variants exist, all of which derive from the Roux-en-Y gastric bypass (RYGBS) developed by the Swiss surgeon César Roux (Fig. 2). The variant developed by the Italian surgeon Nicola Scopinaro (1974) is characterized by a short common intestinal segment, which results in a predominantly malabsorptive mechanism. 2. Systemic metabolic impact of mixed bariatric surgery (Roux-en-Y gastric bypass surgery [RYGBS] and variants) The combination of decreased energy intake from food and malabsorption would be expected to result in at least partial deficiencies in the absorption of various nutrients [5] (Fig. 2). Vitamin B12 deficiency is related to decreases in both intrinsic factor and acidification [6,7]. Decreased acidification can also lead to iron deficiency responsible for anemia. Patients may lack fat-soluble vitamins (A, D, E, and K) [8,9], and the lower vitamin D stores may cause calcium deficiency, often with secondary hyperparathyroidism, which may persist even after vitamin D repletion [10]. In clinical practice, the most consistently prescribed vitamin supplement is intramuscular vitamin B12. Calcium and vitamin D supplements are also frequently given. The other vitamins, nutrients, and ions are prescribed on an as-needed basis.
http://dx.doi.org/10.1016/j.jbspin.2016.02.013 1297-319X/© 2016 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
272
B. Uebelhart / Joint Bone Spine 83 (2016) 271–275 Table 1 Changes in body mass index, bone mineral density, and T-scores in 62 women with morbid obesity before and 12 months after Roux-en-Y gastric bypass surgery.
Body mass index (kg/m2 ) Bone mineral density (g/cm2 ), femoral neck Bone mineral density (g/cm2 ), lumbar spine T-Score (SD), femoral neck T-Score (SD), lumbar spine *
Before surgery
12 months after surgery
43.9 ± 4.2 1.1 ± 0.11
29.1 ± 4.5* 0.98 ± 0.11*
1.1 ± 0.12
1.06 ± 0.13*
1.1 ± 0.98 0.68 ± 1.2
0.13 ± 0.98* 0.25 ± 1.2*
P < 0.005 versus the value before surgery [17].
serum compounds reflecting activity of the calcium-parathyroid hormone-vitamin D axis. Only recently have retrospective data on fractures after bariatric surgery become available. Fig. 1. Examples of restrictive and malabsorptive bariatric procedures. Restrictive bariatric procedures consist in decreasing the size of the stomach. Techniques include transverse gastrectomy (A), sleeve gastrectomy (B), and implantation of an inflatable band around the proximal stomach (C). Malabsorptive bariatric procedures involve creating a bypass between the jejunum and the ileum. In the Payne procedure (D), a 35-cm long segment of proximal jejunum is anastomosed to the ileum 10 cm proximal to the ileocecal valve. The distal jejunum and proximal ileum form a blind loop, through which food does not travel, and where bacterial overgrowth may develop.
3. Impact of bariatric surgery on bone The decreased absorption of vitamin D and calcium would be expected to substantially increase the risk of osteomalacia. This expectation is not borne out by the data in the literature. The anecdotal case-reports published to date describe patients with clinical, laboratory, or radiological features indicating suspected osteomalacia, without histological documentation (no bone biopsy or mineralization rate measurement by double tetracycline labeling). Whether these features are entirely ascribable to bariatric surgery remains unclear. For instance, 1 patient was African-American, and the risk of vitamin D deficiency is known to be markedly increased in blacks [11]. Another patient was dependent on corticosteroid therapy for severe asthma [12]. Many published studies of bariatric-surgery patients monitored bone mineral density (BMD), serum bone turnover markers, and
Fig. 2. Mixed Roux-en-Y gastric bypass surgery and resulting malabsorption. The Roux-en-Y procedure creates three small-bowel loops: (A) receives food but no bile or pancreatic secretions; (B) receives the bile and pancreatic secretions; and (C) receives the outputs from loops A and B. There is malabsorption of vitamin B12, fatsoluble vitamins (A, D, E, and K), iron, and calcium. In contrast, oxalate is absorbed in increased amounts because of the diminished formation of non-absorbable calciumoxalate complexes that are normally eliminated in the feces.
3.1. Bone mineral density (BMD) Studies consistently found decreased BMD values, which were usually measured by dual-energy X-ray absorptiometry (DXA). These decreases occurred despite calcium and vitamin D supplementation. Early BMD decreases were demonstrated using various study designs, including a cross-sectional evaluation several years after bariatric surgery [13], a 2-year prospective study after gastric banding [14], and a comparison of data collected preoperatively, then 1 to 4 years after bypass gastric surgery [15–18]. The BMD decline starts within the first year after surgery, then continues at a slower pace. The hip is the most severely affected site, with an up to 10% decrease compared to the preoperative value. Bone loss occurs less consistently at the spine and only rarely at the radius. The BMD decrease is larger in postmenopausal women than in younger women before the menopause. Despite the magnitude of the bone loss, given the baseline values, the postoperative T-scores usually remain within the normal range. For instance, in a study of 62 women with morbid obesity who were evaluated preoperatively then 1 year after RYGBS, both the BMD and the T-score values diminished significantly yet remained within the normal ranges (Table 1) [17]. Fig. 3 shows the size of the BMD decreases after gastric bypass surgery [18]. In this study, BMD values were measured over a 9-month period in 25 patients. The BMD declines were largest at the hip, where the values decreased by 6% at the femoral neck and 8% at the greater trochanter. Bone mineral content (BMC) showed smaller declines. In this study, mean weight loss was 13% after 3 months and 27% after 9 months. A similar discrepancy between BMD and BMC values was documented in another study (Table 2), which evaluated 70 patients with morbid obesity before and 1 year after RYGBS [16]. After 1 year, as is usual with this procedure, the patients had lost about 30% of their body weight and 54% of their fat mass. The preoperative to postoperative changes measured using DXA (GE Lunar densitometer) were significant and BMC showed a larger decline (−9%) compared to BMD (−3%). Oddly, enough, there was a significant 6% decrease in total bone surface area. This finding suggests that the large decrease in soft-tissue thickness related to the up to 50% decrease in fat mass may substantially affect the accuracy of DXA measurements. The weight loss, which is chiefly due to a decrease in body fat, strongly influences the accuracy of BMD measurements yet is often not specified in study reports. Other measurement tools such as quantitative computed tomography (QCT) may be less sensitive than DXA to the effects of the initial excess body fat and subsequent major weight loss. This possibility has been assessed by comparing DXA and QCT used to obtain measurements of lumbar-spine phantoms and of healthy volunteers. Changes in the thickness of the soft tissues and body
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Table 2 Changes in anthropometric parameters and bone mineral density and content in 70 patients with morbid obesity before and 12 months after Roux-en-Y gastric bypass surgery. Patients took 1 g of supplemental calcium and 800 IU of supplemental vitamin D per day [16]. Before surgery (mean ± SD) Weight (kg) Body mass index (kg/m2 ) Total body fat (kg) Bone mineral content (g) Bone mineral density (g/cm2 ) Total bone surface area (m2 )
132.81 48.06 75.21 2968.6 1.26 2356.16
± ± ± ± ± ±
26.52 7.3 21.25 71.44 0.03 35.4
fat were simulated. The results suggest that an increase in body fat thickness within the soft tissues has a major adverse effect on the accuracy of bone measurements, most notably at the lumbar spine, and that this effect is greater with DXA than with QCT [19]. Although more reliable, QCT involves greater patient exposure to radiation. BMD changes were evaluated using both DXA and QCT in 30 patients with morbid obesity during the first 12 months after mixed bariatric surgery and in 20 non-operated obese patients. At the end of the 12-month follow-up, the surgically treated group had a mean weight loss of 37 ± 2 kg and the non-operated group a mean weight gain of 3 ± 2 kg. Both DXA and QCT showed an about 3% decrease in BMD at the spine in the surgically treated group. At the femoral neck and total hip, BMD was decreased by DXA but not by QCT [20]. 3.2. Laboratory parameters involved in bone metabolism Many published studies have addressed this issue, and their findings are conflicting. Most studies are prospective or retrospective evaluations of patients with morbid obesity, whose data
Fig. 3. Changes in bone mineral density and content at various sites 9 months after Roux-en-Y gastric bypass surgery [18]. Nine months after Roux-en-Y gastric bypass surgery, bone mineral density values (A) measured by DXA (Hologic QDR-4500A) are significantly decreased at all measurement sites (spine, total hip, femoral neck, trochanter, distal third of the radius, and whole body). The decreases in bone mineral content (B) are significant only at the femoral neck and total hip. Ultrasound attenuation values at the heel are provided for purposes of comparison. The data are mean ± SD. Compared to preoperative values: *P < 0.05, **P < 0.01, ***P < 0.001.
12 months after surgery (mean ± SD) 90.31 32.64 34.46 2700.82 1.22 2216.28
± ± ± ± ± ±
17.29 4.13 13.63 45.36 0.015 43.51
P-value
Change (%)
0.001 0.001 0.001 0.001 0.001 0.001
−32 −33 −54 −9 −3 −6
collected before and after bariatric surgery were compared. Many found no differences or abnormalities, particularly regarding serum calcium, parathyroid hormone, and 25-OH-vitamin D [15–17,19]. It should be borne in mind, however, that calcium and vitamin D supplements are prescribed routinely after bariatric surgery. Other studies comparing patients before and after surgery showed secondary parathyroid hormone elevation which, in some cases, was clearly ascribable to persistently low 25-OH-vitamin D levels throughout follow-up [10,21]. An important point is that the main source of vitamin D is not food but, instead, synthesis in the skin via a mechanism activated by ultraviolet radiation in sunlight. Consequently, the prevalence of vitamin D insufficiency or deficiency among operated or non-operated patients with morbid obesity is probably similar to that in the general population. In contrast, the absorption of supplemental vitamin D (a fat-soluble vitamin) decreases after bariatric surgery, and vitamin D insufficiency is therefore difficult to correct. Consequently, serum 25-OH-vitamin D levels should be assayed regularly, supplements given in higher doses than recommended in the general population, and intramuscular vitamin D administered if needed. Finally, vitamin D can be sequestered in excess body fat that may persist despite the postoperative weight loss [22]. Whatever the mechanism, patients who have had bariatric surgery to treat morbid obesity are at increased risk for severe vitamin D deficiency. They are therefore classified as a population at risk and should undergo serum 25-OH-vitamin D assays at regular intervals [23]. Alterations in bone turnover are the most often reported abnormalities. The bone resorption marker C-terminal telopeptide (CTX, the C-terminal end of type I collagen, which is released into the bloodstream during osteoclastic resorption) increases after bariatric surgery. This increase in a bone resorption marker is not consistently accompanied with parathyroid hormone elevation or vitamin D insufficiency. Other factors, such as hormones, may therefore be involved [24,25]. Bone resorption marker elevation has also been reported in patients after RYGBS compared to matched non-operated obese patients, both 1 year after surgery [18] and up to 5 years after surgery [26]. The adverse bone changes seen after bariatric surgery are widely ascribed to the decreased nutrient absorption and reduction in mechanical loading related to the weight loss. Nevertheless, a growing body of evidence suggests a role for changes in the release of hormones produced in fat tissue, i.e., adipokines, and in the gastrointestinal tract (peptide YY, glucagon-like peptide-1, and ghrelin) [27–29]. The most extensively studied hormones are the two main adipokines, leptin and adiponectin. Leptin is produced by adipocytes and its levels therefore decrease when body fat is lost after bariatric surgery. A strong correlation has been reported between the decrease in body mass index (BMI) and serum leptin levels [30]. In a prospective study of 20 patients who underwent bariatric surgery, a serum leptin decrease predicted increased bone resorption with CTX elevation, suggesting an effect of leptin on bone cells [31]. Adiponectin is also produced by adipocytes, although in smaller amounts in obese patients. Serum adiponectin levels may correlate negatively with BMD. Gastrointestinal
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hormones, of which one effect is to control appetite and feelings of satiety, may contribute to the changes in bone metabolism, although their effect remains unclear [29].
the close patient follow-up with the prescription of supplements to correct the main surgery-related deficiencies, particularly in calcium and, above all in vitamin D.
3.3. Fractures
Disclosure of interest
The incidence of fractures after bariatric surgery to treat morbid obesity is generating avid interest, particularly given the possible BMD decline and combination of deleterious biological changes including calcium and vitamin D deficiency, secondary hyperparathyroidism, and accelerated bone turnover. Nevertheless, the available information is scant. A descriptive retrospective study was conducted in 167 patients from a possible participant pool of 444 [32]. The patients were interviewed by telephone 12 to 60 months after RYGBS to treat morbid obesity. Among them, 8 (5%) reported having had a fracture since their surgical procedure, after a mean postoperative follow-up of 2.4 years. Although this fracture rate is low, important findings are that 57 (34%) patients experienced one or more falls postoperatively and that only 15 (9%) reported taking vitamin D supplements. A population-based retrospective cohort study reported in 2012 used data collected between January 1987 and December 2010 from 625 primary-care practices in the UK. All patients treated with bariatric surgery for morbid obesity and all bone events such as fractures were recorded. The 2079 operated patients had a mean age of 45 years (and still had BMI values > 30 kg/m2 ). They were compared to non-operated patients matched on age and weight. During the mean follow-up of 2.2 years, no significant increase in the frequency of fractures was noted in the bariatric-surgery group. A nonsignificant trend towards a higher fracture rate 3 to 5 years after surgery was noted in the subgroup with the greatest decrease in BMI [33]. A second study on the fracture risk after bariatric surgery was published in 2014 [34]. Again, a retrospective cohort design was used. The study included only 258 patients with a history of bariatric surgery, living in Minnesota and included in the Rochester Epidemiology Project. Mean age was 44 ± 10 years. The mean follow-up of 7.7 years was substantially longer than in the previous study. In this cohort, 79 patients experienced 132 fractures, yielding a 2.3-fold increase in relative risk compared to the overall population in the Rochester Epidemiology Project. The operated patients were not matched to the controls on weight, which may have induced bias, since excess weight may be an independent risk factor for fractures, at least at some sites. 4. Conclusion Bariatric surgery induces significant health benefits in patients with morbid obesity. Weight loss is known to have adverse effects on bone in other situations, and bariatric surgery induces malabsorption with deficiencies in a number of factors. Nevertheless, the studies have shown little or no increase in the fracture risk after bariatric surgery. This finding should be interpreted in the light of the large reduction in body fat and invites questions about possible links between adipose tissue and bone tissue, which may be modest or related to other mechanisms. The decrease in BMD values shown in DXA studies should be viewed with circumspection, as the considerable weight loss affects the accuracy of DXA. QCT measurements may be more reliable. Finally, bone resorption markers seem to increase consistently, although the underlying pathophysiological mechanism remains obscure. Hypotheses that may explain the limited impact on bone of bariatric surgery include the persistence of excess weight even after a period of considerable weight loss, persistence of normal BMD and T-score values, and probably
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